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in 2011 in cambodia , environmental samples were collected from 4 lpms each week for 7 weeks , including during the khmer new year festival ( figure 1 ) . two of the markets were in phnom penh , the capital city : orussey market ( m1 ) and chamkar doung market ( m2 ) , which also served as an overnight resting place and a place to keep unsold birds from various markets . the third market ( m3 ) was in takeo ( takeo province ) , and the fourth ( m4 ) was in kampong cham ( kampong cham province ) . local chickens , sampov ( domesticated mallards ) , and kaki campbell ducks ( domesticated muscovy ducks ) were the only live poultry observed in the markets . other poultry species were usually available only upon customer request , or they were sold dead . prevalence of influenza a(h5n1 ) virus positive environmental samples from live poultry markets , by collection week , during the khmer new year festival , cambodia , 2011 . m1 , orussey market ( phnom penh ) ; m2 , chamkar doung market ( phnom penh ) ; m3 , takeo market ( takeo province ) ; m4 , kampong cham market ( kampong cham province ) . samples positive for the matrix , hemagglutinin 5 , and neuraminidase 1 genes by quantitative real - time reverse transcription pcr were considered positive for subtype h5n1 virus . in rare instances , neuraminidase 1negative samples that were positive for the matrix and hemagglutinin genes were considered positive for subtype h5n1 virus . during the study , we observed that chickens and ducks were mixed together in cages or stalls . in each market , we collected environmental samples from 45 poultry cages or from stalls where poultry were gathered . from each sampling site , we collected the following into sterile 50-ml tubes : 50 ml of water used by poultry for drinking , 50 ml of water used to wash carcasses or found on the floor near the slaughtering area , 4050 g of soil / mud , and 23 g of fresh feces present on the soil . feathers ( 1020 g ) dropped by birds were gathered and placed in sterile plastic bags . virus in water , soil , and mud samples was concentrated , as described ( 6,12,13 ) , in the biosafety level 3 laboratory at institut pasteur , phnom penh . samples were then tested by quantitative real - time reverse transcription pcr ( qrt - pcr ) targeting the matrix ( m ) , hemagglutinin 5 ( h5 ) , and neuraminidase 1 ( n1 ) genes . feces and feather samples were homogenized with sterile phosphate - buffered saline before nucleic acid extraction and testing . samples were considered subtype h5n1 virus positive if qrt - pcr was positive for the m , h5 , and n1 genes . the n1 qrt - pcr we used is less sensitive than those used for detection of the m and h5 genes . free embryonated hen eggs for virus isolation ( 6 ) . of 502 samples collected , 90 ( 18% ) were positive for subtype h5n1 virus by qrt - pcr , and 10 ( 2% ) were positive by virus isolation ( table ) . we did not detect > 1 positive sample at a time in each cage sampled ; thus , each positive sample corresponded to 1 contaminated sampling site . no correlation was observed between viral load measured by qrt - pcr and the ability to isolate the virus in eggs . the overall positivity rate for detection of rna was > 20% for water , feather , and soil / mud samples ; the rate was significantly lower for feces samples ( 6% ; p<0.05 ) ( table ) . the virus was isolated from 8 ( 6% ) water samples and 2 ( 2% ) soil / mud samples . * qrt - pcr , quantitative real - time reverse transcription pcr ; m1 , orussey market in the capital city of phnom penh ; m2 , chamkar doung market in phnom penh ; m3 , a market in takeo , takeo province ; m4 , a market in kampong cham , kampong cham province . free embryonated hen eggs for virus isolation . the percentage of samples that were positive was significantly different ( by test ) for feces vs. water ( p = 0.0007 ) , feces vs. soil / mud ( p = 0.0003 ) , and feces vs. feathers ( p = 0.0005 ) . the percentage of samples that were positive was significantly different ( by test ) for water vs. feces ( p = 0.001 ) and water vs. feathers ( p = 0.009 ) . the percentage of environmental samples that were positive was significantly different ( by test ) for m4 vs. m1 ( p = 0.002 ) , m4 vs. m2 ( p = 0.002 ) , and m4 vs. m3 ( p = 0.0008 ) . compared with the market in kampong cham ( m4 ) , the markets in phnom penh and takeo ( m13 ) had a higher percentage of samples positive for h5n1virus ( 8% vs. > 20% ; p<0.05 ) . overall , the level of environmental viral contamination in lpms was highest at the beginning of the study ( i.e. , 4 weeks before the khmer new year , when poultry sales began for the annual festival ) and corresponded with intense movement of poultry within the country and higher densities of poultry populations on farms ( 2,4 ) ; contamination levels tended to progressively decrease , reaching low levels 2 weeks after the event ( figure 1 ) . the full genomic sequence of 4 strains and the hemagglutinin sequence of 3 other isolates were generated ( genbank accession nos . phylogenetic analyses showed that the virus strains detected during this study belong to lineage 6 , a group of viruses that seems to be endemic to cambodia ( 14 ) ( figure 2 ) , and not to lineage 5 , a more regional group of viruses that was also circulating in cambodia at that time and that includes strains originating from cambodia and vietnam . sequence analyses did not detect reassortment events or mutations associated with higher virulence or increased transmission to humans . sequences for a virus detected in march 2011 in m3 ( takeo ) clustered with sequences for strains isolated from 2 subtype h5n1 virus infected humans in february near phnom penh and in april in prey veng province , respectively . this finding suggests that the strain detected in takeo was part of a phylogroup that circulated in different regions of the country for several months . sequences for that strain did not cluster with those for the isolates from humans in phnom penh and prey veng province ; however , the strain shared a high degree of homology with a strain detected a week later in phnom penh , suggesting the cocirculation in markets of strains with different origins . phylogenetic relationship of the hemagglutinin ( ha ) gene among various influenza a(h5n1 ) strains ; ha sequences for 48 strains ( 36 from cambodia , 11 from vietnam and one from china ) were included in the analysis . black triangles indicate viruses detected during this study of environmental samples from live poultry markets in cambodia . phylogenetic trees were generated by using the distance method and applying the neighbor - joining algorithm with bootstrap analysis ( 1,000 replicates ) . the trees were rooted to a / goose / china / guangdong/1/96 ( h5n1 ) . lineage numbers 16 , clades , and subclades indicate strains that are grouped in closely related phylogenetic lineages , as described ( 14 ) . hpai a(h5n1 ) virus circulation in cambodia has traditionally been monitored by using the moderately sensitive egg inoculation method to test cloacal and tracheal swab samples from birds randomly selected from lpms or farms . our results show that a more effective approach especially before and during the main annual festivals , when the movement of poultry within the country is increased would be to use highly sensitive qrt - pcr to test environmental samples from lpms . in our study , water samples proved to be the best choice for isolation of infectious subtype h5n1 virus ( table ) . the lower detection rate of virus among feces samples was expected because the analysis of such samples represents viral shedding by only 1 or a few birds . available sequence data from other surveillance efforts indicate that all strains detected in this study originated in cambodia . in cambodia , birds not sold the same day they arrive at a live poultry market are transported to an overnight resting place , which is sometimes another market ( 7 ) . such movement of poultry could increase exposure to environmental contamination with hpai a(h5n1 ) virus and thus contribute to virus spread among poultry . it is not known what effect the high levels of hpai a(h5n1 ) virus contamination in lpms in cambodia have on human health ; the effect should be evaluated by conducting clinical and serologic surveillance of vendors and poultry workers .

in cambodia , influenza a(h5n1 ) virus surveillance at live poultry markets ( lpms ) relies on virus isolation from poultry specimens ; however , virus is rarely detected by this method . we tested 502 environmental lpm samples : 90 were positive by pcr , 10 by virus isolation . virus circulation could be better monitored by environmental sampling of lpms .

the ability of lasers to induce hair growth was incidentally noted as early as 1967 when mester et al . used low - level laser therapy ( lllt ) to treat cancer in mice with shaved backs . since then , hypertrichosis has been recognized to be a possible side - effect of laser treatment . first described in 2002 with intense pulsed light therapy , this phenomenon has now been widely acknowledged to occur with an incidence rate ranging from 0.6% to 10% with low fluences and all laser types . it is thought to be the result of suboptimal fluences that are too low to induce thermolysis , but high enough to stimulate follicular growth . eventually , lllt has been developed for the treatment of androgenetic alopecia ( aga ) . as opposed to other currently marketed systems , the laser comb utilizes hair parting teeth for optimal delivery of laser energy to the exposed scalp . in 2007 , the hairmax laser comb ( lexington international , llc ) received 510 ( k ) clearance from the food and drug administration ( fda ) for the treatment of aga for men , and 2011 for women . this clearance means that the device is considered a moderate - risk medical device by the fda and is thereby solely screened for safety . the hairmax laser comb has been tested in a company - sponsored study of 110 male patients with the claim of a significant increase in mean terminal hair density when compared to a sham device . avram and rogers conducted the first independent blinded study of lllt and hair growth with seven patients and found that on average , there was a decrease in the number of vellus hairs , an increase in the number of terminal hairs , and an increase in shaft diameter . a consensus written by hair loss experts states that based on anecdotal experience , lllt , particularly 650 - 900 nm wavelengths at 5 mw , may be an effective treatment option for patients with aga . in recent times , kim et al . reported an increase of hair density with the use of lllt , when compared to the sham device in a 24-week , randomized , double - blind , sham - device - controlled trial . to evaluate efficacy of the 655 nm - hairmax laser comb either as monotherapy or as concomitant therapy for treatment of male and female aga , we performed a retrospective observational study of global photographic assessments of patients in an office - based setting . patients who had purchased a hairmax laser comb between july 2011 and july 2013 for treatment of aga at the center for dermatology and hair diseases prof . treb were retrieved for assessment of global photographic images performed at follow - up visits . patients on concomitant treatment had been treating with topical minoxidil or oral finasteride for at least 9 months , before starting therapy with the hairmax laser comb . patients used the hairmax laser comb at home according to instructions 3 times weekly between 8 and 15 min depending on the model purchased ( advanced 7 , lux 9 , or professional 12 ) . global photographs were performed at 3 , 6 , 12 , and 24 months of treatment follow - up in a standardized manner with a stereotactic camera device of canfield scientific inc . , in which the patient 's chin and forehead are fixed and on which digital camera and flash device are mounted , ensuring that view and lighting are the same at consecutive visits , thus enabling precise follow - up of the same scalp area of interest with frontal and vertex views . global photographs were evaluated by two of the authors ( am and rmt ) , and scored as significant , moderate , or no improvement . in the case of diverging opinions , in total , 32 patients with aga were involved in the study , of which 21 were females , aged 22 - 73 ( mean : 43.6 15.19 standard deviation [ sd ] ) , and 11 were males , aged 20 - 70 ( mean : 39 15.01 sd ) total mean : 42 15.1 sd . the duration of hair loss in years for men and women was mean 7.1 5.2 sd . the duration of lllt in months for men and women was mean 8.7 5.2 [ table 1 ] . the patient characteristics , with respect to gender , age , classification of aga according to ludwig and hamilton - norwood scales , duration of hair loss , and concomitant treatments are recorded in table 2 . the results for the scoring of the global photographic assessment in relation to treatment duration with the hairmax laser comb are demonstrated in table 3 . in summary , eight patients ( three female , five male ) showed significant improvement , 20 patients ( 14 female , six male ) moderate improvement , and four patients ( four female , zero male ) no improvement [ figure 1 ] . of 32 patients , the hairmax laser comb was used as monotherapy in six patients ( two female , four male ) , and as a concomitant therapy in 26 patients ( 19 female , seven male ) . in the monotherapy group , two patients ( one female , one male ) showed significant improvement [ figure 2 ] , four patients ( one female , three male ) moderate improvement , and zero patients no improvement [ table 3 ] . in the concomitant therapy group , six patients ( two female , four male ) showed significant improvement [ figures 3 and 4 ] , 16 patients ( 13 female , three male ) moderate improvement , and four patients ( four female , zero male ) no improvement . there was no statistical significant difference between lllt monotherapy and concomitant therapy with either minoxidil and/or finasteride ( p = 0.829 ) , and regarding male or female aga ( p = 0.091 ) [ table 4 ] . improvement of alopecia in relation to the variables : age , duration of hair loss , and duration of lllt patient characteristics graphic summary of results monotherapy in a 54-year - old male ( a ) before treatment , and improvement after ( b ) 6 months , and ( c ) 12 months of low - level laser therapy scoring of global photographic assessment in relation to treatment duration concomitant treatment with topical 5% minoxidil in a 55-year - old male adding on low - level laser therapy ( lllt ) to 4 year pretreatment with 5% topical minoxidil solution ( a ) before , and ( b ) after 3 months of added lllt concomitant treatment with topical 5% minoxidil and 1 mg oral finasteride in a 34-year - old male ( a ) before , ( b ) after 9 months treatment with 1 mg oral finasteride and topical 5% minoxidil solution bid , and ( c ) after 3 months after adding on low - level laser therapy comparative assessment of efficacy between monotherapy and concomitant for male and female androgenetic alopecia treatment was well tolerated and no serious adverse events were reported . . currently , topical 2% and 5% minoxidil solution and 1 mg oral finasteride are the treatments with the highest levels of medical evidence , but patients who exhibit intolerance or poor response to these treatments are in need of additional treatment modalities . although low - level energy lasers have been therapeutically used in medicine for photobiostimulation in a variety of indications more than 30 years , it has only recently found the attention of the scientific community for the treatment of aga . we have chosen the 655 nm - hairmax laser comb for several reasons : first , it represents the device with the most clinical study reports regarding its efficacy , secondly , the cost of the device is affordable , and thirdly , the device is simple enough for patients to use at home . finally , the fact that the device is safe , for which it received 510 ( k ) clearance from the fda for the treatment of aga , was also an important consideration . our study demonstrates clinical efficacy of the device for treatment of male and female aga , both as monotherapy and as concomitant therapy , in terms of clinically relevant improvement of appearance of hair . of 32 patients , eight patients ( 25% ) showed significant improvement , and 20 patients ( 62.5% ) showed moderate improvement in global photographic assessments . the effect was observed as early as 3 months of treatment , and was sustained up to a maximum observation time of 24 months . the technology appears to work better for some than for others , and predictive factors which will most benefit from lllt are to be determined . it seems though , that patients with intermediate alopecia ( hamilton - norwood iii and iv , and ludwig i and ii , respiratory ) respond best , since effective photobiostimulation depends on a minimum of hair for effective photobiostimulation , and on a maximum of hair for the laser beam to reach the scalp without absorption or interference from existing hairs . the hypothesized mechanisms of action of lllt are increased adenosine tri - phosphate ( atp ) production , modulation of reactive oxygen species ( ros ) , and induction of transcription factors . the proposed cellular chromosphere responsible for the effect of visible light is cytochrome c oxidase ( cox ) with absorption peaks in the near infrared , and mitochondria the likely site for the initial effects . it is believed that lllt displaces nitric oxid from cox allowing an influx of oxygen to bond to cox and progress forward in the respiratory process to atp production and ros signaling . these effects in turn lead to increased cellular proliferation , modulation in levels of cytokines , growth factors and inflammatory mediators , and increased tissue oxygenation . while the effects of these biochemical and cellular changes have broadly been studied in both animal models and clinical studies with patients , and have shown benefits in diverse conditions , such as increased healing in chronic wounds , improvements in sports injuries and carpal tunnel syndrome , pain reduction in arthritis and neuropathies , and amelioration of damage after heart attacks , stroke , nerve injury and retinal toxicity , the effects on hair growth stimulation have only recently gained the attention of the scientific community . from our own observations , we share with other authors the opinion that lllt represents a safe and potentially effective treatment option for patients with aga who do not respond or are not tolerant to standard treatment of aga . moreover , combining lllt with topical minoxidil solution and oral finasteride may act synergistic to enhance hair growth . due to the known beneficial effect on wound healing , it is conceivable that lllt as an adjunctive therapy in hair transplant surgery may also reduce postoperative shedding , reduce healing time , and increase graft patency . the scientific basis for such an approach is given , but there is a need for controlled studies with a higher number of patients to establish an increase in efficacy of combination regimens .

background : androgenetic alopecia ( aga ) is the most common form of hair loss in men and in women . currently , minoxidil and finasteride are the treatments with the highest levels of medical evidence , but patients who exhibit intolerance or poor response to these treatments are in need of additional treatment modalities.objective:the aim was to evaluate the efficacy and safety of low - level laser therapy ( lllt ) for aga , either as monotherapy or as concomitant therapy with minoxidil or finasteride , in an office - based setting.materials and methods : retrospective observational study of male and female patients with aga , treated with the 655 nm - hairmax laser comb , in an office - based setting . efficacy was assessed with global photographic imaging.results:of 32 patients ( 21 female , 11 male ) , 8 showed significant , 20 moderate , and 4 no improvement . improvement was seen both with monotherapy and with concomitant therapy . improvement was observed as early as 3 months and was sustained up to a maximum observation time of 24 months . no adverse reactions were reported.conclusions:lllt represents a potentially effective treatment for both male and female aga , either as monotherapy or concomitant therapy . combination treatments with minoxidil , finasteride , and lllt may act synergistic to enhance hair growth .

ewing 's sarcoma family of tumors are a group of small round - cell neoplasms , which include ewing 's sarcoma ( ews ) , primitive neuroectodermal tumor ( pnet ) , askins tumor , pnet of the bone , and extraosseous ewing 's sarcoma ( ess ) . ewing 's sarcoma / peripheral primitive neuroectodermal tumor , presumed to be neuroectodermal in origin , most often occurs in the bone and soft tissues of children and young adults . the intracranial extraosseous ewing 's sarcoma ( cns - ess ) is extremely rare and often misdiagnosed as central nervous system pnet ( c - pnet ) or as other primary intracranial neoplasms . an 11-year - old female presented with a history of headache for one year , which increased in intensity over the last one month . she had repeated episodes of vomiting for one month and a left temporal scalp swelling , which was gradually increasing in size . on examination there was bilateral papilledema , but no other focal neurological deficits were detected . the left temporal scalp swelling was mildly tender , firm , immobile , and non - pulsatile with ill - defined margins . the computed tomography scan ( ct scan ) of the brain showed a rounded , well - defined , heterogeneously hyperdense , enhancing lesion in the left temporoparietal region , with a mass effect and destruction of the left temporal bone , extending into the scalp , suggesting the possibility of a meningioma . no evidence of calcification was noted within the lesion [ figure 1 ] . magnetic resonance imaging ( mri ) of the brain showed a left temporal lesion , hypointense on t1 , heterointense on t2 , with heterogeneous enhancement [ figure 2 ] . a significant mass effect was detected with a midline shift to the right , of 15 mm . preoperative ct scan of the brain showed a rounded , well - defined , heterogeneously hyperdense , enhancing lesion in the left temporoparietal region , with a mass effect and destruction of the left temporal bone extending into the scalp , suggesting the possibility of meningioma . no evidence of calcification was noted within the lesion preoperative mri of the brain showed a left temporal lesion , hypointense on t1 , heterointense on t2 , with heterogenous enhancement the patient underwent left temporoparietal craniotomy and decompression of the lesion . the operative findings suggested that the lesion was extradural , with erosion of bone in some areas and involvement of the overlying temporalis muscle . the histopathological examination showed round - to - oval cells arranged in lobules , separated by a thin vascular channel , having vesicular nuclei , with indistinct nucleoli . it was negative for cd20 , cd3 , myosin , and glial fibrillary acidic protein . the overall features were compatible with a primitive neuroectodermal tumor ( pnet ) , with a possibility of ewing 's sarcoma in the temporal region . the tumor was positive for t ( 11 ; 22 ) ( q24 ; q12 ) translocation detected by fluorescent in situ hybridization ( fish ) in the tumor biopsy sample . the findings of further metastatic workups , including ct scans of the thorax and abdomen and a bone scan with technetium tc-99 m , were negative . ews / pnet 's are characterized by immunoreactivity to the surface antigen cd99 / mic2 , which is expressed in up to 97% of the cases a postoperative ct scan of the brain revealed a large extradural and subdural hematoma in the left frontotemporal region , with a postoperative craniotomy defect and scalp edema . the child went on to receive 12 weeks of chemotherapy with vincristine , doxorubicin , and cyclophosphamide , alternated with ifosfamide and etoposide . the treatment was completed with the same combination of chemotherapeutic drugs for another 24 weeks . james ewing ( 18661943 ) first described the tumor , establishing that the disease was different from lymphoma and other types of cancer known at that time . in 1921 , he described a lethal primary bone lesion that affects children and young adults and most frequently originates in the long bones ( 47% ) , pelvis ( 19% ) or ribs ( 12% ) . the skull is rarely involved , probably in less than 4% of the cases , with the frontal and parietal bones being the most commonly affected . extraosseous ewing 's sarcoma ( ees ) has been recognized as a distinct disease entity that afflicts young adults in the second and third decades of life , with equal sex predilection . the ees commonly involves the paravertebral regions of the spine and in rare instances , these lesions arise in the intracranial compartment , where they have been commonly misdiagnosed as c - pnet , because of the similarity in their histological appearance . very few cases of the central nervous system extraosseous ewing 's sarcoma ( cns - ees ) have been reported in pathology literature.[611 ] jay et al . was probably the first to describe a patient with an isolated posterior fossa mass that histologically resembled a medulloblastoma , but demonstrated the t(11;22 ) ( q24;q12 ) translocation , which confirmed cns - ees . as far as our knowledge goes , this is the seventh case we are reporting . the differential diagnosis of an intracranial round cell tumor is primitive neuroectodermal tumor ( neuroblastoma ) , lymphoma , rhabdomyosarcoma , and ewing 's sarcoma . the histological examination reveals that these tumors are composed of small , undifferentiated neuroectodermal cells and frequently demonstrate immunohistochemical and/or electron microscopic features of glial or neuronal differentiation . recent advances in the molecular classification has allowed a clear pathological distinction between c - pnet and cns - ees . cns - ees is known to demonstrate in 97% of the patients , a strong membrane expression of the mic-2 gene product , designated cd99 , which is specifically recognized by the monoclonal antibodies o13 and hba71.[1316 ] in addition , the chromosomal translocation t(11 , 22)(q24;q12 ) , detected by fish , is found in more than 90% of ees . this nonrandom translocation is not found in the central primitive neuroectodermal tumors ( c - pnet ) such as the medulloblastoma and supratentorial pnet . although , cns - ees is histologically similar to c - pnets such as the medulloblastoma , it differs significantly in clinical behavior , treatment , and prognosis . the treatment options available for patients with cns - ees are similar to those of ees elsewhere in the body and include multimodality treatment comprising of surgery , chemotherapy , and radiation . patients with c - pnet also require surgery ; however , the chemotherapeutic and radiation therapy protocols differ from those used for cns - ees . multiagent chemotherapy regimens including cyclophosphamide , ifosfamide , doxorubicin , dactinomycin , and etoposide have been shown to be effective in localized ewing 's sarcoma , in various trials . the primary treatment for localized ess consists of neoadjuvant chemotherapy , with a combination of vincristine , doxorubicin , and cyclophosphamide , alternating with ifosfamide and etoposide , given for 12 to 24 weeks , followed by definitive local treatment of surgery or radiation , or surgery and postoperative radiation directed at the primary site . the treatment is completed with administering chemotherapy with a similar combination for a total of 36 to 49 weeks . because of the small number of patients , the prognosis of cns - ees is not clearly known , although it has been suggested that patients with ees that arises from structures within or around the cns may have a more favorable outcome than patients with c - pnet .

ewing 's sarcoma / peripheral primitive neuroectodermal tumors occur most often in bone and soft tissues of children and young adults . the intracranial manifestation of the disease is rare , and when present , this is often misdiagnosed with other varieties of primary brain tumors . we report such a case of extraosseous ewing 's sarcoma , which was initially suspected to be a case of meningioma in an 11-year - old girl .

during 20052010 ( time span needed to cover the study area ) and during the months more favorable for infection ( october april ) , foxes were either shot at night or trapped . therefore , a grid of 5 km 5 km to 10 km 10 km , depending on the department size , was superimposed over the sampling area , and no more than 1 fox was collected in each square . the geographic district where the sample was taken was then noted , and each fox was randomly allocated geographic coordinates within the commune ( a french administrative division of 10100 km ) . staff were trained by the anses - nancy laboratory ( national reference laboratory for echinococcoses ) ; that laboratory also confirmed any unrecognized specimens . for time- and cost - effectiveness during the analysis , we used the segmental and sedimentation counting technique ( 12 ) . the distribution of e. multilocularis prevalence in foxes was modeled against geographic coordinates by using a generalized additive model with a logistic link function and a thin plate regression spline on 300 knots ( 13 ) . analyses and graphic displays were conducted by using arcgis 9.3 , r 2.14.0 and the r packages maptools 0.810 , mgcv 1.712 , sp . 0.991 , and splancs 2.0129 . eighty - five could not be assigned a commune code and were not kept for further analysis , except to compute e. multilocularis prevalence in departments . the mean number of foxes collected by department was 84.95 ( sd 25.76 ) , which represents a mean of 1.56 foxes per 100 km ( sd 0.57 ) . for 4 departments , ( 36 , 61 , 67 , and 69 ) , full sampling urban areas , such as departments 93 , 95 , and 91 , also were undersampled because of human population density and high urbanization , all factors preventing easy fox sampling . the prevalence varied widely among departments , from 0 ( 95% ci 05% ) to 54% ( 95% ci 42%64% ) ( table 1 ) but was locally higher in some areas ( figure 2 ) . the mean prevalence in the entire studied area was 17% ( n = 3,307 ; 95% ci 16%19% ) . the prevalence in the historically echinococcosis - endemic area was 41% ( n = 789 ; 95% ci 37%44% ) and represented > 55% of all infected foxes and furthermore , in comparing our results with those of earlier similar studies during the same season with the same technique , we detected a significant increase of e. multilocularis prevalence in foxes over time in most of these departments ( table 2 ) . model - predicted prevalence ( a ) and standard error ( b ) of echinococcus multilocularis in foxes , france , 20052010 . 1 = 100% our study confirms the presence of e. multilocularis in areas where it is known to be endemic and indicates its presence in 25 additional departments . however , we can not discard the possibility that e. multilocularis was present but remained undetected during the 1980s1990s . that e. multilocularis could have remained undetected if it were not already at a very low prevalence in general isolated human cases recorded in the early 2000s outside areas to which it is known to be endemic corroborate this possibility ( 3 ) . the same uncertainty applies in other parts of europe ( 14 ) . taken as a whole , these findings indicate that the transmission intensity of e. multilocularis through fox populations in the occidental part of the european focus area is likely to have increased during the late 1990s and led to a much higher average prevalence than previously reported . furthermore , infected foxes close to large - scale conurbations , such as paris and its large suburban surrounding departments ( 93 , 91 , and 77 ) ( figure 1 ) amounting to 11,728,240 inhabitants , may create new conditions for human exposure similar to those already described in other highly urbanized cities , such as in switzerland , germany , and eastern france ( nancy ) , but on a much larger scale . we believe that the public needs to be proactively informed and protected , including through awareness initiatives among urban residents and , in specific areas ( 15 ) , more direct action toward the parasite may be considered . monitoring the possible further extension of the parasite westward and southward and the evolution of prevalence in foxes in the historically and the newly echinococcosis - endemic areas also are essential .

during 20052010 , we investigated echinococcus multilocularis infection within fox populations in a large area in france . the parasite is much more widely distributed than hitherto thought , spreading west , with a much higher prevalence than previously reported . the parasite also is present in the large conurbation of paris .

prosthetic joint infections ( pji ) are a serious complication associated with total knee replacement ( tka).1 fungal pji is a rare occurrence with few cases reported.123456 phelan et al . reported the first case of candidal pji in 1979.3 candida albicans is the most commonly isolated fungus.3 to the best of our knowledge , this is the first fungal pji reported from india , with candida tropicalis being the causative organism . a 62 year old hypertensive non diabetic female presented with pain , swelling in the left knee and difficulty in walking in the left knee for the last 6 weeks . a 15 cm vertical midline surgical scar healed by primary intention of the initial tka was present on anterior aspect of knee . radiologically , there was osteolysis over the anterior femoral cortex , posterior femoral condyles and under the tibial base plate [ figure 1 ] . complete hematological study and urine microscopy revealed no significant abnormality besides elevated erythrocyte sedimentation rate ( esr ) ( 75 mm at 1 hour ) and c - reactive protein ( crp ) ( 84 mg / l ) . anteroposterior ( a ) and lateral radiographs ( b ) of knee joint showing osteolysis around femoral and tibial components . tka was done 2 years ago knee joint aspiration was carried out under sterile conditions . characteristics of the aspirate were 5 ml fluid , cloudy with low viscosity , white blood cell count was 15,000/cubic mm , with 68% polymorphonuclear leucocytes . gram staining was negative , but 10% koh mount , done to rule out fungal infection as a standard hospital protocol , was positive suggesting a fungal infection . a decision to perform 1 stage of revision tka was taken after consultation with the patient and her family . in consultation with infectious disease specialist there was turbid synovial fluid , granulation tissue , implant loosening and adherent cement synovial fluid and tissue was sent for culture and sensitivity studies . implant removal , debridement and antibiotic ( vancomycin ) plus antifungal ( amphotericin b ) impregnated cement spacer insertion was done [ figure 2 ] . medical therapy included intravenous fluconazole 400 mg od for 6 weeks followed by oral fluconazole 400 mg bd for 12 weeks . sabouraud dextrose agar and the rapid api 20 microtube system were used for identification of species . peroperative clinical photographs showing first stage of revision total knee replacement , after implant ( a ) removal and cement spacer inserted ( b ) anteroposterior radiograph of the knee joint showing cement spacer patient was followed up at weekly intervals and after 20 weeks , the esr ( 23 mm at 1 hour ) and crp ( 6.3 postoperative period was uneventful and patient was discharged on oral fluconazole 400 mg bd for 10 weeks . peroperative clinical photograph showing second stage of revision total knee replacement with final implants the surgical wound healed adequately and after physiotherapy , a painless range of motion of 10 - 90 with a stable knee was obtained . patient maintained status quo until last followup 24 months after 2 stage of revision surgery [ figure 5 ] . anteroposterior ( a ) and lateral ( b ) photographs of knee joint at 24 months followup showing implant in situ fungal pji is known to occur in patients who are immunocompromised , have a underlying systemic illness or prolonged use of antibiotics.12345 despite this almost half the cases occur in patients without any identifiable risk factor.3 our patient had no identifiable risk factor . c.albicans is the most common cause for fungal pji reported in english literature.12345678910 most of the reported cases , do not have systemic fungal disease.4 wu and hsu reported a patient with preoperative cutaneous candidiasis who developed candidal pji.10 no primary source of candidal infection was identified in our case . there is very minimal probability of being implanted during the primary surgery ( the primary tka was over 2 years and symptoms are 6 weeks old ) . late infections probably are hematogenous ; however , a definitive answer can not be given . debridement with successful retention of the implants and suppressive antifungal therapy has been reported.4678 in few initial reports , surgeons performed debridement and resection arthroplasty alone , but this led to poor functional outcomes.3 delayed reimplantation offers the best chance to a successful functional outcome.123 we followed the same principle and performed a two stage revision arthroplasty . one in vitro study on fungal biofilm has shown c.albicans producing quantitatively more biofilm than candida parapsilosis , candida glabrata and c. tropicalis . these films have rapidly developed resistance to fluconazole.11 the optimal time to reimplantation has been debated.3 hwang et al . have performed reimplantation at an average of 9.5 weeks.1 it has been recommended that in cases of pji with unusual or virulent organisms , the period between resection and reimplantation should be prolonged.3 after keeping patient on an extended course of antifungal therapy in consultation with infectious disease specialist , we performed a delayed reimplantation at 20 weeks . we ensured that the esr , crp was normalized ; repeat aspiration was negative prior to reimplantation surgery . amphotericin b is the gold standard , but is nephrotoxic and may not be useful for long term administration.310 fluconazole has demonstrated fewer side effects and can be used long term in patients . successful treatment with fluconazole as the sole antifungal agent has been reported.367 a high bio - availability , extended half - life , absence of serious side effect and high concentration in joint fluid make fluconazole an excellent choice.10 our choice was fluconazole for the above mentioned reasons . we followed the recommendations of infectious disease society of america and gave fluconazole in a combination of parenteral and oral formulation for a total period of 30 weeks [ table 1].123710 the cement spacer was loaded with amphotericin b , based on previous literature , for local action , but we do not have any analysis of the elution rate or the concentration it achieved in the joint . at present , there is no consensus on the type , dose or efficacy of antifungal used in cement spacers.12310 further research is required in this area . to conclude based on our experience and review of literature , we say that fungal pji , though rare , is a serious complication and is more difficult to manage than bacterial pji . resection arthroplasty with antifungal therapy followed by delayed reimplantation offers the best possible result . despite this , further modalities of treatment including options during 1 stage of revision tka , the choice and total duration of antifungal therapy and time of reimplantation should be explored .

fungal prosthetic joint infection after total knee arthroplasty ( tka ) is a rare complication . lacunae exist in the management of this complication . 62 year old lady presented with pain and swelling in left knee and was diagnosed as candida tropicalis fungal infection after tka . she underwent debridement , resection arthroplasty and antifungal plus antibiotic loaded cement spacer insertion , antifungal therapy with fluconazole followed by delayed revision tka and further fluconazole therapy . total duration of fluconazole therapy was 30 weeks . at 2 year followup , she has pain less range of motion of 10-90 and there is no evidence of recurrence of infection .

a 41-year - old male injection drug user was brought to the emergency department unresponsive , febrile and hypotensive . initial investigations revealed a white blood cell count of 19.310/l ; urinalysis , chest x - ray and abdominal computed tomography were all unremarkable . fluid resuscitation , vasopressor support and empirical antibiotic therapy with intravenous ( iv ) piperacillin / tazobactam , vancomycin and clindamycin were initiated . following resuscitation , the patient provided a vague history : he was well until the day of admission , at which time he developed a headache , severe fatigue and generalized malaise . his medical history was significant for hepatitis c and previous episodes of bacteremia related to injection drug use . blood cultures collected on admission grew b cereus ( four of four bottles ) and serratia marcescens . blood cultures were persistently positive for b cereus until day 14 of admission . on day 29 , the patient developed a small antecubital abscess that was drained and cultured b cereus . the patient received a total of six weeks of iv vancomycin and was discharged home . nine days following the admission of case 1 , a 49-year - old man with a history of daily heroin and crystal methamphetamine injection drug use presented to hospital with confusion and agitation . he was afebrile , with no obvious focus of infection on history or physical examination . his medical history was significant for recently diagnosed hiv infection and hepatitis c. initial laboratory results showed a white blood cell count of 13.110/l . blood cultures collected on admission grew b cereus and lactobacillus , and the patient was switched to iv vancomycin and ciprofloxacin . three subsequent blood cultures were positive for b cereus ; blood cultures eventually cleared on day 14 of admission . iv vancomycin was continued for a total duration of eight weeks and the patient was discharged . twenty days after case 1 was admitted to hospital , a 33-year - old man with a history of heroin and cocaine injection drug use presented to the emergency department with confusion . his medical history included hepatitis c and previous episodes of methicillin - resistant staphylococcus aureus infective endocarditis , one of which necessitated a tricuspid valve replacement . the patient left hospital against medical advice , but was called to return the following day when blood cultures returned positive for gram - positive bacilli , subsequently identified as b cereus . repeat blood cultures were drawn and iv vancomycin therapy was initiated . only the initial blood culture ( one of two bottles ) grew b cereus , and all subsequent blood cultures were negative . the patient received a total of two weeks of iv vancomycin and was discharged home . the b cereus isolates from the present cluster of three cases were submitted to the british columbia public health microbiology and reference laboratory for pulsed - field gel electrophoresis ( pfge ) analysis to determine genetic relatedness . pfge was performed for b cereus using smai restriction endonuclease for digestion and based on the parameters described by liu et al ( 5 ) . additionally , the vancouver police department was able to provide five samples of confiscated heroin ( dry powder ) for microbiological analysis . the samples of confiscated heroin were randomly chosen and were not related to the patients who presented to hospital . of the five samples of heroin provided , three grew b cereus from microbiological culture . coagulase - negative staphylococci ( three of five ) and escherichia vulneris ( one of five ) were also recovered in culture . given the preliminary findings from the pfge performed on the clinical isolates of b cereus , the organisms recovered from the heroin samples were not submitted for further genetic analysis . a common source for the cluster was not confirmed . a 41-year - old male injection drug user was brought to the emergency department unresponsive , febrile and hypotensive . initial investigations revealed a white blood cell count of 19.310/l ; urinalysis , chest x - ray and abdominal computed tomography were all unremarkable . fluid resuscitation , vasopressor support and empirical antibiotic therapy with intravenous ( iv ) piperacillin / tazobactam , vancomycin and clindamycin were initiated . following resuscitation , the patient provided a vague history : he was well until the day of admission , at which time he developed a headache , severe fatigue and generalized malaise . his medical history was significant for hepatitis c and previous episodes of bacteremia related to injection drug use . blood cultures collected on admission grew b cereus ( four of four bottles ) and serratia marcescens . blood cultures were persistently positive for b cereus until day 14 of admission . on day 29 , the patient developed a small antecubital abscess that was drained and cultured b cereus . the patient received a total of six weeks of iv vancomycin and was discharged home . nine days following the admission of case 1 , a 49-year - old man with a history of daily heroin and crystal methamphetamine injection drug use presented to hospital with confusion and agitation . he was afebrile , with no obvious focus of infection on history or physical examination . his medical history was significant for recently diagnosed hiv infection and hepatitis c. initial laboratory results showed a white blood cell count of 13.110/l . blood cultures collected on admission grew b cereus and lactobacillus , and the patient was switched to iv vancomycin and ciprofloxacin . three subsequent blood cultures were positive for b cereus ; blood cultures eventually cleared on day 14 of admission . iv vancomycin was continued for a total duration of eight weeks and the patient was discharged . twenty days after case 1 was admitted to hospital , a 33-year - old man with a history of heroin and cocaine injection drug use presented to the emergency department with confusion . his medical history included hepatitis c and previous episodes of methicillin - resistant staphylococcus aureus infective endocarditis , one of which necessitated a tricuspid valve replacement . the patient left hospital against medical advice , but was called to return the following day when blood cultures returned positive for gram - positive bacilli , subsequently identified as b cereus . repeat blood cultures were drawn and iv vancomycin therapy was initiated . only the initial blood culture ( one of two bottles ) grew b cereus , and all subsequent blood cultures were negative . the patient received a total of two weeks of iv vancomycin and was discharged home . the b cereus isolates from the present cluster of three cases were submitted to the british columbia public health microbiology and reference laboratory for pulsed - field gel electrophoresis ( pfge ) analysis to determine genetic relatedness . pfge was performed for b cereus using smai restriction endonuclease for digestion and based on the parameters described by liu et al ( 5 ) . additionally , the vancouver police department was able to provide five samples of confiscated heroin ( dry powder ) for microbiological analysis . the samples of confiscated heroin were randomly chosen and were not related to the patients who presented to hospital . of the five samples of heroin provided , three grew b cereus from microbiological culture . coagulase - negative staphylococci ( three of five ) and escherichia vulneris ( one of five ) were also recovered in culture . given the preliminary findings from the pfge performed on the clinical isolates of b cereus , the organisms recovered from the heroin samples were not submitted for further genetic analysis . a common source for the cluster was not confirmed . b cereus has been reported as a cause of extraintestinal infections , including those of the musculoskeletal , ocular , respiratory , cardiovascular and central nervous systems ( 6 ) . injection drug use is often attributed as an etiological factor , with reports of cellulitis ( 4 ) , endophthalmitis and panophthalmitis ( 3,7,8 ) , and endocarditis ( 1,6,9,10 ) . the prognosis of bacteremia and native valve endocarditis with b cereus is typically good , with prompt antibiotic therapy of adequate duration being suitable for recovery ( 2 ) . conversely , high morbidity and mortality have been observed with prosthetic valve endocarditis , and authors of a review on the subject recommend prompt valve replacement in conjunction with iv antibiotics ( 11 ) . no guidelines exist for treatment of invasive b cereus infections , and reports in the literature describe clinical recovery with two to four weeks of iv antibiotics for bacteremia , and four to six weeks for endocarditis ( 2 ) . published susceptibility reports describe complete susceptibility of b cereus to vancomycin , quinolones , gentamicin , carbapenems and tigecycline ; intermediate susceptibility to clindamycin , tetracycline and erythromycin ; and high - level resistance to trimethoprim / sulfamethoxazole , penicillins and cephalosporins ( 12 ) . in the present study , case 1 was treated with a prolonged six - week course of iv vancomycin for b cereus bacteremia because of persistently positive blood cultures for the first 14 days . case 2 was treated for mitral valve endocarditis with an eight - week course of iv vancomycin and his blood cultures cleared over a two - week period . although case 3 had a prosthetic tricuspid valve , there was no evidence of endocarditis and only a single initial positive blood culture . he received a two - week course of iv vancomycin , despite the possibility that this was a culture contaminant . all patients in the cluster shared the risk factor of injection drug use , having recently injected heroin . b cereus infections have been sporadically associated with injection drug use , particularly with heroin . these rare occurrences were first reported ( 9 ) and reviewed ( 1 ) in the 1970s . b cereus , a known contaminant related to drug use , is resistant to heat and capable of surviving in harsh environments . a report from 1983 conducted in washington , dc , found that nearly one - half of injection paraphernalia and 32% of heroin samples were contaminated with bacillus species ( 13 ) the microbial burden was significantly higher on the injection paraphernalia than the heroin itself , and brown heroin ( mainly from mexico ) was found to have a higher burden compared with white heroin ( mainly from overseas ) . the authors speculated that heroin users experience frequent transient episodes of bacillus species bacteremia , which are rarely of clinical significance . in the literature , one case exists with a largely conclusive link of a b cereus infection to contaminated heroin ( 4 ) . a patient with cellulitis provided a heroin sample , and both his wound aspirate and heroin cultured b cereus , which was found to be indistinguishable through pfge . in our cluster possible explanations for our cluster not having a common source include increasing microbial burden of heroin in general , supported by the burden found on the randomly acquired heroin or , particularly , contaminated injection paraphernalia among users . b cereus infections are an underappreciated cause of bloodstream infections in injection drug users , for which the treatment requires prompt identification and antibiotic coverage . our observation of three unrelated but temporally associated cases of b cereus infection in heroin users suggests that suspicion of b cereus infection in this patient population may become increasingly warranted .

bacillus cereus is a bacteria commonly found in nature that is most frequently implicated as the cause of gastrointestinal illness caused by ingestion of contaminated food ; however , there are also reports of extraintestinal infections , although rare . this article describes three cases in which b cereus bacteremia occurred among injection drug users living in vancouver , british columbia , within a short period of time . pulsed - field gel electrophoresis was performed to determine whether these three isolates were related .

cyanotic congenital heart disease is still a common occurrence and many patients with uncorrected cardiac lesions present for various non - cardiac surgery . this case report is aimed at presenting a case of labor epidural analgesia and subsequently epidural anaesthesia in a patient with uncorrected pentalogy of fallot . a 22-year - old primigravida was admitted to the labour ward with history of 8-months amenorrhoea . she was known to have cyanotic congenital heart disease since childhood , and was not on any regular medications or follow - up . she also gave a history of palpitations , giddiness and blurring of vision , which improved over the course of pregnancy . echocardiogram [ figure 1 ] at the 4 month revealed pentology of fallot ( pof ) and hence she was advised therapeutic termination of pregnancy , for which she had refused . echocardiography image of the patient with pentology of fallot showing atrial and ventricular septal defect on pre - anesthetic check up , grade ii clubbing and peripheral cyanosis were present . electrocardiogram ( ecg ) showed normal sinus rhythm , right axis deviation and right bundle branch block . echocardiography revealed malpositioned great vessels , double - outlet right ventricle with severe pulmonary stenosis , large subaortic ventricular septal defect with significant overriding of aorta , moderate - sized atrial septal defect with left arterial blood gas showed ph 7.38 , pao2 48 mmhg , paco2 34 mmhg and sao2 of 84% . as the patient was getting frequent painful contractions that were associated with tachycardia , the obstetricians requested for labour analgesia . with a strict aseptic technique , in sitting posture at l3/4 interspace , 25 g fentanyl was injected intrathecally using a 25 g bevel cut spinal needle . this was followed by placement of an 18 g epidural catheter at the l2/3 interspace . the patient had excellent pain relief immediately , with a visual analogue score of 0 . continuous electrocardiography ( ecg ) , pulse oximetry and non - invasive blood pressure monitoring were performed during the labour . labour progressed normally with an outlet forceps - assisted vaginal delivery of a healthy male baby within 2 h. apgar at birth was 8/10 and 10/10 after 5 min . five hours following delivery , the patient started complaining of severe pain at the episiotomy site . examination revealed a huge vulval haematoma that required immediate drainage . in the operating theatre , under full cardiac monitoring , epidural analgesia was provided with 10 ml of 0.125% bupivcaine and 50 g of fentanyl . the patient was haemodynamically stable , with the oxygen saturation between 80 and 85% throughout the surgical procedure . the rest of the post - partum period was uneventful and the patient was discharged on the 7 day of admission to the hospital . tetralogy of fallot ( tof ) is the most common cyanotic congenital heart defect seen in around 56% of congenital heart malformations . it is characterized by anterior and superior infundibular septal displacement , ventricular septal defect , aortic override , infundibular obstruction and right ventricular hypertrophy . when the tof is associated with atrial septal defect , it is commonly referred to as pof . there is an association between tof and chromosomal defects seen in 15% of the population , with the possibility of genetic transmission to the offsprings . there is fall in systemic vascular resistance ( svr ) , increase in blood volume and increase in cardiac output secondary to increased heart rate and stroke volume , and a physiological left ventricular hypertrophy . the pathophysiology of tof depends on the level of right ventricular outflow obstruction . when the obstruction is mild , the patients present with increased pulmonary blood flow ( acyanotic fallot or rose tetrology ) . acyanotic fallot is more commonly seen in adults , while children present with significant right ventricular outflow obstruction , right left shunt and cyanosis . maternal cyanotic cardiac lesions lead to an impaired uteroplacental perfusion and diminished foetal oxygenation , leading to a higher incidence of miscarriages , premature births and low birth weight babies . anaesthetic management for patients with cyanotic heart disease requires a thorough understanding of the pathophysiology , events and medications , which alters the magnitude of the right - to - left intracardiac shunt . decreased svr , increased pulmonary vascular resistance and increased myocardial contractility increase the magnitude of the right - to - left shunt . the choice of anaeshetic technique is crucial in the management of patients with cyanotic heart disease . sympathetic blockade seen in regional techniques may increase shunt by decreasing svr , leading to decreased ventricular filling and cardiac output . pharmacological agents that decrease svr increase the magnitude of the right - to - left shunt and accentuate arterial hypoxemia . also , intermittent positive pressure ventilation and positive end expiratory pressure cause increases in pulmonary vascular resistance and decrease pulmonary blood flow . providing adequate analgesia , maintenance of uterine placental perfusion , preventing aortocaval compression and minimization of sympathetic block by maintaining intravascular volume are the goals of anaesthetic management . in cyanotic congenital heart diseases ( tof , pof ) , administration of labour analgesia during early labour is advisable to limit increases in pulmonary vascular resistance and consequent right - to - left shunting . small incremental doses of local anaesthetic drugs with opioids are preferred over large bolus doses to avoid abrupt reduction in svr , which may cause reversal of shunt flow and hypoxemia . intravenous fluids should be carefully monitored to prevent deficits or excesses , leading to shunt worsening and patient 's decompensation . adequate pain relief with minor haemodynamic changes should be aimed when regional anaesthesia is considered . shrivastava et al . reported administration of epidural block to a patient with uncorrected tof for caesarean section . mendes et al . described a case where labour analgesia was administered in uncorrected tof that was diagnosed during gestation . as an institutional practice , we employ combined spinal epidural labour analgesia , which is an effective and safe technique . it allows the use of subarachnoid opioids , such as fentanyl or sufentanil , leading to faster analgesic effect , lower sympathetic and motor block . placing an epidural catheter allows administration of low concentration of local anaesthetic with minimal haemodynamic changes . the pathophysiology and the haemodynamic derangements of pof are more or less similar to tof , eventually depending on the magnitude of shunt . the anaesthetic management of patients with pof is not commonly reported in the literature owing to the rarity of occurrence . recent advances in cardiac interventions and surgery have enabled more number of women with congenital heart disease to thrive well into their childbearing years . although pregnant women with congenital heart disease are rarely reported around the world , a thorough understanding of the pathophysiology and anaesthetic management of these patients is essential . the choice of anaesthesia in these patients requires thorough understanding of problems , careful titration of drugs and maintaining haemodynamic stability . our patient with pof was managed with labour analgesia and subsequently epidural anaesthesia for drainage of vulval haematoma with successful outcome .

tetraology of fallot is the most common congenital heart disease causing intracardiac right - left shunts . it is characterized by presence of ventricular septal defect , aortic overriding , pulmonary artery outflow obstruction and right ventricular hypertrophy . when these features are associated with atrial septal defect , it is often referred to as pentology of fallot ( pof ) . if the lesions remain uncorrected , they can cause significant morbidity and mortality to the patient . pregnancy and labour in such a patient present with significant haemodynamic changes , which can be challenging to the anaesthesiologist . our patient with pof was managed with labour analgesia and subsequently epidural anaesthesia for drainage of vulval haematoma with successful outcome .

dynamic factors have a significant role in causing cervical spondylotic myelopathy ( csm ) . in patients with cervical ossification of the posterior longitudinal ligament ( c - opll ) , mild symptoms of myelopathy the pathomechanism of cervical myelopathy caused by c - opll remains unknown . despite spinal stenosis ( 6 mm < space available for the spinal cord < 14 mm ) , myelopathy may not develop in patients with severe range limitations of the cervical spine . this possibility indicates that not only static factors but also dynamic factors , such as listhesis or hypermobility at the discontinuity of the ossified lesion , have important roles in the development of myelopathy , especially in mixed and segmental oplls . multidetector - row computed tomography ( mdct ) has given a better understanding of spinal ligament ossification . unlike the tsuyama classification based on lateral radiographs , ossification morphology and bone continuity between each vertebrae are shown more clearly by mdct . previously , we reported that ossification morphology at each disc segment was divided into 3 groups : the connection department , coating part , and non - connection department of opll . we previously used mdct to measure spinal cord cross - sectional areas ( sccsas ) during flexion and extension . in that report it is the possible that myelopathy is aggravated by dynamic factors , even in the connection department of opll . however , we did not investigate the sagittal range of motion ( rom ) and ossification of the anterior longitudinal ligaments . previously , we reported that the incidence of spinal cord injury in the stoppage department of ossification was 64% the purpose of this study was to measure rom by mdct , to investigate the influence of dynamic factors on the spinal cord of patients with c - opll . and the roms of adjacent intervertebral disc in connected vertebrae and those of others were investigated for each morphology . from january 2006 to august 2010 , a total , of 110 patients ( 80 men and 30 women ) with c - opll were enrolled in this study . in addition , 99 patients ( 64 men and 35 women ) who had lumbar disc herniation determined by mdct were defined as normal controls . patients with opll , fused vertebrae , and spinal instability were excluded from this normal control . the aims of this study were explained to all patients before myelography and ct scanning , and all patients gave informed consent to their participation . preoperative ct scans after myelography were performed in all subjects in maximum neck flexion and extension . ct scans were obtained ( 1-mm - thick axial helical ) with sagittal and coronal reconstruction using 64-line , multi - slice unit ( light speed vct ; ge healthcare bio - sciences , piscataway , nj , usa ) . the rom at each disc level between c2/3 and c7/t1 in sagittal view was measured using synapse enterprise - pacs ( fujifilm medical co. , ltd . , ossification morphology at each disc segment was divided into 6 groups : covered disc , covered vertebra , unconnected vertebra , connected vertebra ( continuous ) , connected vertebra ( localized ) , and others ( fig . the covered disc group was defined as comprising either cranial or caudal vertebra connected by ossification , with the other intervertebral disc not completely covered by ossification . the covered vertebra group was defined as comprising either cranial or caudal vertebra connected by ossification , with the other intervertebral disc completely covered by ossification . the unconnected vertebra group was defined as coprising either cranial or caudal vertebra connected by ossification , with ossification completely covering the vertebra , including other cranial and caudal intervertebral discs or vertebrae . the connected vertebra ( continuous ) group was defined as comprising both cranial and caudal vertebrae connected by ossification , of the continuous type according to the tsuyama classification . in addition , the connected vertebra ( localized ) group was defined as comprising both cranial and caudal vertebrae connected by ossification , that was the localized type according to the tsuyama classification . the others group was defined as vertebrae with osteophytes , disc ossification , or no problematic features . the ossification morphology was defined at the biggest and longest place in much mdct slice . ossification morphology at each disc segment was divided into 6 groups : covered disc , covered vertebra , unconnected vertebra , connected vertebra ( continuous ) , connected vertebra ( localized ) , and others . in addition , the roms of adjacent intervertebral disc in connected vertebrae ( continuous and localized ) and those of others were investigated for each group . roms during neck flexion and extension were measured once on two different days by a spinal surgeon , and average values were adopted . the stat view 5.0 software ( abacus , berkeley , ca ) analysis of variance with a post hoc test ( kruskal -wallis test ) was used to perform comparisons between the groups . a p - value < 0.05 was considered to be statistically significant . the rom of the patients with c - opll was significantly smaller than that of the normal controls . there were 122 disc levels in the covered disc group , 114 disc levels in the covered vertebra group , 12 disc levels in the unconnected vertebra group , 40 disc levels in the connected vertebra ( continuous ) group , 20 disc levels in the connected vertebra ( localized ) group , and 340 disc levels in the others group ( fig . 2 ) . number of intervertebral disc according to each classification the average roms were 6.4 4.6 in the covered disc group , 4.8 4.3 in the covered vertebra group , 4.8 3.8 in the unconnected vertebra group , 2.9 2.3 in the connected vertebra ( continuous ) group , 2.8 2.4 in the connected vertebra ( localized ) group , 6.0 4.3 in the others group , and 8.1 4.2 in the normal control . the average rom of the covered disc group was significantly higher than that of the connected vertebra ( continuous ) group and connected vertebra ( localized ) group . in addition , the average rom of the normal control was significantly higher than those of the covered disc group , covered vertebra group , connected vertebra ( continuous ) , and connected vertebra ( localized ) groups . the average rom of the connected vertebra ( continuous ) group was significantly lower than those of the covered disc group , others group , and normal control group ( fig . the average rom according to each classification the average roms of the roms of adjacent intervertebral disc in connected vertebrae ( continuous and localized ) and those of others were investigated for each group shown in table 2 and fig . 4 , were 5.9 4.8 and , 6.5 4.6 in the covered disc group , 5.5 4.3 and , 4.5 4.3 in the covered vertebra group , 3.8 1.7 and , 5.3 4.5 in the unconnected vertebra group , 2.9 2.5 and , 2.9 2.2 in the connected vertebra ( continuous ) group , 3.0 2.5 and , 2.5 2.3 in the connected vertebra ( localized ) group , and 4.8 4.7 and , 6.0 4.3 in the others group , respectively . there were no significant differences between the adjacent intervertebral disc in connected vertebrae and others . the average rom of adjacent connected vertebra ( continuous and localized ) and that of except adjacent connected vertebra ( continuous and localized ) the tsuyama classification is the most widely used criteria for classifying c - opll . on the basis of lateral radiographs alone , c - opll can be roughly classified into 4 types : ( 1 ) continuous type , which is a continuous ossified mass extending over several vertebrae ; ( 2 ) segmental type , which is a segmental ossification behind each vertebral body ; ( 3 ) mixed type , which is a mixture of these 2 types ; and ( 4 ) localized type , which includes other types , ( e.g. , circumscribed ossification of the ligament corresponding to the level of the intervertebral disc ) . in addition , mdct has enabled better understanding of ossification of spinal ligaments than provided by lateral radiographs , because the ossification morphology and bone continuity between each vertebrae have become clear . previously , we had described ossification morphology at each disc segment that had been divided into 3 groups : the connection department , coating part , and non - connection department of opll . we had used mdct to measure sccsa during flexion and extension , and sccsa did not show statistically significant differences in ossification morphology . it is possible that myelopathy is aggravated by dynamic factors , even in the connection department of opll . therefore , we reclassified these groups more finely , and examined rom at each segment using a new classification . ossification morphology at each disc segment was divided into 6 groups : covered disc , covered vertebra , unconnected vertebra , connected vertebra ( continuous ) , connected vertebra ( localized ) , and others . the average rom in the covered vertebra group was quite similar to that in the unconnected vertebra group . the average rom in the connected vertebra ( continuous ) was quite similar to that in the connected vertebra ( localized ) group . we used the former classification to classify the covered vertebra group and unconnected vertebra group as the coating part . similarly , we had classified the connected vertebra ( continuous ) group and connected vertebra ( localized ) group as the connection department . it is not necessary to each distribute , re - classification that we increase cases is desirable . the influence of dynamic factors on the cervical spine has been investigated by flexion extension magnetic resonance imaging ( mri ) . matsunaga et al . showed that in patients with c - opll , involvement of not only chronic pathological compressive factors caused by opll but also of circulatory and dynamic factors were thought to be important in the development and aggravation of myelopathy . morio et al.suggested that important factors in the onset or aggravation of myelopathy are related to pathological compression by opll , cervical soft disc herniation , a developmentally narrow spinal canal , and a local or non - proportional hypermobility . previously , we reported that sccsa by mdct was measured to elucidate the influence of dynamic factors . there were no significant differences in the dynamic changes of sccsa between the connection department , coating part , and non - connection department of opll . it has also been suggested that the influence of dynamic factors is less in patients with mature continuous opll . acute spinal cord injury associated with c - opll can be induced by minor cervical trauma , and there is often radiographic evidence of trauma , termed cervical spinal cord injuries without radiographic evidence of trauma ( sciworet ) . described the pathogenesis of central cord injury in the cervical spine as the result of a hyperextension mechanism , with subsequent compression of bony spur , a herniated disc , or a buckled ligamentum flavum . onishi et al . reported that sciworet with c - opll occurred at the edge of opll or oall . previously , we reported that the incidence of spinal cord injury in the stoppage department of ossification was 64% there were no significant differences between the adjacent intervertebral disc in connected vertebrae and others for each group , but the average rom of the connected vertebra ( continuous and localized ) group was significantly lower than that of the covered disc group and normal control group . dynamic factors were reduced at the continuous segment : therefore , frequency of sciworet at the continuous segment may be less likely to happen from other segments . the limitations of this study were that the examination of the spinal cord changes relied on mri signal intensities . second , it will be necessary to examine the differences between rom based on mdct and rom based on x - ray . we should closely observe the natural course of patients with c - opll from dynamic factors even in patients with mature c - opll , and it will be necessary to consider sciworet with respect to dynamic factors . this study was performed to measure rom in patients with c - opll by mdct , and to investigate the influence of dynamic factors on the spinal cord . and rom of adjacent intervertebral disc in connected vertebrae ( continuous and localized ) and those of others were investigated for each group . ossification morphology at each disc segment was divided into 6 groups : covered disc , covered vertebra , unconnected vertebra , connected vertebra ( continuous ) , connected vertebra ( localized ) , and others . the average rom of covered disc group was significantly higher than that of connected vertebra ( continuous , localized ) . the average rom of connected vertebra ( continuous ) group was significantly lower than that of covered disc group , others group , and normal control . there was no significant difference between rom of adjacent intervertebral disc in connected vertebrae and others , but the average rom of the connected vertebra group was significantly lower than that of the covered disc group and normal control group . dynamic factor was reduced at continuous segment , but it was not increased in adjacent intervertebral disc . each author certifies that they had no commercial associations ( e.g. , consultancies , stock ownership , equity interest / licensing arrangement , etc . ) that might pose a conflict of interest in connection with the submitted article .

abstractthe purpose of this study was to measure range of motion ( rom ) in patients with cervical ossification of posterior longitudinal ligament ( c - opll ) by multidetector - row computed tomography ( mdct ) , and to investigate the influence of dynamic factors . the study included 101 patients with c - opll and 99 normal control patients . preoperative mdct were taken in all subjects in maximum neck flexion and extension . rom at each disc level between c2/3 and c7/t1 in sagittal view was measured . ossification morphology at each disc segment was divided into 6 groups : covered disc , covered vertebra , unconnected vertebra , connected vertebra ( continuous ) , connected vertebra ( localized ) , and others . the relationship between rom and the group of ossification morphology was also investigated . rom of adjacent intervertebral disc in connected vertebrae ( continuous and localized ) and those of others were investigated for each group . the average rom of covered disc group was significantly higher than that of connected vertebra ( continuous , localized ) . the average rom of connected vertebra ( continuous ) group was significantly lower than that of covered disc group , others group , and normal control . there was no significant difference between rom of adjacent intervertebral disc in connected vertebrae and others , but the average rom of the connected vertebra group was significantly lower than that of the covered disc group and normal control group . dynamic factor was reduced at continuous segment , but it was not increased in adjacent intervertebral disc .

mutism is defined as an inability or unwillingness to speak , resulting in the absence or marked paucity of verbal output . it is a common presenting symptom seen in various disorders , including psychiatric as well as medical disorders . though , it often is the main focus of clinical attention , both for the patients and the treating physicians , it rarely presents as an isolated disability and often occurs in association with other disturbances in behavior , thought processes , affect , or level of consciousness . despite its association with a variety of neuropsychiatric disorders , mutism has received relatively little attention in the psychiatric literature . mutism occurs in a number of conditions , both functional and organic , and a proper diagnosis is important for the management . we hereby present three cases , who presented with mutism as the presenting symptom and the differential diagnosis and management issues related to these cases are discussed . the literature on mutism , including psychiatric , neurologic , toxic - metabolic , and drug - induced causes , is also selectively reviewed . a 26-year - old unmarried male educated upto high school presented with abrupt onset progressive complaints of not speaking at all and decreased oral intake for the past 2 days . this was also associated with anxiety symptoms and hiccups that would occur in episodes for hours together . there was no other significant history suggestive of any organicity or psychosis , mood disorder , or any history of substance use . the patient had past history of an episode of acute stress reaction with mutism around 7 years back when he witnessed murder of his friend . also , he would have episodes of mutism in between lasting few hours to 1 day around three to four times in the last 3 years . positive findings in the mental status examination ( mse ) were that the patient was following commands given to him , he would respond in non - verbal manner or by writing , his eyes were open and movements were normal , he would cough and clear throat when asked to do so , would have hiccups ( around 20 times in interview of around 30 min ) , and his psychomotor activity ( pma ) was decreased . a diagnosis of dissociative ( conversion ) disorder - motor type was made and the patient was started on sertraline 50 mg per day along with chlorpromazine 100 mg per day . he was engaged in supportive psychotherapy and suggestion under pentothal was given and patient showed improvement in symptoms . he was subsequently discharged and had been maintaining well for the past 9 months of follow up . a 29-year - old unmarried male was brought by police personnel with acute onset complaints of not speaking for 9 and a half months and history of irrelevant talks for 2 weeks associated with inability to speak in between . the patient had been under trial for the last 3 years for alleged charge of rape and murder . he would ask for his daily requirements by gestures / writing down . he would however maintain his routine daily chores and his vegetative functions were maintained . mse revealed a young male with little speech output and occasional irrelevant talks in between . on formal questioning , he reported sadness of mood but did not reply to other questions asked . a provisional diagnosis of depressive stupor versus dissociative stupor was kept and started on imipramine 50 - 125 mg per day along with risperidone 2 mg per day and lorazepam 1.5 mg per day in divided doses . lorazepam 4 mg was given on stat basis , with no improvement in his symptoms . he would speak out of the context and would start quarreling with jail inmates for no apparent reason . history from patient 's father was also taken and no pervious history of psychiatric illness or substance use other than tobacco was obtained . , it was observed that the patient had rashes present on dorsum of left hand . mse revealed that eye contact could be established but not maintained , decreased pma , his speech was decreased in output but was clear and comprehensible , his mood was sad but affect appeared euthymic with full range as shown by facial expressions . he would also on occasions give approximate answers to various questions asked ( e.g. date : said 10th instead of 9th , month : said december instead of november , ) . though , he would talk irrelevantly and would give wrong / approximate answers when talked too . information from collateral sources revealed that he was told to behave in this manner to plead his case . skin opinion was taken and a diagnosis of factitious dermatitis was made which further supported our diagnosis . a 35-year - old married male was brought by police personnel with chief complaints of not speaking for the last 3 months . the patient had been under trial for the last 6 months for the alleged charge of setting fire in a cowshed . he would however ask for food by non - verbal communication / gestures and would perform all his daily chores normally as reported . history reviewed from wife and elder brother reveled history of 18 years history characterized by violent abusive behavior , wandering behavior , irritability , decreased sleep , restlessness , muttering to self , and at times reporting that other would harm him , associated with withdrawn behavior and socio - occupational dysfunction . on one occasion , he became mute also and did not talk for a period of around 4 months associated with sadness of mood and decreased interest in surroundings . 6 months back , he had symptoms of muttering to self , would often roam about naked and get irritable on minor issues . mse revealed decreased pma , rapport not established , eye to eye contact could not be maintained , he was mute and would communicate nonverbally appropriately . a diagnosis of schizophrenia was entertained , and he was started on risperidone 6 mg per day and lorazepam 4 mg per day . a 26-year - old unmarried male educated upto high school presented with abrupt onset progressive complaints of not speaking at all and decreased oral intake for the past 2 days . this was also associated with anxiety symptoms and hiccups that would occur in episodes for hours together . there was no other significant history suggestive of any organicity or psychosis , mood disorder , or any history of substance use . the patient had past history of an episode of acute stress reaction with mutism around 7 years back when he witnessed murder of his friend . also , he would have episodes of mutism in between lasting few hours to 1 day around three to four times in the last 3 years . positive findings in the mental status examination ( mse ) were that the patient was following commands given to him , he would respond in non - verbal manner or by writing , his eyes were open and movements were normal , he would cough and clear throat when asked to do so , would have hiccups ( around 20 times in interview of around 30 min ) , and his psychomotor activity ( pma ) was decreased . a diagnosis of dissociative ( conversion ) disorder - motor type was made and the patient was started on sertraline 50 mg per day along with chlorpromazine 100 mg per day . he was engaged in supportive psychotherapy and suggestion under pentothal was given and patient showed improvement in symptoms . he was subsequently discharged and had been maintaining well for the past 9 months of follow up . a 29-year - old unmarried male was brought by police personnel with acute onset complaints of not speaking for 9 and a half months and history of irrelevant talks for 2 weeks associated with inability to speak in between . the patient had been under trial for the last 3 years for alleged charge of rape and murder . he would ask for his daily requirements by gestures / writing down . he would however maintain his routine daily chores and his vegetative functions were maintained . mse revealed a young male with little speech output and occasional irrelevant talks in between . on formal questioning , he reported sadness of mood but did not reply to other questions asked . a provisional diagnosis of depressive stupor versus dissociative stupor was kept and started on imipramine 50 - 125 mg per day along with risperidone 2 mg per day and lorazepam 1.5 mg per day in divided doses . lorazepam 4 mg was given on stat basis , with no improvement in his symptoms . cat scan head plain and contrast was also normal . on evaluation , he would follow simple commands and was able to write properly on persuasion he would speak out of the context and would start quarreling with jail inmates for no apparent reason . history from patient 's father was also taken and no pervious history of psychiatric illness or substance use other than tobacco was obtained . , it was observed that the patient had rashes present on dorsum of left hand . mse revealed that eye contact could be established but not maintained , decreased pma , his speech was decreased in output but was clear and comprehensible , his mood was sad but affect appeared euthymic with full range as shown by facial expressions . he would also on occasions give approximate answers to various questions asked ( e.g. date : said 10th instead of 9th , month : said december instead of november , ) . though , he would talk irrelevantly and would give wrong / approximate answers when talked too . information from collateral sources revealed that he was told to behave in this manner to plead his case . skin opinion was taken and a diagnosis of factitious dermatitis was made which further supported our diagnosis . a 35-year - old married male was brought by police personnel with chief complaints of not speaking for the last 3 months . the patient had been under trial for the last 6 months for the alleged charge of setting fire in a cowshed . he would however ask for food by non - verbal communication / gestures and would perform all his daily chores normally as reported . history reviewed from wife and elder brother reveled history of 18 years history characterized by violent abusive behavior , wandering behavior , irritability , decreased sleep , restlessness , muttering to self , and at times reporting that other would harm him , associated with withdrawn behavior and socio - occupational dysfunction . on one occasion , he became mute also and did not talk for a period of around 4 months associated with sadness of mood and decreased interest in surroundings . 6 months back , he had symptoms of muttering to self , would often roam about naked and get irritable on minor issues . mse revealed decreased pma , rapport not established , eye to eye contact could not be maintained , he was mute and would communicate nonverbally appropriately . a diagnosis of schizophrenia was entertained , and he was started on risperidone 6 mg per day and lorazepam 4 mg per day . gradually the patient started showing improvement in symptoms . some of these besides mutism are as follows : aphonia : defined as the absence of definable laryngeal tone i.e. loss power of vocal chords to adduct.aphasia : this is a disorder of the content of speech , seen generally in organic conditions and occasionally as gargon aphasia in schizophreniadysarthria : a motor speech disorder characterized by difficulty in articulation of speech . any of the speech subsystems ( respiration , phonation , resonance , prosody , articulation and movements of jaw and tongue ) can be affected . aphonia : defined as the absence of definable laryngeal tone i.e. loss power of vocal chords to adduct . aphasia : this is a disorder of the content of speech , seen generally in organic conditions and occasionally as gargon aphasia in schizophrenia dysarthria : a motor speech disorder characterized by difficulty in articulation of speech . any of the speech subsystems ( respiration , phonation , resonance , prosody , articulation and movements of jaw and tongue ) can be affected . one important aspect in case b was that one should keep a possibility of malingering in such group of patients . though case c was also brought by police personnel and was under trial , he had past history of psychotic illness and also his crime was not that serious / grave as compared to case b. the points favoring our diagnosis in respective cases have been summarized in table 1 . besides psychiatric causes , there are other many causes of mutism . differential diagnosis of mutism regarding the frequency of various causes of mutism , besides case reports describing mute patients , there are few studies that report a series of patients presenting with mutism and describing various diagnostic categories . some of these studies are summarized in table 3 . one must perform a thorough physical and systemic examination to rule out organic causes for mutism . also , at times , observation for some time period may be warranted and should be done to reach final diagnosis . the utility of pentothal interview in some cases can be therapeutic also as in our case a. besides being a useful tool to differentiate organic from functional conditions , it can be used to give suggestions and thus help in the immediate management of dissociative disorders . to conclude , it is important to recognize the correct cause for proper management of mutism . though our cases had psychiatric cause for mutism , one must have a high index of suspicion and look for various other non - psychiatric causes for mutism , as this will decide the management and prognosis of the patient .

mutism , defined as an inability or unwillingness to speak , resulting in an absence or marked paucity of verbal output , is a common clinical symptom seen in psychiatric as well as neurology outpatient department . it rarely presents as an isolated disability and often occurs in association with other disturbances in behavior , thought processes , affect , or level of consciousness . it is often a focus of clinical attention , both for the physician and the relatives . mutism occurs in a number of conditions , both functional and organic , and a proper diagnosis is important for the management . we hereby present three cases , who presented with mutism as the presenting symptom and the differential diagnosis and management issues related to these cases are discussed . the authors also selectively reviewed the literature on mutism , including psychiatric , neurologic , toxic - metabolic , and drug - induced causes .

it has speedily replaced cervical cancer as the most common cancer among indian women . according to figures from the national cancer registry , one in every 25 indian women is likely to suffer from breast cancer at some point of time . fine needle aspiration ( fna ) cytology has become widely accepted as a reliable diagnostic tool for diagnosing breast masses . it is a simple , quick , safe , less invasive , and less expensive method with high sensitivity and specificity . the diagnostic categories used in fna cytology of the breast masses are inadequate ( c1 ) , benign ( c2 ) , atypical , probably benign ( c3 ) , suspicious of malignancy ( c4 ) , and malignant ( c5 ) according to the national cancer institute ( nci ) guidelines in 1996 . however , howell , and kanhoush et al . suggested the use of a single term , such as equivocal , to describe inconclusive ( c3 & c4 ) diagnoses on breast fna cytology . very few studies are available in the english literature analyzing histopathology outcome of c3 ( atypical lesion ) and c4 ( suspicious lesion ) lesions . our study aims to correlate fine needle aspiration ( fna ) cytology of breast lump diagnosed as c3 and c4 lesions with histopathological examination . this retrospective study was done at the department of pathology of our institute for a period of two years , from september 2010 to august 2012 . fnas were done by a pathologist with all aseptic precautions using 20 ml syringe and 23 g needle . the needle was placed within the lesion , and a vacuum was applied by gently withdrawing the plunges of the syringe . the needle was moved back and forth within the lesion , and negative pressure was released prior to withdrawing the needle . samples were smeared onto glass slides and stained with may - grunwald - giemsa ( mgg ) after being air dried . cases diagnosed as atypical , probably benign ( c3 ) , and suspicious of malignancy ( c4 ) were selected for further study . fna findings of studied smears were then compared with corresponding histopathology findings , obtained with core needle biopsy , excisional biopsy , or mastectomy specimens . based on these findings , sensitivity , specificity , positive predictive values , and negative predictive value of c4 category in diagnosing breast malignancy were calculated . diagnostic value of cytological diagnosis was assessed by comparing the percentage of benign or malignant histological diagnosis in categories c3 and c4 using chi- square test of significance after yates correction . during the study period , a total of 1093 fna cytology of breast lumps were done , out of which 86 ( 7.8% ) had inadequate ( c1 ) smears . out of 1007 satisfactory fna smears , 85 ( 8.43% ) were classified in category c3 ( n = 59 , 5.85% ) and category c4 ( n = 26 , 2.58% ) . of these , 24 cases of c3 category ( 40.67% ) and 16 cases of c4 category ( 61.53% ) had available histologic follow - up data and were included in the study . among the c3 category , 9 ( 37.5% ) of c3 cases revealed malignant findings , and 15 ( 62.5% ) of c3 cases revealed benign findings on histologic evaluation ( table 1 ) . infiltrating ductal carcinoma ( n = 8) was the most common malignant diagnosis , followed by infiltrating lobular carcinoma ( n = 1 ) . the commonest benign lesion in c3 category was fibroadenoma ( n = 8) , fibrocystic change with atypia ( n = 4 ) , and fibrocystic change without atypia ( n = 3 ) ( table 2 ) . among the c4 category , 14 ( 87.5% ) cases revealed malignant findings , and 2 ( 12.5% ) cases revealed benign findings on final histopathologic analysis ( table 1 ) . the common benign lesions in category c4 were fibrocystic change with or without atypia ( table 2 ) . the difference proportion of malignant cases between categories c3 ( 37.5% ) and c4 ( 87.5% ) was statistically significant ( p = 0.005 ) . sensitivity , specificity , positive predictive values , and negative predictive value of c4 category in diagnosing breast malignancy were 60.8% , 88.2% , 87.5% , and 62.5% , respectively . the fine needle aspiration cytology ( fnac ) has achieved great importance in diagnosis and management of palpable breast lesions . due to simplicity , safety , and diagnostic accuracy , this procedure has become a widely used adjuvant diagnostic technique in management of breast lumps [ 46 ] . the national cancer institute recommends five categories for diagnosis of breast aspiration cytology in order to bring a degree of uniformity to the diagnostic reporting . these categories are unsatisfactory ( c1 ) , benign lesion ( c2 ) , atypical , probably benign ( c3 ) , suspicious , probably malignant ( c4 ) , and malignant ( c5 ) . however , some authors believe that c3 and c4 should be categorized in the same category [ 2 , 3 ] . in order to investigate this hypothesis further , we reviewed our fna cases in c3 and c4 and correlated with available histopathological findings to determine the accuracy of c3 and c4 categories . our study had 86 ( 7.8% ) inadequate fna smears ( c1 ) in concordance with previous reports in the range 0.725.3% . so our study found fewer inadequate smears compared with other previous studies because fna was performed by experienced pathologist of the department . diagnosis of c2 ( benign ) was rendered as an adequate sample showing no evidence of significant atypia or malignancy and if representative , a negative report . we gave cytological diagnosis of atypical , probably benign ( c3 ) when , although the overall pattern of aspirate was benign , there were a population of cells , which showed nuclear pleomorphism , and/or some loss of cellular cohesiveness with nuclear and cytoplasmic changes ( figures 1(a ) and 1(b ) ) . a diagnosis that was suspicious of malignancy ( c4 ) usually referred to fnas that contain cells with some malignant features ( figures 1(c ) and 1(d ) ) in the absence of overtly malignant cells or a aspirate with only scanty number of abnormal cells , or poorly prepared / preserved , but abnormal cells . in our study , based on 1093 cases of breast fna , the equivocal diagnostic categories c3 and c4 comprised 8.4% of cases . this proportion is in range ( 417.7% ) with as reported by others [ 3 , 4 , 812 ] indicating that these categories were not underused or overused in our study . in our study , among the c3 category , 37.5% cases revealed malignant findings on histopathological evaluation ( false negative ) . this result also is in concordance with reported literature values where c3 category revealed malignant diagnosis in 8.652% cases with most reports having values more than 30% [ 3 , 8 , 13 ] . infiltrating ductal carcinoma ( idc ) was the most common malignant diagnosis of our study followed by lobular carcinoma ( table 2 ) . in c4 category , our study had 87.5% cases with malignant diagnosis , and 12.5% ( false positive ) cases yielded benign diagnosis on histopathological examination . this is similar to other previous studies where 8197% malignancy was reported in c4 category [ 3 , 8 , 13 ] . results include small tumor size , hypocellularity and inadequate sampling during aspiration , few histological tumor types such as low nuclear grade , lobular carcinoma , scirrhous carcinoma , and well - differentiated intra - cystic carcinoma . the most attributed cause of false negative rate reported in the literature is sampling error particularly in small tumor . we also underdiagnosed one case of lobular carcinoma as being atypical , probably benign ( c3 ) on fnac . review of smear of this case showed few abnormal dissociated cells with slight nuclear atypia against background of benign clusters of epithelial cells and scattered bare nuclei . majority of false negative cases in our study were diagnosed as infiltrating ductal carcinoma on histopathological examination . however , on careful review , there were few discohesive clusters with nuclear atypia and nuclear crowding . presence of naked nuclei in background , lack of discohesion , and apparent monolayered nature of majority of epithelial clusters led to underreporting of these cases as c3 in cytology . the two false positive diagnoses in our study involved smears that were classified as c4 on cytology but yielded fibrocystic change with or without atypia on histopathological examination . the first case showed mild atypia on histology while the second case showed florid hyperplasia leading to high cellularity and slight loss of cohesion resulting in overdiagnosis on fnac . in other study also , increased cellularity , loss of cohesion , and nuclear atypia in aspirates from fibroadenoma , fibrocystic disease , and in intraductal papilloma led to erroneous interpretation . in other published reports also , epithelial proliferation of ductal / lobular hyperplasia accounted for false positive results [ 16 , 17 ] . while the false positive results could lead to overtreatment of an unnecessary or excess surgery , hence in c3 category , we advise that fna should not be used as sole modality , and results must be interpreted in correlation with clinical and imaging findings ( triple test ) to reduce error and allow proper management of each patient . our study thus supports that the recommendation of others [ 9 , 18 , 19 ] that use of triple test is important for proper management of patients , with fna results in c3 category . similarly , for c4 category with high incidence of malignancy on histopathological examination , we recommend that such patient should definitely have the diagnosis confirmed by histological examination as suggested by other authors also [ 3 , 20 ] . thus it is important for both pathologist and clinician to understand not only the benefits but also the limitation of cytological diagnosis from fna specimen . we feel that it is still useful to maintain the equivocal diagnostic categories c3 and c4 separately , since in our study approximately two thirds of patients who were diagnosed as c3 had benign lesions where about 80% of those in c4 category had malignant diagnosis . fnac is simple , safe , cost - effective , and accurate method for initial diagnosis and guiding treatment of breast masses . however , one must be aware of possibility of false positive and false negative results . also the category of atypia , probably benign ( c3 ) , and suspicious of malignancy ( c4 ) provides a strategy for classification of equivocal cases and allows separation of these cases into clinically useful groups with different probabilities of malignancy and thus different management .

introduction . according to the national cancer institute ( nci ) guidelines in 1996 , breast lesions are categorized as c1 to c5 on fine needle aspiration ( fna ) cytology . very few studies are available in the english literature analyzing histopathology outcome of c3 ( atypical , probably benign ) and c4 ( suspicious , probably malignant ) lesions . our study aims to correlate fna cytology of breast lump diagnosed as c3 and c4 lesion with histopathological examination . methods . during a period of 2 years , 59 cases of c3 and 26 cases of c4 were retrieved from total 1093 cases of breast fna . all the cases were reviewed by two cytopathologists independently . the final 24 cases of c3 and 16 cases of c4 categories were correlated with histopathological diagnosis . result . among c3 category , 37.5% revealed malignant findings , whereas of c4 category , 87.5% were malignant on histopathology . this difference was statistically significant ( p = 0.0017 ) . sensitivity , specificity , positive predictive values , and negative predictive value of c4 category in diagnosing breast malignancy were 60.8% , 88.2% , 87.5% , and 62.5% , respectively . conclusion . although fnac is simple , safe , cost - effective and accurate method for diagnosis of breast masses , one must be aware of its limitations particularly in c3 and c4 categories . also , since both these categories carry different probabilities of malignancy and thus different management , we therefore , support maintaining c3 and c4 categories .

panthothenate kinase - associated neurodegeneration ( pkan ) , formerly termed as hallervorden - spatz disease is a rare chromosomal disorder first described by hallervorden and spatz in 1922 . the characteristic features in patients with pkan include dystonia , muscle spasm , cognitive dysfunction , and seizure disorder . the anaesthetic concerns include difficult airway management , increased risk of gastric aspiration , dehydration , and post - operative respiratory and renal insufficiency . here , we report a case of successful anaesthetic management of a 9-year - old intellectually disabled male child with pkan , posted for ophthalmic surgery under general anaesthesia ( ga ) . a 9-year - old boy weighing 20 kg , diagnosed case of pkan , admitted at our institute with a history of right eye lid oedema with maggots for debridement . he had a history of fall 7 days back and sustained injury over the right eyeball from a wooden stick . the child also had a history of intermittent abnormal flexor posturing and spasm of both the upper limbs for last 7 years , which became persistent and fixed during last 2 years . he also reported of frequent falls due to progressively worsening spasm and was unable to perform any definitive motor function . he had a history of generalised tonic - clonic seizures for the past 3 years and was on syrups of sodium valproate and lorazepam . since admission to our institute physical examination revealed cognitive dysfunction , facial dysmorphism , rigidity and involuntary movements of upper limbs . airway examination showed microstomia , micrognathia , retrognathia , modified mallampatti class ii , with normal thyromental distance and neck movements [ figure 1 ] . magnetic resonance imaging ( mri ) brain revealed specific pattern of hyperintensity within hypointensity of anteromedial globus pallidus with eye - of - the - tiger child with panthothenate kinase associated neurodegeneration presenting with right eyelid oedema and maggots high - risk consent was obtained from the child 's parents and a bed was arranged in the paediatric intensive care for post - operative ventilation if required . on the day of surgery , oral antiepileptics and iv ranitidine 20 mg and routine antibiotics were administered as iv cannula was in situ . a difficult airway cart including supraglottic devices , video - laryngoscope , and fibreoptic bronchoscope ( fob ) were kept ready to manage the anticipated difficult airway . the child 's father was allowed to stay in the operating room ( or ) till induction . standard monitoring including electrocardiogram , pulse oximetry ( spo2 ) , and non - invasive blood pressure ( nibp ) were attached . before induction , his vital signs recorded were a heart rate of 116 beats / min , nibp 86/38 mm hg , respiratory rate 26/min and spo298% . iv fentanyl 2 mcg / kg was administered , and the child was pre - oxygenated with 100% oxygen ( 6 l / min ) for 3 minutes . for induction , iv propofol was administered in titrated doses ( total of 35 mg ) and anaesthesia was then gradually deepened with halothane ( 1to 3% in 100% o2 ) . after ensuring adequate depth of anaesthesia ( loss of eyelash reflex and relaxed jaw ) , check video - laryngoscopy proseal laryngeal mask airway ( plma ) of size 2.0 was inserted in the first attempt and suction catheter was passed through the gastric channel . as adequate tidal volume was achieved with manual ventilation , assisted pressure support ventilation ( pressure support ventilation with apnoea backup ventilation using the drager primus anaesthesia machine ) was started and anaesthesia was maintained with isoflurane ( 1.0 to-1.2 mac ) in o2 : air ( fio20.5 ) . topical procaine anaesthetic drops ( 0.5% ) were instilled in the operating eye and 200 mg iv paracetamol were administered for intra - operative analgesia . antiemetic prophylaxis ( 2 mg of ondansetron ) was given 10 min before the end of surgery . on the completion of surgery , isoflurane was turned off and 100% o2 was administered . when adequate tidal volume and regular respiration were achieved , the plma was removed after gastric and oropharyngeal suctioning . child was turned left lateral and was observed in or for next 10 minutes , before shifting to post - anaesthesia care unit ( pacu ) . there was no episode of seizure , muscle spasm , vomiting or airway obstruction noticed postoperatively . panthothenate kinase associated neurodegeneration is a rare , autosomal recessive , neurodegenerative disorder characterised by the accumulation of iron in the basal ganglia of the human brain . the responsible gene ( pank 2 ) for the disease has been localised in the short arm of chromosome no . 20 , which is required for the phosphorylation of pantothenic acid in the formation of coenzyme a. defective phosphorylation results in under - utilisation of cystine in the body . this excessive cystine causes chelation of iron resulting in excessive free radical generation , lipid peroxidation , axonal dystrophy , and apoptotic cell death resulting in neuraxonal degeneration . the onset of disease is usually in the first or second decade of life ; however , it can occur at any age . it may be familial or sporadic , and the average survival time after the diagnosis is about 10 to-15 years . characteristic neurological features include progressive rigidity ( oromandibular rigidity , trismus , dysphagia ) , involuntary movements ( chorea , athetosis ) , seizures , cognitive dysfunctions , visual impairment ( optic atrophy , retinitis pigmentosa ) , and difficulties in articulation , swallowing , and chewing . these signs and symptoms influence the pre - anaesthetic preparation of the patient , as well as intra - operative and post - operative anaesthesia management . reviewed the case reports concerning the anaesthetic management of patients with pkan and found successful and safe use of anaesthetic drugs like opioids ( fentanyl , remifentanil ) , inhalational agents ( nitrous oxide , halothane , sevoflurane , isoflurane ) , induction agents ( propofol , thiopentone ) , and muscle relaxants ( succinylcholine , vecuronium , pancuronium ) . there are several reports of autopsies revealing muscle wasting secondary to poor nutrition and diffuse axonal changes in the brain which may involve upper motor neuron lesions to an unpredictable extent , thereby increasing the possibility of hyperkalaemic cardiac arrest . intrathecal baclofen to relieve spasticity and dexmedetomidine during mri were also used in these patients . presence of involuntary movements ( chorea , athetosis ) , rigidity and seizures interfere with the placement of iv cannula , arterial line , positioning for regional anaesthesia and awake intubation . involuntary movements may not completely disappear with the induction of anaesthesia and reappear on emergence from anaesthesia . attempts for awake intubation techniques like fob and tracheostomy under local anaesthesia can intensify these involuntary movements . the child reported here was mentally disabled , uncooperative , and had signs of difficult airway with a progressive neurological disorder . although awake fob is the gold standard for difficult airway management , it is unsuitable for such patient . this child was also having risk of aspiration and endotracheal intubation is considered to be a gold standard for securing the airway in these patients . however , successful airway management using plma in a patient with difficult airway and at increased risk of gastric aspiration has been reported in the literature . supraglottic airway devices have advantages in ophthalmic surgery as they cause minimal changes in haemodynamics , intraocular pressure , minimal trauma to the airway and decrease intubation and extubation response . we chose plma as it allows the passage of suction catheter through the gastric tube and protects against gastric aspiration . video - laryngoscopy was done to assess cl grading to be prepared for intubation in the emergent situation . keegan et al . reported reintubation and mechanical ventilation in the post - operative period due to the dynamic upper airway obstruction and acute respiratory failure in an 11-year - old girl with pkan for stereotactic thalamotomy . emergency tracheostomy during induction and re - intubation in the post - operative period may be needed . hence , all the necessary preparations should be done and made available to secure the airway in such scenarios . we avoided neuromuscular blockade as ophthalmic surgery did not need muscular paralysis , and lungs were ventilated with assisted pressure support ventilation with etco2 monitoring . sevoflurane was also avoided during induction as seizure - like movements of the extremities have been observed during induction of anaesthesia with sevoflurane . there are several case reports of sevoflurane provoking seizure like activity , particularly in children and in conjunction with high concentrations and hypocapnia . therefore , propofol was used for induction of anaesthesia using its antiepileptic properties to our benefit . we could successfully manage the child with pkan and difficult airway using plma without muscle relaxants for ophthalmic surgery . no case has been reported in the literature using proseal lma for airway management in a child with pkan .

panthothenate kinase - associated neurodegeneration ( pkan ) ( hallervorden - spatz disease ) is a rare autosomal recessive chromosomal disorder characterised by progressive neuroaxonal dystrophy . the characteristic features include involuntary movements , rigidity , mental retardation , seizures , emaciation . the anaesthetic concerns include difficult airway , aspiration pneumonia , dehydration , and post - operative respiratory , and renal insufficiency . we report successful anaesthetic management of a 9-year - old intellectually disabled male child with pkan , scheduled for ophthalmic surgery under general anaesthesia .

both age and diabetes mellitus ( dm ) are independent prognostic predictors of hospital mortality in acute coronary syndrome ( acs ) . an analysis on the in - hospital events and 6 months outcomes in elderly patients with acs who were included in the grace registry showed that the more elderly , the higher risk are the patients , the less frequently coronary angiography , and revascularization are used in spite of an increasing grace risk score . there is paucity of data in kingdom of saudi arabia ( ksa ) despite the high percentage of elderly diabetic patients and the high prevalence of dm . acute coronary syndromes ( midas ) study aimed to monitor the adherence to evidence - based therapy of diabetic patients with acs and to describe the in - hospital outcomes of diabetic patients in the setting of acs . we present the characteristic risk profile and points of concern in the management of elderly patients in the ksa in comparison to the international data . midas is an observational registry and diagnostic , monitoring , or therapeutic procedures were not applied to the patients . dm patients presenting with non st elevation acute coronary syndrome were enrolled into the study at the time of admission to the emergency room or the coronary care unit in five hospitals in ksa . primary clinical outcome measure was in - hospital death or myocardial infarction ( mi ) . midas did not interfere with the medical care of the patients , which was done according to local practice . the mean age was 67 15 years and there was female predominance ( 64% ) . baseline characteristics for multicenter international diabetes acute coronary syndromes patients the utilization of glycoprotein iib / iiia inhibitors in international midas was 37.4% , predominantly tirofiban , in comparison to 18.3% in ksa ( p = 0.046 ) . there was marked underutilization of glycoprotein iib / iiia inhibitors in ksa in those 65 years ( 12.7% ) in comparison to 22.5% in those < 65 years ( odds ratio 0.56 ) . meanwhile , the utilization of gp iib / iiia in international midas elderly population decreased from 40.8% in those aged < 65 years to 35.7% in those aged 65 years with odds ratio 0.87 [ figure 1 ] . gp iib / iiia utilization based on age group on the contrary , the utilization of clopedogril / ticlopidine in ksa was 96.8% exceeding the international figure of 74.7% ( p < 0.0001 ) . surprisingly , the utilization of clopedogril / ticlopidine in ksa in those aged 65 years ( 98.2% ) was higher than those aged < 65 years ( 95.8% ) [ figure 2 ] . the percentage of early coronary angiography approach in ksa was less than that of the international data with further drop of the percentage in saudi elderly population ( 25.5% in those aged over 65 years ) in comparison to 49.3% in those aged < 65 years with odds ratio 0.52 . meanwhile , there was mild drop in the international figure ( 42.5% in those aged 65 years in comparison to 53.4% in those aged < 65 years with odds ratio 0.80 ) [ figure 3 ] . in contrast , the percentage of per cutaneuos coronary intervention procedures in saudi elderly patients ( 23.6% in those aged 65 years ) was very close to those aged < 65 years ( 25.4% ) , but much less than the international elderly ( 65 years ) , who had percutaneous coronary intervention ( pci ) in 42.5% [ figure 4 ] . clopedogril utilization based on age group percentage of early coronary angiography approach based on age group percentage of pci based on age group the percentage of patients who had coronary artery bypass graft in elderly ksa ( 65years ) was 7.3% in comparison to 12.7% in those aged < 65 years . the international figure in those aged 65 years ( 8.9% ) did not show remarkable difference in comparison with those aged < 65 years ( 9.4%)[figure 5 ] . one study in saudi subjects showed that , in those aged over 60 years , the prevalence of non insulin dependant diabetic mellitus was 28.82% in males and 24.92% in females . furthermore , dm was the most prevalent risk factor for coronary artery disease , present in 56% of patients . however , data regarding the adherence to evidence - based therapy in this group of patients are lacking . elderly are at the risk of being under - treated both medically and by interventions as supported by recent registries and statements ; however , the available data from ksa are few . the mean age of midas patients ( 65 years ) was similar to that of grace registry ( 66 years ) and ncdr action registry ( 64 years ) . data from midas showed , in general , satisfactory use of evidence - based therapies . however , there were significant differences in utilization of different lines of treatment based on age . elderly patients were under - treated in the invasive arm in term of coronary angiography , pci , and coronary artery bypass graft ( cabg ) . this was more marked in elderly saudi patients . despite the current strong recommendations for their use in diabetics presenting with acs , there was marked underutilization of gp iib / iiia inhibitors in elderly saudi midas patients as well as those aged under 65 years . this underutilization was obviously due to fear of bleeding , taking into consideration that recent reports and guidelines showed more concern about the increased risk of bleeding upon using double or triple antiplatelet therapy in combination with heparin . in contrast , the use of clopedogril / ticlopidine in ksa was in total compliance and it exceeded the international data and the 86% achieved by the top 10% performing hospitals in action registry . this observation might have been related to the use of clopedogril in patients who did not receive gp iib / iiia inhibitors due to the fear of bleeding . although coronary angiography approach in ksa was matching in those aged less than 65 years , there was significant difference in the saudi elderly population , probably due to fear of complications . in contrast , the percentage of pci procedures in saudi elderly patients was very close to those aged less than 65 years . this might be explained by the bad coronary anatomy of saudi diabetic patients , who are noted to have high glycosylated hemoglobin ( hba1c ) . this percentage was close to that of patients who had cabg in the setting of acute coronary event in the saudi project for assessment of coronary events ( space ) registry ( 9% ) ; whereas in the space registry , the percentage of early coronary angiography ( 60% ) and pci ( 39% ) exceeds that of the saudi midas population . this also might be related to the difference in the number of the centers that have cardiac catheterization laboratories in each study . one of the restriction on these data is the selective involvement of certain cardiac centers , however , this will invite for further studies in this group . elderly ksa patients tend to have less use of utilization of gp iib / iiia and early coronary angiography and cabg but not clopedogril / ticlopidine . this concern needs further attention by health authority , since elderly patients represent a very high - risk group that may benefit the most from intensive medical therapy and early coronary angiography .

background and purpose : elderly diabetics ( dm ) who present with acute coronary syndrome ( acs ) constitute a very high risk group . we present the pattern of management of elderly patients ( > 65 years ) in the kingdom of saudi arabia ( ksa ) in comparison to the international data extrapolated from a multicenter international diabetes - acute coronary syndromes ( midas).materials and methods : dm patients presenting with unstable angina or non - st - segment elevation myocardial infarction ( mi ) at the time of admission to the hospital were collectively enrolled into the midas study . a total of 3624 patients were enrolled ; 142 were from saudi arabia . primary clinical outcome measure was in - hospital death or mi . we present the data of ksa based on the age of the patients in comparison to the international registry.results:baseline characteristics were typical for dm presenting with acs , with mean age of 67 15 years , males , constituted 36% of patients while 94% of patients were dm type 2 . there was marked underutilization of glycoprotein iib / iiia inhibitors in those aged over 65 years with a decrease from 22.5 to 12.7 in ksa ( odds ratio 0.56 ) patients . the percentage of early coronary angiography approach in ksa was less than that of the international data with further reduction of the percentage in saudi elderly population ( from 49.3% to 25.5% with odds ratio 0.52).conclusions : in elderly saudi diabetic patients admitted with acs , there is tendency for underutilization of gp iib / iiia , early coronary angiography , and revascularization that needs to be addressed .

one of the most common challenges faced by the dentist is the restoration of endodontically treated teeth , more so because of its brittleness as compared to vital teeth . the success of endodontically treated teeth is related to the position of the tooth in the dental arch , occlusal contact , proximal contact , structural loss of tooth , and periodontal condition of endodontically treated teeth . the changes that accompany the root canal therapy and the thickness of the residual walls and cusps will determine the selection of the restorative materials and the procedures for endodontically treated teeth . the important factor of treatment plan to be considered for a severely damaged tooth is evaluation of tooth for occlusion , esthetics , to access the remaining tooth structure after removal of all caries and old restorations , canal configuration , control of plaque , and eliminate periodontal infection . loosening of teeth and fracture of teeth is one of the most common failures for post and core . the incidence of vertical root fracture in endodontically treated teeth with post and core was observed more in older patients , who usually have reduced alveolar bone height . metal posts were commonly used for the past many years , however with increased demands of esthetics , the use of tooth color post and core was introduced in the market and are becoming popular . the purpose of the present in vitro study using finite element analysis ( fea ) was to evaluate the stress distribution caused by the different alveolar bone height and the type of post used . fea is a computerized method for predicting how a product reacts to real - world forces , vibration , heat , fluid flow , and other physical effects . it works by breaking down a real object into a large number ( thousands to hundreds of thousands ) of finite elements , such as little cubes and uses a complex system of points called nodes , which make a grid called a mesh . this mesh is programmed to contain the material and structural properties which define how the structure will react to certain loading conditions . the mesh acts like a spider web and from each node there extends a mesh element to each of the adjacent nodes . once the geometry , materials , and boundary conditions are set , the next step is to run the fea software to obtain a physical displacement at each node . the strain data that is observed is then used to compute the stress data at each node . a graphical postprocessor is then used to process all of this data and display it superimposed over the geometry model of the part with color coded stress . the finite element method is a highly approved method to simulate biophysical phenomena in computerized models of teeth and their periodontium . the finite element method is considered to be an extremely useful tool to simulate the mechanical effects of chewing forces acting on the periodontal ligament ( pdl ) and on the dental hard tissues . the null hypothesis is that bone height and the type of postmaterial show no difference in the stress distribution of endodontically treated teeth . the study was conducted using a three - dimensional ( 3d ) finite element model and were analyzed using fea . the 3d model was fabricated using commercially available software ansys workbench v13.0 ( ansys inc . , canonsburg , pennsylvania , u.s.a ) to represent an endodontically treated mandibular second premolar restored with a full ceramic crown restoration . the graphical user interface of ansys enables the user to work with 3d models and also generate results from them . although pdl thickness differs according to age , position , and individual variations , the thickness of the pdl was modeled as a 0.25 mm thin layer around the root . the measurements used in the tooth model were taken as described by wheeler 's and model was simulated with the help of an intel core i7 processor , with 8 gb ram , 64 bit operating system . the modulus of elasticity and poisson 's ratio for the elements involved in the study are shown in table 1 . the models included a porcelain crown , dentin , composite core , alveolar bone , gutta percha filling , and posts ( carbon fiber post and titanium alloy post ) . discretization was done by generating mesh containing 9,82,759 nodes and 6,56,093 elements for the model of 2 mm alveolar bone height from cement enamel junction ( cej ) and 9,48,119 nodes and 6,35,849 elements for the model of 4 mm alveolar bone height from cej . the base of the alveolar bone was kept static , and a load of 300 n at an angle of 60 to the vertical was applied to the triangular ridge of the buccal cusp in a buccolingual plane . the relationship of alveolar bone height at 2 mm , 4 mm , and the type of the post used was calculated using von mises stresses . the fea showed the stress distribution in all the structures as shown in figures 1 and 2 . as shown in table 3 , the maximum stresses in dentin were observed in the carbon fiber post in alveolar bone height of 4 mm from the cej , and the minimum stresses in dentin were observed with a titanium alloy post with alveolar bone height of 2 mm from the cej . ( a ) stress distribution in dentin with carbon fiber post and alveolar bone height of 2 mm from cement enamel junction . ( b ) stress distribution in cement with carbon fiber post and alveolar bone height of 2 mm from cement enamel junction . ( c ) stress distribution in post with carbon fiber post and alveolar bone height of 2 mm from cement enamel junction . ( d ) stress distribution in dentin with titanium post and alveolar bone height of 2 mm from cement enamel junction . ( e ) stress distribution in cement with titanium post and alveolar bone height of 2 mm from cement enamel junction . ( f ) stress distribution in post with titanium post and alveolar bone height of 4 mm from cement enamel junction ( a ) stress distribution in dentin with carbon fiber post and alveolar bone height of 4 mm from cement enamel junction . ( b ) stress distribution in cement with carbon fiber post and alveolar bone height of 4 mm from cement enamel junction . ( c ) stress distribution in post with carbon fiber post and alveolar bone height of 4 mm from cement enamel junction . ( d ) stress distribution in dentin with titanium post and alveolar bone height of 4 mm from cement enamel junction . ( e ) stress distribution in cement with titanium post and alveolar bone height of 4 mm from cement enamel junction . ( f ) stress distribution in post with titanium post and alveolar bone height of 4 mm from cement enamel junction previously , other methods have been used to analyze stress concentration in the tooth structures like the photoelastic studies . the advantage of fea is that the experimental condition can be kept identical in all the models , which is not possible in the experimental human study . in the present study , the fea showed changes in the stress distribution between the two models at 2 mm and 4 mm alveolar bone height from cej . in this study , a load of 300 n was applied although a higher load may be observed in the clinical conditions . the maximum load in the present study was observed in the dentine , and the minimum load was seen in the cement . the major finding , in this study , is that the bone height was a significant factor in the stress distribution . the stress in the dentin , post , and the cement was much higher in the model with the alveolar bone height of 4 mm from cej compared to model of better bone support of 2 mm alveolar bone height from the cej . this shows that the height of the bone plays an important factor in tooth stability . moreover , it was observed that higher alveolar bone height supports stronger forces until root fracture . in the present study carbon , fiber postmodel showed higher stress value in dentin at both levels of bone height as compared to titanium post . a material with a higher modulus of elasticity altered the natural biomechanical behavior of the tooth . moreover , studies by chuang et al . and strub et al . have also shown that post with young 's modulus similar to the dentin is an effective method of reducing the root fracture risk . the internal canal architecture of the tooth may be modified because of severe carious involvement and during root canal instrumentation resulting in greater canal diameter . therefore , it is important that the selection of the cementing medium for the post be carefully evaluated . it has been observed that the modulus of elasticity of the cement layer is more important to the stress concentration of root filled teeth than the thickness of the cement layer . moreover , cements with elastic modulus similar to dentin could reinforce weakened root and reduced stress in dentin . the use of unidirectional glass fibers customized post , modeling the internal anatomy of the root canal can be considered effective , less invasive , and suitable for restore endodontically treated teeth . in this study was chosen for postcementation , which has a modulus of elasticity of 18.3 , which was almost similar to the dentin [ table 1 ] . in the present study , stress was observed more in endodontically treated tooth with a post where the alveolar bone height was 4 mm from cej as compared to 2 mm from cej . stresses in the dentin were almost similar when the carbon fiber post was compared to titanium post . however , stresses in the post and the cement were much higher when titanium post was used as compared to carbon fiber post . within the limitations of the study , it can be concluded that the bone height and the type of the post plays an important role in stress distribution of endodontically treated teeth .

objective : a three - dimensional ( 3d ) finite element analysis ( fea ) on the stress distribution of endodontically treated teeth with titanium alloy post and carbon fiber post with different alveolar bone height.materials and methods : the 3d model was fabricated using software to represent an endodontically treated mandibular second premolar with post and restored with a full ceramic crown restoration , which was then analyzed using fea using fea ansys workbench v13.0 ( ansys inc . , canonsburg , pennsylvania , u.s.a ) software.results:the fea showed the maximum stresses of 137.43 mpa in dentin with alveolar bone height of 4 mm when the titanium post was used , 138.48 mpa when carbon fiber post was used as compared to 105.91 mpa in the model with alveolar bone height of 2 mm from the cement enamel junction ( cej ) when the titanium post was used and 107.37 mpa when the carbon fiber post was used.conclusions:stress was observed more in alveolar bone height level of 4 mm from cej than 2 mm from cej . stresses in the dentin were almost similar when the carbon fiber post was compared to titanium post . however , stresses in the post and the cement were much higher when titanium post was used as compared to carbon fiber post .

are commonly used on the other hand an opioid consumption is traditionally common in iran . the effects of different addictives on body systems have been reported ; however , there is not enough information about different blood parameters ( 2 ) . the effect of some psychoactive substances on commonly observed diseases like coronary artery disease , diabetes mellitus and some psychiatric disorders has been investigated , but effects of long - term use of these substances on endocrine system have not been studied enough ( 3 ) . studies have demonstrated controversial results about effects of psychoactive substances on hypothalamic - pituitary axis and thyroid function ( 4 ) . psychoactive substances have many different effects on physiologic and neuroendocrine functions in humans ( 5 ) . it has been demonstrated that endogenous opioids like -endorphin , enkephalins and opiate receptors influence neuroendocrine regulation ( 6 ) . previous studies showed that some psychoactive substances modulate immune function and affect resistance to bacterial , viral and protozoan infections ( 7 , 8) . monitorization of the psychoactive substance use can be done objectively by urine analysis . since substance concentrations in urine are higher than blood , urine is the preferred material for determination of substance use . testing schedules and determination of cut - offs are important for confirmation of the psychoactive substance use ( 9 ) . since polydrug abuse is common worldwide , determination of the effects of only one drug is difficult ( 10 ) . recent studies demonstrated controversial results about the effects of opium on serum electrolytes , lipid markers and glucose metabolism . defining the real side effects of these psychoactive substances may increase awareness about disadvantages of consumption ( 11 ) . studies about the effects of psychoactive substances on different biochemical and hematological parameters were limited in number ( 2 , 12 ) . this study was conducted to determine the effects of different psychoactive substances on serum biochemical parameters . this study was conducted on 324 patients and 69 controls admitted to erenkoy mental health and neurology training and research hospital between january 2013 and january 2014 . patients were determined according to the diagnostic and statistical manual of mental disorders , fourth edition dependent group involves subjects determined as at least one or more than one type of psychoactive substance users . in the control group urine toxicology results were negative . levels of toxicology parameters were determined using a hitachi model 902 automatic analyzer ( hitachi high - technologies corporation , roche diagnostics ) with an enzyme immunoassay ( microgenics cedia fremont , california , usa , for urine toxicology ) . after hospitalization , each patient s first urine and blood sample before treatment were taken into account for comparison . cases and controls with accompanying diseases like diabetes , cancer , metabolic disorders etc . are excluded from the study . urine samples were tested simultaneously for heroin , cannabinoids , cocain , benzodiazepins , opiates , buprenorfine , amphetamines , extacy and ethyl glucuronide . routine biochemistry parameters were measured using the architect ci 4100 ( abbott diagnostics products ) automatic biochemistry analyzer . this study was approved by the ethics committee of erenkoy mental health and neurology training and research hospital . spss ibm 20.0 software ( chicago , illinois , usa ) was used for statistical analysis . spss ibm 20.0 software ( chicago , illinois , usa ) was used for statistical analysis . a total of 324 patients ( 316 males and 8 females ) and 69 controls ( 64 males and 5 females ) were involved in this study . the median ages of psychoactive substance users and controls were 26.5 ( 23 - 34 ) and 27 ( 20.5 - 34.5 ) years , respectively ( table 1 ) . the concentration of biochemical parameters in the serum of the substance - dependent group was compared to the control group ( table 2 ) . we found a statistically significant difference in gamma - glutamyl transferase ( ggt ) , uric acid , creatinin , urea , albumin , aspartate aminotransferase ( ast ) medians between the patient and control groups ( p < 0.05 ) . abbreviations : alp , alkaline phosphatase ; alt : alanine aminotransferase ; ast : aspartate aminotransferase ; crp , c - reactive protein ; ggt , gamma - glutamyl transferase ; hdl , high density lipoprotein ; ldh , lactate dehydrogenase ; and ldl , low density lipoprotein . forty - six out of 424 addicts tested positive for only opium ( cut - off , 300 ng / ml ) . several biochemical parameters in the opium - dependent group were compared to the control group ( table 3 ) . there was a statistically significant difference in the serum concentrations of sodium and albumin between the opium - dependent and the control groups ( p < 0.05 ) . moreover , sixty - nine patients were tested positive for only cannabinoids ( cut - off , 50 ng / ml ) . biochemical parameters did not show any significant difference in the cannabinoid - dependent group compared to the control group ( p > 0.05 ) . thirteen out of all addicts were tested positive for only benzodiazepine ( cut - off > 300 ng / ml ) . there was a statistically significant difference in ggt , urea , glucose , sodium , total protein , and ast levels between the benzodiazepine - dependent group and control group ( p < 0.05 ) . also , 12 patients were tested positive for only ethyl glucuronide ( cut - off > 500 ng / ml ) . a statistically significant difference was found in triglyceride and ggt levels between the ethyl glucuronide and control groups ( p < 0.05 ) . clinical observations demonstrated that adverse effects of psychoactive substances were associated with the addiction period and route of administration . psychoactive substance users commonly have nutritional problems since they spend their money largely for drugs ( 13 ) . coexistence of psychiatric disorders in drug addicts is also important since some psychiatric disorders may cause loss of appetite and poor nutritional status and changes in biochemical parameters ( 14 ) . clinical studies showed that long - term use of opium and heroin can affect serum glucose , potassium , calcium , uric acid and cholesterol levels ( 12 ) . in our study , we found a significant difference in ggt , uric acid , creatinine , urea , albumin , and ast medians between the dependent and control groups ( p < 0.05 ) . studies about the effects of opium addiction on blood glucose showed that the opium - dependence decreased fasting blood glucose temporarily without any effect on hemoglobin a1c ( 15 ) . we found a statistically significant decrease in glucose levels only in patients tested positive for benzodiazepine ( p < 0.05 ) . some psychoactive substances may affect gluconeogenesis so that blood glucose levels may decrease , especially in cases with poor nutrition . some people believe that psychoactive substances like opium can have beneficial effects on blood lipid profile and cardiovascular disease , but clinical observations demonstrated that opium can increase risk of atherosclerotic plaque formation and adversely affect lipid profile in animal models ( 16 ) . we found a statistically significant increase in triglyceride levels in ethylglucuronide group ( p < 0.05 ) . in our study , we did not found statistically significant difference in total cholesterol , low density lipoprotein ( ldl ) , and high density lipoprotein ( hdl ) levels between dependent and control groups ( p > 0.05 ) . cardiovascular side effects of some psychoactive substances may not be attributed to changes in lipid profile . there is a need to conduct a prospective study with the larger sample size for the prevalence of the cardiovascular disease . another study , which was performed on opium addicts showed that serum adiponectin levels were decreased but no significant change was observed in serum leptin levels . it was also indicated in previous studies that a decrease in adiponectin levels can be associated with an increased risk of metabolic disorders like insulin resistance and cardiovascular disease since it has known antidiabetic and antiatherogenic effects ( 17 ) . changes in nutritional patterns may also be related with changes in albumin levels in these patients ( 18 ) . we found a statistically significant difference in albumin levels between the drug - dependant and control groups . in our study , the amount of total protein showed a significant difference only in the benzodiazepine dependent group ( p < 0.05 ) . since in our study , patients with significant derangements were referred to specialized medical centers for further assessment and excluded from the study , changes in their albumin levels may not be due to viral infections or metabolic disorders . in a previous study , it has been demonstrated that morphine consumption for long period in animal models increases uric acid and creatinine levels ( 19 ) . we found a statistically significant decrease in uric acid and creatinine levels in the dependant group compared to the control group ( p < 0.05 ) . poor living conditions and nutritional factors like low protein intake may likely to contribute to changes in biochemical parameters in psychoactive substance users . these effects on renal system include changes in urinary output and urinary sodium excretion ( 20 ) . divsalar et al . showed that a sodium level in the heroin - dependent group did not change ; however , it was significantly high in the ex - heroin dependent group compared to the control group . however , no significance difference was found in potassium and calcium levels between the ex - heroin dependent and control groups ( 14 ) . we found that the concentration of sodium in the serum of the opium - dependent and benzodiazepine dependent groups was significantly increased compared to the control group ( p < 0.05 ) . no statistically significant difference was observed in calcium levels between the dependent and control groups ( p > 0.05 ) . routine biochemistry , and hematology parameters , and vitamin , and mineral levels are affected by nutritional factors . determining the differences in biochemical parameters , vitamin and mineral levels between addicts and healthy subjects may help to define individuals at nutritional risk and provide these patients with the corrective nutritional programs ( 18 ) . in this study we tried to describe the extent of changes in various blood parameters due to psychoactive drug use . our study involves a range of psychoactive substances like heroin , cannabinoids , cocaine , benzodiazepine , opiate , buprenorphine , amphetamine , extacy , ethyl glucuronide and their potential effects on many biochemical parameters . raising awareness about potential adverse effects of psychoactive substances health problems associated with physiological side effects of these substances may increase economic burden on health care resources . therefore , in psychoactive substance users defining the real need for intensive monitoring and treatment programs are extremely important .

background : psychoactive substances affect mainly central nervous system and brain function causing changes in behavior.objectives:the purpose of this study was to determine the effects of different psychoactive substances on serum biochemical parameters.patients and methods : the study included 324 drug dependents , and 69 controls . the patient group was determined according to dsm - iv ( the diagnostic and statistical manual of mental disorders , fourth edition ) criteria . all patients and control subjects were tested for routine biochemical parameters and urine toxicology parameters for psychoactive substance use . cases and controls with accompanying diseases like diabetes , cancer , metabolic disorders etc . are excluded from the study . moreover , an association between urine toxicology results and changes in biochemical parameters was evaluated for statistical significance.results:there was a statistically significant difference in the gamma - glutamyl transferase ( ggt ) , uric acid , creatinine , urea , albumin , aspartate aminotransferase ( ast ) medians between the dependent and control groups ( p < 0.05 ) . we found a statistically significant difference in sodium and albumin levels between the opium - dependent and control groups ( p < 0.05 ) . in the benzodiazepin dependent group , we found a significant difference in ggt , urea , glucose , sodium , t protein , and ast levels ( p < 0.05 ) . moreover , a statistically significant difference was observed in triglyceride and ggt levels between the ethyl glucuronide and control groups ( p < 0.05).conclusions : in psychoactive substance dependents , serum routine biochemistry parameters can be used to predict the need for intensive monitoring and treatment programs .

clinical presentations vary from nonspecific systemic symptoms ( e.g. , fever , myalgia , palpitation , chest pain , dyspnea ) to fulminant hemodynamic collapse and sudden death . infections ( viral , bacterial , fungal , protozoal , parasitic ) , toxins , immunological syndromes , and hypersensitivity can cause myocarditis . among these lewin et al . reported that seven explanted hearts from 288 heart transplants ( 2.4% ) had histological evidence of hypersensitivity myocarditis . unlike other forms of myocarditis , the prognosis of hypersensitivity myocarditis is excellent , usually improving after administration of the causative drug is ceased . , we report a case of hypersensitivity myocarditis , as confirmed by cardiac magnetic resonance imaging ( cmr ) and endomyocardial biopsy ( emb ) , which subsequently improved after cessation of the causative drug and administration of prednisolone . she had a history of hypertension , transient cerebral ischemic attack , and osteoarthritis in both knees . her blood pressure was 91/53 mmhg , pulse rate was 63 beats per minute , respiration rate was 20 breaths per minute , and body temperature was 37. upon physical examination , heart sounds were normal without murmur . multiple itchy erythematous lesions were present on the hands , buttocks , abdomen , and trunk ( fig . the results of laboratory examinations were as follows : white blood cell count , 9,140/mm ; eosinophil count , 1,380/mm ; hemoglobin , 10.3 g / dl ; platelet count , 123,000/mm ; c - reactive protein level , 1.7 mg / dl ; and erythrocyte sedimentation rate , 72 mm / sec . the levels of brain natriuretic peptide , creatine kinase - mb ( ck - mb ) , and troponin - i were 944 pg / ml , 56.73 ng / ml , and 38.85 ng / ml , respectively . initial electrocardiography showed st segment elevation 1 mm in leads ii , iii , avf , v5 , and v6 ( fig . emergency coronary angiography was performed under the assumption of acute st segment elevation myocardial infarction at the inferolateral wall , but coronary atherosclerosis was not evident . echocardiography showed the " sparkling " appearance of the left ventricular ( lv ) myocardium , concentric lv hypertrophy , and mild hypokinesia on the anterior , anterolateral , and posterior walls from the mid - lv to the apex with 50% lv ejection fraction . peripheral blood eosinophilia , skin rash , and a history of taking multiple medications suggested hypersensitivity myocarditis . 3 . management of heart failure using aldosterone and furosemide was initiated promptly . on the second day of hospital admission , however , dyspnea worsened , and newly developed bilateral pulmonary congestion was noted on chest radiography . therefore , cmr and emb were carried out to confirm the diagnosis of hypersensitivity myocarditis . contrast - enhanced cmr ( ce - cmr ) showed high signal intensities in circular and nodular patterns mainly in the epicardium and septum of the left ventricle ( fig . these patterns suggested infiltrative myocarditis , such as amyloidosis , sarcoidosis , or eosinophilic myocarditis . emb obtained from the septum of the right ventricle revealed lymphocytic and eosinophilic infiltration in the interstitium and perivascular area , findings that were consistent with a diagnosis of hypersensitivity myocarditis ( fig . 5 ) . levels of ck - mb and troponin - i were normalized on days 6 and 9 , respectively . the peripheral eosinophil count decreased from 1,380/mm to 620/mm on day 2 and was normalized ( 50/mm ) on day 4 . the skin rash disappeared almost completely after use of 5 mg prednisolone , and the patient was discharged from the hospital on day 12 . echocardiography at the 6-month follow - up showed normalized regional wall motion abnormalities and improved lv systolic function from 50% to 70% of the ejection fraction . at the 6-month follow - up , ce - cmr showed that previously high signal intensities in circular patterns in the epicardium of the left ventricle had disappeared and the oval - shaped area of high signal intensity in the lv septum had decreased in size ( fig . eosinophilic myocarditis can be classified according to cause and includes those types associated with systemic disease ( e.g. , hypereosinophilic syndrome , churg - strauss syndrome , malignancies ) , parasitic infections ( e.g. , toxocara canis ) , and drugs or vaccines ( hypersensitivity myocarditis ) . eosinophilic myocarditis associated with hypereosinophilic syndrome is usually underpinned by a history of peripheral eosinophilia ( > 1.5 10/l ) lasting > 6 months and is related to systemic involvement ( e.g. , central nervous system , gastrointestinal tract , heart , skin , or lung ) . in the present case , hypereosinophilic syndrome and parasitic infection were excluded because the patient did not have a history of prolonged eosinophilia , other organ involvement , or ingestion of raw meat . instead , she had a history of taking multiple medications , urticaria , and peripheral eosinophilia drug - related myocarditis can be classified into five types : 1 ) hypersensitivity myocarditis ; 2 ) toxic myocarditis ; 3 ) endocardial fibrosis ( e.g. , ergotamine tartrate , methysergide , phentermine , fenfluramine ) ; 4 ) drug - induced cardiomyopathy ( e.g. , anthracycline , chloroquine ) ; and 5 ) giant cell myocarditis . numerous medications , including clozapine , sulfonamide , penicillin antibiotics , methyldopa , and some antiseizure drugs , have been reported to be associated with hypersensitivity myocarditis . delayed hypersensitivity is the main pathogenesis and occurs from several days to months after administration of the causative agent . hypersensitivity myocarditis is not easy to recognize because the clinical features suggestive of drug hypersensitivity reactions ( e.g. , urticaria , angioedema , malaise , fever , eosinophilia ) do not occur uniformly . however , if tissue necrosis or deterioration of clinical status is observed , corticosteroid and cytotoxic agents can be used . emb is the gold standard tool in the diagnosis of myocarditis . according to the dallas criteria , eosinophils may be a minor component of postviral and giant cell myocarditis but are predominant in hypersensitivity and parasitic myocarditis as well as hypereosinophilic syndrome . lymphocytic and eosinophilic infiltrates with slight myocyte necrosis were observed in our case , which coincided with hypersensitivity myocarditis . myocarditis is often a focal process , so sampling error may occur and increase the false - negative rate . a previous study of endomyocardial samples obtained from the hearts of patients who died of myocarditis performed at the mayo clinic reported a false - negative rate of 37% for the right ventricle . other limitations of emb include the aggressiveness of the procedure as well as the delay until confirmation of the result . the lake louise criteria were found to have a sensitivity of 67% , specificity of 91% , accuracy of 78% , positive predictive value of 91% , and negative predictive value of 69% , when the criteria were compared with clinical or histopathological data . mahrholdt and sechtem reported recently that cmr - guided biopsy improved the sensitivity of emb . thus , the combined application of cmr and emb may yield diagnostic synergy and overcome some of the limitations of cmr or emb when applied individually . in our case , we performed cmr - guided emb on the right ventricular septum , in which we detected regional high signal intensity on late gadolinium enhancement . in conclusion , careful history taking ( especially with regard to drugs ) , thorough physical examination , and clinical suspicion can help in recognizing hypersensitivity myocarditis both accurately and promptly . cmr - guided emb is a valuable tool for the early and appropriate diagnosis for hypersensitivity myocarditis . our patient recovered completely after cessation of administration of the causative drug and short - term administration of prednisolone for rapidly worsening hypersensitivity myocarditis .

myocarditis often occurs due to viral infections and postviral immune - mediated responses . hypersensitivity myocarditis is a rare form of myocarditis . numerous drugs can induce myocarditis , which is typically reversible after withdrawal of the causative agent . here , we report a case of hypersensitivity myocarditis that was probably triggered by amoxicillin and that resolved completely with heart failure management as well as discontinuation of the drug . a 68-year - old woman presented with acute chest pain mimicking acute coronary syndromes , but the coronary angiography was normal . a recent history of taking medications , skin rash , and peripheral eosinophilia suggested a diagnosis of hypersensitivity myocarditis , which was confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy .

birt - hogg - dub syndrome ( bhds ) is an inherited autosominal dominant genodermatosis that predisposes individuals to the development of fibrofolliculomas ( ff ) , trichodiscomas ( td ) , and acrochordons of the face , neck , and upper trunk ( 1 ) . there is also an increased risk for lung cysts , spontaneous pneumothorax , and renal carcinomas in affected people , and some patients may also develop colorectal polyps and cancers ( 2 - 4 ) . the disease is caused by germline mutations in the bhd ( also known as flcn ) gene located in 17p11.2 encoding folliculin , a new protein with unknown function ( 5 ) . we report a patient with bhds in which mutation analysis subsequently revealed a novel mutation . a 31-yr - old woman visited the department of dermatology for evaluation of long - standing mildly pruritic facial papules that she had had for 10 yr ( fig . previously she had been treated with co2 laser and aldara ointment with the impression of verruca or syringoma but with little effect . physical examination revealed several firm , flesh - colored , dome - shaped , papular lesions ranging from 2 to 5 mm in diameter , distributed on the face and neck area . the patient had a history of pneumothorax ; otherwise , her medical history was not notable . one sample showed concentric layers of cellular fibrous tissue around hair follicles with an aritifactual cleft separating the fibroma from adjacent connective tissue ( fig . also in another sample , a raised papule composed of connective tissue surrounded by a lateral collarette was seen ( fig . staining with alcian blue and elastin stain revealed an unencapsulated loosely woven admixture of collagen and thin elastic fibers with mucin . periodic acid - schiff ( pas ) staining showed multiple thin and thick walled blood vessels with pas - positive basement membrane within the substane of the tumor . . computed tomographic scan of the chest , abdomen , and pelvis showed multiple cysts on both lower lung zone , with sizes ranging from 1.4 - 2.4 cm and a small amount of pneumothorax noted on the left anterior basal hemithorax . there was no family history of renal tumors , colon carcinoma , or other benign or malignant neoplasm . however , the patient reported that her two aunts died of ' lung disease ' ( diagnosis unknown ) and one of her older sisters was remembered to have had multiple tumorous lesions . both of her older sisters passed away at an early age but she did not know the cause of death . molecular analysis of the bhd gene was performed after informed consent from the patient . all the coding regions of the bhd gene ( exons 4 - 14 ) were amplified using polymerase chain reaction ( pcr ) with oligonucleotide primers we designed ( table 1 ) . the amplified pcr products were sequenced using the abi 3100 genetic analyzer ( applied biosystems / hitachi , foster city , ca , u.s.a . ) . sequencing analysis revealed a novel deletion mutation ( p.f519lfsx17 [ c.1557delt ] ) in the bhd gene exon 14 of the patient ( fig . this mutation results in producing the truncated protein folliculin , which is caused by frameshift of amino acid sequence in the bhd gene product . also , this deletion mutation has not yet been found in the normal populations , indicating that this mutation is the real cause of the syndrome in this case . bhds was recently found to be caused by heterozygous loss - of - function mutations in the bhd tumor suppressor gene on chromosome 17p11.2 , which encodes the novel protein folliculin . fluorescent in situ hybridization has shown the expression of bhd mrna in many normal tissues including the skin and its appendages , the distal nephron of the kidney , stromal cells , and type 1 pneumocytes of the lung ( 6 ) . the function of the bhd gene in tumorigenesis , however , has not yet been elucidated . the defective protein in patients with bhds may affect the cell 's cytoskeleton , disrupting the extracellular matrix and affecting the regulation of cellular proliferation ( 7 ) . because patients with bhds have inactivating mutations in the bhd gene , and many bhds tumors exhibit loss of heterozygosity , the bhd gene is considered to be a tumor suppressor gene ( 7 ) . fluorescent in situ hybridization showed that bhd mrna was strongly expressed in the proliferating epithelial strands of ffs but not expressed in the renal tumors of patients with bhds . genotype - phenotype correlation remains to be evaluated for bhds , but it was recently suggested that significantly fewer renal tumors were observed in patients with the c - deletion than those with the c - insertion mutation in the exon 11 hotspot ( 9 ) . to date , several different bhd germline mutations have been identified with mutations affecting all translated exons ( 4 - 11 ) with the exception of exons 8 and 10 . 4 ) . clinical diagnosis of bhds requires a minimum of 10 skin lesions clinically compatible with ffs and at least one histologically proven ff ( 5 , 9 ) . ff and td present as asymptomatic single or multiple dome - shaped papules commonly located on the head , neck , back , and arms . however , many researchers now consider perifollicular fibroma in patients with bhds to actually represent ff ( 10 ) . thus , based on clinical and histological findings , our patient could be diagnosed as bhds . since its description in 1977 bhds patients are 9.3 times more likely to develop a renal tumor than unaffected persons , and are 32.3 times more likely to develop a spontaneous pneumothorax ( 12 ) . older age and male gender increase the risk for renal tumors , whereas the risk of spontaneous pneumothorax is inversely associated with age ( 12 ) . between 15% and 30% of bhds - affected patients , patients develop renal tumors much earlier than unaffected persons , typically developing tumors in their 20s or 30s instead of in their 70s and often presenting with multiple , bilateral renal cancers . in the absence of strictly defined guidelines , it is recommended that patients with clinical manifestations of bhds undergo abdominal computed tomography and/or renal ultrasound at the time of diagnosis . siblings should have a complete physical examination with biopsy of lesions suspicious for ff / tds beginning in their 20s . routine screening for renal pathology may begin if they have ff or at age 40 yr . tumors less than 3 cm are observed , whereas tumors larger than 3 cm are treated with nephron - sparing procedures including partial nephrectomy ( 14 ) . spontaneous pneumothorax was more likely to occur in younger patients with bhds ( 12 ) . patients with bhds should be informed of the increased risk and educated on the signs and symptoms of pneumothorax . our patient was diagnosed with pneumothorax in her 20s but other concominant abnormalities were not found . however , as the risk of renal tumors increases with age we advised the patient to have regular screening . the risk for colon polyps and colon cancer was not increased in bhds ( 12 ) , so screening for colon pathology may not be warranted . however , routine screening by colonoscopy is included in the currently recommended guideline for all patients aged > 50 yr . the decision to undergo examination at an earlier age should be discussed with the patient . the actual incidence of bhds is unknown , and the disease is most likely underdiagnosed . it is imperative that physicians recognize the skin lesions of bhds and institute proper screening to detect other manifestations of the disease , such as renal tumors and lung cysts . patients with numerous facial and truncal papules resembling ffs are candidates for biopsy . in summary , we report a case of bhds with a novel mutation , which is the first report in korea .

birt - hogg - dub syndrome ( bhds ) is an autosomal dominant genodermatosis characterized by cutaneous hair follicle tumors ( fibrofolliculoma or trichodiscoma ) , pulmonary cysts , and increased risk of renal neoplasia . the genetic alteration for bhds has been mapped to chromosome 17p12q11 , and the gene in this region has been cloned and believed to be responsible for the bhds . mutations in the bhd gene ( also known as flcn ) have been described in the patients with bhds . we present a case of a 30-yr - old korean woman with multiple mildly pruritic papules on her face and neck area . the patient had several firm , flesh - colored , dome - shaped , papular lesions measuring between 2 to 5 mm . except for a history of pneumothorax her medical records were not remarkable . mutation analysis of the bhd gene was performed , and a novel deletion mutation ( p.f519lfsx17 [ c.1557delt ] ) causing truncation of the gene product , folliculin , was found in the exon 14 . the actual incidence of bhds is unknown , but it is most likely underdiagnosed . so it is imperative that doctors recognize the skin lesions of bhds and institute proper screening to detect other manifestations of the disease . here , we report a case of bhds with a novel mutation , which is the first report in korea .

gastrocnemius muscle is commonly used as a local flap for coverage of soft tissue defect in the upper third of the leg . the arc of muscle flap extends from the lower thigh , entire knee joint , popliteal fossa and upper third tibia . gastrocnemius muscle is a workhorse flap to cover upper third tibial defects because of its wide arc of rotation , easy dissection and a reliable vascular pedicle . the limiting factors in the case of gastrocnemius muscle are difficulties in covering middle one - third tibial defects . one of the most challenging areas in reconstructive surgery is the closure of soft tissue defects of the middle third leg because of a small quantity of local tissue available for reconstruction , poor vascularisation and subsequent poor healing encountered in this region . methods for coverage have evolved from the bipedical flap , local skin flaps ; cross - leg flap , soleus flap and microvascular free flaps . however , all these techniques have its inherent limitations . the inferiorly based hemi gastrocnemius muscle flap can be useful for reconstruction of the middle third of the leg . the majority of these arterial communications are arranged in bundles , although isolated , single ones are not infrequent . all these studies were experimental and in 1983 , bashir first reported only three clinical cases of inferiorly based gastrocnemius muscle flap which was supplied from the lowermost vessel across the raphe . after that , some authors also proposed the use of inferiorly based flap , but not many clinical applications were reported . atchabahian and masquelet performed the anatomic study in thirty legs showing that it is not possible to raise this flap in almost 25% of patients due to small calibre of communicating branches . till now , no indian studies have been carried out , and the reliability of the pedicle of such a flap needs to be further investigated . if this flap is feasible than it may be a reliable alternative for coverage of middle 1/3 lower leg defects , especially when other flaps are not available and free flaps are not indicated . the objective of this study was to conduct a cadaveric study in the large specimen to determine the consistency of arterial communication between two heads of gastrocnemius muscle using radio - opaque contrast with future application of taking one head of muscle distally based for coverage of middle third defect of the tibia . this study was conducted over a period of 1 year in the department of surgery - plastic surgery unit and department of forensic medicine ; in government medical college in central india . sixty specimens of gastrocnemius muscle were harvested from thirty fresh cadavers and studied . before study institutional ethical committee permission was obtained . cadavers with any congenital anomaly , fractures or crush injury and previous surgeries around knee joint were excluded from the study . a posterior longitudinal midline incision was given extending from 5 cm above the knee joint up to achilles ' tendon . deep fascia was incised longitudinally and retracted exposing the superficial surface of the gastrocnemius muscle . mobilisation of muscle started at lower muscle tendon junction in the loose areolar tissue between gastrocnemius muscle and soleus . sharp dissection was required to separate the muscle from aponeurosis which develops on its anterior surface . a detachment of two heads of gastrocnemius muscle from femur was then done with careful dissection of the neurovascular pedicle . popliteal artery ligated and divided just after it has given medial and lateral sural arteries and before bifurcation . medial sural artery ligated and divided and 20 ml contrast given through popliteal artery . in remaining thirty specimens lateral sural artery ligated and divided and 20 ml contrast given through popliteal artery . digital x - rays of gastrocnemius muscle specimen were taken , and collaterals between two bellies in lower half were noted , and the distance of collaterals from the muscles top edge was also noted . after harvesting the muscle , the communications were studied using radio - opaque contrast injection using digital x - ray technique . we found the communications between both bellies of the gastrocnemius muscle in all specimens in both legs [ table 1 and figures 14 ] . presence of communication between bellies right leg - medial sural artery ligated and lateral sural artery injected left leg - medial sural artery ligated and lateral sural artery injected right leg - medial sural artery injected and lateral sural artery ligated left leg - medial sural artery injected and lateral sural artery ligated in the right leg , mean distance of communications from the upper edge of the medial belly was 15.88 cm ( maximum 23.66 cm and minimum 12 cm ) considering that mean length of the medial belly was 19.41 cm , communications were present in distal 3.53 cm . the mean distance of communications from the upper edge of the lateral belly was 14.72 cm ( maximum 18.8 cm and minimum 10 cm ) and mean length of the lateral belly was 17.41 cm , therefore , communications were present in distal 2.69 cm [ table 2 ] . right leg - distance of communication from upper edge of muscles in the left leg , mean distance of communications from the upper edge of the medial belly was 16.01 cm ( maximum 19.91 cm and minimum 13 cm ) , the mean length of the medial belly was 19.80 cm . the mean distance of communications from the upper edge of the lateral belly was 13.78 cm ( maximum 16.38 cm and minimum 8.2 cm ) mean length of the lateral belly was 16.84 cm , therefore , communications were present in distal 3.06 cm . communications were consistently present between the two bellies of the gastrocnemius muscle in lower part across the raphe [ table 3 ] . reconstruction of lower extremity defects can be a difficult task because of the lack of intervening muscle between the skeletal elements and the skin , and the limited mobility of the overlying skin . although microsurgical procedures provide excellent results in the head and neck region , the success rate is usually lower in the lower limbs . it requires a long operative time ; experienced skilful technique ; and patent vascular status of the recipient site . free flap transfer to the lower limb in chronic posttraumatic conditions is known to have a higher complication rate with flap loss in up to 10% of cases . despite recent advances in microsurgical techniques , leading to major improvements in the quality of lower limb reconstruction , coverage of lower leg defects by loco - regional flaps remains indicated in selected cases . a local random - pattern skin flap has an indistinct perfusion pattern and is limited in size . defects of the middle third of the tibia can be covered with the soleus flap . however , the defect will be covered by the least vascularised part of the muscle ; the volume of the flap is often too small to fill the defect . local fascio - cutaneous flaps can provide an alternative for coverage of middle one - third tibial defects , but it may be in the zone of trauma hence not very safe . the cross - leg flap has the disadvantage of long - term immobilization and two stage procedure . the anterior tibialis flap is a useful option for providing soft tissue to cover open tibial injuries in the middle and distal thirds of the tibia . it is limited by the transition of the muscle to the tendon in the distal third of the tibia . in 1983 , bashir treated many severe lower injuries due to high - velocity missiles and he described the alternate method of covering a defect in the middle third of leg and the upper part of lower third using the medial head of the gastrocnemius muscle as an inferiorly based flap . he used medial head gastrocnemius muscle flaps as an inferiorly based in three cases with no failure rates . after that , there was isolated reports of using distally based gastrocnemius muscle for coverage of middle third tibial defects . mathes and nahai also proposed the use of an inferiorly based flap after having made a rough mention to anastomotic vessels . the vascular basis of this flap is the vessels across the distal half of the raphe between the muscle heads . tsetsonis et al . studied the 14 fresh cadaveric gastrocnemius muscles to describe the anatomy of the communicating ( anastomotic ) vessels between the gastrocnemius muscle heads and record the extent of their supply potential . anastomotic veins were dissected along the raphe after perfusion of each muscle with 0.1% methylene blue solution . he described mean distance 4.7 cm of lowest anastomotic vessels from the lower pole of the corresponding medial head . regarding arterial cross - supply , it was clearly evident that each head could be vascularised solely from the contralateral one , mostly through these bundles . nevertheless , the location of this vessel varies significantly and can not be detected preoperatively . measurements demonstrated that although this vessel is not found at a constant level , it is invariably detected in the lower third of the medial gastrocnemius head 's length and in 93% of cases , in the lower fourth . given that the venous communication between the heads has been documented as well , the authors think that an inferiorly based flap of the medial gastrocnemius head for defects of the middle third of the tibia might be both reliable and applicable ; however , for reasons of safety , the muscle heads should remain attached along their lower third . in 2008 kishk did a study by performing inferiorly based hemigastrocnemius flap in a reconstruction of middle third leg defect with exposed tibia in 19 patients and concluded that inferiorly based hemigastrocnemius muscle flap based on the vascular bundles between the two heads can be useful for reconstruction of the middle third of the leg . one flap ( 5.2% ) was lost in the early postoperative period because of venous congestion related to inadequate tunnelling of the flap . this is the first study conducted on a larger number of cadavers ( sixty specimens of gastrocnemius muscle were harvested from thirty fresh cadavers ) . we observed communications between the two bellies of gastrocnemius muscles in all specimens . in the right leg , the mean length of the medial belly was 19.41 cm and communications were present in distal 3.53 cm and mean length of the lateral belly was 17.41 cm and communications were present in distal 2.69 cm . in the left leg , the mean length of the medial belly was 19.80 cm and communications were present in distal 3.79 cm and mean length of the lateral belly was 16.84 cm and communications were present in distal 3.06 cm . the distal communications between gastrocnemius bellies are not constant in their location , but all the connections were present in distal 3.79 cm of raphe . therefore , the precise pivot point for distal rotation of muscle can not be ascertained but while taking distally based flap of gastrocnemius roughly 1/3 of distal attachment or distal 3.79 cm of connection between raphe should be maintained to preserve the vascular communications between the bellies . a study by tsetsonis et al . showed mean distance 4.7 cm of lowest anastomotic vessels from the lower pole of corresponding medial head , therefore , our study support more distal pivot point for muscle head rotation . our study supports the future application of inferior based gastrocnemius muscles flap to cover defects of the middle third leg . it is a simple technique allowing rapid , durable , and reliable coverage of these defects without sacrificing a major vessel to the foot . no donor site morbidity and functional deformity , with primary closure of donor site . this is the large study on sixty specimens of thirty fresh cadavers and first reported from india . we found communications between both bellies of the gastrocnemius muscle in all sixty specimens in both legs in indian population . although communications between gastrocnemius bellies are not constant in their location , they were present in all specimens . our study supports the future application of inferior - based hemigastrocnemius muscles flap to cover defects of middle third leg safely . when distally based hemigastrocnemius flap is planned , roughly 1/3 of distal attachment or distal 3.79 cm of connection between raphe should be maintained to preserve the vascular communications between the bellies .

introduction : gastrocnemius muscle is a workhorse flap to cover upper third tibial defects but has a limitation in covering middle one - third tibial defects . the inferiorly based hemi gastrocnemius muscle flap can be useful for reconstruction of the middle third of the leg . the arterial communication between the gastrocnemius muscle heads has been demonstrated , the consistent location , however , was not studied in large specimens.materials and methods : this study was conducted on sixty specimens of gastrocnemius muscles harvested from thirty fresh cadavers to determine arterial communication between two heads of gastrocnemius muscle using radio - opaque contrast with future application of taking one head of muscle distally based for coverage of middle third defect of tibia . a total of 60 specimens were obtained from thirty fresh cadavers . in thirty specimens , medial sural artery ligated and divided and 20 ml iohexol ( 350 ) given through popliteal artery . in remaining thirty specimens lateral sural artery ligated and divided and 20 ml iohexol ( 350 ) given through popliteal artery . digital x - rays of gastrocnemius muscle specimens were taken , and collaterals between two bellies in lower half were noted and the distance of collaterals from the muscles top edge was also noted.results:we found the communications between both bellies of the gastrocnemius muscle in all specimens in both legs . the mean distance of communications from the upper edge of the medial belly was 15.88 cm and from upper edge of the lateral belly was 14.72 cm in the right leg , respectively . the mean distance of communications from upper edge of the medial belly was 16.01 cm and from upper edge of the lateral belly was 13.78 cm in the left leg . the distal communications between gastrocnemius bellies were not constant in their location , but all the connections were present in distal 3.79 cm of raphe.conclusion:this study supports the future application of inferior - based hemigastrocnemius muscles flap to cover defects of middle third leg . when distally based hemigastrocnemius flap is planned roughly 1/3rd of distal attachment or distal 3.79 cm of connection between raphe should be maintained to preserve the vascular communications between the two bellies .

disability evaluation typically requires an assessment of the activities of daily life ( adl ) and instrumental adl ( i - adl ) . in japan , a physical disability certificate is based on the patient 's adl and i - adl grades . the independent adl scale , which is widely considered within the field of rehabilitation medicine to be a particularly important component in the evaluation ( 1 , 2 ) , considers both individual and universal factors ( fig . assessment is performed by analyzing the results of test activities relating the patient 's personal life . for example , adult independence refers to a person who does not require external care in daily life , whereas child independence includes care within the family and school life . such personal factors have been nurtured through development in the community and belong to the community 's values and customs . the universal factors , on the other hand , are measured against the common rule of humanbeings . furthermore , disability evaluation should also include assessment for the supporting system in the community - based rehabilitation ( cbr ) and other problems . these other problems , which relate to objective signs , the timing of evaluation and multiple impairments , are still under fierce debate . , japan officially recognizes three forms of the identification booklet for the disabled , one for physical disability , one for mental disability , and another for psychological disability . during the course of this investigation , several reports issued by the ministry of health , labor and welfare of japan , including the outline of the systems and basic statistics in annual reports on health and welfare 1998 - 1999 social security and national life from white paper and reports were reviewed ( 3 ) . data concerning the annual change in the number of people with physical disabilities by type and age per 1,000 people were used to analyze total disability evaluation , while the annual change in the number of children with physical disabilities by type and age was used to analyze child disability evaluation . the number of people with physical and mental disabilities was used to determine the relationship between welfare facilities and the home in the community . finally , several data related to the elderly were used to anticipate bigger problems in future . the results of this study , as provided in detail in the appendices to this report , are summarized as follows . recent trends in the last 10 yr suggest a sharp rise in physical disabilities and internal disorders among the elderly ( table 1 , 2 ) . data on children by type ( table 3 ) and age ( table 4 ) shows an increase in the rate of internal disorders and young children with physical disabilities . data on the overall number of people with disabilities ( table 5 ) reveals that 28.5% of patients in health care facilities have mental retardation , whereas only 5% have physical disabilities . data suggesting bigger future problems for the elderly are also presented in fig . 2 and table 6 and 7 . in japan , disability is categorized under three identification booklets : 1 ) physical disability , which is classified by four subgroups , 2 ) mental disability , and 3 ) psychological disability . the classification of the physically disabled subgroups ( table 1 - 4 ) was very useful for determining the problems for government policy on welfare and public health . the increasing rate of internal disorders within the physically disabled has become a major theme for following global welfare services in the future . a multi - system for evaluating disabilities has resulted in many welfare services , depending on the various kinds of disabilities . however , the achievements of the welfare system , based on different types of disabilities , have led to a complex or confused service system . the system has also been affected yearly by the changing social community around persons with disabilities . accordingly , the increasing ratio of the elderly population has prompted the development of a new disability evaluation related to practical adl . to cite another example , mental disability has been evaluated from infancy because of a lack of social response . as such , most people with mental disability usually tend to receive the identification booklet up to the age of 18 yr . however , table 5 shows that , in japan , adults with mental disability tend to be less adaptive to the community than those with physical disability . therefore , the ministry of health , labor and welfare of japanese government has started to rearrange many welfare services to be more suitable to a small community around persons with disabilities . moreover , the concept of preventing disabilities is emphasized not only in rehabilitation medicine , but also in cbr , indicating that disability evaluation needs another factor of support system based on their community . thus , it is important to think about the disability evaluation according to the characteristics of age , impairment and assistive environment . in the field of cbr , disability evaluation has recently become important for measuring the effects of rehabilitation treatment in medical insurance and decision of the grade of welfare service volume in japan . while the first and second groups have been historically well - established without any disagreement on the classifications of disability type , the third group concerning psychological disability has recently been questioned with respect to the visibly less apparent disabilities relating to cognition , memory , attention , emotion , and social behavior after traumatic head injury . although the new system to evaluate and support such a disability group is under development throughout the country , problems with classification continue to be debated .

to examine the current state and social ramifications of disability evaluation in japan , public data from annual reports on health and welfare 1998 - 1999 were investigated . all data were analyzed based on the classification of disabilities and the effects of age - appropriate welfare services , which have been developed through a half - century of legislative efforts to support disability evaluation . these data suggest that disability evaluation , while essentially affected by age and impairment factors at a minimum , was impacted more by the assistive environment for disabilities . the assistive environment was found to be closely linked with the welfare support system related to a global assessment in the field of community - based rehabilitation .

a 39-year - old caucasian male with no significant past medical history presented to the emergency room reporting a two - week history of a worsening cough associated with the production of rusty sputum , pleuritic chest pain , and intermittent fevers , as well as an unintentional 30-pound weight loss over the preceding several months . a chest x - ray revealed a large cavitary lesion in the superior segment of the left lower lobe and a smaller cavitary lesion in the right mid - lung ( figure 1 ) . the presence of these cavities was confirmed on a computer tomography ( ct ) scan of the chest ( figure 2 ) . he was started on empiric treatment with ceftriaxone and clindamycin , then placed in respiratory isolation until three sputum smears were negative for acid - fast bacilli . hiv antibody was positive ; his cd4 count was 19/l and his viral load was 121,000/ml . gram stain and acid - fast stain on bronchial washings were negative , but pneumocystis jirovecii was revealed by silver staining . he was not hypoxic at rest and did not desaturate with exertion , so prednisone was not given . trimethoprim / sulfamethoxazole ( two double - strength tablets t.i.d . ) was begun , after which he defervesced , his cough diminished , and he was discharged . however , culture of the bronchial washings also yielded brevibacterium , which was initially considered to represent a contaminant . he had been given an appointment at an hiv clinic to begin anti - retroviral therapy within his first week as an outpatient , but did not keep this appointment because he felt unwell . the patient returned eight days after discharge , complaining of persistent fevers of up to 104.5f . trimethoprim / sulfa methoxazole was immediately discontinued owing to concern that the drug had induced agranulocytosis . he had been started on azithromycin during his first hospital stay for prophylaxis against mycobacterium avium and this drug was continued into his second hospitalization . early in his second hospital course , the bronchial cultures from his first admission returned from a state reference laboratory with a final speciation of rhodococcus equi . at this point , the patient was started on imipenem/ cilastatin , vancomycin , rifampin , and ciprofloxacin , all antibiotics with reported efficacy against this resistance - prone organism . the organism was resistant to trimethoprim/ sulfamethoxazole but sensitive to imipenem and ciprofloxacin , so these medications were continued as purposeful double coverage to maximize macrophage penetration and to avoid the development of resistance during monotherapy . coverage for co - infection with pneumocystis could not be accomplished effectively because the patient became completely intolerant of oral intake in the setting of neutropenic colitis , and intravenous pentamidine caused a significant transaminitis . his inability to tolerate any medications by mouth also precluded the initiation of anti - retroviral therapy . two weeks after re - admission , the patient began to experience intermittent right - sided weakness and paresthesias , with a contrast ct of the head demonstrating edema at the left posterior frontal corticomedullary junction . magnetic resonance imaging ( mri ) of the brain revealed a hyperintense 1.01.71.7-cm lesion centered within the subcortical white matter of the left posterior central gyrus , as well as other smaller multifocal lesions ( figure 3 ) . he was started on steroids and phenytoin ; neurosurgeons were consulted for a biopsy but recommended serial imaging because there are reports describing the dissemination of rhodococcus to the brain , and the patient was already on appropriate treatment for this pathogen . however , the patient 's neurological status deteriorated over the next week and he developed a right lower facial droop and word - finding difficulties . a repeat ct scan showed interval worsening of the vasogenic edema around his left parietal and right occipital lesions . a nodule was surgically removed from the left parietal lobe , with the pathology showing cysts consistent with toxoplasma gondii bradyzoites . despite the commencement of pyrimethamine and the increase of azithro mycin from prophylactic to treatment doses his final head ct revealed diffuse cerebral edema and interval development of leptomeningeal enhancement throughout the posterior fossa . his family decided to withdraw care five days after surgery , and he died . figure 3magnetic resonance image of the brain two weeks after re - admission . magnetic resonance image of the brain two weeks after re - admission . first of all , pneumocystis jirovecii , while still the most common opportunistic infection in aids patients , is not the most frequent etiology of cavitary lung lesions in this immunocompromised population . the typical radiographic appearance of pneumocystis pneumonia produces bilateral interstitial infiltrates . when pneumocystis cavities do arise , they may result from the outgrowth of cystic disease , from the breakdown of normal lung tissue by hyperactive elastase - elaborating macrophages , or from vascular invasion by the organism leading to intrapulmonary thrombosis and necrosis of down - stream tissues . various radiographic case series estimate the incidence of cavitary lesions in hiv - positive pneumocystis patients at less than 10 percent , although the advent of high - resolution ct scans has lowered the threshold for detection of cavities . lung cavitation in pneumocystis patients still constitutes an uncommon manifestation of a common disease , and finding pneumocystis in a patient with cavitary pneumonia should prompt widening of the differential diagnosis , while still recognizing the potential role of pneumocystis as a co - pathogen . other causes of cavitary disease include , but are not limited to : tuberculosis , mycobacterium kansasii , invasive pulmonary aspergillosis , pseudo monas aeruginosa , nocardia asteroides , or any complicated bacterial pneumonia , as well as neoplasms like kaposi 's sarcoma and non - hodgkin 's lymphoma . as this case demonstrates , rhodococcus equi should also be considered as an infectious cause of lung cavitation in an aids patient . identification of the rhodococcus organism was delayed in our case owing to initial confusion of the pathogen with brevibacterium . brevibacterium and rhodococcus both belong to the group of coryneform bacteria ( indeed , rhodococcus equi was originally known as corynebacterium equi because of its morphology ) . however , while brevibacterium casei has been associated with rare cases of sepsis in aids patients , it is not known to have the same predilection for the lungs as rhodococcus . rhodococcus equi is a facultative aerobic , nonspore - forming gram - positive coccobacillus that classically produces a salmon - pink pigment and may manifest positive acid - fast bacilli stain results . because of the tendency to confuse rhodococcus with other coryneform flora or mycobacteria , the microbiology laboratory should be alerted to the practitioner 's concerns about the presence of this organism , especially in patients with compromised cell - mediated immunity who present with cavitary pneumonia . in retrospect , our patient was found to have lived and worked in an area with plentiful livestock , almost certainly coming into contact with soil contaminated by herbivore manure . rhodococcus is usually acquired in humans through inhalation of such soil , followed by hematogenous spread from the lungs to other sites . the organism does not necessarily show a nocardia - like tropism for the central nervous system but the brain is one of the most common sites of extrapulmonary infection . in an hiv - positive or otherwise immunocompromised patient , the principle of ockham 's razor should be invoked cautiously . the propensity of aids patients to present with two or more synchronous infections can complicate diagnosis significantly and lead to inadequate treatment . in this case , the presumption that the patient 's lung cavities were caused by pneumocystis led to treatment with high - dose trimethoprim / sulfamethoxazole , which is not uniformly effective against rhodococcus and was demonstrably unsuccessful in this case . then , the presumption that the patient 's cerebral lesions arose from disseminated rhodococcus delayed the proper diagnosis of toxoplasma gondii , the most common opportunistic infection in the central nervous system of an aids patient . the patient was treated with pyrimethamine and azithromycin after toxoplasma was diagnosed , but drugs with sulfa moieties , such as sulfadiazine , were withheld owing to concern for further toxicity after he had already experienced agranulocytosis attributed to trimethoprim / sulfamethoxazole . the unfortunate clinical course described in this case report may have been accelerated by both endogenous and exogenous insults to the immune system in a patient whose cell - mediated immunity had been decimated already by a previously unrecognized hiv infection . while trimethoprim / sulfamethoxazole is the preferred agent for pneumocystis jirovecii pneumonia , it caused agranulocytosis in this patient . his neutropenic colitis further limited his treatment options and precluded the initiation of antiretroviral therapy , which could have led to a more favorable outcome by bolstering the lymphoproliferative response to his multiple infections , especially his fatal toxoplasma encephalitis . this case is a sobering reminder of the iatrogenic harm that can stem from an incorrect diagnosis , and provides a cautionary tale for the practitioner who assumes parsimoniously that a single etiology explains the entirety of a patient 's pathology .

a 39-year - old male with newly diagnosed hiv had cavitary pneumonia initially attributed to pneumocystis jirovecii but actually caused by rhodococcus equi . after neurological deterioration , he was found to have intracerebral lesions caused by toxoplasma gondii . this case underscores the inability to rely on the search for a unifying diagnosis ( ockham 's razor ) in hiv - infected patients .

robinia pseudoacacia ( black locust ) is the main honey - bearing tree that grows spontaneously in romania , especially in the plains and hills . only flowers are used for their alkalizing , antispasmodics , anti - tussives , sedatives effect , other parts of the plant especially bark and seeds are toxic [ 1 - 3 ] . flavonoids with phenyl - propane compounds and tannins are part of complex category of polyphenols . they are a valuable group of plant origin compounds of great interest in phytotherapy and pharmacology [ 5 , 6 ] . in the chemical composition of robinia pseudoacacia l. species have been cited in the literature the presence of the following flavonoids : robinin ( kaempferol-3-o - ramnozil - galactozil-7-ramnozid ) and acacetin-7-o - rutosid , apigenin , diosmetin , luteolin but also secundiflorol , mucronulatol , isomucronulatol and isovestitol . our previous studies on the chemical composition revealed the presence of several bioactive compounds such as phytosterols , which are present in the flowers , and other lipidic compounds as those from the seeds of sunflower [ 8 , 9 ] . the purpose of this study was the qualitative and quantitative analysis of the flavonoids in different plant parts specifically in flowers , leaves , bark and seeds of robinia pseudoacacia using thin layer chromatography coupled with photo - densitometry . this is a simple and rapid method , applied for separation , identification and quantitative determination of chemical compounds with the main advantage that allows the possibility to investigate one or more components without their previous isolation and purification . herbal product was harvested in may- june ( flowers , leaves ) and october ( seeds and bark ) from two different geographical areas : plain ( craiova , dolj county ) and hill ( rmnicu vlcea , vlcea county ) . herbal product was drying immediately after harvest at ambient temperature and then it was sprayed . methanolic flowers extracts : 1 g powdered herbal material was wetted with 5 ml methanol . after 2 - 3 minutes was added 10 ml methanol and stirring at approx . herbal material was filtered and the filter and herbal material was washed with methanol up to 10 ml extract . extracts were noted as follows : r1 - robinia pseudoacacia seeds extracts from plain area ( craiova ) , r2 - robinia pseudoacacia seeds extracts from hill area ( rmnicu vlcea ) , r3 - robinia pseudoacacia flowers extracts from plain area ( craiova ) , r4 - robinia pseudoacacia flowers extracts from hill area ( rmnicu vlcea ) , r5 - robinia pseudoacacia leaves extract from the plain area ( craiova ) , r6 - robinia pseudoacacia bark extract from plain area ( craiova ) . was performed under the following conditions : stationary phase : silica gel g60 f254-precoated tlc plates ( merck ) ; mobile phase : ethyl acetate ethylmethyl ketone formic acid water ( 50:30:10:10 , in volumes ) ; solution to analyze : 20% methanolic extractive solutions from the different parts of robinia pseudoacacia ( r1- r6 ) ; standard solutions : ruthoside 1,22 mg / ml ( roth ) and hyperoside 1,1 mg / ml ( merck ; darmstadt , germany ) methanol solutions ; stationary phase : silica gel g60 f254-precoated tlc plates ( merck ) ; mobile phase : ethyl acetate formic acid water ( 50:30:10:10 , in volumes ) ; about 510 l of the sample and reference compounds have been applied on the plate as 10 mm bands ; migration distance : 15 cm ; migration time : 40 min ; detection : uv light ( 254 nm ) and natural products reagent ( np / peg ) , in fluorescence . for flavonoid compounds when using the two revealing reagents , we obtained yellow , yellow green and yellow orange spots . the thin layer chromatography has been accomplished by using the above mentioned experimental conditions . in tlc coupled with photo- densitometry , the chromatographic plate was scanned with a desaga cd60 photo- densitometer scanner after spraying with iron chloride ( anisaldehyde ) . the photo - densitometer parameters : in reflection mode , deuterium lamp , = 254 nm , minimum area read : 100 . " in situ " uv - vis spectra for the main flavonoids were obtained using the photo - densitometer . device parameters are : deuterium and tungsten lamp , wavelength 254 nm , wavelength interval for uv vis spectra in situ 200500 nm , slit width 0.2 mm , repetition four times / position . herbal product was harvested in may- june ( flowers , leaves ) and october ( seeds and bark ) from two different geographical areas : plain ( craiova , dolj county ) and hill ( rmnicu vlcea , vlcea county ) . herbal product was drying immediately after harvest at ambient temperature and then it was sprayed . methanolic flowers extracts : 1 g powdered herbal material was wetted with 5 ml methanol . after 2 - 3 minutes was added 10 ml methanol and stirring at approx . herbal material was filtered and the filter and herbal material was washed with methanol up to 10 ml extract . extracts were noted as follows : r1 - robinia pseudoacacia seeds extracts from plain area ( craiova ) , r2 - robinia pseudoacacia seeds extracts from hill area ( rmnicu vlcea ) , r3 - robinia pseudoacacia flowers extracts from plain area ( craiova ) , r4 - robinia pseudoacacia flowers extracts from hill area ( rmnicu vlcea ) , r5 - robinia pseudoacacia leaves extract from the plain area ( craiova ) , r6 - robinia pseudoacacia bark extract from plain area ( craiova ) . was performed under the following conditions : stationary phase : silica gel g60 f254-precoated tlc plates ( merck ) ; mobile phase : ethyl acetate ethylmethyl ketone formic acid water ( 50:30:10:10 , in volumes ) ; solution to analyze : 20% methanolic extractive solutions from the different parts of robinia pseudoacacia ( r1- r6 ) ; standard solutions : ruthoside 1,22 mg / ml ( roth ) and hyperoside 1,1 mg / ml ( merck ; darmstadt , germany ) methanol solutions ; stationary phase : silica gel g60 f254-precoated tlc plates ( merck ) ; mobile phase : ethyl acetate formic acid water ( 50:30:10:10 , in volumes ) ; about 510 l of the sample and reference compounds have been applied on the plate as 10 mm bands ; migration distance : 15 cm ; migration time : 40 min ; detection : uv light ( 254 nm ) and natural products reagent ( np / peg ) , in fluorescence . for flavonoid compounds when using the two revealing reagents , we obtained yellow , yellow green and yellow orange spots . the thin layer chromatography has been accomplished by using the above mentioned experimental conditions . in tlc coupled with photo- densitometry , the chromatographic plate was scanned with a desaga cd60 photo- densitometer scanner after spraying with iron chloride ( anisaldehyde ) . the photo - densitometer parameters : in reflection mode , deuterium lamp , = 254 nm , minimum area read : 100 . " in situ " uv - vis spectra for the main flavonoids were obtained using the photo - densitometer . device parameters are : deuterium and tungsten lamp , wavelength 254 nm , wavelength interval for uv vis spectra in situ 200500 nm , slit width 0.2 mm , repetition four times / position . flavonoid spots appear at 254 nm in uv light as dark spots and after the revelation with np / peg reagent acquire yellow - green fluorescence . by comparing the rf sized , color and intensity of spots was possible to identify the following components : hyperoside and acacetin-7-o - ruthoside ( figure 1 ) . the other components separate on chromatographic plate could not be identified if they belong to flavonoids class . the results led to the identification of flavonoids in flowers ( r3 , r4 ) and leaves ( r5 ) , less in bark ( r6 ) . separation of ruthoside and hyperoside was made at the following rf values : 0.13 , respectively 0.35 . tlc - chromatogram in uv ( 254 nm ) for the samples of robinia pseudoacacia ( r1-r6 ) and for the standard solutions ( hyperoside , ruthoside ) rf values for the analyzed flavonosides and for the reference compounds after the photo - densitographic evaluation was made , some densitograms showed the presence of flavonoids in different concentrations . figure 2 ( a - d ) contains the overlapped tlc - densitograms for the robinia pseudoacacia methanolic extracts from flowers ( r3 , r4 ) , leaves ( r5 ) and bark ( r6 ) with the standards ( uv 254 nm ) . the analysis of methanolic flowers extracts revealed that the flowers collected from the plain area have higher flavonoid content than those harvested from the hill . tlc - densitograms in uv ( 254 nm ) for the samples of different parts of robinia pseudoacacia : a r6 in figure 3 are presented the overlapped densitograms of methanolic extracts from flowers , leaves , bark and seeds of robinia pseudoacacia . the densitograms of flower , leaves , bark and seeds extracts of robinia pseudoacacia from overlapping densitograms of the four vegetative organs of the plant it was found that flavonoids are mainly present in flowers and leaves , but in bark and seeds are in insignificant amounts . for quantitative determinations , five points calibration curves were built , under the same chromatographic and densitometric conditions . we obtained equations with good correlation coefficients . in table 2 the data of the calibration curve for ruthoside are shown . the data for the calibration curve , expressed in ruthoside coefficient x = 3679.2 correlation coefficient r2 = 0.9996 standard deviation ( sd ) = 4.389263 with desaga cd60 photo - densitometer was performed uv - vis spectra on 200 - 500 nm for ruthoside and hyperoside . maxima of absorption were at 260 respectively 350 nm for hyperoside , and at 210 , 320 respectively 410 nm for ruthoside . after analyzing the results we could determinate that flavonoids from flowers and leaves of robinia pseudoacacia have similar structures with hyperoside and ruthoside . it is known that flowers are consumed in various foods so robinia pseudoacacia may become a valuable source of antioxidants in human nutrition . the flowers have the highest content of flavonoids , ranging from 0.15 to 0.9 mg / ml . the flowers harvested in the plains have a higher concentration of hyperoside ( 0.9 mg / ml ) compared with the flowers taken from the hill ( 0.54 mg / ml ) . the leaves are rich in ruthoside ( 0.98 mg / ml ) compared with the flowers ( table 3 ) . in the seeds and bark are insignificant amounts of flavonoids . concentration of hyperoside and ruthoside within the analyzed extracts in figure 4 ( a , b ) is shown the variation of flavonosids concentrations in the studied samples and quantity in plant . the variation of hyperoside and ruthoside concentration : a - in methanolic extracts , b - in plant the qualitative and quantitative analysis of flavonoids compounds was made using two chromatographic methods : thin layer chromatography ( tlc ) and tlc coupled with photo - densitometry . it was investigated the presence of hyperoside and ruthoside in methanolic extracts obtained from different parts of the plant : flowers from plains and hill area , leaves , seeds and bark . the identification was made by comparing the spots rf values with the rf values for ruthoside and hyperoside . thus , we conclude that the methods of analysis used demonstrates that robinia pseudoacacia flowers and leaves have the highest concentration of flavonoids , compounds with pharmacological benefic potential ( heard protective , reducing low - density lipoproteins , anti - ulcerous and liver protective , antimicrobial ) and relatively low toxicity .

the purpose of this study was the qualitative and quantitative analysis of flavonoids from robinia pseudoacacia using two different techniques of analysis : thin layer chromatography ( tlc ) and tlc coupled with photo - densitometry . the results obtained by chromatographic analysis showed a higher concentration of flavonoids in flowers than in leaves . the flowers harvested in the plains have a higher concentration of hyperoside ( 0.9 mg / ml ) compared with the flowers collected from the hills ( 0.54 mg / ml ) . the leaves are richer in ruthoside ( 0.98 mg / ml ) compared with the flowers .

the technique of lymphatic mapping and sentinel lymph node biopsy ( slnb ) has emerged in the last two decades as a minimally invasive approach to evaluate regional lymph node basins in patients with intermediate and high - risk primary cutaneous melanoma . in particular , slnb is now recommended as a staging procedure for patients with t2 , t3 or t4 melanomas and clinical uninvolved regional lymph nodes ( clinical stage ib and ii ) and suggested also for patients with t1 melanomas and pathologic features associated with an increased risk of nodal micrometastases ( ulceration , high mitotic rate , ) . also positron emission tomography ( pet ) with 18f - fluorodeoxyglucose ( 18f - fdg ) has been extensively investigated in patients with melanoma and plenty of studies have shown its effective role in detecting distant metastases , further increased after the introduction of co - registered computed tomography ( ct ) scan ( 18f - fdg pet / ct ) . in this article , we introduce a case of pt4b thigh melanoma , in which both procedures were performed , together with ultrasonography . an 82-year - old white male , with a clinically - confirmed cutaneous melanoma of the right thigh , presented to our unit to undergo lymphoscintigraphy , in order to perform slnb at the same time of tumor excision . lymphoscintigraphy with tc - nanocolloids was performed on a hybrid system philips single - photon emission computed tomography / computed tomography ( spect / ct ) precedence 16 slices ( philips healthcare , eindhoven , the netherlands ) after intradermal injection of the radiopharmaceutical around the primary lesion ( four separate injections , 0.1 ml for each aliquot , total activity 100 mbq ) . low dose helical ct scan was performed : 120 kv , 100 ma , d - dom control dose , 3 mm slice thickness , 1.5 mm detector collimation , pitch 0.8 , rotation time 0.75 s. spect scan was acquired with the following parameters : 128 128 matrix size , 120 view angle , 10 s time / angle , 5 mm pixel size . spect / ct images showed uptake of the radiocolloids in a right inguinal lymph node . on ct co - registered images , anyway , another lymph node with no radiopharmaceutical uptake but with suspicious aspect ( globular morphology , absence of hilum ) was detectable in the crural region , much closer to the primary tumor [ figures 1 and 2 - left panel ] . axial views of single - photon emission computed tomography / computed tomography ( ct ) lymphoscintigraphy with tc - nanocolloids . tracer uptake can be seen in the site of injection / primary tumor ( green arrow ) and in a right inguinal node ( yellow arrow ) , while there is no uptake in a crural node with suspicious aspect on ct images ( red arrow ) volume rendering of technetium - labeled radiocolloids single - photon emission computed tomography / computed tomography ( left panel ) and f - fluorodeoxyglucose positron emission tomography / computed tomography ( right panel ) . the arrows show the sites of primary lesion ( green ) , true sentinel crural node ( red ) , false sentinel inguinal node ( yellow ) for this reason , and due to the adverse pathologic features of the removed lesion ( clark 's level iv , breslow 's depth 4.6 mm , ulceration , 89 mitoses / mm , poor inflammatory infiltrate , pt4b ) , the patient was further staged with a f - fdg pet / ct scan after surgery . pet / ct showed pathologic uptake of the tracer in the suspected right crural lymph node , which was removed : no other nodal or visceral metastases were seen [ figures 2 - right panel and 3 ] . histology demonstrated signs of chronic inflammation and no neoplastic cells in the inguinal lymph node ( analysis of slices from the whole node with hematoxylin and eosin ( h and e ) stain and confirmation with immunohistochemical staining for s-100 protein in each blank slide ) , while a massive metastasis from melanoma was seen in the crural node ( h and e ) . no significant uptake can be seen in the site of the removed primary tumor ( green arrow ) and right inguinal node ( yellow arrow ) , while high metabolic activity is demonstrated in the crural node ( red arrow ) neither inguinal lymphadenectomy nor systemic therapy was proposed , due to age and co - morbidity ( hypertensive cardiomyopathy ) and a follow - up based on abdominal , and inguinal ultrasonography was organized . ten months after surgery the patient developed a metastatic disease , further depicted by a follow - up f - fdg pet / ct scan [ figure 4 ] . follow - up f - fluorodeoxyglucose positron emission tomography / computed tomography scan ( 1 year after tumor excision ) : multiple secondary lesions can be seen in right inguinal nodes , in the liver and in many skeletal segments the prognostic factors for cutaneous melanoma have been recently revised in the 7 edition of the american joint committee on cancer ( ajcc ) ( 2009 ) , based on analysis of data for over 50,000 patients of ajcc database . apart from the features of the primary lesion ( thickness , mitotic rate , ulceration ) , the histologic status of regional nodes has been confirmed as the most powerful independent predictor of survival in clinically node - negative patients . the technique of slnb , first proposed in the 1980s , made inroads once it was clear that the treatment of regional node disease while still microscopic afforded a survival benefit compared to waiting for clinically evident disease . this strategy , minimally invasive , allows the use of more aggressive surgical approaches and systemic therapies only in higher - risk patients , with occult stage iii disease . it has shown high sensitivity ( especially when performed with spect / ct - aided lymphatic mapping and multiple peri - tumour injections ) with very low false - negative rate , mainly related to technical problems associated with identification of the true sentinel node ( sn ) by nuclear medicine physicians and surgeons and errors in tissue sampling and interpretation by pathologists . thus , even if new and more sensitive molecular techniques have already shown promising results , slnb with pathological assessment is now the recommended staging procedure for all stage i and ii patients with primary melanomas > 1.0 mm in thickness . nonetheless , with the introduction and the development of noninvasive metabolic imaging techniques ( such as f - fdg pet / ct ) also in patients affected by melanoma , the hypothesis that even slnb could be avoided and replaced by the analysis of tumor metabolism in the lymphatic basin has emerged . in the last 15 years , almost 20 papers concerning the diagnostic performance of f - fdg pet / ct in comparison to slnb ( and ultrasonography ) can be found in literature , all pointing out , with few exceptions , a very low sensitivity of f - fdg pet / ct in discovering small lymph node metastases if compared with slnb . in this scenario , our report looks somewhat interesting , suggesting the possible utility of pet / ct even in the evaluation of regional disease in selected patients . the key point seems to be the missed identification of sentinel lymph node by lymphoscintigraphy , probably due to the obstruction of lymphatic flow to the true sn and the consequent deviation of the flow to another node . this situation has already been described in some papers about sns in melanoma and also in breast cancer . in 2009 , for example , lam et al . described three cases in which preoperative lymphoscintigraphy failed to show sns containing metastatic melanoma ( all with significant tumor involvement ) , that were discovered by ultrasound and then confirmed by fine - needle aspiration biopsy and histopathology . the same circumstance was previously described by estourgie in 2003 in two breast cancer patients : in that report , both lymphoscintigraphy with tc - nanocolloid and patent blue dye administration failed to identify the true sn , completely invaded by tumor and discovered by intra - operative palpation of the biopsy wound . what seems new here is that not only lymphoscintigraphy , but even preoperative ultrasonography failed to identify the metastatic crural node . in this setting , in our opinion , a double lesson can be learnt . first , this report confirms that a small risk of missing sentinel lymph node by lymphoscintigraphy exists ( especially in thick melanoma ) and highlights the added value of a hybrid tomographic study ( spect / ct ) , that allows a morphologic evaluation of the interested region too . second , it shows that f - fdg pet / ct , usually performed for n staging ( for the well - known lack of sensitivity in the study of the lymphatic basin ) , could give important information also about regional disease in selected patients . the selection of the staging procedures to perform should always be individualized , considering general and local features of the disease , and evaluating together with the patient the risks and benefits of each technique .

the american society of clinical oncology guidelines recommend sentinel lymph node biopsy ( slnb ) for all patients with melanoma tumors of intermediate thickness ( between 1 and 4 mm ) . in case of patients with thick melanoma tumors ( > 4 mm ) , slnb may be recommended as well , for staging purposes and to facilitate regional disease control . we report a case of an 82-year - old man , undergone excision of a cutaneous melanoma of the right thigh , which shows some limitation of slnb in thick melanoma . lymphoscintigraphy , performed as single - photon emission computed tomography / computed tomography ( spect / ct ) , failed to identify the real sentinel lymph node , as tracer uptake was seen in a right inguinal node . due to the presence on ct co - registered images of another suspicious node ( with no radiopharmaceutical uptake ) in the crural region , and considering the high - risk pathologic features of the removed primary lesion , a 18f - fluorodeoxyglucose positron emission tomography / ct ( 18f - fdg pet / ct ) staging scan was planned . pet / ct showed high metabolic activity in the suspected crural lymphadenopathy . histopathology demonstrated massive invasion of the crural ( sentinel ) node and no metastatic cells in the inguinal node . this report highlights both the higher accuracy of lymphoscintigraphy , when performed as spect / ct and the potential utility of 18f - fdg pet / ct in regional staging .

recognition of the impact of ventilator - induced lung injury on morbidity and mortality in patients with acute respiratory distress syndrome ( ards ) has led to an ongoing search for ventilation strategies that limit further damage to the already injured lung . in this issue of critical care , bollen and colleagues present the results of a multicentre randomised controlled trial , comparing high - frequency oscillatory ventilation ( hfov ) with conventional ventilation as the primary ventilation mode for adults with ards . hfov applies a continuous distending pressure to the lung around which pressure oscillations are generated . these pressure swings are attenuated by the time they reach the alveolar level , resulting in very small delivered tidal volumes . hfov is theoretically ideal for lung protection , as this minimal tidal variation in alveolar volume may allow clinicians to recruit the lung , minimising atelectrauma and oxygen toxicity , while still avoiding volutrauma from tidal overdistension . however , potential drawbacks to hfov also exist , most notably the fact that the majority of adults must have their spontaneous respiratory efforts suppressed since their inspiratory flow demands are often greater than the constant flow of gas in the circuit . this need for heavy sedation ( and frequently neuromuscular blockade ) means that hfov may not be an appropriate therapy for patients with mild forms of acute lung injury . an extensively studied and accepted therapy in neonates , hfov is still an emerging ventilator mode in adults . previous work in this area has shown that hfov is safe and effective in improving oxygenation in ards patients who are failing conventional ventilation [ 3 - 5 ] . however , when hfov is considered as a primary ventilatory mode to prevent ventilator - induced lung injury , only one clinical trial has been previously published . mortality was not the primary outcome of this study and the control group arguably did not receive what would today be considered optimal conventional ventilation ; nevertheless , a tantalising trend towards improved mortality was seen in the hfov group of this study . consequently , hfov in adults with ards remains a therapy with significant potential , but one requiring considerably more data before it can be endorsed for routine use . in the study under consideration , bollen and coworkers set out to determine the effect of hfov on the rate of survival without mechanical ventilation or oxygen dependence at 30 days , compared with conventional ventilation . unfortunately the trial was stopped early , after recruiting only 61 patients because of declining enrolment , and a further 11% of subjects had incomplete follow - up for the primary endpoint . although no differences were detected in any primary or secondary endpoint , this study only had sufficient power to detect extreme differences in outcome between groups . this low power was further eroded by the fact that 18% of patients crossed over to the alternative therapy , making detection of a difference between groups highly improbable . interpretation of these results is further complicated by the fact that the two treatment groups differed significantly in numbers as well as in baseline hypoxia ( oxygenation index of 25 in the hfov group , versus 18 in the control group ) . furthermore , comparison and integration of these results with the existing body of knowledge regarding hfov in ards are made more difficult by the lack of very explicit ventilation protocols . because it is very clearly how a ventilator mode is used , not just which mode is chosen , clear descriptions of the ventilator protocols and the adherence to them are essential for interpreting the results of comparative trials of ventilation strategies and modes . despite these limitations , hoc analysis , the authors found that the subgroup of patients with the most severe hypoxaemia ( highest oxygenation indices ) tended to benefit from hfov compared with those undergoing conventional ventilation . as discussed by the authors , this finding may relate to the fact that the ' safe ' window for lung protective mechanical ventilation , in which both overdistension and cyclical tidal recruitment and derecruitment are avoided , is so narrow in severe lung injury that conventional ventilation is no longer able to accomplish the goals of lung protection . the implications of this finding are for future investigators to consider stratifying the randomisation of patients by oxygenation index , or indeed to limiting enrolment to those patients with the most severe forms of ards . the potential benefits of this latter decision in terms of potential increased effect size would need to be weighed carefully with an inevitable decrease in the number of potential study patients , which might threaten both the feasibility and generalisability of the study . indeed , another important lesson from this study is that future randomised trials must be collaborative multicentre efforts , because even in centres with a special interest in ards a realistic estimate of the recruitment rate into such trials is somewhere in the range of one patient every other month . ultimately , many of the questions regarding the use of hfov in patients with ards remain unanswered : in which patients , at what time and using what settings should hfov be applied ? several studies have documented worse outcomes when patients received longer periods of conventional ventilation before initiation of hfov , suggesting that an early transition to hfov might be needed [ 3 - 6 ] . lung volume recruitment is vital in hfov and is affected by both the hfov settings and the use of lung volume recruitment manoeuvres . a strategy targeting lung volume was instrumental in the successful application of hfov in newborn infants , and a comparable protocol has been found to be safe and effective in adults . the decision and method of weaning hfov back to conventional mechanical ventilation are even more indistinct , with no clear direction with respect to the priority of airway pressure , frequency and pressure amplitude ( p ) in weaning . these issues only underline the importance of explicit ventilation protocols so as to standardise across treatments and allow comparison between them . although the utility of hfov as rescue therapy is clearer , its precise role as primary therapy in patients with ards remains unclear . the trial by bollen and colleagues serves to demonstrate the challenges and complexities in studying mechanical ventilation protocols in a heterogeneous population of sick patients , and the necessity for explicit protocols to guide treatment and experimental methods .

in this issue of critical care , bollen and colleagues present the results of a multicentre randomised controlled trial , comparing high - frequency oscillatory ventilation with conventional ventilation as the primary ventilation mode for adults with acute respiratory distress syndrome . the study was stopped early after recruiting only 61 patients because of declining enrolment , and although no differences were detected in any primary or secondary endpoint , this trial only had sufficient power to detect extreme differences in outcomes between groups . this editorial attempts to put these results in context with previous work and highlights challenges to be addressed in future studies .

an epileptic seizure is defined as a transient symptom of abnormal excessive or synchronous firing of some or many of the brain s cells , or neurons . the outward effect can be as dramatic as convulsions with wild thrashing movements ( tonic - clonic seizure ) or as mild as a brief loss of awareness ( absence seizure ) . sometimes seizures consist of repeated full body slumps , with the person simply losing body control and crashing to the ground . it has been found that initial , thoughtfully chosen medication can make almost 50 percent of patients seizure - free for extended periods of time . if an initial drug fails , another well - chosen drug may make an additional 14 percent of patients seizure - free . if that drug fails , too , then the likelihood of rendering someone with epilepsy seizure - free is poor . more than 30 percent of patients with epilepsy will not have seizure control even with the best available medications . despite the introduction of many new anticonvulsant medications , these figures have remained consistent over time . working with families whose children had epilepsy , we realized that there were no books written for parents to help them cope . to fill the void , my colleague , eileen vining , m.d . , my coordinator / counselor , diana pillas , and i decided to team up to write one . the result was seizures and epilepsy in childhood : a guide for parents,3 published by the johns hopkins press in 1993 . it contained three pages on the ketogenic diet . sensing a need for a separate book that focused solely on the diet , the dietitian millicent kelly and i collaborated with my daughter , jennifer freeman , a freelance writer , to write the epilepsy diet treatment : an introduction to the ketogenic diet , a shorter book specifically about the ketogenic diet . it was 1993 , and charlie abrahams , the two - year - old son of jim abrahams , the hollywood producer of airplane and naked gun , continued to suffer many uncontrollable drop seizures each day , despite extensive medical intervention . as abrahams has stated , after thousands of epileptic seizures , an incredible number of drugs , dozens of blood draws , eight hospitalizations , a mountain of eegs , mris , cat scans , and pet scans , one fruitless brain surgery , five pediatric neurologists in three cities , two homoeopathists , one faith healer , and countless prayers , charlie s seizures continued unchecked , his development delayed , and he had a prognosis of continued seizures and progressive retardation . researching epilepsy treatments himself , abrahams found our book , seizures and epilepsy : a guide for parents,3 with its three pages on the ketogenic diet . after a phone call , he brought charlie to johns hopkins , where the toddler first fasted , according to our protocol . within several days gradually taken off his medications , charlie has remained seizure - free , on no medications , for the past 19 years . jim was outraged that in all his conversations with medical experts and other parents , he had never been told of the diet . determined to make information about the ketogenic diet available to parents and physicians , he was instrumental in bringing the 1994 dateline nbc news magazine program , an introduction to the ketogenic diet , featuring his friend , the actress meryl streep , to the public . the foundation funded a seven - year study and published 2,500 copies of our shorter book , which sold quickly and attracted a more established publisher , demoshealth . the foundation also funded the production of several dvds explaining the diet to parents , dietitians , and physicians . despite offering them free to physicians at national and regional epilepsy meetings , there were few takers a sign that much work still needed to be done . a big breakthrough in promoting the diet finally came in 1997 , when an abrahams - directed , made - for - tv movie , first do no harm , also with streep , was followed by a flood of thousands of phone inquiries and about 150 patients seeking help with the diet from johns hopkins . the new patients allowed us to gather important data about the diet s effectiveness and its side effects . the reports from johns hopkins were the first of an avalanche of abstracts and articles on the clinical outcomes of children who were treated , including outcomes of the diet s various aspects and modifications . the huge increase in the number of clinical abstracts was presented annually at american epilepsy society meetings . the foundation has since been the moving force behind increasing physicians knowledge about the diet and in training parents and dietitians in its use . at the third international conference on dietary therapies for epilepsy and other neurological disorders , organized by the foundation in 2012 , close to 500 physicians , dietitians , and parents from 30 countries around the world honored streep for her role in reintroducing the diet . the conference promoted in the foundation s newsletter , ketonews included cooking demonstrations and exhibits , testimonials from parents , and a professional symposium . at first , most epileptologists did not believe that a diet could be as effective as drugs , although multiple large studies documented the diet s effectiveness . but these studies were uncontrolled , and since many were based on the large johns hopkins patient population , there was a tendency for physicians to discount the results as biased by enthusiasts . finally , two blinded crossover studies one from the cross group in england4 in 2008 , the other funded by the national institutes of health at johns hopkins in 2009documented the diet s effectiveness in children in a controlled fashion . although there are currently no large studies in adults , anecdotal reports indicate the diet s effectiveness , although it appears adults have more difficulty adhering to its rigidity.5 the outcome of children with uncontrolled seizures who are placed on the diet is shown in the figure ( see below ) , which summarizes data from johns hopkins studies6 and is similar to many reports from other centers . it is notable that 33 percent of the children with intractable seizures were seizure - free , or had only rare seizures , after being on the diet for one year , and 27 percent of the children whose seizures had previously been uncontrollable by medications had no seizures or only rare seizures three to six years after initiating the diet , although by that time most of the children were off the diet and all medications . some with continued seizures remain on the diet because it has decreased the number of medications the children need to take as well as the consequent side effects . no anticonvulsant drugs have been studied for that duration or have shown that rate of beneficial effects . the diet is rarely used as the initial treatment for epilepsy , but should be strongly considered when two anticonvulsants , properly used , have failed . however , the diet may be the initial treatment of choice in infantile spasms and other despite considerable recent research , how the diet exerts its beneficial effects remains unknown.6 it is not solely the ketosis , the accompanying acidosis , the lipidosis , or any of the other chemical changes that have been investigated that are responsible . a recent study9 suggests that episodic fasting , in addition to the diet , is even more effective than the diet alone in controlling seizures . learning the mechanisms by which the diet controls epilepsy may give us a better understanding of epilepsy itself . modifications of the ketogenic diet , such as the modified atkins diet , the medium - chain triglyceride ( mct ) diet , and the low - glycemic diet ( lgd ) have been developed as alternatives to the rigidity of the classic version . these diets , all of which have been found to have degrees of effectiveness , may be more acceptable to adolescents and adults.5 although large studies of these diets have yet to be performed , uncontrolled studies suggest that they may be effective . if tried , and the individual s seizure control is less than satisfactory , the more rigid , classic ketogenic diet is recommended.1 while the classic ketogenic diet may cause complications1 such as kidney stones,9 lipidemia , and gastrointestinal symptoms , problems are rarely serious and easily managed . vomiting is common in the early stages of fasting and may be relieved with small doses of glucose . constipation is common and may be relieved with small amounts of medium - chain triglyceride oil ( mct ) or a readily available laxative such as miralax . carnitine is rarely needed , but sugar - free multivitamins and minerals such as calcium are recommended . calcium oxalate and uric acid kidney stones occur in 15 to 20 percent of patients and can be treated or prevented by the administration of potassium citrate . plasma lipids are also known to rise slightly , but they return to normal levels after six months . the rare patient with familial dyslipidemias has been seen , and therefore lipid levels should be checked occasionally.1 generally , children whose seizures are controlled by the diet are tapered off it after two years . but if seizures continue , or recur , the child should remain on the diet longer . some patients have remained on the diet for more than 25 years without adverse effects . the resurgence of interest in the ketogenic diet has led to some very preliminary studies of its use in conditions other than epilepsy . neurodegenerative disorders provide a unique opportunity to study cellular protection through diet.6.9,11 animal models and anecdotal human reports suggest that glucose restriction and the ketogenic diet may have beneficial effects on brain tumors.7,8 tumors rapidly metabolize glucose but are unable to utilize ketones as an energy source . brain tissue , on the other hand , is able to use both . glioblastoma implanted in rodents rapidly regresses on a glucose - restricted ketogenic - like diet . anecdotal reports and preliminary studies in humans have found tumor regression on ketogenic diets . the dramatic findings in glioblastoma may also be true of other brain tumors and perhaps other systemic tumors . there are also anecdotal reports of the diet s benefits6,9,11 in modifying alzheimer s disease , parkinsonism , amyotrophic lateral sclerosis , and possibly posttraumatic brain injury , stroke , and severe hyperactivity . however , such studies are needed to prove or disprove the diet s usefulness . the diet , or a modified form of it , may also be useful in the management of diabetes . preliminary reports of its use in inflammatory disease and the management of pain are also of interest and deserve further study.6 although it has taken 20 years to reintroduce the once - abandoned ketogenic diet , it has become an important new therapy especially for difficult - to - control seizures in children . as more dietitians are trained , and more physicians become aware of the diet , it is used increasingly throughout the world.1 guides to its use are now available in many languages and in many countries , thanks to the charlie foundation and its british cousin , matthew s friends . the idea of food as medicine has been a controversial topic in this country for many years . but the statistics do nt lie , nor do the hundreds of young people who will tell you how their lives were changed because of it .

editor s note : epilepsy and seizures affect nearly 3 million americans of all ages . the incidence is greater in african - americans and in socially disadvantaged populations , and about 200,000 new cases of epilepsy are diagnosed each year . despite these alarming figures , no magic pill exists to eliminate convulsions . while drugs work for some , others find them ineffective . what seems to work just as well , if not better , especially in children , is a relatively unknown , high - fat diet . the author , john m. freeman , m.d . , one of the nation s leading advocates for its use , writes about the evolution of the diet and its struggle for acceptance .

surgical site infections ( ssis ) as one of the most common causes of nosocomial infections is accounted for 20 to 25% of all nosocomial infections worldwide ( 1,2 ) . the ssis are the most common complication following surgery , with reported rates up to 30% ( 2 , 3 ) . these infections place a substantial burden on healthcare cost as a result of increased post - operative morbidity and mortality ( 2 , 4 - 7 ) . they are responsible for 30 to 40% of the deaths in the postoperative period ( 8) . with regard to the multifactorial condition of ssi , it is important to detect these factors , to investigate the procedures that bear the highest risk and , if possible , define suitable indices that can predict the risk of ssi ( 9 ) . the present study was conducted to establish the patterns and risk factors of surgical site infections at imam reza hospital in iran between 2006 and 2011 . the ssi was identified based on the presence of icd-10-cm diagnosis code in hospital discharge records of patients admitted to general surgery ward of imam reza hospital , mashhad , iran between 2006 and 2011 . surgical site infections were defined according to the cdc ( the centers for disease control and prevention ) criteria . all patients who met inclusion criteria were enrolled into the study . by using a standardized data collection form predictor variables including patient characteristics , preoperative , intra - operative and postoperative data were obtained . study data included type of surgery , wound class , infection degree , incision site , type and duration of operation , type of prophylaxis and duration of antimicrobial therapy , use of drain , preoperative and postoperative hospital stay . data were analyzed using the spss software patients diagnosed with surgical site infections who were identifiable based on the presence of icd-10-cm diagnosis code in hospital discharge records were included . patients with more than one surgery during hospitalization and those who underwent minor surgery ( surgeries that does nt require anesthesia or respiratory aid ) were excluded from the study . descriptive statistics such as frequency table is derived for categorical variables and mean and standard deviation ( sd ) for numerical variables . descriptive statistics such as frequency table is derived for categorical variables and mean and standard deviation ( sd ) for numerical variables . retrospective review of patients medical records showed that 95 patients fulfilled the inclusion criteria . study population included 51 ( 53.7% ) males and 44 ( 46.3% ) females with age ranged 12 - 88 years . the patients were admitted for various procedures of both elective ( 62.1% ) and emergency ( 37.9% ) operations as shown in table 1 . colectomy ( 13.7% ) was the leading procedure followed by umbilical herniation ( 12.6 ) and appendix perforation ( 12.6% ) ( table 1 ) . patient history of smoking , addiction , past history of diseases ( including hypertension , diabetes and autoimmune diseases ) and medications ( corticosteroid and antibiotic therapy ) were assessed . nineteen patients ( 19.7% ) were addicted to opium 8 ( 8.3% ) with diabetes , other factors ratio was less than 8% for each . except one case ( laparoscopic gastric binding ) , all patients had undergone open surgery ( 96.8% ) . the highest incidence of infection were identified in patients with midline incision above and below the umbilicus ( 40% ) followed by midline incision below the umbilicus ( 8.4% ) and above the umbilicus ( 4.7% ) . the organ involvements were also recorded based on the information contained in the operation description sheet . in most cases ( 26% ) all abdominal viscera such as appendix , colon , small intestine , ovaries and fallopian tubes have been involved during operations . the small intestine and the colon involvement alone occurred in 21.1% of cases ( table 2 ) . the highest incidence of wound infections was observed in 44 patients ( 46.3% ) with clean - contaminated wounds . ninety nine patients ( 30.5% ) had contaminated and 20 patients ( 21.1% ) had clean wounds , and 2 cases identified as dirty wounds . the highest degree of infection ( 65.3% ) was serous secretion without wound dehiscence ( table 3 ) . the mean duration of surgery , pre - operative and post - operative hospital stays was 2.91.45 hours , 1.021.42 and 7.756.75 days respectively . the missing data included duration of surgery and pre - operative and post - operative hospital stay in 40% and 33% of patients , respectively . surgical drains were used in 44.2% of cases and in 82.1% of cases , the wound was closed initially . only for 4.2% of patients , ceftriaxone and metronidazole were administered for 2.1% of patients ; and equal proportions of patients received metronidazole and erythromycin or ceftriaxone , metronidazole and ciprofloxacine ( 1.1% ) . the most antibiotics prescribed post - operatively were the combination of ceftriaxone and metronidazole ( 51.6% ) . in this study , the mean age was 47.13 years with standard deviation of 19.60 years . there were 51 ( 53.7% ) males and 44 ( 46.3% ) females in age range of 12 - 88 years . this could be explained by multiple risk factors in males such as addiction to opium . in accordance with our study , previous studies have shown that patients suffering from pre - morbid diseases , such as diabetes mellitus and hypertension are at high risk of developing ssi ( 6 - 8 , 10 , 11 ) . cigarette smoking was significantly found to be associated with ssi in other studies ( 5 , 10 , 2 ) . in contrast , in our study only 3.2% had a history of cigarette smoking ; on the contrary 20% were addicted to drugs , which showed significant association with development of ssi . in the present study the patients were admitted for various procedures including both elective ( 62.1% ) and emergency ( 37.9% ) operations . the higher rate of ssi in elective surgeries can be explained due to the higher rate of contaminated and clean contaminated wounds in elective surgeries of our institution . colectomy ( 13.7% ) was the leading procedure followed by umbilical herniation ( 12.6% ) , and appendix perforation ( 12.6% ) ( table 1 ) . the highest incidence of infection were identified in patients with midline incision above and below the umbilicus ( 40% ) followed by midline incision below the umbilicus ( 8.4% ) and above the umbilicus ( 4.7% ) . fiorio et al meta - analysis on 3066 surgical procedures demonstrated highest incidence of ssi in small bowel ( 16.3% ) and colon surgery ( 12.5% ) ( 7 ) . our findings confirmed previous knowledge that surgeries with an increased microbial load in the operative field are associated with higher risk of ssi ( 7 , 13 ) . for a long time , surgical wound classification has been recognized as an important predictive factor in developing surgical site infections after surgery ( 6 , 7 , 14 - 16).in our study , as well as previous studies , the incidence of ssi was statistically higher in clean contaminated ( 46.3% ) and contaminated ( 30.5% ) wounds . a prolonged pre - operative hospital stay has been reported to increase the rate of surgical site infection ( 17 ) . a length of operation of more than 3 hours leads to 4 times higher risk of ssi ( 9 ) . in present study , the means for duration of surgery , pre - operative and post - operative hospital stay were 2.91.45 hours , 1.021.42 and 7.756.75 days , respectively . this is not in accordance with the literature regarding the risk of ssi determined by the duration of the surgery and pre - operative hospital stay ( 5 - 7 , 9 ) . in addition , the use of surgical drains has been reported to be associated with an increased risk of ssi which was confirmed in this study ( 28 - 30 ) . this can be explained by using routine antibiotics for every procedure , and also it necessitates the use of antibiotic policy regarding different therapeutic procedures for these patients . the most prescribed antibiotics used post - operatively were ceftriaxone -metronidazole ( 51.6% ) and metronidazole ( 8.4% ) . this investigation had limitations because of missing data including prophylactic antibiotics and icd-10-cm diagnostic code in hospital discharge records . the comparison of ssi incidence between hospitals from various locations and countries must always be attentive , due to specific characteristics for each place and patient population that make it difficult to reach valid conclusions . the ideal situation would be for each hospital to critically analyze its own data , preferably focusing on the historical series and then particularizing it for various types of surgery . surgical site infection is highly related to the type of wound , namely contaminated and clean contaminated wounds and associated with higher rate of ssi . also , it seems that there is a converse relation between length of surgical incision and the rate of ssis . in short , we found that the type of surgery considered to be the main risk factor in developing ssi .

background : the present study was conducted to establish the patterns and risk factors of surgical site infections in our institution between 2006 and 2011 . methods : this was a retrospective cross - sectional study . the surgical site infection ( ssi ) was identified based on the presence of icd-10-cm diagnostic code in hospital discharge records . by using a standardized data collection form predictor variables including patient characteristics , preoperative , intra - operative and postoperative data were obtained . results : ninety five patients fulfilled the inclusion criteria . the patients were admitted for various procedures including both elective ( 62.1% ) and emergency ( 37.9% ) operations . colectomy ( 13.7% ) was the leading procedure followed by umbilical herniation ( 12.6 ) and appendix perforation ( 12.6% ) . the mean age was 47.13 years with standard deviation of 19.60 years . twenty percent were addicted to opium . midline incision above and below the umbilicus ( 40% ) had the highest prevalence of infection . most patients ( 46.3% ) had cleancontaminated wounds and 30.5% had contaminated one . the quantitative variables which were also measured include duration of surgery , pre - operative and post - operative hospital stay with the mean of 2.91.45 hours , 1.021.42 and 7.756.75 days respectively . the most antibiotics prescribed post - operatively were the combination of ceftriaxone and metronidazole ( 51.6% ) . conclusion : the contaminated and clean - contaminated wounds are associated with higher rate of ssis . also , there was a converse relation between length of surgical incision and rate of ssis . in overall , we found type of surgery as the main risk factor in developing the ssis .

it is also called benign mixed tumor of skin as it contains both epithelial and mesenchymal components . the most common presentation is a small , slow - growing , subcutaneous nodular mass in the head - neck region . until now , only few cases of cytological diagnosis of chondroid syringoma have been reported . here , we are presenting a unique case of eccrine chondroid syringoma of forearm , diagnosed by fine - needle aspiration cytology ( fnac ) and subsequently confirmed by histopathology . a 33-year - old male presented with a nodular swelling over left forearm for 1 year . on examination , it was a firm to hard , nontender , mobile , subcutaneous mass measuring 2 cm 1.5 cm . fine - needle aspiration was done with 22 g needle attached with 20 ml disposable syringe . on cytological examination , smears were moderately cellular comprising of clusters of round to oval cells and abundant chondro - myxoid ground substance . the epithelial cells were monomorphic , round to oval , medium sized having moderate amount of cytoplasm , bland round to oval nuclei with finely dispersed chromatin [ figure 1a and b ] . smaller myoepithelial cells having plasmacytoid appearance with dark nuclei were interpreted within clumps of epithelial cells [ figure 1a ] . ( a and b ) smears show tight clusters of benign round to oval epithelial cells and myoepithelial cells in fibrillary chondro - myxoid ground substance ( leishman giemsa stain , 400 ) on excision , the mass was encapsulated , partially covered with skin , firm to hard in consistency and measuring 2 cm 1.5 cm 1 cm . cut surface of the tumor was solid , gray tan in color and without any necrosis or hemorrhage . on histopathological examination , the tumor was encapsulated with a large area of cartilaginous differentiation . the cellular areas were composed of cuboidal to polygonal cell nests or islands , irregularly distributed among abundant chondro - myxoid stroma [ figure 2 ] . the epithelial cells were also arranged in acinar and ductular pattern in some areas [ figure 2 ] . section show epithelial cell clusters in tubules , ducts , cords and nests and chondro - myxoid stroma with an area of cartilaginous tissue ( h and e , 100 ) excision site was healthy during the postoperative period and no recurrence was observed after 6 months of follow - up . nasse , first described a case of skin tumor containing both epithelial and mesenchymal components in 1892 . hirsch and helwig introduced the name chondroid syringoma and subsequently used as alternate to the term mixed tumor of skin . chondroid syringomas are defined as benign adnexal tumors containing both epithelial and mesenchymal elements with histological resemblance to benign mixed tumors of salivary glands . chondroid syringomas commonly present as nontender , firm , nodular , subcutaneous or intra - cutaneous masses of 0.5 - 3 cm diameter . previous literature have recorded a male predisposition and wide age range of 20 - 80 years . though most of the cases involve head and neck areas , cases involving trunk , extremities , axillary and scrotal areas the lesion was located at dorsal surface of left forearm , relatively a rare location . pailoor et al . reported a case of cytological diagnosis of chondroid syringoma involving little finger . chondroid syringomas are difficult to diagnose clinically because a wide range of nodular skin lesions simulate it such as , dermoid cyst , neurofibroma , dermatofibroma , pilomatrixoma , cutaneous histiocytoma and seborrheic keratosis . in the majority of the cases confirmatory diagnosis histologically chondroid syringomas can be categorized into two types - apocrine and eccrine , as classically described by headington . the apocrine types exhibit branching tubular pattern with cyst formation ( tubulo - cystic ) , lined by double cell layers ( cuboidal and flattened ) . whereas eccrine types show single layer of cuboidal epithelial cells surrounded by chondro - myxoid stroma . on immunohistochemistry , the inner cuboidal layer shows positive staining with epithelial markers like cytokeratin , whereas outer layer expresses mesenchymal markers such as vimentin , s-100 protein , neuron specific enolase and glial fibrillary acidic protein . though histopathology is a gold standard , fnac can suggest a diagnosis of chondroid syringoma on the basis of thick mucoid aspirates exhibiting distinct biphasic cell population of epithelial and myoepithelial cells in a fibrillary chondro - myxoid stroma . however sometimes , the aspirates may lack distinct biphasic cell populations or show predominantly monophasic cells , which create diagnostic difficulties . cytology is rarely applied for preoperative assessment of these nodular lesions . even in cases undergoing aspiration , smears are , usually , interpreted as benign adnexal tumors without proper categorization . previous literature have shown that accurate cytological diagnosis of chondroid syringoma is difficult . still fnac should be recommended to establish benign nature of the neoplasm and to differentiate from other common nodular skin lesions such as epidermal cyst , neurofibroma , cutaneous benign fibrous histiocytoma , etc . local excision with a cuff of normal tissue is desirable management in chondroid syringoma to avoid recurrence . malignant counterpart of chondroid syringoma is extremely rare , which may arise in a preexisting benign chondroid syringoma or may arise de novo . fine - needle aspiration cytology can be used as a useful preoperative diagnostic tool for diagnosis of cutaneous and sub - cutaneous lesions . diagnosis of chondroid syringoma can be possible by careful evaluation of a smear containing biphasic ( epithelial and myoepithelial ) cell population with chondro - myxoid fibrillary matrix in a mucoid aspirate obtained from a sub - cutaneous nodule . present case is a good example of cytological diagnosis of chondroid syringoma with histopathological correlation , which will encourage future workers to utilize this simple , cost effective diagnostic procedure for preoperative definitive diagnosis of this benign neoplasm helping clinicians to formulate proper management protocol with reduction of postsurgical recurrences .

chondroid syringoma is a rare benign adnexal tumor of sweat glands with microscopic resemblance to the salivary gland pleomorphic adenoma . cytology is rarely utilized for preoperative assessment of these slow - growing , small , nodular lesions . definitive cytological diagnosis is also quite difficult , and majority of the aspirates are evaluated as benign adnexal tumors leading to mandatory histopathological examination for pinpoint diagnosis . here , we report a case of chondroid syringoma of forearm , which was diagnosed by cytology and also confirmed after histopathological examination . pinpoint cytological diagnosis can help early formulation of necessary management protocol .

recombinant tissue plasminogen activator ( rt - pa ) has been used for a long time in the therapy of acute ischemic insult . the application of intravenous thrombolysis for ischemic stroke has already been established as a standard treatment throughout the world . for various reasons , however , only a small proportion of ischemic stroke patients were treated with alteplase,1 so we know little about the side effects of this drug . hypersensitivity to alteplase is uncommon and has been estimated to occur in less than 0.02% of patients who receive it for the treatment of acute myocardial infarction.2 however , anaphylactic reaction by alteplase may also occur more in acute ischemic stroke patients.2 a little known complication of acute stroke treatment with systemic rt - pa thrombolysis is orolingual angioedema . this has occurred in 2% of patients for thrombolysis.3 there is an increased risk for the occurrence of angioedema during the therapy with alteplase,3,6,10 especially in patients receiving angiotensin - converting enzyme inhibitors . angiodema by alteplase is usually only reported on from larger clinics so this present study is unique because it has been performed in a peripheral hospital with a small stroke unit . this means that the results of this study , combined with those of previous studies , can offer greater insight by discussing a broader spectrum than was previously available . among the patients given recombinant tissue plasminogen activator intravenously for acute ischemic stroke in this hospital ( vinzentius - hospital , landau , germany ) , one had lingual angioedema . this was a 63- year - old patient , who was at home in bed at 11 pm . his wife came into the bedroom and saw her husband lying motionless and mute in bed . he diagnosed a right hemiparesis and dysphasia , possibly due to a stroke . after arriving at hospital , a cranial ct to exclude intracranial hemorrhage after exclusion of contraindications for thrombolytic therapy , it was suggested that lysis with alteplase could solve a left - sided media infarction with flaccid hemiparesis on the right , right - sided facial paralysis , dysphasia , and dysphagia . additionally , and unrelated to the onset of the current problem , he had arterial hypertension , diabetes mellitus type 2 , obesity , and chronic obstructive pulmonary disease . the man was taking a beta - blocker , angiotensin - converting- enzyme ( ace ) inhibitor and , if needed for pain relief , non - steroidal anti - inflammatory drugs ( nsaids ) , diuretics , inhalants , and benzodiazepine . the patient met the criteria for intravenous alteplase treatment of acute ischemic stroke ( within a window of time of 80 minutes ) and was given 0.9 mg / kg alteplase after a 10% bolus initially with the remaining drug infused over 60 minutes . due to his high body weight ( 120 kilograms ) , the next day , a head computerized tomography ( ct ) scan was performed and no hemorrhage could be seen but a big demarcation of the left middle cerebral artery was inspected . he recovered from the angioedema , but his right hemiparesis , speech disturbance , and dysphagia remained . after this event , all records of patients with stroke after thrombolytic therapy were examined for similar events in order to avoid angioedema by alteplase in the future . the aim of this study was to determine the incidence of angioedema by alteplase in a peripheral hospital with a minor stroke unit in comparison to other published results . furthermore , this study aims to answer the question whether the occurrence of angioedema through alteplase is dependent on other factors , such as the number of thrombolysis occurrences . all stroke patients in this study had their heads scanned by ct or magnetic resonance imaging ( mri ) . a ct scan of all patients was done in order to exclude a brain hemorrhage , prior to thrombolysis . the lysis therapy was carried out within the time frame of 3 hours for all stroke patients . after performing the thrombolysis , the author thoroughly examined records of 730 patients after cerebral ischemia that underwent thrombolysis . after further research , these consisted of eight men 47.06% ( 95% confidence interval : + /23.73% , 23.33% to 70.79% ) and nine women 52.94% ( 95% confidence interval : + /23.73% , 29.21% to 76.67% ) ( figure 1 ) . these patients all had cerebral ischemia and severe clinical symptoms and were treated by lysis with alteplase within the therapeutic time frame of 3 hours . the average age of these patients was 69.94 years with a standard deviation of 11.82 years . a 63-year - old male patient had an angioedema with macroglossia during the treatment with alteplase in this hospital . the immunoglobulin e of this patient was within the reference range of immunoglobulin e ( 0150 u / ml ) . the immunoglobulin g from this patient with macroglossia during treatment with alteplase was slightly increased at 17.4 the author measured the relative chance of cases having a positive outcome for both sexes with angioedema and without side effects . the proportion of cases having a positive outcome in angioedema under treatment with alteplase was 3.3 ( 95% confidence interval : 0.15% to 71.90% ) , ( p = 0.4423 ) between male and female . the odds of getting an angioedema under alteplase in two groups of men and women was 3.8 ( 95% confidence interval : 0.13% to 107.32% ) , ( p = 0.4335 ) . the disease prevalence in angioedema under treatment with alteplase was 5.88% ( 95% confidence interval : 0.98% to 28.76% ) . the sensitivity , specificity , as well as disease prevalence were expressed as percentages for interpretation . the sensitivity is the probability that a test result will be positive when an angioedema under alteplase is present . the specificity is the probability that a test result will be negative when an angioedema under alteplase is not present . the two - sided significance of independence by fisher s exact test was calculated for angioedema by alteplase in the thrombolysis of patients with acute ischemic stroke . the author measured the relative chance of cases having a positive outcome for both sexes with angioedema and without side effects . the proportion of cases having a positive outcome in angioedema under treatment with alteplase was 3.3 ( 95% confidence interval : 0.15% to 71.90% ) , ( p = 0.4423 ) between male and female . the odds of getting an angioedema under alteplase in two groups of men and women was 3.8 ( 95% confidence interval : 0.13% to 107.32% ) , ( p = 0.4335 ) . the disease prevalence in angioedema under treatment with alteplase was 5.88% ( 95% confidence interval : 0.98% to 28.76% ) . the sensitivity , specificity , as well as disease prevalence were expressed as percentages for interpretation . the sensitivity is the probability that a test result will be positive when an angioedema under alteplase is present . the specificity is the probability that a test result will be negative when an angioedema under alteplase is not present . the two - sided significance of independence by fisher s exact test was calculated for angioedema by alteplase in the thrombolysis of patients with acute ischemic stroke . although the application of tissue plasminogen activator has been established as a standard therapy for ischemic stroke globally , it is known that a small proportion of patients are currently treated with thrombolytic drugs.1 it was remarkable to learn that only a small number of therapies use alteplase . according to the results of this study , the occurrence of angioedema as a side effect by the administration of alteplase does not depend on the number of thrombolysis occurrences . allergic reactions to thrombolysis can occur but are most commonly seen during therapy with streptokinase.4,5 allergic reactions may also occur as reported in rare cases in the treatment of myocardial infarction with alteplase.5 the aforementioned orolingual angioedema by alteplase was reported in recent studies.3 the prevalence of the disease was increased to three times in this study of angioedema under treatment with alteplase , as compared with other studies . the frequency of side effects under alteplase is the same in the present study as it is in studies published in other literature.6 hill and colleagues reported in their work the similar prevalence of reaction with orolingual angioedema after alteplase treatment of stroke.6 in view of these studies , the incidence of orolingual angioedema under treatment with alteplase of ischemic stroke seems to undergo a significant variations . immunoglobulin g or m were found to be increased in the serum some days or weeks after therapy with alteplase.7 in this case , immunoglobulin g from this patient with macroglossia during treatment with alteplase was slightly increased . the immunoglobulin e antibody was found in the serum of one patient with anaphylaxis under treatment with alteplase.8 the immunoglobulin e was normal in this study . the angioedema as a side effect of alteplase seems to arise rapidly even during treatment , as in this case . also , in the two patients studied by hill and his colleagues , the angioedema occurred within 1 hour.2 a possible cause of orolingual angioedema by alteplase is thought to be the concomitant use of ace inhibitors , as suggested in various scientific literature . risk of angioedema by alteplase was associated with angiotensin - converting enzyme inhibitors with a relative risk of 13.6% , such as hill and his colleagues described.6 also krmpotic and fernandes described an increased risk of anaphylaxis in patients concomitantly being treated with angiotensin - converting enzyme inhibitors , as illustrated in a case report describing a patient who experienced an urticarial rash , hypotension , tachycardia , orolingual angioedema , and airway obstruction following intravenous administration of alteplase.9 possible pharmacologic interactions resulting in excessive serum bradykinin and subsequent systemic hypersensitivity responses are discussed.9 okada reported a 75-year - old woman with an orolingual angioedema considered as a complication associated with alteplase and taking ace inhibitors.10 also , the patient in this study took an ace inhibitor to control blood pressure . an interaction between his ace inhibitor and the treatment with alteplase is assumed to be likely . orolingual angioedema is a potentially life - threatening complication of treatment with alteplase in acute ischemic stroke . the advice , according to the findings of this study , is the introduction of a guedel airway tube in the mouth of the patient with acute ischemic stroke prior to the thrombolysis with alteplase for at least four hours with the readiness of an imminent possible intubation .

alteplase ( recombinant tissue plasminogen activator ) has been used in the treatment of acute ischemic stroke for 10 years . the application of this drug is considered safe and effective . however , alteplase is also associated with side effects . the author is reporting on an unusual side effect of angioedema that is triggered by alteplase . angioedema occurs through alteplase according to this study at a frequency of 5.88% ( 95% confidence interval : 0.98% to 28.76% ) . in this case immunoglobulin g was slightly increased . the relative risk to get an angioedema compared between the two genders is elevated in men 3.3 ( 95% confidence interval : 0.15% to 71.90% ; p = 0.4423 ) , who were 3.3 times more likely to suffer than women . the use of angiotensin - converting - enzyme ( ace ) inhibitors is considered a possible risk factor for the occurrence of angioedema with concomitant administration of tissue plasminogen activator . the angioedema may occur with use of alteplase at any time , so treatment with this drug must always be carried out in intensive care and doctors must be ready for intubation if necessary .

recent advances in high - throughput sequencing technologies have greatly increased the scale and scope of genomics research , and this was evident throughout the recent biology of genomes meeting at the cold spring harbor laboratory . here in one of several talks that investigated the causes , dynamics and phenotypic effects of regulatory change , mike snyder ( stanford university , stanford , usa ) used chromatin immunoprecipitation followed by dna sequencing ( chip - seq ) to examine the variability in transcription factor binding among individuals in yeast ( saccharomyces cerevisiae ) and human . in both species , significant variation was observed , and the amount of binding was strongly correlated with gene expression . much of the observed binding variation could be associated with specific single nucleotide polymorphisms ( snps ) and structural changes to the genome . on the basis of the patterns of variation , snyder suggested that gene regulation may work like a government , with global regulators and local regulators all having strong effects , but with some focused on a more limited set of loci . snyder 's talk introduced two themes that appeared throughout the meeting : the widespread adoption of high - throughput sequencing as an analysis strategy ; and a focus on identifying and understanding regulatory elements . axel visel ( lawrence berkeley national laboratory , berkeley , usa ) continued these themes in a talk that highlighted the limitations of using comparative genomics to identify enhancers . by performing chip - seq with the enhancer - associated p300 protein on mouse forebrain and embryonic heart tissue , he and colleagues identified a large number of heart enhancers with very low evolutionary conservation compared to forebrain enhancers . this surprising result suggests that deep pathway conservation does not imply regulatory sequence conservation , that enhancer conservation is not predictive of function , and that there are global differences in enhancer conservation between tissues . li ding ( washington university , st louis , usa ) described how sequencing samples from the same patients at different stages of the same cancer can help track changes that have occurred during cancer progression , and possibly lead to improved drug therapies . thanks to an efficient pipeline , their genome - sequencing center can analyze tumor / pair samples in only 12 days . the analysis of about 150 cancer genomes using this pipeline has enabled comparisons of different cancer genomes from different points of view , including mutation rate , mutation spectrum , copy number variation and structural variation . the results showed by elaine mardis ( washington university , st louis , usa ) are an example of how powerful these tools are and what they are able to achieve . she presented the analysis of the relapse genome of an acute myelogenous leukemia patient and a comparison with the genome sequenced at initial presentation . interestingly , this study was able to pinpoint relapse - specific mutations most likely involved in disease progression . one of the largest open issues in human genetics deals with the question of ' missing heritability ' : given the generally high estimates of heritability for many complex traits ( such as genetic susceptibility to complex diseases ) , why have genome - wide association studies ( gwas ) identified variants that explain only a small fraction of the heritable variation we know is out there ? one hypothesis suggests that rare variants of large effect , which will generally be missed by gwas , are a crucial component of this missing variability . richard durbin ( wellcome trust sanger institute , cambridge , uk ) and others described progress on the 1000 genomes project , which by next year will generate low - coverage ( around 4 ) whole - genome sequence data from more than 2,000 individuals . this dataset , in conjunction with new imputation algorithms for base - calling low - coverage data , will provide a near - complete catalog of rarer variants ( for example , minor allele frequency 0.005 ) across the human genome , which in turn will facilitate efforts to identify rare variants affecting disease susceptibility . jeffrey barrett ( wellcome trust sanger institute , cambridge , uk ) addressed the subject of ' synthetic associations ' . it has been proposed that many gwas hits are not the result of common variants of modest effect , but rather are artifacts caused by linkage to multiple rare ( but highly penetrant ) variants . barrett 's talk outlined several compelling sources of evidence suggesting that these synthetic associations are likely to be quite rare . so , while rare variants may or may not explain the ' missing heritability ' problem , they are not a probable cause of the associations already discovered by gwas . one alternative approach to understanding the genetic architecture of complex traits is to use a more tractable genetic system . barak cohen ( washington university , st louis , usa ) presented detailed genetic analyses of sporulation efficiency in the yeast s. cerevisiae . for this phenotype , just four snps ( located in three transcription factor genes ) combine to explain 87% of the total phenotypic variation , although very little of this ( around 25% ) could be ascribed to additive effects . cohen also described a thermodynamic model that might explain the strong interactions ( epistasis ) observed among snps . this and other work raises the possibility that gene - gene interactions may be a large part of the answer to the missing heritability question . next - generation sequencing technologies now enable researchers not affiliated with genome centers to conduct their own genome - sequencing projects . peter donnelly ( oxford university , uk ) described some preliminary findings from the panmap project , a collaborative effort to sequence and analyze the genomes of ten western chimpanzees ( pan troglodytes verus ) . donnelly and colleagues were especially interested in the evolution of recombination rates , and the recent fusion between chimpanzee chromosomes 2a and 2b can be used as a ' natural experiment ' to estimate if and how chromosome position influences recombination rate . the results suggest that recombination rates are more affected by chromosomal position than they are by local sequence context . another exciting genome project was described by svante pbo ( max planck institute for evolutionary anthropology , leipzig , germany ) . as a follow - up to the recent publication of the neanderthal genome , pbo and colleagues have now generated roughly 2 coverage of the whole genome from an unclassified hominin fossil found in denisova cave in southern siberia . preliminary results suggest that the denisova fossil is more closely related to neanderthals than to modern humans , though the divergence between neanderthal and the denisova fossil is larger than the divergence between any two extant modern humans . further studies will be needed to clarify the precise evolutionary relationships between this fossil and other hominin groups . several talks gave exciting glimpses of how next - generation sequencing technology can enable novel , high - throughput experimental analyses . rob mitra ( washington university school of medicine , st louis , usa ) introduced a promising new technology for investigating the regulatory networks of development across a cell lineage . by attaching a transposase to a transcription factor , mitra forces the insertion of a transposon ' calling card ' near the site of dna - binding events . these transposons , and thus binding sites , can then be identified by next - generation sequencing . as these transposons survive cell divisions , the binding history of a transcription factor can be traced though a cell lineage . the method has been applied successfully in yeast and tests are in progress in vertebrates . if successful , this approach would yield a powerful tool for decoding how regulation drives tissue - specific development . although the meeting focused primarily on humans and model organisms , considerable attention was given to the large quantities of diverse data being generated by the sequencing of microbial communities through projects such as the global ocean sampling expedition and the human microbiome project ( hmp ) . katherine pollard ( gladstone institutes , university of california , san francisco , usa ) argued that traditional approaches to genomic analysis must be significantly adapted to take advantage of the new kinds of information in metagenomic data , which is produced by shotgun sequencing the dna extracted from environmental samples . she showed that phylogenies inferred from metagenomic sequence reads allow new ways of defining species , such as operational taxonomic units ( otus ) , of discovering novel otus , of defining and comparing microbial community diversity , and of estimating microbial ranges in geographic and niche spaces . in regard to the human microbiome , jennifer wortman ( university of maryland school of medicine , baltimore , usa ) emphasized the hmp 's goal of discovering potential correlations between changes in microbial community composition and the health of the human host . referencing studies of the vaginal and gut microbiomes , she showed that different types of communities require bioinformatic tools with different levels of resolution and specialization . by sequencing the complete genomes of several closely related microbes collected from coastal ocean populations , b jesse shapiro ( massachusetts institute of technology , cambridge , usa ) took a step towards understanding microbial speciation with his presentation of a well - supported sympatric model of speciation in which populations are ecologically differentiated by a set of niche - specific genes . finally , james taylor ( emory university , atlanta , usa ) offered an integrated vision of how we might aim to do science in the age of next - generation sequencing . he emphasized two fundamental directions : first , increasing access to the ability to perform large - scale computational analyses ; and second , and perhaps more important , ensuring that such analyses are done in a way that supports and encourages the integrity of scientific investigation . taylor demonstrated by an analysis of a mitochondrial genome resequencing experiment that commercial cloud computing platforms can be used in conjunction with galaxy , a web - based genome analysis tool , to facilitate large - scale analyses that potentially involve multiple software programs , while maintaining the transparent provenance of the data and parameters . the resulting record of every step of the workflow guarantees that an analysis is reproducible and can be clearly communicated . taylor also noted that in order to completely guarantee reproducibility , the original data themselves must be stored permanently , which raises another challenge for this new scientific paradigm . new experimental technologies are giving individual labs the opportunity to conduct large - scale genomic studies that were unimaginable just a few years ago . however , the data generated on this scale present new challenges in interpretation , analysis and data management . given the quality of the science presented at this meeting , we are confident that the community will find creative and collaborative solutions for these issues .

a report on the 23rd annual meeting on ' the biology of genomes ' , 11 - 15 may 2010 , cold spring harbor , usa.meeting reportrecent advances in high - throughput sequencing technologies have greatly increased the scale and scope of genomics research , and this was evident throughout the recent biology of genomes meeting at the cold spring harbor laboratory . here we describe some highlights of the meeting .

urinary incontinence occurs in 10 - 40% of women , affecting more than two hundred million women worldwide . stress urinary incontinence is the most common form , accounting for about 50% of all types of incontinence . stress urinary incontinence is the involuntary urination resulting from increase in stress , where urine leaks without bladder contraction , and peaks in women aged 45 to 49 yr . affecting 65% of women aged 45 to 49 , urinary incontinence creates hygienic as well as social problems ( 1 , 2 ) . depending on the pathophysiology , stress urinary incontinence is divided into anatomic incontinence caused by urethral hypermobility and intrinsic sphincter deficiency ( isd ) . surgical treatments for anatomic incontinence include bladder neck suspension performed through the abdomen or vagina , or the midurethral sling operation using tape . surgical treatments for isd include sling operation , urethral submucosal injection or creation of an artificial urethral sphincter using fat tissue , teflon , collagen , or silicon . however , a perfect treatment method applicable to all types of incontinence has not yet been created . . stem cells are commonly categorized as embryonic or adult , according to their source . unlike embryonic stem cells , which are not easily obtained for clinical application , adult stem cells can be extracted from human cord blood without harm , making clinical application relatively easy . adult stem cells are present in minute quantities as multipotent cells that multiply and differentiate in response to damaged tissue or increased stress . yiou and his team reported that intrinsic satellite cells in striated muscle are useful in the regeneration of damaged rhabdomyosphincter in mice ( 3 ) . yokoyama and his team reported that injection of muscle - derived progenitor cells ( mdpcs ) into the mouse urethra yielded better durability than injection of bovine collagen ( 4 ) . tracy and his team reported improved sphincter contractibility induced by injection of allogeneic muscle derived progenitor cells into the urethra of a mouse with severed nerves ( 5 ) . strasser and his team , who were first to conduct a human clinical study , performed transurethral injection of autologous muscle - derived stem cells using transurethral ultrasound and reported improved symptoms , a thickened urethral sphincter , and improved urethral sphincter contractibility ( 6 ) . human cord blood stem cells can transform into other cell types ( transdifferentiation ) and are expected to be useful in the treatment of patients with dysfunction in periurethral nervous tissue , smooth muscle , striated muscle , urethral mucosa , submucosal connective tissue and various other tissues . our objective was to evaluate the safety and efficacy of periurethral cord blood stem cell injection for treatment of stress urinary incontinence . this study was carried out from july , 2005 to july , 2006 at the cha gangnam medical center and school of medicine , cha university , with irb approval . the procedure was completed on 39 women with urinary incontinence who had signed informed consent forms . all had previously tried conservative treatment , and one had been treated with other surgical method for the disorder , without success . all patients were given a quality - of - life questionnaire and incontinence impact questionnaire prior to the procedure . history , physical examination , urine test , urine culture , general blood test , routine chemistry , cotton - swab test , urodynamic study , and hla typing were performed on the patients . the umbilical cord vein was pricked after normal delivery and then the human umbilical cord blood was collected in an aseptic collecting bag ( national red cross , korea ) containing 23 ml of citrate - phosphate - dextrose - adenine ( cpda-1 ) and stored at -70. after thawing at 37 , cord blood cells were separated into a low - density mononuclear fraction ( < 1,077 g / ml ) by ficoll - paque plus ( ge healthcare ab , uppsala , sweden , http://www.amersham.com ) . to briefly summarize the separation method , diluted cord blood was carefully poured into a 15 ml tube which contained ficoll ( ficoll : diluted cord blood=3:4 ) . the mixture of diluted cord blood and ficoll was centrifuged at 1,800 rpm for 30 min and mononuclear cells were carefully drawn out from the top layer . the cells were stored in 50 ml tubes with saline , and the withdrawn mononuclear cells were centrifuged three times at 1,800 rpm for 10 min . the cells were collected afterward and the supernatant was discarded . saline ( 50 ml ) was mixed with the remaining cell pellet and the process of centrifuging at 1,000 rpm for 10 min was repeated twice . the cell pellet was resuspended with 50 ml saline , and 10 l was removed . all parts of the transurethral umbilical cord blood stem cell injection were performed by one operator . antibiotic was given to the patient prior to periurethral umbilical cord blood stem cell ( ucbsc ) injection . after the vagina and perineum were sterilized , local anesthesia was given in the vicinity of the urethra in the 4 and 8 o'clock positions with 1% lidocaine . using a 30 26 french cystoscope , stem cells removed from human cord blood were verified in the hla test , and hucb mononuclear cell suspension in saline solution ( mean , 4.31.910 cells per 2 ml ) were injected into the urethra under cystoscope in the 4 and 8 o'clock positions . two injections per patient ( 1 ml each ) were performed in submucosal area of the proximal - urethra . injection continued until the urethral mucosa was completely closed , while the inflation of urethra mucosa was observed through the cystoscope . patients were informed to immediately visit the clinic in case of any postoperative complications . as follow - up , physical examination and liver function tests were performed on a weekly basis for the following month . outcomes were evaluated by comparing patients ' voiding diaries and perceptions . to compare patients ' perceptions , the patient satisfaction test was performed 1 month , 3 months , and 12 months after the procedure . a 3-month postoperative urodynamic study was also used to monitor the objective improvement of urinary incontinence following periurethral ucbsc injection . a urodynamic study was conducted on ten patients who had a mucp result of less than 30 cmh2o before the stem cell transplantation 3 months after the procedure . mean age of the 39 patients treated in the study was 51.57.6 yr . all patients had stress urinary incontinence ; 22 had urethral hypermobility , eight had intrinsic sphincter deficiency , and nine had mixed stress urinary incontinence . one of the patients had previously undergone a surgical method to treat incontinence ( table 1 ) . two patients stopped the injection due to pain during the procedure , but were not included in the study . none of the cases had voiding dysfunction , urinary retention , urinary tract infection or graft versus host disease ( gvhd ) resulting from the procedure ( table 2 ) . three patients discontinued the 1 month postoperative patient satisfaction test . 28 ( 77.8% ) showed more than 50% improvement , and eight ( 22.2% ) reported no improvement in the 1-month postoperative patient satisfaction test . in the 3-month postoperative patient satisfaction test , 29 ( 80.5% ) continuously showed more than 50% improvement . finally , in the 12-month postoperative patient satisfaction test , 26 ( 72.2% ) continuously showed more than 50% improvement ( table 3 ) . in addition , a 3-month postoperative urodynamic study conducted on five patients with stress urinary incontinence due to isd and five patients with mixed stress urinary incontinence verified that in all ten patients the maximal urethral closing pressure ( mucp ) values were increased by more than 30 cmh2o ( table 4 ) . the mucp values were significantly improved in the isd and mixed stress urinary incontinence patients after 3 months . recently , stem cell therapy has been tried for urinary incontinence under the concept that urinary incontinence is essentially a degenerative disease , so stem cell may play a role in regenerating the damaged sphincter . various types of tissue have been used as the source of stem cells for the treatment of urinary incontinence . first , harvesting stem cells from the aged patient 's own muscle is advantageous since rejection complications are minimized . but unfortunately , the restoration efficiency of stem cells decreases with age ( 7 ) . renault , thornell and their team reported that the restoration efficiency of stem cells in skeletal muscle declines in direct proportion with age ( 4 - 6% vs. 1 - 2% ) ( 8,9 ) . jejurikar and his team reported that stem cell growth and transference also decrease with age ( 10 ) . thus , the therapeutic efficacy of transplanted stem cells obtained from the patient 's muscle is poor . second , taking muscle from the patient 's arm is an invasive procedure associated with complications of bleeding or infection . gluckman and his team have successfully conducted cord blood transplantation ( cbt ) procedures since 1988 ( 11 ) . it also has been investigated in many animal models of various degenerative diseases , such as spinal cord injury model and cerebral ischemia model , with some promising results ( 12 - 14 ) . cbt has a low risk of causing gvhd and viral contamination , requires less stringent hla matching and is easily performed . furthermore , cord blood stem cells are obtained from a large source of donors . as far as we know , this is the first use of human cord blood stem cells for treatment of urinary incontinence . periurethral ucbsc injection is a very short , minimally invasive outpatient procedure that is not associated with complications . human cord blood stem cell therapy improved different types of stress urinary incontinence 3 months after the procedure in 80% of our study patients . a urodynamic study conducted on ten patients who had a mucp result of less than 30 cmh2o before the stem cell transplantation showed improved function of greater than 30 cmh2o in mucp 3 months after the procedure . unfortunately , the number of patients studied was too small to allow comparison of therapeutic efficacy for the different types of stress urinary incontinence . long term follow - up of more than a year and investigation into the mechanism of stem cell therapy are goals for our next study . in conclusion , periurethral injection of human cord blood stem cells was effective , at least for the short term , with a lower incidence of surgery related complications compared to previous surgical methods .

our objective in this study was to evaluate the safety and efficacy of transurethral cord blood stem cell injection for treatment of stress urinary incontinence in women . between july 2005 and july 2006 , 39 women underwent transurethral umbilical cord blood stem cell injection performed by one operator at a single hospital . all patients had stress urinary incontinence . the patients were evaluated 1 , 3 , and 12 months postoperatively . no postoperative complications were observed . 28 patients ( 77.8% ) were more than 50% satisfied according to the patient 's satisfaction results after 1 month , 29 patients ( 83% ) were more than 50% satisfied according to the patient 's satisfaction results after 3 months , and 26 ( 72.2% ) continuously showed more than 50% improvement after 12 months . intrinsic sphincter deficiency and mixed stress incontinency improved in the ten patients evaluated by urodynamic study . our results suggest that transurethral umbilical cord blood stem cell injection is an effective treatment for women with all types of stress urinary incontinence .

descrever as principais caractersticas clnico - radiolgicas de pacientes com histoplasmose simulando cncer de pulmo . estudo descritivo e retrospectivo baseado na anlise dos pronturios mdicos de 294 pacientes diagnosticados com histoplasmose no laboratrio de micologia da irmandade santa casa de misericrdia de porto alegre , em porto alegre ( rs ) entre 1977 e 2011 . o diagnstico de histoplasmose foi estabelecido por cultura , exame histopatolgico ou identificao de bandas m ou h por imunodifuso . aps identificar os pacientes com leses macroscpicas e com achados compatveis de malignidade em radiografia ou tc de trax , os pacientes foram divididos em dois grupos : pacientes com histria de cncer e leses simulando metstases ( grupo hc ) e pacientes sem histria de cncer com leso simulando neoplasia primria ( shc ) . dos 294 pacientes com histoplasmose , 15 apresentaram leses simulando neoplasia primria ou metstases ( 9 e 6 nos grupos hc e shc , respectivamente ) . a idade dos pacientes variou de 13 a 67 anos ( mediana , 44 anos ) dos 15 pacientes , 14 ( 93% ) apresentaram leses pulmonares no momento da internao . a sndrome clnica e radiolgica da doena neoplsica no se limita a malignidade , e , portanto , as doenas infecciosas granulomatosas devem ser consideradas no diagnstico diferencial . capsulatum ( h. capsulatum ) can produce a broad spectrum of clinical manifestations , ranging from self - limiting respiratory complaints to progressive , life - threatening infections . primary pulmonary infection results from the inhalation of airborne microconidia , and the vast majority of infections are self - limiting - in most cases , the infection is limited to the lungs - however , since the onset of the aids epidemic , disseminated histoplasmosis has been reported with greater frequency . air currents can carry the microconidia for miles , exposing unsuspecting individuals to indirect contact with a contaminated site . in addition , the fungus can be present at environmental sites that are not visibly contaminated with droppings from birds or bats , thus reducing the chance that histoplasmosis will be suspected . in brazil , histoplasmosis is a recurrent topic in pulmonology . a review of the literature revealed that there have been cases of histoplasmosis mimicking malignancy . the rarity of this manifestation prompted our study , the objective of which was to describe the main clinical and radiological characteristics of patients with histoplasmosis mimicking cancer . this was a retrospective descriptive study based on the analysis of the medical records of the 294 patients diagnosed with histoplasmosis between 1977 and 2011 at the mycology laboratory of the santa casa sisters of mercy hospital of porto alegre in the city of porto alegre , brazil . the study was approved by the human research ethics committee of the hospital ( protocol no . the diagnosis of histoplasmosis was established by culture , histopathological examination , or immunodiffusion testing ( identification of m or h precipitation bands ) . after identifying the patients with macroscopic lesions , as well as with radiological and ct findings consistent with malignancy , we divided the patients into two groups : patients with a history of cancer presenting lesions mimicking metastases ( hc group ) ; and patients without a history of cancer presenting at least one lesion mimicking primary cancer ( nhc group ) . the radiological criteria for inclusion in the groups were the following : having multiple lesions ; having a higher prevalence of pulmonary lesions in the lower lobes ( hc group ) ; or having a solid solitary lesion with homogenous soft - tissue attenuation and without benign calcification or spiculated margins . of the 294 patients diagnosed with histoplasmosis , 15 presented with lesions mimicking primary neoplasia or simulating metastases . the most common clinical symptoms of the 15 patients , 9 had a history of cancer and presented with lesions simulating metastases ( hc group ; figure 1 ) , and 6 patients had no history of cancer and presented with at least one lesion mimicking primary malignancy ( nhc group ; figure 2 ) . figure 1pulmonary histoplasmosis in a 29-year - old female patient with a history of melanoma and treatment with antineoplastic agents ( patient 5 ) . the ct scans reveal multiple , sharply circumscribed , randomly distributed nodules , predominantly in the left lung . figure 2histoplasmoma in a 66-year - old male patient with arterial hypertension ( patient 11 ) . in a , a posteroanterior chest x - ray and , in b , a ct scan of the chest revealing a homogeneous consolidation ( 3 cm in diameter ) in the upper segment of the right lower lobe . the age of the patients ranged from 13 to 67 years ( median , 44 years ) . of the 15 patients , 14 ( 93% ) presented with pulmonary lesions at the time of hospitalization . in all 15 patients , the diagnosis of histoplasmosis was made by demonstrating oval budding yeasts , typical of h. capsulatum , on biopsy specimens stained with methenamine silver . the diagnosis was confirmed by culture in only 4 cases , although culture was requested in only 5 . seven patients were tested for the presence of specific antibodies to h. capsulatum , and 6 of those 7 tested negative . table 1clinical findings , radiological findings , diagnoses , treatment , and outcomes of the 15 patients with histoplasmosis mimicking primary or metastatic lung cancer . patients with a history of cancer patientage , years / genderprimary diseaseclinical presentationchest x - ray findingssite(s ) of infectiondiagnosistreatmentoutcomehistidhcult158/mmultiple myelomadisseminatedconsolidationlung , mediastinal lymph node , adrenal gland+ndnduntreateddied240/fcarcinoid tumorpulmonary / histoplasmomanoduleslung+ndsurgeryimproved332/mlymphomadisseminatedmasslung , skin+++untreateddied467/msquamous cell carcinomapulmonary / histoplasmomamass , consolidationlung+nditraconazoleimproved529/fmelanomapulmonarynoduleslung+ndnot reportednot reported613/flymphomadisseminatednoduleslung , larynx+ndnditraconazoleimproved750/fpancreatic adenocarcinomadisseminatednoduleslung , pleura+nd+untreateddied858/mlymphomadisseminatedpulmonary infiltrateslung+nd+not reportednot reported954/fbreast carcinomapulmonarymasslung+ndndsurgeryimprovedpatients without a history of cancerpatientage , years / genderprimary diseaseclinical presentationchest radiographic findingssite(s ) of infectiondiagnosistreatmentoutcomehistidhcult1025/maidsdisseminatednormalpharynx , skin+ndndamphotericin bimproved1166/marterial hypertensionpulmonary / histoplasmomamasslung , lymph node+nditraconazoleimproved1263/fnonepulmonary / histoplasmomamasslung+ndsurgeryimproved1325/fnonepulmonary / histoplasmomamasslung++itraconazoleimproved1413/mnonedisseminatednodulelung , mediastinal+ndnditraconazoleimproved1567/mliver transplantpulmonarymasslung+ndnot reportednot reportedhist : histopathology , tissue section ( h&e and grocott - gomori methenamine silver);idh : immunodiffusion for histoplasma capsulatum;cult : culture on sabouraud dextrose agar and mycosel(r);nd : not determined . : histopathology , tissue section ( h&e and grocott - gomori methenamine silver ) ; : immunodiffusion for histoplasma capsulatum ; : culture on sabouraud dextrose agar and mycosel(r ) ; the results of the present study underscore the fact that the clinical syndrome of neoplastic disease is not confined to malignancy and that granulomatous infectious diseases must be considered in the differential diagnosis . excluding histoplasmosis from the differential diagnosis of pulmonary lesions can delay the diagnostic process . there are sporadic reports of patients with histoplasmosis that have been misdiagnosed as having head and neck cancer , primary lung cancer , or lymphoma . in such cases , the cytological examination of the pleural fluid can suggest neoplasia , because giant cells in which h. capsulatum is present could be mistaken for malignant lymphoblasts . it is of interest that histoplasmosis granuloma might be associated with a type of lung carcinoma . on ct scans , as well as on scans made with more advanced imaging techniques , such as positron emission tomography , histoplasmosis can mimic malignant lesions . immunocompromised patients , such as those in our hc group , are more susceptible to disseminated disease . in the literature , approximately two - thirds of patients with chronic disseminated histoplasmosis present with oropharyngeal or laryngeal involvement , which is almost invariably the clinical feature that leads to the diagnosis , and one of our patients ( patient 6 ) presented with this type of lesion . in addition , adrenal involvement has been found in over half of all patients with disseminated histoplasmosis , the lesions being more commonly found in the zona reticularis ; this could be due to the presence of higher downstream concentrations of cortisol , en route from secretion to the medullary central venous system . three of the patients in the hc group had disseminated disease . of those 3 , only 1 was submitted to autopsy ( case 1 ) , which showed adrenal involvement . cutaneous lesions of disseminated histoplasmosis are infrequent , being most commonly found in individuals who are infected with hiv , which nearly none of our patients were . the patients in the nhc group demonstrated that histoplasmosis could occur in individuals who are not apparently immunocompromised . because imaging findings often mimic other granulomatous infections and neoplastic processes , they are not considered diagnostic . histoplasmosis in the mediastinum is an uncommon diagnosis that has a presentation similar to that of other benign and neoplastic conditions encountered in the chest . the principle that a solitary circumscribed pulmonary nodule is diagnostic of carcinoma unless proven otherwise has been well established ( patients 4 , 11 , 12 , and 13 ) , especially in cases of enlarging histoplasmoma . the diagnostic approach depends on the type of infection and the amount of microconidia inhaled . a variety of tests , including culture , specific staining for fungal cells , antigen detection , and serologic tests for antibodies , are used for the diagnosis of histoplasmosis . the sensitivity of laboratory tests depends on the clinical manifestation of histoplasmosis ( disseminated , chronic pulmonary , or self - limiting ) . we observed these differences and the importance of using more than one diagnostic method . in our cohort , the patients with histoplasmoma ( patients 11 and 12 ) showed no specific antibodies to h. capsulatum ; this also can happen in immunocompromised patients with positive cultures . this information can be helpful because the absence of specific antibodies is usually associated with the absence of infection in immunocompetent patients . in conclusion , histoplasmosis should be considered in the differential diagnosis of primary and metastatic lung cancer , because delaying treatment can allow severe manifestations of the former to occur .

objective : to describe the main clinical and radiological characteristics of patients with histoplasmosis mimicking lung cancer . methods : this was a retrospective descriptive study based on the analysis of the medical records of the 294 patients diagnosed with histoplasmosis between 1977 and 2011 at the mycology laboratory of the santa casa sisters of mercy hospital of porto alegre in the city of porto alegre , brazil . the diagnosis of histoplasmosis was established by culture , histopathological examination , or immunodiffusion testing ( identification of m or h precipitation bands ) . after identifying the patients with macroscopic lesions , as well as radiological and ct findings consistent with malignancy , we divided the patients into two groups : those with a history of cancer and presenting with lesions mimicking metastases ( hc group ) ; and those with no such history but also presenting with lesions mimicking metastases ( nhc group ) . results : of the 294 patients diagnosed with histoplasmosis , 15 had presented with lesions mimicking primary neoplasia or metastases ( 9 and 6 in the hc and nhc groups , respectively ) . the age of the patients ranged from 13 to 67 years ( median , 44 years ) . of the 15 patients , 14 ( 93% ) presented with pulmonary lesions at the time of hospitalization . conclusions : the clinical and radiological syndrome of neoplastic disease is not confined to malignancy , and granulomatous infectious diseases must therefore be considered in the differential diagnosis .

schizophrenia and related psychoses are chronic disorders with an onset usually in early adulthood that affect patients all over their life and generally have moderate prognosis . several previous [ 1 , 2 ] and more recent [ 3 , 4 ] studies have suggested that early intervention is crucial for the improvement of the prognosis and outcome of these disabling disorders both medium- and long - term . however , the results of such studies have been criticized by others , and it is supported that the effectiveness of current protocols of early intervention is not superior to standard care [ 5 , 6 ] . moreover , it has been recently proposed that adequate funding and good clinical governance are critical in ensuring service quality and maintaining continuity of care , whether the early intervention in psychosis service is specialized or integrated within a generic mental health team . despite the ongoing debate about the effectiveness of specialized early intervention services , at recent years several such services have been developed worldwide for the early detection , intervention and comprehensive care of people who experience a first episode of psychosis ( fep ) . the first step for the establishment of new services is the estimation of the needs of a defined area . this study aimed to explore the needs and provide epidemiological data on fep patients in the prefectures of ioannina and thesprotia in greece . this is the first greek study on the rates of first episode of psychosis in a defined catchment area . the epidemiologic survey was performed in the context of the recently established , early intervention service ( eis ) of the university hospital of ioannina . the catchment area of the prefectures of ioannina and thesprotia belongs to the epirus region , north - western greece , and has a population of about 220000 inhabitants . mental health services of the area comprise the inpatient and outpatient psychiatric department of the university hospital of ioannina , the outpatient psychiatric department of the general state hospital , the outpatient department of the social insurance organization ( ika ) , and the mobile mental health unit ( mmhu i - t ) which delivers services in rural and remote areas . although in greece care is public , a large proportion of patients prefer to be examined by private practice physicians . there is no registration system for the first diagnosed psychotic patients , so for the performance of a reliable epidemiological survey data should be obtained from all those who may have examined and treated such patients . data for first episode psychotic patients during a two - year period ( 2008 and 2009 ) were obtained by reviewing the medical records of the patients examined in the two hospitals , ika and the mmhu i - t . for patients treated in the private sector , data was obtained by personal communication with the 12 treating psychiatrists of the area for the aforementioned period . all diagnoses were made by treating clinicians according to icd-10 criteria , as this classification is officially used in the country . however , only clinicians of the eis regularly use a standardized assessment interview , while their private sector colleagues rely only on usual clinical assessment . however , there is evidence that stability of icd-10 psychotic - disorder diagnoses over time is high . duration of untreated psychosis ( dup ) was calculated by the first author ( vp ) with the retrospective application of the principles of the symptom onset in schizophrenia ( sos ) inventory to the patients information as recorded at their charts ( public sector ) , or as provided by treating psychiatrists ( private sector ) . for the determination of patients socio - economic status we used an adapted form of the uk classification system , which has been used in previous research . more specifically , three social classes were defined , namely upper ( corresponding to the class i ) , middle ( comprising classes ii and iii ) and lower ( comprising classes iv and v ) , respectively . this adaptation was based on economic criteria of the patients families rather , than on their working status , since a large proportion of patients were very young , were still students and may have never worked . the statistical package of the social sciences ( spss 19.0 ) was used t perform all analyses . analysis was made with the use of the student t - tests and the statistical level for significance was chosen at p<0.05 . a total of 132 fep patients were examined in the 2-year period in the catchment area . most of the patients ( 81 or 61.4% ) were diagnosed and treated by private practicing psychiatrists . the majority of patients examined in the public sector ( 45 out of 51 , 88.2% ) were referred to the eis . data regarding base - line symptom severity were not available for private sector patients , because private practice psychiatrists do not regularly use assessment tools . statistical analysis showed no differences between the two sectors in terms of patients age , gender , family and social status , profession and dup . education was associated with the treatment setting selection , and college education was predictive of the use of the public sector ( p<.001 ) . first episode patients who had a history of alcohol / substance abuse were more likely been treated in the private sector ( p=.021 ) . a positive family history of a psychiatric disorder was associated with treatment in the public sector ( or 0.43 , 95% ci 0.20 - 0.92 , p=0.028 ) . there was an interaction of the variables substance abuse and family history . logistic regression showed that treatment setting was determined by the combination of these two variables , and that patients who were abusing alcohol or substances and had no family psychiatric history were less likely been treated in the public sector ( or 0.19 , 95% ci 0.04 - 0.90 , p=0.036 ) . the acquisition of data on the rates on fep in a defined area is essential for planning and providing mental health services . we were able to identify 132 fep cases who received treatment in every available setting in our catchment area in a 2-year - period this makes an annual incidence rate of 30 new cases per 100000 which is within the range reported in previous research in different countries . in our study this may reflect patients attitudes toward hospital psychiatric treatment ; or it may be that the eis unit , where most public sector cases were referred had just been established at the time of the study . moreover , at that time financial crisis in greece was in the beginning and more patients could afford treatment in the private sector . however , this is a relevant finding , because most patients did not receive the comprehensive multidisciplinary care delivered by the eis unit of the university hospital of ioannina . moreover , it has been suggested that specialized first - episode psychosis services may effectively address the issues of involving and educating families about psychosis as well as stigma . it is not known whether this is the case in the private sector in our country . on the other hand , preference for the psychiatric private sector is widespread in western countries , and there is evidence that , with the exception of some university centers , the quality of treatment in the public sector is poor [ 14 , 15 ] . notably , there was not a single case of first episode patient treated by the mmhu , but patients from rural areas would be rather examined by outpatient hospital services or private practicing psychiatrists . the mmhu delivers services since 2007 and has contributed significantly to the reduction of hospitalizations of chronic psychotic patients living in rural and remote areas of the prefectures of ioannina and thesprotia . we assume that perceived stigmatization of fep patients and their families in these rural areas prevents them from seeking help by a local mental health service . immigrants comprised only a small proportion of the patients ( 8 cases , 6% ) . the immigrant population in our catchment area is estimated at 4.4% , mostly at working age . it has been demonstrated , that migration is associated with high incidence rates of psychosis . in a recent study at a socioeconomically deprived area of inner london immigrants were over - represented among fep cases . from a total of 484 fep patients , only 23.1%% were british , while the proportion of british in the population at risk was as high as 41.6% . recent evidence in our country suggests that immigrants experienced higher degrees of inequity in primary health care that is possibly caused by their restricted access to social insurance health care . this may be the case of some fep cases which go unrecognized in this population . we assume that fep immigrant patients may have problems of access to the mental health system , resulting from socioeconomic reasons , insurance issues and barriers within the system , i.e. difficulties in language and little appreciation of the culture and adversities of this population by mental health staff and primary care physicians . conceivably , efforts should be made for the identification of such cases by the mental health system . duration of untreated psychosis was not significantly different for patients been treated in the private or the public sector ( mean duration 18.2 and 22.5 months , respectively ) . the interval between the onset of psychotic symptoms and treatment initiation has been shown to be a predictor of outcome , and shorter dup has been associated with better chance for recovery [ 21 , 22 ] . it is unknown whether private sector care providers can make efforts to reduce dup , but public health services should arrange initiations for facilitating access to mental health care and educating the public regarding psychotic illness in young persons . according to statistical analysis , education was associated with treatment setting selection , and having or being studied in college predicted treatment in the public sector . this finding is not easy to be interpreted and it is not known whether this level of education contributes to the development of a positive attitude toward the public health system . another finding of statistical and probably clinical significance was that patients with a history of alcohol or substance abuse were more likely to be treated in the private sector . it may be possible that the public sector physicians tend to underestimate the role of alcohol or substance abuse in psychopathology . this is supported by the relatively low rates of 11.8% of alcohol / substance abuse recorded for public sector patients , compared to previously reported , much higher rates . or , that dual diagnosis patients would prefer the perceived less restricted context of the private sector . no matter the explanation , dual diagnosis patients , who are a particular challenging subgroup , would not receive a more intensive and comprehensive care provided by the multidisciplinary eis team . the selection of the private sector as treatment setting was found merely to be determined by the combination of having a history of alcohol or substance abuse and a negative family psychiatric history . this means that patients with a positive family history for mental disorder would prefer to be treated in the public health system . perhaps the families of those fep patients , who were familiar with mental illness , were aware of the early intervention service of the university hospital , where most public sector cases were treated . however , there is evidence that families with a past history of psychiatric hospitalization of a family member were less likely to recommend other family members to mental health services , as indicated by the long delay between onset of psychotic symptoms and first admission which was found to be independently predicted by a family history of psychiatric hospitalization [ 24 , 25 ] . regarding illness severity at baseline , we have to note that panss scores were not available for patients treated in the private sector . our data are supposedly complete because we obtained data from every resource in the area patients could seek mental health care . a small number of cases may have been missed if they have been examined in other cities , such as the capital of greece , athens or the second large city , thessaloniki . other cases may have been missed if they were hospitalized in private hospitals in other cities , as in our region there is no private inpatient facility . a possible explanation for such a preference may be the perception that in those large cities with well - organized private facilities , fep patients would receive better care ; or it was the perceived stigmatization that led patients and families to seek care in other cities . we believe that the number of such cases is small , and we also assume that these patients were difficult to receive optimal long term care due to distance from their treating service which would render regular follow - up difficult . it should be mentioned that the structure of the health system in greece which is largely based on private practice physicians makes any epidemiologic survey performance a difficult task . for example , in the large population cities of athens and thessaloniki where there are many psychiatrists working in private practice , an effort to collect epidemiological data would be extremely difficult . patients diagnoses at the private sector were made according to usual clinical examination and history of the patients , without the use of a diagnostic interview , or other instrument . moreover , dup was calculated retrospectively , by applying the principles of sos to the information at patients charts , without interviewing the patients and other informants . in our catchment area most first episode patients are been treated by private sector clinicians . the selection of the private sector as treatment setting was found merely to be determined by the combination of having a history of alcohol or substance abuse and a negative family psychiatric history . immigrants comprised a small proportion of the patients , despite evidence of higher rates of psychotic disorders in this population . the results of this first greek study on the rates of first episode of psychosis in a defined area are relevant and may inform clinical practice and mental health policy .

this is the first greek study presenting epidemiologic data on first - episode psychosis ( fep ) patients in a defined catchment area . data for first episode psychotic patients during a two - year period ( 2008 and 2009 ) were obtained by all the mental health providers in the area , public or private . a total of 132 fep patients were examined in the 2-year period in the catchment area . most of the patients ( 61.4% ) were diagnosed and treated by private practicing psychiatrists . statistical analysis showed no differences between the two sectors in terms of patients age , gender , family and social status , profession and duration of untreated psychosis ( median duration 6 months ) . patients who were abusing substances and had no family psychiatric history were less likely been treated in the public sector . immigrants comprised only a small proportion of the patients , probably because they have difficulties in accessing the mental health system .

esophageal achalasia is a rare motility disorder of the esophagus involving the smooth muscle layer and the lower esophagus sphincter ( les ) , with its incomplete relaxation and increased tone . this pathology is characterized by difficulty in swallowing , regurgitation , and sometimes chest pain . specific tests for diagnosis of esophageal achalasia are barium swallow and esophageal manometry . esophago - gastro - duodenoscopy with or without endoscopic ultrasound can be also performed to rule out the probability of cancer . for management , dilation or stretching of the esophagus , surgery and injection of muscle relaxing substances ( botulin toxin ) in the esophagus were foreseen . we present a case of esophagus achalasia diagnosed for intense rest and effort dyspnea , persistent cough , arterial hypotension , and chest discomfort . 12-leads ecg showed sinus rhythm with pulse rate at 95 beats / min . left axial deviation and diffuse disorders of repolarization were also seen . chest x - ray revealed massively dilated esophagus along the right cardiac border [ figure 1 ] . ct of the chest showed esophageal body dilatation filled with food remaining that compressed the left atrium [ figure 2 ] . the esophageal manometry evidenced body esophageal a - peristalsis , with low amplitude of esophageal body contraction and failed relaxation of les after water swallow . left atrial compression induced by an extrinsic structure was seen at two - dimensional - trans - thoracic echocardiography ( 2d - tte ) . this structure has an elongate form and was filled of liquid drinking to differentiate esophagus from any cardiac formation [ figure 3 ] . diastolic mitral inflow pattern showed an e / a waves ratio = 1.1 ; dt measured 210 msec . ; ivrt was 87 msec . three dimensional echocardiography ( 3d - tte ) pointed out the extracardiac roundish esophageal cavity compressing left atrium , clearly separated from the heart structures [ figure 4 ] . the same evaluation performed in parasternal approach ( at level of aortic root ) consented to identify the pulmonary trunk and its subdivision in right and left pulmonary arteries [ figure 5 ] . antero - posterior chest x - ray that shows poorly defined borders at the median and lower right lobe and at the lung base ct of the chest pointed out extrinsic compression at level of the left atrium by dilated esophagus ( arrow ) two - dimensional echocardiography recorded in apical 4 chambers view showing an extrinsic compression on the left atrium due to a dilated and lengthened formation evidenced after drinking a liquid ( arrow ) ( a ) three - dimensional echocardiography performed in apical 2-chambers view . evidence of a round structure ( arrow ) compressing left atrium ; ( b ) three - dimensional echocardiography in the same approach . more evident dilated esophagus ( arrow ) located below to the cardiac plane and separated from the cardiac structures three - dimensional echocardiography performed from the parasternal approach intermediate between the long and short - axis view , at level of aortic root . clear evidence of dilated esophagus ( arrow ) compressing the lower segment of the pulmonary trunk the symptoms are a consequence of the left atrial compression that reduces its volume causing an impairment of left ventricular diastolic filling . in addition , as a consequence of increased left atrial pressure , pulmonary pressure also rises causing an intense dyspnea leading to pulmonary edema . esophageal achalasia is usually diagnosed by chest x - ray , ct , mri , and esophageal manometry . functional magnetic resonance imaging ( fmri ) has been recently proposed for the evaluation of the esophagus motility . but , the test of choice for diagnosing its extrinsic compression of left atrium by esophageal achalasia is two - dimensional echocardiography ( 2d - tte ) . at 2d - tte , the achalasia moves asynchronously with the atria in contrast to intrinsic atrial structures . in our case , 2d - echocardiography performed in apical long - axis view evidenced the compression of left atrium by an extracardiac structure corresponding to the dilated esophagus evidenced by the liquid drink . nevertheless , 2d - tte is limited to the cases with acceptable sonographic window . in the presence of a poor sonographic space , trans - esophageal echocardiography three - dimensional trans - thoracic echocardiography ( 3d - tte ) was also performed in our patient . this was firstly carried out in an individual with esophageal achalasia . in our patient , 3d - tte records consented to better appreciate the esophagus compressing the left atrium and the lower part of the pulmonary trunk . even though 3d - tte is not explanatory than 2d - tte , it consented to better evaluate the dilated esophagus separated from the left atrium and compressing this same and some neighboring structures without the liquid drink too

esophageal achalasia is a motility disorder characterized by impaired relaxation of the lower esophageal sphincter and dilatation of the distal two - thirds of the esophagus . this condition may be a non - frequent reason of extrinsic compression of left atrium . in turn , this can be a cause of some hemodynamic changes such as chest discomfort , dyspnea or reduced exercise tolerance , systemic hypotension and tachycardia . we describe a case of a patient with esophagus achalasia compressing the left atrium and inducing hemodynamic compromise . the diagnostic methods , as chest x - ray , computed tomography ( ct ) , manometry , and 2d - trans - thoracic echocardiography ( tte ) demonstrated the esophagus dilation , the impaired relaxation of the lower esophageal sphincter , and its compression on the left atrium . three - d trans - thoracic echocardiography ( 3d - tte ) was firstly performed also . this last examination pointed out better than 2d - tte the extrinsic compression of the left atrium due to the esophagus dilatation . therefore , 3d - tte is a true improvement for the echocardiographic diagnosis of the left atrial compression induced by esophageal achalasia .

a 52-year - old male , 30-pack - year current smoker , visited the emergency room complaining of severe chest pain and dyspnea . a chest x - ray showed a large amount of pneumothorax in the right pleural cavity ( fig . initial computed tomography showed diffuse lung emphysema , sequelae of tuberculosis in the right lung , and multiple bullae in the right upper and lower lobes . surgery was required because of continuous air leakage through the chest drain for 4 days after a closed thoracostomy . after multiple wedge resections of the right upper and lower lobes , the resection sites were covered with an absorbable polyglycolic acid sheet ( neoveil ; gunze ltd . , a mixture of 40 mg of viscum album extract ( european mistletoe , abnoba viscum f ; abnoba helmittel gmbh , pforzheim , germany ) with 50 ml of normal saline was administered into the pleural space by needle instillation upon the visceral and parietal pleura . until the second postoperative day , the recovery was uneventful , with both lung fields clear on chest x - ray ( fig . the patient started to complain of worsening dyspnea even at rest , and a follow - up chest x - ray showed loculated right pleural effusion and bilateral lung infiltration . arterial blood gas analysis under 5 l of oxygen inhalation showed that arterial oxygen pressure ( pao2 ) was 42.0 mm hg and oxygen saturation was 78.9% . after intubation and mechanical ventilator support , the follow - up arterial blood gas analysis showed a pao2 of 66.9 mm hg under with a fraction of inspired oxygen of 60% . in addition , the follow - up complete blood cell count showed a white blood cell count of 10,940/mm , a neutrophil percentage of 88.0% , and a lymphocyte percentage of 10.0% . bronchoscopy indicated that bronchial secretion was minimally purulent , and there were no abnormal findings suggesting the presence of bronchitis or pneumonia ( fig . , the patient was diagnosed with acute respiratory distress syndrome ( ards ) resulting from insult and an immunologic response to viscum album . methylprednisolone ( 50 mg / day ) was administered starting on the fourth postoperative day . though the initial signs suggested the development of ards , the clinical course after mechanical ventilator support was quite smooth , with good response to glucocorticoid therapy . the lung infiltration on the chest x - ray rapidly resolved after 3 days of steroid administration . the patient was discharged in good general condition on the 16th postoperative day ( fig . 3 ) . a follow - up chest x - ray 1 month after discharge showed no pleural effusion and no abnormal lung infiltration . many therapeutic options have been used to treat uncontrolled air leaks from the lung or pleural effusion . among these , chemical pleurodesis using sclerosing agents , such as tetracycline , erythromycin , hydrophilic fumed silica , and talc powder , is one of the most important treatment modalities . irritation of the pleura by instilled chemical agents promotes the sealing of the visceral pleural defect and prevents fluid accumulation . however , chemical pleurodesis is also associated with many complications , such as high fever , severe chest wall pain , fibrothorax , empyema thoracis , and acute respiratory failure . it is believed that transpleural absorption and intrapulmonary deposition of sclerosing agents occur via lymphatic stomata in the parietal pleura , resulting in the development of ards . the instilled drugs induce diffuse inflammation , pleural coagulation , fibrinolytic imbalance , formation of fibrin adhesions , and recruitment and subsequent proliferation of fibroblasts and collagen production in the pleural space . several new chemical agents are being investigated for their efficacy as pleurodesis agents with fewer complications , and viscum album extract is one of the most promising . abnoba viscum f is an extract of viscum album ( european mistletoe ) , which grows on trees of the genus fraxinus . this extract is one of the most frequently prescribed medications for the complementary treatment of cancer patients in a number of european countries . it is known to stimulate the immune system , thereby enhancing quality of life and alleviating the side effects of chemotherapy and radiotherapy , which may improve survival . in addition , viscum album instilled into the pleural cavity can induce diffuse inflammation and pleural coagulation / fibrinolytic imbalance , causing the formation of fibrin adhesions , recruitment and subsequent proliferation of fibroblast , and collagen production in the pleural space . these reactions irritate the pleural surface , thus promoting the sealing of pleural defects and preventing fluid accumulation . complications of viscum album pleurodesis have been reported and are mostly minor , including transient pleural effusion , a mild burning sensation , and mild fever episodes ; there have been no reports of serious complications . viscum alum can also serve as an effective agent for chemical pleurodesis in the treatment of congenital chylothorax and pneumothorax with continuous air leak . cho et al . reported a case of viscum album - related ipsilateral acute pneumonitis after wedge resection for pneumothorax , and stated that it was self - limiting and had a benign clinical course . however , in our case , the patient complained of progressive dyspnea with chest pain 2 days after wedge resection and chemical pleurodesis with viscum album . the follow - up chest x - ray showed loculated pleural effusion and bilateral lung infiltration . the blood gas analysis result and chest x - ray findings met the criteria of ards . the materials used in surgery , such as neoveil and fibrin glue , are unlikely to be related to the development of ards , and we could not find any report of such an association . in addition , the intraoperative course and postoperative course were similar to that of any other routine wedge resection , and otherwise uneventful . furthermore , the pathophysiology of ards is thought to be related to immune reaction , which is the modality of action for viscum album as a pleurodesis and antitumor agent . therefore , we assumed that the immune response to the viscum album extract was the cause of this episode of ards . this is the first documented case of viscum album - related ards , to our knowledge . respiratory deterioration was acute and progressive , which required placing the patient under intubation and mechanical ventilation . fortunately , the response to steroid therapy was almost instantaneous and the patient showed almost full recovery without any notable sequelae or relapse after scheduled tapering down of the steroid . based on our experience , even though viscum album pleurodesis is considered to be a generally safe and effective procedure without serious complications , patients must be carefully monitored for signs of acute respiratory failure , which might be serious if appropriate treatment is not applied in time . in addition , the pathophysiology of ards due to the immunologic response to viscum album extract must be investigated by scientific research , including animal studies .

a 52-year - old male patient who underwent multiple wedge resections experienced postoperative acute respiratory distress syndrome in both lungs after viscum album pleurodesis . despite initial rapid deterioration in clinical condition and rapid progression of bilateral lung infiltration , he exhibited a relatively smooth clinical recovery with marked response to glucocorticoid treatment . our case report suggests that care must be taken to guard against the development of acute respiratory complications in the use of viscum album for pleurodesis . however , in view of the clinically benign course , initial aggressive management of complications can prevent suffering and sequelae .

we evaluated the current distribution and potential spread of the rat lungworm within areas of the gulf coast region and midwestern united states by sampling rodent populations in regions of louisiana and oklahoma that were predicted by an ecologic niche model to contain suitable and unsuitable habitat ( 9 ) . we used a quantitative pcr ( qpcr ) taqman assay ( life technologies , foster city , ca , usa ) ( 10 ) to test for the parasite in tissue samples and further evaluated these samples through dna sequencing analysis . a total of 43 rodents and 3 shrews were collected from mccurtain county in southeastern oklahoma , and 42 rodents were collected in louisiana ( technical appendix ) . we also obtained 56 rattus norvegicus rat brain and lung tissue samples from the city of new orleans mosquito , termite , and rodent control board . flotation was performed on all 148 lung samples , and all samples were negative for adult a. cantonensis rat lungworms . known adult rat lungworms were used as controls for molecular analyses ( technical appendix ) . we tested for rat lungworm internal transcribed spacer 1 ( its1 ) dna by using a taqman qpcr on an abi 7500 system ( 10 ) . a total of 134 blood samples and 137 brain samples contained dna suitable for analysis . after qpcr , 34 of the 271 total tissue samples were classified as putatively positive for rat lungworm and sequenced , generating a 267-bp fragment of the its1 region ( technical appendix ) . on the basis of dna sequencing , 3 brain samples were identified as containing a. cantonensis dna ( genbank accession nos . 32 , 70 , and 76 ) , which were identified as 1 hispid cotton rat ( sigmodon hispidus ) and 2 brown rats ( rattus norvegicus ) , respectively ( table 1 ) . a comparison of the 3 brain samples with those in genbank by blast analysis ( http://blast.ncbi.nlm.nih.gov/blast.cgi ) showed a match with rat lungworm ( genbank accession nos . * wma , wildlife management area . * http://blast.ncbi.nlm.nih.gov/blast.cgi wma , wildlife management area . all sequences were aligned by using muscle in mega 5.2 ( http://www.megasoftware.net/ ) , manually inspected for consensus , and compared with the 267-bp fragment generated from the known sample of rat lungworm . maximum - likelihood phylogenetic analysis was performed by using sequence data for the its1 region of a. cantonensis ( genbank accession no . gu587759.1 ) , 2 closely related species , a. vasorum ( the french heartworm , gu733324.1 ) and a. costaricensis ( a parasitic nematode , ( gu587745.1 ) , and sequences obtained from the rodent hosts . maximum - likelihood phylogenetic analysis grouped sequences from rat hosts 32 , 70 , and 76 with a. cantonensis with high bootstrap support ( figure ) . maximum - likelihood bootstrap consensus phylogenetic tree showing the relationship between rat lungworm sequences generated in this study and other angiostrongylus spp . because the rat lungworm poses a major health risk to humans and wildlife worldwide , more work is needed to shed light on the location , dispersal , and influence of this parasite in new geographic regions . although previous reports document rat lungworms in the gulf coast region of the united states ( 5,11 ) , little is understood regarding their prevalence within definitive hosts and their dispersal throughout the southeastern united states . as expected , our analysis indicated that r. norvegicus rats from louisiana harbored rat lungworms . positive samples were collected from densely populated areas with high tourist activity , thereby increasing the risk for transmission to humans . moreover , rat lungworms were identified outside their known habitat and in a new rat host species ( s. hispidus ) in oklahoma , an area predicted to lack suitable habitat for the parasite ( 9 ) . our results provide a new perspective on the distribution of rat lungworms in the united states and indicate a northward range expansion that substantially increases the risk for disease spread within humans and wildlife . because endemic and novel pathogens require different and highly specialized disease management strategies , it is crucial to determine whether a pathogen is novel or endemic ( 12 ) . previous work has described the a. cantonensis rat lungworm as a novel pathogen in the southeastern united states . however , it is now characterized as endemic to this region , and our results strongly support this notion ( 11 ) . such changes in epidemiologic classification of rat lungworms accentuate the need for techniques that monitor the extent to which parasites infiltrate new geographic areas and potentially pose threats to humans and native wildlife . one such threat includes an increasing prevalence of angiostrongyliasis , which should receive increased scrutiny in patients with eosinophilic meningitis from localities characterized by paratenic and intermediate hosts . rat lungworm was found in a previously undocumented mammalian host , s. hispidus rats , which strongly suggests that this parasite is an endemic pathogen . although vegetation is their primary food source , s. hispidus rats will eat invertebrates ( 13 ) . whether these rats directly ( by intentional consumption of host ) or indirectly ( by consumption of host or free third - stage larvae on vegetation ) consume the parasite , we can not rule out the possibility that acquisition of the parasite could occur in this species and enable further range expansion for rat lungworms . s. hispidus rats are a known host for another closely related angiostrongylus species , a. costaricensis , which lends additional support for the notion that s. hispidus rats might act as a host for rat lungworms . alternatively , s. hispidus rats might simply be an accidental / dead end host for this parasite . although wildlife might become infected with the parasite , not all wildlife are definitive hosts ( 5,11 ) . additional field and laboratory studies will clarify the role that s. hispidus rats play in the spread of the rat lungworm . because many terrestrial species remain taxonomically nondescribed , there is strong potential for continual emergence of unknown pathogens worldwide ( 14 ) . global travel , human encroachment into wildlife habitat , and climate change will influence distribution and emergence of disease ( 2,15 ) . by incorporating field epidemiology with molecular genetic techniques to determine the geographic distribution of pathogens , major advances can be made in preventing the spread of wildlife diseases to human populations . our results illustrate this point and highlight the need for future work to incorporate and refine these techniques and their application to epidemiology and wildlife disease surveillance . technical appendix . additional details on geographic range expansion for rat lungworm in north america .

using quantitative pcr analysis and dna sequencing , we provide evidence for the presence of rat lungworm ( angiostrongylus cantonensis ) in oklahoma , usa , and identified a potentially novel rat host ( sigmodon hispidus ) . our results indicate a geographic range expansion for this medically and ecologically relevant parasite in north america .

sbp is a common and severe complication in cirrhotic patients ( 3 ) , and is the major cause of mortality and morbidity among them ( 4 ) . bacterial infection due to complications such as hepatic encephalopathy or hepatic failure , disruption of homeostasis , and renal insufficiency are common causes of the increased morbidity and mortality rates in cirrhotic patients ( 5 , 6 ) . one of the required measures for sbp patients is rapid diagnosis of peritonitis for empirical antibiotic treatment ( 7 , 8) . diagnosis of sbp is based on the number of ascetic fluid cells as polymorphonuclear cell count ( pmn ) 250/mm in ascetic fluid . also , only 50 to 70% of a patient s positive cultures for ascetic fluid are generally reported ( 9 - 11 ) . due to limitations such as the time - consuming process for the diagnosis of peritonitis ascetic fluid and the lack of access to appropriate laboratory facilities , reports of negative cultures could be delayed ( 12 , 13 ) . given these circumstances , numerous studies have been done on the available assessment techniques and rapid diagnosis of peritonitis . it seems that some inflammatory cytokines can be used to determine the presence and severity of an inflammatory response and organ failure ( 14 - 16 ) . the c - reactive protein is an acute phase protein that is produced predominantly by liver hepatocytes after stimulus by many cytokines and conditions such as infection or inflammation ( 17 - 20 ) . the marker is one of the most common clinical and inflammatory indicators that can be measured in any laboratory ( 21 , 22 ) . a few studies have shown increased levels of this marker in cirrhotic patients ( 1 , 2 , 23 ) . for instance , in the study by preto - zamperlini et al . , increased serum levels of crp in children with sbp were demonstrated ( 24 ) . we investigated the accuracy , sensitivity , and specificity of crp compared to the pmn count of cultured ascetic fluid for the diagnosis of sbp in children . this prospective study was conducted as a single - center cross - sectional cohort study during july 2013 to august 2014 in the department of pediatric gastroenterology in nemazee teaching hospital , which is affiliated with shiraz university of medical sciences , the major referral center in southern iran . this study was approved by the ethics committee of shiraz university of medical sciences , and all parents were asked to provide informed consent . all patients aged two months to 18 years , regardless of gender , who were admitted for liver disease and ascites were candidates for the sample for our study , and underwent abdominal paracentesis procedures for clinical suspicion of sbp . the exclusion criteria were as follows : 1 , receiving antibiotics during the past week or outside the hospital for any reason ; 2 , history of abdominal surgery in the past month ; 3 , renal dysfunction ; 4 , secondary bacterial peritonitis ; 5 , peritonitis carcinomatosis ; 6 , pancreatic peritonitis ; 7 , malignancy , or 8 , tuberculosis . children with other sources of infection were also not included , along with children with evidence of nephritic syndrome or heart failure . based on the exclusion and inclusion criteria , 150 children with liver disease samples were sent to a specialized laboratory and subjected to laboratory , cytology , and bacteriology culture evaluation . wbc counts ( sysmex , usa ) , erythrocyte sedimentation rate ( esr ) , crp levels , prothrombin time ( pt ) , international normalized ratio ( inr ) , serum total protein levels , serum albumin levels ( sigma aldrich , st . louis , usa ) , alanine transaminase ( alt ) levels , and aspartate transaminase ( ast ) levels ( sigma aldrich , st . diagnosis of sbp was based on pmn cell count 250/mm in ascetic fluid ( 25 ) . in this study , serum was obtained from patients within the first hours of admission for measurement of crp . quantitative crp was measured by the immunoturbidimetry method ( biorex , antrim , uk ) . data were expressed as means sd for quantitative variables , and as frequencies for qualitative variables . the normality was continuously assessed with a kolmogorov - smirnov test . for the crp marker compared to the pmn count by means of a positive culture test , sensitivity , specificity , positive predictive value ( ppv ) , and negative predictive value ( npv ) were calculated according to a standard formula . also , the area under the curve ( auc ) of the receiver operating characteristic ( roc ) curves was applied to assess the predictive power of crp . the data were assessed by simple linear regression analysis to determine the correlations between crp values and other markers related to liver function , such as albumin , protein , pt , and bilirubin levels . statistical analysis of the data was performed using the spss 19 ) spss inc . , il , chicago , usa ) software package . this study was approved by the ethical committee of shiraz university of medical sciences ( no . information about 150 patients with cirrhosis of the liver was investigated ; 72.7% of the patients presented without sbp , and 27.3% of patients were diagnosed with sbp . the most common symptoms in patients without spb were abdominal pain ( 67.9% ) and abdominal distension ( 66.05 % ) . in patients with sbp , the most common clinical symptoms were also abdominal pain ( 70.7% ) and abdominal distension ( 58.5% ) . the etiology of cirrhosis revealed that the most common causes of cirrhosis were biliary atresia ( 29.3% ) , neonatal hepatitis ( 19.26% ) , and wilson s disease ( 17.9% ) in patients without sbp . in patients with spb , the most common causes of cirrhosis were also biliary atresia ( 31.7% ) , neonatal hepatitis ( 24.4% ) , and wilson s disease ( 17.7% ) . among the 150 cases , 17 cases had positive cultures for the following : e. coli ( n=7 ) ; acinetobacter ( n = 2 ) ; klebsiella ( n = 2 ) ; streptococcus pneumoniae ( n = 2 ) ; and enterococcus ( n = 3 ) . the different results of the laboratory findings of cirrhotic patients without sbp and those with sbp are shown in table 2 . evaluation of ascites fluid showed that the mean sd of total cell counts in patients with sbp ( 1986.54 234.54 ) was significantly higher compared to the counts for patients without sbp ( 725.46 134.35)(p < 0.0001 ) . the means sd of white blood cell ( wbc ) count and polymorph nuclear cell ( pmn ) count in patients with sbp were significantly higher than the counts for patients without sbp ( p < 0.0001 ) ( table 2 ) . abbreviations : alp , alkaline phosphates ; alt , alanine aminotransferase ; ast , aspartate aminotransferase ; crp , c - reactive protein ; esr , estimated sedimentation rate ; inr : international normalization rate ; ldh : lactate dehydrogenate ; pt : prothrombin time ; pmn : polymorphonuclear cell ; wbc : white blood cell . the means and standard deviations of protein and albumin levels in patients with sbp were higher than the corresponding rates in patients without sbp ( p < 0.0001 ) . similar to the case with the other markers mentioned , the mean sd of ldh in patients with sbp was higher than the corresponding rate in patients without sbp ( p < 0.0001 ) . the means sd of both wbc and pmn counts were higher in patients with sbp ( 13587.6 240.4 vs. 8029.4 332.3 , p = 0.005 , and 3024.5 265.4 vs. 1766.54 435.3 , p = 0.345 , respectively ) . the means sd of inflammatory markers such as crp and esr were significantly higher in patients with sbp in contrast to the rates for patients without sbp ( p < 0.05 ) ( table 2 ) . table 3 and figure 1 show the area under the curve and the predictive values of crp for the diagnosis of sbp in children with liver disease . the percentages for sensitivity and specificity of the crp marker for sbp in cirrhotic patients according to the pmn count of ascetic fluid were 69% and 90.25% , respectively ( table 3 ) . abbreviations : auc , area under curve ; npv , negative predictive value ; ppv , positive predictive value ; sen , sensitivity ; spe , specificity . figure 2 shows the relationship between the levels of crp and total protein based on the presence ( positive ) or absence ( negative ) of sbp in cirrhotic patients . as shown in figure 2 , in both patients with and without sbp , the increased crp levels were associated with increased total protein . however , this increase in patients with sbp showed higher severity than the increase in patients without sbp . our results showed a significant correlation between total protein and crp levels in children with and without sbp ( p = 0.029 , p = 0.006 , respectively ) . figure 3 shows the relationship between albumin levels and crp levels in patients with and without sbp . the results showed that in patients with sbp , increased levels of crp were associated with increased albumin levels , which was significant ( p = 0.002 ) . however , this result was not observed in patients without sbp ; the levels of crp albumin in patients without sbp decreased significantly ( p = 0.013 ) . the same results were revealed for bilirubin ( figure 4 ) , in that with increased crp in patients with sbp , bilirubin levels increased significantly ( p = 0.003 ) , while in patients without sbp with increased levels of crp , bilirubin levels decreased ( p = 0.011 ) . the relationship between the crp levels with pt among the patients is shown in figure 5 . increased protein level was associated with significantly increased pt ( p = 0.006 ) . however , in patients with sbp , pt did not change significantly according to the level of crp changes ( p = 0.697 ) . sbp is a frequent and serious complication in cirrhotic patients that is associated with high in - hospital mortality rates of 20% - 30% , poor prognosis , and recurrence of over 70% in the first year of life . early antibiotic treatment can reduce the mortality and morbidity of sbp , which requires performance and rapid diagnostic tests ( 26 ) . although extensive studies have been conducted for laboratory testing efficiency and various markers for the diagnosis of sbp ( 24 , 26 ) , the first report on the highly significant correlation between crp and sbp was only published recently ( 24 ) . in the study by preto - zamperlini streptococcus pneumoniae was the most cultured organism ( 24 ) . in our study , e. coli was the most frequently cultured organism . the serum wbc counts were significantly higher in the sbp group compared to the counts for patients without sbp . this finding was similar to the results of preto - zamperlini et al.s study ( 24 ) . measurement of crp in cirrhotic patients determined that serum crp levels were significantly higher in patients with sbp compared to patients without sbp . in the study by preto - zamperlini , the crp level was significantly higher in cases with sbp than in cases without sbp ( 24 ) . in the study by yuan et al . , it was concluded that crp is a better marker than wbc count for diagnosis of patients with chronic hepatitis b and spb ( 27 ) . esr was significantly higher in patients with sbp compared to patients without sbp . in another study by viallon et al . , the authors reported that crp is significantly higher in adult cirrhotic patients with sbp compared to those that had sterile ascites fluid ( 28 ) . the serum total bilirubin levels were not significantly different between children with sbp and those without sbp . this finding was similar to those of other studies ( 24 , 29 ) . in our study , albumin levels were significantly higher in the sbp group compared to the non - sbp group . in contrast to our study , albumin levels were significantly higher in the non - sbp group compared to sbp group in the study by preto - zamperlini et al . et al.s study , no significant difference was found between sbp patients and those with non - sbp ascites ( 30 ) . this difference may be due to the difference in sample size or the histories of albumin infusion . in our study , no significant difference was found between the two groups in terms of pt and inr . this result is similar to the study by vieira et al . , who reported that these markers in patients with and without sbp were not significantly different ( 30 ) . in contrast to the above study , a significant difference was found in the study by preto - zamperlini et al . crp was a significant indicator of infection in hospitalized children with cirrhosis ( 31 ) . the difference between the severity of liver disease in these studies may be the cause of these differences . the results of our study showed no significant difference regarding the age and sex of the patients with and without sbp . as mentioned above , serum wbc count , esr , and crp may be good indicators of sbp in children with liver disease . however , further studies are required in this field because most of the available studies have been conducted on adult patients . another limitation is the lack of serial measurement of crp and the lack of finding a correlation between crp and prognosis and recurrence of sbp . another limitation is the lack of serial measurement of crp and the lack of finding a correlation between crp and prognosis and recurrence of sbp .

backgroundthe diagnosis of peritonitis as a complication of cirrhosis is an important clinical problem.objectivesthe aim of this study was to evaluate serum c - reactive protein levels as a diagnostic factor for spontaneous bacterial peritonitis ( sbp ) in child patients with liver disease.methodsin this study , 150 children diagnosed with liver disease and ascites upon admission to nemazee teaching hospital ( shiraz , iran ) were examined . patients were divided into spontaneous bacterial peritonitis and sterile ascetic fluid groups according to the pmn count 250/mm3 in the ascetic fluids . routine laboratory tests were conducted and quantitative c - reactive protein ( crp ) levels were measured for all of the patients . accuracy , sensitivity , and specificity of crp was evaluated for diagnosis of sbp.resultsof 150 cirrhotic patients , 109 patients presented without sbp ( 52.29% male , mean age : 5.02 4.49 years ) and 41 patients presented with sbp ( 51.21% male , mean age : 4.71 years ) . cell counts , protein levels , albumin levels , and lactate dehydrogenize ( ldh ) levels of the ascetic fluid and serum samples in the sbp group were higher than the rates for those without sbp ( p < 0.05 ( . the mean sd of crp in the sbp group ( 36.89 23.43 ) increased significantly compared to the rate among those without sbp ( 21.59 15.43 , p = 0.001 ) . the percentages for sensitivity and specificity of crp , the diagnosis of sbp based on the pmn count 250/mm3 , and cultured ascites were 69.23% , 90.25% , 88.43% , and 84.32% , respectively . the areas under the curve of crp for sbp based on the pmn count 250/mm3 and cultured ascites was 0.94 ( ci 95% : 0.90 to 0.96 ) and 0.85 ( ci 95% : 0.84 to 0.92 ) , respectively ( p < 0.001).conclusionsour study showed that crp is a marker with high sensitivity and specificity for the diagnosis of sbp in cirrhotic children .

the differential diagnosis of mediastinal masses includes primary lung cancer , metastatic cancer , neurogenic tumor , cysts and infections.12 the bronchogenic cysts are the most common cystic lesions of the mediastinum.3 in some cases , these lesions could mimic solid masses.4 most patients with posterior mediastinal cysts are asymptomatic , and the cysts are discovered incidentally during other imaging studies . the possible symptoms include chest pain , cough , dyspnea and dysphagia.356 the differentiation between a solid and cystic lesion by the imaging modalities available , such as computed tomography ( ct ) , magnetic resonance imaging ( mri ) and endoscopic ultrasonography ( eus ) , is not always easy.47 eus has provided a minimally invasive approach to the diagnosis of benign mediastinal cysts.8 in the largest retrospective study done to date , it has been demonstrated that a hypoechoic eus pattern does not exclude the diagnosis of a cyst.8 our report describes two cases of intramural bronchogenic cysts and reviews the role of eus in dealing with such cases . an 80-year - old female was admitted to our hospital due to retrosternal pain , fever , coughing and weight loss of 20 pounds in a month . a eus - guided fine needle aspiration ( fna ) of this lesion was indicated . 2 ) showed a paraesophageal anechoic round mass with a starry - sky pattern , negative doppler and posterior acoustic enhancement . the follow - up showed good evolution and diminution of the cyst size 1 month later in the radiological control . a computed tomography - scan showing a mediastinal paraesophageal mass . endoscopic ultrasonography with a linear array ultrasound endoscope showed an anechoic round mass with a starry - sky pattern and the needle inside the lesion . a 42-year - old male was referred to our institution due to a submucosal lesion in the distal third of the esophageal wall . it had a homogenous , hypoechoic aspect , with well defined borders , posterior acoustic enhancement , and measured 5 cm in its largest diameter . the patient was discharged on the same day without treatment of antibiotics , and no infectious complications were observed during follow - up . the lesion was homogenous , hypoechoic , with well defined borders and posterior acoustic enhancement . an 80-year - old female was admitted to our hospital due to retrosternal pain , fever , coughing and weight loss of 20 pounds in a month . a eus - guided fine needle aspiration ( fna ) of this lesion was indicated . 2 ) showed a paraesophageal anechoic round mass with a starry - sky pattern , negative doppler and posterior acoustic enhancement . the follow - up showed good evolution and diminution of the cyst size 1 month later in the radiological control . a computed tomography - scan showing a mediastinal paraesophageal mass . endoscopic ultrasonography with a linear array ultrasound endoscope showed an anechoic round mass with a starry - sky pattern and the needle inside the lesion . a 42-year - old male was referred to our institution due to a submucosal lesion in the distal third of the esophageal wall . it had a homogenous , hypoechoic aspect , with well defined borders , posterior acoustic enhancement , and measured 5 cm in its largest diameter . the patient was discharged on the same day without treatment of antibiotics , and no infectious complications were observed during follow - up . the lesion was homogenous , hypoechoic , with well defined borders and posterior acoustic enhancement . an 80-year - old female was admitted to our hospital due to retrosternal pain , fever , coughing and weight loss of 20 pounds in a month . a eus - guided fine needle aspiration ( fna ) of this lesion was indicated . 2 ) showed a paraesophageal anechoic round mass with a starry - sky pattern , negative doppler and posterior acoustic enhancement . the follow - up showed good evolution and diminution of the cyst size 1 month later in the radiological control . a computed tomography - scan showing a mediastinal paraesophageal mass . endoscopic ultrasonography with a linear array ultrasound endoscope showed an anechoic round mass with a starry - sky pattern and the needle inside the lesion . a 42-year - old male was referred to our institution due to a submucosal lesion in the distal third of the esophageal wall . it had a homogenous , hypoechoic aspect , with well defined borders , posterior acoustic enhancement , and measured 5 cm in its largest diameter . the patient was discharged on the same day without treatment of antibiotics , and no infectious complications were observed during follow - up . the lesion was homogenous , hypoechoic , with well defined borders and posterior acoustic enhancement . about 46% to 67% of all mediastinal lesions are malignant.910 reported accuracy of diagnosis for malignant lesions in the mediastinum is only about 83%.11 therefore , it is important to perform a good evaluation of these lesions to avoid unnecessary surgical procedures . bronchogenic cysts originate from the aberrant development of the ventral primitive foregut during embryonic development . they share a similar developmental background with esophageal duplication cysts.34612 about 85% percent of bronchogenic cysts arise in the mediastinum in close relationship to the trachea , main bronchi , and carina . occasionally , bronchogenic cysts become engulfed in the growing esophagus.13 eus can accurately distinguish a solid from a cystic lesion , and with fna it 's possible to collect materials from suspicious or atypical lesions.8 in comparison with the other imaging modalities ( ct and mri ) , eus is better at differentiating solid from cyst lesions.214 ct and mri may misdiagnosed a cystic duplication lesion as a solid lesion in about 70% of cases.2 the feature that distinguishes a cyst in eus is a round or tubular anechoic structure with a negative doppler signal and posterior acoustic enhancement.1 sometimes in eus examinations , bronchogenic cysts may resemble smooth muscle tumors and gastrointestinal stromal tumors ( gist ) due to their round or oval shape with well - defined borders and homogeneous and hypoechoic internal echo pattern . the echogenicity can be attributed to the mucoid content of the cyst.8 in the first case , weight loss , fever and an apparent mediastinal solid lesion on ct raised the possibility of a lymphoma . the starry - sky pattern on eus probably correlated with the mucoid content of the cyst . the lesion was hypoechoic and apparently with its origin at the fourth layer , raising the possibility of a gist . mediastinal cyst biopsy is not always necessary and the literatures report cases of severe infection after eus - fna.81516 the use of antibiotics before and after the procedure has already been evaluated in small clinical studies with promising results.214 however , another study shows infectious complication after eus - fna despite the use of a prophylactic antibiotic.17 at the moment , there is no consensus regarding antibiotic prophylaxis use before eus - fna . in our cases , just the first patient received antibiotics and none of them had infectious complications after eus - fna . there is little description in the literature about the macroscopic appearance of the material obtained from eus - fna . the macroscopic appearance of the material collected from bronchogenic cysts with eus - fna was often described to be like mucoid / mucinous,3811 grayish white mucus,2 thick , brownish fluid,16 or yellowish fluid.14 in our cases , both patients had a mucous content in the material obtained by eus - fna . bronchogenic cysts could be managed conservatively and/or by surgery depending on the clinical aspects of patients with this problem.18 finally , there is also controversy in the literature regarding the need to perform eus drainage of the cyst content . based on the infection risk related to eus - fna , some studies favored drainage,14 but not all of them.28 in our two cases , we did not perform eus drainage and the patients did not develop infectious complications related to eus - fna . in conclusion , they are rarely mediastinal lesions , which can explain the lack of more satisfying clinical trials and of more useful guidelines to assist physicians . current literatures are still controversial about some points such as the need of eus - fna , eus - drainage and the use of antibiotic prophylaxis during interventional eus ( fna or drainage ) .

the differentiation between a solid and cystic lesion is not always easy . eus has provided a minimally invasive approach to the diagnosis of benign mediastinal cysts . our report describes two cases of intramural bronchogenic cysts and reviews the role of eus in dealing with such cases . we conclude that the bronchogenic cysts are still a challenge despite evolution of the imaging studies .

dependence on addictive drugs spread all over the world and the side effects of addiction , it is necessary to study the function of drugs in animal trials especially in placenta . many behavioral problems in addicted mother s infants indicated the effects of opioids on embryo ( 1 , 2 ) . the majority of studies focused on the embryo , whereas they neglected to study the placenta as an important organ . disruptive effects of consumption of opioids in human samples and laboratory animals were well conducted . the research showed that consumption of opiate materials by pregnant mothers cause delay in embryonic development and malfunctions , such as spinabifida ( 1 , 3 ) . in accordance to previous studies , high blood corticosteron concentration of pregnant mother attenuate placenta and embryo . the capacity of placenta for displacement and releasing food materials depends on the placenta s shape , size and transferring factors . as morphine is small and imploring molecule , it can easily pass through blood barrier and placenta and then become effective on embryonic cells ( 4 - 6 ) . as placenta in mammals is the most important part to exchange materials between embryonic and maternal blood , the size of the placenta is directly related to food material transporting ( simple and active transport ) ( 2 , 4 , 6 ) . the morphine effects were presented with mio , kappa and delta opioids receptors and activating of these receptors caused several changes , including decrease in the camp , an increase in output of -k+ ion and a decrease in input of ca - ion ( 7 , 8) . on the other hand , the ca - ion has important role in secretion of estrogen and progesterone hormone from placenta , stableness and embryonic development ( 9 , 10 ) . by progress of pregnancy , placenta can act as a gland that secrets progesterone , estrogen and other enzymes that are needed for embryonic development and considered as an alternative for ovary secretion hormones ( 6 , 11 ) . therefore , morphine can interfere and causes dysfunction in placental secretion operating and delay in placental development ( 5 , 10 ) . several experiments have shown that morphine administration cause the decrease of placenta weight in rabbits ( 12 , 13 ) . on the other hand , because the placenta is a protective barrier , it can prevent the input or output of some materials . placental barrier as a protective mechanism is often considered against pathogenic factors ( 2 , 14 , 15 ) . disorders in the development of placenta cause placental disability in exchanging endocrine and protective acts in embryo function ( 6 ) . the importance of mother s blood corticosteron concentration in placenta development and the effects of morphine on delay of placental development are the major reasons for the present research that consider the oral morphine administrations effect on the placenta of addictive mothers on 10 and 14 days of pregnancy . the animals were housed 2/cage to a temperature of ( 24 10c ) and controlled environment with a 12-h light / dark cycle and were provided with food and water . this experimental study was accomplished with financial support of baqyiatallah ( a.s . ) university of medical sciences as a thesis project . all experiments were conducted in accordance with standard ethical guidelines and approved by the local ethical committee ( the baqiyatallah ( a.s . ) university of medical sciences committee on the use and care of animals , 86/143 , apr 15 , 2007 ) . in this study , prepared morphine sulphate from iran temad co , was used orally . twenty - four female wistar rats were divided into four equal groups consisting of six animals each . the female rats were mated into 2 groups with one adult male rat . after pregnancy ( with the observation of vaginal plug and existence of sperm in vagina ) , they were separated from male rats the next morning and kept in the same coed - groups . thereafter ( 0 day of pregnancy ) , experimental group received a daily dose of 0.05mg / ml morphine ( 5 mg per 1000 ml potable water from city pipeline for 12 rats ) ( 15 ) . also , 1ml bloods were collected from retro - orbital sinus at 13 days of pregnancy . finally plasma corticosterone was assessed by rat corticosterone elisa kit ( eia-4164 ; drg instruments gmbh , germany ) in both experimental groups . in 10 and 14 days of pregnancy , the animals were anesthetized with chloroform and placenta were removed and transferred to 10% formalin solution for 10 days , then , placenta were put in tissue processing molding , then blocks were sagittaly sectioned with 5um thickness and serially by microtome ( 15 , 16 ) . these slices were put on slides and stained with hematoxylin and eosin methods ( h&d ) . after staining , slides were studied microscopically . differences between all groups were calculated by a one - way analysis of variance ( anova ) and post - hoc duncan test by using the spss / pc computer program ( version 9.1 ) . statistical significance between the two measurements result were considered statistically significant when p < 0.05 . the thickness of portion placenta , blood cisterns surface , and number of cells in the experimental and control groups was measured with motic software . the system used included a microscope connected to a computer and a monitor with software which could take photos from slides . subsequently , the number of cells on each layer was counted randomly and compared with that of the experimental groups . our results showed that the oral morphine consumption in pregnant rats increased the placenta concentration of corticosteron at day 13 of pregnancy in comparison with control group . in addition morphine administration in pregnant rats placenta showed , thickness of maternal part has increased in 10 and 14 days placentae ( table i ) . in contrast , significant decrement in thickness of placenta in embryonic part was shown ( table i ) . also , increment in cells number of placenta in maternal and embryonic part in experimental groups was assessed ( table i ) , thereby decrement in blood pools surface of placenta in maternal and embryonic part in 10day experimental groups was shown in this study ( table i ) . indicates effect of administration of oral morphine on placenta and plasma corticosterone concentration in rats result were considered statistically significant when p < 0.05 . effect of administration of oral morphine on the10 , 14 days of placenta portions thickness and cell number and lacuna area development furthermore , plasma corticosterone concentration in rats which received oral morphine on the 13 day of pregnancy and comparison of control and experimental groups . changes in thickness of the placenta portion in experimental(b1 ) and control(a1 ) group in the 10-day old placenta by 40 ( two arrowheads ) . morphologic changes on 10-day old placenta in experimental group ( b2 ) indicates placenta cells and blood lacuna of placenta shuch as indicates placenta cells and blood lacuna in control group ( a2 ) in 10 days placenta with zoom 100 , ( a one head arrow ) . the changes of thickness in placenta layer in 14-day old placenta in experimental(b3 ) and control(a3 ) groups zoomed 40 ( two heads arrow ) . the changes of the blood cisterns and the number of placenta portion cells in 14-day old placenta in experimental ( b4 ) and control ( a4 ) groups , zoomed 100 ( one head arrow ) . results of the present study showed that morphine consumption during pregnancy can cause delay in the development of embryonic and maternal portion of placenta . on pregnant mother , concentration of corticosteron at blood plasma will increase at second period of pregnancy so we measured corticosteron concentration at 13 days after pregnancy ( 17 , 18 ) . in agreement with this subject , our data also indicated the oral morphine administration increased blood plasma corticosteron concentration on addictive pregnant mothers ( table i ) . increase in corticosteron density of the blood plasma of the pregnant female mice can justify the side effects in embryos of these mothers . in addition the results of these studies were consistent with previous ones , which indicated that cortisol administration could delay differentiation of placental cells ( 1 , 5 ) . regarding the fact that embryonic development is the result of placental natural function and due to the essential function of that is the hormone secretion and material exchange , any disorder in normal function of fetal and maternal portion of placenta can cause abnormality on embryo growth ( 3 , 16 , 19 ) . morphologic studies have shown that if physiologic changes of spiral veins occur during pregnancy , trophoblast cells will attack placenta and blood flow will increase at this site and finally placental villi disrupting will appear ( 6 , 20 , 21 ) . morphologic and morphometric results have shown the oral morphine effect on both embryonic and maternal parts of placenta ( table i ) . also our study indicated that oral morphine administration in pregnant mouse caused corticosteron secretion in experimental group ( 5 , 10 , 17 ) . fowden and forhead declared , the increase of placing embryo and placenta in exposure of glococorticoides cause attenuation of embryo and placenta , and this will directly change the cell cycle from mitotic to differentiated state ( 5 , 6 , 10 ) . also corticosteron induces proliferation of cytotrophoblast cells of maternal and fetal portion of placenta ( 6 , 17 , 22 ) by stimulation of procytotrophoblastic cells to shortening of interphase ( 5 , 17 , 23 ) , so cells do not have enough time for growth , protein synthesize , replication , and enough growth , and finally cause disorder in normal function of placental fetal cells ( 6 , 7 , 23 ) , in contrast lead to late differentiation of placental cell and embryonic development ( 5 , 7 , 10 , 19 ) . results of present research together with above data showed high level of corticosteron by morphine administration raised maternal portion thickness and number of these cells in placenta of day 10 and 14 of pregnancy . in addition morphine consumption has decreased more placenta fetal portion in contrast to maternal portion and this increment cause severs abnormality at embryo ( table i ) . the previous studies indicated oral morphine administration in the 9 day of pregnancy attenuate neural tube and neural plate evolution and development of frontal cortex in embryo were reduced in the 17 day of pregnancy ( 15 , 16 , 24 , 25 ) . the major role of placenta is material exchange between maternal blood and placenta and secretory substances such as steroids , peptides , cytokine and glycoproteins release from mother blood and enter to embryo by placenta . otherwise because consumption and production of nutrition material were determined by placenta any disorder in functionality of fetal placental portion ( 5 , 6 , 11 ) cause delay in development of embryo and placenta . during pregnancy in parallel with vessel angiogenesis , thickness of fetal placenta portion will decrease , so material exchanges become more and finally morphine uptake increases and decrease in thickness of fetal placenta portion is the effect of this increment ( 14 , 20 , 23 ) . so , speed of morphine transition and disruptive effects have direct ratio with decrease of fetal layer thickness . in present research , effect of morphine resulted decrease in abnormal thickness in embryonic unit of experimental group compared to control group in 10 and 14 day old placenta , and decrease of blood cisterns surface , also number of cell in both 10 and 14 day old placenta in experimental group compared to control group are consistent with increase of corticosteron concentration ( table i ) . the other researches of morphine effect on placenta fetal portions of both groups indicated , morphine causes decrease in blood cisterns area and these data not only are consistent with koulin s and doppler s researches , but also they are valuable to research in human . in other researches , it was shown ; that the morphine consumption orally and by injection indicated the same effect ( 20 , 26 , 27 ) . the effective factors on blood vessel contraction are corticosteron and opioides receptors on the membrane of placental cells ( 2 , 3 , 7 ) , that located on placental villi and be contracted by morphine stimulation and resulted decrease in blooding , embryonic hypoxia and delay in embryonic development ( 20 , 28 ) embryonic portion of placenta basically give rise to cyncytiotrophoblast cells and these cells play important role in embryonic development through secretory function , like estrogen and progesterone hormone ( 10 , 17 ) and disorder in the secretion of these cells cause delay in placental and embryonic development ( 6 , 19 ) and can aggravate embryonic abortion . according to studies , morphine administration caused embryonic abortion and decrease in babies weight in pregnant rabbits ( 12 ) . in total , these results indicated oral morphine consumption causes the unusual increment in plasma corticosteron density and delay in placenta fetal and maternal portion development in wistar rat but it was not identified if present study results are due to morphine or corticosteron effect or both of them . although behavioral disorders in infants or embryonic abortion from addictive pregnant mothers need to be studied more .

background : previous studies have shown that morphine consumption during pregnancy may delay embryo development or cause abnormal nervous system function . objective : the present study focused on the effect of maternal morphine consumption on development of placenta and blood corticosteron concentration in addictive pregnant mothers . materials and methods : 24 female rats , 170 - 200 g weight , were used . the experimental groups after pregnancy received an oral dose of 0.05 mg / ml of morphine by tap water while the control group received only tap water . on 10th and 14th day of pregnancy , rats were anesthetized and placenta removed surgically , 1ml blood was collected from each pregnant mother from retro - orbital sinus , the concentration of blood corticosteron was determined by corticosteron elisa kit after centrifugation . the fixed tissue was processed , sectioned and stained with hematoxylin and eosin . placenta was studied microscopically according to the thickness of layers , area of blood cisterns , and the number of cells . results : comparing the plasma corticosteron concentration of the treatment and the control groups , not only a severe increase in the treatment group was detected , but also the thickness of maternal and embryonic portions of the placenta at day 10th and 14th of gestation was different significantly ( p0.05 ) . furthermore , an increase in number of cells in maternal and embryonic portion of placenta and a decrease in blood cistern area were demonstrated in both the experimental and the control groups . conclusion : the effects of morphine , including an increase in blood concentration of corticosteron , in dependent pregnant mothers were seen . development of placenta in the experimental group was delayed .

dental implantation and fixation of screws for any reason are performed by drilling the bone and the success of these operations depend on many factors . through these factors , thermal injuries occurring due to temperature raise during drilling , the threshold level for thermal injuries on the bone is the 47c for a minute and the temperature can raise that level easily during drilling by rotational burs 1,3 . as a consequence of thermal injury , bone is not only resorbed but also replaced with fat cells 4 . as a result , the mechanical structure of the bone is weaken 5 . to prevent the bone from the temperature raise during drilling , various irrigation systems are used and mostly , sterile saline solutions are the material of choice 6,7 . although , to our knowledge , there is not a scientific data in the literature , there is a belief among the surgeons that cooled saline irrigation is more effective than the uncooled saline irrigation to protect the bone from the thermal injuries . the purpose of the present study was to investigate the effect of the irrigation temperature on the bone healing . for this aim , standardized drilling and miniscrew placement was performed in the tibias of 18 sprague dawley rats with rotating bur uncooled , cooled with 25c and 4c saline irrigation . experiments were designed to determine the effect of irrigation temperature on the bone after osteotomy and miniscrew placement . for this aim 3 months old weighing approximately 350 to 450 g 18 sprague - dawley rats were maintained at 22 0.5 c on a 12-h light/12-h dark cycle with free access to water and standartized food in pathogen free separate cages . all of the experiments were performed at the istanbul university , institutes of experimental science laboratories ( istanbul , turkey ) . maintenance and all experimental procedures performed were fully in accordance with principles established by the existing governmental acts and approved by the university institutional animal welfare committee . animals were divided randomly in to 3 groups of 6 animals and 3 experiments were performed . anesthesia was induced with ketamine hcl ( 100 mg / kg i.p . , ketalar , parke davis ) by the injection through the peritonium of the rats and maintained with xylozin hcl ( 23.32 mg / ml i.p . , rompun , bayer ) . after the induction of anesthesia , operation sites were shaved and the rats were placed and stabilized on the operation table . skin incision was performed parallel to the long axis of the right femurs and the bone was exposed by the dissection of hamstring and quadriceps femoris muscles . the drill speed was set to be 20,000 rpm , which is similar to that used during osteotomies by rotational systems and saline irrigation speed was standartized by using saline - dispencer . all of the holes were drilled with standard burs manufactured for 2 mm miniscrews and standart 2 mm wide 5 mm length titanium miniscrews ( bone screw kit , biohorisons , usa ) were inserted . in the group one , holes were drilled without irrigation ( figure 1 ) . in the group two , holes were drilled with 25c ( 2c ) saline irrigation and in the group three , holes were drilled with 4c ( 2c ) saline irrigation ( figure 2 ) . after the drilling and the miniscrew placement ( figure 3 ) , muscle and fascia layers were closed with simple resorbable 4.0 sutures ( vicryl 4 - 0 , ethicon ) and finally the skin incisions were closed with continious 3.0 sutures ( silk 3.0 , dogsan ) . postoperative antibiotics ( gentamicin , 0.5 mg / kg ) and analgesics ( xylocaine 0,5 mg / kg ) were given subcutaneously . the positions of the miniscrews were controlled by cone beam ct scanning . during post - operative period , all of the animals were controlled day by day and none of them were lost . at the end of three weeks , animals were killed and right femurs of them were harvested . then , the specimens were sent to the pathology laboratory ( istanbul university , institute of oncology , department of pathology , istanbul , turkey ) for the histopathological evaluation . the cutting line was started parallel to the transverse axis of femurs at about 4 mm apart from femoral heads , where the first hole preparation was made . the specimens were fixed in 10% formalin for one week and decalcified in 10% formic acid solution ( merck , darmstadt , germany ) for 25 days . the decalcified specimens were embedded in paraffin and cut into 3 m thick sections on charged slides using a microtome ( leica microsystemic rm 2125 , germany ) , and routine hematoxylin and eosin ( h&e ) staining was performed . the sections were examined with a light microscope ( olympus bx60 microscope ) attached to a digital camera ( olympus e-330 ) which connected to a computer . a histomorphological review was performed by a single blinded oral pathologist to evaluate the presence of infection , necrosis , fibrosis and new bone formation . all screw hole surroundings were evaluated by histopathologically with light microscope under 20 , 40 , 100 and 200x magnifications . the score was made up of 0 - 5% as ( - ) , 5 - 30% as ( + ) , 30 - 60% as ( + + ) and 60% and over as ( + + + ) to evaluation of new bone formation and fibrosis according to their surface covering at 40x magnification . the scores for infection and necrosis were determined by occurring in a standardized area at 20x magnification . the infection was determined if inflammatory cells were observed in the healing area the ( + ) score and if there were no inflammatory cells the ( - ) score were given . for necrosis the ( - ) score was given , if there was no necrosis whereas the ( + ) score was given if there was . the statistical differences between the control and test groups were compared by ki - square and fisher tests . in this research , all of the statistical evaluations were performed by using the ncss software ( ncss inc . , 2007 , usa ) . ki - square and fisher tests were performed for the evaluation of the definitive statistical methods and also qualitative datas . the distribution difference of the new bone formation between 4c , 25c and control groups were observed as statistically significant ( p=0,031)(table 1 ) . the new bone formation of the control group was evaluated significantly lower than the 4c and 25c groups ( p=0,020 , p=0,049 ) , however , there was no statistically significant difference evaluated between the 4c and 25c groups statistically(p=0,637)(table 2 ) . statistically significant difference was observed between 4c , 25c and control groups regarding the distribution of the infection presence ( p=0,0001)(table 3 ) . the presence of the infection in the control group 9 ( % 75 ) , was observed as significantly higher than the 4c and 25c groups ( p=0,0001 ) , but no statistically significant difference was seen between the 4c and 25c groups ( p=1)(table 4 ) . the distribution of the bone necrosis existence between 4c , 25c and control groups were observed significantly different ( p=0,0001 ) ( table 5 ) . the existence of the bone necrosis in the control 11 ( % 91,7 ) , group was evaluated significantly higher than the 4c and 25c groups ( p=0,0001 ) , but , no statistically difference was observed between the 4c and 25c groups ( p=1 ) ( table 6 ) . no statistically significant difference was observed between 4c , 25c and control groups regarding the distribution of the fibrosis existence ( p=0.355)(table 7 ) . the fibrosis distribution of the control group was not significantly different than the 4c and 25c groups ( p=0,334 , p=0,164 ) , and also , no statistically significant difference was observed between the 4c and 25c groups ( p=0,232 ) ( table 8) . the temperature rise on the bone during osteotomies performed by rotational systems is affected by various factors 8 - 10 . some of these factors are bone density , and the location of the osteotomy , in particular the amount of cortical versus cancellous bone , which may be influential . other important factors pertain to the drilling , including the speed at which the drill rotates , the sharpness of the margins on the drill , the thickness of the drill , and the force with which the drills applied to the bone 11 . regardless of the reason for , this temperature rise can cause damage or impaired healing on the bone 1,3 . as previously mentioned , the accepted threshold level that is required for the thermal injury on the bone is 47c for a period of 1 minute 1,3 . for the protection of the bone from the thermal damage during osteotomy , saline solution is routinely applied to the drill and the osteotomy site in surgical practice . and also , most of the surgeons prefer cool saline solutions and they believe that it is more effective than the normal solutions for the reduction of the temperature . in the literature , there are some studies indicating the effect of the saline application on temperature rise 11 , on the contrary , others indicate that application of saline solution to the rotational system to bone interface during osteotomy do not reduce the temperature during the osteotomy to any significant degree 12,13 . in the authors ' knowledge , this is the first study focuses on the effect of the irrigation temperature to reduce thermal rise . at the same time , it is evaluated in this study that application of saline solution is effective or not for the reduction of the thermal damage . in the present study we evaluated the specimens in terms of new bone formation , presence of infection , necrosis and fibrosis our study demonstrated significant difference regarding the necrosis values between control group ( without irrigation ) and the group irrigated with 25c and 4c saline ( figures 4 - 6 ) . however copious saline irrigation was useful for cleaning the operation area from any remnants of the drill . although there was no statistically significant difference between the group irrigated with 25c and 4c saline for new bone formation , latter group had numerous osteoblasts and more prominent osteoblastic rim around the trabeculae of new bone ( figures 4,5 ) . these results indicate that there is no disadvantage to use 25c saline irrigation , but it may be better to use 4c saline irrigation for rapid healing . in this study , it is verified that the use of saline irrigation is not only useful to reduce temperature rise on the bone during osteotomy , but also effective for cleaning the osteotomy site from any bony remnants .

objective : osteotomies , performed by rotational instruments , can cause temperature rise on the bone and elevated temperature can disrupt the bone healing . when the osteotomies are performed for the insertion of miniscrews , the bone healing disruption may cause stability loosening or failures . saline irrigation is mostly used for the prevention of the heat generation during osteotomy.purpose : the purpose of this study was to evaluate the effect of the saline irrigation temperature on bone healing.material and method : standardized drilling and miniscrew placement was performed in the tibias of 18 sprague dawley rats with rotating bur uncooled , cooled with 25c and 4c saline irrigations . after the 21 days , the difference in healing was observed between the uncooled and cooled groups.results : although there was no statistically significant difference between the group irrigated with 25c and 4c saline for newly bone formation , osteoblasts were seen more active and bone marrow was more dynamic in group 4c than group 25c . there is no disadvantage to use 25c , but it may be better to use 4c for rapid healing .

the temporomandibular joint ( tmj ) is a joint present above the spine . from a kinematic standpoint , the alignment of the tmj directly affects the stability and alignment of the spine , and the tmj is the only bilateral joint among all joints in the human body1 . when the position of the lower jaw is misplaced , it is generally pushed toward the rear of the head . in this case , due to the homeostasis of the human body that tends to maintain balance in any event , the center of gravity of the head leans toward the rear of the head to make the entire head lean backward . when the position of the tmj is changed , the axis of the center of gravity of the head is changed , leading to misalignment of the entire spine . the position of the tmj is closely related with masticatory functions , and this factor is important for control of the entire body s postures such as the functions of the cerebellum , vestibula functions , oculomotor functions , and proprioceptive senses2 . mouth guards are used in a wide range of sport activities in order to increase the stability of the tmj , the importance of which has been emphasized , to protect the tmj from external resistance , and to protect teeth and periodontal tissues . they are also used in patients with any stomatognathic disability that may affect exercise habits or postures or any abnormality in occlusion in order to induce normal occlusion . thanks to the development of science , these mouth guards have been developed into many shapes fit for their purposes depending of their manufacturing methods and materials . mouth guards can be largely divided into three types based on their manufacturing methods . stock - type mouth guards ( stm ) are ready - made mouth guard that can not be adjusted , and boil - and bite - type mouth guards ( btm ) are those that are to be molded by the user . finally , custom - made mouth guards ( ctm ) are those made from models after obtaining impressions of the teeth of the athletes who will use them . with regard to materials , those made of soft materials have been developed for the prevention of sport injuries , and those made of hard materials have been developed for oral functions and alignment3 . all oral appliances including mouth guards developed with a wide range of methods and materials are called mandibular orthopedic repositioning appliances ( moras ) . moras are known to affect the relief of neck stress and postures , improve respiratory functions4 , and improve body balance4 . thus , moras affect the entire body by causing changes in the stomatognathic system . however , since studies of the relationship between muscle activation and a mora that directly affects body balance are insufficient , basic data on the effects of a mora on the entire body are insufficient . therefore , the purpose of this study was to measure the muscle activities of the trunk muscles and upper limb muscles during maximum isometric contraction when tmj alignment was achieved with a mora in order provide basic data on the effects of a mora on the entire body . the present study was conducted with healthy adults in their 20s ( males=10 , females=10 ) who had not been diagnosed with any medical conditions within the last six months . all the subjects voluntarily participated in this study and signed an agreement for this experiment that stated that they were able to reject participation anytime if they wanted . an 8 ch surface electromyography ( myosystem dts , noraxon u.s.a . inc . , scottsdale , ca , usa ) system was used to measure the muscle activities of the upper limb muscles and neck muscles of the subjects during maximum isometric contraction when a mora was used and when no mora was used . the myoresearch xp master edition 1.06 program was used to store and process electromyographic signals with a sampling rate of 1,000 hz , a 20500 hz band - pass filter , a 60 hz notch filter , and iwc - dts electrodes ( 9113a - dts ) . the sites for electrodes were shaved with a razor , and the horny substance was removed with sandpaper . the electrodes were attached after cleaning the sites with an alcohol swab to ensure collection of accurate electromyogram data . agcl emg surface electrodes were applied with a 3 cm center - to - center spacing over the lumbar and cervical erector spinae , upper trapezius , biceps , triceps , rectus abdominis , internal abdominal obliques , external abdominal obliques , and sternocleidomastoid muscle . the maximum isometric contraction of each muscle was achieved in the manual muscle testing position5 . regardless of whether a mora was used or not , all the measurements were conducted when the tmj was closed at the maximum force . the root mean square data of each muscle was measured for five seconds in maximal voluntary isometric contraction . the level of muscle activation during maximum isometric contraction was expressed as % mvic by calculating the relative muscle contraction of the 100% average muscle contraction in the middle one second of a 3-second measurement , i.e. , by ignoring the first and last second of the measurement . the mora used in the experiment was made of hard - type splint 020 ( easy - vac gasket , 3a medes , goyang , south korea ) , and ortho - jet ( fast curing orthodontic acrylic resin , lang dental , wheeling , il , usa ) was used to set the occlusion of the hard - type mora . to obtain elaborate maxillary and mandibular casts of the study subjects , the subjects impressions were obtained using alginate impression materials and plaster casts were made . when mandibular centric bites were obtained , each subject was instructed to bite down on cotton rolls on both sides of his / her oral cavity and maintain the state for approximately five minutes to eliminate the effects of teeth on the muscles and stabilize the muscles . to eliminate the effects of gravity on the mandibular bites , the maxillary cast was attached to a semi - adjustable articulator using a facebow , and the mandibular cast was attached to the semi - adjustable articulator using the obtained mandibular centric waxbite . a random point was marked on the attached gingiva between the right canine tooth and the first premolar of the attached maxillary and mandibular casts on the working model , the distance between the maxillary and mandibular casts was measured based on the marked point , and the incisal guide pins of the articulator were lifted so that each of them was lifted by 3 mm from their position . the prepared primary mora was mounted on the maxillary working cast , the occlusal vertical dimension was increased by 3 mm at the centric occlusion , and the maxillary overbite - type primary mora was attached to the maxillary front teeth and set at the lifted occlusal vertical dimension by covering it with paraffin wax . then , the mora was adjusted using a self - curing resin so that all teeth would evenly come into contact with the centric occlusion , canine guidance would be given during lateral movements to the left and right , and the front teeth group would be evenly guided anteriorly during anterior movements . although the deep fossae formed by the occlusal tables of antagonist teeth are generally not included in moras that are widely used to treat tmj disorders , 1 mm deep fossae were artificially formed so that all cusp tips of antagonist teeth would come into contact with the mora evenly and no locational change would occur . the fabricated moras were placed into the oral cavities of the study subjects and adjusted so that all teeth would evenly come into contact with them so that the centric relation and centric occlusion would match and the mutually protected occlusion would be precise . the occlusions were adjusted so that anterior movements would be guided by the front teeth group and lateral movement would be guided by the canines . then , the set occlusal vertical dimension was rechecked , and the experimental moras was completed . the subjects general characteristics were checked through percentage and frequency analyses , and the differences in the muscle activities of individual muscles between using mora and not - using mora , were analyzed using independent t - tests . the maximum isometric contractions of the trunk and upper limb muscles when a mora was used were compared with those when no mora was used . the results showed that the sternocleidomastoid muscle , cervical and lumbar erector spinae , upper trapezius , biceps , triceps , rectus abdominis , and internal oblique and external oblique muscles all showed significant increases in maximum isometric contractions when using a mora ( table 1table 1 . comparison of upper limb and trunk muscle activation during maximum isometric contraction between each condition ( unit : % mvic)musclewithout a morawith a morascm*111.6 6.0125.4 15.6c - es*115.0 8.2138.1 18.0ut*114.5 7.7123.7 9.2biceps*114.7 5.1125.2 7.6triceps*111.2 4.9120.9 8.6ra*116.0 6.3128.8 6.7iao*116.3 4.2128.1 5.0eao*117.7 5.1128.1 6.0l - es*118.7 4.7130.8 6.2mean sd , p<0.05 . scm , sternocleidomastoid muscle ; c - es , cervical erector spinae ; iao , internal abdominal oblique ; eao , external abdominal oblique ; l - es , lumbar erector spinae ; ra , rectus abdominis ) ( p<0.05 ) . scm , sternocleidomastoid muscle ; c - es , cervical erector spinae ; iao , internal abdominal oblique ; eao , external abdominal oblique ; l - es , lumbar erector spinae ; ra , rectus abdominis human postures are determined and maintained by the coordinated movements of muscles , proprioceptive senses , the sense of equilibrium , and the positions and functions of joints6 . among joint positions , the position of the tmj , which is characterized as a bilateral joint , can control the position of the head , which is the heaviest part of the body , and thus it affects the stability and functions of the entire body2 . therefore , the present study was performed to examine the effects of the use of a mora that can provide positional changes and stability to the lower joint , which in turn moves the tmj , on the body . the maximum isometric contractile power of the trunk and upper limb muscles when a mora was used was compared with that when no mora was used , and the results showed significant increases in power in all the muscles measured . given these results , it seems like the increase in stability of the tmj resulting from use of a mora affected the stability and balance of the entire body so that the maximal isometric contraction of the trunk and upper limb muscles increased7 . muscle activation is closely related to the stability of the spine and the entire body8 , and proper body alignment increases the muscle activation of distal part of the body9 , 10 . according to the results of a study conducted by bates and atkinson11 , a mora affects the tmj and moves it into its normal position . therefore , moras can be widely used in treating craniomandibular disorders , and treatment with them can improve motor abilities , muscle strength , endurance , and concentration12 , 13 . the results of these studies indicate that use of a mora is one method of increasing muscle activation in the entire body in stable positions . therefore , the use of a mora is considered to be a method for normal adults to improve the stability of the entire body through improvement of the stability of the tmj ; that is , the proximal improvement in stability improves not only muscle strength with increased muscle activation but also stability during exercises .

[ purpose ] the purpose of this study was to measure the muscle activities of the trunk muscles and upper limb muscles during maximum isometric contraction when temporomandibular joint alignment was achieved with a mandibular orthopedic repositioning appliance in order provide basic data on the effects of mandibular orthopedic repositioning appliance on the entire body . [ subjects ] the present study was conducted with healthy korean adults in their 20s ( males=10 , females=10 ) . [ methods ] an 8 channel surface electromyography system was used to measure the muscle activities of the upper limb muscles and neck muscles of the subjects during maximum isometric contraction with and without use of a mandibular orthopedic repositioning appliance . [ results ] the maximum isometric contractions of the trunk and upper limb muscles when mandibular orthopedic repositioning appliance were used were compared with those when no mandibular orthopedic repositioning appliance was used . the results showed that the sternocleidomastoid muscle , cervical and lumbar erector spinae , upper trapezius , biceps , triceps , rectus abdominis and internal oblique and external oblique muscles all showed significant increases in maximum isometric contractions with a mandibular orthopedic repositioning appliance . [ conclusion ] the use of a mandibular orthopedic repositioning appliance is considered to be a method for normal adults to improve the stability of the entire body with the improvement of the stability of the tmj . the proximal improvement in stability improves of the proximal thereby improving not only muscle strength with increased muscle activation but also stability during exercises .

hip dislocations are mostly due to low velocity injury in children younger than 3 years . a 25 month old child presented to our casualty following a fall from a slide 3 hours prior to presentation . an x - ray of the pelvis was taken which showed a posterior hip dislocation on the right side . the child had an emergency closed reduction under general anaesthesia followed by a broom stick plaster cast with hips in 30 abduction . the child was reviewed at 6 and 18 months with mri scans at 6 and 18 months . paediatric hip dislocation ( less than 3 years of age ) is a very rare entity whose incidence is on the rise due to the increase in road traffic accidents . the key stone in proper management is clinical suspicion , early recognition and promptreduction ( within 6 hours ) . also gentle manipulation during reduction has a definite role in preventing iatrogenic chondrolysis and osteonecrosis of femoral head . the periosteum is thick in children , the bones are soft and elastic and can absorb quite some force because of the soft spongy nature . hence dislocations are rare in paediatric age group . however with the increasing number of motor vehicles plying on our roads and the ever present risk of road traffic accidents , there is a recent change in the above trend . most of the paediatric injuries are the result of low velocity accidents . in case of high velocity injuries there has been case reports of traumatic hip dislocations in childhood mostly in the western world . most of the published articles in literature include the adolescent population ( 12 - 17 years ) . there are very few case reports of such dislocations in children < 3 years . here we present a case report of a child ( age 25 months ) with traumatic posterior dislocation of the hip following low velocity injury . a 25 month old male child presented to our casualty following a slip and fall from a slide while playing in a park . he had severe pain in the right hip and limb was adducted and internally rotated . an emergency radiograph of the pelvis taken in emergency showed a posterior dislocation of his right hip[fig.1 ] . gentle traction with minimal rotation was sufficient to achieve reduction , the congruency of which was checked under image intensifier . once congruency was confirmed , an above knee broom stick plaster was applied to both lower limbs with hips in 30 abduction . check radiographs[fig.2 ] was taken along with a mri[fig.3 ] of the hip to check if there was any traumatic injury to the physes . he was kept on the plaster for 6 weeks following which plaster cast was removed and child mobilized with as tolerated weight bearing . follow - up x - ray was taken at 6 weeks[fig.4 ] and serial mri scans taken at 6 and 18 months [ fig.5 & fig.6 ] showed no chondrolysis or osteonecrosis . he had restriction of flexion of knee beyond 120 at 6 weeks which improved to 140 by 8 weeks . x - ray following closed reduction and plaster application showing concentric reduction . mri taken immediately following closed reduction showing minimal marrow edema in head and neck area . x - ray taken at 6 weeks following removal of plaster cast showing stable hip with no re - dislocation . m r i at 6 months showing normal physeal plate with no avn m r i at 18 months showing normal femoral head anatomy and physes however with the everpresent danger of motor vehicle accidents in our crowded and chaotic roads , this rarity may become more common . in most children however , hip dislocations are mostly due to low velocity accidents which occur during playing . there are a few reports in western literature of hip dislocation in peadiatric population , most of them are case reports . there has been only two case reports of children less than 3 years with hip dislocation . also most of the reports emphasizes the need to do urgent reduction within the golden period ( i.e 6 hours ) . the risk of osteonecrosis in one study was 5.7% in acute cases vs 47.8% in old neglected cases undergoing reduction procedures . the severity of the injury is also an important predictor for the development of osteonecrosis . also important is that during closed reduction , care is to be taken not to perform forceful manipulation as this greatly increases the risk of iatrogenic physeal separation . as is with our case gentle traction with minimal rotation is enough to reduce the joint . the method of immobilization varies with the authors from skin traction to plaster cast application but we found that results with plaster cast are more predictable with better patient cooperation . child abuse is also a possible etiology of hip dislocation in children when a child presents with a doubtful history and injuries in various stages of healing . in our patient , the immediate post - reduction mri showed a small linear posterior labral tear which had healed in subsequent mri scans taken at 6 months in literature there are case reports of traumatic hip dislocations in childhood ( < 3 years ) in the western archives . here we present a case report of a traumatic hip dislocations in a child < 3 years in indian population . paediatrichip dislocations are a medical emergency which requires a great deal of suspicion to detect early and treat appropriately . our patient had excellent recovery and functional outcome because of early reduction within the golden period ( 6 hours ) . although he had a labral tear , the soft tissues healed with immobilisation without any further intervention with no permanent disability . we therefore conclude that traumatic hip dislocations in children < 3 years is an uncommon injury but a keen lookout is a must for early diagnosis and treatment . however a high degree of suspicion combined with early and prompt reduction is the keystone in management . this is to ensure a good functional outcome and prevention of complications like osteonecrosis and chondrolysis .

introduction : hip dislocation in a child less than 3 years is a very rare event . only a few case reports have been documented in western literature . it is rarely reported from indian population . hip dislocations are mostly due to low velocity injury in children younger than 3 years . we report such a case of hip dislocation in a 2 year old child.case report : a 25 month old child presented to our casualty following a fall from a slide 3 hours prior to presentation . his right lower limb was adducted and internally rotated . there was severe pain on attempting movements . an x - ray of the pelvis was taken which showed a posterior hip dislocation on the right side . the child had an emergency closed reduction under general anaesthesia followed by a broom stick plaster cast with hips in 30 abduction . congruency of reduction was checked with image intensifier before plaster application . the plaster was removed at 6 weeks and gradual weight bearing started . the child was reviewed at 6 and 18 months with mri scans at 6 and 18 months . there were no signs of avascular necrosis or chondrolysis.conclusion:paediatric hip dislocation ( less than 3 years of age ) is a very rare entity whose incidence is on the rise due to the increase in road traffic accidents . the key stone in proper management is clinical suspicion , early recognition and promptreduction ( within 6 hours ) . also gentle manipulation during reduction has a definite role in preventing iatrogenic chondrolysis and osteonecrosis of femoral head .

biliary cast syndrome is defined as the presence of casts within the intra- and/or extrahepatic bile ducts , causing obstruction and cholangitis , eventually complicated by multiple strictures , ductal dilation , and/or liver microabscesses.1,2 this is an uncommon condition , but is more frequently described in liver transplant patients.3,4 only a few reports have described biliary cast syndrome in nonliver transplant patients ; these included patients with antiphospholipid antibody syndrome , b - cell non - hodgkin lymphoma , cholecystectomy , and those who had undergone allogeneic hematopoietic stem cell transplantation.4 - 10 the exact pathogenesis of biliary casts remains uncertain ; however , many factors have been suggested as playing an etiological role in their formation . theoretically , anything that increases viscosity and/or hinders the flow of bile may precipitate cast formation . therefore , biliary sludge is known to be a prerequisite for cast formation.4 here we present one case of biliary cast syndrome , which developed in a nonliver transplant patient who had biliary sludge for a long period of time , providing evidence that long - standing biliary sludge may lead to cast formation . an 80-year - old man was admitted with a complaint of abdominal pain and fever . the patient 's history included brain surgery due to head trauma approximately 1 year ago ; he had remained in a bed - ridden state since then . the patient had a blood pressure of 109/66 mm hg , a heart rate of 122 beats / min , a respiration rate of 30 breaths / min , and a body temperature of 38.4. physical examination revealed tenderness at right upper quadrant of abdomen . laboratory examination revealed a hemoglobin of 14.2 g / dl ( normal range , 13 to 17 ) ; white blood cell , 29,900/mm ( normal range , 4,000 to 10,000 ) ; platelet , 296,000/mm ( normal range , 130,000 to 350,000 ) ; total bilirubin , 2.5 mg / dl ( normal range , 0.22 to 1.2 ) ; aspartate aminotransferase ( ast ) , 742 iu / l ( normal range , < 40 ) ; alanine aminotransferase ( alt ) , 422 iu / l ( normal range , < 40 ) ; alkaline phosphatase ( alp ) , 1,593 iu / l ( normal range , 66 to 220 ) ; and -glutamyl transpeptidase 1,321 we performed percutaneous transhepatic cholecystostomy for the purpose of immediate decompression of the biliary tract . follow - up tubography via percutaneous cholecystostomy showed multiple tubular filling defects in the extrahepatic bile duct ( fig . endoscopic retrograde cholangiopancreatography ( ercp ) revealed the same features ; therefore , we performed endoscopic sphincterotomy followed by basket retrieval of the black colored tubular structures from the extrahepatic bile duct ( fig . histology of the biliary tubular structures showed aggregates of bile pigmented amorphous materials , consistent with biliary cast ( fig . currently , almost 16 months after the removal of the biliary cast , he was found to be asymptomatic and maintained a normal range of liver biochemistries . one year before admission , he had suffered head trauma after falling from his bicycle . he underwent emergent brain surgery , followed by management in the intensive care unit ( icu ) for several weeks . after that , he was stable but remained in a bedridden state . at approximately 1 month after the brain surgery , his liver biochemistry , which had remained in the normal range since admission , began to deteriorate : a bilirubin of 0.5 mg / dl , ast of 51 iu / l , alt of 92 iu / l , alp of 361 iu / l , and -glutamyl transpeptidase of 525 iu / l . we performed an investigation of possible causes for abnormal liver biochemistry , such as drugs , viral infections , and etc . however , an abnormal ultrasonographic finding , gallbladder distention filled with a large amount of sludge , was proven to be the only cause of abnormal liver biochemistry ( fig . , the patient did not show acute cholangitis ; in addition , he maintained stable vital signs and had no complaints . considering the poor general status with bed - ridden state , he received only supportive care with intermittent blood tests . 5 shows the patient 's liver biochemistry during the past year , showing wax and wane , with constant deterioration , since 4 months before developing acute cholangitis and being admitted to the hospital . pathophysiology of biliary cast formation is unclear ; however , hepatic infarction , fasting related gall bladder hypocontractility , biliary infection , biliary ischemia due to hypotension induced sepsis , bile pigment load due to absence of a gallbladder after cholecystectomy , and benign biliary stricture are included in suggested factors for biliary cast formation in nonliver transplant patients.4 - 10 these conditions are eventually predisposed to hindrance of bile flow , and thereby result in biliary sludge formation . this case provided evidence to demonstrate that the presence of long - standing biliary sludge may lead to development of biliary casts . we initially noticed gallbladder sludge in the patient at about 1 month after brain surgery . development of gallbladder sludge can be explained by the brain surgery and an icu setting , which both appear to be recognized risk factors for sludge formation due to gallbladder hypocontractility.11 the gallbladder sludge then migrated into the bile duct over a long period of time , which can be explained indirectly by long - standing and gradually increased abnormal liver biochemistry ; biliary cast formation might then have developed and was observed as acute cholangitis in the present case . there is no recommended standard management protocol for removal of biliary casts and each case should be viewed individually . although data are limited , five of eight nonliver transplant patients ( table 1 ) underwent successful removal of biliary casts by ercp only . therefore , ercp is thought to be a reasonable step to take prior to considering laparotomy , particularly in nonliver transplant patients . however , reports on liver transplant patients showed that endoscopic management was still effective only in 25% of liver transplant patients with cast formation and that many patients experiencing endoscopic treatment required retransplantation.12,13 in conclusion , our case is a great example of biliary cast syndrome , showing that long - standing biliary sludge may lead to cast formation .

development of biliary casts is very unusual , especially in patients who have not undergone liver transplantation . variable causes of biliary cast formation in nonliver transplantation patients have been suggested . however , stasis of bile flow and/or gallbladder hypocontractility is known to eventually result in the promotion of biliary sludge and subsequent cast formation . here we present one case of biliary cast syndrome , which developed in a nonliver transplant patient who had biliary sludge for a long period of time , providing evidence that long - standing biliary sludge may lead to cast formation .

a 64-year - old , 164 cm , 70 kg woman had a five - year history of hypertension and diabetes mellitus . she experienced insomnia , nausea , visual hallucination and left - side tingling sensation 4 months ago and memory impairment and gait disturbance became evident clinically 2 months ago . at that time , she underwent brain magnetic resonance imaging , which did not demonstrate abnormality . the patient presented with generalized myoclonus , progressive gait disturbance , and deviation of the left eye 1 month ago . brain mri showed t2 hyperintensity of the right dominant cortex , caudate nucleus , putamen , and thalamus on diffusion - weighted sequences . electroencephalogram showed nearly continuous high voltage 1 - 1.5 hz periodic sharp waves in the frontal area bilaterally . under the suspicion of cjd the operating room was cleared of unnecessary equipment and the wall of operating room was covered with vinyl chloride monomers . all staff members involved with the operation wore liquid - repellent gown , face - masks with plastic transparent shield visor , and double gloves ( fig . the mental status of the patient ranged from stupor to semicoma and vital signs were stable . anesthesia was induced with a bolus injection of propofol 1.5 mg / kg in combination with remifentanil infusion at 0.5 g / kg / min . anesthesia was maintained with oxygen 5 l / min , propofol 50 - 150 g / kg / min , and remifentanil 0.05 - 0.1 g / kg / min total intravenous anesthesia . almost every equipment applied was of single - use nature , including face - masks , oropharyngeal airway , laryngoscopic blade , endotracheal tube , ambu bag , o2 flowmeter , and stethoscope . the surgeon used hand - drill instead of air - drill , and the entire surgical procedure took 40 minutes . the patient recovered in the operating room and was subsequently transferred to the private ward . western blot demonstrated a misfolded , protease - resistant , pathogenic form of prion protein in the brain tissue . prion proteins are normal cellular proteins that have undergone a structural change rendering the abnormal protein resistant to degradation . sporadic cjd ( scjd ) is the most common form and accounts for 85% of cases . it is a rapidly progressing illness with an onset of older age group and a median duration of four months . it is resulted from various types of therapeutic interventions including contaminated surgical equipment , corneal or dural transplants , or treatment with human - derived pituitary growth hormone . in 1974 , the first case of icjd was reported in a 55-year - old woman whose symptoms began 18 months after corneal transplant surgery . we had an experience a case of icjd in a 53-year - old woman whose symptoms began 23 years after brain tumor resection and dura mater grafting . in addition , deaths from cjd have been reported in neurosurgeon and pathologist . in iatrogenic transmission , various latencies , from several months to several decades , have been reported . variant cjd ( vcjd ) affects mainly young individuals with an average age of 29 years , and the median duration of illness is 14 months . a new aggressive human form , known as vcjd , was first descrided in the uk in 1996 . symptomatic patients are divided into those who have definite , probable or possible cjd , or vcjd . asymptomatic patients are those with no clinical symptoms , but are at risk of disease development due to family history or medical history ( e.g. a history of previous dural graft ) . definite diagnosis of cjd requires pathological confirmation , either at autopsy or from brain biopsy . cjd is rare but due to their unusual resistance to standard decontamination methods and the consequent risk of patient - patient transmission , management of the infected and , possibly infected patients requires additional precautions . in the most routine clinical contacts no additional precautions are required and isolation nursing is unnecessary . when a patient known to have , or suspected of having cjd is scheduled for anesthesia , special precaution is required thorough the procedure . the operating room should be cleared of all unnecessary equipment , and staffing kept to minimum . the patient should be scheduled last on the operating list where possible , to allow extended cleaning of room surfaces prior to its next use . staff must wear a disposable liquid - repellent gown over a plastic apron , gloves , mask and goggles or full - face visor for procedure . asymptomatic at risk patients the above precautions also apply , but gowns may be reprocessed if not of single - use . invasive procedures , such as central venous cannulation and spinal anesthesia , mandate the use of full aseptic procedures including mask and eye protection . whenever possible , disposable anesthetic equipment should be used and incinerated afterward , which includes face - masks , oropharyngeal , nasal and laryngeal mask airway , laryngoscope , and tracheal tubes . when non - single - use instruments are applied , they should be treated according to the patient 's and the tissue risk . high risk tissues for cjd are those in brain , spinal cord , and posterior eye , and medium risk tissues are those in the anterior eye , olfactory epithelium and in vcjd lymphoid tissue . instruments exposed to procedure involving these tissues should be destroyed in cases of definite or probable cjd . in remaining group of patients ( those with possible infectivity ) , instruments exposed to procedures involving high and medium risk tissues should be quarantined until a definite diagnosis has been confirmed . quarantined instruments may be used again for the same patient during the course of their treatment . farling and smith stated that ventilators must not be used again for other patients except those with a definitive diagnosis of cjd . in our case , we used ambu - bags with tiva , instead of anesthetic machines with vaporizers . cjd incidents panel recommends that the anesthetic circuit should be disposed of , single - use filters should always be used and there is no requirement to quarantine the anesthetic machine . it may be recommended to recover the patient in the operating room to avoid additional contamination . however , anesthesiologists should be aware of the nature of cjd and recommended precautions in handling of patients with cjd because it is potentially iatrogenically transmissible . this knowledge is necessary to provide optimal care for the patient and minimize the risk of transmission between hospital workers and patients .

creutzfeldt - jakob disease ( cjd ) is a fatal neurodegenerative disorder in which accumulation of the pathogenic prion protein induces neuronal damage and results in distinct pathologic features . this abnormal prion is an infectious protein and resistant to methods of sterilization currently being used . therefore , management of definite , or suspected cjd patients requires additional precautions . we report our experience of a patient who had undergone brain biopsy for suspected of cjd . the patient was confirmed to have sporadic cjd .

papillary thyroid carcinoma being the most common type of differentiated thyroid malignancy has a predilection for spread through the lymphatic system and thus commonly involves the central and lateral compartmental lymph nodes of the cervical region . soft tissue metastasis is even rarer and amenable to radioiodine treatment similar to metastatic lesions in the lung and bones when they concentrate iodine . the concerned case is unique in the sense that the involvement simultaneously of three soft tissue organs is present with different iodine - concentrating abilities , whereas a review of the literature did not find the simultaneous presence of iodine - concentrating metastasis in one organ , iodine - nonconcentrating metastasis in another organ , and multiorgan soft tissue metastasis in the same patient . the case report also emphasizes possible hematogenous route of metastasis which is rare in papillary thyroid malignancy . a 42-year - old male patient with a history of total thyroidectomy and bilateral cervical nodal dissection positive for papillary carcinoma thyroid was referred to our department for a follow positron emission tomography - computed tomography ( pet - ct ) scan for evaluation of lung nodules and muscle lesions that he developed five years after primary treatment . during the follow - up , prompted by elevated thyroglobulin levels , an iodine-131 whole body scan and single photon emission tomography - computed tomography ( spect - ct ) [ figure 1 ] showed positive lesions , one in the liver and another in the left gluteal region . a fludeoxyglucose ( fdg ) pet - ct scan [ figure 2 ] was done to find more lesions and revealed metabolically active lesions in liver segment vi [ figure 3 ] and the left gluteus and a new paraspinal muscle lesion at the nape of the neck [ figure 4 ] , whereas the lung nodules were metabolically inactive [ figure 5 ] . a post - therapy scan [ figure 6 ] at a therapeutic dose of 200 mci of iodine-131 revealed iodine concentration in the liver and a gluteal lesion , whereas there was no concentration in lung nodules and neck lesion . the present fdg pet ct scan [ figure 7 ] as a response evaluation six month post treatment revealed a metabolic response in the liver and gluteal lesion [ figure 8 ] , but an increasing size of the neck lesion [ figure 9 ] and lung nodules [ figure 10 ] . presently , the patient is put on redifferentiation therapy with sorafenib and suppressive doses of thyroxin . the single photon emission tomography - computed tomography ( spect ct ) scan shows iodine - concentrating lesion in left gluteal muscle left gluteal lesions were metabolically active in pretherapy positron emission tomography - computed tomography ( pet ct ) study the new lesion at nape of neck fludeoxyglucose ( fdg ) activity but not lung nodules the 200 mci post - therapy scan concentration in liver and gluteal lesion but no concentration in neck lesion and lung nodules . the positron emission tomography - computed tomography ( pet ct ) scan after six months iodine therapy shows treatment response in liver soft tissue deposit in the neck demonstrating increase in size and fdg uptake ( disease progression ) papillary thyroid carcinoma is the most common type of differentiated thyroid carcinoma accounting for at least 70% of all follicular cell - derived thyroid malignancies and is considered to be a relatively indolent tumor in which distant metastasis and death are rare . the five - year survival rate for papillary thyroid cancer according to the stage is 100% for stage i and ii , 93% for stage iii , and 51% for stage distant metastasis is the principal cause of death in cases of well - differentiated thyroid carcinomas . about 10% of papillary carcinomas develop distant metastasis , with about 50% of patients having such metastasis at the time of diagnosis . the prognosis of these patients is poor , and over 50% of the patients are likely to die within five years , irrespective of the histology of the tumor . distant metastasis , although relatively uncommon , has been known to occur most commonly in the lungs , followed in frequency by bone and brain ( 0.1 to 5.0% ) . isolated cases of soft tissue metastasis have been documented in the orbit , skull , skin , muscles , liver , spleen , pancreas , and adrenal gland.[613 ] metastatic lesions have also been documented in silent or occult thyroid neoplasms . radioactive iodine treatment is considered to be the first line of treatment for distant metastasis from thyroid carcinomas that concentrate a significant amount of radioiodine . unlike our patient who developed metastatic disease and related symptoms five years after treatment of primary disease , for patients who develop distant metastatic disease at the time of initial diagnosis , a positive iodine-131 whole body scan post treatment of primary lesions in the neck makes way for successful radioiodine treatment of metastasis . however , solitary metastatic lesions which do not concentrate radioiodine can be dealt with surgical removal and/or external beam radiation . to add to the confusion , our patient showed radioiodine concentration in one of the muscle lesions and liver but no concentration in another muscle lesion and lung nodules . consequently , the muscle lesions responded to radioiodine treatment , whereas the neck lesion and lung nodules showed progression over the period of treatment . the patient has been put on a suppressive dose of thyroxin and redifferentiation therapy . in the past , retinoic acid , thalidomide , and rosiglitazone showed efficacy in redifferentiation therapy of iodine - nonconcentrating thyroid malignancy metastatic lesions ; however , currently , sorafenib ( 400 mg twice daily ) and sunitinib ( 50 mg daily for 28 days followed by 14 days of no treatment per cycle ) , approved for other indications , show promise for thyroid cancer .

distant soft tissue metastasis and the simultaneous presence of iodine concentrating and nonconcentrating lesions in papillary thyroid cancer are extremely rare . the concerned patient , a histopathologically proven case of papillary thyroid cancer with nodal metastases treated with total thyroidectomy , bilateral cervical nodal dissection , and radioablation , subsequently developed lung , muscle , and liver metastasis . triggered by increased thyroglobulin , the iodine-131 whole body scan and 200 mci iodine-131 post - therapy scan showed a left gluteus maximus lesion and a liver lesion . fludeoxyglucose ( fdg ) positron emission tomography - computed tomography ( pet - ct ) scan intended to find additional lesions revealed iodine and fdg nonconcentrating bilateral pulmonary nodules and a single fdg avid hepatic and two muscle metastases . although fdg concentration in metastatic pulmonary nodules is generally low , the ct characteristics were classical for metastatic lesion . a follow - up fdg pet - ct study six months after 200 mci iodine-131 radioablation showed treatment response in muscle and liver lesions but not lungs .

first described by kaijser in 1937 , eosinophilic enteritis is an uncommon gastrointestinal disorder characterized by symptoms of abdominal pain and partial obstruction . laparotomy and biopsy reveals pathologic findings of eosinophilic infiltration of bowel wall in the absence of parasitic or extraintestinal disease . with less than 300 cases reported in the literature the utility of laparoscopy makes it an ideal tool for evaluation of bowel obstructions of uncertain etiology . a paucity of cases appears in the laparoendoscopic literature describing serosal eosinophilic jejunitis diagnosed during diagnostic laparoscopy . this patient 's presentation with colicky abdominal pain and emesis while suggestive of acute cholecystitis , is suspicious in the absence of liver enzyme abnormalities and poorly localized pain . leukocytosis with eosinophilia was present on routine laboratory examination raising the possibility of eosinophilic enteritis in the differential diagnosis of this patient 's distention and pain . exploratory laparoscopy revealed a loop of inflamed , thickened jejunum and the presence of turbid peritoneal fluid . a 54-year - old woman presented with chief complaints of colicky epigastric pain and emesis of two weeks duration , exacerbated by eating . she is a retired nurse who emigrated from the philippines eight years ago with no history of recent foreign travel or known infectious disease contacts . physical examination demonstrated mild tenderness to deep palpation in the epigastric area without rebound or guarding . a barium contrast study of the small bowel suggested a segment of narrowing in the proximal jejunum ( figure 1 ) . 99mtechnicium - iminodiacetic acid ( hida ) scan revealed normal visualization of the biliary system and gallbladder . esophagogastroduodenoscopy showed normal esophageal and gastric mucosa . computed tomography of the abdomen with oral and intravenous contrast upper gastrointestinal barium contrast study demonstrating extrinsic luminal narrowing of the proximal jejunum . computed tomogram of the abdomen with oral and intravenous contrast showing a thickened loop of proximal small bowel . video laparoscopy was performed under general anesthesia with an infraumbilical and three additional access ports . upon entry to the abdomen , after performing an uneventful cholecystectomy and intraoperative cholangiogram , the transverse subxyphoid port site was extended to three centimeters in length and the questionable loop of jejunum externalized . after repair of the enterotomy the bowel was returned to the abdomen and the wounds closed in layers . pathologic examination of the peritoneal fluid revealed a red blood cell count of 280,000/mm and a white blood cell count of 22,000/mm , with eosinophilia . dense eosinophilic infiltration of the bowel serosa with normal histological mucosa was seen ( figure 3 ) . photomicrograph ( hematoxylin and eosin stain , magnification 320x ) of biopsied jejunal wall with a dense subserosal infiltration of eosinophils and a normal muscularis . she was discharged on postoperative day three and at four months follow - up remains asymptomatic . eosinophilic enteritis most frequently involves the stomach and proximal small bowel . lesions in the esophagus , colon , terminal ileum and gallbladder identified mucosal infiltration in 23 , muscle layer disease in 12 , and subserosal involvement in only five cases . ten patients had classic abdominal symptoms and peripheral blood eosinophilia , but no demonstrable gastrointestinal lesions . hematologic studies show a range of blood eosinophilia from 8.5 to 80% of the total leukocyte count , with as many as one - fourth of patients having a normal eosinophil count . fifty to 75% of patients with this disorder report a history of allergic hypersensitivity . the presenting symptoms can vary depending on the segment of gastrointestinal tract involved as well as the depth of bowel wall eosinophilic infiltration ( table 1 ) . patients with mucosal disease report abdominal pain , diarrhea , nausea and vomiting , and may manifest signs of intestinal malabsorption and protein losing enteropathy . the presentation of disease localized to the muscle layer disease is usually partial or complete obstruction . clinical manifestations of eosinophilic enteritis serosal disease occurs infrequently with a total of 28 cases reported . presentation with eosinophilic ascites , an elevated peripheral blood eosinophil count , and dramatic response to steroid treatment characterize this form of the disease . the eosinophil count of the ascitic fluid is usually elevated while abnormalities in the erythrocyte sedimentation rate and peripheral eosinophil count are variable . the radiographic presentation , depending on the segment involved , can suggest crohn 's disease , gastric outlet obstruction , or may simply show non - specific bowel wall thickening , as illustrated in this case . the character of this patient 's pain in the light of normal liver enzymes and a leukocytosis with eosinophilia prompted our investigation with computed tomography in an attempt to localize the affected segment of bowel . the pathophysiology of this condition may be secondary to a derangement in the release of eosinophil major basic protein . it remains unclear whether our patient 's symptoms were attributable to her gallbladder disease or were a manifestation of ongoing serosal eosinophilic infiltration of her jejunum . furthermore , although remote from the site of the gallbladder , it is possible that enteritis might have been a sequelae of chronic cholecystitis . perhaps more aggressive investigation of local bowel abnormalities in acute cholecystitis will reveal some degree of eosinophilic infiltration . the affected loop of jejunum appeared grossly abnormal through the videoscope ; our impression may , however , have been biased by the preoperative radiographic findings . whether or not the loop of jejunum in question would have appeared sufficiently abnormal as to prompt further investigation during a routine laparoscopy will remain in question . the extension of the subxyphoid port site with extracorporeal wedge resection of the intestine added minimal morbidity and cost to our procedure . given the number of laparoscopic procedures currently performed and the probable underdiagnosis of eosinophilic enteritis , we recommend patients undergoing laparoscopy who show evidence of peripheral blood eosinophilia , ascites , or ill - defined gastrointestinal symptoms undergo a thorough laparoscopic exploration of the abdomen . a sample of intraperitoneal fluid can easily be obtained to rule out an infectious or neoplastic disease process , along with a minimally invasive biopsy or resection of bowel accomplished . while previous cases of eosinophilic enteritis have been managed successfully with sodium cromoglycate , the current recommended treatment is a short course of high dose prednisolone ( 40 milligrams per day for one week ) followed by a maintenance regimen ( 5 to 10 milligrams per day ) . treated with this regimen had complete resolution of their symptoms and a return of their peripheral blood eosinophil count to normal within four weeks .

as the popularity of laparoscopic cholecystectomy continues to grow , evaluation of patients with documented cholelithiasis and concomitant vague abdominal complaints becomes less rigorous . we present the case of a patient with chronic cholecystitis documented by history and ultrasonography , incidentally noted on laboratory examination to have peripheral blood eosinophilia . at the time of laparoscopy , an inflamed segment of jejunum was discovered . limited laparotomy and wedge biopsy revealed active eosinophilic enteritis .

despite the fact that thanks to advancement in medicine , progression of treatment and care equipment , and the constant advancements in gynecology and obstetrics , premature neonates can have a better survival , leading to positive outcomes in pregnancy , the problem of complications and premature neonates still exists . although weight less than 1500 g occurs in only 1 - 2% of the neonates , it accounts for a high proportion of neonatal mortality , and short- and long - term complications of childhood such as developmental defects . according to the latest reports of who in 2006 , premature birth accounts for 31% of iranian neonates mortality . this rate of low weight neonates mortality can be reduced by prevention of infection and provision of appropriate nutrition . achievement of an appropriate and standard growth of neonates in a short time period and improvement of neural and physical development is among the important goals of premature neonates feeding . the important fact in premature neonates nutrition is that in most of the cases , transfer of nutrients from the mother to the fetus occurs in the last gestational weeks leading to fetal weight gain ; therefore , the neonates with premature birth are deprived of such nutrition based on their gestational age of birth and mostly experience after birth growth disorder . among the major causes for after birth growth disorder is the low calorie and protein received by the neonates on the first days after birth , of which compensation is difficult and often leads to serious complications such as a lifelong disorder in neural development , cerebral palsy , and mental retardation . the quality and quantity of nutritional support in the first weeks after birth not only lead to a higher survival of premature babies and neonates in a very critical condition , but also facilitate their brain and neural development . the maximum time interval of human brain growth is between the first trimester and 18 months post birth . there are evidences showing that the brain is more vulnerable to nutritional deprivation and that not providing nutrients may lead to lowered iq and behavioral disorders in the long term . to receive correct nutrition and with regard to lack of coordination in their sucking and swallowing , premature neonates need to receive adequate fluid and energy either through a venous line or gavage . they also need a strong sucking ability , coordination in swallowing , blocking larynx and nasopharynx with epiglottis and uvula , and natural movements of the esophagus for oral feeding . in addition , any feeding method not involving oral nutrition deprives the infant from experiencing sucking and swallowing opportunities and hungry - sated natural cycle ; the longer the non - oral feeding , the more difficult the nutritional problems . unfortunately , most of the premature neonates do not receive adequate amounts of protein and calorie after birth and are involved in growth limitation and malnutrition , which leave notable effects on their height , weight , and nervous system . inappropriate weight gain leads to prolonged hospitalization of neonates in the ward and , consequently , more risk of sepsis . the risk of nutritional problems in neonates and , consequently , the incidence or progression of low weight due to premature birth , or treatment and care processes all act as a barrier in independent oral feeding of neonates . for instance , tube feeding lowers sucking function and its motor development in premature neonates . this type of feeding also prevents appropriate mother - neonate interaction during feeding . before discharge , the infants are usually able to take all of their needed nutrients through breastfeeding , which needs an intervention to facilitate their nutritional progression and to let them be discharged from the hospital earlier . the time interval between initiation of oral feeding and full oral feeding can be a few days or months in premature neonates , leading to a prolonged hospitalization and mothers anxiety . prolongation of hospitalization may also result in higher financial burden to the family and health system . during premature neonates hospitalization period in neonatal intensive care unit ( nicu ) , their feeding method may need a change in cases such as low - volume milk feeding , taking complements with milk , or cessation of mother 's milk due to prolonged hospitalization . in these cases , feeding should be administered through another method and not through breastfeeding . cup feeding is applicable for the neonates who , despite having proper swallowing ability , do not have appropriate sucking . it is also recommended for those neonates who can not be breastfed well to reinforce their sucking power . palady is similar to a teaspoon with a tongue stud and is used for the neonates who can not be directly breastfed . this tool is traditionally used in india to feed the neonates and is very healthy . a study conducted in 2012 in india showed that preterm healthy neonates over 30 weeks of gestational age could be fed by palady and reach oral feeding earlier leading to their earlier transfer from nicu to their mothers . there were no complications reported , such as vomiting and aspiration , among the neonates fed by palady and breastfeeding . therefore , it seems that palady method has no conflict with breastfeeding . in a study conducted in england in 2007 , the results showed that the neonates received a lower volume of milk in palady method compared to bottle feeding ( due to high amount of wasted milk ) and more time was consumed in palady method to feed the neonate . a study in india showed that the infants fed by palady received the maximum volume of milk in the shortest possible time , and cup feeding had the highest milk wastage . the infants also experienced a longer period of calmness . with regard to the controversial results of studies conducted on the volume of mother 's milk received through palady and cup methods , and as the neonates are fed by cups in few nicus and no study aiming at comparison of the two feeding methods concerning weight gain and reaching full oral feeding was found , the researcher conducted the present study to investigate the effect of palady and cup feeding methods on premature neonates weight gain and their reaching full oral feeding time interval . this is a clinical trial irct registration number irct2015090518561n4 that was conducted on 69 premature neonates in the nicus of al - zahra and shahid beheshti hospitals of isfahan in may - september 2014 after obtaining an informed consent from the subjects . the study was conducted on 69 premature neonates aged 29 - 32 gestational weeks , selected through convenient sampling . the subjects were assigned to cup ( n = 34 ) and palady ( n = 35 ) feeding groups by random allocation ( lotto ) . inclusion criteria were : birth weight 900 - 1000 g , gestational age 29 - 31 weeks ( fertilization age was 32 weeks and did not exceed 33 weeks ) , exclusive breastfeeding or feeding with enriched mother 's milk , neonates hemoglobin not lower than 8 mg / dl and hematocrit not less than 30 , iranian nationality , absence of severe disabling conditions such as cerebral hemorrhage ( grade ii and iii ) , or congenital defects , and no limitation in feeding with mother 's milk . exclusion criteria were : parents loss of interest to continue in the study , neonates death or critical clinical conditions , neonates discharge before the end of study , and a sudden change affecting neonates nutritional status , such as cerebral hemorrhage or intestinal problems such as necrotizing enterocolitis . researcher began the intervention after explanation of the research goal and method to neonates parents and obtaining their consent . data collection tool was a demographic information record note , neonates feeding checklist , and neonates weight monitoring checklist . from the first day after birth , intravenous full nutrition or total parental nutrition ( tpn ) was started based on a standard protocol for the neonates in both groups . the subjects meeting the inclusion criteria received either cup or palady feeding according to relevant physician 's order recorded in neonates medical file . in each shift , one oral feeding was administrated ( 3 times a day ) for seven sequential days ( total of 21 feedings through cup or palady method ) . it should be noted that according to physician 's order , breastfeeding was not administered at all during 7 days of the study . before intervention , the researcher washed hands and hugged the neonate in semi - follower 's position based on hands hygiene compliance instruction and used a neonate apron around the neonates neck . the cup was gently laid on neonate 's lower lip so that the milk would touch the neonate 's lip in a way that the neonate could actively swallow milk . this process continued until the entire required amount of milk was taken . for palady method , the researcher washed hands , and palady was held by its side and laid on neonate 's mouth corner . full oral feeding refers to 8 times of oral feeding in a day with observation of no oxygenation disorder , apnea , and bradycardia in neonates during feeding . the neonates were weighed in equal conditions with identical scales ( seca digital scales , made in germany ; with an accuracy of 10 g ) in nicu before they were fed and while they were not wearing apron , and their weights were recorded . data were analyzed by descriptive ( frequency distribution tables , distribution , mean , and sd ) and inferential ( chi - square , mann - whitney , and independent t - tests ) statistical tests in spss 14 . the present study was approved by the ethics committee of isfahan university of medical sciences and all ethical considerations including subjects volunteer participation and confidentiality of their data were respected . the present study was approved by the ethics committee of isfahan university of medical sciences and all ethical considerations including subjects volunteer participation and confidentiality of their data were respected . the results showed a significant difference in subjects demographic variables such as sex , gestational age , number of phototherapy days , rank of birth , delivery mode , mother 's disease , multiple neonates , mother 's smoking and addiction , type of feeding , phototherapy , and antibiotic therapy between two groups ( mann - whitney , chi - square , and independent t - tests ) . independent t - test showed that mean length of hospitalization and the time interval to reach full oral feeding were significantly lower in palady group compared to the cup group ( p < 0.001 ) [ table 1 ] . independent t - test showed that mean weight change in neonates was significantly higher 7 days after intervention in the palady group than in cup group , compared to the beginning of intervention ( p < 0.001 ) [ table 2 ] . means of hospitalization length and time interval to reach full oral feeding comparison of weights 1 and 7 days after intervention in the two groups , time to reach full oral feeding compared to the first day after intervention , weight on the 7 day after birth compared to birth weight in the two groups the present study investigated the effect of palady and cup feeding on premature neonates weight gain and reaching full oral feeding time interval . results show that weight gain and the time interval to reach full oral feeding were significantly lower in palady group compared to the cup group . mean weight change in neonates was significantly higher in palady group 7 days after beginning the intervention , compared to the cup group . a study in 2012 showed that premature neonates with gestational age of 30 weeks could be fed by palady from the second day after birth . the authors reported that palady feeding could improve premature neonates nutritional function within a couple of days , so that they could be transferred to their mothers . the fact reported in the study that premature neonates fed by palady could reach full oral feeding earlier is in line with the present study . the authors suggested feeding the neonates with physiological stability and a gestational age of 30 weeks through palady method from the second day post birth . in the present study , the neonates with approximately 30 weeks of gestational age were started on palady feeding based on relevant physician 's order . most of the studies have investigated the volume of milk taken and the amount of mother 's milk wasted in palady and cup feeding . narayaran et al . showed that the neonates on palady feeding had more weight gain as they received the highest amount of milk in the shortest time and had longer periods of calmness . the highest wastage of milk was found in neonates fed through cup feeding , which is consistent with the present study result . but the time interval of reaching full oral feeding was not compared in neonates being fed by palady and cup methods . , in a pilot study on premature neonates , concluded that the neonates received lower volume of milk in palady method compared to bottle feeding , and palady method took more time that could lead to less weight gain , which is not in line with the present study result . a study conducted in turkey in 2013 showed no significant difference in the neonates fed by cup and bottle concerning weight gain , nutritional problems , and the time consumed for feeding . the authors also reported that cup feeding significantly increased the probability of exclusive feeding with mother 's milk in premature neonates 3 and 6 months after discharge . they suggested using cup feeding as a transitive traditional method to feed premature neonates during their hospitalization . compared the effects of bottle and cup feeding on oxygenation and weight gain in premature neonates and reported no significant difference between groups in the weight gained during the first week of oral feeding . meanwhile , better effect of cup feeding , compared to bottle feeding , was revealed when the neonates were discharged and they showed more interest in breastfeeding . a study in tabriz , iran , conducted in 2012 showed that the group that had increased milk volume of 30 ml / kg / day fared better concerning the time needed for reaching birth weight and full oral feeding , compared to the other group . although there is a bulk of research on premature neonates feeding , there is no consensus on the feeding methods and the age of beginning oral feeding in premature neonates . our obtained results show that the time interval to reach full oral feeding was shorter in palady group compared to cup feeding . change in mean weight was higher in palady group subjects 7 days after beginning the intervention , compared to that at the beginning of intervention and the cup group . therefore , palady method is suggested to feed premature neonates with stable physiological condition from the second day after birth or with a gestational age of 30 weeks . meanwhile , further studies with a larger sample size of premature neonates are needed before recommending this method as a routine . therefore , conducting another study with a higher number of subjects and focusing on low birth weight infants , and comparing its results with the present study are suggested . based on the obtained results , it can be concluded that administration of palady feeding for premature neonates with physiological stability at 30 weeks of gestational age in nicu leads to increased weight gain and a shorter time interval to reach full oral feeding .

background : premature neonates feeding is of great importance due to its effective role in their growth . these neonates should reach an independent oral nutrition stage before being discharged from the neonatal intensive care unit . therefore , the researcher decided to conduct a study on the effect of palady and cup feeding on premature neonates weight gain and their reaching full oral feeding time interval.materials and methods : this is a clinical trial with a quantitative design conducted on 69 premature infants ( gestational age between 29 and 32 weeks ) who were assigned to cup ( n = 34 ) and palady ( n = 35 ) feeding groups through random allocation . the first feeding was administrated either by cup or palady method in each shift within seven sequential days ( total of 21 cup and palady feedings ) . then , the rest of feeding was administrated by gavage.results:mean hospitalization time ( cup = 39.01 and palady = 30.4 ; p < 0.001 ) and mean time interval to reach full oral feeding ( cup = 33.7 and palady = 24.1 ; p < 0.001 ) were significantly lower in palady group compared to cup group . mean weight changes of neonates 7 weeks after the intervention compared to those in the beginning of the intervention were significantly more in palady group compared to the cup group ( cup = 146.7 and palady = 198.8 ; p < 0.001).conclusions : the neonates in palady group reached full oral feeding earlier than those of cup group . subjects weight gain was also higher in palady group compared to the cup group . premature neonates with over 30 weeks of gestational age and physiological stability can be fed by palady .

we present here a 30-year - old female patient presenting as a case of hard palate perforation . after thorough evaluation , a biopsy from that site was taken , which shows granulomatous inflammation and positive for tuberculosis polymerase chain reaction ( tb - pcr ) . tb of the palate is a rare entity and that too without any sign of pulmonary tb is exceptional , which prompted us to do the case reporting . she was started on antituberculous regimen , and within the short span , her response was dramatic . during the 6 week of prenatal period , infectious causes of palatal perforation are leprosy , tertiary syphilis , tb , rhinoscleroderma , naso - oral blastomycosis , leishmaniasis , actinomycosis , histoplasmosis , coccidioidomycosis , and diphtheria . examples are lupus erythematosus , sarcoidosis , crohn 's disease , and wegener 's granulomatosis . . other drugs ( heroine , narcotics ) can also be responsible for this . sometimes , following a tooth extraction during the 6 week of prenatal period , palatal shelve coalesces to form the hard palate . infectious causes of palatal perforation are leprosy , tertiary syphilis , tb , rhinoscleroderma , naso - oral blastomycosis , leishmaniasis , actinomycosis , histoplasmosis , coccidioidomycosis , and diphtheria . examples are lupus erythematosus , sarcoidosis , crohn 's disease , and wegener 's granulomatosis . other drugs ( heroine , narcotics ) can also be responsible for this . sometimes , following a tooth extraction , a 30 year old female patient presented with complaints of nasal regurgitation of foods , slurring of speech and low grade fever for 2 months . no epistaxis , no weight loss , focal deficit , weakness of any limb were reported . on examination , the patient 's vitals were normal ; she was afebrile , and she had no pallor , icterus , cyanosis , clubbing , and lymphadenopathy . oral examination suggested of perforation of size 3 cm 2 cm in the hard palate [ figure 1 ] . systemic examination was within normal limit ( wnl ) . on biochemical examination , renal function test , liver function test and serum electolytes was wnl range . urine routine / microscopy and hepatitis b surface antigens and hepatitis c virus antibodies were negative . photomicrograph showing hard palate perforation chest x - ray was wnl , contrast - enhanced computed tomography of the chest was wnl . biopsy from the margin of perforation was suggestive of granulomatous inflammation with possibilities of tb and granulomatous polyangiitis . primary origin of oral tb is very rare ; more often , it is secondary to pulmonary tb . in secondary oral tb , the bacilli reach the oral mucosa by hematogenous or lymphatic spread from distant source . in primary oral tb , there is direct inoculation of the mycobacterium due to break or loss of the natural barrier resulting from trauma , inflammatory conditions , leukoplakia , tooth extraction , or poor oral hygiene . tb is a chronic , granulomatous infectious disease caused by mycobacterium tuberculosis through inhaling contaminated droplets and less so by mycobacterium bovis or other atypical mycobacteria . factors that attribute to relative resistance of oral cavity to tb are protective effect of saliva , presence of saprophytes , resistance of striated muscles to bacterial invasion , and thickness of protective epithelial covering . floor of mouth , soft palate , gingiva , lips , and hard palate can be involved ; however , palate and tongue are most common . if there is the presence of constitutional symptoms of tb such as long duration of fever and weight loss , we have to look for any evidence of tubercular infection . tissue diagnosis such as biopsy from local site is confirmatory of diagnosis . for primary care physician , especially in developing country like india , tb is one of the differential diagnoses to be kept in mind whenever we are dealing with some atypical manifestations of some diseases . the aim of this case report is to highlight the fact that in oral cavity lesions , when making a differential diagnosis , the diagnosis of oral cavity tb also needs to be kept in mind as medical treatment in this condition is excellent and precious resources could be saved both in time and money .

tuberculosis ( tb ) is a major public health problem in developing countries . lung is most common affected organ , however extra pulmonary tuberculosis ( eptb ) is also not uncommon . the clinical manifestations of eptb may be non - specific that mimics other diseases and is usually misdiagnosed . therefore , high clinical suspicion of eptb infection is important , especially in endemic areas . here , we present a case of hard palate perforation that proved to be tuberculous in origin . the diagnosis was made by histo - pathological examination and positive tb polymerase chain reaction ( pcr ) .

aggressive angiomyxoma ( aa ) is a rare benign soft tissue tumour usually affecting the pelvis and perineum of young women . magnetic resonance imaging ( mri ) is crucial in the management of aa patients for its diagnostic contribution and for the preoperative assessment of the actual tumour extension . given the current development of less aggressive therapeutics associated with a higher risk of recurrence , close follow - up with mri is fundamental after treatment . in this context , diffusion - weighted ( dw ) imaging has already shown high efficacy in the detection of early small relapses in prostate or rectal cancer . we report here a case of pelvic aa in a 51-year - old woman examined with dynamic contrast enhancement and dw - mri , including apparent diffusion coefficient mapping and calculation . to our knowledge , this is the first description of dw - mri in aa reported in the literature . here , aggressive angiomyxoma ( aa ) is a benign soft tissue tumour with myxoid and vascular components that arises mostly in the lower pelvis and perineum in women of reproductive age . most of them ( > 90% ) occurred in young women , usually in the second to fourth decade . the risks of local extension and postoperative local relapse justify surgical excision of the tumour . imaging and particularly magnetic resonance imaging ( mri ) are fundamental for the clinical management of aa . precise preoperative assessment of local extension is crucial to plan the best surgical approach for tumour removal involving as little mutilation as possible . mri allows the monitoring of the response to possible preoperative treatment such as hormone therapy . finally , it is also crucial during the patient 's follow - up after initial treatment . for a few years now , classical mri coupled with diffusion - weighted ( dw ) sequences has developed in oncology , leading to improvements in the detection and characterization of tumours , treatment response monitoring , and detection of recurrence [ 3 , 4 ] . to our knowledge , we report here the first case of pelvic aa explored with dw - mri and dynamic contrast enhancement ( dce)-mri . in july 2011 , a 51-year - old woman presented to her general practitioner with an incidentally discovered renitent mass in the internal part of the left buttock . initial ultrasound ( us ) showed a well - circumscribed mass initially evoking a lipoma . due to the large volume of the mass , she was otherwise asymptomatic with a performance status score of 0 on the who scale . us showed a superficial , soft , hypoechoic , well - limited , solid mass . mri showed a bulky perineal and intrapelvic tumour displacing rather than infiltrating the vagina , anal canal , and rectal structures . the mass was well limited , hourglass - shaped and had a maximum diameter of 11 cm ( fig . t2-weighted imaging showed typical high signal intensity with layered strands of lower signal intensity and swirled architecture . a fat linear structure of high signal intensity on t1- and t2-weighted images was present inside the mass . its significance was unknown , perhaps representing neighbouring tissues trapped when the tumour was growing . after intravenous contrast injection , the mass was greatly and heterogeneously enhanced , exhibiting a layered pattern ( fig . regions of interest located in the layers demonstrated the same profile curves of progressive enhancement with variable intensity . apparent diffusion coefficient ( adc ) mapping showed a high value in the tumour , estimated at 2 10 ( 0.15 ) mm / sec . it also showed disease extension , notably through the pelvic diaphragm , which made a combined transperineal and laparoscopic abdominopelvic approach necessary . before surgery , the examination under general anesthesia showed that the mass was soft , renitent , and seemed to come from the pelvic cavity through the levator ani muscles . tumour excision was monobloc and macroscopically complete , without any rectal or vaginal resection or tumour capsular rupture . macroscopic examination of the surgical specimen showed a firm , partly circumscribed tumour measuring 16 12 6.5 cm . a cut section showed a homogeneous , glistening , and gelatinous appearance without any hemorrhagic or necrotic areas . microscopic analysis showed a monotonous hypocellular proliferation of small nonatypical stellate - shaped cells arranged in a myxoid stroma , along with numerous , variably sized vessels . no mitosis or necrosis could be seen . in its periphery , the proliferation infiltrated the nontumour adipose tissue , and resection margins were focally involved by the tumour cells . immunohistochemical analysis showed strong expression of cd34 , and estrogen and progesterone receptors by tumour cells , without expression of desmin , cd117 , -catenine , and mdm2 , nor epithelial ( pancytokeratin , ema ) , smooth muscle ( -smooth actin , h - caldesmon ) , and schwann cell ( ps100 ) markers . after surgery , no adjuvant treatment was given , and the patient was regularly monitored clinically and radiologically . at her last visit , in october 2012 , more than 1 year after the diagnosis , the patient was alive with an excellent performance status and without any recurrence of the disease on pelvic dw - mri . aa is a compliant tumour that grows slowly in the perineal or pelvic region and can cross the pelvic diaphragm . classically , the tumour shows finger - like projections at the periphery and into the surrounding tissue without infiltrating or invading adjacent organs . in general , the tumour is well limited and large ( often more than 10 cm in diameter ) at the time of diagnosis , and its consistency is soft or renitent [ 1 , 6 ] . histologically , aa is a benign hypocellular tumour , composed of scattered spindle or stellar cells , embedded in a loose myxoid matrix with a few collagen fibers and abundant vessels of varying sizes . frequently , tumour cells show positive immunohistochemical staining for desmin , smooth muscle actin , muscle - specific actin , and hormone receptors . rare and recent molecular analyses have identified translocation in the 12q1315 region involving the hmga2 gene . aggressiveness is related to the high rate of local recurrence after surgery because of frequent incomplete excision . this can be due to the absence of a preoperative diagnosis and estimation of the actual extent of the tumour , or to a particular strategic location of the mass near the urethra , vagina , anal sphincter and rectum , with frequent extension through the pelvic diaphragm , making complete resection difficult . the formerly high rate of relapse has decreased from ~75 to 1030% during the last 20 years thanks to improved imaging techniques , which allow a more complete surgical resection . aa in men is unusual and affects the genitourinary tract especially the scrotum and inguinal region [ 1 , 4 ] . most patients present with a slow - growing palpable or visible mass in the pelvi - perineal region . other signs may include discomfort or pain due to the mass , or signs related to pressure effects on adjacent organs such as dyspareunia and dysuria . morphological imaging like computed tomography ( ct ) checks for the absence of pelvic hernia , gynaecological prolapse or myoma . vaginal cysts , gartner cysts and bartholin cysts are frequent and easy differential diagnoses that do not show significant enhancement except if infected . in that case , mri will usually show peripheral enhancement of the wall of the cyst with variable thickness , which is totally different from the aa pattern of enhancement . the lack of macroscopic fat on ct and mri sequences with and without fat suppression can rule out infiltrating angiolipoma and lipoma or liposarcoma with or without myxoid component [ 7 , 8 ] . endometriomas and melanomas show typical high signal intensity on t1-weighted images without signal intensity dropout on fat - suppressed images . myxoma is mainly an intramuscular tumour that occurs in older patients , and whose enhancement does not show the same features as aa . mri is also a helpful diagnostic tool with in - phase and opposed - phase sequences showing microscopic fat inside the angiomyofibroblastoma . other diagnoses such as myxoid neurofibroma , myxoid - type malignant fibrous histiocytoma , myxofibrosarcoma , vaginal botryoid pseudosarcoma , and rhabdomyosarcoma are made by histological analysis of the tumour . in general , mri will help with the preoperative diagnosis by showing typical images of aa , as in our case . this is all the more important because , if the final diagnosis is obviously based on histology and immunohistochemistry , a preoperative diagnosis may be difficult to obtain from a percutaneous biopsy . typical images show the lesion as a well - limited mass , displacing rather than infiltrating adjacent organs and muscles , with content rich in water , loose myxoid matrix , and hypervascularity . finger - like projections into neighbouring adipose tissue can be present and are relatively characteristic of aa . classically , us without contrast injection shows a homogeneous and hypoechoic mass , sometimes cystic , that may be misleading . ct scan shows an enhanced mass , which is iso- or hypoattenuating relative to muscle [ 7 , 11 ] . mri shows very characteristic aspects : an isointense tumour ( more rarely hypointense ) relative to muscle on t1-weighted images , and hyperintense on t2-weighted images ( high water content and loose myxoid matrix ) [ 2 , 5 , 7 ] . the tumour enhances avidly and heterogeneously after intravenous gadolinium contrast administration , reflecting its inherent vasculature [ 2 , 5 , 7 , 8 ] . a typical mri feature of aa is the presence of an internal layered pattern and/or swirled architecture , which is described in 83% of cases on t2-weighted mri or on t1-weighted mri after intravenous contrast injection [ 2 , 5 , 6 , 7 , 8 , 9 ] . our case perfectly illustrated these mri findings , allowing us to suspect the aa diagnosis before surgery . preoperative mri is also crucial to determine the true extent of the disease and plan the most optimal surgical approach . the importance of accurate preoperative diagnosis and extent screening is clearly reported . in our case , an abdominoperineal approach was chosen as the tumour extended above the pelvic diaphragm on mri , allowing complete resection . during treatment finally , mri is very helpful in order to detect local relapses during follow - up . because of its high sensitivity in detecting tumour presence , its noninvasive nature , and its ability to provide valuable qualitative and quantitative information , dwi has become indispensable for characterizing lesions , and for monitoring the response to nonsurgical therapy and the patient 's follow - up after treatment . this is already well documented for the detection of prostate or rectal cancer relapse . to our knowledge the typical architecture of the tumour was seen on t2-weighted images and b0 sequences ; however , it disappeared both as the b value increased and on adc mapping imaging even in a mass more than 10 cm in diameter . dwi also showed a high value of tumour adc measurements in the region of 2 10 mm / sec , comparable with adc calculations in myxoid tumours . the persistence of high tumour signal intensity on dwi with a high b value suggests the possibility of easy and earlier relapse diagnosis using these types of sequences . furthermore , we can hypothesize that normal mri using dw sequences during patients follow - up is probably an effective way to confirm the absence of recurrence . however , aa can theoretically be polymorphous , and more patients in larger case series are needed to confirm these first observations . due to the rarity of this disease , wide surgical resection is the treatment of choice , sometimes after preoperative angiographic embolization to decrease the size of the tumour . but , because of its frequently large size and location in close proximity to vital organs ( urogenital tract and rectum ) , wide excision is not always possible and/or may cause significant morbidity in young patients . furthermore , the prognostic value of extensive surgical resection to obtain clear margins is questioned . a review of over 100 cases published in 2000 by chan et al . showed that patients with clear resection margins have similar chances of remaining disease free ( 50% at 10 years ) compared with those having tumour - involved resection margins ( 40% ) . these observations explain that incomplete resection is acceptable nowadays if followed by long - term follow - up and careful monitoring for timely identification and prompt resection of relapse . treatment involving chemotherapy and radiotherapy has been disappointing , probably due to the low mitotic activity of the tumours [ 1 , 11 ] . aa is likely hormone dependent as suggested by the reproductive age of the patients , the few cases reported during pregnancy , and the frequent expression of hormone receptors . thus , gonadotropin - releasing hormone agonists have been administered to aa patients in the postoperative as well as in the preoperative setting with dramatic responses , facilitating surgery or avoiding mutilating surgery [ 10 , 13 , 14 ] . one case report of aa treated exclusively with gonadotropin - releasing hormone agonists was published in 2003 . two cases of successful control of recurrent aa with relatively high doses of external radiotherapy have been reported , but a literature analysis shows a definite shift towards less morbid treatments . after treatment , long - term follow - up is required since late recurrences have been described up to 14 years following treatment . recurrence rates are variable in the literature and probably depend on when patients were treated ( related to surgical and mri quality ) . . found a recurrence rate in the region of 50% between 1984 and 1998 . . otherwise , 71% of recurrences occurred within the first 3 years , regardless of the initial tumour size and patient 's age . periodic clinical examination may be insufficient and imaging studies , such as mri , are fundamental . they may detect recurrence early , when the tumour is smaller in size , making surgery easier to perform or allowing the use of less morbid percutaneous ablative therapeutic strategies such as radiofrequency ablation or cryotherapy . mri is crucial in the management of aa patients for its diagnostic contribution and preoperative assessment of the actual extent of the tumour . during eventual neoadjuvant treatment , it allows monitoring of the tumour response and , after treatment , it is very useful for detecting recurrences . here , we presented the use of mri in a typical case of aa . however , this case report is also the first description in the literature of aa with complete dce and dwi analysis . we have updated the current knowledge on aa and , furthermore , we recommend the use of diffusion sequences in the follow - up of young patients treated for aa , regardless of what type of treatment they have previously had .

introductionaggressive angiomyxoma ( aa ) is a rare benign soft tissue tumour usually affecting the pelvis and perineum of young women . magnetic resonance imaging ( mri ) is crucial in the management of aa patients for its diagnostic contribution and for the preoperative assessment of the actual tumour extension . given the current development of less aggressive therapeutics associated with a higher risk of recurrence , close follow - up with mri is fundamental after treatment . in this context , diffusion - weighted ( dw ) imaging has already shown high efficacy in the detection of early small relapses in prostate or rectal cancer.case reportwe report here a case of pelvic aa in a 51-year - old woman examined with dynamic contrast enhancement and dw - mri , including apparent diffusion coefficient mapping and calculation.conclusionto our knowledge , this is the first description of dw - mri in aa reported in the literature . here , knowledge about imaging features of aa will be reviewed and expanded .

the management options for an anastomotic leak ( al ) vary from conservative management to reoperation . a major al may require esophageal diversion that leads to discarding of the native esophagus . to retain the native esophagus , a redo anastomosis with or without vascularized flaps or a conservative approach with adequate nutritional supplementation have all been described in the literature , however , the reported success of conservative treatment is quite variable . there is no controversy regarding the conservative management of minor leaks , but the management strategies for major anastomotic disruptions are still not standardized . gastroesophageal reflux is associated with a significant number in patients of ea and is one of the factors preventing the closure of al leading to failure of conservative treatment . we performed transgastric feeding jejunostomy ( fj ) with decompressing gastrostomy in patients of ea with anastomotic dehiscence and studied its effect on healing . from january 2006 to october 2012 , 20 consecutive neonates with major al , fulfilling the inclusion criteria , were prospectively studied . all the leaks were identified in the chest tubes and these patients were managed with a decompressing gastrostomy and transgastric fj . transgastric fj was used for enteral nutrition , and none of the patients received total parenteral nutrition ( tpn ) . in our study , a major leak was defined as the presence of either more than 20% of the total nasogastric feeds draining out through the intercostal drain or < 20% of total nasogastric feeds with chest complications ( pneumothorax , persistent collection , and lung collapse ) , increase in ventilatory parameters and worsening general condition of the neonate . patients with a major leak who developed pneumothorax or persistent collections were considered for insertion of a second intercostal chest drain ( icd ) . the patients with high icd output draining more than 20% of the feeds and those with continuing chest complications underwent gastrostomy and fj and formed the subjects of this report [ figure 1 ] . the patients with a minor leak and those who improved with a second icd were excluded from the study . algorithm for management of major anastomotic leak a transgastric fj was done by selecting an area in the body of the stomach as is done for gastrostomy . a hole was created within a purse string suture through which a malecot 's catheter of suitable size and a 6 fr infant feeding tube were introduced . the malecot 's catheter was kept inside the stomach while the feeding tube was guided across the duodenum into the jejunum . the purse string was tightened , and the stomach was fixed to the abdominal wall in a watertight manner at the exit of the tubes . a gastrostomy tube was used for decompression while the jejunostomy was used for feeding purpose . the objectives of the study were to analyze the effect of fj and gastrostomy in terms of decrease in the chest tube output , improvement of lung complications , change in parameters of ventilation , and subsequent anastomotic healing . over a period of 6 years , 20 patients with major anastomotic dehiscence were analyzed . the birth weight of patients ranged from 1.6 to 3.3 kg ( mean-2.2 kg ) . all patients underwent primary end to end anastomosis of the esophagus ( vicryl 5 - 0 ) with ligation of fistula and 15 patients required mobilization of the lower pouch also . as per the management protocol , after primary repair , the patients were nursed in head up position , and the feeds were started by transanastomotic feeding tube on 2 postoperative day in all the patients , except two who had associated jejunal and rectal atresia . al was clinically noted in all these patients from 3 to 5 postoperative day with chest tube showing evidence of saliva . all the patients of al were managed conservatively , and the feeding was continued through the nasogastric tube . the contents of the leak were saliva mixed with feeds , and the amount was more than 20% of nasogastric feeds in all the patients . the first chest drain was effective in 75% of the patients , whereas a second icd was required in the remaining 25% ( 5/20 ) for persistent pneumothorax or collection . on an average , the patients underwent gastrostomy and fj on the 12 postoperative day ( range 8 - 15 days ) after an adequate trial of conservative management . after fj and gastrostomy , the condition of lungs improved gradually in 53% of patients ( 8/15 ) with single chest tube over next 8 - 10 days who could then be extubated . the rest of the patients required prolonged ventilation due to persistent high chest tube output , and associated heart and gastrointestinal diseases . there was a gradual reduction in chest tube output and improvement in the condition of chest in these patients also . on an average , the postoperative ventilation was required for 25 days ( 14 - 51 days ) . enteral nutrition could be started through the jejunostomy in two - thirds ( 14/20 ) of the patients on the 2 postoperative day . esophagogram demonstrated healing of the anastomosis and leak free patency after an average of 1.5 months ( range 1 - 3 months ) when oral feeds could be instituted . of these six , two developed jejuno - cutaneous fistulas as a complication of jejunal intubation , two necrotizing enterocolitis and one each had associated jejunal and rectal atresia . remaining two patients had severe associated congenital heart anomalies . in the follow - up , gastroesophageal reflux was noted in seven patients , and six of them had a resolution of the reflux over next 2 years . four patients developed stricture , out of which two were amenable to multiple dilatations , but the other two required resection of the strictured segment and end to end anastomosis . one had a rare complication of pseudo - diverticulum that required excision [ figure 2 ] . the overall incidence of al age after surgical repair of ea is around 15 - 17% but major leakage is approximately 3.5% . the main factors held responsible for anastomotic dehiscence are the use of certain suture materials such as silk , devascularization secondary to extensive dissection , excess tension on the sutures , small and friable lower segment , technically poor suturing techniques , and inaccurate mucosal apposition . current management of als depends on the clinical condition of the patient and the extent of leak . labeled involvement of more than one - fourth circumference of the esophagus as a major leak . chavin et al . reported 11 cases of als , seven of which were considered in contrast to the above - mentioned studies , we defined the of degree of al as major or minor based not only on chest tube output but also the presence or absence of pneumothorax , chest collection , and lung collapse . major leaks usually occur in early postoperative period ( < 48 h ) and may require additional procedures such as rethoracotomy or esophageal diversion to tide over the situation . however , minor leaks detected on the routine contrast study on 5 - 7 day postoperatively usually heal spontaneously , with or without strictures . when anastomotic dehiscence occurs , the choice between surgical and conservative management can be difficult . initially , a conservative approach was advised as long as the lungs were maintained in an expanded state although this required careful and prolonged monitoring . inability to prevent lung complications and deliver adequate enteral nutrition via nasogastric route necessitated surgical intervention . in addition , tpn is required for these patients , which has its own short and long - term complications and availability may be an issue in developing countries . however , many a times , the decision to abandon the wait - and - see approach and reoperate is both complex and crucial . some authors advice early thoracotomy and reanastamosis , with good results . in most cases , the recently operated friable tissue is further jeopardized by being constantly in contact with salivary and possibly gastric juices from the leak . another approach to manage major als involves a cervical esophagostomy and gastrostomy followed by gastric , colonic , or jejunal interposition at an appropriate time , like a staged procedure . apart from abandoning the native esophagus , consequences of interposition grafts such as poor motility , severe gastric reflux and the tenuous nature of the blood supply especially in jejunal grafts make these less than ideal . primary gastric pull up in patients with als has also been described but is not feasible , most of the times , due to sepsis , and poor general condition . use of anticholinergic medications , to reduce the drain output , during the conservative approach has also been described recently . none of the above - mentioned approaches have turned out to be ideal and free of complications . with this background , we describe an innovative addition in the form of an fj with gastrostomy , which is feasible in an acute setting without rendering the native esophagus unusable in future . our results even though not very encouraging show significant improvement in a subset of patients who did not require esophageal replacement after major al . first , it is less time consuming and requires less anesthesia time in the friable , septic cohort of patients with major al . furthermore , gastrostomy drainage in the early period helps in decreasing the reflux which is an aggravating factor for al . third ; an ability to institute early enteral feedings is a major advantage which could be done in the majority of our patients . this improved the overall well - being , avoided complications of parenteral nutrition and provided breast milk during this crucial period . nonavailability of silastic tubes which are more suitable for jejunostomy forced us to use simple nasogastric tubes although these are likely to become hard with the passage of time . many complications such as accidental dislodgment of the tube , bowel perforation with peritonitis , and a jejunocolic fistula formation have been described in the literature and were noted in our patients as well . in the initial part of the study , the decision for doing fj was delayed as it was based on lung condition and chest tube output . there was a tendency to continue conservative management in the presence of good lung condition even with persistent chest tube drainage . in the later part of study , the patients underwent the procedure at an earlier stage as a result of the experience gained and showed better outcomes . we do not claim that this procedure is an ideal way of managing major anastomotic dehiscence but can be considered in a septic cohort of patients who would otherwise end up with an esophageal replacement . it can also be considered at centers , which can not provide long - term tpn . although many of our patients required secondary procedures to normalize the esophageal tube , yet they had the benefit of native esophagus . the mainstay of treatment of most esophageal al after tracheoesophageal fistula repair includes adequate chest drainage , treatment of infection , observation , and maintenance of proper nutrition . protocolized treatment can lead to better results , avoiding the therapeutic dilemmas , and delay in interventional decisions . gastrostomy and fj are feasible in this crucial period and may help in salvaging the native esophagus .

aims : to investigate the role of feeding jejunostomy ( fj ) in patients of esophageal atresia with anastomotic leak ( al ) to decrease the degree of gastroesophageal reflux ( ger ) and its effect on anastomotic healing.materials and methods : twenty neonates , with major al and severe ger after primary repair were managed with decompressing gastrostomy and transgastric fj and analyzed prospectively.results:male to female ratio was 1.7:1 . mean birth weight was 2.2 kg . anastomotic gap ranged from 0 to 4 cm . the amount of leak was more than 20% of nasogastric feeds . gastrostomy and fj was done on an average of the 12th postoperative day , after observing the general condition , chest tube output , lung expansion , and ventilatory requirement . there was a drastic reduction in chest tube output and lung expanded in all patients . average hospital stay was 36 days ( 8 - 80 days ) . sixty percentage patients were discharged successfully on fj . esophagogram demonstrated healing and leak free patency after an average of 1.5 months . ger was noted in seven patients , four developed stricture , and one had pseudodiverticulum in follow-up.conclusion:decompressing gastrostomy and fj can be an alternative to managing major als . it helps in healing of anastomotic dehiscence and in preserving the native esophagus .

given that controversy exists regarding how best to manage the treatment of women with gdm , data from successful clinical programs often can assist in the decision - making process . the following sections of this article share our practical approach for such clinical decision - making but should not be considered to be extrapolated from statistically significant data nor always consistent with prevailing guidelines from major professional societies . our gdm management program , located in a rural setting , serves more than 300 women per year who have some form of diabetes in pregnancy . the program is in its tenth year , and more than 90% of the babies from these pregnancies are born at a weight appropriate for gestational age . our patients often present with unique social , geographic , and financial barriers that hamper access to resources such as high - quality foods and exacerbate food insecurity . they typically have cultural practices governing food choices that do not fit within the recommended dietary prescriptions and traditional guidelines of recognized and highly regarded professional societies . the primary factor associated with successful gdm management in our patient population is patient empowerment . when patients are told that they failed a glucose tolerance test , often the only portion of the message they hear is that they have simply failed . that message does not set the necessary tone for building patients self - confidence in their ability to control their disease for the duration of their pregnancy . although achieving euglycemia is the primary goal in gdm care , providers must simultaneously protect each woman s birth story . enabling her to take control of her blood glucose allows for gdm to be considered only a small part of her pregnancy experience rather than an overwhelming stressor centered on failure and fear . medical nutrition therapy ( mnt ) is the cornerstone of initial gdm therapy ( 12 ) . many women can manage their glucose with thoughtful meal planning , provided there are no barriers to following the detailed recommendations . these barriers , including depressed socioeconomic status , exist among our patients , and providers often revisit the inability to overcome such obstacles , furthering the concept of failure . empowering patients newly diagnosed with gdm should focus on the positive self - care behaviors they are able to achieve , such as remembering to check blood glucose levels or completing a meal diary . no consensus exists regarding the threshold at which medications should be started in gdm management ( 13 ) . the decision - making process we have used has yielded successful outcomes for our population for many years . we use the sweet success clinical guidelines for care as our program framework ( 14 ) . we consider adequate glycemic control to be 80% of fasting and postprandial values in the target range . we use a fasting blood glucose ( fbg ) goal of 6089 mg / dl and a 1-hour post - meal target of 100129 mg / dl . oral diabetes agents can be used successfully in pregnancy . about 25% of our patients with gdm use glyburide successfully to manage their blood glucose during pregnancy . all providers who care for the women with gdm should be able to determine ideal candidates for this medication ( 10 ) . fbg , weeks of gestation , and weight gain to date are the three main data points we consider when deciding whether glyburide may be a successful option for a given patient . because glyburide is a secretagogue , its success is dependent on the patient having a healthy and functioning pancreas that can respond well to the drug . if a patient s fbg is significantly elevated , providers should suspect that she may not have the physiological capacity to secrete the elevated amount of insulin required during pregnancy , and glyburide is unlikely to correct this problem ( 15 ) . glyburide also potentiates weight gain , so it is important to assess total weight gain to date and consider how long the patient may need to use glyburide ( 16 ) . recommendations in the literature state that glyburide can be used predictably when fbg is < 110 mg / dl after 25 weeks gestation ( 12 ) . we are more conservative in our patient selection , using glyburide for patients with an fbg 100 mg / dl in the third trimester who have not exceeded the recommended weight gain for their bmi based on the institute of medicine s guidelines . after 1 week of data gathering , if a patient s fbg is above target but < 100 mg / dl despite mnt , we typically start glyburide 2.5 mg at bedtime . if the postmeal glucose values are slightly above target but not severely elevated to > 200 mg / dl , we also would add an equivalent morning dose . we continue to discuss and encourage physical activity and mnt so the patient can bring the effects of all three components to bear on her glycemic management . we download glucose meters and evaluate meal diaries weekly , in person or remotely , titrating medication dosages accordingly to reach and maintain an 80% glycemic control rating . if control is suboptimal at the maximum dose , the patient is switched to insulin . the literature describes the failure rate of glyburide to achieve euglycemia to be in the range of 1540% ( 13 ) . we experience a much lower rate of 6% in our population , and we attribute this to the fact our cohort has a much lower starting fbg value than is typical in relevant research studies . additionally , our glyburide cohort has experienced no significant adverse neonatal outcomes ; we have had no documented admissions to the inpatient pediatric department for neonatal hypoglycemic episodes . however , our overall cohort on glyburide is relatively small , and these outcomes are not sufficiently powered to be statistically significant . metformin was originally derived from an herbal folk remedy using the french lilac plant and was found in 1929 to lower blood glucose in rabbits . it did not become available in europe until 1958 and did not receive fda approval for type 2 diabetes treatment until 1994 . metformin has been shown to be comparable to insulin in achieving glycemic control in pregnancy ( 7 ) . it can be used in the treatment of gdm as monotherapy or in conjunction with insulin . metformin is associated with less maternal weight gain and hypoglycemia than glyburide ( 12 ) . it has been shown to have a failure rate of 1046% in achieving glycemic control in pregnant women with diabetes ( 7 ) . choosing candidates for metformin treatment of gdm maternal side effects of metformin , including nausea , vomiting , and diarrhea , are common ( 10 ) . adding a medication with this particular set of side effects to a pregnancy state can be problematic from the standpoint of patient satisfaction and may limit adherence to the care plan . side effects often can be diminished by starting women on a low - dose regimen of 500 mg twice daily for the first week of therapy and then titrating doses to an effect based on blood glucose data as therapy continues . in our cohort , metformin has not been tolerated as well as glyburide because of its gastrointestinal side effects . we tend not to use metformin as a first - line oral glycemic agent or as monotherapy because most patients are diagnosed with gdm in the third trimester of pregnancy , and optimal glycemic control must be achieved and maintained relatively quickly . instead , we view metformin as a useful tool for patients with a high degree of insulin resistance . for our gdm patients who are on high doses of insulin with frequent titrations for example , we have patients with mealtime doses of a fast - acting analog insulin approaching 80100 units , with matching basal insulin doses . we see significant improvement in insulin effect with the addition of metformin within 12 weeks in these patients , and this mirrors the experience reported elsewhere ( 12,17 ) . oral diabetes agents can be used successfully in pregnancy . about 25% of our patients with gdm use glyburide successfully to manage their blood glucose during pregnancy . all providers who care for the women with gdm should be able to determine ideal candidates for this medication ( 10 ) . fbg , weeks of gestation , and weight gain to date are the three main data points we consider when deciding whether glyburide may be a successful option for a given patient . because glyburide is a secretagogue , its success is dependent on the patient having a healthy and functioning pancreas that can respond well to the drug . if a patient s fbg is significantly elevated , providers should suspect that she may not have the physiological capacity to secrete the elevated amount of insulin required during pregnancy , and glyburide is unlikely to correct this problem ( 15 ) . glyburide also potentiates weight gain , so it is important to assess total weight gain to date and consider how long the patient may need to use glyburide ( 16 ) . recommendations in the literature state that glyburide can be used predictably when fbg is < 110 mg / dl after 25 weeks gestation ( 12 ) . we are more conservative in our patient selection , using glyburide for patients with an fbg 100 mg / dl in the third trimester who have not exceeded the recommended weight gain for their bmi based on the institute of medicine s guidelines . after 1 week of data gathering , if a patient s fbg is above target but < 100 mg / dl despite mnt , we typically start glyburide 2.5 mg at bedtime . if the postmeal glucose values are slightly above target but not severely elevated to > 200 mg / dl , we also would add an equivalent morning dose . we continue to discuss and encourage physical activity and mnt so the patient can bring the effects of all three components to bear on her glycemic management . we download glucose meters and evaluate meal diaries weekly , in person or remotely , titrating medication dosages accordingly to reach and maintain an 80% glycemic control rating . we titrate until the maximum glyburide dose of 20 mg / day is reached . if control is suboptimal at the maximum dose , the patient is switched to insulin . the literature describes the failure rate of glyburide to achieve euglycemia to be in the range of 1540% ( 13 ) . we experience a much lower rate of 6% in our population , and we attribute this to the fact our cohort has a much lower starting fbg value than is typical in relevant research studies . additionally , our glyburide cohort has experienced no significant adverse neonatal outcomes ; we have had no documented admissions to the inpatient pediatric department for neonatal hypoglycemic episodes . however , our overall cohort on glyburide is relatively small , and these outcomes are not sufficiently powered to be statistically significant . metformin was originally derived from an herbal folk remedy using the french lilac plant and was found in 1929 to lower blood glucose in rabbits . it did not become available in europe until 1958 and did not receive fda approval for type 2 diabetes treatment until 1994 . metformin has been shown to be comparable to insulin in achieving glycemic control in pregnancy ( 7 ) . it can be used in the treatment of gdm as monotherapy or in conjunction with insulin . metformin is associated with less maternal weight gain and hypoglycemia than glyburide ( 12 ) . it has been shown to have a failure rate of 1046% in achieving glycemic control in pregnant women with diabetes ( 7 ) . choosing candidates for metformin treatment of gdm maternal side effects of metformin , including nausea , vomiting , and diarrhea , are common ( 10 ) . adding a medication with this particular set of side effects to a pregnancy state can be problematic from the standpoint of patient satisfaction and may limit adherence to the care plan . side effects often can be diminished by starting women on a low - dose regimen of 500 mg twice daily for the first week of therapy and then titrating doses to an effect based on blood glucose data as therapy continues . in our cohort , metformin has not been tolerated as well as glyburide because of its gastrointestinal side effects . we tend not to use metformin as a first - line oral glycemic agent or as monotherapy because most patients are diagnosed with gdm in the third trimester of pregnancy , and optimal glycemic control must be achieved and maintained relatively quickly . instead , we view metformin as a useful tool for patients with a high degree of insulin resistance . for our gdm patients who are on high doses of insulin with frequent titrations for example , we have patients with mealtime doses of a fast - acting analog insulin approaching 80100 units , with matching basal insulin doses . we see significant improvement in insulin effect with the addition of metformin within 12 weeks in these patients , and this mirrors the experience reported elsewhere ( 12,17 ) . clinicians need to have a clear understanding of selection criteria for appropriate candidates for these treatment options . because debate continues about the best use of these agents in gdm management , real - life successes of high - volume programs that achieve positive outcomes with these agents can serve as examples that can be extrapolated to other programs and clinics .

in brief the oral agents glyburide and metformin are both recommended by many professional societies for the treatment of gestational diabetes mellitus ( gdm ) . both therapeutic modalities have published safety and efficacy data , but there remains much debate among experts . providers need a clear treatment plan for gdm based on a predictable level of clinical success in obtaining treatment goals . the proper selection of ideal candidates is paramount in achieving clinical success with the use of these medications in the treatment of gdm . this article presents clinical strategies for using oral agents in the management of gdm based on a pragmatic approach taken in a group of rural native american women .

it is important to maintain the validity of historical control data for assessment of toxicities , especially carcinogenicity . in carcinogenicity studies for novel pharmaceuticals and chemicals , peto s test is commonly employed as one of the tools of statistical analysis for evaluation of the carcinogenicity of test chemicals . in such a statistical analysis for carcinogenicity , the types of tumors observed should be categorized as common or rare tumors based on the incidence from the historical control data in the test facility . gotemba laboratory , bozo research center inc . ( gotemba , shizuoka , japan ) , has used fischer 344 rats for carcinogenicity studies since the 1990s , as well as other major strains including sprague - dawley ( sd ) and wistar rats . the historical control data for common tumors in f344 rats in our facility were reported previously . in the present report , we update the data from the last 5 years and compare them with previous data to examine the transition of tumor incidences over the years . data were newly collected from the control groups of 4 carcinogenicity studies using f344 rats that were started between 2005 and 2009 ( terminally sacrificed between 2007 and 2011 ) at gotemba laboratory , bozo research center inc . ( table 1table 1 . outline of the studies ) . in each carcinogenicity study , male and female specific pathogen - free ( spf ) rats of the fischer f344 strain , f344/ducrlcrlj , were obtained from atsugi breeding center , charles river laboratories japan , inc . the animals were 4 or 5 weeks old on arrival and used at 6 weeks of age after 1 or 2 weeks of quarantine / acclimatization . all animals were housed in animal rooms in an spf rodent barrier facility with periodic microbiological monitoring . animals rooms were maintained at a temperature of 23 3c with a relative humidity of 50 20% , air ventilation at 10 to 17 times per hour and 12-hour illumination ( 07:00 to 19:00 ) . male and female rats were housed individually in bracket - type stainless steel wire mesh cages ( w254d350h170 mm ) . the animals were allowed free access to powdered diet ( radiation sterilized crf-1 , oriental yeast co. , ltd . , each study was conducted in compliance with laws and guidelines concerning animal welfare as follows ; the law for the humane treatment and management of animals ( law no . 105 ) , the standards relating to the care and management of laboratory animals and relief of pain ( notification no . 88 of the ministry of the environment , japan ) , guidelines for proper conduct of animal experiments ( science council of japan ) and the guide for animal care and use of our facility . animals were inspected at least twice daily for gross abnormalities or mortality and given a detailed physical examination weekly . the animals in gavage studies were also handled at the daily oral gavage administration . body weights and food consumption were recorded at least once each week for the first 13 weeks and at least once every 4 weeks thereafter until the end of the study . all animals , including dead or moribund animals , were subjected to detailed necropsy . all gross lesions were recorded , and all organs and tissues of all animals were taken for routine histopathological examination . histopathological peer review was conducted by an eminent veterinary pathologist ( dacvp ) in all studies shown in table 1 except for study a. before the collection of control data , all neoplastic and preneoplastic lesions were reviewed by one pathologist in order to ensure consistency of the diagnostic criteria . first , in - house historical control data for the incidences of all tumors were collected ( data not shown ) , and then the tumors showing incidences of more than 5% in either the present or previous historical data were listed ( tables 2 and 3table 2 . comparison of tumor incidence in male fischer 344 rats ) . for the incidence ( percentage ) of each tumor , statistical analysis was performed with the analysis of variance ( anova ) followed by the bonferroni t - test among the 3 periods ( 19901999 , 20002004 and 20052009 ) . data were newly collected from the control groups of 4 carcinogenicity studies using f344 rats that were started between 2005 and 2009 ( terminally sacrificed between 2007 and 2011 ) at gotemba laboratory , bozo research center inc . ( table 1table 1 . outline of the studies ) . in each carcinogenicity study , male and female specific pathogen - free ( spf ) rats of the fischer f344 strain , f344/ducrlcrlj , were obtained from atsugi breeding center , charles river laboratories japan , inc . the animals were 4 or 5 weeks old on arrival and used at 6 weeks of age after 1 or 2 weeks of quarantine / acclimatization . all animals were housed in animal rooms in an spf rodent barrier facility with periodic microbiological monitoring . animals rooms were maintained at a temperature of 23 3c with a relative humidity of 50 20% , air ventilation at 10 to 17 times per hour and 12-hour illumination ( 07:00 to 19:00 ) . male and female rats were housed individually in bracket - type stainless steel wire mesh cages ( w254d350h170 mm ) . the animals were allowed free access to powdered diet ( radiation sterilized crf-1 , oriental yeast co. , ltd . , each study was conducted in compliance with laws and guidelines concerning animal welfare as follows ; the law for the humane treatment and management of animals ( law no . 105 ) , the standards relating to the care and management of laboratory animals and relief of pain ( notification no . 88 of the ministry of the environment , japan ) , guidelines for proper conduct of animal experiments ( science council of japan ) and the guide for animal care and use of our facility . animals were inspected at least twice daily for gross abnormalities or mortality and given a detailed physical examination weekly . the animals in gavage studies were also handled at the daily oral gavage administration . body weights and food consumption were recorded at least once each week for the first 13 weeks and at least once every 4 weeks thereafter until the end of the study . all animals , including dead or moribund animals , were subjected to detailed necropsy . all gross lesions were recorded , and all organs and tissues of all animals were taken for routine histopathological examination . histopathological peer review was conducted by an eminent veterinary pathologist ( dacvp ) in all studies shown in table 1 except for study a. before the collection of control data , all neoplastic and preneoplastic lesions were reviewed by one pathologist in order to ensure consistency of the diagnostic criteria . first , in - house historical control data for the incidences of all tumors were collected ( data not shown ) , and then the tumors showing incidences of more than 5% in either the present or previous historical data were listed ( tables 2 and 3table 2 . comparison of tumor incidence in male fischer 344 rats ) . for the incidence ( percentage ) of each tumor , statistical analysis was performed with the analysis of variance ( anova ) followed by the bonferroni t - test among the 3 periods ( 19901999 , 20002004 and 20052009 ) . the tumors with incidences of more than 5% in the past and present data are indicated in table 2 ( males ) and table 3table 3 . the two left columns are our previous data and the right column is the present data . the incidences of c - cell adenoma in the thyroid were 17.4% and 20.1% for males and 11.5% and 11.8% for females in 19901999 and 20002004 , respectively , and 30.8% for males and 24.4% for females in 20052009 , and the incidence tended to increase in both sexes in recent years . the incidence of pancreatic islet cell adenoma in males was 10.5% in 19901999 , 17.1% in 20002004 and 20.5% in 20052009 . the incidence of uterine adenocarcinoma was 3.3% in 19901999 , 12.0% in 20002004 and 13.5% in 20052009 . thus the incidences of pancreatic islet cell adenoma in males and uterine adenocarcinoma tended to increase from around 2000 as stated in the previous report . in the historical control data that were published between 1987 and 2011 , the incidences of c - cell adenoma in the thyroid of f344 rats were 9.2 to 15.42% in males and 6.7 to 12.14% in females . it was reported that c - cell tumor developed with a high incidence in wistar and f344 rats but that it developed with a low incidence in sd rats . meanwhile , the incidence of c - cell tumor in female harlan sd rats ( 25.43% ) in the national toxicology program ( ntp ) was far higher than that in the historical control data in female charles river sd rats ( 7.21% ) and the above data from f344 rats . therefore , it seems that there are differences in tumor incidence between the substrains of suppliers . the cause of the increased incidence in c - cell adenoma in the present survey was unclear . calcium and vitamin d content in the diet was not responsible because identical formula diets were used consistently in our facility . chronic progressive nephropathy ( cpn ) , a common age - related lesion in rats , is known to induce secondary hyperparathyroidism . however , the incidences of cpn in 20052009 , which were graded as moderate / severe , were 6% in males and 2% in females , and they were comparable to or lower than those in our previous data . therefore , a relationship between cpn and increased c - cell adenoma could be ruled out . our series of surveys demonstrated that the historical control data for spontaneous tumors fluctuated over the years . in our survey , all the rats came from the same breeder , and were housed under the same laboratory conditions . the fluctuations of tumor incidences might be caused by some sort of factor from animals other than environmental factors , although genetic drift is rarer in the inbred f344 strain than in the outbred wistar and sd strains . we hope that our historical control data will help in the evaluation of carcinogenicity studies at other facilities .

historical control data of tumor incidence were collected from the control groups ( 215 animals of each sex ) in four recent carcinogenicity studies that were started between 2005 to 2009 ( terminally sacrificed between 2007 and 2011 ) at bozo research center inc . ( gotemba , shizuoka , japan ) using fischer 344 rats ( f344/ducrlcrlj ) . these data were compared to the previous historical control data ( from 1990 to 2004 , previously reported ) in the same facility . in the results , the incidence of c - cell adenoma in the thyroid tended to increase in both sexes in recent years ( 30.8% for males and 24.4% for females in 2005 - 2009 ) as compared with the previous data ( 17.4% and 20.1% for males and 11.5% and 11.8% for females in 19901999 and 20002004 , respectively ) . in addition , the incidences of pancreatic islet cell adenoma in males and uterine adenocarcinoma tended to increase from around 2000 and remained high in recent years ( incidences of islet cell adenoma in males of 10.5% , 17.1% and 20.5% in 19901999 , 20002004 and 20052009 ; incidences of uterine adenocarcinoma of 3.3% , 12.0% and 13.5% in 19901999 , 20002004 and 20052009 , respectively ) . there was no apparent difference in the incidence of other tumors .

worldwide , tumours account for the majority of cases of large bowel obstruction with diverticular disease and volvulus accounting for the remainder . volvulus commonly affects the sigmoid , caecum and transverse colon in the decreasing order of frequency with caecal volvulus accounting for < 1% of causes of large bowel obstruction . additionally , the bascule subtype accounts for < 10% of cases presenting with caecal volvulus . we present the case of a 58-year - old patient who presented with symptoms of intestinal obstruction and had characteristic radiological findings of a caecal volvulus a 58-year - old female with a past medical history of a large intrathoracic hiatus hernia presented to her general practitioner and was subsequently referred to our surgical department with symptoms of sudden onset severe epigastric pain associated with vomiting and abdominal distension . her abdomen was generally tender , maximally in the epigastric region , although she was not peritonitic . the admission erect chest radiograph showed a large hiatus hernia and an elevated right hemidiaphragm with a large loop of distended bowel ( fig . 1 ) . subsequent computed tomography ( ct ) scan demonstrated an almost completely intrathoracic stomach with a degree of volvulus , and the liver medially displaced by a loop of large bowel felt to be caecum ( fig . 2 ) . since the patient remained otherwise well , bidirectional endoscopy was performed , and given that a volvulus point could not be identified and the ileocaecal junction was not identified , contrast studies were requested ( figs 35 ) which demonstrated an incomplete obstruction caused by a volved caecum rotated anteriorly and cephalad . figure 1:erect chest radiograph , showing a large hiatus hernia and large loop of bowel elevating the right hemidiaphragm . figure 2:ct coronal section demonstrating caecum medially displacing the liver and causing an upward pressure on the right hemidiaphragm . figure 3:a large bowel contrast study showing the flow of contrast from the collapsed transverse colon into the dilated , upwardly displaced caecum . figure 4:coronal section of contrast - enhanced ct demonstrating contrast filling upwardly displaced caecum . figure 5:axial section of contrast - enhanced ct demonstrating whirl sign at the point of volvulus . erect chest radiograph , showing a large hiatus hernia and large loop of bowel elevating the right hemidiaphragm . ct coronal section demonstrating caecum medially displacing the liver and causing an upward pressure on the right hemidiaphragm . a large bowel contrast study showing the flow of contrast from the collapsed transverse colon into the dilated , upwardly displaced caecum after the contrast study partial resolution of symptoms occurred but given the development of free fluid in her contrast ct scan , the decision was taken to manage her surgically . a midline laparotomy was performed , with the finding of a freely mobile , grossly distended caecum flipped anteriorly over the ascending colon as demonstrated on her ct scan ( fig . 6 ) . additionally , there was no evidence of a gastric volvulus ( suggesting partial twisting ) and since her stomach was completely intra - abdominal , there was no need to address her hiatus hernia at that point in time . the patient was admitted to the high dependency unit post - operatively , made a good recovery and was discharged home within a week of surgery . caecal volvulus accounts for 1% of all causes of large bowel obstruction [ 1 , 2 ] . the mechanism of caecal volvulus has been well documented and can be explained by the presence of an excessively mobile caecum or incomplete fixation of the ascending colon to the retroperitoneum during embryogenesis . additionally , caecal volvulus can be described as organoaxial ( true caecal or caecocolic volvulus ) or mesenteroaxial ( caecal bascule ) . the latter describes the folding of the caecum anteriorly over the ascending colon and accounts for 10% of all caecal volvulus , while the former describes the twisting of the terminal ileum , caecum and ascending colon . interestingly , our patient had an incidental finding of a gastric volvulus on imaging , the aetiology most likely related to her large hiatus hernia , a known risk factor for gastric volvulus . the embryological theory as highlighted above for volvuli affecting the large bowel may also be applicable to the stomach . a review of 561 patients with caecal volvulus found that they commonly presented with symptoms of bowel obstruction abdominal pain , abdominal distension , constipation , nausea and vomiting . physical findings included abdominal distension , hyperperistalsis , peritoneal signs , abdominal mass and absent bowel sounds . it is reasonable to assume that patients with the bascule subtype may have intermittent subacute obstruction due to the flopping of the caecum back into its anatomical position . additionally , this subtype is less likely to strangulate as the mesentery is not frequently twisted when compared with the organoaxial subtype . risk factors commonly described for caecal volvulus include previous abdominal surgery , high fibre intake , chronic constipation and distal obstruction [ 57 ] . . found that ct findings of whirl , ileocaecal twist , transition points , x marks the spot and split wall have high specificity for caecal volvulus . additionally , they found that the absence of distal colonic decompression made the diagnosis of caecal volvulus unlikely . diagnostic confusion may exist between sigmoid and caecal volvulus ; however , the location of the mesenteric twist ( ct whirl sign ) is highly accurate in distinguishing the two . swirling strands of soft tissue attenuation within a background of fat attenuation and gives the appearance of a hurricane on a map. barium enema has been historically used to confirm the presence of a volvulus , assess the distal colon and may also have a therapeutic effect . factors such as patient co - morbidities and the viability of the bowel should be taken into account when managing caecal volvulus . the authors agree that right hemicolectomy is associated with the lowest recurrence and complication rates compared with detorsion alone , detorsion and caecopexy and caecostomy . additional options when faced with non - viable bowel and where primary anastomosis is not suitable include ileostomy and mucus fistula . minimally invasive procedures may play a role in the management of patients without perforation or gangrenous bowel and provides a reasonable treatment option for this condition .

caecal volvulus is a rare cause of intestinal obstruction , with the bascule subtype accounting for < 10% of all cases of caecal volvulus . it is associated with significant morbidity and mortality if left undiagnosed . we present the case of a 58-year - old female who presented to our surgical department with symptoms of intestinal obstruction . she had various radiological investigations , which supported the diagnosis of a caecal volvulus of the bascule subtype . she was subsequently managed surgically and had a right hemicolectomy and ileocolic anastomosis . her recovery was uneventful and she was discharged within 1 week of having her operation . fortunately , caecal volvulus of the bascule subtype is rarely encountered ; however , clinicians need to be aware of its presentation and subsequent management options so that clinical outcomes are improved .

the traditional management of the gastrointestinal bleeding due to this etiology has been conservative management with blood transfusion , balloon tamponade of varices , and drugs to lower splanchnic pressure followed by sclerotherapy or banding . in refractory cases , splenectomy and devascularization in emergency situation or shunt surgery in elective situation however , when this situation presents in early infancy with gastrointestinal bleeding and hypersplenism , the management option is complicated by lack of established protocols . further , it is known that the gastrointestinal bleed due to portal hypertension is severe and repetitive , particularly in infancy . a 4-month - old male child was referred to us with repeated episodes of melena and progressive abdominal distension . the baby had umbilical sepsis at 3 week , treated with intravenous antibiotics for 7 days . at 2 months of age , baby developed progressive abdominal distension , associated with a low grade fever , and repeated bouts of melena . during hospitalization in a remote district hospital , he was found to have low hemoglobin ( 5 g / dl ) , leukopenia , and thrombocytopenia requiring blood transfusion . a second admission for melena prompted the physician treating the baby to refer the baby for further investigation and management . at admission blood investigations revealed hemoglobin levels of 6.5 g / dl , total leukocyte count of 2,800/mm and a platelet count of 39,000/mm . a complete coagulation profile done to rule out any congenital coagulation defects was found to be normal . the endoscopic examination revealed grade 4 esophageal varices with daughter varices , with a normal stomach and duodenum . ultrasonography ( usg ) [ figure 1 ] , contrast computed tomography ( ct ) scan , magnetic resonance imaging ( mri ) abdomen [ figures 2 and 3 ] and endoscopy were done in another hospital before admission to our center . the diagnosis at this stage was established as extrahepatic portal venous obstruction ( ehpvo ) leading to portal hypertension and esophagogastric varices with hypersplenism . the parents were offered medical or surgical management for the condition highlighting the outcome of both approaches . since they were from a remote district with no local medical facility and baby was small , they opted for surgical management . ultrasonography abdomen at the level of porta , portal vein not visualized , multiple collaterals seen magnetic resonance imaging axial section at the level of porta hepatis showing absence of portal vein mr angiography coronal plane showing collaterals along inferior mesenteric vein and splenomegaly on midline exploration , he was found to have ascites , large congested spleen . splenic vein was identified by lifting the transverse colon cranially so that the pancreas got rotated along the whole body and tail . pancreaticosplenic vein disconnection was done with individual ligation of tributaries and a good segment of splenic vein dissected for side - to - side anastomosis with left renal vein . the rest of the surgery was performed as the original description of mitra et al . . it was possible to construct a 1 cm long patent wide anastomosis despite the splenic vein being 5 mm across . the spleen was visibly changing on the operating table itself after the shunt was allowed to function . intravenous anticoagulation was started in the perioperative period and continued till the 10 postoperative day . , the hematological parameters steadily kept improving and spleen gradually regressed to half its size . the platelet count had reached over 100,000/mm , total leukocyte count had risen to 6,400/mm and hemoglobin was 10.5 g / dl . doppler evaluation was done on the 10 postoperative day to confirm shunt patency . at 6 months follow - up , spleen is just palpable with no features of hypersplenism and esophageal varices have regressed . most indian studies have highlighted ehpvo to be the major cause of portal hypertension and the commonest cause of major upper gastrointestinal bleeding in children . the cause of ehpvo is unknown in majority of cases , but congenital malformation of the portal vein or acquired thrombosis following umbilical sepsis , umbilical vein catheterization , and pyelephlebitis following intestinal infection are some of the risk factors . the management of acute hemetemesis in portal hypertension consists of resuscitation with blood and endoscopic banding and/or sclerotherapy , which controls the bleeding in 95% . these nonsurgical procedures , that is , endoscopic banding and sclerotherapy in pediatric age group requires state of art instruments and expertise which is not universally available and is followed by significant incidence of rebleed . these episodes are well - tolerated in the majority ; however , mortality rates up to 31% have been reported . there is no universally acceptable guideline on the management in case of recurrence of such bleeds and furthermore , there is controversy regarding best therapeutic option with endoscopic management on one side and surgery with or without splenectomy on the other . the timing and indication to give up the medical management and opt for shunt surgery is not clear with most of the series on shunt surgery reporting on average three to four bleeding episodes before the patients bismuth et al . , had suggested surgical option even with one episode of variceal bleeding especially in infants as there are high chances of rebleeding in this age group . the longest follow - up study following shunt surgery has reported 5 and 10 year survival rates greater than 95% in children with negligible rebleeding rates . endoscopic band ligation requires expertise and these patients need to be followed - up much longer to record the incidence of rebleed from ectopic varices ( fundal , duodenal , and ileal varices ) and reappearance of new varices . surgical management of ehpvo may be nonselective shunts or selective shunts , partial shunts , and the more recently introduced rex shunt . nonselective shunts enable complete decompression of portal system by diverting total portal blood flow away from liver . selective shunts divert blood of gastroesophageal - splenic segment and maintain blood flow in mesenteric segment which enables portal decompression with maintenance of hepatopetal portal perfusion , mesenteric venous pressure , and hepatotropic factors . mitra et al . , published the first major report of successful treatment in portal hypertension patients by side - to - side lienorenal shunt . the youngest baby reported in literature treated by a shunt surgery was a 7-month - old . the risk and complications arising from thrombosis can be more catastrophic in a rex shunt than the mitra 's lienorenal shunt as the venous drainage of entire small bowel is at risk in the rex shunt as opposed to mitra 's shunt where only the ipsilateral kidney is at risk . rex shunt had demonstrated increase in growth spurt thought to be due to increased blood supply of liver and probable release of growth factors and insulin like growth factors . however , similar improvement in somatic growth after side to side lieno - renal shunt for portal hypertension has been reported in two separate prospective studies from chandigarh . endoscopic treatment has not been able to demonstrate growth spurt in babies and children seen after shunt surgery and requires babies and children having enough blood volume to withstand bleed , proximity to facility for blood transfusion , and center where rebleeding episode can be managed . he had serious and recurrent gastrointestinal bleeding leading to need for several admission and blood transfusion . in view of the life - threatening risk of the condition , we had to offer treatment which has been well - tolerated by the baby with significant improvement . the shunt surgery for portal hypertension essentially depends on the presence of a shuntable vein which is defined by the size across and tortuosity of the vein allowing downward mobilization towards the renal vein . in the technique described by mitra , since it is a side to side shunt it can be done in small caliber splenic vein in small babies with the dual advantage of preserving the spleen . mitra shunt ( spleen preserving side - to - side lienorenal shunt ) is an ideal option for the surgical management of symptomatic portal hypertension in early infancy .

extrahepatic portal vein obstruction ( ehpvo ) is the commonest cause of portal hypertension presenting with gastrointestinal bleeding and splenomegaly . medical management of this condition may provide relief , but involves repeated hospital visits and endoscopic procedures . surgery is an effective curative solution by lowering portal venous pressure with effective shunting of venous blood from splanchnic to systemic circulation . shunt surgery for such a small baby has not been previously reported and splenectomy has its own problems . similarly , banding or sclerotherapy in such babies is not without risk . among the various shunt options , mitra shunt ( spleen preserving , side - to - side lienorenal shunt ) , developed and standardized in our own country , stands out as the most optimum surgical treatment for ehpvo in early infancy . we report a 4-month - old baby , youngest recipient of mitra shunt reported in literature with successful outcome .

this study was conducted in accordance with a protocol approved by an institutional animal care and use committee of the national institutes of health . all laboratory work with potentially infectious materials was conducted in a biosafety level facility at the rocky mountain laboratories ( division of intramural research / national institute of allergy and infectious diseases / national institutes of health ) . three cynomologus macaques were vaccinated with 1 dose of 10 pfu of vsvg / lasvgpc , a live - attenuated , recombinant viral vaccine in which the vsv surface glycoprotein has been replaced with those of lasv , by intramuscular injection as described ( 4 ) . another age - matched control animal was vaccinated with an irrelevant vsv - based vaccine ( vsvg / andvgpc ) ( 5 ) . at 28 days postvaccination , the 4 nhps were challenged with a lethal dose of lasv ( 10 50% tissue culture infectious doses [ tcid50s ] ) ( 9 ) . the control animal showed signs of lassa fever 710 days postinoculation and was euthanized 13 days postchallenge because of severity of disease . classic indicators of lassa fever , including decreased total protein and albumin ; increased serum levels of alanine aminotransferase , aspartate aminotransferase , amylase , blood urea nitrogen , and alkaline phosphatase ; and hematologic abnormalities , including thrombocytopenia and lymphopenia , were apparent in this animal . virus isolation conducted for select tissue samples showed lasv titers of 57 log10 tcid50/g of tissue ; blood samples collected on day 10 and at the time of euthanasia ( 5 and 6.25 log10 tcid50/ml , respectively ) showed viremia . in contrast , the 3 animals vaccinated with vsvg / lasvgpc resisted lethal lasv challenge and did not demonstrate any clinical signs of disease or any hematologic or biochemical indicators of lasv infection . at no point in the study was virus found in blood samples collected regularly from these 3 animals , even when tested by sensitive reverse transcription pcrs . an elisa with serum samples collected 45 days postchallenge demonstrated equivocal antibody titers ( 100 ) against a recombinant lasv nucleocapsid protein in 1 nhp . the other 2 animals did not show seroconversion , which suggested that vaccination caused nearly sterile immunity against lasv ( table ) . * vsv , vesicular stomatitis virus ; vhf , viral hemorrhagic fever ; lasv , lassa virus ; gpc , glycoprotein precursor ; np , nucleocapsid protein ; ebov , ebola virus ; gp , glycoprotein ; vp40 viral protein 40 ; nd , not determined . titers are indicated as reciprocal endpoint dilutions from elisas for recombinant antigens ( lasv np , ebov gp , and vp40 ) , or whole virus preparations ( vsv ) . approximately 90 days after the original vaccination with vsvg / lasvgpc , the 3 nhps were vaccinated with a single dose of 10 pfu of vsvg / ebovgp by intramuscular injection as described ( 3 ) . an additional nhp was vaccinated with a control vaccine as outlined above and served as the inoculation control . at the time of vaccination , the 3 macaques had a robust vsv - specific antibody response with titers of 25,600 , as determined by a whole virus elisa ( table ) . despite this finding , the 3 animals that received the vsv - based ebov vaccine mounted an efficient response to the ebov glycoprotein ( table ) and were completely protected when challenged 28 days later with a lethal dose of ebov ( 10 pfu ) ( 10 ) . hematologic and serum biochemistry values remained constant throughout the study , and virus was not found in blood samples collected regularly and tested by using real - time reverse transcription pcr . in contrast , severe ebov hemorrhagic fever developed in the control animal , which was characterized by increased serum concentrations of alkaline phosphatase , aspartate aminotransferase and alanine aminotransferase ; thrombocytopenia ; and viremia ( 7 log10 tcid50/ml whole blood ) beginning 36 days postchallenge . this animal was euthanized 7 days postchallenge , and titration of selected tissue samples showed ebov titers of > 9 log10 tcid50/g tissue . an elisa conducted at the conclusion of the study ( 42 days post ebov challenge ) showed increased antibody responses to vsv ( titers = 102,400 ) and seroconversion to the ebov viral protein 40 antigen ( titers 1,6006,400 ) in the 3 surviving nhps ( table ) , which is consistent with published results ( 10 ) . because of the remote locations where vhf agents are present , an overall shortage of health care professionals and clinics in these locations , and mobility of human populations , any vaccine against these pathogens would ideally need to elicit a protective immune response after a single vaccination . for this reason , replication - competent viral vectors are considered leading vhf vaccine candidates . as the vsvg / ebovgp vaccine heads toward clinical trials , it is necessary to clarify the potential limitations of using the vsv platform against multiple vhf agents . a major drawback for many viral vector platforms is preexisting immunity against the vector itself , which can decrease or nullify the essential protective immune response , which results in vaccine failure . design of the vsv - based vaccines , which encode and express glycoproteins from various pathogens without its own glycoprotein ( 11,12 ) , suggest that preexisting immunity would not influence protective efficacy of individual vaccinations ( 12 ) . results of this study demonstrate that multiple vsv vaccines can be used in a population without any deleterious effect on overall protective efficacy .

we demonstrated that previous vaccination with a vesicular stomatitis virus ( vsv)based lassa virus vaccine does not alter protective efficacy of subsequent vaccination with a vsv - based ebola virus vaccine . these findings demonstrate the utility of vsv - based vaccines against divergent viral pathogens , even when preexisting immunity to the vaccine vector is present .

laparoscopic nissen fundoplication is an established operative procedure with a low morbidity and mortality for patients with symptomatic hiatus hernias . however , a rare but a serious life - threatening complication : para - oesophageal hernia , can occur following an uneventful operation . we describe a case here that was initially a diagnostic conundrum , had a successful outcome following an early corrective surgery . a 52-year - old fit and healthy gentleman with no previous cardiovascular or respiratory co - morbidity was admitted for an elective laparoscopic nissen fundoplication . at operation , a large hiatal defect of 5 cm and a moderate size sac was found ( fig 1 ) that was mobilised and adhesions divided to obtain 3 cm of oesophageal length in the abdomen . following division of the upper short gastric vessels , a posterior hiatal repair with seven interrupted ethibond stitches and a loose 360 degree full wrap with the fundus of the stomach with three interrupted ethibond stitches were performed . wrap was further fixed to the diaphragm and right crus with another three ethibond stitches ( fig . 2 ) . hiatus hernia with portion of stomach seen going into the chest crural repair with fundoplication during the sac dissection , the patient developed tension pneumothorax due to an iatrogenic tear of the right pleura requiring a chest drain . he was closely observed in the high dependency unit with pain relief through pca ( morphine ) and intravenous paracetamol and oral feeding commenced post - operatively . arterial blood gas showed po2 of 10.7 and pco2 of 6.54 on 60% oxygen and an early post - operative chest x - ray revealed bilateral pulmonary infiltration ( fig . non - cardiogenic pulmonary oedema was suspected and the patient was started on 5mmhg pressure cpap . early post - op chest x - ray showing patchy shadowing/ consolidation over the left side of chest on day 1 , patient complained of a central retro - sternal chest pain . in the absence of air leak , the right sided chest drain was removed and the pca was increased to 1.5mcg boluses of morphine . auscultation consistently showed decreased air - entry in the lung bases . on day 3 , a repeat chest x - ray showed a left lower lobe collapse above the gastric bubble in the mid zone of the chest ( fig . ctpa done on the same day to exclude pulmonary embolism confirmed a para - oesophageal hernia that was pushing against the left lung base . ultrasound scan of the left chest also showed movement of the diaphragm below the gastric bubble . chest x - ray on 3rd post - op day showing prominent left sided collapse/ consolidation post - op ct - scan demonstrating the left sided pleural effusion with collapse /consolidation & patchy opacification on the right side . at laparotomy , 700ml of blood - stained fluid and a large paraoesophageal hernia involving the body of the stomach with vascular compromise that had slipped through the potential space between the wrap and the left crus into the left hemi - thorax created by extensive hiatal dissection was found . hiatal repair and the 360 degree wrap fixed to the diaphragm and right crus were all completely intact . reduction of the stomach restored the circulation and a gastropexy was done to the anterior abdominal wall with five interrupted ethibond stitches . post - operatively , the patient suffered from acute lung injury requiring prolonged intubation and ventilation including a tracheostomy . he made a successful albeit a slow recovery and was discharged from the intensive care unit after 21 days . post - operative para - oesophageal hernia is a recognised but a rare and serious complication of laparoscopic nissen fundoplication being reported in 0.8 - 6.7% cases ( 1 - 3 ) . reduced postoperative pain from adequate analgesia , early oral intake and return to activity raising the intra - abdominal pressure can lead to the development of early para - oesophageal hernias before true hiatal scar tissue formation . there is literature evidence of higher incidence amongst surgeons leaving the hiatus open compared to those closing it ( 5 ) . intra - operative left sided pneumothorax and the use of cpap in the early post operative period has also been associated with the development of post - operative paraoesophageal hernias ( 6 ) . posterior hiatal cruroplasty , avoidance of postoperative retching and vomiting through regular use of prophylactic antiemetics reduces its frequency ( 7 ) . however , they can be asymptomatic or can present with postprandial symptoms of gastric compression that includes chest pain and breathlessness ( 8) . prompt diagnosis is essential to prevent gastric necrosis , perforation , bleeding and even death ( 9 ) . in patients with diagnostic dilemmas or suspicion for paraoesophageal hernias with previous laparoscopic nissen fundoplication should undergo a contrast computerised tomography of the chest and abdomen or a barium swallow ( 2 ) . in our case , the operation was technically challenging due to the size of the hernia and the hiatal defect . however , the hernial sac was completely mobilised and a thorough posterior crural hiatal repair followed by a 360 degree wrap was performed . the wrap was further fixed to the diaphragm and right crus ; thus closing any possible hiatal free space . the pneumothorax during the procedure was again on the right side settling uneventfully within 24 hours of the operation . the possible explanation for the development of this acute large paraoesophageal hernia in our case could be the immediate feeding and the distension of the stomach that was caused by the use of high cpap post - operatively to maintain oxygenation : thus pushing the body of the distended stomach into the left chest through the dissected hiatus . the persistent central retro - sternal chest pain with raised troponin and bilateral pulmonary infiltrations added confusion . there is literature evidence that varied clinical presentation can make diagnosis difficultand can even elude experienced radiologists as was evident here . revision surgery can be technically challenging and is associated with higher morbidity ( 10 ) . our patient suffered an acute lung injury following the second surgery and required prolonged intubation , active support and extended hospital stay . we present here such a case to remind us of the risk of non invasive ventilation in a post operative patient of laparoscopic nissen fundoplication that was initially a diagnostic challenge , but , had a successful outcome due to the vigilant approach and a prompt surgical intervention .

we describe a case of an acute paraoesophageal hernia in the early post - operative period following a laparoscopic nissen fundoplication . patient developed intraoperative tension pneumothorax requiring an immediate chest drain and subsequently needed respiratory support of a continuous positive airway pressure ( cpap ) ventilation . a short discussion of this rare but deleterious complication and the difficulty of making a prompt diagnosis are included as delayed revision surgery can be technically challenging with a poor outcome .

benign primary intramural tumors of the esophagus are rare and account for approximately 2% of all esophageal tumors . most of them are esophageal leiomyomas ; less frequent are schwannomas or malignant masses such as gastrointestinal stromal tumors ( gist ) . endoscopic ultrasound biopsy or frozen section biopsy during the operation does not differentiate the tumors . we report a case of benign esophageal schwannoma causing progressive dysphagia in a 37-year - old woman . a 37-year - old woman presented due to symptoms of chest pain during swallowing of solid food for 3 months . the physical examination was noncontributory . computed tomography of the chest showed a soft tissue mass in the lumen of the upper esophagus ( fig . endoscopic ultrasound identified the mass at 19 cm from the incisors , but the biopsy was nondiagnostic . computed tomography scan showing concentric soft tissue lesion surrounding the esophagus bronchoscopy and pulmonary function test of the patient were normal . the right chest was opened through a right anterolateral thoracotomy at the fifth intercostal space . the intramural tumor 3.5 3 3 cm was enucleated without erosion of the mucosa ( fig . the esophageal wall allowed primary closure of the muscular layers , and the native esophagus was preserved . enucleated esophageal schwannoma ( 3.5 3 3 cm ) histopathological examination of the tumor revealed spindle - shaped cells in a fasciculated and disarrayed architecture and nuclei in a palisading pattern ( fig . immunohistochemically the tumor was positive for s100p and gfap , and negative for cd34 , cd117 , sma , desmin and h - caldesmon ( fig . spindle - shaped cells in a fasciculated and disarrayed architecture and nuclei in a palisading pattern . a ) 40 , b ) 200 immunohistochemical studies revealed s100 protein positivity postoperative recovery was uneventful , and there has been no evidence of recurrence to date . esophageal schwannoma is uncommon and difficult to diagnose in preoperative investigations due to its similarity to other intramural esophageal tumors ( leiomyoma , gist , oesophageal cysts or cancer ) . these tumors more frequently develop in women and are often located in the upper and mid esophagus . malignant schwannoma has also been reported [ 1 , 2 ] . symptoms of this tumor include dysphagia , dyspnea [ 1 , 3 ] , chest pain , and hematemesis , and appear when the tumor increases in size . imaging studies ( positron emission tomography , computed tomography , and magnetic resonance imaging ) are useful for the confirmation of esophageal tumor [ 1 , 4 , 5 ] . endoscopic ultrasonography - guided fine needle aspiration biopsy is not always useful for diagnosis , as in our cases . the value of frozen section is limited , and it can lead to diagnostic pitfalls . final diagnosis is possible upon positive immunohistochemical studies for s-100 protein and negative staining for smooth muscle markers such as sma , cd34 , and cd117 . surgical excision of the tumor is the method of choice , because chemotherapy and radiotherapy are ineffective . the option of enucleation is recommended when : the tumor is well encapsulated , a clear margin is achievable , and there is sufficient redundant mucosa to close the defect . in our case enucleation with video - assisted thoracoscopic surgery ( vats ) is possible for small tumors ( 2 cm ) . for large tumors ( 8 cm ) with broad adjacent to the muscular layer and an extensive mucosal defect , esophagectomy with gastric pull - up is recommended [ 3 , 7 ] .

schwannomas of the esophagus are rare peripheral nerve tumors . a 37-year - old woman with dysphagia was found to have an intramural tumor of the upper esophagus . the lesion was revealed on computed tomography . endoscopic ultrasound biopsy was nondiagnostic . through right thoracotomy , the mass was enucleated from the wall of the esophagus . benign schwannoma was diagnosed only after immunological staining examination .

a true aneurysm of the inferior thyroid artery ( ita ) is extremely rare15 ) . despite its rarity , several authors have recommended aggressive management because the lesion has the potential to be highly lethal4 ) . surgical ligation and/or excision and endovascular embolization were reported as possible treatments for this rare disease6 ) . here , we present a case of ruptured ita aneurysm successfully treated with embolization . to the best our knowledge , this is the first report of parent arterial embolization using a single pushable coil for ita aneurysm . a 69-year - old woman was hospitalized in a stupor and was diagnosed with subarachnoid hemorrhage due to rupture of an anterior communicating artery aneurysm . during hospitalization , she developed pneumonia , which worsened and required endotracheal tube insertion , and eventually tracheostomy , despite nearly complete neurologic recovery . the bleeding was too abrupt and massive to be controlled , and the source could not be identified . temporary hemostasis was achieved with manual compression followed by meticulous packing of gauze and pad . neck computed tomography ( ct ) angiogram with three - dimensional reconstruction demonstrated a saccular aneurysm of the right ita ( fig . the patient was immediately prepared for endovascular intervention because the tentative hemostasis and poor general condition of the patient made surgical exploration risky . after groin site puncture , conventional angiography through the thyrocervical trunk ( tct ) revealed an ita aneurysm 8 mm in diameter ( fig . the right tct was superselected , and a microcatheter was placed adjacent to the aneurysm . a single pushable embolization coil ( 18s , 3/2 , tornado embolization microcoils soft , cook , bjaeverskov , denmark ) was inserted and placed in the parent artery immediately proximal to the aneurysm ( fig . the aneurysm was no longer visible on angiogram 10 minutes after insertion of the coil ( fig . 2c ) . follow - up ct three days after embolization evidenced the complete disappearance of the aneurysmal sac ( fig . . detailed history taking to investigate possible causes of the rare aneurysm did not reveal any history of previous neck surgery , percutaneous procedure , or trauma . follow - up angiography on the seventh postoperative day confirmed the absence of the aneurysmal sac . although ita aneurysm is the most common form of tct aneurysm , there have been fewer than 25 cases reported in the literature13 ) . among these , only four cases were treated by coil embolization alone4,5,9,10 ) . various clinical manifestations of these aneurysms have been reported , including palpable neck mass , hoarseness , dysphagia , respiratory distress , or evaluation of a possible thyroid nodule1,8,12,14 ) . ita aneurysms are widely considered to require aggressive management , because mortality has resulted from conservative management in all but one case4 ) . moreover , a report on the only patient who survived conservative management did not include follow - up data , and such treatment was not recommended . an abrupt death could result from hypovolemia due to excessive blood loss into soft tissues or the thorax , including the pleura and mediastinum , or respiratory distress due to airway compression by the hematoma itself . surgical ligation and/or excision , endovascular embolization , and a combination of these tactics have been reported as a treatment of ita aneurysm4,13 ) . among these methods , surgical ligation could be the most suitable , especially in cases of rupture , because the mass effect of the hematoma remains troublesome for airway maintenance after coil embolization . pop et al.13 ) reported a case of ruptured ita aneurysm treated with aneurysmal coil embolization followed by surgical excision . they suggested that embolization had the advantage of easy detection and embolization , while surgical exploration and excision was needed for hematoma evacuation to decompress the airway . surgery , however , also has the disadvantage of risks including recurrent laryngeal or phrenic nerve injury and wound site infection13 ) . in the present case , the aneurysm ruptured during blunt dissection , although it is unclear if the rupture was caused by direct contusion of the aneurysmal sac by hemostat forceps or tearing of previously adhesive aneurysmal sac to adjacent soft tissue by blunt dissection . sharp surgical tool or monopolar electrocautery that could incur an arterial injury was not used at the timing of event . however , there was no absolute evidence of a true aneurysm like pre - procedural image or pathologic specimen in this case . there were several reports about iatrogenic aneurysm near thyroid gland , following vascular catheterization2 ) , percutanous needle biopsy of adjacent organ8 ) and radiotherapy3 ) . there was also a case report of tracheostomy - related pseudoaneurysm that developed in superior thyroid artery11 ) . however , those authors described that it was a revision tracheostomy and they found densely fibrotic change at that site that may leaded blunt injury . moreover , in most cases of iatrogenic pseudoaneurysm , there were delayed intervals between traumatic events and aneurysmal developments , except in that case of penetrating injury . in this case , tornado , the single pushable coil that contains numerous fibrous hairs , completely ablated the vessel within several minutes with minimal mass effect . this method could be also beneficial even in a case of pseudoaneurysm that contains a fragile wall . mass effect from a hematoma was not a problem in this case due to prompt manual compression . selective angiography is the diagnostic modality of choice , particularly in emergency settings , because it can be promptly transformed into a therapeutic procedure . the author suggests that embolization of the parent artery using a pushable coil is a simple and effective treatment modality for ita aneurysm with rupture .

we present a unique experience of urgent parent arterial embolization for treatment of an aneurysm of the inferior thyroid artery ( ita ) that bled during tracheostomy . the event happened to a 69-year - old female patient with subarachnoid hemorrhage and hospital - acquired pneumonia that required tracheostomy . abrupt and massive bleeding developed during the procedure , and the source could not be identified . under manual compression , angiography revealed an 8-mm aneurysm that arose from the inferior thyroid artery . the superselected parent artery of the aneurysm was successfully occluded with a single pushable coil . the patient 's postoperative course was uneventful .

computed tomography ( ct ) of the lungs is an invaluable adjunct in the diagnostic work - up of lung disease . the normal lung has a characteristic pattern of x - ray attenuation , with each region 's attenuation ( in hounsfield units ) being determined by the average of the relative content of air ( most negative ) , fatty tissue , normal tissue , water ( zero ) , blood , and exogenous contrast ( most positive ) , excluding bone that comprises a part of the chest wall . the attenuation pattern is converted to a composite grayscale image corresponding to the anatomical structures such as airspaces , airways , and blood vessels . in a normal lung , the overall attenuation depends mostly on the degree of aeration ( air content ) and the degree of perfusion ( blood content ) . thus , any regional abnormality of either perfusion or aeration translates into visible heterogeneity on ct study of the lungs , referred to as heterogeneous lung attenuation . another important mechanism of heterogeneity is increased lung attenuation , caused either by thickening of interstitium or filling of alveoli with fluid , cells , or both [ table 1 ] . systematic analysis and interpretation of heterogeneous lung attenuation is therefore a valuable tool for diagnosis of lung disease . the topic of interpreting heterogeneous lung attenuation is extensively covered in specialized radiology literature , but is not well - known outside the specialty . heterogeneous lung attenuation has been described in the literature with terms such as mosaic perfusion ( mp ) , ground glass opacification ( ggo ) , and mosaic attenuation ( ma ) . these terms are often interchangeably used without consideration of the subtle underlying pathophysiological differences that were intended when these terms were coined . herein , we have presented a simple schema of how pathological changes in lung correspond to changes in ct appearance . we have highlighted these differences using illustrative cases and have provided an algorithmic approach to relating them back to the underlying pathogenesis . we have intentionally avoided using the term mosaic because heterogeneity is not always a mosaic patchwork limited by interlobular septa , as defined by the fleischner society and illustrated by a case example in [ figure 1 ] . we have also preferred to explicitly make the distinction between heterogeneous aeration / perfusion , where possible , based on ct features . ( a ) heterogeneous lungs without a polygonal mosaic pattern ( b ) in a case of chronic pulmonary thromboembolism evident by dilated main pulmonary artery , eccentric filling defects , and mural calcifications for the systematic analysis of heterogeneous lung attenuation , the first question to be addressed should be - which region is abnormal ? one can be easily be tempted into regarding the denser region as abnormal when encountered in the lungs . for example , in cases with ggo , the dense region will be clearly much more attenuating than a normal lung , leading the radiologist to confidently conclude the presence of ggo . however , when the attenuation differences are subtle , the help of ancillary findings becomes essential . this is where we must ask the question whether the heterogeneity corresponds to differences in blood flow or due to differences in aeration . blood flow into the lung depends upon a number of factors , including the concentration of blood vessels , their calibre , and the driving pressure . the last can be usually neglected since it is a systemic parameter and not a regional one . blood vessel concentration can be reduced by destruction of vessels , as in vasculitis or advanced emphysema . the calibre of blood vessels can be affected either by occlusion as in chronic thromboembolism , remodeling , or redistribution as in pulmonary arterial or venous hypertension or reflex vasoconstriction secondary to hypoxia , bronchoconstriction , or bronchial obstruction . the final result of each of these mechanisms , whether primarily vascular or not , is varying perfusion and heterogeneous attenuation . regions with increased blood flow will be denser than regions with decreased perfusion and usually represent the relatively normal appearing lung , which is easy to confuse with a ggo . the regions of relative hyperlucency show diminished calibre of vessels , but the total number of vessels is normal . this suggests that the dense area is the normal lung and there is vasoconstriction leading to reduced blood flow and , therefore , increased lucency in the diseased portion of the lung , which is commonly secondary to local small airway disease . clinically , this was a patient with unexplained progressive obstructive lung disease , with no history of smoking but a history of chemical fume exposure . the lungs demonstrate no architectural distortion other than mild dilatation of the bronchi and no evidence of emphysema . given the clinical context of significant chemical fume exposure and progressive obstructive disease with a lack of response to glucocorticoids or bronchodilators , detailed pulmonary function testing by impulse oscillometry confirmed that there was a severe fixed , small airways obstruction , with near normal upper airway resistance , consistent with the diagnosis . due to the lack of definitive therapeutic options such as transplant , conservative medical management this vignette represents a typical scenario , where a finer interpretation of the heterogeneous lungs was helpful in guiding clinical diagnosis . notably , the relatively increased attenuation of the adjacent lung was originally misconstrued as ggo . it was most likely redistribution of blood flow , away from the diseased lung and toward the normal lung leading to slight hyperattenuation . the hyperlucent regions show diminished calibre of vessels and mild segmental and subsegmental bronchial dilatation . a clinical diagnosis of bronchiolitis obliterans was made in view of history of chemical fume exposure , progressive disease , and lack of response to glucocorticoids distinguishing between primarily aeration ( airway ) from perfusion ( vascular ) etiologies on a single set of images is not straightforward and must be clinically correlated . for example , a history of deep venous thrombosis and no wheeze in the above patient would have been more consistent with prior pulmonary thromboembolism to the affected area with reduction in vascular calibre . comparing the usual inspiratory ct scans to an expiratory scan can sometimes be helpful , since airway disease - related heterogeneity is further enhanced during expiration , as in the case of asthma [ figure 3 ] , while vascular disease is relatively unaffected . this is rarely needed or done in actual practice because of the availability of other tests as well as cumulative radiation concerns and is not discussed further . however , an important corollary is that a modest degree of heterogeneity can be seen in normal individuals , especially on unintentional expiratory scans [ figure 4 ] . a give - away for an expiratory scan is the bowing of the trachea , as seen in [ figure 4 ] . inspiratory ( a ) and expiratory ( b ) thin - section ct images of a 35-year - old male with known asthma and shortness of breath . the lungs demonstrate heterogeneous attenuation , more pronounced on the expiratory scan , indicating areas of air trapping unintentional expiratory scan in a patient involved in a car accident demonstrating inhomogeneous lungs due to air trapping . bowing of the posterior wall of the trachea indicates an expiratory phase examination patients with pulmonary hypertension may also demonstrate heterogeneous perfusion on ct chest resulting from a redistribution of blood flow to the central zones caused by peripheral vasoconstriction or due to variable lung perfusion [ figure 5 ] . this is more common in patients with pulmonary artery hypertension ( pah ) due to vascular disease as compared to pah secondary to cardiac or primary lung disease . there are other signs of pulmonary hypertension such as dilated central pulmonary arteries , larger geographic hyperlucent areas in the lung peripheries , or segmental and subsegmental patterns of variable attenuation . a patient with chronic pulmonary thromboembolism with dilated main pulmonary arteries , wall calcifications , and heterogeneous lungs . peripheral pruning of the vessels and variable vessel calibre indicate a vascular etiology ggo refers to increased attenuation of the lung parenchyma on high - resolution ct ( hrct ) without obscuring the underlying vascular or bronchial margins , thus differentiating it from consolidation [ figure 6 ] . ggo results from volume averaging of abnormalities that are too small to be clearly delineated on hrct , such as thickened interstitium , minimal fluid , cells , or fibrosis in the alveoli . in a case of patchy ggo , the size and the number of vessels are generally similar in the hazy lung parenchyma as compared to the rest of the lung [ figure 7a ] . in some situations , there may even be reduced vascularity in the dense portions of the lung because of shunting of blood away from the affected areas of the lung , such as in acute chest syndrome in a case of sickle cell disease due to pulmonary microvascular occlusion [ figure 7b ] . this is opposite to what is seen in heterogeneous perfusion , where the increased attenuation is due to increased blood flow [ figure 7c ] . ( a ) ggo seen as increased attenuation of the lung parenchyma on hrct without obscuring the underlying vascular or bronchial margins . ( b ) consolidation in a case of aspiration pneumonia presents as homogeneous increased parenchymal attenuation in the lower lobes obscuring the vascular and bronchial margins with air bronchogram ( a ) a case of atypical pneumonia demonstrating similar size of vessels in hazy and normal areas of the lungs . ( b ) a 6-year - old with sickle cell disease with ggo in the posterobasal segment of the right lower lobe and decreased vascularity within the ggo as compared to the normal lung . ( c ) a case of bronchiolitis obliterans demonstrating heterogeneous attenuation in which the abnormal hyperlucent areas demonstrate diminished vascularity in an acute setting , the presence of ggo on hrct usually indicates active and ongoing process , such as active inflammation or edema . a lobar or segmental distribution can be seen with bacterial pneumonias or infarcts [ figure 8 ] . intrinsic causes are usually systemic in origin . for example , central and posterior - dependent distribution is present in early hydrostatic edema and , often , there is associated septal thickening , with underlying redistribution of blood flow [ figure 9a ] ; peripheral and basal distribution is seen in capillary endothelial damage associated with intrinsic hypersensitivity disorders such as early scleroderma lung [ figure 9b ] and other early idiopathic interstitial lung diseases . extrinsic conditions that manifest as diffuse and symmetric ggo include acute injury caused by toxic fume inhalation , hypersensitivity reactions , acute disseminated air - borne infection , or opportunistic and viral infections [ figures 10a and b ] . other pathological conditions such as inflamed or neoplastic regions of the lung may also manifest as ggo [ figure 11 ] . pulmonary thromboembolism with wedge - shaped ggos in a segmental distribution suggestive of infarcts ( a ) congestive heart failure with diffuse bilateral ggo and septal thickening . ( b ) early scleroderma with peripheral basal distribution of ggo ( a ) a case of h1n1 pneumonia with bilateral ggo with a predominant bronchovascular and subpleural distribution and consolidation . ( b ) atypical pnenumonia of unknown microbiological origin with a peripheral distribution a 53-year - old male with sob and hemoptysis with patchy ggo and septal thickening on hrct , diagnosed as brochioloalveolar carcinoma on pathology effects of gravity and the resultant dependent distribution help distinguish aspiration from other conditions . the poorly demarcated ggos in [ figure 12a ] have a posterior and gravity dependent distribution . [ figure 12b ] , the clinical history was of shortness of breath , chest tightness , and spitting of blood , indicating pulmonary hemorrhage as the most likely etiology of the ggo . focal , geographic non - segmental ggo in the setting of trauma and usually with a peripheral distribution is indicative of pulmonary contusions [ figure 12c ] . ( a ) a 56-year - old male with a history of chest pain and fall on ct shows ggos in a posterior distribution , suggestive of aspiration . inhomogeneous attenuation secondary to airway or vascular disease and ggo represent distinct processes within the general category of heterogeneous lung attenuation , as depicted schematically in [ figure 13 ] . table 2 mentions the most important features of each of these processes on ct study of the lungs that permit reliable discrimination from each other . often , the picture can be mixed due to multiple processes existing simultaneously with heterogeneity due to some combination of regional differences in aeration , perfusion , and abnormal alveolar filling or interstitial thickening . this combination is encountered more frequently in real practice because of the close interdependence of lung aeration and perfusion through complex reflex mechanisms . for example , in [ figure 14 ] , the patient with pulmonary arterial hypertension is additionally suffering from pulmonary edema , seen as ggo and septal thickening . a similar picture may be seen when patients with airway disease additionally develop lower respiratory infections . in such settings , it is important for the interpreting physician to identify each process and provide a differential diagnosis so that correct therapeutic decisions can be made . a decision - tree algorithm that highlights key steps of the thought process is also presented [ figure 15 ] that can help in the differential diagnoses . while such aids are only an adjunct to experience and clinical follow - up , they can be useful in providing guidance at clinical crossroads . airway disease ( left ) can lead to ( 1 ) gas trapping and reflex vasoconstriction seen as hypoattenuating regions with fewer or thinner blood vessels . ( 3 ) complete loss of ventilation can lead to atelectasis , crowding of blood vessels , and hyperattenuation . vascular disease can also lead to heterogeneous lungs ( right ) due to ( 4 ) increased vascular resistance and hypoperfusion ( e.g. , pulmonary hypertension ) that contrasts with normal lungs and vascularity ( arrow ) and ( 5 ) regions of increased perfusion features of forms of heterogeneous lung attenuation a patient with pah is additionally suffering from pulmonary edema , seen as diffuse bilateral ggo , and septal thickening . variable perfusion and ggo contribute to lung heterogeneity flowchart for assessment of heterogeneous lung attenuation in summary , heterogeneous lung attenuation , a commonly encountered finding on ct of the lungs , is not as non - specific as commonly thought and systematic analysis can illuminate the diagnostic road .

computed tomography ( ct ) chest is widely used as an adjunct to clinical examination and pulmonary function tests in the evaluation of unexplained dyspnoea . in such patients , heterogeneous lung attenuation is a common finding on ct . heterogeneous lungs can be caused by varying regional aeration , varying regional perfusion , and ground glass opacities ( ggo ) representing airspace or interstitial pathology . it does not serve the referring clinicians or the patients well if the radiology report simply mentions the heterogeneity of the lungs without due analysis of the cause of heterogeneity and a meaningful differential diagnosis . therefore , it is imperative for the radiologist and the treating pulmonologist to have an in - depth understanding of the pathogenesis of pulmonary heterogeneity . this , in conjunction with clinical data , can narrow the differential diagnosis or , at times , lead to specific diagnoses . the purpose of this review is to familiarize readers with the ct representation of heterogeneities in aeration and perfusion of the lung , relate patterns of ggo to underlying pathology , and provide illustrative case studies highlighting the radiological approach to heterogeneous lungs .

while superficial non - ampullary duodenal tumors are relatively rare , the frequency of their detection has recently increased due to the widespread use of endoscopy and continual improvements in endoscopic techniques ( 1,2 ) . although there are no established indications or treatments for superficial non - ampullary duodenal tumors ( 2,3 ) , appropriate treatment is necessary for lesions that are histopathologically diagnosed to be high - grade dysplasia or which measure at least 20 mm in diameter , as these present a high risk of malignancy ( 2,4 ) . endoscopic treatment for superficial non - ampullary duodenal tumors is technically challenging because of the anatomical features of the duodenum and a high incidence of adverse events , such as perforation ( 2 - 5 ) . for many years , surgical repair has been the standard treatment for iatrogenic gastrointestinal perforations . however , surgical procedures in the duodenum are relatively invasive , and they are also associated with significant morbidity and mortality . for these reasons , endoscopic closure of gastrointestinal perforation has recently been introduced as an attractive alternative ( 6 - 8 ) . the over - the - scope - clipping system ( otsc system , ovesco endoscopy ag , tbingen , germany ) is an endoscopic device used to mechanically compress gastrointestinal tract tissue ( 9 ) . the otsc system is composed of an applicator cap with a mounted otsc clip , a thread fitted to the otsc clip to assist clip release , and a hand wheel for clip release . the otsc clip is deployed by rotating the hand wheel to pull the thread connected to the otsc clip . the otsc twin grasper with two jaws , which can be separately opened as an assistive device to approximate tissue , is also available ( 10 ) ( fig . the otsc system has made the closure of gastrointestinal tract defects , such as perforations , anastomotic insufficiency , and fistula , as well as hemostasis in difficult - to - treat non - variceal bleeding , possible ( 6 - 10 ) . it also helps to achieve a more reliable closure , as its wide mouth allows it to hold a greater amount of tissue than the conventional through - the - scope clip ( ttsc ) ( 8,10 ) . we herein describe a patient in whom the otsc system was useful for the treatment of a duodenal perforation caused by endoscopic submucosal dissection ( esd ) . the otsc system is composed of an applicator cap with a mounted otsc clip , a thread fitted to the otsc clip to assist clip release , and a hand wheel for clip release . the otsc twin grasper with two jaws , which can be separately opened as an assistive device to approximate tissue , is available ( reproduced with the permission of ovesco endoscopy ag , tbingen , germany ) . a 39-year - old male with no clinical history was referred to our hospital for close examination and treatment of a duodenal tumor detected by screening radiography of the stomach . on upper gastrointestinal endoscopy performed at our hospital , a reddened , sessile , elevated lesion measuring approximately 30 mm in diameter was detected in the anterior wall of the duodenal bulb , and a whitish lower elevated area spread around the lesion ( fig . 2a ) . magnifying endoscopy with narrow - band imaging ( olympus gif type h260z , olympus , tokyo , japan ) revealed leaf - like villous structures of various sizes . the widths of the villi were greater than those in the surrounding normal areas ( fig . chromoendoscopy with indigo carmine clearly showed the border of the lesion and the unevenness of its surface ( fig . a reddened , sessile , elevated lesion measuring approximately 30 mm in diameter was observed in the anterior wall of the duodenal bulb , and an area of whitish lower elevation extended around the lesion . c : magnifying endoscopy with narrow - band imaging combined with water - immersion technique . spraying of indigo carmine clearly showed the border of the lesion and the unevenness of its surface . we performed esd to confirm the histopathological diagnosis , because the accuracy of diagnosing duodenal tumor by biopsy is low , and because the risk of malignant transformation is high for tumors measuring at least 20 mm in diameter . although a mixture of glyceol and hyaluronic acid was locally injected into the submucosa , the elevation of the lesion was insufficient , and submucosal dissection was difficult ( fig . was changed to snaring with circumferential incision , which caused a full - thickness perforation measuring approximately 18 mm in diameter ( fig . since the lesion was located in the anterior wall of the duodenal bulb , the resected lesion was not inverted into the peritoneal cavity , and the tumor was not exposed to the peritoneal cavity . since arterial bleeding was observed from the full thickness resection site , hemostasis by cauterization was performed with hot biopsy forceps ( radial jaw 4 hot biopsy forceps , boston scientific , marlborough , usa ) at the perforated site . the endoscope ( olympus gif type q260j , olympus ) was immediately withdrawn . after being attached to an 11/6 t otsc system ( fig . both edges of the perforation were grasped with both jaws of the otsc twin grasper , which can be opened separately , in positions of correct approximation ( fig . the grasped tissue was pulled into the applicator cap , and the otsc clip was then deployed while also performing continuous suction ( fig . 3f and g , supplementary material ) . the procedure was completed after the effective closure of the perforation was confirmed by the dilation of the duodenum under insufflation . transcutaneous needle decompression ( supercath , medikit , tokyo , japan ) was immediately performed for decompression after pneumoperitoneum . thereafter , the patient fasted , was intravenously administered antibiotics and proton - pump inhibitors , and was intubated by nasogastric suction . seven days after the procedure , the absence of leakage was confirmed by a gastrografin swallow ( fig . the tumor size in the resected specimen was 2725 mm , and the pathological diagnosis was tubular adenoma with low - grade dysplasia . on follow - up upper gastrointestinal endoscopy performed one month later , the perforation was closed by the otsc clip ( fig . upper gastrointestinal endoscopy performed one year later showed disengagement of the otsc clip and scarring of the resection site ( fig . a : although a mixture of glyceol and hyaluronic acid was locally injected into the submucosal layer , the elevation of the lesion was poor , and submucosal dissection was difficult . b : resection of the lesion by snaring with a circumferential incision resulted in a full - thickness perforation measuring approximately 18 mm in diameter and arterial bleeding from the full thickness resection site . c : the applicator cap with a mounted otsc clip was attached to the tip of the endoscope . d : the left edge of the perforation was grasped with one jaw of the otsc twin grasper . e : the other jaw of the otsc twin grasper was opened to grasp the right edge of the perforation while grasping the left edge with one jaw . f : the grasped tissue was pulled into the applicator cap , with continuous suctioning . while endoscopic treatment for superficial non - ampullary duodenal tumors is a challenging technique that is often associated with procedural accidents , the otsc system was shown in this patient to be useful for the management of such iatrogenic events . esd is widely accepted as a treatment for gastrointestinal tumors because of its high en bloc resection rate , which makes accurate histopathological evaluation possible . however , the usage of this technique to treat duodenal lesions remains controversial due to its technical difficulty and its high incidence of procedural accidents ( 1 - 3,5 ) . based on excellent long - term outcomes , some endoscopic centers consider that piecemeal resection by endoscopic mucosal resection is acceptable , and refrain from aggressively performing duodenal esd from the viewpoint of safety ( 3 ) . indeed , the incidence of adverse events in duodenal esd has been reported to range from 6.7 - 36.6% for intraprocedural perforations and 0 - 14.3% for delayed perforations ( 1 - 5 ) , being markedly higher than their incidences in other parts of the gastrointestinal tract . moreover , emergency operations have been performed in 3.3 - 25.0% of the patients who underwent duodenal esd due to the conversion of esd to surgery necessitated by intraprocedural uncontrollable perforation or delayed perforation ( 1 - 5 ) . this is due to the anatomical features of the duodenum , such as a narrow lumen , precipitous flexure that makes the endoscope unstable , abundant brunner 's glands in the submucosal layer that inhibit proper mucosal lifting , rich submucosal vasculature , and thin muscle layer associated with a high incidence of perforation ( 1,3,4,11 ) . in this patient , the otsc system was shown to be useful for closing an acute iatrogenic duodenal perforation . conventionally , ttscs have been used for the endoscopic closure of gastrointestinal perforations . however , due to the narrow wingspan of the ttsc , multiple clips were needed for the repair , the leak rate after the repair of large perforations exceeding 1 cm was significant , and the treatment ended in mere surface layer closure rather than in full - thickness closure ( 6,7,10 ) . the otsc system , on the other hand , has higher gripping and holding strengths ( 10,11 ) and it is designed to achieve full - thickness closure of perforations with diameters up to 3 cm ( 6 ) . it has been reported to be particularly effective for closing defects and leaks without causing fibrosis at the edges ( 8,10 ) . according to a systematic review of the clinical outcomes of endoscopic closure of acute iatrogenic gastrointestinal perforations , the success rate using the otsc system was remarkably high , namely at 87.8% ( 7 ) . few short- or long - term adverse events associated with otsc placement have been reported ( 8) , thus indicating its safety as an endoscopic device . in duodenal esd , it is necessary to pay attention not only to intraprocedural but also delayed perforation , due to exposure of the post - esd ulcer to bile and pancreatic juice and to excessive thermal injury to the muscle layer ( 1 - 5,11 ) . complete closure of a post - esd ulcer is useful for preventing delayed perforation ( 2,3,11 ) . the usefulness of the otsc system for complete closure of duodenal post - esd ulcers has been reported ( 11 ) . provided a complete resection can be achieved , the otsc system may therefore become useful not only for closing intraprocedural perforations , but also for preventing delayed perforations ( 2,11 ) . in conclusion , the otsc system is considered to be a safe and efficient device for closing gastrointestinal perforations . for endoscopists who perform endoscopic treatments in the duodenum , which are technically difficult and associated with a high incidence of procedural accidents , endoscopic closure with the otsc system a full - thickness perforation measuring approximately 18 mm in diameter was endoscopically closed with the otsc system .

endoscopic treatment for superficial non - ampullary duodenal tumors is technically difficult and challenging due to the anatomical characteristics of the duodenum . it is frequently complicated by procedural accidents , such as perforation . surgical repair has long been the standard treatment for acute iatrogenic gastrointestinal perforation . however , endoscopic closure has recently emerged as an attractive alternative . in the patient presented herein , the over - the - scope - clipping system ( otsc system ) was found to be useful for closing a duodenal perforation that had occurred during endoscopic submucosal dissection . for endoscopists who perform endoscopic treatment of the duodenum , endoscopic closure with the otsc system is considered to be a technique that is necessary to master .

spasticity after stroke is an indicative sign of damage to the upper motor neuron system and the cerebral cortex . in 1980 , lance defined spasticity as a velocity - dependent increase in muscle tone with exaggerated tendon jerks , resulting in hyperactive muscle activity1 . clinical assessments of spasticity should include quantification through validated scoring systems such as the ashworth scale2 , modified ashworth scale3 ( mas ) , tardieu scale4 , and modified tardieu scale5 . fonseca et al . used a portable spasticity measurement device and reported that there was no statistical difference between mas and stiffness measured by the device6 . they decomposed the stiffness of the paralyzed foot ankle of a hemiplegic patient into different components . although the above - mentioned quantification methods have been used frequently in clinical situations , patients have to rest on a bed or in a chair during the assessment . however , some patients do not develop spasticity when they are at rest , instead they develop and have spasticity when they begin to walk . to measure spastic stiffness during walking , we developed a novel device . we verified the device s functionality by testing it on an able - bodied individual and an equinovarus patient after stroke . an adjustable posterior strut ankle - foot orthosis ( aps - afo ) was used . a duralumin strut , 5 mm thick , 20 mm wide , and 280345 mm long , was attached to the foot portion of the patients aps - afo ( taps - afo , tims adjustable posterior strut , tomei brace , aichi , japan ; and raps - afo , remodeled adjustable posterior strut , tomei brace , aichi , japan ) . the length of the strut was adjusted ( 280345 mm ) according to the length of the patients lower leg ( fig . 1.torque sensor mounted on an adjustable posterior strut ankle - foot orthosis and sensor interfaceml : medial - lateral ; ap : anterior - posterior ) . the angle of the ankle joint of the aps - afo was set at 5dorsal flexion . to measure torque in the anterior - posterior ( ap ) and medial - lateral ( ml ) directions , two torque sensors were attached to the strut with eight strain gauges configured into two full - bridges . the output of the torque sensors was transferred to a pc ( sotec wa5512 , intel core 2 duo , processor t5500 [ 1.66 ghz ] windows vista home premium redmond , wa , usa ) via a sensor interface ( pdc-300b , kyowa , japan ) . two mechanical switches were placed on the bottom of the afo at the heel and toe in order to define the gait phase . torque sensor mounted on an adjustable posterior strut ankle - foot orthosis and sensor interface ml : medial - lateral ; ap : anterior - posterior because of the geometric non - uniformity of the metal strut and asymmetric adherence of the strain gauges , bending in the ap direction interfered with the output of the torque sensor monitoring in the ml direction and vice versa . thus , interference - free calibration was needed ( equation ) . calibrated torque ( true torque ) was calculated by multiplying the measured strain with the known calibration matrix.calibrated torque = measured strain calibration matrix ( 1 ) the calibration matrix was obtained by using equation ( 2 ) . we determined the applied torque , which was calculated from the product of different sand weights ( 20 , 15 , 10 , 5 , 1 , 0 , 1 , 5 , 10 , 15 , and 20 kg ) , length of the strut ( 0.15 m ) , and the acceleration due to gravity ( 9.8 m / s ) . the outputs of the torque sensors at each applied torque were used for the measured strain , and then , we obtained the left side and the first member of the right side by using equation ( 2).applied torque = measured strain calibration matrix + error ( 2 ) the calibration matrix was calculated using the least squares method , which minimizes the sum of the squares of the error . the result is shown in equation ( 3).calibration matrix = ( [ measured strain ] [ measured strain ] ) [ measured strain ] [ applied torque ] ( 3 ) , where the notation ( ) and [ ] denote the inverse and transposed matrices , respectively . the subjects of our study were a 34 years old able - bodied male subjects and a 30 years old equinovarus left hemiplegic female patient ( with right putaminal hemorrahage ( intracranial hemorrhage ) ) . both subjects walked on a treadmill at the speed of 1.2 km / h . this study and experiment procedure were approved by the local ethics committee of nanakuri sanatorium at fujita health university ( approval no . ap and ml directions torques in nm are shown in the 1st and 2nd columns of equation ( 4 ) , respectively . the corresponding strains in are shown in the 1st and 2nd coloumns of equation ( 5 ) , respectively . by substituting the equations ( 4 ) and ( 5 ) into the equation ( 3 ) , the calibration matrix was obtained as follows.0.0012 0.0006 0.0019 0.0498 ( 6 ) to understand the characteristics of the device , we applied the torques of the ap direction alone by using sand weights , and we obtained the calibrated torque , which was derived from the calibration matrix . in the ap direction , deviation from the expected value was 0.39 nm on average and was 0.62 nm at the maximum . the linearity , defined by the ratio of the average deviation to the full scale , was 1.3% . in the ml direction , deviation from the abscissa was 0.25 nm on average and was 0.48 nm at maximum . we applied the torques of the ml direction alone by using sand weights and obtained the calibrated torque , derived from the calibration matrix . in the ml direction , deviation from the expected value was 0.024 nm on average and was 0.031 nm at the maximum . deviation from the abscissa was 0.12 nm on average and was 0.16 nm at the maximum . the torque and heel toe motion of an individual with a normal gait is shown in fig . 2.torques of an able - bodied individual in the anterior - posterior ( ap ) and medial - lateral ( ml ) directions . the torque in the ap and ml directions , the toe switch status , and the heel switch status are shown . when the switches were on , it indicated that the sole was in contact with the floor , and the line was in the upper position , however when they were off , the line was in the lower position . first , the heel contacted the floor ( the belt of the treadmill , initial contact phase ) , and then the heel and toe made contact with the floor ( mid - stance phase ) . this was followed by releasing the heel and leaving the toe in contact with the floor ( late stance phase ) . finally , both switches were off , indicating that the foot left the floor ( swing phase ) . torques of an able - bodied individual in the anterior - posterior ( ap ) and medial - lateral ( ml ) directions the peak of the plantar flexion torque occurred immediately after heel contact ( the first half of the load reaction phase ) and then it gradually decreased towards the mid - stance phase . in the ml direction , eversion torque was at its maximum after the heel contact , which decreased gradually and extinguished in the swing phase . 3.torques of an equinovarus patient in the anterior - posterior ( ap ) and medial - lateral ( ml ) directions . the heel and toe made contact at almost at the same time , with the subject showing a flat foot during initial contact with the floor . during all phases , plantar flexion torque was observed in the ap direction and inversion torque was observed in the ml direction . in the late swing phase a large planter flexion and inversion torque was observed , typically a result of spastic muscle hypertonia . torques of an equinovarus patient in the anterior - posterior ( ap ) and medial - lateral ( ml ) directions calibrated torque in the ap direction was approximately proportional to the applied torque and the calibrated torque in the ml direction was negligible . similarly , calibrated torque in the ml direction was approximately proportional to the applied torque and calibrated torque in the ap direction was negligible . interference between the torque in the ap and ml directions was sufficiently compensated by the calibration matrix , which achieved our requirement . the observed torque in normal gait shows a small plantar flexion torque at initial contact and the first half of the load reaction phase which decreases towards the mid - stance phase . these findings agree with those of perry8 the equinovarus gait had planter flexion , and inversion torques was observed in all phases . in the stance phase , torque around the ankle joint is caused by body weight , floor reaction force , and muscle contractions ; thus , it is difficult to separate these individual torques . in the swing phase , the torque caused by the body weight and floor reaction force disappears and the torque caused by the muscle contraction alone can be observed . torque observed in the swing phase of the equinovarus patient s ankle joint , which was much larger than the torque observed in the swing phase of the able - bodied individual , must be a result of an increase in muscle tone ( spastic contraction ) .

[ purpose ] to develop a device for measuring the torque of an ankle joint during walking in order to quantify the characteristics of spasticity of the ankle and to verify the functionality of the device by testing it on the gait of an able - bodied individual and an equinovarus patient . [ subjects and methods ] an adjustable posterior strut ( aps ) ankle - foot orthosis ( afo ) was used in which two torque sensors were mounted on the aluminum strut for measuring the anterior - posterior ( ap ) and medial - lateral ( ml ) directions . two switches were also mounted at the heel and toe in order to detect the gait phase . an able - bodied individual and a left hemiplegic patient with equinovarus participated . they wore the device and walked on a treadmill to investigate the device s functionality . [ results ] linear relationships between the torques and the corresponding output of the torque sensors were observed . upon the analyses of gait of an able - body subject and a hemiplegic patient , we observed toque matrices in both ap and ml directions during the gait of the both subjects . [ conclusion ] we developed a device capable of measuring the torque in the ap and ml directions of ankle joints during gait .

human hydatid disease is caused by echinococcus granulosus , a cestode that is commonly lodged in the liver . several endemic regions exist ; however , the disease may be observed anywhere in the world . surgery remains the main modality of treatment , despite advances in medical and minimally invasive radiological therapies . in the last decade , laparoscopic surgery has become a part of the discussion of this issue , and several studies have reported encouraging results . whatever the technique , surgeons should focus on safe evacuation and sterilization of the cyst 's cavity . on the other hand , obliteration of the cavity with greater omentum herein , we report our series of patients with hydatid disease of the liver who underwent laparoscopic surgery , including omentoplasty and fixation of the omentum with helical fasteners . between january 1998 and april 2000 , 13 patients ( 5 men and 8 women ) , mean age 36 years ( range 23 to 63 years ) with hydatid disease of the liver were considered for laparoscopic surgery at our department . in the patient who had two , both of the cysts were in the right lobe . the cysts ' localizations were as follows : five in segment 8 , five in segment 5 , three in segment 4 , and one in segment 2 . the diagnoses were made with computerized tomography ( ct ) , ultrasonography ( us ) , and specific serological examinations . five patients were primarily diagnosed with us and 8 with ct . nevertheless , ct studies were added to the first group to have an optimum morphological evaluation . no evidence or suspicion existed of biliary rupture upon clinical findings and radiological studies ( history of cholangitis or jaundice , evidence of dilatation of the biliary tree , or connection with the cyst ) . indirect hemagglutination tests ( iht ) and elisa tests were done as serological tests and were positive in all patients . the patients who had evidence of biliary rupture , a history of recurrence , cysts deep or difficult to access in liver ( central or posterior localizations ) , multiple cysts ( more than two with unfavorable localizations ) , large cysts ( > 15 cm in diameter ) , and cysts with thick , calcified walls were not considered candidates for laparoscopy . the urinary bladder was catheterized , a nasogastric tube was placed , and antibiotics were administered half an hour prior to the operation . the first trocar was inserted at the umbilicus and a 30 laparoscope was used to visualize the peritoneal cavity . the operating surgeon stood at the patient 's left side ; the camera assistant managed the laparoscope from the left for right - sided cysts and from the right for left - sided cysts . the patient was placed in deep trendelenburg position and the subdiaphragmatic area was filled with 200 to 300 cc of 10% povidone - iodine for right - sided cysts . the cyst then was punctured with a veress needle and the cyst 's fluid was aspirated as much as possible . the cyst was refilled with 20% hypertonic saline , which is a potent scolocidal agent and left for 5 minutes . during this procedure , a 5-mm aspirator was placed beside the puncture point to prevent any fluid spillage into the peritoneal cavity . the insertion of the locking trocar into the cavity to minimize the contamination by the cyst 's fluid . worth , texas , usa ) was inserted from a point nearest to the cyst that was immobilized with a grasper . then this trocar , which was primarily designed to avoid inward and outward movement through the abdominal wall , was inserted into the cyst , and the umbrella - like lock was opened immediately . the cyst was pulled upwards and pinched between the abdominal wall and the umbrella lock of the trocar ( figure 1 ) . a 10-mm aspirator was inserted through the trocar and the cyst 's contents , including germinative membrane and daughter cysts , were aspirated . the superficial and visible part of the cystic wall was excised with an electrosurgical hook or shears , and the specimen was removed from the abdominal cavity within an endobag . the cystic cavity was then explored with a laparoscope to check whether any remnants of the cyst , biliary rupture , or hemorrhage were present . an adequate portion of greater omentum was pulled and inserted into the cyst 's cavity . the omentum was fixed to the cut edges of the cyst wall with a helical fastener ( pro tack , auto suture , norwalk , connecticut , usa ) , an instrument designed to fix mesh patches in endoscopic hernia surgery ( figure 2 ) . the drain was removed and the patient was discharged if no bile or ascites drainage were present . albendazole was administered , 10 mg / kg / day , for 6 months postoperatively , and an intermittent therapy regimen was planned as a 4-week course of drug therapy and 2 weeks of no treatment . radiological controls with ct and us were performed in the sixth month , and then annually . no perioperative complications such as bleeding occurred during application of the helical fasteners . in 1 case , with a single cyst in the right lobe , bile leakage was observed postoperatively , whereas no evidence of biliary rupture had been found during exploration . the biliary drainage gradually tapered off and ceased spontaneously on postoperative day 9 without any further intervention . except for this case , no early or late complications occurred . no radiological recurrence was observed in an average length of follow - up of 17 months ( range 4 to 36 months ) . in the last decade , laparoscopic treatment of hydatid disease of the liver has been carried out in many centers . a variety of techniques have been suggested for the surgical treatment of hydatid disease , all to sterilize the cysts , but the most commonly performed ones , both conventional or laparoscopic , are pericystectomy , simple drainage , or unroofing with omentoplasty . however , regardless of the method , the surgical principles are sterilization of the cyst cavity , careful evacuation of the cyst 's content without intraperitoneal spread , investigation of the biliary rupture , and obliteration of the cyst 's cavity . to succeed in laparoscopic hydatid disease surgery , these objectives are best reached with the meticulous selection of patients . as for current opinion obliteration of the cyst 's cavity with greater omentum has been reported to provide further benefits concerning prevention of postoperative abdominal complications . for this purpose , we modified it by securing an omental flap to the edges of the excised cavity with helical fasteners that are designed to fix mesh patches in video endoscopic hernia surgery . this allows a better and faster fixation of greater omentum that may easily drop into the peritoneal cavity . a critical point while applying this method is to apply fasteners only to the edges of the remnant of the cyst wall and to avoid injury to the liver . the other hand , spread of cystic fluid into the peritoneal cavity may result in peritoneal hydatidosis . we have used a locking ( or umbrella ) trocar , as previously described by seven et al , and a 10-mm rigid aspirator to evacuate the cyst 's contents . when approaching right - sided cysts , we filled the subdiaphragmatic space with 10% povidone - iodine ( betadine ) , to take measures against intraperitoneal spread , and 20% hypertonic saline solution was used to sterilize the cystic cavity . the scolocidal effect of povidone - iodine has been demonstrated in several experimental studies . although the use of 20% hypertonic saline solution to sterilize the cavity is now widely accepted because of it 's safety and ease of application , we preferred povidone - iodine for filling the pericystic area . in our series , except for 1 patient with 2 cysts that allowed easy access , we excluded patients with multiple cysts . although not contraindicated , multiple cysts are not suitable for laparoscopy . in such cases , maneuver of laparoscopic devices becomes exceptionally difficult unless the surgeon uses an excessive number of ports . also , cysts deep into the liver have increased surgical risks , such as difficult identification , bleeding , or the inability to check for biliary rupture . khoury et al reported on a patient who developed anaphylaxis on laparoscopic evacuation of a hydatid cyst , localized deep into the liver . it should be kept in mind that even minimal contact of cystic fluid with blood or with the peritoneal surface may lead to anaphylactic shock , and this contact is not preventable in deep cysts . therefore , an open surgical technique must have priority in deep cysts because the surgeon 's ability to prevent cyst fluid from contact with blood is significantly more difficult . another question concerning difficult cases for laparoscopy is biliary rupture . in a series of 328 patients , erguney et al reported a biliary rupture rate of 10.3% . in the preoperative evaluation , evidence of jaundice , right upper quadrant abdominal pain , cholangitis , or dilated biliary tract must warn the surgeon of a possible biliary rupture and a decision in favor of laparoscopic surgery should be reconsidered . one patient was overlooked on preoperative assessment in our series and presented with biliary fistula during the postoperative course . nevertheless , biliary drainage ceased with conservative management . spiliadis et al performed endoscopic sphincterotomy for complicated hydatid disease of the liver and 80% of patients suffering from postoperative biliary fistulas were successfully treated . endoscopic sphincterotomy by ercp ( endoscopic retrograde cholangiopancreatography ) is the treatment of choice for persistent biliary fistulas . with growing experience , laparoscopy seems to be quite feasible in hydatid disease of the liver . however , laparoscopy should not limit the surgeon 's performance in every surgical step of hydatid disease surgery . in many instances , omentoplasty with helical fasteners provides an easy and effective obliteration of the cyst 's cavity during laparoscopic access .

objectives : the objectives of this study were to investigate the characteristics and outcome of patients with hydatid disease of the liver who were laparoscopically managed at our clinic and to define technical details including an effective method of omentoplasty with helical fasteners.methods:between january 1998 and november 2000 , 13 patients , mean age 36 years ( range 23 to 63 years ) , with hydatid disease of the liver were considered for laparoscopic surgery in our department . all the patients underwent laparoscopic surgical interventions.results:in all patients , laparoscopic cystotomy , unroofing , and omentoplasty with helical fasteners , which were originally designed for endoscopic hernia repair procedures , were performed . no conversion to laparotomy was necessary . in 1 case , with a single cyst in the right lobe , bile leakage was observed . no radiological recurrence was observed in an average follow - up of 17 months ( range 4 to 36 months).conclusions : obliteration of the residual cystic cavity decreases postoperative complication rates , so an effective omentoplasty is essential especially for laparoscopic procedures . laparoscopy is quite feasible to perform in hydatid disease of the liver , and the use of helical fasteners allows effective omental flap fixation .

hyperuricemia is a condition that is significantly associated with markers of metabolic syndrome such as dyslipidemia , glucose intolerance , high blood pressure , and central obesity , which are accepted as risk factors for developing cardiovascular disease . hyperuricemia is probably associated with glucose intolerance due to various mechanisms ; however , the most important is the association between insulin and renal resistance to absorption of urates . hyperuricemia has been associated with insulin resistance ; however , there are few studies where the association of hyperuricemia - insulin resistance and beta cell function is evaluated . a modest positive association between concentrations of uric acid and incidence in type 2 diabetes mellitus was observed in a cohort of a chinese population . it was reported recently in another cohort that uric acid is a risk factor for development of dm2 . at the same time , another study demonstrated that serum uric acid values may be useful as predictors of dm2 in adults who are glucose intolerant . cohort studies support the fact that uric acid is a risk factor for developing dm2 ; in a meta - analysis by kodama et al . , the authors concluded that the variability of the results and control of confounding variables should be considered in the final analysis of competitive models for interpreting the results regarding the role of uric acid as a risk factor for developing dm2 . in a study that reported beta cell function with homa in subjects with hyperuricemia , failure of beta cells to compensate for the variation in insulin sensitivity these studies from different population samples established an association between serum uric acid and prevalence of dm2 , however a temporal effect between uric acid and different phases of insulin secretion can not be shown by these data . the role of uric acid as a continuous variable and its relationship to insulin secretion without hyperuricemia in patients with dm2 in a model such as the clamp has not been evaluated . the aim of this study was to determine the relationship between serum concentrations of uric acid with insulin secretion in adults with dm2 without hyperuricemia using the hyperglycaemic clamp technique . a cross - sectional analytical study was carried out in 45 subjects of both genders . subjects were between 40 and 60 years of age and were classified as overweight or grade i obesity and diagnosis of dm2 < 5 years of evolution according to the american diabetes association ( ada ) criteria . blood pressure was less than 130/80 mm hg . subjects denied use of any medications known to affect metabolism . at the time of the study , patients were not taking hypoglycemic agents approved for glucose control or they were unaware as to the effects of uric acid . the study protocol was reviewed and approved by the hospital - based ethics committee , and written informed consent was obtained from all volunteers . subjects were selected from metropolitan guadalajara , jalisco , mexico living in the same residential area and of similar socioeconomic status . for all participants , a clinical history was done using the following determinations ( weight , height , body mass index ( bmi ) , waist circumference ( wc ) , hip circumference ( hc ) , waist / hip ratio ( whr ) , and blood pressure ( bp ) ) followed by laboratory tests to determine glucose , hba1c , creatinine , uric acid , total cholesterol ( tc ) , triglycerides ( tg ) , very - low - density lipoprotein cholesterol ( vldl - c ) , high - density lipoprotein cholesterol ( hdl - c ) , low - density lipoprotein cholesterol ( ldl - c ) , and serum insulin concentrations . serum glucose was determined using the glucose - oxidase technique ( boehringer mannheim gmbh , mannheim , germany ) , with an intra- and interassay coefficient of variation < 3% . for determination of hba1c levels , ion - exchange high - performance liquid chromatography was carried out ( bio - rad laboratories , hercules , calif ) with an intra - assay coefficient of variation of 2.8% and 3.5% and intera - ssay coefficient of variation < 3.0% . creatinine , uric acid , and lipid profile ( tc , hdl - c , tg , ldl - c , and vld - cl ) were measured enzymatically ( ortho - clinical diagnostics , johnson & johnson company , rochester , ny , usa ) with an intra- and interassay coefficient of variation < 2% . insulin concentrations were measured using the microparticle enzymatic immunoassay method ( abbott diagnostics division , japan co. ltd . ) with an intra- and interassay coefficient of variation of 3.3 and 3.8% , respectively . to determine the phases of insulin secretion , hyperglycemic clamp technique was performed . briefly , two venous accesses were installed : the first was retrograde over hand veins through a 19-gauge butterfly catheter used for sample taking during the test . the hand was wrapped in a thermal pillow to achieve a local temperature of 40c in order to arterialize the blood . a 20% dextrose infusion was initiated : a priming dose for 14 min equivalent to 240 mg / kg body weight followed by a maintenance dose based on body weight , basal glucose , and the glucose required throughout the test ( 6.9 mmol / l above basal value ) . at 2 , 4 , 6 , 8 , and 10 min , 5 ml of blood was taken and , after that , each 10 min for 120 min for insulin determination . at 5 min intervals , an additional 1.5 ml blood sample was taken for glucose determination to calculate the estimate of glucose metabolism as well as to adjust the rate of dextrose infusion . at the end of the test ( 120 min ) , dextrose infusion was maintained for 30 min as a precaution to avoid hypoglycemia . with the above - mentioned results and using a calculator program , first ( 010 min ) and late ( 10120 min ) phases of insulin secretion as well as total insulin concentration ( 0120 min ) were calculated . area under the curve was determined using integration of polynomials for glucose regressions and phases of insulin secretion results were converted to the international system of units and presented as mean standard deviation ( sd ) . pearson bivariate correlations between uric acid and clinical and laboratory variables to establish a relationship with the gender spearman correlation were performed . the relationship of uric acid with insulin secretion and other adjusted variables was determined with the pearson correlation test . forty - five patients were recruited into the study ( table 1 ) . there were 21 ( 46.6% ) males and 24 ( 53.4% ) females . there was no statistical significance in age according to gender ( 48 4 versus 48 5 years , p = 0.850 ) or in bmi ( 29.8 2.7 versus 30.6 3.0 kg / m , p = 0.419 ) between males and females , respectively . a positive relationship was observed for male gender , bmi , wc , and fasting insulin according to the bivariate correlation ( table 2 ) . we observed a positive correlation between uric acid and total insulin secretion r = 0.295 ( p = 0.049 ) ( table 3 ) . also a positive correlation adjusted for bmi was demonstrated for the first and second phases , respectively , r = 0.438 ( p = 0.022 ) , r = 0.433 ( p = 0.022 ) as well as in total insulin secretion r = 0.439 ( p = 0.024 ) ( table 4 ) ; variables that were found significant in the bivariate model with uric acid were not significant in correlation with the phases of secretion . the association of hyperuricemia and development of dm2 have been observed by various investigators . however , there are no previous studies showing the possible relationship of serum uric acid with different phases of insulin secretion using a hyperglycemic - hyperinsulinemic clamp technique in subjects with dm2 without hyperuricemia . the mechanisms by which uric acid is involved in beta cell function or glucose concentrations and even the development of dm2 in the long term are uncertain . it is accepted that the most important mechanism may be that of the association of insulin resistance on renal absorption of urates . likewise , inhibition of uricase in a rat model revealed a decrease in serum insulin and hyperglycemia and rapid removal of basal insulin in in vitro secretion as well as reversing the effect of the removal of uric acid , suggesting an interference with the mechanism of insulin secretion . another study reported evidence of the involvement and role of uric acid on the alteration of the primary function of the beta cell and suggests the presence of an arginine residue combined with a critical site of the cell . the default is probably due more to an alteration in the secretion from the stimulus with a secretagogue than to an adverse effect on the viability of the beta cell . recent studies have reported the pro - oxidative capacity of uric acid in the differentiation of preadipocytes to adipocytes , an increase in reactive oxygen species ( ros ) by activation of the nadph oxidase , and sustained inflammation , mechanisms that may promote insulin resistance and impaired insulin secretion . insulin secretion was stimulated with l - arginine , and it was observed that in subjects with hyperuricemia and insulin resistance beta cell function increased from its compensatory state . in a study comparing four study groups ( control , type 2 diabetes : with and without obesity and type 1 diabetes ) , c - peptide levels were increased in patients who had type 2 diabetes and obesity . this apparently was related to the previously mentioned information concerning residual arginine in the beta cell as well as reporting on the stimulation of insulin secretion in pancreatic tissue of rat where it was observed that uric acid has no influence on insulin secretion when stimulated to euglycemic concentrations ( 100 mg/100 ml ) . however , when insulin secretion was stimulated to hyperglycemic concentrations ( 300 mg/100 ml ) , insulin secretion was increased by the addition of uric acid > 100% . in the present study , hyperglycemic clamp ( 200 mg/100 ml ) technique was used to stimulate insulin secretion , and a positive relationship was demonstrated between the serum concentration of uric acid and the total phase of insulin secretion . the first phase of secretion was the most important one and it influenced in an important way on the positive correlation ; this was probably caused by a compensatory response of the beta cell in subjects with dm2 without hyperuricemia . serum concentration of uric acid showed a positive relationship with the total phase of insulin secretion ; even in states prior to hyperuricemia , uric acid can play an important role in the function of the beta cell in patients with dm2 .

to determine the relationship between serum concentrations of uric acid and insulin secretion with hyperglycaemic clamp technique among adults with type 2 diabetes mellitus ( dm2 ) without hyperuricemia , we carried out a cross - sectional study on 45 patients of both gender . we observed correlation between uric acid with male gender r = 0.710 ( p = 0.001 ) . also correlation between uric acid and total insulin secretion was positive r = 0.295 ( p = 0.049 ) . as well as a positive correlation adjusted for body mass index was demonstrated for the first , second , and total phases of insulin secretion , respectively , r = 0.438 ( p = 0.022 ) , r = 0.433 ( p = 0.022 ) , and r = 0.439 ( p = 0.024 ) . serum concentration of uric acid showed a positive relationship with the total phase of insulin secretion ; even in states prior to hyperuricemia , uric acid can play an important role in the function of the beta cell in patients with dm2 .

a flow diagram of the algorithm is shown in figure 1 . to implement this procedure for a given model it is necessary to define bounds for input parameters and model outputs ( e.g. , steady states or dynamic behavior ) . if bounds can not be defined empirically , feasible ranges of parameter values can be asserted from physiological knowledge or theoretical considerations . for example , the tissue concentration of a species may not be known , but typical weight and water content of that tissue may be known , which allows us to put an upper limit on the species concentration . overview of algorithm for efficient generation and prevalencebased selection of virtual patients . to generate virtual patients from a model , the prior information ( green boxes ) a virtual population is constructed by selecting from this population with probability proportional to the prevalence in the real population relative to the prevalence in the plausible population . this selection is optimized to produce the best virtual population given the patients in the plausible population . we have provided a detailed description of terminology , definitions , and the derivation of this algorithm in table 1 and the supplementary material . we define these patients as a parameter set for which every component of the model ( whether it be the parameter values themselves , computed species concentrations , or combinations of these that are experimentally measurable ) falls into a biologically plausible range . from this plausible population we can then select the virtual population such that it matches the empirical distribution of interest . this is achieved by calculating a probability of inclusion of a plausible patient into the virtual population . this probability is computed from both the empirical distribution and the density of plausible patients ( see supplementary materials for more details ) . an overview of the terminology used in this article an important prerequisite to this approach is the ability to generate a large number of plausible patients within the region of the empirical data . to accelerate this process we take an initial parameter guess ( within the predefined bounds ) and optimize this choice until the required outputs are within physiologically plausible ranges . rather than optimize to specific points , it is more efficient to be agnostic as to where in the plausible ranges the optimization routine ends . to implement this we shift the typical cost function f(p ) we would use optimizing a model to a new function , g(p ) , where we consider both as purely dependent on the parameter if we constrain parameters using a number of model outputs mi(p ) , with data di then f ( in the simplest , unweighted case ) would be : f(p ) = (mi(p)di)2 . to generate plausible patients , we modify this sumofsquared errors expression to : g(p ) = imax[(mi(p)li+ui2)2(ui2li2)2,0]where ui and li are the predefined plausible upper and lower bounds , respectively , for mi(p ) . this expression ensures that if mi(p ) is in the plausible range then the contribution of the corresponding term in the expression is zero . the effect of replacing f(p ) with g(p ) is visualized in 2d in figure 2 . outputs of the model contribute to the cost function to be minimized by considering the sum of squared errors ( sse ) from an associated experimental observation . for each observation we define a physiologically plausible range ( arrows in a , b ) and shift the sse associated with that observation so that it is zero if the model output is in this range ( a , b ) . combining these transformations in each dimension leads to a broader cost function that is minimized by many points , rather than one ( black rectangle in c ) . to test this approach we used a previously published model of cholesterol metabolism.17 we chose this model because we could use publicly available data from the nhanes database16 to establish the empirical multivariate distribution for ldl cholesterol , hdl cholesterol , and total cholesterol ( ldlc , hdlc , and tc , respectively ) . note that the distribution of these variables is well approximated by a multivariate lognormal distribution ( supplementary figure 1 ) . for the remainder of the article we will describe these variables , either as model outputs or from nhanes , in log units ( prior to taking the logarithm , units are mg / dl for cholesterol measures ) . the published version of this model does not explicitly calculate ldlc or tc ; instead , the outputs are hdlc and nonhdlc . from these two quantities tc is easily calculated . for full comparison with the nhanes data we introduced a new parameter to the model , input_ranges.m gives details on parameter and output ranges for the van de pas model . also in the supplementary material is the code used in this case , which is easily modifiable for application to other models . as expected , the initial plausible population does not match the populationlevel statistics of the nhanes data ( figure 3 ) but covers the empirical distribution ( i.e. , where there are likely to be empirical observations there are plausible patients ) . comparison of the initial plausible population ( n = 300,000 ) with nhanes multivariate distribution ( ( ac ) black dotted lines estimated pdf , supplementary figure 1ac . ( df ) 2d projection of the 95% confidence surface of the estimated probability density function ) . once calculated , we established that most of the plausible patients are highly unlikely to be in the final distribution ( figure 4 ) . this is due to the relative density of the plausible population to the empirical distribution . with these probabilities , only 2% of the plausible population was selected to be in the virtual population ( inset , figure 4 ) . based on examining goodnessoffit of the distributions it appears , in this case , there is no further value in increasing the size of the plausible population ( supplementary figure 2 ) . the red histogram ( main figure , and figure inset ) is a virtual population that matches nhanes data , and is selected from the plausible population ( blue histogram ) based on displayed probability . the distribution of an example selection fits the nhanes data well ( figure 5 ) . the 1d histograms ( when normalized for comparison with the nhanes probability density function ) are indistinguishable from the data ( figure 5 a c ) and the correlations between variables also match the data based on visual predictive check . the virtual population ( red dots and red histogram ) matches the mean , variance , and covariance of the multivariate experimental distribution ( ( ac ) black dotted lines estimated probability density function , supplementary figure 1ac . ( df ) 2d projection of the 95% confidence surface of the estimated pdf ) . when selecting a subset of vps from a larger population , one concern is that the selected subset of vps does not reflect the variability of the original ensemble , which was generated from the biologically plausible range of the parameters . analyzing the final fitted population , we found little change in either the distribution of parameters or the correlation structure between the parameters ( figure 6 and supplementary figure 3 ) . this also shows that despite the virtual population being constrained against the nhanes data the parameter values of the virtual population ( figure 6 b ) are only slightly better constrained than those of the plausible population . furthermore , correlations between parameters are only slightly increased in the virtual population ( figure 6 d ) vs. the plausible population ( figure 6 c ) . at least in this case , constraining all outputs into realistic ranges is a more stringent constraint than selection of a virtual population . violin plots of the plausible and virtual populations ( a , b , respectively ) parameter values ( normalized to each parameter 's upper and lower bounds ) and correlation matrix of the plausible and virtual population ( c , d , respectively ) . one of the primary uses for qsp models is to prospectively simulate the effects of a dynamic perturbation ( pharmacological or otherwise ) in populations of interest . due to the underconstrained nature of these models it would be difficult to have confidence in the simulation results if we simulated a single parameterization of that model , even if that set of parameters is an excellent fit to the available data . for example , imagine creating a single hypercholesterolemia vp to simulate the effect of various anticholesterol therapies . for the baseline characteristics of the vpop , we have good data for the expected mean ldl and hdl ( e.g. , a prior clinical cohort ) , but we could still choose to mechanistically represent hypercholesterolemia several ways using the same model . we could increase cholesterol production , decrease clearance , or apply some combination of both . our choice of how to parameterize that vp could have significant consequences for the sensitivity of the followon therapy simulations . having impaired production vs. clearance of ldl could lead to differential responses to statins ( production ) vs. antiproprotein convertase subtillisin / kexin type 9 ( clearance ) . a better approach is to explore the underconstrained nature of these models and sample the biological uncertainty in the creation of plausible patients by varying mechanistic parameters , such as production and clearance rates , within biologically reasonable ranges . simultaneously , we need to constrain the higherlevel observables of the model based on known population distributions ( e.g. , the baseline characteristics of a clinical trial cohort ) . an appealing aspect of the approach we outline is that , since the algorithm is probabilistic , once the plausible patients are generated any number of subpopulations can be selected as long as the generated patients reasonably cover the full range of the ( sub)population . additionally , for any particular population , any number of vpops can be reselected to bootstrap the sensitivity of the model predictions to the choice of vpop . achieving an acceptable fit to the data distribution however , if we have higherorder density functions , we will likely require additional gains in efficiency , above and beyond what is presented here , in methods for generating sufficient plausible patients . one potential avenue , for a future iteration of this algorithm , may be to use methods that follow a directed search through the parameter space , such as using markov chain monte carlo ( mcmc ) algorithms.18 , 19 , 20 however , it should be noted that the method presented here is in fact a hybrid approach because the simulated annealing step , used to generate a plausible patient is essentially an mcmc method . the advantage of this approach is it generates plausible patients ( and hence virtual patients ) independently which is critical for the purpose of making a virtual population . also , once the plausible population is established new virtual populations , suitable for new applications , can be selected . however , a limitation of our approach is the computational cost of generating large plausible populations , which may make this method unfeasible in models that are slow to simulate . it should be noted that prior methods13 , 14 generated smaller virtual populations in larger models , partly due to the computational cost of running the models . nevertheless , the computational efficiency of a model does not alter the necessity for exploring the parameter space ( which in this context equates to larger virtual populations ) . we therefore advocate for the optimization of large models for speed , such that a fuller exploration of parameter uncertainty is possible ( either via the method presented here or alternatives ) . it is important to remark that the larger the model ( specifically , in terms of the number of poorly constrained parameters ) the greater the necessity for larger virtual populations to attempt to account for the uncertainty inherent in such a model . an advantage of our technique over prior approaches is that it is relatively unbiased , while still leveraging all available information on possible parameter values . the approach by klinke may overweight spurious model solutions , whereas the approach by schmidt et al . requires binning of parameter values into mechanistic axis which , for axes containing more than one parameter , requires an assumption about the correlation between parameters in the population of interest that may not be supported by available data . as an introduction to this algorithm , we demonstrated how to generate a vpop that matches the baseline characteristics of a population or clinical cohort ; however , in practice , a dynamic model should be constrained additionally against as many inscope perturbation experiments as possible ( determined by available data ) . for this example , simulating changes in ldlc and tc to standardofcare lipid therapies , such as statins and ezetimibe , would likely be an important step before using the model to predict the response to a novel mechanism . ideally , information would be available detailing the distribution of the data before and after the application of therapy ( i.e. , not just summary statistics ) . the therapeutic response can be treated as a baseline constraint for vp selection , just as we used hdlc and tc at baseline . we have applied this approach , without major adaptation , to an unpublished model of chronic kidney disease ( 42 ordinary differential equations ( odes ) , 200 parameters ) and to a model of body weight change6 ( 8 odes , 50 parameters ) ; we have made a brief summary of the results in these cases available.21 one challenge that we foresee , for virtual populations in general ( i.e. , not specific to this approach ) , is development of efficient ways to combine populations when merging distinct models . we believe that for two models that have large validated virtual populations , navely combining every possibility will be computationally daunting . quantitative systems pharmacology models are becoming established as a valuable component of the drug discovery and development process . communicating their complexity and uncertainty to an interdisciplinary project team is a critical but challenging component of their utility . virtual populations are one tool that we have found to be successful in exploring mechanistic and parametric uncertainty in an intuitive framework that is easily understandable by most audiences . however , despite their widespread use , there are very few published methods for generating virtual patients and forming virtual populations . here we have contributed an approach to efficiently generate virtual patients and construct a virtual population for which each patient is weighted equally . plausible populations , made up of plausible patients each of which is a candidate to become a virtual patient . because a large plausible population is necessary , models that are slow to integrate ( for example , with dynamics across multiple timescales ) may not be good candidates for this approach . however , in cases where quantitative predictions are required and the model is amenable to thorough examination of parameter space , we have found this method to be an improvement over previous approaches . supporting information click here for additional data file . supporting information click here for additional data file . supporting information click here for additional data file . supporting information click here for additional data file .

quantitative systems pharmacology models mechanistically describe a biological system and the effect of drug treatment on system behavior . because these models rarely are identifiable from the available data , the uncertainty in physiological parameters may be sampled to create alternative parameterizations of the model , sometimes termed virtual patients . in order to reproduce the statistics of a clinical population , virtual patients are often weighted to form a virtual population that reflects the baseline characteristics of the clinical cohort . here we introduce a novel technique to efficiently generate virtual patients and , from this ensemble , demonstrate how to select a virtual population that matches the observed data without the need for weighting . this approach improves confidence in model predictions by mitigating the risk that spurious virtual patients become overrepresented in virtual populations .

a 46-year - old female with a history of diabetes mellitus , morbid obesity , peripheral vascular disease , and dense peripheral neuropathy was initially treated in another facility ( private outpatient clinic ) for a calcaneal puncture wound with multiple incision and debridement procedures . the patient had a history of smoking for many years and also sustained a calcaneal osteomyelitis secondarily to the original infection with staphylococcus aureus and pseudomonas aeruginosa organisms ( fig . ( a ) preoperative picture of the left calcaneal osteomyelitis with the large wound at initial presentation . ( b ) preoperative angiography showing the popliteal artery occlusion . in our facility , the patient had immediate non - invasive vascular studies that were followed with a lower extremity angiography that showed a vascular occlusion of the popliteal artery around the popliteal fossa ( fig . the patient had agreed to quit smoking and was educated on a diabetic diet regimen with tight control over her blood sugars . at that time , the vascular surgery team performed a lower extremity bypass surgery ( femorotibial ) with the use of a saphenous vein graft while our team performed a simultaneous aggressive debridement of all the necrotic bone and soft tissue . intraoperative bone and soft tissue cultures and biopsies were also obtained . a postoperative regimen of deep vein thrombosis prophylaxis ( low molecular heparin ) and intravenous antibiotics based on the culture results ( keftazidim : 2 g 3 doses and vancomycin : 500 mg 3 doses ) were initiated and the patient 's vascular status of the lower extremity was monitored for approximately 3 weeks . a significant improvement of the skin temperature and blood perfusion of the limb was observed and it was confirmed with further doppler non - invasive vascular studies . at that time , the patient then had further surgical debridement and closure of the large calcaneal defect with a reverse flow sural neurofasciocutaneous flap . at the beginning of the surgery the exact bone resection was defined with a macroscopical inspection under loop magnification ( 6 ) combined with blue methylene fast staining and successive immediate multiple irrigations with normal saline solution . the procedure was followed with the flap dissection of the sural artery and associated neurovascular structures that were identified and ligated proximally . the flap 's pivot point was located distally over the defect area and approximately 57 cm proximal of the lateral malleolar area . the flap was innervated with end - to - end coaptation of the sural nerve at the distal end of the lateral plantar nerves with epineural sutures . the sural flap was then rotated to the defect area and was secured without any skin tension ( fig . the donor area was covered with a split thickness skin graft that was harvested from the ipsilateral thigh . the rest of the uncovered areas were grafted with split thickness skin from the ipsilateral thigh . ( a ) intraoperative picture showing harvesting of the large sural pedicle flap to cover the calcaneal resected osteomyelitis with a severe soft tissue loss . ( b ) immediate postoperative picture showing the insetting of the sural flap at the recipient area with minimal skin tension . during the first postoperative week , the flap sustained a superficial venous congestion and approximately 5% of the flap coverage was lost due to skin necrosis . the venous congestion was managed with the use of a vasodilating agent buflomedil hydrochloride ( 600 mg 1 over 24 h ) and an oral micronized purified flavonoid fraction ( mpff ; daflon , a vasoprotector and venotonic agent ) . the epidermal necrosis was healed after a minor surgical revision and loose reattachment of the flap margins . during the postoperative period the patient continued the intravenous antibiotic therapy for 2 months , followed by oral antibiotic therapy for more than a 1-month period . the patient was also kept non - weight bearing for approximately 3 months after the initial surgery . the flap was completely healed and the patient was ambulatory with a custom molded shoe at 4 months postoperatively ( figs . 3 and 4 ) . final postoperative outcome and range of motion of the ankle at 7-month follow - up . the majority of diabetic foot ulcerations with underlying osteomyelitis are clinically unsuspected and often masked by infected and necrotic soft tissue . if the treatment of osteomyelitis in a diabetic foot ulceration is not adequate , the risk of lower limb amputation will increase ( 2 ) . chronic diabetic foot ulcerations with exposed or probing to bone upon clinical examination may be treated for osteomyelitis . newman et al . ( 3 ) observed that osteomyelitis was present in 100% of diabetic foot ulcers in which the underlying bone was also exposed . palpation of bone in the depths of infected pedal ulcers in patients with diabetes is strongly correlated with the presence of underlying osteomyelitis. in our case report , the chronicity of the calcaneal exposure coupled with the inadequate soft tissue coverage led to the incidence of calcaneal osteomyelitis , which was surgically resected and covered with a reverse flow sural neurofasciocutaneous flap closure . the advantages of this flap compared to other covering methods are the simplicity of the design , the dissection of the pedicle sural flap that can be carried out with a loop magnification without the need for microsurgical instrumentation or anastomosis along with the preservation of the principle vascularization of the lower limb , and the need for only one operation . the sural flap constitutes for a well - vascularized cutaneous islet and offers the possibility of covering a broad range of areas with cutaneous defects in the distal malleolar areas . the sural flap can also be used in cases with serious peripheral vascular compromise as long as the peroneal artery is intact or when a microsurgical procedure is contraindicated . one of the few disadvantages of this flap is that by sacrificing the sural nerve , an inevitable anesthesia area appears over the lateral aspect of the foot that usually is well tolerated by the diabetic patient ( 57 ) . ( 8) was the first to describe the vascularization of the skin in the lower limb and the arteries that follow the trajectory of the peripheral nerves . the sural nerve projects distally in the leg and is in close approximation with the lesser saphenous vein . this nerve is supplied by the superficial sural artery in the proximal third of the calf and by fasciocutaneous branches arising from the peroneal artery in the distal half of the leg along with the suprafascial course of the sural nerve . the sural artery anastomoses with the peroneal artery by means of 35 fasciocutaneous perforators that ensure adequate inverse perfusion of the flap . the peroneal artery supplies the sural artery and venous anastomoses circulate along this artery to ensure venous return . several authors have demonstrated that the main anastomosis of this arterial network is located around 5 cm proximal to the lateral malleolus ( 914 ) . some surgeons do not include the sural nerve in the flap based on the existence of a perforated branch of the peroneal artery that by itself is capable of perfusing the graft without the need to transfer the accompanying nerve ( 9 , 10 , 2 , 15 , 16 ) . in our case report , in addition , some authors have advocated the utilization of a doppler test prior to the intervention that will confirm the integrity of the peroneal artery , its anastomosis with the fasciocutaneous branches , and the precise localization of the pivot point on which the flap should rotate ( 6 , 9 , 12 ) . additional lower extremity angiography may also be needed if the peroneal artery has questionable viability . in our case report the size of the flap was quite large ( 6.515 cm ) and although ( according to the literature ) the complication rates increase secondarily to the harvested pedicle flap size , we did not observe a significant postoperative edema and any donor side morbidity . in this case report , other alternatives for flap closure could have included the utilization of a free flap , lateral supramalleolar flap , and/or the posterior tibial perforator flap . free flap reconstruction of defects requires a lengthy and costly hospitalization , microsurgical training and experience , special instruments , and a two - team surgical approach . the long operative time and functional donor - site morbidity are major disadvantages of this method , especially in patients with diabetes mellitus and multiple associated comorbidities . the lateral supramalleolar skin flap offers a range of coverage similar to that of the sural flap but the dissection is more difficult and offers no more advantages when it is compared to the sural flap . theoretically , the sural flap does not cover as distally as the supramalleolar flap but it has been reported that the distally based sural flap is more reliable regarding the minimal venous congestion and has the ability to cover large weight - bearing areas of the foot ( 5 ) . finally , the posterior tibial perforator flap could have provided another alternative but its main disadvantages included a more difficult dissection and a larger learning curve ( 6 ) . in conclusion , the sural neurofasciocutaneous flap is a simple and reproducible method that can be utilized with a low rate of complications and needs to be considered for soft tissue coverage of any difficult to close calcaneal wound with concomitant osteomyelitis in patients with diabetes mellitus . the authors have not received any funding or benefits from industry to conduct this study .

the treatment of calcaneal osteomyelitis in diabetic patients poses a great challenge to the treating physician and surgeon . the use of a distally based sural neurofasciocutaneous flap after an aggressive debridement of non - viable and poorly vascularized tissue and bone that is combined with a thorough antibiotic regimen provides a great technique for adequate soft tissue coverage of the heel . in this case report , the authors describe the aforementioned flap as a versatile alternative to the use of local or distant muscle flaps for diabetic patients with calcaneal osteomyelitis and concomitant large wounds .

a 20-year - old female with extensive terminal ileal and colonic crohn 's disease was initially successfully managed on a drug regimen of prednisolone and mesalazine which helped to induce remission . this maintained her disease remission but was associated with neutropenic sepsis , necessitating the withdrawal of the thiopurine therapy with subsequent clinical and endoscopic disease flare . this required an infusion dose and frequency escalation to maintain clinical response . after 58 weeks of infliximab therapy , the patient was requiring 10 mg / kg 6 times weekly and hence was transferred to the fully human anti - tnf- injection adalimumab for loss of response to infliximab . initially this strategy regained disease control , but due to relapse at 40 mg every other week , the dose was increased step - wise to 80 mg weekly which fortunately maintained remission . during her treatment with adalimumab the presence of purple - coloured plaque - like lesions primarily on her abdomen figure 1 demonstrates the presence of psoriasis which is presumed to be a result of treatment with adalimumab . tnf- has been identified as a key cytokine in the pro - inflammatory pathways that drive diseases such as inflammatory bowel disease and rheumatoid arthritis . anti - tnf- agents such as infliximab and adalimumab are widely used in the treatment of these conditions and have been shown to have an impact on pro - inflammatory and apoptotic pathways . they are also effective in the treatment of the dermatological and rheumatological manifestations of psoriasis . however , there have been a number of cases reported where such agents may be responsible for new onset or worsening of psoriasis . a study of 126 patients who underwent treatment with anti - tnf- inhibitors demonstrated evidence of psoriasis in 76 individuals , palmoplantar pustular psoriasis in 37 cases and psoriasis of the nails in 6 cases . there is mounting evidence that a key innate immune pathway for triggering common human autoimmune diseases , including psoriasis , involves plasmacytoid dendritic cell precursors and type 1 interferon ( ifn ) production . a recent study involving immunohistochemical staining of skin biopsy specimens for myxovirus - resistance protein a ( mxa , a surrogate marker for lesional type 1 ifn activity ) demonstrated increased staining in tnf- inhibitor - induced psoriasis compared with psoriasis vulgaris . research suggests that a psoriasiform eruption during anti - tnf- treatment seems to be a class effect without any confirmed predisposing factors and does not specifically require treatment discontinuation . further studies are however needed to determine the exact mechanism of and appropriate treatment for anti - tnf--induced psoriasis .

anti - tnf- agents are currently utilised for the treatment of a vast array of autoimmune conditions including inflammatory bowel disease , rheumatoid arthritis , ankylosing spondylitis and psoriasis . it is however noted that such therapeutic strategies have been linked to the specific induction of cutaneous - based reactions such as dermatitis , erythema multiforme and psoriasis . here we present the case of a young female patient with crohn 's disease who developed psoriasis following treatment with the anti - tnf- drug adalimumab and highlight the possible pathogenetic mechanisms involved in such an occurrence .

a 72-year - old woman presented for further examination of a right breast lump . according to the patient , the lump had been present for at least 10 years . she complained of discomfort of recent onset in the right breast . on physical examination , a soft , mobile , 10 cm mass , which occupied nearly the entire right breast , was palpated . on mammography , a large circumscribed mass surrounded by a water - density capsule the mass was a mixture of isodense and fat densities and had dystrophic calcifications in a branching pattern . 1a , b ) . on ultrasonography ( us ) , the mass was very heterogeneous and completely encompassed in a thin echogenic pseuduocapsule of compressed breast tissue , which was compatible with hamartoma . however , a careful us examination revealed an irregular hypoechoic mass of 1.4 cm with a non - parallel orientation within the hamartoma ( fig . 1c ) . a retrospective review of the mammograms revealed focal asymmetry , which correlated with the suspicious mass on us ( fig . 1a , b ) . the lesion was early enhanced and a washout on enhanced mri scans ( fig . surgical excision for entire mass was done and the diagnosis from the frozen specimen of the suspicious area was idc . , there was no evidence of local recurrence of the idc or any distant metastasis . mammary hamartomas , a term applied to breast tumors in 1971 by arrigoni et al . ( 13 ) , have also been referred to as lipofibroadenomas , adenolipofibromas , and fibroadenolipomas ( 1 ) . hamartomas may present as tender or non - tender palpable lumps , but are often discovered incidentally during a screening mammography ( 1 , 14 ) . the typical mammographic feature of hamartomas is a circumscribed fibrofatty mass ( 15 ) . on us , most mammary hamartomas have circumscribed margins , an oval shape , and heterogeneous internal echogenicity ( 16 , 17 ) . the clinical , radiologic , and histologic findings of the previously described 14 cases of malignant hamartomas and the current case are summarized in table 1 . the mean patient age was 56.3 years ( range , 25 - 78 years ) . the size of the hamartomas range from 1.5 - 12.0 cm in diameter and the size of the associated carcinomas range from 0.3 - 3.5 cm in diameter . of the described 15 cases , mammography was obtained in 12 cases , of which 10 showed the typical appearance of hamartomas with suspicious features , such as clusters of microcalcifications , pleomorphic micocalcifications , and spiculated masses . the remaining two cases had the typical appearance of a hamartoma with no suspicious features , thus co - existing malignancies were unexpected findings at the time of tumorectomy . us findings were available in only six cases , of which four had suspicious masses with irregular margins , hypoechogenicity , or a non parallel orientation within the hamartomas ; and two cases were diagnosed pre - operatively as carcinomas by us - guided fine needle aspiration or core needle biopsies and underwent one - step curative surgery ( 6 , 7 ) . as stated above , the majority of cases had suspicious findings within the hamartoma on mammography or us . radiologists therefore need to pay careful attention in order to detect subtle suspicious findings , even though mammography or us may show typical hamartomas . among the 15 cases described here , 12 had carcinomas that were confined to the hamartomas and the remaining three cases had carcinomas that involved both the hamartomas and adjacent normal breast tissue . if carcinomas involve both the hamartoma and normal breast tissue , it is difficult to determine whether the carcinoma arises within the hamartoma or an isolated carcinoma which initiates growth nearby later extends into the hamartoma . however , in the majority of cases described here , including the current case , the carcinomas were located within the hamartomas , ( 2 - 5 , 7 , 8 , 10 - 12 ) thus we believe that the malignancies arose within the hamartomas . in conclusion , breast hamartomas have generally been classified as rare , benign tumors , and carcinomas occur only rarely . radiologists should recognize that malignancy may co - exist or develop in hamartomas and be alert to the presence of suspicious features within a hamartoma .

mammary hamartomas are typically a benign condition and rarely develop into malignant lesions . only 14 cases of carcinomas associated with a hamartoma have been documented in the literature . in this case report , we describe a case of invasive ductal carcinoma within a hamartoma in a 72-year - old woman . mammography , ultrasonography , and magnetic resonance imaging showed the features of a typical hamartoma with a suspicious mass arising in it . this case illustrates the importance of identification of unusual findings in a typical mammary hamartoma on radiologic examinations .

the vein of marshall ( vom ) is an embryonic remnant of the left superior vena cava.1 ) the ligament of marshall ( lom ) , which contains nerves , fibrous tissues , and muscle bundles ( marshall bundle ) , is adjacent to the vom.2 ) the lom is a trigger of ectopic beats initiating paroxysmal atrial fibrillation ( af)3 ) and is innervated by the arrhythmogenic autonomic nerve.4 ) moreover , the lom is connected to the neighboring left atrium ( la ) including the perimitral area and lateral ridge , and may be a part of the re - entrant circuit . therefore , the lom may play a role in the initiation and maintenance of af or atrial tachycardia ( at ) . recently , the feasibility of injection of pure ethanol into the vom was demonstrated ; the adjunctive effect to pulmonary vein isolation ( pvi ) was indicated.5 ) in addition , vom ethanol infusion assists in consisting achieving bidirectional perimitral isthmus ( pmi ) block.6 ) however , the effectiveness of the infusion in persistent atrial fibrillation ( peaf ) , which is an extensive substrate in the la , is unclear . in the present case , af was terminated by ethanol infusion adjunctive to complex fractionated atrial electrogram ( cfae ) guided ablation in a patient with peaf . a 64-year - old male presented with a 6-month history of symptomatic drug refractory peaf . the patient was admitted for catheter ablation of af . transthoracic echocardiogram revealed normal ejection fraction of 55 - 60% with mildly enlarged la of 43.8 mm in the anterior - posterior diameter . cardiac magnetic resonance ( cmr ) imaging revealed late gadolinium enhancement ( lge ) in 20% of the la surface including the anterior and posterior wall . cfaes in the la were mapped for 6 seconds using ensite navx system three - dimensional automated software ( endocardial solutions , st . the cfaes were predominantly located at perimitral , septal area and left atrial appendage base ( fig . activation pattern at the high clustering of cfae was mapped using high density 20-pole catheters ( afocus ii ; st . the activation patterns obtained from three af beats of unipolar recordings at each cfae site were classified into four categories : 1)complete reentry , 2 ) incomplete reentry , 3 ) wave collision , and 4 ) wave breakup with conduction block . we preferentially targeted cfae areas with complete or incomplete reentry pattern because these sites might play an important role as rotor . in this case , only the perimitral area had re - entrant , rotor - like electrical activity ( fig . , we assumed that the perimitral area could be the critical site for af perpetuation . therefore , we decided to infuse ethanol into the vom as an add - on to radiofrequency ablation . at first , cannulation into coronary sinus was performed by ablation catheter ( therapy coolflex ; st . paul , mn , usa ) and 8 fr sheath ( sl1 sheath ; st . paul , mn , usa ) . to confirm the existence and feasibility of vom , ( 7 fr ; cordis , miami , fl , usa ) was subselectively engaged into the vom and then a hi - torque floppy ii angioplastic guidewire 0.014 ( abbott , santa clara , ca , usa ) was advanced into the vom as far as possible . a ryujin plus otw 2.020 mm angioplasty balloon catheter ( terumo , tokyo , japan ) was advanced into the vom over the angioplastic wire and inflated at the ostium of vom . engagement of the balloon catheter into the vom was confirmed by injecting contrast medium into the vom ( fig . 2b ) , and 1 cc of 100% ethanol was injected into the vom three times ( fig . each injection was delivered over 1 minute through a balloon lumen and flushed with normal saline . within 30 seconds after the first ethanol injection la local activation time mapping demonstrated macro - reentrant at , the circuit of which involved reentry around the mitral annulus in a counterclockwise fashion ( fig . bidirectional block of pmi line was achieved after ablation within cs adjunct to pmi ablation ( fig . this case report demonstrates that ethanol infusion into the vom can effectively eliminate cfaes at pmi . in addition , we suggest that activation mapping at cfaes area during af can identify the critical cfaes that maintain the peaf . even though the underlying etiology of cfae has not been fully elucidated , cfaes are considered as slow conduction or pivot sites , which represent continuous reentry of the fibrillatory waves.7 ) based on these theories , cfae guided ablation is widely used for modifying the extensive substrate of the la and/or right atrium in patients with peaf . however , whether cfae reflects slow conduction or pivot site , or only wave collision that overlaps different wavelets at the same area is contentious . moreover , 90% of continuous cfae sites do not overlap over lge on cmr and occur at non - lge and patchy lge sites.8 ) therefore , identification of the critical pivot site perpetuating af among the continuous fractionated electrogram is necessary . in the present case , we performed unipolar activation mapping at the cfae areas using a high density circular catheter to identify critical pivots and preferentially targeted the sites with complete or incomplete reentry pattern because these areas might be crucial for the perpetuation of af . among three cfaes sites , only the pmi area had complete reentry pattern and ablation at this site easily lead to termination of af . therefore , this case suggests the usefulness of unipolar mapping to identify the true cfae sites which is related to the persistence of af . however , there is limitation of unipolar mapping , which includes difficulty in positioning the lasso catheter at the la septum , la lateral ridge and below the la appendage . the present case highlights that peaf can be terminated and organized to at by ethanol infusion into the vom . valderrbano et al.5 ) demonstrated the feasibility of ethanol infusion into vom adjunct to pvi ; ethanol infusion decreased voltage around pmi and the la lateral ridge . in addition , ethanol infusion in the vom has an adjunctive effect in perimitral flutter ablation.6 ) the proximal portion of lom has complex muscle fiber connections to cs adjacent to pmi.1 ) the mid - portion of lom is directly connected to the la lateral ridge and pulmonary veins.1 ) these muscle fiber connections can act as an anchor of re - entry . therefore , ethanol infusion into the vom can lead to substrate modification at pmi and la lateral ridge . moreover , the pmi area and la lateral ridge are too thick to achieve transmural lesion only by endocardial ablation . therefore , ethanol infusion in the vom can be an effective intervention for achieving transmural scar and facilitating durable conduction block at this area . however , in this case , bidirectional block of pmi was not achieved by only ethanol infusion , but required endocardial pmi and intra - cs ablation adjunct to ethanol infusion . the transmurality and bidirectional block could be achieved by pmi ablation in only 15% of patients.9 ) this finding suggests that ablation of pmi concurrent with endocardial or epicardial lateral ridge may be needed to achieve transmural lesion in most cases . therefore , ethanol infusion into vom can be applied to the patients with peaf , especially when cfaes clusters at pmi area and the la lateral ridge .

we report the case of a 64-year - old male with persistent atrial fibrillation ( af ) terminated by ethanol infusion into vein of marshall as add - on therapy . three - dimensional automated complex fractionated atrial electrogram ( cfae ) during af revealed clustering of cfae at perimitral isthmus ( pmi ) and its unipolar mapping showed rotor - like activation , which was suggested to be critical in the perpetuation of af . af was organized to atrial tachycardia ( at ) by 100% ethanol infusion in the vein of marshall . adjunctive radiofrequency ablation at pmi successfully terminated at and led to bidirectional block of pmi .

therefore finding of new and effective antimicrobial agents derived from new resources for such resistant bacteria is of an over riding importance . nowadays , scientists and clinicians are looking for more efficient drugs , derived from natural and herbal resources , against microbial and viral infections ( 1 ) . plants are considered as rich sources of antibiotic treatment medications and eucalyptus leaf with its antimicrobial properties have been used in the treatment of infectious diseases formerly in ancient medicine ( 2 - 5 ) . several compounds have been extracted from eucalyptus as biological sources such as uglobals , grandinol , macrocarpals , eucalymin , robostadial , 1 , 8-eineole and eucalypton with antimicrobial and remedial activities ( 1 , 6 - 9 ) . the major compound of eucalyptus is 1 , 8-cineole with antimicrobial specifications ( 3 , 5 ) . they used dilution method to measure the mic of eucalyptus oil on the e. coli - sp11 bacterium and estimated value was about 2.5 l / ml ( 10 ) . study by adebolla et al . designed to evaluate the antimicrobial effect of five different eucalyptuses via diffusion in agar revealed that the obtained mic for candida albicans and gram positive and negative bacteria was 5 mg / ml ( 5 ) . antimicrobial activity of eucalyptus oil on 22 bacteria and 12 fungi via disc diffusion method conducted in a study by pattnaik et al . ( 11 ) and results showed that the eucalyptus oil is effective against 22 kinds of bacteria and 11 kinds of fungus . the mic of bacteria was between 0.16 to 20 l / ml where it was 0.25 to 10 l / ml for fungus . they mentioned that diluted 1/100 v / v oil is necessary to prevent microbes activities . escherichia coli , staphylococcus aureus and aspergillus are all sensitive to the dilution 1/500 v / v and bacillus subtillis was sensitive to the dilution 1/250 v / v ( 12 ) . ( 13 ) studied the antimicrobial oil of the greek eucalyptus and used gram positive bacteria staphylococcus aureus and gram negative ones such as escherichia coli , klebsiella and pseudomonas aeruginosa . the results showed that the eucalyptus oil reacted against all bacteria and fungi effectively and the mic was estimated 0.3 to 0.6 mg / ml ( 13 ) . currently the antimicrobial extract and oil of eucalyptus have been registered in the pharmacies of england , france , germany , india , japan and united state . according to recent studies eucalyptus has shown an enormous antimicrobial activity and it also applied to produce new chemical compounds form other antibiotics ( 1 ) . the aim of present study was to evaluate antimicrobial activity of e. camaldulensis , e. polycarpa , e. malliodora and e. largiflorence on the staphylococcus aureus atcc25923 and other clinical resistant series . the ratification of bacterium series to ensure the materials and kinds of the supplied bacteria , gram stain , oxidase experiments , coagolase , dnase , catalase , movement in the semi - solid environment , the fermentation of mannitol , hemolysin , sensitivity to basitracin and culture in the liquid medium with 15% salt were carried out . essential oil extraction and diagnosis of it s chemical compounds eucalyptus leaves supplied from fadak garden in dezfoul city ( southwest of iran ) in july 2003 . we cut 50 g of the dried eucalyptus into pieces and oil extracted by distillation apparetus in 200 ml of distilled water . the distillation velocity was between 2 to 3 ml / min and the process lasted 3 h. acquired essential oil was injected to gc / ms instrument in order to separation . the gc - ms instrument ( hewlett - packard 5973 bston hp-5ms ) was kept at 60c for 3 min after injection where it can increase the temperature up to 220c and keep at this temperature for 5 min . the velocity of gas carrying helium was 1 ml / min and analysis gas chromatography was 70 ev / min , in which the compounds were separated and analyzed . the estimation of mbc and mic by the dilution method in the tube and the second culture in agar dilution method was used to measure mic . colony made from 24 h culture of bacterium inoculated to mooler hinton berath culture medium . this suspension was inoculated at 37c for about 4 to 6 h in order to get the bacteria to the dynamic level and compared to macfarland 0.5 standard at last . as a result was diluted to the proportion of 1/100 in order to reach 10 bacteria in each ml . to measure the mic , 1 ml of mooler hinton berath culture was poured in 10 tubes and mixed right after adding 1 ml of the essential oil to the first tube . one ml of first tube was added to the second and 1 ml of the second to the third tube respectively . then 1 ml of the microbial suspension was added to each tube to make 1/4 to 1/2048 concentrations . the tubes were incubated at 37c and mic was appointed by the growth or non - growth of the bacterium in the tubes . mbc was also measured by the second culture in mooler hinton agar medium ( 1 , 6 , 18 , 19 ) . the measurement of the zone of inhibition of bacterium adjacent to the eucalyptus essential oils the intended bacterium is distributed on mooler hinton agar medium with concentration of 0.5 macfarland and then some small holes were made on them . 50 l of the essential oils were added to each hole and the plate was incubated at 37c for 24 h. finally , after 24 h , the diameter of the zone of inhibition were measured ( 1 , 15 - 17 ) . relatively simple biochemical tests ( e.g. , positive reactions for coagulase , nuclease , alkaline phosphatase and mannitol fermentation ) can be used to differentiate s. aureus . results obtained from the chemical analysis of eucalyptus essential oils by gc / ms has been showed in table 2 . the obtained results from the ratification of staphylococcus aureus series the results obtained from the chemical analysis of eucalyptus essential oils by gc / ms minimum inhibitory concentration ( mic ) and the minimum bactericide concentration ( mbc ) of the essential oils eucalyptus spp by dilution method in the tube and the second culture in agar were summarized in table 3 . each of the oils was tested at concentrations ranging from 1.95 to 62.4 g / ml and 1/512 to 1/16 v / v . minimum inhibition concentration ( mic ) of the eucalyptus essential oils for e. camaldulensis 1/256 v / v was equal to 3.9 g / ml , for e. largiflorence 1/512 v / v was 1.95 g / ml , for e. malliodora 1/256 v / v was 3.9 g / ml and for e. polycarpa 1/128 v / v was 7.8 g / ml . minimum inhibitory concentration ( mic ) and the minimum bactericide concentration ( mbc ) of the essential oils eucalyptus spp by the dilution method in the tube and the second culture in agar each oils were test for mic and mbc concentration were presented as g / ml ( v / v ) antibacterial activity of the essential oils e. largiflorence , e. malliodora , e. polycarpa and e. camaldulensis ( zone of inhibition in mm ) were 26 , 22 , 18 and 20 mm , respectively . staphylococcus aureus is also considered as one of the resistant sample to drugs and pathogen agents in human , therefore it seems necessary to find out antimicrobial materials from alternative sources such as plants . eucalyptus is one of the herbal drugs with antimicrobial effects . in present study mic of the essential oils of e. malliodora , e. polycarpa , e. camaldulensis and e. largiflorence were evaluated and estimated 3.9 , 3.9 , 1.95 and 7.8 l / ml , respectively . the diameter of the zone of inhibition adjacent to essential oils was estimated 20 , 22 , 26 and 19 mm respectively . the results showed that these essential oils can strongly prevent the growth of staphylococcus aureus atcc 25923 and other clinical resistant bacteria . the obtained results are in line with other studies . however , mic of the e. largiflorence essential oils and diameter of zone of inhibition in comparison to other essential oils showed potent antimicrobial activity and inhibitory effect . this suggested e. largiflorence as an effective antimicrobial agent among all kinds of eucalyptus ( 1 ) . in addition in present study , the antimicrobial activity of eucalyptol was examined that showed a potent inhibitory effect on staphylococcus aureus atcc 25923 . eucalyptol acts as a main substance of the eucalyptus oil ( 14 ) . on the other hand 1 , 8-cineol and -pinene present in the chemical compounds of all four kinds of eucalyptus , where e. largiflorence essential oil has the most antimicrobial activity comparing to others . antibacterial activity of these essential oils were decreased when 1 , 8-cineol and -pinene were less than normal levels . consequently -pinene and 1 , 8-cineol are both considered as the most important antimicrobial substance of the eucalyptus oil ( 13 ) . last studies showed that eucalyptus oil has a widespread antimicrobial effects against the positive and negative gram bacteria ( 1 , 5 ) . also there are other studies proved antimicrobial compounds in eucalyptus and indicated the relation between traditional reported consumption and experiments have done in laboratories ( 6 , 11 ) . therefore , extract of the eucalyptus oil as an effective antimicrobial substance can be used in treatment of bacterial infections like skin injuries , acnes and lung infections ( 1 , 2 , 5 , 6 , 11 ) . eucalyptus has been showed a wide spectrum of antimicrobial and anti - cancer activities and used in design of new antibiotics ( 1 , 2 ) . it was concluded that the essential oils of eucalyptus is effective against staphylococcus aureus in - vitro , although more detailed studies require using these compounds in clinic and infectious disease .

because of its resistance to antibiotics , staphylococcus aureus causes many of problems in hospital and society . as one of the main reasons of clinical infections it can cause to serious surgical and cutaneous infections and pneumonia . the inhibitory effect of the essential oils include ; eucalyptus largiflorence , e. camaldulensis , e. malliodora and e. polycarpa as a natural and herbal antimicrobial substances on staphylococcus aureus atcc 25923 and other antibiotic resistant series separated from clinical samples were evaluated . the minimum inhibition concentration ( mic ) of the eucalyptus essential oils was appointed by the dilution method in the tube and the results revealed that the values for the e. camaldulensis 1/256 v / v , e. largiflorence 1/512 v / v , e. malliodora 1/256 v / v and e. polycarpa 1/128 v / v were 3.9 g / ml , 1.95 g / ml , 3.9 g / ml and 7.8 g / ml , respectively . eucalyptol is the major compound of the eucalyptus essential oil . the mic of the pure eucalyptol appointed by the dilution method in the tube was equal to 1.95 g / ml . in conclusion , anti staphylococcus activity of the eucalyptus essential oils suggested it s clinically useful potentials , although further studies are required .

the concept of cancer stem cells ( csc ) arose from the discovery that a majority of cells from some human leukemia ( acute myeloid leukemia ) , at different stages of differentiation , originated from transformed undifferentiated pluripotent stem cell . this led to the hypothesis , then the theory , that as in the normal somatic stem cells ( ssc ) and their derived tissues , a small population of cells , the cancer stem cells ( csc ) would reproduce ad infinitum and generate the very diverse , limited lifespan , multi - lineage differentiated majority of cells in a cancer , called the derived population cells ( dc ) ( fig . 1 ) . this was the concept of an aberrant stem cell system , a system gone awry . in agreement with such a scheme , csc were assumed to originate from somatic stem cells ( ssc ) and to represent a minor , qualitatively distinct , eternal population , transforming deterministically and irreversibly in a limited lifespan , more or less differentiated hierarchy of derived cells that would constitute the bulk of phenotypically diverse cancer cell populations . of course clinicians , frustrated by the only partial and transient success of their therapies , liked the idea . if the concept was valid , they would have to deal with one well - defined , but difficult to identify and study , population of cells responsible for a cancer . this would allow them to solve the problem of a cancer with one therapy well aimed at these cells . for industry the definition of different causal populations of cells in different patients would also allow proposing combinations of diagnoses and treatments for each patient . the experimental support of the concept was essentially that in xenotransplant experiments in immunologically deficient mice , only a minor fraction of the injected cells would generate tumors : the cancer stem cells . the origin of the csc in the transformation of ssc seemed logical . in cell - shedding tissues , like the skin and mucosae , it makes sense , as only the ssc would have the time to accumulate the range of mutations necessary for cell transformation . however , if the first oncogenic event is to confer an increase in loco of the lifespan to the cells , this would not be necessary . in fact , in experiments in various models in which an oncogene was expressed all during the cells reproducing and differentiating sequence , the transformation took place at the stage of pluripotency as well as of unipotency and even later ( for review , see ref . , although , to our knowledge , it was not formally expressed , the concept of a minor population of cells , responsible for the progression and evolution of a cancer cast a doubt about the validity and interest of the work on epigenetics and transcription expression performed in bulk tumors , in which most of the cells would be degenerate or terminally differentiated . the fundamental results of such studies in our knowledge of the biology of cancer and on prognostic diagnosis disagree with this concept : for instance gene expression allows to clarify and treat specifically breast and other cancers . the notion of csc as a qualitatively distinct population of cells has been implicit and sometimes expressed . it is not supported by the various experimental tests applied to the cells ( transplants , sphere formation in vitro , cell sorting with biomarkers , etc . ) which always show overlaps with other cells ( dc ) . on the other hand , if properly transplanted in fully immune - compromised mice , more than one - third of human melanoma cells generate tumors , i.e. , would be csc . even in acute lymphoid leukemia , intratumor heterogeneity also bears against the concept of one population of cells generating all the cells in a cancer . for example , the intratumor heterogeneity of human glioblastomas and other tumors suggests a multiclonal evolution compatible with the stochastic but not the csc model . another implied property of csc is , as for ssc , the irreversibility of the transformation in more differentiated cells , dc . this property , in fact , is now questioned for ssc and embryonic stem cells ( esc ) , since the expression of just 4 transcription factors has now been shown to be sufficient to convert fully differentiated cells to an esc state , and progenitor cells spontaneously revert to ssc upon crypt cloning . as for csc dc cell interconvertibility , the constant conversion of a few csc cells in many multiplying dc is certainly easier to demonstrate than a rare reversion of these numerous dc into a tiny minority of csc . the irreversibility is not valid in the case of human melanoma and is disproved by the regeneration over time in culture of a diversified cell population from purified dc and by the generation of cancer cells with stemness properties spontaneously following oncogene expression in primary p53-null mouse cells or metastasis or following emt induction in cell lines . conversely , csc , emt , chemoresistance characteristics are acquired by lung cancer cell lines after treatment with anti egfr drugs . linked to the concepts of irreversibility and qualitative nature of csc to dc transformation the deterministic character of the conversion was even related to the semiconservative character of dna replication , an asymmetric cell division , of one csc to one conserved csc and one derived cell . this deterministic character opposes all the evidence in favor of stochastic mechanisms of cancer cell diversity . of course , again , if these properties applied only to csc , the therapeutic problem would also converge on this cell population . however if csc multiply fast ( vide infra ) , it should be related to another attribute . indeed abcg drug transporters and enhanced dna repair have been observed in some cancer cells . however , again , the congruence of these properties with the other proposed csc properties has not been demonstrated . the analogy between ssc and csc has even been extended to the concept of the niche . in fact , rapidly dividing supposed csc are often found in preferential sites of the tumor , e.g. , near capillaries . however , it is a farfetched extrapolation to interpret these favorable spaces as preordained sites , the niche . it seems simpler , even if less spectacular , to assume that an oxygen - rich environment is more favorable for proliferation . the use of biomarkers , allowing purifying , to some extent , csc by cell sorting , has greatly contributed to the expansion of the field ( e.g. , cd44 , cd133 , ald4 ) . however , the validity of these biomarkers is cast in doubt by one disturbing fact . although the question was asked several times in reviews , sequential cell sorting purifying csc having all the properties and biomarkers of csc has , to our knowledge , never been reported . in fact , the fraction of cells expressing one biomarker in breast csc was not expressing another biomarker . with this and other methodologies , the separation of a proportion of cells by any criterion ( whether seeding capacity , sphere formation , biomarker - based cell sorting , etc . ) assumes that the property used is stable in tissue , i.e. , cells in a negative phase of any fluctuating property ( e.g. , epigenetic , transcriptional , feedback linked control ) will be missed . of course this would not apply to a qualitatively irreversibly well - defined csc population ! in fact , any criterion used to define a cell population applies to those cells that answer it at the moment it is used . in fact some of them are good markers for normal tissue adjacent to a tumor . in the csc literature , there has always been an ambiguity with regard to the proliferative or quiescent state of the csc cells . in fact , the normal stem cell models have opposite characteristics : while esc are strongly proliferative , ssc were , until recently , considered as rarely dividing cells . this was even used , for some ssc , as a criterion to identify them by the remnants of their dna labeling . however , even for some ssc , it is now accepted that there may be 2 interconverting populations of ssc , one quiescent , one proliferating . the concept of quiescent csc , while useful to explain the continued presence of cancer cells after therapy , does not fit in with other proposed properties of the supposed csc : e.g. , the spheroid formation assay , which allows purification to some extent csc by selective growth , the sp cells which extrude drugs and which would soon disappear if they reproduced less than other cancer cells . moreover , this concept is even more incompatible with the existence of csc in cell lines : they would soon disappear . with the progressive abandonment of claimed ssc and esc properties , the csc concept has evolved toward the existence of very competitive cancer cells continuously generating a majority of cells , less active , degenerating , and with limited reproduction capacity and even survival potential . it explained the important discrepancy between cell proliferation rates , evaluated by tritiated thymidine labeling of biopsies , and the measured in vivo tumor growth rate in breast cancers . this has been confirmed and visualized more directly by the more sophisticated method of linear tracing in experimental models in which the expression of an oncogene is induced at a chosen time and the consequences examined in the cell of origin of the tumor and in its successive descendants . the hierarchy of progressively more diversified tumor phenotypes , in fact , reproduces the well - known behavior of cells in developing metastases . it is easily explained by the fact that most genetic ( and probably epigenetic and others ) events , when not neutral , lead to loss of competitiveness and much more rarely to an increase of competitiveness . in the case of cancer cells , as in esc , the default state of the cell is differentiation , which may be due to loss of the stem cell program . in this framework , the different characteristics of so - called csc do not necessarily coexist in the same cells . in fact , in several cases , cells that exhibit the biochemical markers of csc are precisely not those that have the functional characteristics of sphere formation and tumorigenicity . the progressive simplification and evolution of the definition of csc has been called euphemistically a paradigm shift and described as the plasticity of csc , plasticity and clonal diversity of csc , stemness as a flexible quality of cancer cell , this constantly evolving definition has of course made the concept an elusive target for critical analysis . reprogramming stemness with nanog and lin28 may even reverse back the cancer character of sarcoma cells and , as shown more than 30 y ago , the oncogenic potential of teratocarcinoma cells after grafting in blastocysts was reversed . is stemness not rather a property or phenotype that cancer cells may have , lose , and even acquire , like the other hallmarks of cancer , rather than the definition of a distinct population of cells ? in the present stage of uncertainty , the use of a precise well - defined terminology based on operational definitions would certainly clarify a literature confused by the use of the variously defined , constantly changing , fuzzy concept of csc . the literature proposes such definitions : the cell of origin of a tumor ( cot ) is the one in which the original oncogenic event(s ) occurred . the tumor initiating cell ( tic ) is the cell that first showed the signs of transformation and initiated the tumor . it may not necessarily be the cell of origin : for instance , in linear tracing experiments the expression of the oncogene begins at the time chosen by the experimenter , but the transformation may occur at a later stage of the cell evolution ( e.g. , pluripotent cell ) . cell of origin and tic identity may bear on the phenotype of the resulting tumor . the tumor propagating cell ( tpc ) or cancer repopulating cell is the already committed cancer cell that is able to generate a tumor ; for instance , in xenotranplants the cancer cell transplant does not initiate a cancer , it merely propagates it in a new site . xenotransplants can be orthoptic ( implanted at the site of the naturally occurring tumor ) or ectopic ( other sites ) . in situ and metastatic propagations should be distinguished . cancer stemloids would be the rapidly dividing , evolving cells of the cancer that generate the slower dividing , more differentiated derived cells . this is a phenotype adopted for example by disseminated tumor cells , which at some time may explode in metastatic growth . in some cases , ( e.g. , cd44++ cd24- cells , cd133 + cells , aldehyde dehydrogenase - expressing cells adh , etc . ) should be called by their operational property , e.g. , cd133 cells etc . cancer cells expressing an embryonic stem cell program , essential for maintaining dedifferentiation , and thus repressing the expression of the various differentiation programs that constitute the hierarchical descendants of these cells , are just cells expressing the stemness esc program or pluripotency . such a program may totally or partially overlap with other programs developed at some time by cancer cells , such as the epithelial the 3 programs stemcellness , emt , and radioresistance can be induced together by emt inducing transcription factors ( e.g. , zeb ) in some cell lines . thus , stemness would be a hallmark or a phenotype of cancer , probably linked to dedifferentiation , characterizing in a cancer some cells at some time . there would not be a separate population of csc , just as there is no population of cancer emt cells ! the stemness could be a functional ( transplant , hierarchy , etc . ) or / and a biochemical ( expression of esc inducing transcription factors ) property or hallmark . in fact , the state of any given cell in a tumor results from the programs expressed , at the time of the investigation , by this cell . this is more or less reversible depending of the mechanisms involved , genetic , epigenetic , or resulting from a signaling equilibrium . presumably , a large majority of tumor cells with a differentiated phenotype and a limited lifespan will never revert to active dedifferentiated phenotype . of course , if to treat a cancer one had to target one population of well - defined csc , the aim of therapeutic research should be to find drugs for this target . our and other analyses bear against this approach . on the other hand , if , as the evidence suggests , we have to deal with a constantly evolving diversified population of cells , the best therapies should then , as in the case of hiv , be simultaneous multi - target therapies : hit most of the cells at the same time , not allowing cells already resistant to one therapy to survive and permit some of them to acquire later resistance to another therapy .

the cancer stem cells ( csc ) hypothesis represents a pathological extrapolation of the physiological concept of embryonic and somatic stem cells . in its initial definition , it encompassed the hypothesis of a qualitatively distinct population of immortal cancer cells originating from somatic stem cells , which generate in xenotransplants by a deterministic irreversible process , the hierarchy of more differentiated finite lifespan derived cells , which constitute , themselves , the bulk of the cancer . these csc would express specific biomarkers and gene expressions related to chemo- and radioresistance , stemness , epithelial mesenchymal transition , etc . no convincing congruence of several of these properties in one cell population has been demonstrated . the concept has greatly evolved with time and with different authors ( the plasticity of cancer stem cells ) , leading to a minimal definition of cells generating a hierarchy of derived cells . in this article these concepts are analyzed . it is proposed that stemness is a property , more or less reversible , a hallmark of some cells at some time in a cancer cell population , as immortality , dormancy , chemo- or radioresistance , epithelial mesenchymal transition etc . these phenotypic properties represent the result of independent , linked , or more or less congruent , genetic , epigenetic , or signaling programs .

it then leaves the anterior chamber through the trabecular meshwork to the venous system ( outflow ) . normally , there is equilibrium between inflow and outflow that creates normal intraocular pressure ( iop).1,2 any circumstances that affect the formation of aqueous humor or outflow of aqueous humor cause changes in iop . the progression of damage eventually involves the optic nerve and irreversible visual loss.3 glaucoma is the second leading cause of blindness worldwide.4 the only preventable risk factor for the development and progression of glaucoma is iop . correctly measuring iop is very important in diagnosing glaucoma and conducting follow - ups.3 medical , laser , or surgical treatments of glaucoma concentrate on lowering iop . earlier studies have shown that every 1 mmhg drop in iop decreases visual field damage by 10%.5 therefore , precise measurements are very important . . the ideal device must be easy to use , rapid , safe , and precise , irrespective of patient posture or age . albrecht von graefe invented the first tonometer in 1863.6 today , we still have problems precisely measuring iop in some conditions , such as in patients with corneal scar or corneal edema . two different types of applanation tonometers exist . the first calculates iop by measuring the flattened corneal area with constant force . the maklakov tonometer , which was invented in 1885 , is an example of this.6 the second applanation tonometer system calculates iop by measuring the force needed to flatten a constant corneal area . a prototype of this is the goldmann applanation tonometer ( gat ; haay - streit ag , koeniz , switzerland ) , invented in the 1950s . today , the gat is most commonly used and is considered to be the gold standard device for measuring iop.6 a gat is mounted on a biomicroscope and a topical anesthesia - fluorescein dye is used . because it flattens such a small area at the central cornea , measurements are not affected by scleral stiffness . another applanation device is a non - contact tonometer ( nct ; nidek co. , ltd . an nct uses air to flatten the cornea instead of touching it.7 the nct has been available for about 40 years.7 the tono - pen xl ( tpxl ; reichert technologies , depew , ny , usa ) is a small and portable device that has been used since the 1980s . it is an applanation tonometer , and topical anesthesia is needed to measure the iop . in this study , we aimed to compare iop measurements via the three different tonometers we routinely use in our clinic : gat , tpxl ( reichert inc , ny , usa ) , and nidek nct nt-530 ( nidek co. , ltd . , a total of 200 eyes of 200 patients ( 108 female , 92 male ) from our clinic in december 2013 were consecutively included . inclusion criteria were as follows : aged 18 years or more , no recent use of topical - systemic medicine , no use of contact lenses , no ocular surface disease , no significant degree of corneal astigmatism , no ocular pathology such as retinal disease or glaucoma , and no connective tissue disease . all types of iop measurement were taken by three masked physicians via appropriately calibrated tonometers consecutively , with 10-minute intervals . all measurements were carried out at similar times , between 10 am and 11 am , to avoid early - morning changes in corneal thickness due to overnight edema . the eyes were then anesthetized using alcaine 0.5% eye drops ( alcon laboratories inc . , fort worth , tx , usa ) , and a second physician took measurements with the tpxl . finally , alcaine was applied again and a fluorescein strip was applied to the inferior conjunctival fornix . the device has a 5.7-inch color liquid crystal display , and the tilting function offers easy operation for a standing operator . the device has auto puff control ( apc ) , which provides a quieter and softer puff of air for the patient s comfort . if the first puff is too strong , the device automatically uses a softer puff of air . the screen shows the results of three measurements , and their average for each eye is obtained by pressing a button three times . it uses batteries as a power source , and its measurement range is 580 mmhg , according to the user manual . after topical anesthesia is administered , the operator touches the covered tip of the tpxl to the cornea several times . each touch to the anesthetized corneal surface is analyzed and stored by the device for statistical comparison . when four valid readings are obtained , the mean iop and the standard deviation for those readings are shown on the liquid crystal display , which is situated on the side of the device . measuring both eyes takes about 30 seconds , including administration of the anesthetic and the patient s tolerance of the drops . finally , iop was measured via a gat , which takes about 3 minutes , including administration of the anesthetic and fluorescein . we used spss version 20 ( ibm , armonk , ny , usa ) software . the scheffe method was used for post hoc comparison . a p - value of < 0.05 was considered statistically significant . the mean iop was 16.12.8 mmhg ( range 1026 ) with the nct , 16.13.0 mmhg ( range 925 ) with the tpxl , and 15.52.2 mmhg ( range 1022 ) with the gat . figure 1 shows the iop frequency of this study population when measured with the gat . a correlation analysis of nct gat , tpxl gat , and nct tpxl measurements is shown in figures 2 , 3 , and 4 . the mean difference between the measurements in eyes by the different techniques was 0.6 mmhg for nct gat ( figure 5 ) , 0.7 mmhg for tpxl gat ( figure 6 ) , and 0.02 mmhg for nct tpxl ( figure 7 ) . there was no significant difference between groups according to one - way anova with scheffe post hoc comparison test results . p - values were 0.998 for nct tpxl , 0.067 for nct gat , and 0.059 for tpxl gat . gat is still considered the gold standard and most commonly used method of tonometry.9 nevertheless , the main disadvantages of the gat include risk of contamination , the presence of common situations that lead to errors , and that it can not be performed by assistant medical staff . it is commonly affected by corneal stiffness , thickness , scars , irregularities , and curvature . steep corneas , thick corneas ( except edema , which causes false - low readings ) , and against - the - rule astigmatism cause false - high readings.10 thin corneas , with rule astigmatism , cause false - low readings.10 insufficient fluorescein use causes false - low readings , and excessive fluorescein use causes false - high readings . the presence of corneal epithelial defects and previous corneal surgeries also complicate measurements.11 finally , there is a contamination risk , so the tool tip must be cleaned after each use.12 screenings with an nct may be undertaken by non - medical and unlicensed personnel under the supervision of a doctor . because the nct is a non - contact tool , there is no contamination risk.13,14 furthermore , topical anesthetic drops or fluorescein dye are not necessary , which allows for rapid taking of measurements . the table - mounted nct has some disadvantages ( eg , the iops of small children and infants can not be measured , and false - high readings are common if patients tighten their eyelids ) . the tpxl can easily be used in an office environment or in the operating room.8 after undergoing training , assistant health personnel can use the tpxl.15 the nct and tpxl are easier and faster to use than the gat , but suspicions about their results still exist . in this study other studies show similar results.1622 parker et al16 compared nct and gat and found results were concordant between the two devices . in another study , tonnu et al17 compared nct , tpxl , and gat and reported that all three devices showed homologous results.17 however , other studies found contrasting results.23,24 farhood23 showed that nct and gat were not well correlated , and nct measurements gave higher iop results regardless of the patient s age or sex . in particular , when the gat measurement exceeded 24 mmhg , the difference in readings between the two instruments increased . farhood23 reported that the lower the iop as measured by gat , the more reliable the corresponding nct readings . other devices recently introduced to market are the dynamic contour tonometer ( dct ) and the ocular response analyzer ( ora ) . published studies have compared these new devices with gat.2528 carbonaro et al25 compared gat , dct , and corneal - compensated iop with the ora and found similar reliability in all three devices . in this study , we found that measurements taken with the nidek nct and the tpxl agree well with those via the gat in normal subjects . patients with extreme iop levels were not included in this study , and some studies have shown that correlation errors between instruments occur within extreme iops beyond the normal range.23 however , our results showed that devices that are more practical and faster than the gat may be used for screening normal subjects independently from central corneal thickness . further studies that compare more devices in a larger case series are needed , as are studies investigating iop measurement via different devices and comparing different patient groups ( eg , different age groups , patients with previous corneal surgeries or corneal pathologies , or patients with glaucoma ) .

objectivewe aimed to compare intraocular pressure ( iop ) measurements via three different tonometers : the goldmann applanation tonometer ( gat ) , the tono - pen xl ( tpxl ) , and a non - contact airpuff tonometer ( nct).methodsthis was a cross - sectional study of 200 eyes from 200 patients . right eyes of all patients were included in this study . iop was measured via gat , nct , and tpxl by three physicians . each physician used one of the tonometers . measurements via the three devices were compared.resultsthe mean iop was 15.52.2 mmhg ( range 1022 ) with the gat , 16.13.0 ( range 925 ) with the tpxl , and 16.12.8 ( range 1026 ) with the nct . bland altman analysis showed that the mean difference between measurements from the nct and the gat was 0.62.3 mmhg . the mean difference between the tpxl and gat measurements was 0.72.5 mmhg . the mean difference between the nct and tpxl measurements was 0.023.0 mmhg . there was no significant difference between the groups according to a one - way analysis of variance ( anova ) test . p - values were 0.998 for nct tpxl , 0.067 for nct gat , and 0.059 for tpxlgat.conclusionthe nct and tpxl provide iop measurements comparable to those of the gold standard gat in normotensive eyes .

the burden of non - communicable disease in the developing countries is increasing and leading to high mortality rates . nowadays , type 2 diabetes ( t2 dm ) is pandemic and there are no signs of reduction in incidence rates . diabetes is one of the most important risk factors for cardiovascular diseases and is the most prevalent cause of mortality in diabetic patients . metabolic syndrome is highly prevalent in type 2 diabetic patients and is a strong risk factor for cardiovascular diseases in such patients . it is estimated that 16% of people above 20 years of age globally have metabolic syndrome . in iran , this syndrome is dramatically prevalent and close to 34% of people above 20 years old have metabolic syndrome , according to the adult treatment panel ( atpiii ) . differences in genetics , diet , physical activity , age and gender in different societies can affect the prevalence of this syndrome . there is no globally accepted definition for the diagnosis of this syndrome and most studies use the atpiii criteria for defining metabolic syndrome . in 2005 , the international diabetes federation ( idf ) has suggested a definition for the diagnosis of people with metabolic syndrome , which is applicable to different ethnic groups . in the idf criteria , central obesity is a prerequisite and central obesity assessment by waist circumference for different genders and ethnic groups according to idf is necessary . , the appropriate cutoff point for the diagnosis of metabolic syndrome in men and women in kerman has been determined . currently , metabolic syndrome has become an important health problem and there is a need for investigation in this field . considering the fact that diabetic patients with metabolic syndrome also have cardiovascular risk factors , the diagnosis of metabolic syndrome in such patients is very important , and leads to a better disease control and prevention of cardiovascular complications . the present study was performed to determine the prevalence of metabolic syndrome and its related factors in type 2 diabetic patients of kerman , iran . the data used in this study was part of the coronary artery disease risk factors ( kercadr ) study in kerman . in kercadr , 5,900 people were recruited from which 950 people were diagnosed with diabetes and entered into our study in 2013 . the variables evaluated in this study were age , gender , job , education , bmi , total cholesterol , hdl cholesterol , ldl cholesterol , fasting blood sugar ( fbs ) , systolic blood pressure , diastolic blood pressure , waist circumference , triglycerides , smoking , physical activity , the duration of diabetes , history of cardiovascular diseases , and the ratio of waist circumference to hip circumference . data was analyzed by chi - square , t - test , and logistic regression using spss ( revision 20 ) software . the prevalence of metabolic syndrome in people with diabetes was determined according to the below criteria . the atpiii criteria that include three or more of the following items : central obesity : waist circumference more than 102 centimeters in men and more than 88 cm in womentriglycerides 150 mg / dl or using drugs for hyper triglyceridemiacholesterol hdl < 40 mg / dl in men and less than 50 mgr / dl in women or under treatment for low hdl cholesterolhypertension systolic blood pressure more than 130 mmhg or diastolic blood pressure 85 mmhg or being under treatment for hypertensionfbs 100 mg / dl or being under treatment for diabetes or a diagnosis of type 2 diabetes.according to the idf 2005 criteria , central obesity ( waist circumference 94 cm in men and 80 cm in women ) and two or more of these criteria should be present : triglyceride 150 mg / dl or under treatment for hyper triglyceridemiacholesterol hdl < 40 mg / dl in men and less than 50 mgr / dl in women or under treatment for low hdl cholesterol levelshypertension systolic blood pressure more than 130 mmhg or diastolic blood pressure 85 mmhg or being under treatment for hypertensionfbs 100 mg / dl or being under treatment for diabetes or a diagnosis of type 2 diabetes . central obesity : waist circumference more than 102 centimeters in men and more than 88 cm in women triglycerides 150 mg / dl or using drugs for hyper triglyceridemia cholesterol hdl < 40 mg / dl in men and less than 50 mgr / dl in women or under treatment for low hdl cholesterol hypertension systolic blood pressure more than 130 mmhg or diastolic blood pressure 85 mmhg or being under treatment for hypertension fbs 100 mg / dl or being under treatment for diabetes or a diagnosis of type 2 diabetes . according to the idf 2005 criteria , central obesity ( waist circumference 94 cm in men and 80 cm in women ) and two or more of these criteria should be present : triglyceride 150 mg / dl or under treatment for hyper triglyceridemia cholesterol hdl < 40 mg / dl in men and less than 50 mgr / dl in women or under treatment for low hdl cholesterol levels hypertension systolic blood pressure more than 130 mmhg or diastolic blood pressure 85 mmhg or being under treatment for hypertension fbs 100 mg / dl or being under treatment for diabetes or a diagnosis of type 2 diabetes . study is the presence of central obesity ( waist circumference 86 cm in men and 83 cm in women ) plus two or more of these criteria : triglyceride 150 mg / dl or under treatment for hyper triglyceridemiacholesterol hdl < 40 mg / dl in men and less than 50 mgr / dl in women or under treatment for low hdl cholesterol levelshypertension systolic blood pressure more than 130 mmhg or diastolic blood pressure 85 mmhg or being under treatment for hypertensionfbs 100 mg / dl or being under treatment for diabetes or a diagnosis of type 2 diabetes . triglyceride 150 mg / dl or under treatment for hyper triglyceridemia cholesterol hdl < 40 mg / dl in men and less than 50 mgr / dl in women or under treatment for low hdl cholesterol levels hypertension systolic blood pressure more than 130 mmhg or diastolic blood pressure 85 mmhg or being under treatment for hypertension fbs 100 mg / dl or being under treatment for diabetes or a diagnosis of type 2 diabetes . the present study was carried out on 950 patients with diabetes type 2 in which 392 ( 41.3% ) were male and 558 ( 58.7% ) were female . the mean age of the patients was 56.011.6 ( females 55.111.1 and males 57.212.2 ) . the prevalence of metabolic syndrome according to atpiii was 73.4% ( men 64.8% and women 79.4% ) . according to the idf criteria , it was 64.9% ( men 46.7% and women 77.8% ) and according to the new criteria , it was 70.4% ( men 69% and women 71.3% ) . figure 1 compares the prevalence of metabolic syndrome according to the three criteria . shows the prevalence of metabolic syndrome according to the three criteria among type 2 diabetics in different age groups . based on the result of the three criteria , among the females low hdl , high bmi , weight , blood pressure , ldl , total cholesterol , and triglyceride were associated with increased metabolic syndrome prevalence . the compatibility score of the atpiii and idf according to the kappa statistic was 0.49 , for idf and the new kerman criteria was 0.66 , and for atpiii and the new kerman criteria was 0.50 . multivariate logistic regression adjusted for confounders , in people who had metabolic syndrome according to both idf and atpiii criteria , showed that gender , fasting blood sugar , triglycerides , hdl , waist circumference and systolic blood pressure were predictive factors for metabolic syndrome in the population . also in people who had metabolic syndrome according to the three criteria , the same variables were able to predict the incidence of metabolic syndrome . the adjusted or with 95% confidence intervals for factors predicting metabolic syndrome according to both atpiii and idf in the present study , the prevalence of metabolic syndrome in patients with diabetes was 64% to 73% . in studies carried out in ahvaz , the prevalence of metabolic syndrome in diabetic patients was 73.1% ( atpiii ) and 64.9% ( idf ) , in esfahan 65% ( atpiii ) , and in england 94% ( both atpiii & idf ) . in other studies , the prevalence of metabolic syndrome was estimated to be 62.3% and 56.8% ( idf and atpiii ) in india , and 71.1% and 60.4% ( idf and atpiii ) in sub - saharan africa . in the present study , according to the three criteria , the prevalence of metabolic syndrome was higher in women than men . in all other studies , the reason might be less activity , more weight and higher prevalence of dyslipidemia in women . the female gender , fasting blood sugar , triglyceride , cholesterol , hdl , waist circumference and systolic blood pressure were able to predict the prevalence of metabolic syndrome in people with diabetes . in the ahvaz study , the female gender , physical activity , microalbuminuria , serum triglyceride and cholesterol , and in the isfahan study , age , gender , fasting blood sugar , hypertension , bmi , serum triglyceride and serum cholesterol were the predictors of metabolic syndrome . the female gender , cholesterol , and triglyceride in all these studies were a predicting factor . the difference among other variables could be due to differences in data collection , sampling methods and using different criteria in diagnosing people with metabolic syndrome . among the limitations of the present study is that the population was from kerman province and the results may therefore not be generalisable to other populations . the present study shows that the prevalence of metabolic syndrome in people with type 2 diabetes is very high in kerman .

metabolic syndrome is highly prevalent in type 2 diabetics and is a strong risk factor for cardiovascular diseases in such patients . the aim of this study was to determine the prevalence of metabolic syndrome according to the three criteria of atpiii , idf and the new criteria for metabolic syndrome diagnosis in kerman , iran . this cross - sectional study was performed on 950 diabetic type 2 patients . data was analyzed by independent t - test , chi - square and logistic regression using the spss ( revision 20 ) software . the prevalence of metabolic syndrome in kerman was 73.4 , 64.9 , and 70.4% , according to the above criteria . fasting blood sugar , gender , triglyceride , hdl , waist circumference , and systolic blood pressure were related to the prevalence of metabolic syndrome according to the above - mentioned criteria.the prevalence of metabolic syndrome is high in type 2 diabetic patients and the above - mentioned factors exacerbate the situation .

most poor people seek help at public run hospitals where services are free , and those from families below the poverty line ( bpl ) are exempted from payments for medicines and investigations . while this is helpful , there are other hidden costs which the family has to bear . patients often need to buy medicines which are unavailable in the hospital , meet the expenses for food , transport , etc . the total costs usually workout to be well beyond the means of those coming from bpl households . in fact , health care costs often lead to further impoverishment and sets off a vicious cycle of ill - health and poverty , one fuelling the other . this had been investigated in maternal health and it is relevant for scaling up of mental health care too . the financial impact of hospitalization for psychoses needs to be evaluated , especially on the poorer sections of the society . this study aims to assess the treatment related expenses of patients admitted to a government general hospital with psychotic illness . the present study was conducted after getting approval from institutional research board of government medical college , thrissur . patients who meet the international classification of diseases ( icd)-10 criteria for schizophrenia , bipolar mood disorders , and other psychotic conditions were prospectively identified from the psychiatry wards of government medical college , thrissur . they were interviewed after getting informed consent ( written ) and we used specially designed study proforma for data collection . these in - depth interviews were aimed to explore the financial burden experienced by the family during hospitalization . the major components of expenses during the hospital stay were categorized as cost of medicines , investigations , food , travel , and other incidental expenses . the details of medication and investigations were collected from the case records on the last day of hospitalization . we also analyzed the different categories of expenses and calculated the total expenses incurred during hospitalization . all those who had a bpl card issued by the revenue department of kerala were considered as poor . we used descriptive statistics such as mean , median , range , and standard deviation to explain the results . mann whitney u - test was used to compare costs among bpl and above poverty line ( apl ) patients . spearman 's rank correlation coefficient was used for finding out the correlation between study variables . there were 104 cases who received an icd-10 diagnosis of psychosis during the 6-months study period . four cases had to be excluded due to lack of consent and inability to schedule the interviews on the day of discharge . only 3% of the subjects were illiterate while 34% had primary level education , and the rest had education up to high school or more . the number of earning members in each family ranged from 1 to 4 while the average family size was four . pension benefits were available to 29% of the families , but the average pension was only inr 300/month . about a half of all patients ( 49% ) were engaged in skilled , semiskilled or unskilled work , often for daily wages , before the onset of illness . about 21 of them stopped working less than a month prior to admission whereas 13 patients were not working for the last 1 - 6 months . during the hospitalization , about 49% of the caregivers had to cut back work resulting in an average loss inr 1500 from the caregiver income during the hospitalization period alone . nearly half ( 45% ) of the families had availed loans for different purposes , and a significant proportion ( 22.2% ) of them took loans to meet the expenses of hospitalization for psychosis . the expenses incurred during hospitalization included cost of medicines , laboratory investigations , food , travel and other incidental costs . though most patients ( 76% ) received free medicines from the hospital , some drugs had to be purchased . almost a quarter ( 24% ) had to purchase all the necessary medicines from elsewhere . both bpl and apl patients spent almost same amount for purchase of medicines ( z = 0.469 , p = 0.639 ) . more hospital days meant more money spent on medication ( r = 0.442 , p = 0.00 ) . while most patients ( 94% ) needed laboratory investigations , only a minority ( 19.2% ) could get all the investigations done in the hospital itself . many ( 41.5% ) patients had to pay and use other facilities for some investigations . among 94 patients who needed investigations , patients from bpl households spent significantly less amount of money for investigations ( z = 2.682 , p = 0.007 ) and this expense did not depend on the duration of hospitalization ( r = 0.101 , p = 0.320 ) . even though , food was available at free of cost for inpatients from bpl families , the quantity was insufficient . the average cost of food during the hospitalization was inr 1200 , and this increased with the duration of hospital stay ( r = 0.619 , p = 0.00 ) . among the 100 patients admitted in the hospital , 65% hailed from thrissur district and the remaining 35% were from the neighboring districts such as palakkad , malappuram , and ernakulam . majority of patients ( 60% ) made use of vehicles such as car , auto or ambulance for conveyance . the number of persons accompanying the patient on their journey to the hospital was 1 - 5 while 1 - 3 persons accompanied the patient after getting discharged from the hospital . an average cost of travel per patient was inr 396 for their journey to and fro the hospital . the total direct expense of hospital stay was calculated as the sum of cost of medicine , laboratory test , food , travel , and other miscellaneous expenses . the average total expenses including indirect expenses was inr 3975 and this increased with the duration of hospital stay ( r = 0.515 , p = 0.00 ) . almost half of the families ( 46% ) had received financial support from relatives outside their household and this averaged inr 500 . majority ( 67% ) of patients treated for psychosis in a government - run medical college came from low - income households living below the poverty line . the average out of pocket expense was more than 1200 rupees and averaged inr 100/day . the average cost of hospitalization rose to about inr 4000 when indirect expenses are added on . we did not find a significant difference between apl and bpl families in the expenses related to hospitalization except that the patients from bpl families spent less on investigations that were free for them . many families had to rely on hired vehicles for bringing the patient to the hospital . there are schemes that allow reimbursement of the expenses for transport during emergency obstetric care . there is no provision to reimburse the cost of transport of a person who needs hospital admission and care for psychosis . government should extend such schemes to include those who need hospitalization for a psychotic illness . almost half ( 45% ) of the families had availed loans , a clear indication of their strained financial status . about a fifth of these families borrowed money to meet the expenses for the current hospitalization and treatment . this is a matter of great concern as health care costs , especially out of pocket expenses and is a major cause for further impoverishment of poor households . lack of support would lead these families to take more loans and get into a debt trap . our study shows that health care cost , especially the costs associated with management of psychosis is well beyond the financial capability of low - income families . government should recognize this and offer financial support to meet the treatment related expenses of people with psychosis . the model of janani suraksha yojana can be adopted for financing expenses of psychiatric hospitalization . many families are laboring under serious financial strain while they are engaged in the treatment of psychosis . the governments should seriously consider financial support for treatment of poor people affected by major health conditions like psychoses . support should extend well beyond free services and should include strategies to finance the direct and indirect costs of treatment . to the best of our knowledge , this is the first study from india to report the costs associated with hospitalization for people with psychotic illness in a general hospital setting . the treatment of mental illness involves significant expenditure , frequent , and considerable use of health care resources . health care financing in india is vastly different from western countries and some developed economies where in health insurance plays a very large role . even there , the situation is bad , if the provision for third party payment is unavailable . there are schemes like rashtriya swasthya bima yojana ( rsby ) and other health insurance policies under government of india that are running essentially for inpatient service for people from bpl families . people with psychiatric illness were kept out of the benefits of rsby scheme till recently . . a special scheme to support management of psychotic disorders like schizophrenia and bipolar disorders would be helpful to many families . good access to effective treatment and adherence to long - term prophylactic treatment is important in the management of schizophrenia and recurrent bipolar disorder . poverty is a barrier that denies access to good quality mental health care for them . governments and policy makers should design and implement schemes to finance treatment of psychosis that eventually will help to improve outcomes . the cost of care leading to further impoverishment is a real problem , especially in low - income settings . we need to adopt an intervention which goes well beyond the conventional management of illness to prevent this .

background : combination of ill health and poverty poses special challenges to health care providers . mental illness and costs are linked in terms of long - term treatment and lost productivity , and it affects social development . the purpose of the present study is to assess the economic burden of poor families when a family member needs hospitalization due to psychosis.materials and methods : the information was gathered from caregivers of 100 psychotic inpatients of medical college hospital of kerala during a period of 6 months . data regarding components of expenses such as cost of medicine , laboratory investigations , food , travel , and other miscellaneous expenses during their inpatient period were collected by direct personal interview using specially designed proforma . the data were analyzed using epi - info software . the patients below the poverty line ( bpl ) were compared with those above poverty line ( apl).results : there was no significant difference between patients from bpl and apl in respect of amounts spent on the studied variables except for laboratory investigations during the hospital stay.conclusions:the results showed that the studied subjects are facing financial difficulties not only due to hospitalization , but also due to the recurrent expense of their ongoing medication . the study recommends the need of financial support from the government for the treatment of psychotic patients .

compared to hiv - uninfected individuals living with mycobacterium tuberculosis infection ( mtbi ) , people living with hiv ( plhiv ) possess a 2037-fold higher risk of developing tuberculosis ( tb ) . this disease accounts for approximately 25% of all hiv - related deaths [ 13 ] . the prevailing paradigm explaining the immunologic mechanism underlying this epidemiologic phenomenon is that hiv eliminates cd4 t cells , including those presumed to be essential for mtb control . interferon - gamma ( ifn- ) production by t cells in response to an mtb stimulus is the standard immunologic test for mtbi ; however , this measurement does not differentiate mtbi from tb disease . since progression along the tb disease spectrum is a major predictor of mortality for plhiv , there is a critical need for clinical immune biomarkers that reliably predict a patient 's precise tb condition . multiparametric analyses of the immune system have illuminated our insight of the mechanisms of disease pathogenesis and protection [ 410 ] . it is clear now that the immune response to any given pathogen is complex and multifaceted . thus , relying on a single immunologic measure to yield an accurate diagnosis is suboptimal and perhaps even misleading . understanding the dynamics of an immune equilibrium between competing responses may improve our predictive capacity for clinical outcome ( see supplemental figure 1 in supplementary material available online at http://dx.doi.org/10.1155/2016/1478340 ) . for example , during tb infection , anti - inflammatory agents ( such as il-4 , il-10 , and immune checkpoint inhibitors ) prevent host tissue destruction due to excessive cell - mediated immunity [ 1114 ] . in contrast , excessive il-4 or il-10 production may result in a decreased containment of intracellular mtb and therefore theoretically increased risk of tb disease progression [ 15 , 16 ] . to evaluate if the balance between pro- and anti - inflammatory cd4 t cell responses from plhiv subjects with tb correlates with tb progression , we quantified the production of mycobacteria - specific ifn- , il-4 , and il-10 simultaneously . we hypothesized a direct relationship between hiv disease severity and a skewing of the immune equilibrium away from cell - mediated and towards an anti - inflammatory profile . in addition , we profiled the cytokine responses from cd8 , cd56cd3 nk cells , and cd3cd4cd8cd56 ( double negative t lymphocytes ) . as the cd4 t cell compartment wanes with advancing hiv disease status , these immune cell types gain prominence . for plhiv at risk for tb disease development , our objective is to elucidate the effect of hiv progression on the balance of the antimycobacterial immune response . adults with microbiologically confirmed ( genexpert mtb / rif or culture positive ) pulmonary tb ( n = 12 ) were enrolled after completing written informed consent . ethical approval was obtained by all relevant bodies including baylor college of medicine , swaziland children 's foundation , baylor college of medicine irb , and the swaziland ethics committee . blood collected into acd tubes was transported to the laboratory , within 4 hours , and pbmcs were isolated using ficoll density gradient as previously described . to elicit an immune response by the adaptive and innate immune responses , pbmcs were stimulated with mycobacterium bovis whole cell lysate ( 5 g / ml ) for 16 hours which was obtained through bei resources , naid , nih ( mycobacterium bovis , strain af 2122/97 atcc baa-935 , whole cell lysate , nr-31211 ) . stimulation occurred in the presence of brefeldin a ( sigma , 1 g / ml ) , golgi - stop ( bd biosciences , 0.7 g / ml ) , and costimulatory antibodies cd28/cd49 ( bd biosciences , 2.5 g / ml ) . following stimulation , cells were washed and stained for viability ( ghost dye , tonbo biosciences ) , surface antigens , cd3 ( biolegend ) , cd8 ( biolegend ) , cd4 ( ebioscience ) , cd14 ( biolegend ) , and cd56 ( biolegend ) , and intracellular proteins , ifn- ( life technologies ) , il-4 ( bd bioscience ) , and il-10 ( bd bioscience ) . the cells were acquired on a bd lsr ii fortessa flow cytometer as previously described . flow cytometry and statistical analyses were performed using flowjo x ( treestar ) and graphpad 6.0 ( graphpad software ) , respectively . while cd4 t cell ifn- production remains the dogmatic measurement of mycobacterial immunity , it fails to predict which individuals are at increased risk of disease progression . to this end , we hypothesized a more accurate means via a comprehensive immune profile balancing the anti - inflammatory cytokines ( il-4 and il-10 ) compared to inflammatory ones ( ifn- ) . we measured the mycobacteria - specific il-4 : ifn- and il-10 : ifn- ratios from cd4 , cd8 , cd56 , and double negative ( cd3cd4cd8cd56 ) cells . representative dot plots are available in figures 1(a ) and 1(b ) and the gating strategy is available in supplemental figure 2 . as a proxy for hiv progression , we calculated the cd4 : cd8 ratio . participants had a mean age of 24 ( range 1638 ) , 58% female with 100% on antiretroviral therapy ( art ) ( see table 1 ) . as hiv progresses and the percentage of cd4 cells decreases , the percentage of lymphocytes that are cd8 or dn increases ( figure 1(f ) ) ; this association was not seen with cd56cd3 nk cells . similar to previous descriptions , the percentage of cd4 t cells producing mycobacteria - specific ifn- did not correlate with cd4 : cd8 ratio ( spearman r = 0.059 ; p = 0.83 ) ( figure 1(c ) ) , while the percentage of il-4 producing cd4 cells increased with hiv progression ( figure 1(d ) ) . when considering the balance , il-4 : ifn- increased as the cd4 : cd8 ratio decreased ( spearman r of 0.596 ; p = 0.02 ; figure 1(e ) ) . the correlation of increasing il-4 : ifn- ratio with decreasing cd4 : cd8 ratio occurred in both the adaptive ( cd4 and cd8 ) and innate ( cd56cd3 nk cell ) response as well as in the immune response of double negative ( dn ) lymphocytes ( figure 1(e ) ) . while there are many cells capable of producing il-10 ( lymphocytes , granulocytes , monocytes , macrophages , and dendritic cells ) , their production occurred predominantly in nonlymphocytes ( figure 2(a ) ) . in contrast , the contribution from cd56 nk or cd3 t cells was minimal ( figure 2(a ) ) . therefore , we correlated the il-10 production from nonlymphocytes to the total percentage of lymphocytes producing mycobacteria - specific ifn- as an appropriate measure for the balance of pro- and anti - inflammatory immune responses ( figure 2(a ) ) . as hiv disease progressed ( as measured by declining cd4 : cd8 ratio ) , the nonlymphocyte il-10 : lymphocyte ifn- ratio increased ( spearman r = 0.76 ; p = 0.01 ) ( figure 2(b ) ) . therefore , while the percentage of cd4 t cells producing ifn- did not correlate with hiv progression , the balance of anti - inflammatory ( il-4 or il-10 ) and cell - mediated immune responses did . combatting the hiv - tb epidemics ravaging vulnerable populations is going to require significant investments in clinical care and also cutting edge basic and translational research to discover new diagnostics , identify pathways for immunotherapeutics , and develop effective vaccine platforms . here , amongst a cohort of swaziland plhiv with tb disease , we show that the benefit of applying a comprehensive and balanced profile of antimycobacterial immunity is of paramount importance . for progression to tb disease , hiv infection is the greatest risk factor [ 13 ] and , therefore , identification of immune correlates of tb progression amongst plhiv is of utmost importance . the central doctrine of mycobacterial immunity relies on cd4 t cell ifn- production ; however , this measurement fails to differentiate infection from disease , predict those at high risk for progression , or predict vaccine immunogenicity [ 17 , 18 ] . thus , there is an urgent need for reliable immune biomarkers of protection , as well as disease advancement with recent research delineating the roles of cytotoxic t lymphocytes ( cd8 ) [ 4 , 20 ] , nk cells , double negative cells , monocytes , and macrophages . in contrast to the classic approach of only evaluating the cell - mediated mycobacterial immune response , we demonstrate how the simultaneous evaluation of cell - mediated and anti - inflammatory responses improves our understanding of the immune processes at play . in contrast to the premise that ifn- defines mycobacterial immunity best , we show that as hiv disease progresses , both adaptive and innate lymphocyte lineages polarize towards an il-4-dominated anti - inflammatory response . the evidence for hiv promoting a th2 skewing of the immune response is controversial as it is dependent on the methodology ( pcr , elisa [ 22 , 23 ] , or flow cytometry ) and type of stimuli ( antigen - specific versus pmai / i ) . here , using multiparametric flow cytometry to measure the antigen - specific response , we show that hiv progression causes an increase in the cd4 t cell il-4 : ifn- ratio . for the first time to our knowledge , we demonstrate a negative correlation between il-4 and ifn- that occurs amongst not only cd4 t cells , but also cd8 t cells , double negative lymphocytes , and nk cells . these preliminary findings raise interesting questions about the pathophysiology of tb disease progression in the hiv setting . one possible explanation for the increased il-4 : ifn- ratio may be increased cell turnover . gata-3 , the master transcription factor promoting il-4 and inhibiting ifn- , is required for thymic development . it is plausible that as hiv progression results in high lymphocyte turnover , the increasing percentage of gata-3 nave immune cells explains the etiology of il-4 skewing . if this were the explanation , one would expect the ratio to normalize the longer an individual is on suppressive art . our data suggest that cd3 t cells do not produce significant pathogen - specific il-10 . in contrast , the ratio of nonlymphocyte il-10 : lymphocyte ifn- correlates inversely with hiv progression . animal models [ 12 , 14 , 26 , 27 ] suggest that an appropriate balance of anti - inflammatory to proinflammatory immunity is needed to control intracellular mtb . correlation of these animal models with longitudinal human data is needed to identify the ratio at which il-10 is protective versus when it becomes detrimental to the protective cell - mediated response . these preliminary findings in this communication are significant insofar as they begin to define the relationship between hiv disease severity and the immune response equilibrium amongst multiple lymphocyte lineages . replication of these primary findings in longitudinal cohorts of tb exposed plhiv promises to assess the predictive utility il-4 : ifn- or il-10 : ifn- ratios , further elucidating the mechanisms of mtb protective immunity and therefore supporting development of targeted immune therapies .

introduction . our objective is to understand how hiv infection increases the risk of progression from latent tuberculosis ( tb ) to active disease . we understand now that immunity is a balance of competing immune responses by multiple cell types . since t - lymphocyte production of interferon - gamma ( ifn- ) in response to mycobacterium tuberculosis ( mtb ) antigens fails to differentiate disease from latent infection , we applied a comprehensive profiling methodology to define immune biomarkers that reliably predict a patient 's tb risk . methods . we established a cohort of hiv - infected adults with tb disease from swaziland . multiparametric flow cytometry was used to quantify the mycobacterial - specific anti - inflammatory ( il-4 and il-10 ) and proinflammatory ( ifn- ) immune response . results . from 12 hiv - infected swaziland patients with tb disease , the cd4 + , cd8 + , double negative , and cd56+cd3 lymphocytes increase their il-4 : ifn- ratio as hiv disease worsens ( spearman r of 0.59 ; 0.59 ; 0.60 ; and 0.59 , resp . ; p < 0.05 ) . similarly , hiv severity is associated with an increased il-10 : ifn- ratio ( spearman r of 0.76 ; p = 0.01 ) . conclusion . as hiv disease progresses , both the adaptive and innate branches skew away from an inflammatory and towards anti - inflammatory phenotype .

concern regarding facial esthetics is one of the most probable reasons to seek orthodontic and/or surgical orthodontic treatment . the dentition and the occlusal relationship play a vital role in determining the overall perception of facial esthetics . the degree of anteroposterior ( ap ) discrepancy , either dental or skeletal , often serves as an indicator of malocclusion , and by inference the need for the treatment . the treatment plan , orthodontics and/or orthognathic surgery , for patients with more severe problems is frequently dictated in part by esthetic concerns . orthodontic patients and their parents believe that well - aligned teeth are important for an overall pleasing appearance . the decision to undergo orthodontic treatment seems to be motivated by social norms and the beauty culture in their reference group . therefore , the opinion of the laymen is an important parameter in determining the success of orthodontic treatment . orthodontists , however , prefer to use objective parameters instead of opinions for their diagnosis , treatment plan and evaluation of the outcome of their clinical intervention . the objective parameters used by the orthodontists usually include quantitative descriptions of ap , vertical discrepancies , and dental irregularities . studies carried out to relate the laypersons perception of facial esthetics to the orthodontist 's objective parameters of facial and dental value are scarce . it is postulated that laypeople will vary in their subjective viewpoints , and this would be dependent upon the environment that they are exposed to . hence , this study was done to determine the objective parameters used in daily orthodontic practice related to facial esthetics , as perceived by the laypeople in the selected district . the objective parameters used represented ap characteristics ( overjet and anb angle ) , vertical characteristics ( sn - gogn angle ) , and dental esthetics esthetic component of the index of orthodontic treatment need ( ac / iotn ) . this study examined and correlated the contribution of the objective measures representing ap and vertical characteristics , dental esthetics , or their combination that are used in daily orthodontic practice with subjective measures in the assessment of facial esthetics for the test group population . inclusion criteria for subjects for the collection of data are as follows : the age is between 10 and 25 yearshad no dental or facial traumahad no history of orthodontic treatmenthad no congenital defectsnot been wearing glassesthe panel of laypeople should be from different professional backgrounds . the age is between 10 and 25 years had no dental or facial trauma had no history of orthodontic treatment had no congenital defects not been wearing glasses the panel of laypeople should be from different professional backgrounds . about 64 patients were randomly selected after stratification , from the records of the department of orthodontics of a dental hospital . eight boys and eight girls each , in angles class i ; class ii division i ; class ii division ii ; class iii malocclusions , were shortlisted . the objective parameters were obtained from the pretreatment records ( dental casts , cephalograms , extraoral and intraoral color photographs ) [ figures 13 ] of these patients . subjective parameters : 64 laypeople ( 32 males and 32 females ) were chosen from professional colleges in the area . each subject was given a performa having 64 patients ' names and a visual analog scale ( vas ) ( a vas , operationally , a measurement instrument with horizontal line , which is 100 mm in length , anchored by 0 in beginning and 100 at the end representing least attractiveness and most attractiveness parameters marked , respectively . the subject marks on the line , the point that they feel represents their perception of the variable under consideration . the vas score is then determined by measuring the length of the line marked , in millimeters , from the left - hand end of the line to the point that the subject had marked against each patient . a slide show presenting the digital images in the ( a ) frontal view , ( b ) three - quarter smiling view , and ( c ) profile view of each patient was prepared . overjet measurement using ruler anb and sn - gogn sella - nasion - gonion gnathionmeasurement from lateral cephalogram a sample of extraoral photographs of a patient sample of intraoral photographs of a patient the following objective parameters were obtained from the records : overjet was measured on the dental casts as the ap distance between the maxillary and mandibular central incisors at the most labial point of the most prominent incisor [ figure 1]anb angle and sn - gogn angle were measured on tracing of lateral head film [ figure 2]the horizontal sum obtained as the summation of the overjet in millimeters and anb in degreesac / iotn was determined on intraoral pictures [ figure 5 ] by mutual agreement between two independent observers ( as per the guidelines of shaw wc ) . overjet was measured on the dental casts as the ap distance between the maxillary and mandibular central incisors at the most labial point of the most prominent incisor [ figure 1 ] anb angle and sn - gogn angle were measured on tracing of lateral head film [ figure 2 ] the horizontal sum obtained as the summation of the overjet in millimeters and anb in degrees ac / iotn was determined on intraoral pictures [ figure 5 ] by mutual agreement between two independent observers ( as per the guidelines of shaw wc ) . microsoft power point demonstration to laypersons after the collection of data on the varied objective and subjective criteria , the data were subjected to statistical analysis . then , the data were analyzed by one - way analysis of variance ( anova ) test to find out the significant difference between more than two groups followed by tukeys multiple post hoc procedures for pairwise comparison . further , the multiple linear regression was performed to see the influence of independent variables on the dependent variable . the following objective parameters were obtained from the records : overjet was measured on the dental casts as the ap distance between the maxillary and mandibular central incisors at the most labial point of the most prominent incisor [ figure 1]anb angle and sn - gogn angle were measured on tracing of lateral head film [ figure 2]the horizontal sum obtained as the summation of the overjet in millimeters and anb in degreesac / iotn was determined on intraoral pictures [ figure 5 ] by mutual agreement between two independent observers ( as per the guidelines of shaw wc ) . overjet was measured on the dental casts as the ap distance between the maxillary and mandibular central incisors at the most labial point of the most prominent incisor [ figure 1 ] anb angle and sn - gogn angle were measured on tracing of lateral head film [ figure 2 ] the horizontal sum obtained as the summation of the overjet in millimeters and anb in degrees ac / iotn was determined on intraoral pictures [ figure 5 ] by mutual agreement between two independent observers ( as per the guidelines of shaw wc ) . microsoft power point demonstration to laypersons after the collection of data on the varied objective and subjective criteria , the data were subjected to statistical analysis . then , the data were analyzed by one - way analysis of variance ( anova ) test to find out the significant difference between more than two groups followed by tukeys multiple post hoc procedures for pairwise comparison . further , the multiple linear regression was performed to see the influence of independent variables on the dependent variable . the statistical significance for one way anova was set at 5% level of significance ( p < 0.05 ) . the values and standard deviations of the various objective parameters obtained and segregated into angle 's classes [ table 1 ] . one - way anova test done to compare various classes with respect to the different objective parameters indicated that all the parameters , except the vertical parameter ( sn - gogn ; p = 0.1758 , ( p > 0.05 ) not significant ) , showed a statistically significant variation between different classes . overjet , anb , iotn , and horizontal sum were significantly correlated with p value of 0.0000 , 0.0001 , 0.00400 , and 0.0008 , respectively [ table 2 ] . it was deduced that the value of each parameter was significantly different from the same parameter in other class . the esthetic scores ( vas scores ) given by male and female reviewing laypeople were compared [ table 3 ] . it was observed that the comparison of different classes with respect to vas scores given by male and female laypeople was found to be nonsignificant . multiple regression analysis of the subjective parameter , the vas scores ( dependent variable ) with the objective parameters taken , indicated that though the overjet , horizontal sum , and ac ( iotn ) negatively correlated with the objective parameters , only the ac ( iotn ) showed a statistically significant negative correlation [ table 4 ] . a backward stepwise multiple regression analysis of vas scores according to the total sample of laypersons showed a significant correlation between subjective vas score with the ac ( iotn ) [ table 5 ] . the mean and standard deviation of different objective parameters obtained grouped according to angle 's classification comparison of classes with respect to different objective measurements by one - way anova comparison of the different angle 's classes ( i , ii division i , ii division ii , iii ) with respect to visual analog scale scores given by male and female laypersons multiple regression analysis of visual analog scale scores according to the total laypersons ( male and female laypersons ) ( dependent variable ) with objective measurements ( independent variables ) backward stepwise multiple regression analysis of visual analog scale scores according to the total sample of laypersons ( male and female laypersons ) ( dependent variable ) with index of orthodontic treatment need the most commonly used parameter for ap characteristics is angle classification , which is a rough estimate having four discrete classes . for proper orientation of the jaw , combination of anb and overjet has been indicated . the effect of the vertical on facial attractiveness has been studied on constructed profiles or manipulated photographs . most orthodontists use sn - gogn angle for the evaluation of vertical dimensions in daily clinical practice , but the relation of this parameter to facial attractiveness has been debatable . both orthodontists and laymen are well able to use vas scores to judge facial esthetics from photographs in a more or less intuitive way although facial esthetics seem to be subjective and not a well - defined variable . when the various classes of angle 's classification were compared to different objective parameters , all the parameters , except the vertical parameter sn - gogn , showed significant variation between the different classes . these parameters were distinctly different despite overlapping ranges for different classes as indicated by the one - way anova test done between the classes . however , no difference was found between two sexes of patients , when their objective parameters were compared . observed that the objective parameters used in his study showed wide overlapping ranges for different classes and none of them was decisive for angle classification . in our study , however , the objective parameters were distinctly different between the classes but did not differ between the male and female subjects . the comparison of different classes with respect to vas scores given by male and female laypeople did not show significant differences , so it could be deduced that the laypeople were not appreciative of facial beauty with respect to different angle classes . in this study , class i and class ii / division i malocclusions were rated lower than the class ii / division ii and class iii malocclusions as against the previous studies which rated class ii and class iii lower than class i malocclusions . this could be interpreted that the laypeople of the area under study are more appreciative of a protrusive profile as against a straight or retrusive profile . the male laypeople gave higher esthetic scores than female laypeople showing that females were more critical in evaluating both male and female subjects than the males . however , this observation should be subjected to further research . when the esthetic scores given by male and female laypersons were compared with the objective measurements , the ac ( iotn ) and the horizontal sum showed significant negative correlation with the subjective parameters . the horizontal sum , introduced by kiekens et al . appeared to be a useful parameter to measure the horizontal discrepancy . it is related to the dentition ( overjet ) measured from the dental cast and to the skeletal parameter however , when the esthetic values given by males and females separately were compared with the objective parameters , only the ac ( iotn ) significantly correlated with the objective parameters , negatively . a multiple regression analysis of the subjective parameter , the vas scores ( dependent variable ) with the objective parameters taken , indicated that only the ac ( iotn ) was significant and negatively correlated and individually only female laypersons were negatively correlated and significant . the laypeople gave the highest vas score on the factors with a horizontal sum of 7.25 for male and 8.3 for female laypersons . the fact that for the variable horizontal sum , degrees , and millimeters are summed , might be surprising , but it appears to be reliable parameter ( cronbach 's alpha = 0.7391 ) . , matoula and pancherz found that the ap discrepancies , as measured by soft tissue anb , showed minimal correlation with facial attractiveness . however , a trend emerged that would suggest that in faces where the anb varies widely from 5 , the face is considered less attractive . sn - gogn angle , however , is a measure for mandibular rotation or growth direction and not for facial height . found that both orthodontists and layperson are sensitive to small horizontal changes and orthodontists are relatively less sensitive to vertical changes compared to the horizontal changes . studies showed that orthodontists are significantly more likely to choose class i profile as most attractive and vast majority of the orthodontists and laymen considered class ii profile as least attractive . michiels and sather found profiles with increase vertical features or convex or class ii tendency profiles were judged as being most unattractive . in this study , however , class ii division ii and class iii malocclusions were judged as being more attractive than the class ii or class i angle malocclusion . showed that the iotn ( ac ) index appeared robust in its reflection of the perception of malocclusion by children and parents , respectively . assessments were little affected by gender or ethnicity . however , the scores of children and parents were much lower than those of an orthodontist trained in the use of iotn . johansson and follin found that photographs matching higher grades on the ac scale were perceived as the most unattractive , indicating what could be a layperson 's priority when considering an orthodontic treatment policy in tanzania . synonymously , in this study , the ac / iotn appeared to be a valuable indicator of facial esthetics and the higher grades on the scale were considered to be the most unattractive , whereas the lower scales were more attractive . the ac / iotn , a measure of dental esthetics , appears to be the most vital contributor of facial esthetics and addition of horizontal sum increased the explained variance to 35 . this increases the prognostic value of the ac / iotn and horizontal sum when used in combination in evaluating facial esthetics , but the remaining 65% of the variance is left unaccounted for by these parameters and could probably be attributed to other facial features such as the eyes , skin , and hair . the abovementioned study revealed that objective measurement showed overlapping between different angle classes , but the differences were statistically significant for each angle classes . correlation between esthetic scores done by male and female laypersons together with objective measurements showed that only ac / iotn was negatively correlated and a statistically significant parameter . the prognostic value of the ac / iotn increased when used with the horizontal sum in evaluating facial esthetics . thus , horizontal sum was found to be a reliable variable for ap characteristics of the patient . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .

background : the study mentioned was aimed to examine the contribution of the objective measures representing anterior - posterior ( ap ) and vertical characteristics , dental esthetics , or their combination that are used in daily orthodontic practice in the assessment of the facial esthetics.materials and methods : a panel of 64 laypersons evaluated the facial esthetics of 32 boys and 32 girls , stratified over four different angle classes , on a visual analog scale . the relationship between the objective parameters and facial esthetics was evaluated by the backward multiple regression analysis.results:dental esthetics , expressed by the esthetic component of the index of orthodontic treatment need ( ac / iotn ) , appeared to be the most vital indicator for facial esthetics . the horizontal sum , a variable for ap characteristics of the patient , could be a better variable when compared with the overjet.conclusion:addition of this newly defined parameter to the ac / iotn improved the prognostic value from 25% to 35% .

we encountered a woman with a preexisting large focal nodular hyperplasia ( fnh ) of the liver , persisting during two separate pregnancies . her elevated serum -glutamyltransferase and alkaline phosphatase levels before pregnancy were reduced during both pregnancies , but returned to prepregnancy levels after delivery . focal nodular hyperplasia ( fnh ) is a benign lesion of the liver that is not uncommon in adults and is frequently observed in healthy individuals . it is unclear , however , whether pregnancy in women with fnh increases the risks of fnh growth and complications or alters hepatic function in patients . we encountered a woman with a large fnh , who experienced two pregnancies and delivered healthy infants at term uneventfully . the courses of her pregnancies and the effects of pregnancy on fnh , including lesion size and hepatic function were evaluated at the same institution . the patient was a 25-year - old , gravida 0 , para 0 , female , who had been followed up since the age of 18 years at the internal medicine outpatient ward of our institution because of a large fnh . at the age of 13 years , a nodule measuring 8 cm was observed in the patient , at a medical institution near her residence . a biopsy was performed , and on histological analysis of the specimen , she was diagnosed with fnh . because the nodule was located near the hepatic hilus , surgical intervention was not performed . at the age of 25 years , the patient married and moved near our hospital . an mri taken before her first pregnancy showed that the nodule was 11 cm in diameter ( figs.1a and 2a ) . a high intensity area was observed at the center of the lesion , a finding compatible with central scar tissue , with a moderately high intensity area observed at the surface of the lesion . ( c ) during her second pregnancy at 34 weeks of gestation . before becoming pregnant , her liver function tests showed that her serum aspartate aminotransferase ( ast ) and alanine aminotransferase ( alt ) concentrations were in the normal ranges , but her -glutamyltransferase ( ggt ) and alkaline phosphatase ( alp ) concentrations were elevated , to 651 iu / l and 407 u / l , respectively . after conceiving , she was referred by her physician to our outpatient ward at 9 weeks of gestation . during her first pregnancy , her serum concentrations of liver enzymes decreased to the normal range without any medication ( fig.3 ) . magnetic resonance imaging performed at 37 weeks of gestation showed that the size of the fnh was unchanged , with no signs of bleeding or degeneration of the lesion ( figs.1b and 2b ) . the concentrations of aspartate aminotransferase ( ast ) , alanine aminotransferase ( alt ) , lactate dehydrogenase ( ldh ) , alkaline phosphatase ( alp ) , and -glutamyltransferase ( ggt ) are shown in u / l . , she delivered a normal , healthy female infant , weighing 3084 g and with 1 and 5 min apgar scores of 8 and 9 , respectively , by vaginal delivery . her postpartum recovery was normal , except that her serum ggt and alp concentrations became elevated , returning to their prepregnancy levels . this pregnancy was also uneventful ( figs.1c , 2c , and 3 ) and , at 40 weeks of gestation she delivered a normal , healthy male infant , weighing 3130 g and with 1 and 5 min apgar scores of 9 and 10 , respectively , by vaginal delivery . her postpartum course was again uneventful , and both mother and child were discharged after 5 days . the size of the fnh remained the same as before her first pregnancy , despite two pregnancies and deliveries . during both pregnancies , her serum concentrations of liver enzymes after conceiving , she was referred by her physician to our outpatient ward at 9 weeks of gestation . during her first pregnancy , her serum concentrations of liver enzymes decreased to the normal range without any medication ( fig.3 ) . magnetic resonance imaging performed at 37 weeks of gestation showed that the size of the fnh was unchanged , with no signs of bleeding or degeneration of the lesion ( figs.1b and 2b ) . the concentrations of aspartate aminotransferase ( ast ) , alanine aminotransferase ( alt ) , lactate dehydrogenase ( ldh ) , alkaline phosphatase ( alp ) , and -glutamyltransferase ( ggt ) are shown in u / l . her first course of pregnancy was uneventful . at 39 weeks , she delivered a normal , healthy female infant , weighing 3084 g and with 1 and 5 min apgar scores of 8 and 9 , respectively , by vaginal delivery . her postpartum recovery was normal , except that her serum ggt and alp concentrations became elevated , returning to their prepregnancy levels . this pregnancy was also uneventful ( figs.1c , 2c , and 3 ) and , at 40 weeks of gestation she delivered a normal , healthy male infant , weighing 3130 g and with 1 and 5 min apgar scores of 9 and 10 , respectively , by vaginal delivery . her postpartum course was again uneventful , and both mother and child were discharged after 5 days . the size of the fnh remained the same as before her first pregnancy , despite two pregnancies and deliveries . during both pregnancies , her serum concentrations of liver enzymes focal nodular hyperplasia is a common type of hepatic mass in adults , with an incidence of approximately 3% . we encountered a woman who had fnh prior to her first pregnancy and followed her throughout two courses of pregnancy . in contrast , the serum concentrations of liver enzymes were decreased during both pregnancies , and returned to their prepregnancy levels soon after the deliveries . a previous study described the effects of 41 pregnancies on fnh in 37 women , finding that the size of the fnh was not affected by pregnancy . another study evaluating the effects of pregnancy on fnh size in patients found that the mean tumor size before pregnancy was 58.5 22.7 mm . tumor size remained constant in seven of these 20 patients ( 35% ) and declined in 10 ( 50% ) . however , fnh size in multiparous women was assessed using a questionnaire , not by actual measurement . furthermore , that study evaluated only lesion size , not changes in serum enzyme concentrations . in our patient , the fnh was > 11 cm in diameter , the largest fnh reported to date , and its size was not affected by either of her two pregnancies . there have been no reports on changes in the serum concentrations of liver enzymes during pregnancy in women with fnh . in contrast , serum alp and ggt values , which were elevated before and after her pregnancies , decreased to normal levels during her pregnancies . alp and ggt are enzymes present in the cell membranes of the bile duct , gall bladder , pancreas , and kidneys . serum concentrations of alp elevate by placental origin and ggt are not affected in pregnancies in women without fnh , but were shown to be higher in few pregnant women ( < 1% ) with intrahepatic cholestasis . pregnancy may alter the results of liver function tests , with placental steroids playing a role . during pregnancy , the production of placental steroids increases the serum estrogen and progesterone concentrations compared with the nonpregnant state . for example , a 9-year study of 216 women in france showed that neither the size nor the numbers of fnh lesions are influenced by oral contraceptive use . although estrogen receptors were shown to be present in the cytosol and nuclei of hepatic cells including the tissue of fnh , few estrogen receptors are present on the cell surface . estrogen and progesterone affect the mrna expression and activity of cyps ( cytochrome p450 ) in primary human hepatic cells , as shown in a recent study . these findings potentially provide a basis to understand the mechanism of altered drug metabolism during pregnancy . however , further studies are needed to investigate the lowering of serum alp and ggt in fnh . in conclusion , we have described here a single patient with fnh of the liver complicating pregnancy and postpartum delivery twice over a 4-year observation period . fnh size was not affected by pregnancies , whereas liver function test results improved , allowing these enzymes to return to their prepregnancy levels after deliveries . lesion size and abnormally elevated serum liver enzyme concentrations are not indicated for surgery in pregnant women with asymptomatic fnh . our findings indicate that women with large fnh , even those with elevated serum liver enzymes , should not be discouraged from pregnancy .

key clinical messagewe encountered a woman with a preexisting large focal nodular hyperplasia ( fnh ) of the liver , persisting during two separate pregnancies . fnh size was not affected by either pregnancy . her elevated serum -glutamyltransferase and alkaline phosphatase levels before pregnancy were reduced during both pregnancies , but returned to prepregnancy levels after delivery .

in the current issue of critical care , venkatesh and colleagues present a novel study on adiponectin in critical illness . this article , along with the concept of adipose tissue and adipocytokines being involved in the mechanisms of critical illness , requires some commentary . historically , adipose tissue was thought to be an inert tissue that stores energy and protects the body from temperature and injury . in contrast to this concept , it is now evident that adipose tissue is an active endocrine organ secreting many kinds of adipocytokines such as adiponectin , leptin , il-6 , and tnf that may affect metabolism , body weight regulation , and glucose and lipid homeostasis . produced exclusively in the adipose tissue , adiponectin is the most abundant adipocytokine and circulates in the blood at high concentrations , accounting for approximately 0.01% of the total plasma protein [ 3 - 5 ] . studies in rodents demonstrate a role for adiponectin in obesity and insulin resistance . in humans , reduced serum levels of adiponectin in obese subjects compared with nonobese subjects and negative correlations between adiponectin and body mass index ( bmi ) furthermore , serum concentrations of adiponectin have been found to be inversely correlated with insulin resistance in both nonobese and obese subjects and in patients with type 2 diabetes mellitus [ 11 - 13 ] . in spite of numerous clinical studies on adiponectin , however , its exact role in metabolism is unclear and remains to be elucidated , along with the as yet unsolved adiponectin paradox : a decreased concentration of adiponectin in obesity seems paradoxical , since fat tissue is the only known source of this protein . in viuew of that , the paper by venkatesh and colleagues broadens knowledge of the subject and links the function of adipose tissue to the general defense against critical illness . the authors ' suggestion that adiponectin may play a part in the inflammatory response in patients with critical illness is interesting , but it should be considered bearing in mind some limitations of the study . perhaps the major limitation is the lack of data on patients ' bmi . associations between low and high bmi and mortality are well known , as are the correlations between bmi and adiponectin . different bmi values between groups could consequently have influenced the adiponectin results . under these circumstances , furthermore , the associations between serum cortisol and adiponectin in critical care patients demonstrated in this study also require comment . the high standard deviation for cortisol might have been caused by adrenal insufficiency in several patients with very low cortisol levels . in this setting , the group is not homogeneous with respect to adrenal response to stress , and consequently the overall statistical result may be confusing . still , the authors have raised an interesting problem regarding the link between adrenal function and adipose tissue metabolism in critical illness . an increased secretion of glucocorticoids by the adrenal gland is a well - known defense mechanism against hypotension and stress , whereas a decreased cortisol concentration is associated with a worse prognosis . on the basis of this article , therefore , one can propose the hypothesis that a decreased adrenal response presumably inhibits protective adiponectin secretion , thus deteriorating the overall clinical condition . obviously , in face of the above - mentioned study limitations , this tempting hypothesis requires further research . although based on a preliminary study only , the idea shown by venkatesh and colleagues generates new hypotheses meaning we should have a rethink of the role of fat tissue in the critical state in humans . obviously the authors did not investigate the mechanism of decreased adiponectin in critical illness , as it was not the aim of their study . however , the following fact is now evident : being a complicated organ and being spread throughout the body hormone - producing and cytokine - producing machinery , adipose tissue can not stand passively by in the face of severe threat to life , and is involved in numerous inflammatory responses including production of adipocytokines , tnfs , and metabolites of fat catabolism . the nature of these responses remains to be elucidated , however , and noteworthy clinical studies should prompt further efforts in basic research to explain the mechanisms beyond clinical observations . bmi : body mass index ; il : interleukin ; tnf : tumor necrosis factor .

historically , adipose tissue was thought to be a passive tissue that stores energy and protects the body from temperature and injury . in contrast to this concept , it is now evident that adipose tissue is an active endocrine organ secreting many kinds of adipocytokines , including adiponectin . presumably , adipose tissue and its products may have some impact on numerous pathways of response to trauma , sepsis and stress . the discussion on a plausible role of adiponectin in critical illness has been raised by the fact of finding hypoadiponectinemia in critically ill patients . the nature of this phenomenon , however , remains to be elucidated , and noteworthy clinical studies should prompt further efforts in basic research to explain the mechanisms beyond the clinical observation of low adiponectin levels in humans with severe illness .

hepatitis b virus ( hbv ) and hepatitis c virus ( hcv ) infections cause morbidity and mortality in haemodialysis patients . prolonged vascular exposure and multiple blood transfusions contaminated devices , equipments , and supplies , environmental surfaces , and attending personnel may also play a crucial role in the nosocomial transmission of these infections . infections with hepatitis viruses in haemodialysis patients are further promoted by the significant immune status dysfunction developing due to irreversible renal compromise [ 13 ] . furthermore , hepatitis viral infections in haemodialysis patients cause liver disease in renal failure patients undergoing replacement therapy . they also pose a significant problem in the management of these cases as patients with renal failure can not clear the viruses effectively . patients with coinfections with these viruses develop severe clinical presentations and resistance to interferon treatment . there are very limited data available on the occurrence of such infections in haemodialysis patients from this part of the country . the present study aimed to investigate the occurrence of hbv and hcv infections in haemodialysis patients and the risk factors associated with such infections . this study was conducted as a retrospective case - control study involving the haemodialysis patients at a dialysis centre of a tertiary care hospital . all the patients who underwent haemodialysis from january 2004 to june 2012 were included in the study . patients receiving haemodialysis were considered as a case for the study if their serum tested positive for either hbv or hcv . in contrast , the patients receiving haemodialysis were considered as a control if their serum tested negative for all the three viruses . for every case , patients ' medical records were reviewed to obtain details like age , gender , clinical diagnosis , and duration and frequency of dialysis , history of blood transfusions , and past surgeries and these details were recorded in a preformed questionnaire for all cases and controls . further , the results of serological tests ( hbsag , anti - hcv antibodies ) , renal function tests ( serum urea and creatinine ) , and liver function tests were recorded for both groups . duration of dialysis , frequency of dialysis , and the results of biochemical parameters were compared for infected cases and non - infected controls and were analyzed statistically using nonparametric tests and chi - square tests . the present retrospective study was conducted for a period of 102 months , that is , from january 2004 to june 2012 . a total of 180 patients were diagnosed to have chronic kidney disease and were on maintenance haemodialysis during the study period . also , our dialysis unit caters to approximately 15 in - patients per month referred from other departments or hospitals for haemodialysis . therefore , the total number of patients who received haemodialysis at our centre during the study period was 1710 . among these patients , 45/1710 cases ( 2.63% ) were found to be infected with either hbv or hcv and were included as cases for our study . out of 45 cases studied , 26/1710 ( 1.52% ) tested positive for hbsag and 19/1710 ( 1.11% ) tested positive for anti - hcv antibodies . out of 26 cases infected with hbv , 22 ( 84.6% ) were males and 4 ( 15.4% ) were females . among hcv positive cases , 18 ( 94.7% ) were males and 1 ( 5.2% ) was female . among the cases , dual infection with hbv and hcv was seen in two patients , 1 male and 1 female . hbv infection was seen most commonly in the age group of 5060 yrs , whereas hcv was commonest in the age group of 3040 years . mean duration of dialysis for infected cases was 4.8 years while that of the non - infected controls was 3.18 years . there was a statistically significant ( p = 0.008 ) difference between the cases and controls with respect to duration of dialysis ( mann - whitney u test since mean was less than 2 standard deviations , non - parametric tests were used ) . when comparing frequency of dialysis between cases and controls , as it was a categorical variable , chi - square test was applied and there was no statistically significant ( p value = 0.228 ) correlation of the frequency of dialysis between cases and controls . with respect to liver function tests , a significant elevation of ast ( aspartate aminotransferase ) and alt ( alanine transaminase ) values among infected cases ( p value = 0.001 ) was observed in this study . most of the patients ( 80% ) on haemodialysis in our study were anaemic with haemoglobin concentration < 10 g% as shown in figure 1 . the comparison of haemoglobin values among cases and controls is depicted in figure 2 . with respect to renal function tests in cases and controls , mean value of blood urea for cases was 99.85 and for controls was 103.1 , and mean value of creatinine was 22.3 for cases and 8.65 for controls , respectively . no statistically significant difference was observed between both groups with respect to serum levels of urea ( p value = 0.6 ) , creatinine ( p value = 0.228 ) , and haemoglobin ( p value = 0.6 ) . risk factors for acquiring hbv and hcv infections were studied for both groups . among the infected cases , multiple blood transfusions were seen only in 3 cases ( 2 positive for hbsag and 1 for hcv ) . among the three , one case with positive anti - hcv underwent multiple blood transfusions and in the remaining two cases , the history of undergoing surgeries was obtained in nine cases . among the 9 cases , hbv infection was seen in 4 , hcv in 4 , and dual infection was seen in one case . twelve cases were diabetic , with hbv infection in 6 , hcv in 5 cases , and dual infection in 1 case ( figure 3 ) . with respect to similar risk factors in the control group , 14 control patients had diabetes and 4 of them had history of undergoing surgery in the past . only 1 control patient had history of undergoing blood transfusion ( figure 3 ) . patients diagnosed with chronic renal failure ( crf ) on maintenance haemodialysis pose a higher risk for acquiring hbv or hcv infections due to frequent use of blood and blood products and multiple invasive procedures performed in these patients . the literature review points to the fact that viral hepatitis is a serious threat for haemodialysis patients as 1.9% of all deaths among this population were related to the consequence of viral hepatitis . the results from our study demonstrate that the occurrence of hbv and hcv infections in haemodialysis patients is 1.52% and 1.11% , respectively , which is lower than the rates reported from different studies all over the world and india [ 58 ] . an indian study has reported the occurrence of hbv in haemodialysis to vary from 3.4% to 42% , much higher than that seen in our study . the lower rates of infection in our study might be due to decreased transfusion requirements owing to the availability of erythropoietin and better screening of blood and blood products for blood - borne infections . introduction of vaccination for hbv , isolation of hepatitis b virus ( hbv ) positive patients , and regular surveillance for hbv infection at our centre could also have contributed for the lesser rates of infection . occurrence of hcv infection was much less than hbv in our study which was in accordance with a study conducted in spain which reported lesser prevalence rates for hcv infection in haemodialysis ( hd ) patients . another study showed a significant decline of hepatitis c infection among end - stage renal disease patients in central brazil , highlighting the importance of public health strategies such as screening for anti - hcv in blood banks and infection control measures for control and prevention of hepatitis c in the haemodialysis environment . since both of these viruses share a common mode of transmission , we looked for the occurrence of coinfections among the cases studied . among the cases , dual infection with hbv and hcv was seen in two patients , 1 male and 1 female ( 2/45 = 4.4% ) . study from the same centre on the occurrence of coinfections in the general population reported lower rates ( 1.68% ) of dual infections . studies from other centres in india have reported a varying prevalence of coinfections with hbv and hiv ( 940% ) and for hcv and hiv ( 28% ) . the higher occurrence in our study may be due to the study population being restricted to haemodialysis patients and also due to the lesser sample size in the current study . another factor contributing to the higher rates is the enhanced risk of coinfections among chronic renal failure patients on haemodialysis due to multiple transfusions and invasive procedure performed in these patients . however , dual infection with hbv and hcv in our study which was 4.4% , similar to the study conducted in hyderabad . the present study highlights the duration of dialysis as an important risk factor for infection among haemodialysis patients . this observation was in agreement with previous reports in palestine , moldavia , and other studies from different regions of the world [ 1517 ] . duration of dialysis is an important risk factor for acquiring infections as it is related to nosocomial transmission and dissemination of the infections in the dialysis units . on comparison of ast and alt values among cases and controls , this can be explained on the basis of destruction of hepatocytes caused by the immune reaction of body responding to the hepatitis viruses leading to excessive release of the aminotransferases . these findings were in accordance with the studies conducted in karachi and jenin district and gaza strip in palestine [ 1 , 18 ] . in our study , when compared with the control group , 67% of the patients on haemodialysis with hbv / hcv were found to have higher hemoglobin levels . this interesting finding was supported by few studies and was attributed to the increase in rbc counts after infection with hepatitis viruses and also to increased erythropoietin production after hepatic stimulation by chronic infection with hepatitis virus . however , the exact cause for the same is not yet established [ 1922 ] . a study from our centre brings to light that hbv and hcv infections , though less common , continue to remain as an important causes of infection in haemodialysis patients . the risk of exposure increases with the number of dialysis sessions and is maximum in patients on maintenance haemodialysis . interventions to reduce the occurrence of these infections are of utmost need to reduce the risk of long - term complications .

hepatitis b ( hbv ) and hepatitis c ( hcv ) viruses are the most important causes of chronic liver disease in patients with end stage renal disease on hemodialysis . the prevalence of hepatitis infection among hemodialysis patients is high and varies between countries and between dialysis units within a single country . this case - control study was undertaken to estimate the occurrence of hbv and hcv infections in patients undergoing hemodialysis in our tertiary care center . all patients receving hemodialysis at our centre with hcv or hbv infection were included in the study . the total number of patients admitted for hemodialysis during the study period was 1710 . among these , 26 patients were positive for hbv , 19 were positive for hcv , and 2 were positive for both hcv and hbv . mean age of the infected cases in our study was 48.63 years . mean duration of dialysis for infected cases was 4.8 years while that of the noninfected controls was 3.18 years . the mean dialysis interval was twice a week . interventions to reduce the occurrence of these infections are of utmost need to reduce the risk of long - term complications among hemodialysis patients .

the income , prestige , and authority of doctors in most western countries reflects their omnipotence amongst health care professionals and their power within our society . however , concurrent with the increasing number of women entering medicine , there has been a recent decrease in that power . for example , a significant proportion of female family physicians reports being sexually harassed by male patients . sexual harassment is an abusive behaviour perpetrated by those with power on the more vulnerable . the victimization of female doctors could only occur if the offending male patients saw their physicians as vulnerable women rather than powerful professionals , that is , if gender rather than professional role was the primary determinant of power in the relationship . if female physicians are " women first " in the eyes of some male patients , do their overwhelmingly female nurse colleagues also view them through a gender lens ? how will the increasing percentage of women in medicine change professional relationships between doctors and nurses ? this study examines whether the traditional authority of doctors over nurses is eroded when that authority arises solely from profession and not from gender . historically both the gendered role of nursing and the sex of nurses was almost exclusively female . the profession primarily attracted working class or immigrant women whose background fostered unquestioning obedience to authority . the " doctor nurse " game described by stein ( 1967 ) indicated that despite the passage of time , roles had not changed substantially . by showing initiative and making important recommendations , while appearing to defer passively to the doctor 's authority stein revisited the nurse - doctor game in 1990 and argued that nurses had unilaterally decided to stop playing . the change was , in part , attributed to an increasing number of female physicians and male nurses , both of whom were unable to play . nurses ' recent overt refusal to be dominated by physicians is also a reflection of the decrease in power differentials between men and women in western society at large . in contrast to nursing , the gender role and the practitioners of medicine one hundred years ago were male . many nurses and physicians still overtly and covertly resist the equalization of power that true teamwork requires . salvage and smith argue that while assertive nurses resent being put down by doctors , physicians resent being challenged by nurses . obstacles to collaboration include gendered thinking , different styles of learning , models of working , regulatory mechanisms , role ambiguity , and incongruent expectations . nurses generally experience greater satisfaction when communicating with female rather than male physicians and prefer a female managerial style . nurses doubt that physicians ' sex affects their behaviour , although some admit anger or disappointment when female physicians do not exceed the standards nurses set for male physicians . they deny any sexual chemistry that favours male physicians , despite the female doctors ' impression to the contrary . some female nurses describe female doctors in stereotypic terms such as " demanding " , " domineering " , and " bitchy " . female physicians , on the other hand , resent both having to make extra efforts to be nice to nurses , and devising conscious strategies to cultivate egalitarianism and friendship . more than 80% feel that at some time in their careers they have experienced unequal treatment , more intense scrutiny , or a lack of respect from nurses because they ( the doctors ) were female . a recent norwegian study examined the physician 's perspective on what happens to the doctor - nurse relationship when both are women . both male and female physicians thought the relationship was influenced by the doctor 's gender . female doctors perceived that they received less respect or help than did their male colleagues . the physicians interpreted this in two ways , thinking that either nurses ' wishes to reduce status differences between nurses and physicians affect female doctors more than male , or that there is an " erotic game " taking place between male doctors and female nurses . hypothesizing that the sex of the physician could affect nurses ' behaviour , we examined differences in the interaction between female nurses and female and male physicians . a self selected population of nurses working in an urban , university based hospital was asked to complete one of two forms of a three page questionnaire in jan . 2000 . the questionnaire included four clinical vignettes reflecting some previously identified areas of strain in the doctor nurse relationship . in form 1 of the questionnaire the physicians described were female , male , female , and male . in form 2 participants were asked five point likert type questions about nurse physician interactions , their expectations , probable actions , and feelings about the physicians . the questionnaire was pre - tested amongst a small group of hospital nurses to assess face and content validity . letters explaining that the accompanying study 's aim was to examine teamwork in a hospital setting , that participation was voluntary , and that responses would be confidential were left at all patient care planning areas ( nursing desks ) of the hospital . all surveys left at a specific patient care planning area were of the same form . nurses were asked to return questionnaires , whether completed or not , to an identified collection envelope , and to complete only one questionnaire . following the final collection date , letters explaining that responses to the two forms of the questionnaire would be compared to identify differences in interactions between nurses and physicians based on the doctor 's sex , and describing the " nurse - doctor game " were distributed . the analysis compared the responses to each question based on the sex of the physician in the particular vignette ( ie responses to form 1 and form 2 of the questionnaire ) . pearson chi - square analysis was used to test for statistical significance ( p < 0.05 ) . of the three hundred surveys printed , 265 were taken , 197 were returned completed , 2 were returned with no responses , and 66 were not returned . the overall response was 74% ( 199 of 265 taken ) and included approximately 22% of the 900 nurses employed by the hospital . the inpatient nursing specialties were broadly represented amongst the 95% ( n = 177 ) who indicated they were female , the 5% ( n = 9 ) who were male , and the 11 respondents who did not specify . based on the overall sex ratio of respondents these 11 were assumed to be female and included in the analysis .. responses from men were excluded , leaving 188 surveys for inclusion ( 95 surveys of form 1 and 93 of form 2 ) . in the first vignette a physician leaves a suture tray with needles at the bedside , despite a department policy assigning cleanup responsibility to the user of any " sharps " . female nurses expected physicians of either sex , to dispose of the needles ( 85.3% female physician , 86.0% male physician , p = 0.97 ) but were significantly less likely to remove the needles for female physicians ( p < 0.05 ) . nurses expectations of , and conflicts with physicians varied by sex . those surveyed were more likely to feel indifferent about a male physician , and negative about a female physician when the nurse ultimately removed the needles herself ( p < 0.01 ) . in vignette two , the nurse was interrupted while checking a patient 's vital signs and asked to do the same check on the doctor 's patient . nurses were equally unlikely to immediately stop and help a female or male physician ( p = 0.69 ) . however assertive requests by physicians were more likely to be acted upon if the physician were male ( p < 0.03 ) despite near universal resentment of this aggression ( 80% toward females , and 77% toward males , p = 0.89 ) . when physician requests for help were polite , nurses felt positive toward both male and female physicians ( 68.5% toward females , and 65.1% toward males , p = 0.33 ) but , as in vignette 1 , were less likely to help the female physician ( p = 0.17 ) . the nurse wonders if the physician remembers that the mother received meperidine ( a medication that could depress the baby 's breathing and that could be reversed by giving the baby naloxone ) two hours previously . nurses were more likely to suggest to the physician that the newborn needed naloxone , ( 99% were likely or very likely to suggest to female physicians and 97.8% for male physicians , p = 0.24 ) , than they were to tell the physician that the newborn needed naloxone ( 31.8% were likely or very likely to tell a female physician and 26.1% for a male physician , p = 0.21 ) . again , though not statistically significant in this case , there was a trend for nurses to be more forward with female doctors . they were less likely to wait for a female doctor to make her own decision about giving naloxone ( p = 0.15 ) , and more likely to suggest ( p = 0.21 ) or tell ( p = 0.20 ) the female doctor to give the medication . nurses also expected female doctors would respond more positively to their suggestions ( p < 0.04 ) . in the final vignette a doctor on call has just gone to sleep in her / his call room . nurses were asked if they would call the physician for an acetaminophen ( an analgesic ) order . there was , however , a consistent and contrary trend to that observed in the other scenarios . nurses were less likely to call a female physician than a male , regardless of whether the physician had given the nurse a complement earlier in the day ( p = 0.24 ) , or had been rude earlier on ( p = 0.63 ) . nurses were more likely to feel that a male physician 's anger was inappropriate ( p = 0.39 ) . they were less comfortable approaching a female doctor to discuss her anger ( p = 0.38 ) . in this vignette our findings suggest , however , that the process of , and feelings around nurse physician interactions are informed by gender stereotypes . in addition to professional hierarchy , gender appears to account for physicians ' perceived power over nurses . although physicians may well reinforce these same stereotypes this study did not examine their beliefs . overall , nurses ' behaviour was influenced by the sex of the physician . in vignette 1 , those surveyed expected both male and female physicians to remove needles left on a suture tray . they were , however , more willing to clean up after male physicians , and to do so with indifference rather than with the hostility they directed toward female doctors . findings that nurses are statistically less likely to remove needles for female doctors , and to feel somewhat more resentful toward female doctors for whom they have cleaned up , speaks to the primacy of sex over hierarchy in defining the doctor nurse relationship . perhaps nurses feel role confusion because female physicians do not fit into their learned male stereotypes , and instead better fit into traditionally female roles such as " cleaner " . these results corroborate pringle 's subjective findings that nurses do more for male physicians and expect more of female physicians . that nurses were unlikely to drop everything to assist either a male or female physician take a blood pressure is consistent with the increasing autonomy of the nursing profession . assertive physician requests met with resistance from these increasingly confident nurses who commented , " many times doctors feel they have the right to interrupt with little to no consideration for the rns . they feel their job is more important ! " and , " she is perfectly capable of doing vital signs . " pleasant requests for nursing help were more effective . again , however , sex role stereotypes appeared to enter the relationship as nurses accepted aggressive male behaviour and acquiesced more readily to male requests for help . responses to the third scenario suggest that the ' doctor - nurse game ' is alive and well . nurses deferred to the physicians ' status despite knowing what was medically necessary , and would suggest , but not dictate , treatment for the unresponsive baby . as one respondent wrote , " i would be more likely to phrase it in a way that would make him feel in control . " nevertheless , there was again more deference to the authority of male doctors . in the final vignette , respondents showed a non - significant trend toward a more kindly association with female than male physicians . at first this this vignette , however was the only one of the four requiring a nurse to initiate , rather than respond to an action . perhaps nurses are hostile and reactive to female physicians in situations where their expectations ( often based on sex stereotypes ) are not met , such as when women fail to clean up after themselves . however , when the nurse is in control , her less hierarchical relationship with another female , despite the power differential of profession , may foster collegiality . when doctors and nurses are both female , elimination of the power differential of gender diminishes nurses ' perceptions of professional power inequalities . as a result , female nurses appear more comfortable approaching and communicating with female doctors , but are also more hostile toward female physicians ' use of medical authority . these paradoxical behaviours will confuse female physicians if they view themselves as doctors first , rather than as women , and expect nurses to interact with all physicians equally . as females these same physicians may anticipate appreciation for their increased collaboration and egalitarianism , and not understand the nurses ' confusion at the lack of traditional professional hierarchy . perhaps the perception that female physicians are more caring and compassionate than their male counterparts creates conflicts with nurses , who define caring as their function , and may feel their role in health care delivery is threatened by women physicians . in general , the nurses surveyed said they would resist being controlled by physicians . this decrease in the power of medicine over nursing is concurrent with an increase in the number of women physicians in north america . although the feminization of medicine could diminish the power and prestige of all physicians within the health care system , our findings suggest that nurses are more resistant to domination by female , rather than male doctors . changes in power differentials between medicine and nursing appear to be shaped by gender , suggesting that the traditional omnipotence of physicians in the health care hierarchy arose from gender roles , and not solely from profession . written responses may define socially desirable values rather than actual behaviours in clinical situations , however the hostility toward physicians expressed in many of the nurses ' written comments ( not reported here ) mitigates against this concern . because the study was limited to hospital nurses and the scenarios were hospital based as with any study in which participants are self - selected rather than randomly surveyed , selection bias is possible . our relatively high response rate ( 74% ) minimizes , but does not preclude this limitation . written responses may define socially desirable values rather than actual behaviours in clinical situations , however the hostility toward physicians expressed in many of the nurses ' written comments ( not reported here ) mitigates against this concern . because the study was limited to hospital nurses and the scenarios were hospital based as with any study in which participants are self - selected rather than randomly surveyed , selection bias is possible . our relatively high response rate ( 74% ) minimizes , but does not preclude this limitation . historically , the power held by a predominantly male medical profession may have arisen primarily from gender rather than from hierarchical position . current relationships between doctors and nurses appear to be shaped by gender as well as by profession . when nurses and doctors are female the traditional power imbalance between the two diminishes . the effects of this change on the authority of the medical profession , the role of nurses , and on patient care remain undefined .

backgroundthe nurse - doctor relationship is historically one of female nurse deference to male physician authority . we investigated the effects of physicians ' sex on female nurses ' behaviour.methodsnurses at an urban , university based hospital completed one of two forms of a vignette - based survey in january , 2000 . each survey included four clinical scenarios . in form 1 of the questionnaire the physicians described were female , male , female , and male . in form 2 , vignettes were identical but the physician sex was changed to male , female , male , and female . differences in responses to questions based on the sex of the physician in each vignette were studiedresults199 self - selected nurses completed the survey . the responses of 177 female respondents and 11 respondents who did not specifiy their sex , and were assumed to be female based on the overall sex ratio of respondents , were analysed . persistent sex - role stereotypes influenced the relationship between female nurses and physicians . nurses were more willing to serve and defer to male physicians . they approached female physicians on a more egalitarian basis , were more comfortable communicating with them , yet more hostile toward them.conclusionwhen nurses and doctors are female , traditional power imbalances in their relationship diminish , suggesting that these imbalances are based as much on gender as on professional hierarchy . the effects of this change on the authority of the medical profession , the role of nurses , and on patient care merit further exploration .

mechanism - based pk / pd models typically describe first - order physiological processes that require systems of ordinary differential equations . repeatedly solving these complex systems of ordinary differential equations during the iterative estimation of random and fixed effects can be very computationally intensive . another challenge is that mechanism - based models have many parameters to be estimated , permitting more degrees of freedom for which to describe the data . the limited size and breadth of typical experimental data sets do not permit estimation of all of the physiological parameters of complex mechanistic models ; often because many of the pd markers needed to describe the system are lacking and/or the number of samples collected over time too few . statistics suggests that a model should not have more degrees of freedom than are supported by the current analysis data set . however , physiological parameters are useful for extrapolation and may be informed by prior knowledge if the current analysis data set does not support their estimation . markov chain monte carlo ( mcmc ) bayesian estimation approaches allow this to be done in a more statistically rigorous manner . traditional nlme estimation approaches , such as weighted least squares and maximum likelihood , have limited options for incorporation of prior information ; parameters can be fixed to a specific value , or they can be estimated based on the analysis data set . mcmc bayesian approaches allow the incorporation of a probability distribution to the prior knowledge , with means and variance for the model 's prior parameters . the variance of the prior means for the model parameters determines how much weight should be given to the prior relative to current analysis data set ( figure 1 ) . the resulting posterior model is thus based on the combination of prior knowledge and the current experimental data . with bayesian estimation approaches , there is no need to either completely ignore prior knowledge ( an unrealistic prospect for mechanism - based models ) or assume it is correct with absolute certainty . the theory of bayesian statistics goes back to the 18th century , when thomas bayes introduced the theorem for how one may update the probability estimate for a hypothesis as additional evidence is acquired . his theory provided the mathematical equation for indicating that future outcome has a probability that is based on current data and prior knowledge : where the probability of a hypothesis h conditional on a given body of data e is the ratio of the unconditional probability of the conjunction of the hypothesis with the data to the unconditional probability of the data alone ( p(e ) ) . in bayesian model optimization , p(e|h ) is the marginal posterior density for model , given the priors and the analysis data set . bayesian theory fits quite well with the need for mechanistic pk / pd models to incorporate prior knowledge to adequately inform the parameters of the system of ordinary differential equations . this theory has been difficult to implement for statistical modeling until the advent of more powerful computing resources and mcmc sampling approaches . for nearly all statistical models , there is no closed form solution for the bayesian posterior density estimator needed for model optimization ; therefore , computational methods with numerical integration are a necessity . the mcmc sampling technique provides an effective approach for sampling from a distribution of parameters to solve this problem using iterative numerical integration . the mcmc approach samples a distribution of parameters at each iteration that is dependent on the conditional distribution , which is in turn dependent on the values sampled from the previous iterations . the posterior distribution is arrived at through this stochastic , iterative process that is informed by a combination of the current model , the model priors , and the analysis data set . the optimal set of fixed and random effects of the model is derived once the iterative mcmc process has reached a state of equilibrium , often called the the parameters vary stochastically about their means with a defined variance that is based on the optimal relationship between the model / priors and the analysis data . during the initial series of mcmc iterations , efficiently obtaining the stationary can be challenging . there are different approaches to arrive at the stationary distribution , but the most common is to use a burn - in period of mcmc iterations during which a large number of iterations are discarded . following a sufficiently long burn - in period , the posterior parameters will converge to the stationary distribution . this is analogous to convergence to the maximum likelihood using more traditional estimation algorithms , with the exception that there is not convergence to a single maximum likelihood , but rather a probability distribution from which various useful statistics can be derived ( e.g. , mean , median , and sd ) . determining the appropriate number of burn - in iterations to achieve convergence to the stationary distribution is the greatest challenge for model optimization using mcmc bayesian estimation algorithms , particularly with complex pk / pd models . two problems that cause difficulty for convergence to the stationary distribution are as follows : correlation of the parameters with their initial estimates and autocorrelation , which is a systematic sequential within chain correlation . diagnostic tests have been developed to determine whether convergence to the stationary distribution has occurred and include single chain vs. multiple mcmc approaches . many of these convergence diagnostics are available in the bayesian output analysis package available for r or s - plus ( table 1 ) . the geweke and gelman and rubin diagnostics can be plotted as a function of iteration to determine the progress of convergence as a function of the number of iterations . to determine whether the posterior parameters are uncorrelated with their initial estimates , it is typical to perform at least three mcmc with parameters that have different starting values . if the three chains converge to similar posterior distributions as determined by a multiple chain convergence diagnostic ( e.g. , gelman and rubin ) , then it is assumed that they are no longer correlated with their initial estimates . autocorrelation is typically a more difficult problem for bayesian nlme pk / pd modeling because it is often caused by correlation between parameters in the model ( often related to the structure of the model ) and may require tens of thousands of mcmc iterations before the autocorrelation is corrected . the degree of autocorrelation is typically assessed using a lag - autocorrelation plot , which determines the degree of autocorrelation within chains based on the distance ( i.e. , number of iterations or lag ) between the sampled parameters . nonmem and bugs ( winbugs or openbugs ) are two common platforms for implementation of mcmc bayesian estimation for pk / pd modeling . however , neither platform incorporates these convergence diagnostics ; thus , assessment of convergence must be conducted using an external tool . few published examples exist of the application of mcmc bayesian estimation to complex , mechanism - based pk / pd models . the approach has been more commonly adopted in the field of toxicology for physiologically based pk modeling of xenobiotic compounds in humans and animals . this is , in part , due to the fact that environmental toxicologists often need to estimate the risk posed by different xenobiotic agents , which fits in well with the ability of bayesian approaches to provide a posterior probability distribution for the model . in addition , there has been widespread adoption in toxicology of ordinary differential equation modeling software tools such as acslx , which have incorporated mcmc bayesian algorithms . the use of mcmc bayesian nlme approaches for application to clinical pk / pd problems is much less common . in 2007 , jonsson et al published a reanalysis of a mechanism - based pk / pd model of neutropenia , which was the first example of the fully transparent application of mcmc bayesian methods to a complex , hierarchical mechanistic pk / pd problem . they highlighted the difficulties with determining convergence and the time - consuming model optimization process using mcmc bayesian estimation . jonsson and co - authors conclude that the mcmc bayesian approach enables efficient use of all available information from data , scientific evidence , and more reliable predictions based on that information . in the current issue of pharmacometrics & systems pharmacology , leil et al report the application of an mcmc bayesian approach to a mechanism - based pk / pd model for prediction of cyp3a4-mediated drug interactions . these examples demonstrate that the bayesian approach to pk / pd modeling will require a shift in the approach to pk / pd modeling , with more effort being invested in identifying a biologically plausible model and in finding informative priors than in achieving parsimony . the mcmc bayesian approach currently represents the most robust and statistically rigorous manner in which to make use of prior knowledge to develop nlme pk / pd models that can be used to improve decision making in biomedical research and development .

mechanism - based pharmacokinetic / pharmacodynamic models have a fundamental basis in biology and pharmacology and , thus , are useful for hypothesis generation and extrapolation beyond the conditions of the original analysis data . the complexity of these models necessitates the incorporation of prior knowledge to inform many of the model parameters . markov chain monte carlo bayesian estimation offers a robust and statistically rigorous approach for incorporation of prior information into mechanism - based models . this article provides a perspective on the utility of this approach .

metastases to organs such as the liver , bones or central nervous system appear to be a frequent complication of lung cancer , whereas metastases to the suprarenal glands are found less frequently . metastases of lung cancer to the spleen are a great rarity and they are described sporadically . an adrenal gland tumor detected incidentally during imaging tests is described as an incidentaloma [ 37 ] . primary cysts acquiring enormous proportions and hemangiomas are classified as benign tumors [ 9 , 10 ] . metastatic lesions and inflammatory pseudotumors may also be seen , but only very rarely and usually as casuistry [ 11 , 12 ] . splenic lesions may be observed in the course of malignant lymphoma [ 13 , 14 ] . lesions characteristic of sclerosing angiomatoid nodular transformation ( sant ) have also been described . in most cases , the typical characteristics of splenic tumors are established on the basis of histopathological findings , which are obtained by the surgical removal of the tumor or by post - mortem examination [ 8 , 10 , 1618 ] . this work presents a case of simultaneous dissemination of lung cancer to the adrenal gland and to the spleen . a female patient ( age 74 ) was sent from a hospital in zawiercie for further investigations and management of a left lung tumor lesion discovered during x - ray examination . chest surgeons had rejected her from an invasive therapy . however , bronchoscopy was performed and revealed no evidence of pathological bronchial lesions . in this situation the patient was sent to our hospital for the purpose of making the histopathological diagnosis ( history no . 16735/877/09 ) . computed tomography ( ct ) scan showed chest infiltration situated peripherally in the left lung . after establishing the distance , place and depth of the puncture by using ct ( fig . 1 ) , the parietal tumor was visualized by ultrasound and a biopsy was performed . we performed an ultrasound - guided ( free hand technique ) fine - needle biopsy of the lesion using a hitachi eus 515 sonographic machine ( fig . computed tomography imaging scan establishing the distance , place and depth of the puncture ultrasound imaging scan wall located left lung tumor biopsy needle the ultrasound examination of the abdomen revealed a pathological mass in the spleen and in the left adrenal gland ( fig . we also performed in local anesthesia an ultrasound - guided ( free hand technique ) fine - needle biopsy of these lesions . in our case small cell lung cancer was detected in the percutaneous biopsy of the left lung . the same type of cancer as in the left lung was observed in both the adrenal gland and in the spleen ( metastases of small cell cancer ) . imaging methods available to us showed no evidence of cancer metastases in other organs . in the existing literature , we found only a few cases of lung cancer metastases to the spleen [ 2 , 17 , 18 ] . simultaneous metastases of lung cancer to the adrenal gland and the spleen have never been described . the case presented above shows that the metastatic lesion can sometimes be an accessible place to collect tissue for diagnosing the cancer pattern of the primary cancer site . the case is exceptional because the spleen is an organ where lung cancer metastases are not frequently found , while metastases to the adrenal gland alone are common . the case is also unique because the adrenal gland and the spleen are organs where finding concurrent metastases of lung cancer is very rare .

metastases of lung cancer to such organs as the liver , bones or to the central nervous system appear to be a frequent complication of this disease . at the same time , metastases to the adrenal gland are found less frequently . metastases of lung cancer to the spleen are a great rarity and they are described sporadically . our report presents a unique case of left lung cancer with simultaneous metastases to the adrenal gland and to the spleen . all the presented lesions were diagnosed by ultrasound guided biopsy and confirmed by histopathological examination.the patient received combined chemoradiotherapy . she was closely monitored over an 18-month observation period following treatment . no new metastases were reported .

herpes simplex virus ( hsv ) is a double - stranded dna virus with two strains , hsv-1 and hsv-2 . after primary infection , herpesviruses establish a life - long latent infection through persistence in neurons of the dorsal root ganglia and the autonomic nervous system . reactivation can be triggered by local and systemic factors ( e.g. ultraviolet irradiation , tissue damage , fever , physical or emotional stress , immunosuppression ) . some common clinical manifestations of hsv-1 infection include gingivostomatitis ( primary infection ) , herpes labialis , encephalitis , and keratoconjunctivitis . hsv-1 can often be recovered from bronchial secretions , especially in intubated patients , . however , true hsv-1 lower respiratory tract infections in immunocompetent adults are uncommon . we present a case of a hsv-1 lower respiratory tract infection likely linked to marijuana inhalation at the time of an active herpetic orolabial ulcer . a 46-year - old male initially presented with a 1 week history of fevers , headache , non - productive cough , and increasing dyspnea . he was admitted to the hospital and treated with antibiotics , bronchodilators and intravenous and oral corticosteroids for presumed community - acquired pneumonia and asthma exacerbation . he was discharged and completed a 10 day course of antibiotics and an oral prednisone taper without significant improvement in his symptoms . he returned for medical care 2 weeks after illness onset with continued fevers , malaise , and dyspnea with minimal exertion and a persistent non - productive cough with post - tussive emesis . his past medical history included mild asthma , no inhaled or chronic systemic corticosteroid use , and only occasional use of albuterol metered dose inhaler ; hepatitis c , treated with interferon - alpha / ribavirin and achieved sustained virological response 6 years prior to admission ; and depression . his medications were cefpodoxime ; he had completed an oral prednisone taper 2 days prior to admission . the patient quit tobacco 4 years earlier and had a 20 pack - year history . there had been no recent travel and he had one dog at home . on physical examination , the blood pressure was 122/70 mmhg , pulse 60 beats per minute , respirations 20 breaths per minute , and oxygen saturation 96% on 3 l oxygen nasal prong . the patient had evidence of a healed ulcer on the lateral aspect of his left upper lip . there were no active ulcerations noted over the lips , anterior , or posterior oropharynx . the patient had bilateral rhonchi over the mid posterior lung fields and late expiratory wheezing with forced expiration bilaterally . the white blood cell count was 18,900/mm with 65% neutrophils , 20% lymphocytes , 11% monocytes , 3% eosinophils , and 1% basophils . a ct scan of the chest with pulmonary embolism protocol revealed no pulmonary embolism , but demonstrated bilateral bronchial wall thickening , and ground glass opacities in a peri - bronchovascular distribution ( fig . the patient was begun on vancomycin and piperacillin / tazobactam , intravenous methylprednisolone , bronchodilators , and supplemental oxygen . after 2 days , the patient had not clinically improved and he underwent a bronchoscopy with bronchoalveolar lavage and transbronchial biopsy . the biopsy specimen revealed chronic interstitial pneumonitis , squamous metaplasia and herpetic viral inclusions in bronchial epithelial cells ( fig . the patient also had a positive anti - hsv igm antibody level , an elevated anti - hsv-1 igg titer , and negative anti - hsv-2 igg titer . upon additional questioning , the patient recalled that he had a large herpetic ulcer on his left upper lip for 12 weeks approximately 1 month prior to his initial presentation . he had continued to regularly smoke marijuana through a pipe while having the orolabial ulcer . after several days of treatment and clinical improvement , he was switched to oral famciclovir every 8 h for a total of 4 weeks along with a slow oral prednisone taper . he was seen in follow - up 3 weeks after discharge and he reported near complete resolution of symptoms . have been typically described in immunocompromised individuals : burn patients , pregnancy , hiv , malignancy , as well as solid organ and hematopoietic stem cell transplant recipients , , . we present a case of hsv bronchiolitis and pneumonitis in an immunocompetent individual , likely linked to chronic habitual marijuana use . the histopathology from the transbronchial biopsy and the positive anti - hsv igm serology support acute invasive infection and not simply colonization . the squamous metaplasia from chronic marijuana use likely promoted localized viral replication in the lower respiratory tract . squamous epithelial cells are a permissive cell type for hsv replication , and previous reports have highlighted that hsv has nearly always been seen in areas of squamous metaplasia in lower respiratory tract infections . marijuana smoking with deep inhalations at the time of the orolabial herpetic ulcer promoted deep tracheobronchial seeding of hsv . a few cases of hsv esophagitis and pneumonitis have been reported among immunocompetent patients with hsv orolabial ulcers , . tobacco smoking has been associated with an increased risk for community acquired pneumonia and influenza . additional undefined intrinsic host factors , and localized immune and inflammatory changes in the respiratory tract produced by chronic habitual marijuana use , may have also contributed to the development of hsv bronchiolitis and pneumonitis . the short - term corticosteroid use before the second admission may have also played a role . this case serves as a reminder to consider hsv as a potential unusual cause of lower respiratory tract infection / inflammation in individuals with chronic habitual marijuana use .

herpes simplex virus ( hsv ) lower respiratory tract infections in adults are uncommon . we present a case of hsv bronchiolitis and pneumonitis in an immunocompetent individual , likely linked to chronic habitual marijuana use and a herpetic orolabial ulcer . the case serves as a reminder to consider hsv as a potential unusual cause of lower respiratory tract infection / inflammation in individuals with chronic habitual marijuana use .

hallucinations , predominantly visual in nature , can occur in parkinson disease ( pd ) and are often related to the antiparkinsonian drugs . visual hallucinations are a well - recognized problem . besides visual hallucinations , patients with pd uncommonly experience different forms of hallucinations , such as auditory hallucinations . auditory hallucinations occur in 8% to 13% of patients with pd and are generally accompanied by visual hallucinations . auditory musical hallucinations ( amhs ) are rare complex auditory hallucinations in pd that have been reported in only 8 patients . four patients for whom detailed information is available have been documented , and 2 of these patients were deaf ( table 1 ) . in patients with amhs caused by conditions other than pd , amhs are characterized by repetitive and usually uncontrollable musical patterns , unrelated to external stimulation . in december 2005 , a 72-year - old right - handed woman with no clinically significant history of disease , including epilepsy , migraines , or mental disease such as schizophrenia , noticed a tremor in her right hand . in december 2007 , she noted slowness of movement , difficulty in walking in narrow spaces , and the onset of left hand tremor in addition to right hand tremor and presented at our hospital . she showed features of moderate parkinsonism , including masked face , retropulsion , bradykinesia , and right - side - dominant rigidity and resting tremor . the scores on parts i , ii , iii , and iv of the unified parkinson disease rating scale ( updrs ) were 0 , 14 , 24 , and 0 , respectively . the scores on the mini - mental status examination ( mmse ) and frontal assessment battery were normal ( 30/30 ) and decreased ( 16/18 ) , respectively . she was given levodopa ( 250 mg / day ) and immediate - release pramipexole ( 1.5 mg / day ) , and the severity of these symptoms had decreased in may 2008 . in august 2008 , she showed wearing - off phenomenon and had freezing of gait . subsequently , she was given entacapone ( 200 mg / day ) in june 2010 and zonisamide ( 25 mg / day ) in july 2011 . the scores on the mmse and zung depression scale were 29 and 45 , respectively . in july 2012 , selegiline ( 5 mg / day ) was started since the severity of freezing gait had intensified , and the patient frequently fell . she was then given stable doses of levodopa ( 500 mg / day ) , immediate - release pramipexole ( 1.5 mg / day , 3 times per day ) , entacapone ( 200 mg / day ) , zonisamide ( 25 mg / day ) , and selegiline ( 5 mg / day ) . neuroleptic drugs were not used . in december 2012 , we switched from immediate- to once - daily extended - release pramipexole in stable dosage because off - periods had increased . after that , she often had visual hallucinations such as animals or human hands and auditory hallucinations such as rustling sounds . in april 2013 , the amhs were a quiet piano or often songs on a loud radio or background music over other sounds . amhs did not occur every day , but when they did the music persisted all day while the patient was awake . the amhs were unrelated to visual hallucinations as well as other auditory hallucinations of children talking together . the music was unpleasant , but not objectionable , threatening or ego - syntonic , and it did not interrupt her daily activities . although the hallucinations persisted , she requested no further measures to suppress the hallucinations , such as the reducing the doses of anti - parkinsonian drugs or using neuroleptic agents , because the hallucinations were non - threatening and tolerable . in october 2013 , zonisamide was increased to 50 mg / day because off - periods had increased . after receiving the patient 's informed consent , we switched back from extended- to immediate - release pramipexole in a stable dosage in january 2014 to determine whether extended - release pramipexole was causing the amhs . when the patient visited to our hospital 5 day after switching back to immediate - release pramipexole , she reported that recognizable subjects such as animals or persons that she previously saw clearly as visual hallucinations had disappeared , whereas some unrecognizable shadows were often evident . amhs sometimes occurred for several hours , particularly in the early morning or evening , and other auditory hallucinations became faded . twelve days after retuning to immediate - release pramipexole , visual hallucinations rarely occurred , and amhs and other auditory hallucinations had disappeared . among the 5 patients including ours for whom detailed information are available , amhs in pd were non - specific incomprehensible tunes or different familiar or popular songs such as folk or lyrical songs , which were unrelated to an external stimulus . the inability of patients to interrupt amhs might have been uncomfortable , but was not threatening . female sex , hearing impairment , advanced age , psychiatric conditions , cognitive disorders , alcoholism , obsessive compulsive disorders , and neurological conditions ( eg , seizure disorders , stroke , tumors , central nervous systems infections , and brain lesions in the dorsal pons , temporal lobes , and frontal lobes ) were reported as risk factors for amhs . our patient had none of these risk factors except for female sex and advanced age . in the 5 patients including ours , neither cognitive decline nor depression was evident during amhs , and disease severity and off - periods were apparently unrelated to amhs . the intervals between the time of altering treatment with anti - parkinsonian drugs and the onset of amhs were long in 2 previous patients , and the authors did not mention any relation between amhs and anti - parkinsonian drugs . in another patient , however , short - term amhs were elicited by amantadine . in our patient , although other preceding dopaminergic treatments such as levodopa , entacapone , and selegiline might have been prerequisite to the development of the hallucinations , the auditory and visual hallucinations occurred after immediate - release pramipexole was switched to extended - release pramipexole , and similar findings have not been reported previously . several months after that , amhs began . in studies of patients with advanced or early pd , switching from immediate- to extended - release pramipexole was safe , and the most frequently reported side effects were dyskinesia or somnolence . in healthy male volunteers , the pharmacokinetics and tolerability of a once - daily extended - release formulation of pramipexole were similar to those of an immediate - release formulation of pramipexole given 3 times daily . however , 2 patients with pd in whom dopamine dysregulation syndrome developed after switching from immediate - release to extended - release pramipexole have been reported . amhs in pd were non - threatening , and dopaminergic treatment may predispose patients to amhs or be a unique possible cause of amhs .

abstractauditory musical hallucinations ( amhs ) are rare complex auditory hallucinations in parkinson 's disease ( pd ) that have been limited previously . the characteristics of amhs in pd remain uncertain . we describe a 72-year - old woman with pd who presented with amhs . the amhs occurred after immediate - release pramipexole was switched to extended - release pramipexole . the amhs were a quiet piano or often songs on a loud radio or background music over other sounds . the music was unpleasant , but not objectionable , threatening , or ego - syntonic , and it did not interrupt her daily activities . amhs in pd were non - threatening , and dopaminergic treatment may predispose patients to amhs or be a unique possible cause of amhs . the hallucinations can occur after immediate - release pramipexole was switched to extended - release pramipexole .

a two - way process of exchanging or shaping ideas , feelings , and information between dentist and patient has created keen interest in dental society . the best way to achieve effectively exchanging and shaping ideas depend on the credibility of the dentist that is how he defines empathy practically . empathy is to see with the eyes of other , to hear with the ears of another , and to feel with the heart of another ( alfred adler ) . empathy was derived from two greek terms , em and pathos , meaning feeling into and has its origin from the german word einfulung . the basic difference between empathy and sympathy is that empathy means intellectual understanding , while sympathy means sharing sentiments . the american dental education association always emphasized on including empathy as a part of the dental curriculum as it plays an important role in healthy dentist and patient relationship . sherman and cramer reported a similar decline in empathy levels among the dental students during the 2 year of dental training , but in contrary some studies reported vice - versa . in view of such varying empathy findings from different countries , it is the need of the hour to understand empathy levels among dental students in the indian context . the present study is the first of its kind in india and few among the world to explore the empathy level among dental students . to measure the self - reported empathy levels among dental undergraduate and postgraduate students of the dental program ( bds , mds)to review the trend of changes in empathy level with experience , age , and gender among dental undergraduate and postgraduate students . to measure the self - reported empathy levels among dental undergraduate and postgraduate students of the dental program ( bds , mds ) to review the trend of changes in empathy level with experience , age , and gender among dental undergraduate and postgraduate students to measure the self - reported empathy levels among dental undergraduate and postgraduate students of the dental program ( bds , mds)to review the trend of changes in empathy level with experience , age , and gender among dental undergraduate and postgraduate students . to measure the self - reported empathy levels among dental undergraduate and postgraduate students of the dental program ( bds , mds ) to review the trend of changes in empathy level with experience , age , and gender among dental undergraduate and postgraduate students a cross - sectional institutional and self - reporting questionnaire based study was conducted among students pursuing their graduation and postgraduation in two private dental institutions located in the north west part of the country , rajasthan , india . the curriculum in india pertaining dental education offers 5 years course during graduation and 3 years of course during postgraduation . the present study was cleared by the ethical committee of the sdcri and maharaja ganga singh dental college . this research has been conducted in full accordance with the world medical association declaration of helsinki . data were obtained from the 1 to final ( 4 ) year students , interns , and postgraduate students enrolled in bachelor of dental surgery and master of dental surgery program , respectively , in these two institutions from january to april 2015 . the students were briefly explained about the nature of the study , and their written consent was taken . the inclusion criterion for the present study was that students must have completed 6 months following admission . those students who were either unable to provide the required information or incomplete questionnaire form were excluded . the initial sample consisted of 1041 students but after applying the inclusion and exclusion criteria , the final sample comprised 978 students . health profession students ( jspe - hps ) version questionnaire ( already validated ) was administered to assess the empathy level . the questionnaire consists of twenty components using 7-point likert scale ( for every single component ) and score ranges from 20 to 140 with upper values representing greater empathy . along with jspe - hps questionnaire , there are four subcategories measuring different dimensions of empathy such as perspective taking , compassionate care , standing in patient 's shoes , and personal distress . confirmatory factor analysis was used to recognize the dimensionality of the jspe - hps version using ( a ) kaiser 's criteria , ( b ) an eigenvalue ( > 1.25 was used ) , and ( c ) only retaining items if coefficients were 0.30 . after evaluation of results , 3-factor pathway was selected , i.e. , perspective taking , compassionate care , as well as standing in patient 's shoes . the above outcome resulted in approximately 37% of the overall described variance . among the components , ( armonk , ny : ibm corp ) for generation of descriptive , as well as inferential statistics . the statistical significant difference among groups the female : male ratio in the present study was 2.7:1 [ table 1 ] . there was a statistically significant difference reported when empathy was tested in relation to gender ( between males and females ) , as well as for age ( p < 0.05 ) . the lowest and highest mean empathy score was found in postgraduate ( mean = 108.77 , standard deviation [ sd ] = 9.12 ) and 1 year ( mean = 117.23 , sd = 14.19 ) dental students , respectively . empathy score when tested according to experience using anova and post hoc test was found to be statistically substantial ( p < 0.05 ) . different variables retorts on the jefferson scale of physician empathy health profession student 's ten components were computed on subscale-1 and components value arraying between 0.697 and 0.518 describing 22.85% of the variability . the most important component was health - care providers understanding of the emotional status of the patients , as well as that of their families ' . five components were computed on subscale-2 and components value arraying between 0.207 and 0.023 describing 10.18% of the variability . five components were computed on subscale-3 and components value arraying between 0.572 and 0.327 describing 9.34% of the variability . two components were common among subscale 2 and subscale 3 , i.e. , component 14 ( i believe that emotion has no place in the treatment of medical illness ) and component 11 ( patients ' illnesses can be cured only by targeted treatment ; therefore , health - care providers ' emotional ties with their patients do not have a significant influence in treatment outcomes ) . the required cronbach 's alpha value for satisfactory internal consistency should be above 0.70 and in the present study cronbach 's value for subscale 1 , 2 , and 3 were 0.79 , 0.76 , and 0.48 , respectively [ table 2 ] . component analyses and adjusted score correlations of the jefferson scale of physician empathy health profession student 's few components brought out eminent mean values : patients feel better when their health - care providers understand their feelings i believe that empathy is an important factor in patients ' treatment brought out a mean value of 5.27 ( sd = 1.31 ) . the aim of the contemporary study was to define the properties of jse - hps , as well as to measure the empathy among students of dental colleges in sri ganganagar , rajasthan , india . the present study reported that postgraduate students had statistically lower empathy score as compared to all other years of students . this difference may be due to the fact that during the initiation of the dental course , students believe in idealism , i.e. , sharing the feeling of the patients but with the progression of the dental course these feelings vanish , i.e. , idealism gives way to the realization ( means to get through the various level of dental degree meritoriously , requisite is to acquire enormous dimensions of facts ) . hence , significant perspectives such as sharing the thoughts and feelings of the patients are put aside and emphasis swings on facts - based examinations . the mean empathy score of the present study ranges from 103 to 117 which is similar with the other studies among dental and medical students , while in contrary , other studies reported 7890 mean empathy score . while analyzing the empathy among male and female in the present study , females showed higher empathy level than males which is similar with the other studies , but this was against the studies done by rose et al . and babar et al . this might be due to the fact that women 's brains probably show more empathy than men 's brains . when females were probed to recognize other human 's feeling , female 's brain action showed that they themselves feel the same sentiments as well while in contrary male 's brain action showed noetic assessment a more objective position . in the present study , it was found that empathy score differs by age while the same was not reported by babar et al . subscale-1 , 2 , and 3 are parallel with the studies described previously . as empathy is an essential component of maintaining healthy rapport between the dentist and patient , thus amending empathy is the vital chore of health training . recently , bonvicini et al . conducted a study regarding communication skills exercise to find whether it will result in rise of the empathy level or not . the conclusion of the study was that communication skill exercise led to increase in empathy among the students . the present study showed that empathy levels were dropping with the progression of dental course . therefore , the need is to introduce exercise regarding empathy among dental students at the initiation of and during their dental course . however , there is an argument regarding the introduction of training in empathy as newton et al . the author proposes to introduce administrative modifications which motivate students scholastically and sensitively during their dental course . this will result in interprofessional education , growth of team effort principle , as well as alterations in judgment method . hence , results of the present study can be implemented among other dental institutions also . the limitation of the present study is that valuation of empathy was constructed on subjective evaluation of a validated questionnaire ; therefore , observational approaches such as the history - taking rating scale could be used with jse - hps to measure empathy level in dental students . cross - sectional studies make it impossible to understand the process of changes in empathy level through the years of dental course . dental health educators should consider this fall in empathy seriously as early as possible during the dental course . empathy - related teaching exercises must be implemented among the dental students to endorse the growth of empathy so that fall in empathy should be prevented . more longitudinal research is required to investigate the outcome of communication exercise in cultivating empathy among dental students . the authors of this manuscript declare that they have no conflicts of interest , real or perceived , financial or nonfinancial in this article . the authors of this manuscript declare that they have no conflicts of interest , real or perceived , financial or nonfinancial in this article .

background : empathy plays an important role in healthy dentist and patient relationship . hence , the aim of the study is to ( a ) to measure the self - reported empathy levels among dental undergraduate and postgraduate students . ( b ) to review the trend of changes in empathy level with experience , age , and gender among dental undergraduate and postgraduate students.materials and methods : this cross - sectional , questionnaire - based study was carried out in two private dental institutions situated in sri ganganagar , india , with a sample size of 978 . data were obtained from the 1st to final year ( bds ) , interns , and postgraduate students from january to march 2015 . an empathy level of students was assessed by the jefferson scale of physician empathy health profession students version questionnaire . an exploratory factor analysis using kaiser 's criteria was undertaken to appraise the construct validity and dimensionality . based on the results of the factor analysis , three factors were selected ; labeled as perspective taking , compassionate care , and standing in patient 's shoes.results:the majority of the students was female in a equivalent ratio of 1338:618 . there were significant differences in empathy scores by gender and age ( p < 0.01 ) . the lowest and highest mean empathy scores were found in postgraduate ( mean = 108.77 , standard deviation [ sd ] = 9.12 ) and 1st year ( mean = 117.23 , sd = 14.19 ) dental students , respectively.conclusion:dental educators should consider the likely decline in empathy among students as early as possible and adopt communication teaching strategies to promote the development of empathy and reduce the risk of further decline .

the sleeve gastrectomy ( sg ) is the first part of the duodenal switch operation and leaves a lesser curvature tube after excising the fundus and greater curvature portion of the stomach . this surgery has become more and more popular as the first stage in the treatment of obesity [ 1 , 2 ] . minimally invasive surgery is being incorporated into general surgical practice . during the last decade , the advent of the da vinci surgical system ( intuitive surgical , sunnyvale , ca , usa ) has enabled many complex procedures to be performed with minimally invasive techniques in bariatric surgery . roux en y gastric bypass remains one of the most challenging procedures performed by bariatric and general surgeons . sleeve gastrectomies are a less technically demanding procedure , and for this reason , we used them to gain dissection and suturing experience using the da vinci system . this initial experience was used to determine the learning curve in performing the robot - assisted sleeve gastrectomy . between february 2010 and april 2011 , a trained surgeon in advanced laparoscopic surgery ( rv and jmf ) performed 32 consecutive robotic sleeve gastrectomies ( rsgs ) for the treatment of morbid obesity . patients were included according to the waiting list inclusion and all meet the criteria for sleeve gastrectomy . the surgical team consisted of two attending physicians who shared the console and the scrubbed table activities . r. vilallonga trained in a pig model performing 10 nephrectomies prior to beginning the rsg . the two surgeons worked consistently within the same roles ; r. vilallonga was in the console and j. m. fort at the patient 's side in all cases . a 12 mm port was inserted 120 mm inferior and slightly left to the sternum for camera access . for the latter port , we used an extra large 150 mm long trocar ( xcel trocar , ethicon - endosurgery , cincinnati , oh , usa ) . the right 12 mm working port was positioned 6 cm from the midline trocar . the left 12 mm working port was located 6 cm to the left of the midline trocar . an 11 mm trocar was placed laterally to the left hypochondrium ( to allow the table assistant to assist and also to place the left arm of the robot during surgery ) and an 8 mm da vinci trocar was placed under the right hip as laterally as possible ( anterior axillary line ) to allow liver retraction . the 8 mm da vinci trocars were inserted through standard , disposable 12 mm trocars . this double - cannulation technique was used because standard 12 mm trocars are required during the insertion of the staples . all trocars were inserted under direct visualization with the da vinci system camera ( figure 1 ) . at this stage of the procedure , we began recording the docking time ( dt ) . the robotic camera was locked last but was used to insert all robotic cannulas and instruments . the robotic cart was positioned over the patient 's head ( which was covered with head protection designed for this purpose ) . once the general setup was ready , the procedure began with the console surgeon using a grasper in the left hand and a modified harmonic scalpel in the right hand . the third da vinci arm used another forceps in order to retract the liver from the 8 mm trocar placed in the right - hand side of the patient . the greater curvature of the stomach was sectioned at the lowest point in order to reach the lesser epiploic sac . this stage of the procedure is completely robotic and the first assistant does not usually participate . the division of the gastrocolic and gastrosplenic ligament continued exactly as in a standard lsg . the robot ensures precision in the upper part of the stomach , in which you need to avoid any injury to the spleen and properly visualize the vessels . dissection continued up to 5 cm from the pylorus following dissection of the upper part of the stomach . at this stage of the procedure , the anesthesiologist did not encounter any difficulty placing the bougie with the robotic bedside cart . a stapler ( echelon 60 endopath stapler , endoscopic linear cutter straight , ethicon - endosurgery , cincinnati , oh , usa ) , loaded with a green cartridge , was used to divide the stomach from the lowest tip of the greater gastric curvature , 5 cm proximally to the pylorus , towards the lateral edge of the bougie . the right arm was again docked and the left robotic arm was switched to the left lateral 11 mm trocar . this manoeuvre allowed the decannulation of the right arm from the 12 mm trocar without moving the robot and can be performed within a few seconds . the table surgeon inserted a stapler loaded with blue cartridges in order to divide the sleeve up to the end of the upper part . the stomach was then removed from the cavity through the 12 mm trocar . a robotic continuous polypropylene suture ( 3/0 ) ( prolene , ethicon - endosurgery ) the anaesthesiologist filled the sleeve with diluted methylene blue in order to detect any leakage from the staple line . all patients underwent a mandatory upper gastrointestinal tract series with contrast material on the third postoperative day . all patients received nutritional advice and were instructed to follow a liquid and semiliquid diet for 2 weeks . all patients are followed up every 3 months in the outpatient clinic until the end of the second postoperative year and then are seen annually . variables examined included overall operative time , docking time , length of hospital stay , and complications . the patient number at which a < 5% change occurred within a variable gave the minimum number of cases needed to reach the learning curve for that variable . in order to examine the learning curve associated with selected continuous endpoints as the number of operative cases increased robot - assisted sleeve gastrectomy was performed in 32 patients , of whom 12 were males and 20 females . their mean age was 44 years , and the mean bmi was 48.3 kg / m . 8 patients had diabetes , 13 had hypertension , 9 patients had dyslipidemia , and 16 were using a continuous positive airway pressure ( cpap ) device at home at the time of operation . there were no differences between the two cohorts in terms of bmi ( table 1 ) . all patients were included consecutively according to the waiting list order and the eligibility for sleeve gastrectomy . from the first 12 cases that configured cohort 1 , the set - up time gradually decreased to 34.9 minutes as the nurses became more experienced . two laparoscopic and robotic operating tables were always prepared and preparation of the robot was included in this set - up time . the overall operating time ( ot ) decreased from 89.8 minutes in cohort 1 to 70.1 minutes in cohort 2 ; there was less than 5% change in ot after case 19 up to case 32 ( figure 2 ) . this decrease in ot was attributed to better understanding of the technique and the development of a coordinated procedure . however , time from incision to docking decreased from 9.5 minutes in cohort 1 to 7.6 minutes in cohort 2 . the time taken to dock the robotic system also decreased from 9.1 minutes in cohort 1 to 6.6 minutes in cohort 2 . the plateau on the curve for time from incision to docking , docking , and total operative time occurred at the 19th22nd patient with < 5% change from this point ( figure 3 ) . the followup was uneventful for all patients in terms of nausea , vomiting , or stenosis , with a mean followup of 10 months . sleeve gastrectomy is a purely restrictive operation that reduces the size of the gastric reservoir to 60100 ml , permitting the intake of only small amounts of food and imparting a feeling of satiety earlier during a meal . it has been performed laparoscopically with good results . in 2000 , the food and drug administration ( fda ) approved the da vinci surgical system ( intuitive surgical inc , sunnyvale , ca , usa ) for use in general laparoscopic surgery , and since then many surgeons have used this system in order to improve their surgical outcomes . it has also been used in bariatric surgery to complete demanding surgeries such as gbp , which requires high levels of expertise even in trained surgeons [ 6 , 7 ] . our data support the conclusion that both setup and docking of the robot can be achieved within an acceptable time after the learning curve . however this can only be determined by comparing subsequent cases with the first cases performed by each surgeon . unfortunately , the relevant data were not available . set - up time and docking time were recently evaluated for different robotic surgeries , and it was shown that they could be initially time consuming but that they are easy to learn and have steep learning curves . the same was found in our initial experience working with the same scrub - nurse team and the same surgical team members . also , we have not been able to compare the learning curve of rsg procedure to rgbp because only 7 cases have been performed . laparoscopic sleeve gastrectomy can be safely and efficiently performed in a newly established bariatric centre following a mentorship procedure . it is known that sleeve gastrectomy is a less technically demanding procedure compared to gastric bypass . however , when implementing new technologies such as robotic assisted surgery , it can be a more amenable procedure than gastric bypass . in addition , the learning curve has been reported to be shorter for surgeons who initiated their experience at an institution with an established laparoscopic bariatric programme [ 10 , 11 ] . we included more patients in order to determine the number of cases needed to produce a plateau in these variables . some previous articles have suggested that it took 30 robotic cases to perform the procedure in less time than it took for her median laparoscopic times . buchs in his article learning curve for robot - assisted roux - en - y gastric bypass assessed the learning curve using a cumulative sum method . he found the learning curve consisted of two distinct phases : phase 1 ( the initial 14 cases ; mean ot , 288.9 min ) and phase 2 ( the subsequent cases ; mean ot , 223.6 min ) , which represented the mastery phase , with a decrease in ot ( p = 0.0001 ) . however there could be a phase three , a phase four , or even beyond as in our case series . his mean operative time of 223.6 min for phase 2 ( his defined mastery phase ) , which is considerably longer than typical operative times for robotic gastric bypass , makes it very likely that there are more stabilization points in operative time . for this reason , we have to comment that we could have a sample size too small to capture this stabilization phenomenon . however , times and result in terms of complications , outcomes , and results are satisfactory . for this reason , we focused specifically on the set - up and docking times of the da vinci surgical system in order to perform surgery efficiently . according to our data , trained nurses can achieve robotic setup efficiently , and docking can be conducted time effectively by the console surgeon and the first assistant . as shown previously , a trained nurse can complete robotic draping within 35 minutes while the patient is in preparation for anesthesia . the learning curve for docking some authors have observed an increase in operating time when using the robotic system , but we believe that a learning curve is required in order to decrease time loss and potential risks [ 1517 ] . to our knowledge the only previous report of robotic sleeve gastrectomy mentioned the advantages of using this procedure instead of a robotic gastric bypass ( rgbp ) as the first step to introducing robotic surgery to a bariatric unit . they suggested , and we agree , that it is always wiser to start with a less demanding procedure in order to avoid errors in the initial phases of the overall robotic learning curve . in this paper , no data were reported concerning the learning curve before attempting to undergo a rygbp . in our experience , and according to our protocol , we perform sleeve gastrectomy in superobese patients ( bmi > 50 ) and we consider it more suitable for initial robotic training . using robotic assisted techniques , even in part , could be considered in rygbp during a learning curve instead of reinforced staple line rsg . however , we suggest that rsg be completed before rygbp is introduced to routine clinical practice within a bariatric unit . our early experience in rsg suggests that robotic surgery is safe , feasible , and could be an effective alternative to the conventional laparoscopic approach in bariatric surgery . robotic surgery gives all the benefits of the laparoscopic approach , with added benefits in certain challenging surgical cases . however , we believe that bariatric surgeons should be trained in rsg before rygbp . completion of a learning curve is mandatory even in experienced laparoscopic surgeons before undergoing technically demanding robotic procedures such as the rygbp . despite the lack of tactile feedback , the long set - up time , long learning curve , and continued high costs , robotic systems can be used in particularly challenging surgeries . according to our criteria and our results , the learning curve for a console surgeon for sleeve gastrectomy once this point has been reached and the operator is confident in suturing and docking with the robot , more challenging techniques can be considered . in our experience , sleeve gastrectomy can be achieved safely and could be considered as a preliminary step prior to attempting more complex bariatric procedures through a robotic assisted approach . however

objective . robot - assisted sleeve gastrectomy has the potential to treat patients with obesity and its comorbidities . to evaluate the learning curve for this procedure before undergoing roux en - y gastric bypass is the objective of this paper . materials and methods . robot - assisted sleeve gastrectomy was attempted in 32 consecutive patients . a survey was performed in order to identify performance variables during completion of the learning curve . total operative time ( ot ) , docking time ( dt ) , complications , and length of hospital stay were compared among patients divided into two cohorts according to the surgical experience . scattergrams and continuous curves were plotted to develop a robotic sleeve gastrectomy learning curve . results . overall ot time decreased from 89.8 minutes in cohort 1 to 70.1 minutes in cohort 2 , with less than 5% change in ot after case 19 . time from incision to docking decreased from 9.5 minutes in cohort 1 to 7.6 minutes in cohort 2 . the time required to dock the robotic system also decreased . the complication rate was the same in the two cohorts . conclusion . our survey indicates that technique and outcomes for robot - assisted sleeve gastrectomy gradually improve with experience . we found that the learning curve for performing a sleeve gastrectomy using the da vinci system is completed after about 20 cases .

the progress in new antimicrobial agents to multidrug resistant pathogens for the treatment of various infectious diseases is of increasing interest . therefore different plant extracts of many plants have been used locally against various pathogens , which showed positive results . higher plants and their extracts are used for the treatment of infectious disease as traditional medicines from the very beginning of life . but there are only a small percentage of these plants that have been subjected to pharmacological or biological screening . microbes which are free to move around the world cause different infections in human races . in developing countries about 43 percent of total deaths are due to infectious diseases . who claims significant control in major infectious diseases . due to jumbled use of existing antimicrobial drugs pathogenic bacteria have developed resistance against wide range of antibiotics . the -lactamase producers like staphylococcus aureus , escherichia coli , klebsiella pneumonia , and many others have become a major therapeutic problem , resulting in increased treatment failure and health care cost . microbiologists from all over the world are in search to formulate new antimicrobial drugs and evaluate the efficiency of plant products to replace chemical antimicrobial agents . medicinal plants extracts have shown to serve as a cheap source of antimicrobial agents against pathogenic microbes . these extracts have biologically active compounds , which make them attractive fowler for preying these pathogens . annual postharvest losses are resulting due to insect damage , microbial deterioration , and many other environmental factors such as humidity , aeration , temperature , and cleanliness of the massive storage and are expected to be 1025% of production throughout the world . insects are the major problem in stored grain because they destroy the quantity and quality of the grains . it is claimed that 99 families , 276 genera , and 346 species of medicinal plants have environment- friendly insecticidal properties . plant extracts or pure compounds control insects in several ways , including antifeedant , growth inhibitors , toxicity , mortality suppression of reproductive behavior , and fertility . it is expected that only in america about 200 people are dying every year due to this pesticidal poisoning . these problems resulted in renewed interest in formulating new botanical pesticides , which could be nonhazardous , effective , biodegradable , and of low cost and pose less threat to the environment . the aim of the present study was to evaluate the antibacterial , antifungal , and insecticidal activities of different fractions of oxalis corniculata . these include methanol , n - hexane , chloroform , ethyl acetate , and n - butanol soluble fractions . selection of oxalis corniculata fractions was based on the fact that these fractions were not previously screened for these activities . oxalis corniculata was collected from district buner , kpk , pakistan in june 2012 . nisar ahmad , chairman department of botany , kohat university of science & technology , kohat , kpk , pakistan , and a voucher specimen number 169 was stored there in the herbarium . plant was shade dried at room temperature and 1 kg dried plant materials were soaked in methanol to obtain methanolic extract . extract was evaporated under reduced pressure to dryness ; the residue was weighed ( 81 g ) and redissolved in distilled water . the aqueous solution of the plant extract was subjected to different solvents on the basis of increasing polarity like n - hexane , chloroform , ethyl acetate , and n - butanol to get the respective n - hexane , chloroform , ethyl acetate , and n - butanol solvent soluble fractions with the ratio of 15 g ( n - hexane fraction ) , 22 g ( chloroform fraction ) , 16 g ( ethyl acetate fraction ) , 14 g ( n - butanol fractions ) , and 10 g ( aqueous fraction ) , respectively . all the fractions were dried at low pressure using rotary evaporator and stored at 4c . to evaluate the antimicrobial activity of different fractions of oxalis corniculata , nine microbial species were used , five of which were bacterial pathogens including bacillus subtilis ( atcc7966 ) , staphylococcus aureus ( atcc 12600 ) , escherichia coli ( atcc8677 ) , shigella dysenteriae ( atcc29027 ) , and salmonella typhi ( atcc0650 ) and four fungal species including fusarium solani , aspergillus flexneri , aspergillus flavus , and aspergillus niger were taken from culture collection of department of microbiology , kohat university of science & technology , kohat , pakistan . the bacterial strains were subcultured to get fresh cultures of bacteria . for this purpose a single colony from bacterial strain was inoculated on nutrient broth . 14 g of nutrient agar media was dissolved in 1 l of distilled water at ph 7 and autoclaved for 20 minutes at 121c . the media were allowed to cool down to 45c and poured to petri plates ( 14 cm ) for preparing 75 ml of solid media . using sterile cork borer ( 8 mm ) 7 wells per plate the crude extract and fractions were dissolved in dimethyl sulfoxide ( dmso ) at the same concentration of 2 mg / ml to prepare stock solutions . from the stock solutions , the zones of inhibition of crude extract and fractions were measured in mm after 24 hours of incubation at 37c and compared with the zone of inhibition of standard drug cefixime . four fungal strains including aspergillus flexneri , aspergillus niger , aspergillus flavus , and fusarium solani were tested for the antifungal activity . fungal strains were subcultured in potato dextrose agar ( pda ) and incubated for 7 days at 28c . to evaluate the antifungal activity fungal strains were inoculated on the potato dextrose agar plate ( pda ) by point inoculation . 100 l of solution ( 2 mg / ml in dmso ) , pure dmso ( ve control ) , and antibiotic terbinafin 2 mg / ml ( + ve control ) were used . the insects ephestia cautella and tribolium castaneum were taken from department of zoology , kohat university of science & technology , kohat , kpk , pakistan . 60 mm of petri dish was used to conduct the surface film activity of all the extract by dissolving 50 mg / ml of crud extract and fractions in dmso . extracts were sprayed on to the lower part of the petri dish and allowed to dry out . these treated petri dishes having insects were kept at room temperature in a secured place . the result was observed from time to time starting from 30 minutes to 48 hours and finally recorded . the mortality of insects was confirmed by using simple microscope to check any movement of their organs . in last , the living ( if any ) insects were recovered and submitted to their respective department . the percentage mortality rate was determined by the following formula:(1)mortality% = 100number of survival insamplesnumber of survival in control100 . medicinal plants are the most prominent source of natural products against various common infectious microbes . the appearance of multidrug - resistant infectious microbes , high cost of synthetic compounds , and uninvited side effects of certain drugs insisted the new era to search for the new curative agents from alternative and low cost sources like medicinal plants . the current attempt was made due to increasing resistance of different pathogens ( bacteria and fungi ) and insects against available antibiotics and insecticides , respectively . plants extracts and compounds are of innovative interest as safe and health friendly antimicrobial and insecticidal agents . as a result the different fractions of oxalis corniculata were screened for their antimicrobial and insecticidal activities . to assess the antimicrobial activity of oxalis corniculata , the microbial strains used were tested bacterial pathogens including escherichia coli , bacillus subtilis , staphylococcus aureus , salmonella typhi , and shigella dysenteriae ; the fungal species including fusarium solani , aspergillus flexneri , aspergillus flavus , and aspergillus niger were used . for the evaluation of insecticidal activity the insects used were ephestia cautella and tribolium castaneum . the plant solvent soluble extracts showed a broad spectrum of activities against used microbes and insects . the crude extract , n - butanol , and ethyl acetate soluble fractions showed excellent activities against escherichia coli , salmonella typhi , and bacillus subtilis . similarly crude extract , n - hexane , chloroform , and n - butanol soluble fractions were active against shigella dysenteriae but not active in case of ethyl acetate soluble fraction . similarly the crude extract , n - hexane , and soluble fractions were also found to have significant activity against fungal strains including fusarium solani and aspergillus flexneri ; the crude extract , chloroform , and ethyl acetate soluble fractions were active against aspergillus flavus . the n - butanol soluble fraction was only active against aspergillus flexneri ; also chloroform , ethyl acetate , and n - butanol soluble fractions were inactive against fusarium solani . in case of aspergillus niger investigated the methanol and aqueous extracts of o. corniculata leaves for antibacterial activities against 5 bacterial strains : e. coli , s. aureus , p. aeruginosa , p. vulgaris , and b. subtilis . they recorded zone of inhibition in the range of 614 mm against these pathogens among which b. subtilis showed maximum zone of inhibition ( 14 mm ) , while , in our present investigation , the whole plant ( o. corniculata ) crude extract , its solvent soluble fractions , and the isolated compounds were evaluated for antibacterial and antifungal activities and obtained significant results . the maximum toxicity of plant against ephestia cautella and tribolium castaneum was recorded for the crud extract and chloroform soluble fraction with highest mortality rate especially for the tribolium castaneum ( up to 62% ) . n - butanol soluble fraction also showed valuable mortality ( 46% ) in 48 hours as shown in table 3 . the lowest mortality rate was recorded for ethyl acetate and n - butanol soluble fractions against ephestia cautella ( 08% ) after 48 hours ; however it was nonactive till 24 hours . the comparative study shows that the plant is more toxic against tribolium castaneum than ephestia cautella . there is no literature available on the insecticidal activity of oxalis species to compare with the present results . the chloroform soluble fraction was subjected to column chromatography and as a result two known compounds , compound 1 ( figure 1 ) and compound 2 ( figure 2 ) , were isolated whose structures were elucidated with the help of ei , hreims , 1d , and 2d nmr techniques . the two isolated compounds 1 and 2 were subjected to antibacterial , antifungal , and insecticidal activities . the result showed that compound 2 was more active than compound 1 against the tested organisms . both the compounds were active against all the tested bacteria except s. aureus as shown in table 4 . while compounds 1 and 2 showed negative activity against fusarium solani , aspergillus flavus , aspergillus niger , and aspergillus flexneri which indicates that these compounds are inactive against these species of fungi . table 5 shows that insecticidal activity of compound 2 was also potent as compared to that of compound 1 . the present study suggests that oxalis corniculata has good antibacterial , antifungal , and insecticidal properties and can be used for the treatment of infections and control of insects . the plant extracts could be a new source for antibiotics and pesticides with minimum noxious effects on the environment . further studies may also lead to isolate and characterize the active compounds of the plant extracts and to elucidate their biological mechanisms of action .

oxalis corniculata is a common medicinal plant widely used against numerous infectious diseases . the agrochemical potential of methanolic extract , n - hexane , chloroform , ethyl acetate , and n - butanol fractions were assessed to measure the antibacterial , antifungal , and insecticidal activities of the plant . the crude , chloroform , and n - butanol soluble fractions showed excellent activities against escherichia coli , shigella dysenteriae , salmonella typhi , and bacillus subtilis but have no activity against staphylococcus aureus . similarly the crude , n - hexane , and chloroform fractions were also found to have significant activity against fungal strains including fusarium solani , aspergillus flexneri , and aspergillus flavus and have no activity against aspergillus niger . chemical pesticides have shown very good results at the beginning , but with the passage of time the need was realized to use the natural plant sources for the safe control of insects . the current study will provide minor contribution towards it . high mortality rate was recorded for the crude extract and chloroform fraction against tribolium castaneum . the two isolated compounds 5-hydroxy-6,7,8,4-tetramethoxyflavone ( 1 ) and 5,7,4-trihydroxy-6,8-dimethoxyflavone ( 2 ) were evaluated for antibacterial , antifungal , and insecticidal activities . the results showed that compound 2 was more active than compound 1 against the tested bacterial strains and insects .

polycystic ovary syndrome ( pcos ) is a heterogeneous and complex endocrine disorder associated with hyperandrogenism and insulin resistance signs and symptoms such as obesity , abnormal glucose tolerance test or type 2 diabetes , abnormal blood lipid profile , high blood pressure and cardiovascular disease ( 1 ) . this disorder is prevalent and affects 5 - 10% of women of reproductive age ( 2 ) and causes infertility in 75% of these women due to chronic anovulation ( 3 ) . many drugs were used as a treatment for pcos or control its consequences , including metformin ( 4 ) , simvastatin ( 5 ) , atorvastatin ( 6 ) , n - acetyl - cysteine ( nac ) ( 7 ) and flutamide ( 8) . in general , all of these drugs have positive effects in improving hyperandrogenic symptoms and regulation of menstrual cycles , but simvastatin and metformin have been more commonly used than others for treatment and research purposes . in one study , long - term treatment with simvastatin was more effective than metformin for control of hyperandrogenism sign and increased menstrual regulation in women with pco ( 9 ) . there are several published studies regarding the effectiveness of statins administration in women with pco ( 10 , 11 ) , but in comparison with metformin there is no published research about drug administration before or during icsi cycle . simvastatin a drug from statins group , inhibits hmg - coa reductase and reduces cholesterol production , increases liver ldl receptor sensitivity and hdl level , meanwhile decreases tg level in blood circulation ( 12 ) . moreover , statins prevent theca - interstitial cell proliferation in ovaries and therefore reduce total androgen production ( 13 ) . metformin as a biguanid drug , blocks glucose synthesis in liver and enhances peripheral sensitivity to insulin , which finally decreases androgen level in patients with pco and enhances the chance of pregnancy ( 14 ) . according to latest cochrane published study about metformin treatment before and during icsi cycle , live birth or pregnancy rate was not improved ( 15 ) ; the cochrane database announced that although simvastatin improved lipid profile and hyperandrogenism sign , it had no significant effect on pregnancy chance ( 16 ) , of course in natural cycle . we decided to compare the efficacy of both drugs as a pretreatment regiment before icsi cycle in patients with pco . in this prospective , double blind , randomized clinical trial , 40 women with pcos and a history of infertility referring for first icsi cycle to imam khomeini hospital affiliated with ahvaz jundishapur university of medical sciences ( ajums ) were selected based on closed enveloped randomization method from december 2010 to november 2012 to receive simvastatin ( group a ) or metformin ( group b ) . according to the variance of previous studies , the sample size was calculated as 20 patients for each group . in accordance with the guidelines of the declaration of helsinki , after approval of university ethical committee ( eth-3251 ) , the study was submitted on iranian health ministry website for clinical trials ( www.irrct.ir ) . pcos considered as presence of two of the following criteria including menstrual irregularities ( oligomenorrhea or amenorrhea ) , clinical and laboratory findings of hyperandrogenism and polycystic ovaries on ultrasound evaluation . besides , inclusion criteria were aged 20 - 35 years , a history of infertility for at least two years ( either primary or secondary ) , normal tsh and prolactin and candidates for the first cycle of icsi . patients with other causes of infertility , including tubal factors , endometriosis and male factor infertility were excluded . patients who used metformin , lipid control drugs , clomiphene , letrozole or doing iui ( intrauterine insemination ) in the past 3-months before study or having medical problems such as kidney or liver diseases , diabetes or a history of elevated blood lipids were excluded . body mass index ( bmi ) and the score of hirsutism were assessed according to the ferriman gallwey scoring system ( figure 1 ) . in this system , hair growth in a male pattern on a woman shown in four different degrees of severity in 11 different body parts , namely the upper lip , chin , chest , upper back , lower back , upper abdomen , lower abdomen , arm , forearm , thigh and lower leg ( 17 ) . on the third day of menstruation , all patients were evaluated for total testosterone , lh , fsh , tg , total cholesterol , ldl , hdl , fbs , gtt with 75 grams glucose ( blood sugar measured one and two hours after drinking it ) , prolactin and tsh . after getting the first blood sample for biochemical evaluation , in group a , patients received simvastatin 20 mg daily ( osvah pharmaceutical company , iran ) plus low dose oral contraceptive pill ( ocp ) daily for eight weeks . in group b , patients received metformin 500 mg tds ( osvah pharmaceutical company , iran ) plus low dose ocp daily for eight weeks . then , all patients were again evaluated for previous biochemical parameters ( except prolactin and tsh ) and bmi measurement and hirsutism scoring . patients were enrolled in the icsi protocol according to the long protocol ; from the day of twenty - one of the second cycle , subcutaneous superfact ( 0.5 mg daily , triptrolein , hoechst , frankfort , germany ) injection was started . after menstruation on the third day of cycle , both drugs ( simvastatin and metformin ) were discontinued and after vaginal sonography control and reducing superfact to 0.25 mg daily , induction of ovulation with folliotropin alfa ( gonal - f , merck , serono . ovarian response was examined by transvaginal sonography six days later and gonal - f dosage adjusted according to the patient response ; when at least three follicles with a size of 18 mm detected , human chorionic gonadotropin ( hcg ) 10000 units ( profasi . switzerland ) was injected intramuscularly and ovarian puncture was performed 36 - 40 hours later . after ovarian puncture , the number of mii oocytes and after sperm injection , on the day 3 , the number of embryos of grade a was recorded . the incidence of ovarian hyperstimulation syndrome ( ohss ) was reported in the both groups . then , support of luteal phase was started with vaginal suppository of micronized progesterone 400 mg twice daily . the first ultrasound was performed five weeks after embryo transfer in cases of pregnancy positive test . cases of abortion , ectopic pregnancy ( ep ) , ongoing pregnancy ( passing 14 weeks of gestational age ) and negative pregnancy were detected . student s t - test for unpaired data and sample t - test for paired information were used . also chi - square and fisher s tests were used to assess frequency distribution and clinical outcome . regression and anova tests were used for comparison between the groups . for gtt result interpretation , p value < 0.05 was considered as significant and the power of study was 80% . 75% of patients in group a , were obese ( bmi > 30 kg / m ) and in group b , 65% . after eight weeks treatment in both groups , reduction of mean hirsutism score was significant , although it was more meaningful in simvastatin group ( table 2 ) ; this reduction in mean bmi level was not significant ( table 3 ) . biochemical parameters before the treatment in the both groups were not different ( table 4 ) . after eight weeks in group a receiving simvastatin , testosterone , fsh , lh , cholesterol ( chol ) and ldl significantly decreased ; meanwhile hdl level elevated . in group b , after metformin administration the level of fsh , testosterone , tg and chol reduced meaningfully ( table 5 ) . the mean values of three blood sugar measurements ( fbs/1 hour/2 hours ) before starting the treatment were not different between the two groups ( group a : 12208 1658.03 mg / dl vs. group b , 12302 1789.87 after the treatment , roc showed improvement area under curve ( auc ) in glucose tolerance test in the both groups ; although there were no significant differences between the two groups ( p value 0.11 ) ( figure 2 ) . a , before the treatment in metformin ; and c , simvastatin ; b , after the treatment in metformin ; and d , simvastatin . after ovarian puncture , the number of oocytes in phase2 meiosis ( m2 ) in simvastatin treated group was 1.35 1.6 , and in metformin treated group 2 3.87 ( p value 0.48 ) . on the third day after ovarian puncture , the number of grade a embryos in group a was 1.2 1.3 versus 1.1 1.4 in group b ( p value 0.79 ) , which was not significantly different . in the both groups the pregnancy rate in group a was six cases ( 30% ) ongoing and seven cases in group b ( 35% ) . to the best of our knowledge , this is the first published study comparing simvastatin and metformin as a pretreatment regiment for icsi cycle in pcos women and there is one study regarding the effectiveness of simvastatin before ivf ( 18 ) . women with pcos have enlarged ovaries with an increased number of small follicles with more theca cells , which are androgen - producing cells . it is also clear that theca cells of women with pcos produce higher amount of androgens compared with the theca cells of normal women . increased expression of genes involved in androgen production , such as cyp11a and cyp17 has been observed in these cells ( 9 ) . metformin - induced reduction in testosterone is not only because of decreasing size of the ovarian theca cells , but also due to the direct action of metformin . studies have shown that metformin inhibits the production of testosterone and androstenedione in the cultured theca cells . metformin also decreased expression of steroidogenic acute regulatory ( star ) protein and 17-hydroxylase/17 , 20-desmolase ( cyp17 ) ( 19 ) . studies have shown that statins reduce cell proliferation , increase apoptosis and inhibit producing testosterone in humans and rat theca cells ( 10 , 13 ) . the positive effects of simvastatin in reducing hirsutism and testosterone have been confirmed by other researchers ( 5 ) ; this reduction in testosterone level , but not the hirsutism score after metformin administration has been reported , but in our study bmi decreased after six months therapy ( 20 ) . in another study , after six months of treatment , simvastatin improved hyperandrogenism parameters like total testosterone , hirsutism score , total cholesterol , ldl and bmi better than metformin ( 9 ) . lipid profile analysis showed that simvastatin significantly reduced ldl and total cholesterol , and increased hdl . this effect reflects direct competitive prevention of the controlling step of cholesterol production by inhibiting 3-hydroxy3methylglutaryl coenzyme a reductase ( 21 ) . however , metformin significantly decreased triglyceride and ldl by its anti - lipolytic effects , reducing circulating free fatty acid concentrations and therefor the level of triglycerides ( 22 , 23 ) , although this reduction in ldl level in our study was not significant . in the present study , lh and fsh hormones were significantly lower in simvastatin group after treatment , but in the metformin group only fsh concentrations decreased . in women with pco , reduction in fsh level reflects decreased gnrh frequency secretion due to reduction of hypothalamic dopamine and opioid production and from negative feedback of chronically elevated estrone concentration ( increased peripheral aromatization of elevated androstenedione ) and decreased progesterone level ( chronic anovulation ) ( 24 ) . in contrast to fsh , abnormal lh production is due to increased pulse amplitude and frequency secondary to altered pulsatile gnrh secretion ; this elevated lh led to ovarian hyperandrogenism ( 25 ) . metformin directly affected gonadotropin - secreting cells and reduced lh production and elevated fsh level by regulating fsh gene expression ( 26 ) . simvastatin could reduce lh level , but had no effect on fsh ( 11 ) ; this impressive effect for normalized gonadotropins level improved in other study ( 27 ) . simvastatin reduced lh level by decreasing ovarian testosterone production secondary to inhibition of theca - interstitial proliferation . in our study , reduction in lh level was seen in the both groups , although it was more significant in group a ; we could not find any explanation about reduced level of fsh in the both groups . in conclusion , according to only published study about simvastatin administration before ivf cycle ( 18 ) and in agreement with cochrane review about co - administration of metformin and icsi cycle ( 15 ) , the outcome of icsi cycle does not progress significantly , but biochemical parameters , signs and symptom in women with pco improved . these drugs as a pretreatment protocol before icsi cycle could alter the results of cycle if used in more patients , or in longer or higher doses .

background : drugs administration as a pretreatment regiment before icsi cycle in pcos patients could enhance the success rate.objectives:the aim of this study was to compare the effectiveness of metformin with simvastatin in patients with polycystic ovary syndrome ( pcos ) candidates for intra - cytoplasmic sperm injection ( icsi ) before starting the cycle.patients and methods : in this prospective , double blind , randomized clinical trial the efficacy of these drugs was evaluated in 40 women with pco syndrome ( 20 patients in each group ; a : simvastatin and b : metformin ) candidates for icsi . in the both groups , metformin and simvastatin administrated for eight weeks before starting the icsi cycle . endocrine , metabolic and clinical parameters were measured before and after drug therapy ; also , the results of icsi cycle evaluated in the both groups.results:both drugs improved hirsutism score significantly , but simvastatin better than metformin ( group a , 24.5 3.6 p : 0.0001 vs group b , 22.9 5.9 p : 0.003 ) . the reduction in body mass index ( bmi ) was not significant in the groups . simvastatin reduced some biochemical parameters such as fsh , lh , testosterone , total cholesterol , ldl and increased hdl level significantly , whereas metformin decreased fsh , tg , testosterone and total cholesterol significantly . overall , respectively 35% and 30% of patients treated with metformin and simvastatin became pregnant . there was no significant difference between the effects of these two drugs on icsi cycle results like oocyte in meiosis2 ( m2 ) phase ( 1.35 1.6 vs. 2 3.87 , p value : 0.4 ) and the number of grade a , embryo ( 1.2 1.3 vs. 1.1 1.4 , p value : 0.7).conclusions : simvastatin effectively improved hyperandrogenism signs and symptoms in patients with pco , but this effect as a pretreatment regiment was not more expressive than metformin in icsi cycle outcome .

the data was collected from april to may , 2014 at orthopedic in - patient department of a tertiary care teaching hospital , guwahati , assam . the institutional ethical committee permission was taken to conduct this study ( iec approval no . patients who received analgesics in orthopedics ward during study period irrespective of age , sex , diagnosis , and treatment . prescriptions of patients attending orthopedic opd and those who were admitted in other in - patient department . the patients who were absconded or discharged against medical advice were excluded from the study . demographic data comprised age , sex , and address were collected from bed - head ticket information file . the clinical data included diagnosis , name of analgesics , route of administration , duration of treatment with analgesics , any adverse event with analgesics ( if any ) , co - prescribed drugs , and duration of hospital stay were recorded . analgesics prescribed by physicians of orthopedic department of this hospital were considered in this study . the generic names of the drugs were obtained from the indian drug review , 2014 . the study was also assessed to check whether the drugs prescribed were enlisted under nlem , india 2011 or not . the cost of drugs per patient was calculated as per hospital formulary and indian drug review , 2014 . the cost of treatment consisted free drug supplies from this government tertiary care hospital as well as the drugs purchased by the patients from outside this hospital . the common analgesics were classified according to the anatomical therapeutic chemical ( atc ) classification based on their chemical , pharmacological , and therapeutic properties . ddd/100 bed - days were calculated using the following equation . during the time of discharge , analgesic prescriptions pattern , and percentage and averages of the variable were also calculated to compare the data with other findings . patients who received analgesics in orthopedics ward during study period irrespective of age , sex , diagnosis , and treatment . prescriptions of patients attending orthopedic opd and those who were admitted in other in - patient department . the patients who were absconded or discharged against medical advice were excluded from the study . a total 200 patients were enrolled during the study . demographic data comprised age , sex , and address were collected from bed - head ticket information file . the clinical data included diagnosis , name of analgesics , route of administration , duration of treatment with analgesics , any adverse event with analgesics ( if any ) , co - prescribed drugs , and duration of hospital stay were recorded . analgesics prescribed by physicians of orthopedic department of this hospital were considered in this study . the generic names of the drugs were obtained from the indian drug review , 2014 . the study was also assessed to check whether the drugs prescribed were enlisted under nlem , india 2011 or not . the cost of drugs per patient was calculated as per hospital formulary and indian drug review , 2014 . the cost of treatment consisted free drug supplies from this government tertiary care hospital as well as the drugs purchased by the patients from outside this hospital . the common analgesics were classified according to the anatomical therapeutic chemical ( atc ) classification based on their chemical , pharmacological , and therapeutic properties . ddd/100 bed - days were calculated using the following equation . during the time of discharge , analgesic prescriptions pattern , and nonnormal continuous data were presented by median ( interquartile range difference ( iqrd ) . percentage and averages of the variable a maximum number of analgesic prescriptions were found in the age group of 2130 years [ table 1 ] . self - fall fractures ( 72% ) were the most common condition followed by road traffic accident ( 21% ) , infective arthritis ( 4% ) , and congenital condition ( 3% ) [ table 1 ] . prescribing pattern of analgesics in orthopaedic in - patient department of tertiary care hospital : patients characteristics and drug use indicators as per the world health organization ( who ) drug use indicators , out of total analgesics prescribed , 183 ( 62.67% ) were from the nlem , india 2011 and 167 ( 57.19% ) analgesics were prescribed by generic name . the median number of drugs per prescription ( iqrd ) was 5 ( 2 ) [ table 1 ] . as per the core indicators of drug utilization , in this study 111 ( 55.50% ) of patients have received single analgesic ; however , 87 ( 43.5% ) numbers of patients have received two analgesics at a time . the median duration of analgesic therapy was 4 ( iqrd 3 ) days and 40% of analgesic were given for 35 days of duration for the treatment . hospital and patient shared 1647.91 inr ( 76.59% ) and 503.81 inr ( 23.41% ) of the total drugs cost , respectively . in this study , out of 292 most of the analgesics were peripherally acting analgesics ( nsaids ) 157 ( 53.77% ) , combination analgesics ( nonopioid and nsaids ) were 132 ( 45.20% ) , and centrally acting synthetic opioid analgesic i.e. , tramadol 3 ( 1.03% ) [ table 2 ] . diclofenac was the most commonly prescribed analgesic 127 ( 43.49% ) followed by aceclofenac and paracetamol 123 ( 42.12% ) , ibuprofen 24 ( 8.22% ) , ibuprofen and paracetamol 9 ( 3.08% ) , tramadol 3 ( 1.03% ) , aceclofenac 3 ( 1.03% ) , ketorolac 2 ( 0.69% ) , and piroxicam 1 ( 0.34% ) [ table 2 ] . we have observed 223 ( 22.36% ) number of analgesics being coprescribed with gastroprotectives mainly ppis ( proton pump inhibitors ) 164 ( 73.54% ) and h2 blockers 59 ( 26.46% ) [ table 3 ] . total utilization of analgesic during the study in terms of ddd/100 bed - days was 104.01 . utilization pattern of various analgesic and ddd/100 bed - days is shown in table 2 . utilization pattern of analgesics in orthopedic in patients and defined daily dose/100 bed - days at a tertiary care hospital coprescribed drugs with analgesics for patient during hospitalization at a tertiary care hospital fractures are among the most common orthopedic problems , and about 6.8 million people seek medical care attention for fracture in india and most common indication for prescribing diclofenac was fractures . this study reveals that most common indication for hospitalization was fracture and diclofenac was the most commonly prescribed drug . prescribing drugs by generic name , promote the rational use of drugs with regard to safety , efficacy , and cost by permitting the identification of the products by its scientific names . increasing generic prescribing would rationalize the use and reduce the cost of drugs . in this study , 167 ( 57.19% ) globally , nsaids are most commonly prescribed drugs for the management of pain and inflammation and the same has been reflected in this study . despite the wide clinical use of nsaids , essential medicines list has been shown to improve the quality and cost - effectiveness of health - care delivery when combined with proper procurement policies and good prescribing practices . essential drugs list or formulary issued to measure the degree to which practices conform to a national drug policy , as indicated by prescribing from the national essential drugs list or formulary for the type of facility surveyed . in this study , 62.67% analgesics were prescribed from the nlem , india 2011 . the findings from sen and bathini prescribed analgesics from the nlem were 81.94% , salman et al . were 62.20% from nlem , india 2003 and out of the 37 study reports , in 8 studies , 60% of the drugs were prescribed from an essential medicines list . the average number of drugs per prescription is an important parameter while doing a prescription audit . multiple drug prescribing results polypharmacy , this may cause to irrational prescribing and induce adverse effect . in this study , the similar findings were reported in several countries ( indonesia , niger , nigeria , india , ghana , and pakistan ) in which three or more drug were prescribed per prescription . these differences in mean cost of total drugs in this study in comparison with other studies may be due to variation in type and severity of the admitted patient , indications for the admission , different prescribing pattern , or inflation in the price of medications . although the average cost of treatment per patient was high , patient shared only 23.81% of total treatment . coprescribed drugs , i.e. proton pump inhibitors were commonly used for maximum . analyzing the results of these indicators information is obtained about the quality of prescribing the drug to quantity in different circumstances of use ( time , duration , age of the patient , route of administration , etc . ) . the calculation of ddd/100 bed - days for drug utilization is used as a tool to measurement the pattern of consumption of analgesics . in this study , the total drug utilization of analgesics at in - patients department during the study in terms of ddd/100 bed - days was 104.01 . the who has recommended the atc classification / ddd system as a tool for presenting drug utilization research to improve the quality of drug use . however , the recommended dose and the trends in drug utilization with indicator for measuring drug consumption are shown in table 2 . the percentage of analgesics prescribed from essential medicines list and the use of the generic name were found to be satisfactory , but the average number of drug per prescription was high .

objectives : the aim of this study is to evaluate the prescribing pattern of analgesics and analyze the rational use of analgesic in orthopedic in - patient department of tertiary care teaching hospital , guwahati , assam.subjects and methods : an observational and cross - sectional study was carried out for 1 month from april to may 2014 . collected data included age , sex , diagnosis and line of management during the study . the generic name and the average cost of treatment per patient were evaluated using indian drug review , 2014 . the prescribed drugs were assessed with respective national model list of essential medicines ( nlem ) , 2011 and the rationality of prescriptions was determined using the world health organization indicators of drug utilization . the patients details were recorded in a predeigned data collection form and results were analyzed by descriptive statistics.results:out of 200 patients , 123 were male and 77 were female . the average number of analgesic per prescription was 1.46 . in this study , 55.5% of patients had received single analgesic . diclofenac was the most commonly prescribed analgesic ( 43.49% ) . during hospitalization , majority of the patients have received parenteral preparation . gastroprotective agents and antimicrobials were frequently prescribed along with analgesics . out of 292 analgesics prescribed , 183 ( 62.67% ) were from the nlem , india . furthermore , 176 ( 57.19% ) analgesics were prescribed by generic name . the average cost of treatment per patient was 2151.72 inr . utilization of analgesic in terms of defined daily dose/100 bed - days was 104.01.conclusion:the percentages of analgesics prescribing from nlem and the use of analgesic by generic name were found satisfactory . regular educational interventions to improve prescribing practices among physicians at different levels may further promote rational prescribing .

ankylosing spondylitis ( as ) is characterized by progressive ossification of the spinal column with resultant stiffness . as does not typically result in dysphagia as the syndesmophytes are marginal . dysphagia in the elderly is more commonly associated with diffuse idiopathic skeletal hyperostosis ( dish ) . we report the anaesthetic management of a patient with the unusual combination of a rigidly fused spine and focal exuberant anterior osteophytosis . his past medical history was significant for as with previous anaesthetics notable for failed direct laryngoscopy and considerably difficulty with fibreoptic orotracheal intubation . the patient 's presenting dysphagia was first evaluated by the ear nose and throat ( ent ) surgeon whose awake flexible fiberoptic nasoendoscopy revealed a significant bulging of the posterior pharyngeal wall into the airway at the level of the epiglottis . a plain x - ray and computed tomography scan of the spine demonstrated significant anterior cervical osteophytes from c3 to c5 with the largest osteophyte of size equivalent to the diameter of the vertebral body at level c3 and c4 [ figure 1a and b ] . patient was referred to the spine surgery unit and he was scheduled to undergo removal of the exuberant anterior cervical osteophytes for symptomatic relief of his dysphagia . the surgeons requested that an elective pre - operative tracheostomy be avoided , if possible as this would interfere with the planned surgical approach through an incision through the anterior triangle of the neck . in the pre - anaesthetic clinic , after careful evaluation and discussion with the patient , an awake fibreoptic intubation was planned . ( a ) pre - operative plain radiograph of the neck showing anterior cervical osteophytes at the level of the epiglottis , ( b ) pre - operative computerized tomogram showing the anterior cervical osteophyte at the level of the epiglottis with size equal to that of vertebral body after an appropriate period of fasting , patient was brought to the or with both the ent and spine surgery teams in attendance . after standard monitoring was instituted , in the semi - sitting position ; airway topicalization with 2% lidocaine spray was attempted . a right superior laryngeal nerve block and trans - tracheal injection were performed with 2 ml each of 2% lidocaine . patient was placed supine , but as his head did not touch the mattress ( phantom pillow sign ) ; a stack of flannel in the configuration of a ramp was placed under his head , neck , and torso . a modified nasal trumpet ( mnt ) was prepared by inserting a 15 mm universal connector from a 7.0 mm i d tracheal tube into the flanged end of a 30fr nasal airway [ simulated in figure 2 ] . oxygen ( 3 l / min ) was delivered through this airway using the anaesthetic breathing circuit and capnography confirmed a patent airway and adequate spontaneous breathing . into the other nares , the split nasopharyngeal airway ( snpa ) was inserted . the snpa is a 32fr nasal airway , which had previously been cut spirally [ simulated in figure 2 ] . a standard adult fibreoptic bronchoscope ( 5.5 mm ) was loaded with a size 7.0 mm i d reinforced tracheal tube ( lma fastrach tube , vitaid , toronto , canada ) . the bronchoscope was introduced through the snpa and the large posterior pharyngeal wall bulge was evident . advancing and rotating the snpa caudad and posterior to the bony bulge was required to facilitate visualisation of the vocal cords , caudad and posterior to the bony bulge . the vocal cords were sprayed with 2cc of 2% lidocaine and the bronchoscope passed into the trachea without resistance . patient tolerated the procedure well and after confirmation of the appropriate position of the tracheal tube , anaesthesia was induced intravenously and then maintained with sevoflurane in an air - oxygen mixture using controlled ventilation . simulation of the fibreoptic nasal intubation technique through split nasopharyngeal airway with a modified nasal trumpet in situ the surgeons performed a left - sided anterior neck approach to the cervical spine and then proceeded to dissect the pharynx off of the osteophytes . after removal of the bony elements , the pharynx was once again evaluated to make sure there was no soft - tissue pathology . all monitored parameters remained stable . at the end of surgery , the need for a definitive postoperative airway was discussed . the possibility of pharyngeal oedema and anticipated difficult airway due to the as were considered and though leaving the trachea intubated was considered , it was decided that the patient would be best served by an elective tracheostomy . after the oxygen delivery was reduced to fio2 of 0.3 , a tracheostomy was performed and the tracheal tube was removed . he woke up breathing comfortably and was monitored in the post - anaesthetic care unit overnight . the tracheostomy was decannulated on the 3 post - operative day and he was discharged on the 5 post - operative day . when followed - up 6 weeks later , he continued to be doing well - his dysphagia partially resolved and he was able to swallow semi - solid food . as is a chronic , progressive autoimmune exonerative spondyloarthopathy that affects primarily the posterior articulations of the spine and adjacent tissues . as the cervical spine involvement progresses , the decreasing neck extension can progress to a dish is a non - inflammatory enthesopathy causing ossification of the anterior and lateral elements of the spine . interestingly , it is reported as a common cause of dysphagia and aspiration in elderly patients with good results from surgical excision of the osteophytosis . though there have been previous reports of patients with co - existent dish and as the etiology of this patient 's focal osteophytosis is unclear although may be post - traumatic or the result of incomplete fusion of the motion segment [ figure 1a ] . nevertheless , the dish - like presentation of this patient was taken into consideration in our airway management plan . failure of videolaryngoscopy has been reported in dish , attributed to the disparity between size and angulation of the blade and the limited oro - pharyngeal space due to the cervical osteophytes . our planned modified awake fibreoptic intubation and preference for the nasal route was based on these abnormalities and the radiological images . nasotracheal intubation is useful in some anticipated difficult airways and shown to require ( and or produce ) less cervical spine movement . nasal fibreoptic intubation has previously been recommended in patients with lesions of the cervical spine . we believe that if only minimal movement of the neck is allowed ( or possible ) , the nasopharyngeal axis is better aligned with the laryngeal and tracheal axes . in our patient , this is evident from the radiological images [ figure 1a ] . nasal bleeding is a concern with fibreoptic nasal intubation and it may either prevent fibreoptic view or contribute to airway obstruction . we preferred to use the tracheal tube that is available with the lma fastrach because not only is this tube reinforced , its silicone tip is relatively soft and tends to hug the bronchoscope better . we also used two nasopharyngeal airways - one to ensure delivery of adequate oxygen ( mnt ) and the other ( snpa ) to facilitate the fibreoptic intubation [ figure 2 ] . the mnt allows for connection to the anaesthetic breathing circuit and thereby facilitating continuous capnographic monitoring of airway patency and breathing . in addition , as required uninterrupted delivery of positive pressure ventilation and oro - pharyngeal suctioning can be performed while the fibreoptic intubation is being performed . we suggest that the split be performed spirally as cutting it straight through tends to make the spna collapse in the nasopharynx . if the spna is adequately prepared ( warm , soft , and lubricated with local anesthetic gel ) , it allows for nasal fiberoptic endoscopy to be performed with little distress to the awake patient . most importantly , since the snpa can be peeled off the bronchoscope , nasotracheal intubation can be facilitated [ figure 2 ] . when compared to direct nasal endoscopy , the snpa may require less anaesthetic depth and affords for the fibreoptic procedure to repeated atraumatically if required . in our patient , the snpa additionally allowed us to navigate around the hard posterior pharyngeal bulge . we believe the use of these two nasal airways improved the safety and success of the difficult airway in the current patient . the role of tracheostomies in cervical spine surgery is controversial . while they may be necessary in some patients , they may interfere with the surgical access to the spine and increase implant or surgical site infections . airway management for the shared airway is often complicated by pre - operative abnormalities , intraoperative considerations and post - operative complications . this patient 's case report serves to provide additional information on various aspects of airway management for cervical spine surgery . the use of the modified nasal airways and an awake fibreoptic nasal intubation was useful in our patient and should be considered in other similar situations . in such patients with bony hard anterior cervical osteophytes and a stiff spine from as , literally ; safe airway management may lie between a rock and a hard place .

we report the perioperative course of a patient with long standing ankylosing spondylitis with severe dysphagia due to large anterior cervical syndesmophytes at the level of the epiglottis . he was scheduled to undergo anterior cervical decompression and the surgical approach possibly precluded an elective pre - operative tracheostomy . we performed a modified awake fibreoptic nasal intubation through a split nasopharyngeal airway while adequate oxygenation was ensured through a modified nasal trumpet inserted in the other nares . we discuss the role of nasal intubations and the use of both the modified nasopharyngeal airways we used to facilitate tracheal intubation . this modified nasal fibreoptic intubation technique could find the application in other patients with cervical spine abnormalities and in other anticipated difficult airways .

the case we present here is about a 22-year - old female patient referred to the department of conservative dentistry and endodontics with the chief complaint of pain in the left lower back tooth for the past 2 days . her medical history was noncontributory and she gave a dental history of root canal treatment was done in that tooth before 2 months in a dental clinic . on clinical examination , it was found access opening was done in a grossly decayed left mandibular second molar . the treatment was continued by complete caries excauation and canal exploration after rubber dam isolation . on microscopic exploration of the floor of the pulp chamber a canal re is an extra third root in mandibular molars present on the lingual side , which is shorter in length than other two roots . however , here , it is seen on buccal side called as rp . on careful exploration on mesial root , presence of three canals after working length estimation done [ figure 1 ] , all the canals were enlarged until 20 size k file and biomechanical preparation was completed by protaper rotary systems . all three mesial canals were enlarged until f1 , distal canal until f3 and the extra third root on buccal side until f2 with copious irrigation of saline simultaneously . then the master cones checkup were done as shown in figure 2 . then the final irrigation was done with 17% ethylenediaminetetraacetic acid , 3% sodium hypochlorite and by saline . canals were dried with paper points and obturated with gutta - percha cones of respective sizes with kerr sealer . figure 4 shows the post obturation magnified view of floor of the pulp chamber showing the five canals with rp in middle . working length determination post obturation radiograph microscopic image of floor of pulp chamber showing type b rp the mandibular molars usually have two roots with two canals in mesial roots and one canal in distal root . it is more common that mandibular molars having four canals with two in mesial and distal root viz . the first molar . however , recent studies shows there are more chance for a 3 canal in mesial and distal root as middle mesial and middle distal , respectively . this presence in second molar is very rare but , recently few studies of ryan et al . and jain reported with cases of five or six canals in mandibular first molars only . the isthmus connecting the mesiobuccal and lingual or distobuccal and lingual is debrided and left uninstrumented in most of the cases . however , on careful exploration of this isthmus a third canal with a separate path of exit can be seen in many of the cases as reported by deepalakshmi et al . in their four cases . here , in this case of 37 with three mesial canals , all three files and gp points went until full working length independently without any fusion at the apex to exit as one . it seems that in all three canals , there will be isthmus communicating them in between laterally as it travel , these lateral connections were debrided completely with 3% sodium hypochlorite and sealed by the root canal sealer . re is an extra third root in mandibular molar , which is shorter than the mesial and distal roots ; seen in distolingual corner like a distolingual canal in the floor of the chamber . the rp occurrence rate is about 0% , 2% , and 5% in mandibular first , second and third molars respectively . carlsen and alexandersen described two different types of rp : type a : rp in which the cervical part is located on the mesial root complex ; type b : rp in which the cervical part is located centrally , between the mesial and distal root complexes , an additional cusp was present on the buccal side . the complex root canal anatomy stresses the operator to observe the canal morphology with care without underestimating it and missing the extra root and roots canals , which can occur in any cases as a rare finding . thus , the success of endodontics lies in the careful exploration of the canals and debridement of it .

mandibular first molar commonly has two roots , the mesial and the distal root . surprisingly in some mandibular first molar has an unusual extra third root in between mesial and distal root . this extra root is the most commonly seen in lingual side and is called as radix entomolaris . if this extra root is seen on the buccal side , it is termed as radix paramolaris ( rp ) , which is a very rare phenomenon . recently , various case report studies has shown the presence of third canal in the mesial and distal roots of mandibular molars . they are named as middle mesial and middle distal canal , respectively . here , we present a case report of mandibular second molar showing three canals in the mesial root and a rp .

the etiology of aga involves several factors , including genetics , androgens , age and nutrition . some evidence suggests that the digit - length ratio of the index and ring finger ( 2d:4d ) is an indicator of prenatal exposure to sex hormones , with a lower 2d:4d being suggestive of a greater androgen exposure . digit - length ratios have been utilized to determine the effects of prenatal androgen exposure a variety of phenotypic expressions . however , there is a paucity of studies that systemically review the possible positive predictive value of 2d:4d in the development of aga . the study was initiated after approval by the research and ethics committee of jahrom university of medical sciences , approval i d : jums.rec.1393.017 . we performed a single - site , descriptive - analytical study between june 2013 and february 2014 among a racially homogeneous population that they were selected by stratified and randomized sampling . participants did not have a significant history of other types of alopecia ( e.g. iatrogenic scarring alopecia , alopecia areata , etc . ) . a trained team performed digit - length measurements of both hands with vernier calipers and subsequently calculated the 2d:4d . a single trained technician graded baldness using the hamilton - norwood classification scale ; for simplicity these grades were further divided into four stages : no baldness ( i ) , mild ( ii , iii ) , moderate ( iv , v ) and severe baldness ( vi , vii ) . a pearson linear correlation was performed to assess relationships between 2d:4d and age ; a spearman linear correlation to assess relationships between 2d:4d and aga severity , and rocs mode was used to measure the validity of 2d:4d as a predictive test for aga . a total of 1200 men between 20 to 60 years of age with a mean age of 33.2 ( sd : 0.28 ) , enrolled in the study . a total of 53.4% of the participants had normal hair distribution ( aged 29.958.4 years ) , 26.16% had mild hair loss ( aged 34.9710.11 years ) , 15.19% had moderate ( aged 40.359.43 years ) and 4.32% had severe hair loss ( aged 42.289.92 years ) . the mean ratio of the right 2d:4d was 0.992 ( sd : 0.0024 ) , while the left was 0.982 ( sd : 0.0017 ) . no significant differences were identified between left and right hand 2d:4d per subject ( table 1 ) . no significant association was determined between right 2d:4d and aga severity within our entire population ( p=0.384 , r=0.025 ) , also there was no significant association between left 2d:4d and aga severity ( p=0.495 , r=0.028 ) , however a correlation coefficient was identified in subjects above the age of 40 . the receiver operating characteristic ( roc ) analysis of subjects age 40 and above demonstrated the area under curve ( auc ) as 0.502 ( 95%ci 0.391 to 0.613 ) and 0.480 ( 95% ci 0.371 to 0.590 ) for right and left 2d:4d , respectively , as a predictive test for aga ( figure 1 ) . herein , is the largest study to date aimed to explore the utility of a phenotypic expression of in utero androgen exposure in predicting the development of aga . although there was no significant association between right 2d:4d and aga ( p=0.384 , r=0.025 ) , there was a correlation coefficient identified in subjects above the age of 40 . with increasing of age the aga severity increases especially in participants above the age of 40 . in clinical practice , most patients generally express aga by age 40 . therefore , we attempted to evaluate the utility of 2d:4d as a predictive test for aga . based on the roc curve analysis , 2d:4d does not predict the development of aga . further , our findings suggest that increased in utero exposure to androgens does not predispose men to develop aga .

the etiology of androgenic alopecia ( aga ) involves several factors , including genetics , androgens , age and nutrition . digit - length ratio of the index and ring finger ( 2d:4d ) is an indicator of prenatal exposure to sex hormones . there is a paucity of studies that systemically review the possible positive predictive value of 2d:4d in the development of aga . we performed a single - site , descriptive - analytical study among a racially homogeneous population . our results revealed that no significant association was determined between right 2d:4d and aga severity within our entire population ( p=0.384 , r=0.025 ) , however a positive correlation coefficient was identified in subjects above the age of 40 . based on the receiver operating characteristic curve analysis , 2d:4d does not predict the development of aga . aga is truly a multifactorial disease . further , our findings suggest that increased in utero exposure to androgens as a fetus does not predispose men to develop aga .

a previously well 59-year - old lady presented to her gastroenterologist with per rectal bleeding . apart from intermittent inhaled salbutamol for asthma a staging ct of chest / abdomen / pelvis revealed no obvious distal metastatic disease . both lymphatic and venous invasion were noted ; 17 of 18 regional lymph nodes including the apical gland contained metastatic tumour . she received adjuvant folfox-6 ( fluorouracil , oxaliplatin , bolus fluorouracil , and leucovorin ) for six months . repeat ct scan at end of chemotherapy ( january 2007 ) demonstrated two 5 mm lesions in the left lower lobe and right middle lobe of the lung . while metastatic disease could not be ruled out , the lesions were thought to be granulomatous in nature . two low attenuation areas were identified in the liver posteromedially , measuring 8 mm and 15 mm in diameter . a para - aortic lymph node measured 6 mm . repeated 4 months later , a new lobulated 5 mm nodule was noted in periphery of right upper lobe along with more extensive para - aortic and left common iliac lymphadenopathy , suspicious of recurrent disease . pet scanning demonstrated fdg avid disease involving lymph node groups both above and below the diaphragm , and in particular the left para - aortic chain . ct confirmed extensive left para - aortic lymphadenopathy with more focal nodal masses posterior to left renal vein and at common iliac bifurcation . a needle biopsy of the para - aortic lymph node confirmed adenocarcinoma consistent with prior colonic primary . she received a further 6-month course of folfox-6 from 3/3/2008 to 6/8/2008 ; again achieving a good partial response with resolution of the adenopathy and stable disease in the other measurable lesions . in november 2008 the oedema progressed and spread to the thigh , with left iliac fossa tenderness felt at the same time . ct showed no evidence of recurrence at surgical site , as well as decreased size of both right middle lobe lung lesion and left external iliac lymph nodes . the malignant cells were positive for ck20 and negative for ck7 , supporting diagnosis of metastatic colonic carcinoma . p16 was negative and cea / mucin stains were difficult to interpret due to degenerative changes . . per vaginal examination showed the uterus to have a firm and nodular consistency . along with the pv bleeding , the patient reported right upper back pain in a radicular pattern from the lower cervical spine to the right proximal humerus . ct on same day showed a destructive lesion in c7 vertebral body on right side with pathological fracturing . whole body bone scan with spect 19/2/10 showed intense abnormality in body c7 consistent with a metastatic lesion . mri of the spine 19/2/10 showed pathological superior endplate fracture associated with metastatic deposit in the c7 vertebral body . marked right - sided c8/t1 foraminal stenosis was noted with possible right c7 radicular impingement . the patient commenced palliative radiotherapy to the cervical spine in 10 fractions of 30 gy . a dermatitic like eruption on left upper / inner thigh and buttock was noted in april 2010 , which did not respond to treatment with topical steroids ( see figures 2 and 3 ) . she was reviewed by a dermatologist and punch biopsy of left upper thigh was carried out on 28/4/10 . this showed multiple micronodules pleomorphic cells in superficial and mid dermis , showing focal ductular differentiation . she had 3 cycles of folfox , however , this was poorly tolerated due to anaphylactic reactions . colorectal cancer is the second most prevalent malignancy in australia ( excluding nonmelanocytic skin cancers ) . the most common metastatic sites are the regional lymph nodes , liver , lungs , and peritoneum . these include local invasion causing malignant fistula formation into adjacent organs , such as bladder or small bowel . fever of unknown origin , intra - abdominal , retroperitoneal , or abdominal wall abscesses can often be the first manifestation . these presentations are very rare individually , however , there has been no previous case report of a patient with both endometrial and cutaneous features . brand et al . reported a series of 6 patients presenting with per vaginal bleeding in the setting of recurrent colon cancer . only one of the patients in that series received adjuvant chemotherapy prior to per vaginal bleeding . despite aggressive chemo - radiation or surgical management , all patients had recurrence of colonic carcinoma . hu et al . found 124 cutaneous metastases from a series of 12.146 patients with internal malignancies ( 1% ) . 16 of these cases originated from colorectal cancer , equating to a rate of cutaneous metastasis of 0.81% . other authors have found rates of cutaneous metastasis between 2.3 and 6% [ 68 ] . skin metastases from the breast usually occur on the chest , the lung to the chest and upper extremities , and the gastrointestinal tract to the abdomen . these metastases usually manifest as a rapidly growing , mobile nodule . on immunohistochemical staining , ck20 positivity often correlates with colorectal tumours . this case highlights the importance of paying close attention to symptoms and signs in patients with a past history of internal malignancy . it is important to maintain a high index of suspicion to clinical features that may represent a metastatic process . furthermore , tissue diagnosis to confirm the aetiology of a symptom can prove very useful , as shown in this case .

this case highlights two very rare complications of metastatic colorectal carcinoma . it describes a 59 year old female with both cutaneous and endometrial metastases from colorectal carcinoma . while both of these presentations are very unusual , they highlight the need to be vigilant about the detection of metastatic complications during follow up .

we conducted real - time pcr analyses targeting the msp2 gene on genomic ( g ) dna of 12,606 i. scapularis ticks collected across canada ( technical appendix 1 ) . 169 ( 1.3% ) ticks were pcr - positive ( table 1 ) . there were significant differences ( 5 = 129.7 , p<0.001 ) in the proportions of ticks infected with a. phagocytophilum among geographic regions ; with a greater proportion of pcr - positive ticks in manitoba than in ontario , quebec , and the atlantic provinces . * data from these provinces were not included in the statistical analyses because sample sizes ( 20072010 ) were < 100 ticks . we developed pcr - based assays to distinguish the ap - ha strain from the ap - variant 1 strain of a. phagocytophilum based on dna sequence comparisons of the 16s rrna gene of each strain ( technical appendix 1 ) over a much larger region ( 875 bp ) than in previous studies ( 1,3 ) . in addition to the 2 nucleotide differences described previously ( 1,3 ) , a third difference ( at position 536 ) was detected in the aligned sequences ( technical appendix 2 ) . this nucleotide alteration in the dna sequence of the ap - variant 1 strain was associated with a restriction site for the endonuclease kpn2i ( t / ccgga ) that was absent in the sequence of the ap - ha strain . two pcr - rflp assays ( technical appendix 1 ) , developed at different laboratories , were designed on the basis of this sequence difference and tested on 22 amplicons derived from a. phagocytophilum infected ticks collected in minnesota , usa eighteen amplicons remained undigested ( i.e. , a single band of 920 bp ) , and 3 amplicons had 2 bands ( 360 and 550 bp ) , representing the expected patterns for the ap - ha strain and ap - variant 1 strain , respectively ( figure 1 ) . these results were confirmed on the basis of comparisons of the dna sequences of representative samples . the rflp pattern of 1 amplicon , derived from the gdna of a female tick from itasca state park , minnesota , consisted of 3 bands ( 360 , 550 and 920 bp ) ( technical appendix 2 ) , suggesting a mixture of the 2 strains . additional analyses of another 125 amplicons from a. phagocytophilum - infected ticks revealed that 79 ( 63% ) had rflp patterns consistent with the ap - variant 1 strain , and 46 ( 37% ) had rflp patterns of the ap - ha strain . the dna sequences of a subset of these samples ( n = 58 ) showed 100% agreement between rflp pattern and strain type of a. phagocytophilum ( i.e. , 24 of the ap - ha strain and 34 of the ap - variant 1 strain ) . restriction fragment length polymorphism patterns of 16s dna for 7 anaplasma phagocytophilum pcr positive ixodes scapularis ticks . all amplicons were produced by semi - nested pcr and digested with the restriction enzyme kpn2i . we also designed a custom taqman snp genotyping assay ( https://www.lifetechnologies.com/order/custom-genomic-products/tools/genotyping ) to differentiate the two a. phagocytophilum strains on the basis of a nucleotide difference at the 5 end of the 16s rrna gene sequence ( technical appendix 1 ) . the snp assay clearly discriminated between ticks infected with the ap - ha and/or ap - variant 1 strains ( figure 2 ) . of the 142 amplicons tested by this assay , 82 ( 58% ) contained the ap - variant 1 strain , 59 ( 42% ) contained the ap - ha strain , and 1 contained a mixture of both strains , which was in 100% agreement with the results of the rflp analyses and dna sequencing . the results of the snp analyses also revealed a significant difference ( 2 = 40.48 , p<0.001 ) in the proportions of i. scapularis ticks infected with the ap - ha strain among geographic regions ( table 2 ) . a smaller proportion of ticks from central provinces were infected with the ap - ha strain when compared with those from the prairie and atlantic provinces . allelic discrimination plot for the anaplasma single nucleotide polymorphism assay based on the 16s rna gene . blue circles represent samples that contain the ap - ha strain ; green circles represent samples that contain the ap - variant 1 strain . includes 13 ticks listed in table 1 and an additional 11 a. phagocytophilum infected ticks collected by drag sampling at 2 sites in ontario . a small proportion ( 1.3% ) of i. scapularis ticks collected in canada were infected with a. phagocytophilum . the prevalence of a. phagocytophilum-infected ticks differed among geographic regions , but the potential significance of this finding needs to be explored further . although knowledge of the prevalence of a. phagocytophilum infected i. scapularis ticks provides some information for determining the public health risks for hga , the prevalence of the ap - ha strain of a. phagocytophilum in blacklegged ticks should be considered for risk assessment , since the ap - ha strain , and not the ap - variant 1 strain , is most often associated with clinical cases of hga ( 4 ) . for the current study , 3 pcr - based assays were developed to distinguish the ap - ha strain from the ap - variant 1 strain . each of the 3 assays detected the presence of both strains in the gdna of a female tick . mixed infections of both strains in i. scapularis ticks have been reported ( 4 ) , but appear to be uncommon . results of these assays also were 100% concordant with the results of 2 rflp assays ( developed at different laboratories ) that were tested on the same gdna samples . similarly , there was total concordance in the identifications of the a. phagocytophilum strains present within 125 infected ticks collected across canada by using the seminested pcr - rflp assay and the taqman snp genotyping assay . the results of these analyses revealed significant differences in the proportion of blacklegged ticks infected with the ap - ha strain among geographic regions ( p<0.001 ) . the public health implications of these findings need to be examined in more detail , using the molecular assays developed in this study . the taqman snp genotyping assay is ideal for clinical and epidemiologic use where it may be essential to distinguish between the 2 strains of a. phagocytophilum in i. scapularis to assess the potential risk for human infection . however , in a clinical setting , it remains to be established how this assay would be incorporated into or supplement the current diagnostic approach for detecting a. phagocytophilum infections in humans . this test is less technically demanding and takes less time to perform than nested / seminested pcr - rflps and dna sequencing analyses . moreover , this method eliminates the need for postamplification manipulations and technical problems that are sometimes associated with rflp analyses of amplicons produced by nested pcr ( 14,15 ) . nonetheless , given the 100% concordance in the results of the different analytical methods , the pcr - rflp assays provide a reliable and cost - effective approach for distinguishing the ap - ha strain from the ap - variant 1 strain of a. phagocytophilum . the pcr - rflp assays will be particularly useful in research laboratories that lack the capacity to conduct real - time pcrs providing an independent and relatively inexpensive method to confirm the results of the snp assay . samples , dna extraction and prevalence of a. phagocytophilum in i. scapularis genetic test results for a. phagocytophilum

we developed pcr - based assays to distinguish a human pathogenic strain of anaplasma phagocytophilum , ap - ha , from ap - variant 1 , a strain not associated with human infection . the assays were validated on a. phagocytophilum - infected blacklegged ticks ( ixodes scapularis ) collected in canada . the relative prevalence of these 2 strains in i. scapularis ticks differed among geographic regions .

substantial evidence indicates that smoking bans reduce the adverse effects of exposure to tobacco smoke . as a result of this evidence , furthermore , partial smoking bans in indoor public places and workplaces are becoming a common occurrence . however , the issue of implementing complete smoking bans in all indoor public places has been debated in several countries . this disagreement depends on several factors including the societal view of smoking , compliance with existing smoke - free legislation , and other sociopolitical considerations . in 1995 , the republic of korea passed a law that banned smoking in public places . excluded from this ban were restaurants , recreational facilities , and entertainment venues , although some were subject to a partial smoking ban ( i.e. , facilities had to have both smoking and non - smoking areas that were physically separated ) . for example , one type of recreational facility , personal computer ( pc ) rooms , underwent a partial smoking ban . however , it is well - known that individuals within pc rooms will still be exposed to secondhand smoke ( shs ) , as there is air flow between the separated smoking and non - smoking areas . in korea , there are 15,817 pc rooms , all of which provide a facility for individuals to play computer games . survey data indicated that 45.2% of the population spends their leisure time in pc rooms . this percentage is higher than that at cinemas ( 33.5% ) , cafes ( 31.2% ) , or bars ( 26.2% ) . pc rooms became a top priority for the 2011 complete smoking ban placed on public indoor facilities . however , the implementation of this ban on pc rooms was delayed until 2013 . this ban was delayed because owners of pc rooms and smokers groups argued that the ban was not necessary , citing smokers rights and the lack of evidence supporting the effectiveness of a partial ban in protecting individuals from shs exposure . in this study , we investigated the levels of shs exposure in smoking and non - smoking areas of pc rooms prior to 2013 , to determine whether a complete smoking ban in pc rooms in necessary . thus , the results from this study will provide data that will impact the debate on a complete smoking ban in pc rooms . from june to september 2012 , particulate matter ( pm2.5 ) and air nicotine concentrations ( anc ) were measured in the smoking and non - smoking areas of a random sample of 28 pc rooms . pc rooms were located in goyang city , a residential satellite city of the capital seoul . for each pc room , field researchers completed an observational questionnaire on the ventilation , air conditioning , and heating systems as well as the facility s policies on smoking ( e.g. , restricted or permitted smoking , tobacco sales permitted , tobacco advertising allowed ) . monitoring equipment was concealed and measurements occurred in a blind manner ( i.e. , owners , employees , patrons , etc . had no knowledge of this study ) . pm2.5 concentrations were measured using a metone acrocet 531 aerosol particulate profiler ( grants pass , or ) for a minimum of 30 minutes in the smoking and non - smoking areas of each pc room . all pm2.5 concentrations measured were multiplied by 8.33 to adjust for the underestimation associated with monitoring the gravimetric pm2.5 concentration using that machine . anc was measured using passive samplers ( a 37-mm polystyrene sampling cassette holding a teflon - coated glass fiber filter treated with 4% sodium bisulfate and 5% ethanol ) . passive samplers were hung 1 - 2 m from the floor and at least 1 m from open windows and ventilation systems in order to avoid air circulation ( i.e. , dead spots ) . the sampling rate was 24 ml / min and the calculated limit of detection was 0.05 g / m over a 7-day sampling period . exposed filters were extracted and nicotine was analyzed using a gas chromatograph equipped with a nitrogen phosphorous detector ( 7820a , agilent technologies , santa clara , ca ) , with 10% of the samples duplicated . final anc values were calculated by subtracting out background levels measured using blank samples . geometric means ( gm ) and geometric standard deviations were calculated and statistical analyses were performed using sas ver . 9.3 ( sas institute inc . , cary , nc ) . this study was approved by the institutional review board of national cancer center of korea . all pc rooms had centralized air conditioning and heating systems that were functioning during the rooms hours of operation . according to the partial smoking ban implemented at the time this study was performed , all pc rooms were required to obey the following regulations : install a ventilation system for extracting smoke , prohibit the sale of tobacco , ban promotion and advertisement of tobacco , and had to post no smoking signs in non - smoking areas . in all pc rooms , evidence of smoking was identified in both smoking and non - smoking areas in all pc rooms . the gm of pm2.5 concentration in both smoking ( gm , 174.77 g / m ; range , 45.81 to 399.51 g / m ) and non - smoking areas ( gm , 93.38 g / m ; range , 31.57 to 250.48 g / m ) was significantly higher than the guidelines set forth by the world health organization ( who ) . pm2.5 concentrations in smoking areas were approximately twofold higher than those in non - smoking areas ( table 1 ) . the gm of anc in smoking and non - smoking areas was not significantly different , 48.95 g / m ( range , 38.97 to 82.71 g / m ) and 41.30 g / m ( range , 37.75 to 70.38 g / m ) , respectively . we did not observe any difference in the gm of pm2.5 concentrations between pc rooms in which anc was detected ( n=19 ; gm , 98.81 g / m ; range , 41.07 to 250.48 g / m ) and those rooms in which the anc was below the limit of detection ( n=9 ; gm , 82.88 g / m ; range , 31.57 to 239.24 g / m ) ( table 1 ) . on may 16 , 2005 , korea ratified the framework convention on tobacco control , which accelerated implementation of laws protecting individuals from the negative side effects of shs and reduced the prevalence of smoking ( 48.1% males and 6.1% females ) . in june 2011 , the amended national health promotion law expanded the complete smoking ban to include recreational facilities . recreational facilities , such as pc rooms , are a location in which individuals spend the majority of their leisure time . the partial smoking ban implemented prior to the rewritten national health promotion law of 2011 required facilities to construct a wall or air curtain between smoking and non - smoking areas as well as install ventilation systems to combat tobacco smoke . however , the partial smoking ban did not prevent the flow of tobacco smoke between areas . opponents of the 2011 law , including the owners of pc rooms , organized to repeal the complete smoking ban and argued that the law was unconstitutional . this action was ultimately unsuccessful , but did delay implementation until june 8 , 2013 . in this study , we measured the levels of tobacco smoke in pc rooms prior to june 8 , 2013 , during the period of delay of the complete smoking ban . our results indicated that the pm2.5 concentrations and anc in the smoking and non - smoking areas of pc rooms were similar . we observed ancs that were greater than 10-fold higher that those in a previous report of ancs in an entertainment venue in seoul that permits smoking without restriction . the pm2.5 concentration observed in non - smoking areas of pc rooms was very high . the pm2.5 concentration in smoking and non - smoking areas combined was similar to those previously reported in cafes , bars / clubs , entertainment venues , and smoking rooms worldwide [ 11 - 15 ] . our results support previous data in that we observed that shs exposure in pc rooms was very high and that the partial smoking ban is unlikely to protect individuals in non - smoking areas from shs exposure . by means of an official government report and an article in a major daily newspaper , we announced our findings to the public and informed korean citizens that the most effective protection from shs exposure in non - smoking areas is implementation of a complete smoking ban in pc rooms . although our study sampled only a small number of pc rooms in one city , it supports the necessity of a complete smoking ban . the complete ban on smoking in pc rooms has been in force since january 1 , 2014 . we conclude that our research supports the complete smoking ban and may provide the necessary scientific evidence for other countries that have not yet implemented comprehensive smoke - free policies .

purposethe objective of this study was to measure secondhand smoke ( shs ) exposure in personal computer ( pc ) rooms with the purpose of determining the strength of scientific evidence supporting the legislative ban on smoking in pc rooms located in the republic of korea.materials and methodsfrom june to september 2012 , particulate matter ( pm2.5 ) and air nicotine concentration ( anc ) were measured in the smoking and non - smoking areas of pc rooms in goyang city , korea . in 28 randomly sampled pc rooms , field investigators completed an observational questionnaire on building characteristics , smoking policies , and evidence of smoking . the geometric means ( gm ) of pm2.5 and anc in smoking and non - smoking areas were compared.resultsevidence of smoking was identified in both the smoking and non - smoking areas of all pc rooms . the gms of pm2.5 and anc in both areas were high and did not differ significantly ( 174.77 g / m3 and 48.95 g / m3 in smoking areas ; 93.38 g / m3 and 41.30 g / m3 in non - smoking areas ) . overall pm2.5 concentrations were 5.5-fold higher than those listed in the world health organization guidelines.conclusionthis study supported previous reports that a partial smoking ban did not protect individuals from shs exposure . furthermore , the results from our study suggest how research can support policy . countries in which smoke - free policies are not yet comprehensive may find our results useful .

most newborn infants are screened for hearing impairment prior to leaving the hospital . as a result , most parents are prepared for the choices of communication needs during this most important period of development . on the other hand , little attention is paid to the performance of the vestibular sensory system , whose receptors are located in the same area as the cochlear receptors . the vestibular nuclei provide a consistent input to the postural muscle motoneurons particularly during initial postnatal development . the lateral vestibulospinal tract affects the vestibulospinal reflex by synapsing directly with motoneurons innervating extensor muscles and indirectly through spinal cord interneurons . obviously , the development of righting and locomotor skills should parallel sensory system development and motivation . this sensorimotor development has been more extensively studied in nonhuman mammals as they develop motor skills during the first four months [ 3 , 4 ] . the ferret is born with sensory systems that are more immature than that of the rat or cat . the eyes open at about postnatal day 28 ( p28 ) and hearing becomes functional at about p32 . the vestibular receptors mature at about the same rate as the auditory system ; the maculae of the saccule and utricle mature first ( ~p10 ) and the cristae of the semicircular canals develop a little more slowly to reach the adult form at about 24 days after birth , and the ferrets begin walking at about p24 . neonatal removal of the vestibular labyrinths in ferrets and rats has resulted in changes in muscle physiology and muscle fiber type , persistent unstable standing balance , and reduced velocity of locomotion . animals that undergo labyrinthectomies as a juvenile or an adult may have some loss of balance reactions but adapt quickly and do not change the anatomy and physiology of the muscles . in contrast , vestibular receptors have been seen under the microscope in 79-week - old human embryos , but the vestibular reflexes develop a little more slowly in humans as the sensory systems continue to mature and integrate . shumway - cook and woollacott proposed that , normally , children undergo transition to more adult strategies of posture control between the ages of 4 and 6 . examined the gross motor development among young children with bilateral moderate to profound sensorineural hearing impairment ( hi ) . delayed gross motor development was evident in these children and a majority received vestibular hypofunction scores using the southern california postrotary nystagmus test ( prn ) , ayres ( 1983 ) , western psychological services . the prn test measures the responsiveness of the lateral semicircular canal by assessing the vestibular ocular reflex which occurs in response to rotation . it is designed for children of normal intelligence between the ages of 5 and 9 . in comparison , the vestibular evoked myogenic potential ( vemp ) evaluates saccular function by stimulating those receptors and recording the time delay to the evoked emg recorded from the sternocleidomastoid muscle . the primary purpose of this study is the identification of functioning vestibular saccule receptors among children with hearing impairments and correlation of saccular deficits with fine and gross motor developments . a secondary aim was the comparison of motor skills in a group of children with hearing impairment from birth with a group of children that lost their hearing after 2 years of age . thirty - three children ( 20 males , 13 females ) with bilateral severe / profound sensorineural hearing impairments ( his ) ( loss greater than 71 db ) were recruited as a sample of convenience through parent support groups such as the virginia chapter of the ag bell association , the speech - language - hearing association of virginia , and the north carolina triad hitch - up . two other children had tested positively for the connexin 26 gene but most had not been tested for genetic markers . all children were between the ages of 4 and 7 years ( mean = 66.1 12.3 months ) . there were 3 other children that refused the test either prior to any testing or during the test ; 2 were 4 years old and 1 was 5 years old . nineteen of the children had cochlear implants for at least one year prior to testing ( range = 15 years ) . parents or guardians completed forms providing a brief health history on the child and consented to perform the evaluation . most presented audiological documentation . twenty - four of the children had hearing impairment since birth but no other obvious neurologic damage . the child lay supine on a mat on the floor with the investigator in a separate quiet room and frequently a parent was in the immediate proximity . the skin over the sternocleidomastoid ( scm ) muscles and sternum were cleaned with an alcohol wipe . a surface bar electrode ( 2 concave ag / agcl electrodes separated by 3 cm and coated with conductivity gel ) was placed on the scm muscle ( active on the muscle belly , reference on the tendon ) , on the same side as the stimulus , to record the electromyographic potential ( emg ) . the emg was amplified and bandpass filtered ( 8 hz1.6 khz ) . a 10-ohm , 15 pin fa bone vibrator transducer ( cadwell laboratories , inc . , kennewick , wa , usa , with impedence matching adaptor box ) was held against the mastoid process while the child flexed his or her head against gravity to activate the scm while looking at a picture book or playing with a toy . preliminary trials showed that the children were reluctant to use the earphone / ac stimulation ( maybe it was associated with hearing tests ) though they were willing to use the bone conducted stimulus . one hundred s clicks were generated by the cadwell wedge ( kennewick , wa ) at 95 db , 16 hz . 95 db is commonly used in the literature for air- and bone - conducted vemp though there have been reports of a less intense stimulus ( e.g. , 50 db ) . a consistent stimulus the baseline emg activity of the scm was visualized and then 200 tracings of the evoked potential were averaged . the left side was always tested first and the procedure was repeated on the right side . the latency and amplitude of the potential was visualized and quantified using cadwell sierra xp software ( kennewick , wa ) . based on normative data ( using air - conducted vemp ) on young children , a normal p1 latency was in the range of 8.314.4 seconds and the vemp at least 20 mv amplitude . todd et al . have shown a slightly wider range of vemp latencies ( 7.513.9 ) for bone - conducted stimulation than air - conducted stimulation in adults . each child was evaluated using the movement assessment battery for children ( movement abc ) ( psychological corp . , london , england , 1992 ) to assess their proficiency in areas of manual dexterity , ball skills , and static and dynamic balances ( table 1 ) . if the child wore cochlear implants , these were allowed during the motor testing ( but not during vemp testing ) . the raw scores are converted into scaled scores in order to ascertain where the child 's performance lies in relation to the standardized sample . the test has excellent reliability ( r = 0.96 ) and validity in normal children and children with disabilities and from populations in europe and north america [ 1719 ] . student 's t - tests were used to compare the groups of subjects with a limit of p < .05 indicating significance . a vemp was identified on both sides in only 4 of the hi children ( 3 of these children were identified as hi at birth ) . four children with normal hearing of the same age as the four hi children with normal vemp were recruited for comparison . there were no significant differences between these two groups in the total or subscores on the movement abc ( figure 1 ) though the hi children tended to have greater impairment on the manual subtest ( p < .07 ) and ball subtest ( p < it should be noted that power analysis indicated that to reject the null hypothesis correctly at the .05 level , a sample size of 14 was needed . so caution should be taken in the interpretation of this limited number of subjects though the scores indicate that all of the children in figure 1 are functioning similarly to the standardized group . seven children demonstrated a vemp on only one side ( figure 2 ) as measured by the action potential amplitude > 20 v and latency ( mean = 10.3 1.5 ms ) . there was a tendency ( p < .9.26 ) for hi children with one or both sides intact ( n = 11 ) to perform better on the movement abc than hi children with no vemp ( n = 23 ) ( figure 3 ) . of the hi children with an asymmetrical response , one child had a right cochlear implant and vemp only on the left side , while the rest of the children had bilateral cochlear implants ( n = 2 ) or no implants ( n = 4 ) . twenty - four children were hi since birth or within 6 months ( according to the parents ) ; nine children developed hi after the age of two years ( 7 at about 24 months , 2 at about 36 months ) . the children with hi since birth had significantly higher scores ( more developmental delay ) ( p < .01 ) on the manual and balance subtests and the total movement abc ( figure 4 ) . two of the children in each group retained their saccular receptors bilaterally as shown by vemp . no significant difference was seen in the movement abc scores between the hi children with and without cochlear implants ( mean of the total abc scores = 12.6 9.6 and 15.5 9.9 , resp . ) . the results of this study are important to show that many but not all hearing impaired children have saccular deficit ( s ) . a more strategic finding is the importance of the timing of the onset of the hearing impairment and probably saccular loss to the development of balance strategies . the early postnatal period is critical for the vestibular system in experimental models such as the ferret , so that it impacts neuromuscular development of postural muscles and the development of balance strategies . human studies have focused more on motor development in the deaf population as a uniform population or the effect of cochlear implants . there have been several studies of motor development of hi children with mixed results [ 2024 ] . some studies [ 20 , 21 ] that have included hi children younger than 7 years old also include children up to 17 years of age . vestibular hypofunction and supported the need for vestibular testing and repeated motor development testing during preschool and elementary school . it is unknown wether all of the vestibular receptors are lost at the same time as the cochlear receptors but the parents in this study report that the hearing loss was identified in many of the children neonatally , implying the need for very early identification of children with vestibular deficits . the current study found a significant difference in the motor development between the children with a profound hearing loss at birth and those that reportedly developed hi later with those with presumably congenital onset hearing loss demonstrating poorer performance . it is possible that vestibular receptors are more important during the initial six months to a year when the infant is learning to sit and stand . normally children are walking by two years of age , albeit with a wide based gait . it is likely that hi children , who also have a vestibular deficit ( at least a loss of saccular function ) , learn to depend on their vision and joint and skin sensation but it is hypothesized that the developmental milestones such as walking would be delayed without the vestibulospinal reflexes . some of the parents reported that there were 1 - 2 days post implantation when the children seemed to be a little more clumsy , after which the children quickly returned to their presurgical motor coordination . this brief change was not measured , and at the time of this study , the children with and without cochlear implants were not significantly different in their performance of the movement abc . the vemp was normal on at least one side in six ( of 19 ) of the hi children with cochlear implants . this would seem to indicate that the cochlear implant does not have a long - term effect on balance and motor control . saccular function ( tested by air - conducted vemp ) was found in 40% of their subjects but was not correlated with balance ability when tested by the balance subset of the bruininks - oseretsky test of motor proficiency ii . in contrast , horizontal canal function correlated well with the balance score which implies that angular motion and vestibulo - ocular interaction are very important to balance . the saccule detects more linear motion so the correlation of saccule hypofunction with both delayed fine motor skills and balance skills leads one to conclude that the saccule may impact both the vestibulospinal and vestibulo - ocular reflexes though its differential function remains unclear . only the vemp was used in this study and , therefore , only the saccule receptors were studied . there are other vestibular evaluation measures such as videonystagmography ( vng ) , rotary chair , bithermal caloric irrigation , and computerized dynamic posturography which evaluate other vestibular receptors . hence , it is possible that another vestibular receptor may have impacted performance . as with all motor disorders , it is important to take into consideration that vision , somatosensory , vestibular , and sensations are integrated to provide optimal performance of motor control . a limitation of the convenience sample used in this study is that parents who may have been concerned about balance dysfunction may have volunteered their children for this study . the onset of hearing impairment ( congenital versus delayed , potentially progressive ) has an impact on balance and manual skills and overall motor development . how this difference relates to the development or impairment of the vestibular receptors ( in the case of the current study what is happening at the level of the cochlea may parallel what is happening at the level of the vestibular end organs . the absence of vemp bilaterally may predict poor performance on balance and manual dexterity- related tasks although a larger sample would be required to say that this is more than a trend . further research is necessary to correlate the timing of the loss of saccular receptors with motor development in children . early intervention could potentially optimize postural control in children who are identified with vestibular hypofunction .

children with hearing deficits frequently have delayed motor development . the purpose of this study was to evaluate saccular function in children with hearing impairments using the vestibular evoked myogenic potential ( vemp ) . the impact of the saccular hypofunction on the timely maturation of normal balance strategies was examined using the movement assessment battery for children ( movement abc ) . thirty - three children with bilateral severe / profound hearing impairment between 4 and 7 years of age were recruited from a three - state area . approximately half of the sample had one or bilateral cochlear implants , one used bilateral hearing aids , and the rest used no amplification . parents reported whether the hearing impairment was diagnosed within the first year or after 2 years of age . no vemp was evoked in two thirds of the hearing impaired ( hi ) children in response to the bone - conducted stimulus . children who were reportedly hearing impaired since birth had significantly poorer scores when tested with the movement abc .

the first screening method of screening for trisomy 21 was based on the maternal age . since the late 1980s , a test was universalized for three fetoplacental products ( alpha - fetoprotein , unconjugate estriol , and total hcg ) in the maternal serum at the second trimester of gestation . in addition , various sonographic markers such as nuchal fold thickness and femur length in second trimester were introduced , and the nuchal translucency ( nt ) became important as the early screening method for chromosomal abnormality ( 1 - 3 ) . the test , using maternal serum biochemical markers , has a relatively fixed cut - off of 1:270 , and the sensitivity is known to be about 60% . many studies have reported that the thickened nt could identify about 75% of affected fetuses for a false positive rate of 5% , but various cut - offs were used in those studies ( 4 - 7 ) . although many studies have asserted that different cut - offs of nt according to the crown rump length ( crl ) should be used for screening chromosomal aberration , there are few studies actually comparing the sensitivities and false positive rates of nt with different cut - offs within the same group . in this study , we report herein on those values of nt for chromosomal aberration with three different cut - offs , 2.5 mm , 3.0 mm and the 95th percentile for the crl in a korean population . this study was conducted with 2,570 pregnancies by searching our clinical database from january 2001 through december 2001 . the inclusion criteria were singleton pregnancies who examined ultrasonographic fetal nt measurement between 11 weeks and 14 weeks of gestation at our institution and performed regular antenatal care during the pregnancy with known pregnancy outcome . the ultrasonographic scans of fetal nt measurement were carried out by 5 sonographers and 2 obstetricians experienced first - trimester scans more than 5 yr . fetal nt thickness was measured using the transabdominal ultrasonography ( hdi 3000 , atl , bothell , wa , u.s.a . ) in a good mid - sagittal section of the fetus with magnification so that the fetus occupied at least 75% of the image ( 8) . in cases of visualization proved difficult or suspicious findings , a transvaginal ultrasonography was also used . the nt was defined as the black area between the inner skin on the outline echo and the outer border of the soft tissue overlying the cervical spine . the maximal thickness of the black area was measured with a caliper placed on the lines to 0.1 mm when the sagittal section of the fetuses was obtained . at same time , the fetal crl was also measured . great care was also taken to clearly distinguish between the fetal skin and the amniotic membrane . in some cases this could only be achieved by asking the mother to cough or by tapping the maternal abdomen . in some cases , it was helpful to use the cineloop function ( a function that permits the replay of ultrasound images taken in the past few seconds ) to visualize the fetus in a satisfactory position . at least three measurements were taken during the scan and the largest of the three measurements was recorded . we underwent fetal karyotyping in one hundred twenty five women with increased fetal nt ( 2.5 mm ) by chorionic villus sampling or amniocentesis . fetal karyotyping was also offered to women who were maternal age of 35 yr old or more at the time of delivery ( n=158 ) , had a positive result on the triple test ( n=92 ) , had the history of chromosomal abnormality in any previous pregnancy ( n=8 ) , had major fetal structural anomalies on ultrasound examination ( n=12 ) , and others ( n=24 ) . the karyotyping was also performed in intrauterine fetal death ( iufd ) ( n=4 ) cases . among the cases who had not been offered fetal karyotyping , we examined the neonates or stillborn for phenotypic abnormality indicating chromosomal aberrations . we excluded the cases ( n=8 ) who had terminated their pregnancies because of major structural anomaly on antenatal ultrasound without fetal karyotyping . the frequencies of chromosomal aberrations were analyzed and the sensitivities and false positive rates were calculated according to three different cut - offs , namely 2.5 mm , 3.0 mm and the 95th percentile for each fetal crl . we used the data about the 95th percentile of nt for each crl of our institution ( 9 ) . the frequencies of fetuses with increased nt according to cut - offs of 2.5 mm , 3.0 mm , and the 95th percentile of each crl were 7.1% , 4.1% and 6.5% respectively . table 1 shows the types and frequencies of chromosomal aberrations according to the various cut - offs of nt . there were a total of 31 cases ( 1.2% ) of chromosomal aberrations in this study . among these cases , the frequencies of chromosomal aberrations that ultrasonographic nt measurement was thickened than that of 2.5 mm , 3.0 mm , and the 95th percentile of nt measurement at each crl were 11.5% ( 21/161 ) , 15.9% ( 17/89 ) , and 13.2% ( 22/146 ) , respectively . we could detect one more case of trisomy 18 when we used the 95th percentile as the cut - off than the fixed cut - off of 2.5 mm . table 2 shows the sensitivities and false positive rates of nt with each cut - off for screening all the chromosomal aberrations and trisomy 21 . the sensitivity for detection of chromosomal aberrations was high ( 70.9% ) in the 95th percentile as the cut - off compared with the fixed cut - offs . the false positive rate was 3.5% when using 3.0 mm , but the sensitivity was 54.8% . when using the 95th percentile of nt , the sensitivity was higher and the false positive rate was lower than those of using 2.5 mm for detecting chromosomal aberrations . the sensitivities of the nt measurement to detect trisomy 21 with two cut - offs , 2.5 mm and the 95th percentile were same ( 75% ) , and the false positive rate of the 95th percentile ( 6.2% ) was lower than that of 2.5 mm ( 6.8% ) . the various screening methods for detecting chromosomal aberration have been investigated and many studies are ongoing to search for a more efficient screening method . among the various methods , we evaluated the sensitivities and false positive rates of the screening test of nt measurement alone ( not including maternal age ) in the first trimester for chromosomal aberrations by using three different cut - offs in a korean population . the sensitivity of the nt measurement with 3.0 mm as a cut - off was 54.8% in this study . the early studies about nt measurement mainly used 3.0 mm as the cut - off and the reported various sensitivities were from 39% through 93% ( 10 - 12 ) . this wide range of results may be due to the different study populations and/or to an inadequate gestational age at the time of nt measurement . most of these studies were mainly targeted to a high risk population that was scheduled for fetal karyotyping ( 11 , 12 ) , so the sensitivity of detecting an affected fetus with an increased nt would be higher than that used in the general population . on the other hand , some early studies reported low sensitivity in their results ( 13 , 14 ) . in those studies , the adequate gestational age ( in weeks ) of the nt measurement was not established , so cases that measured earlier than 11 weeks of gestation were also included as a large proportion of the subjects . all the cases in which the translucency was not visible or measurable were included in the classification of less than 1.0 mm . the cases under 10 weeks of gestational age had the probability of having an immeasurable nt , and the studies that included these subjects would have results with low sensitivity . currently , the adequate period of the nt measurement is known to be the time between 11 and 14 weeks of gestation ( 8) . in this study , we included pregnant woman in this period . as extensive data is accumulated regarding the first - trimester nt screening of populations at high risk , attention has been drawn to those populations at low risk and general population ( 15 - 17 ) . this data is of major importance because these populations represent the women for whom the vast majority of pregnancies with fetuses having abnormal chromosomes will occur . the results of the present study are similar to those results of hafner et al . they assessed what percentage of chromosomal anomalies could be detected by a nt measured in 4,233 unselected women . they diagnosed one additional down syndrome case by using a sliding scale for the cut - off value with two standard deviations instead of the fixed value of 2.5 mm . so , they suggested that detection rate could probably be improved by raising the values with increasing gestational age . we used the 95th percentile of each crl as the cut - off value in this study , and we could detect one additional case of trisomy 18 . recent studies have reported the sensitivities of nt according to various gestational age - dependent cut - offs for detecting chromosomal abnormality ( 15 , 17 , 18 ) . one of the largest multicenter study ( 18 ) showed that the sensitivity of nt with gestational age - dependent cut - offs for trisomy 21 was 77% for a false positive rate of 5% . we presume the reason for high occurrence of trisomy in this study is that we included two cases of trisomy referred from private clinics with abnormal ultrasound findings in first trimester and another two cases of trisomy with iufd before amniocentesis ( the nt thickness of those cases were all increased over 3 mm ) . although the sensitivities and false positive rates of nt for detecting of chromosomal aberration were changed after excluding those four cases ( 62.9% , 48.1% , 66.6% and 6.4% , 3.6% , 5.8% according to cut - offs 2.5 mm , 3.0 mm , 95th percentile ) , the superiority of 95th percentile nt value as the cut - off for screening test was not changed . this study is the first study to compare the sensitivities of nuchal translucency alone as a screening test for chromosomal aberration with different cut - offs in a korean population . when using the 95th percentile of nt , we identified that the sensitivity was higher than that of fixed cut - off for detecting chromosomal aberrations . so , we can suggest that this cut - off should be used for the nuchal translucency measurement screening method in korean population .

this study evaluated the sensitivities and false positive rates of the screening test using ultrasonographic measurement of thickness of nuchal translucency ( nt ) with different cut - offs for chromosomal aberration in a korean population . we included 2,570 singleton pregnancies undergoing ultrasound between 11 weeks and 14 weeks of gestation in this study . we analyzed the sensitivities of nt alone for screening chromosomal aberration using three cut - offs -2.5 mm , 3.0 mm , and 95th percentile for each crown rump length ( crl ) . there were 31 chromosomal aberrations ( 1.2% ) including 12 cases of trisomy 21 . the numbers of chromosomal aberrations that were detected by nt with different cut - offs of 2.5 mm , 3.0 mm and the 95th percentile crl were 22 , 18 and 23 , respectively . at a threshold of 2.5 mm , the sensitivity and the false positive rate for total chromosomal aberrations were 67.7% and 6.3% , respectively . at 3.0 mm , those were 54.8% and 3.5% , respectively . at the 95th percentile crl , those were 70.9% and 5.8% , respectively . the use of crl - dependent cut - offs for nuchal translucency improves the detection of chromosomal aberrations when compared to fixed cut - offs in a korean population .

tufted angioma is a rare vascular neoplasm clinically characterized by slowly progressive pink to red macules or plaques on the neck , trunk , or shoulders of children or young adults . these tumors follow a benign course of angiomatous proliferation , without any evidence of malignancy . we report herein a case of multifocal tufted angiomas with annular morphology in a child for the rarity of the condition . an 8-year - old boy was referred to us for the evaluation of multiple reddish elevations on the back , which were first noticed 4 years before presentation . starting as two small reddish asymptomatic patches , the lesions gradually became elevated and fresh lesions appeared in the vicinity of the older ones . the lesions have remained stable for the preceding several months . increased sweating over the patches was noted by the parents . family history and past medical history was unremarkable . on examination , two brightly erythematous annular plaques of about 6 cm and 3 cm diameter in addition , several erythematous papules and plaques of varying sizes were seen around the lesions as well as on the right side of the back . routine laboratory tests , blood coagulation profile , and serum biochemistry panel were within normal limits . two annular erythematous plaques and several papules and plaques of varying sizes on the back we considered the differential diagnoses of tufted angioma , sudoriferous angioma ( eccrine angiomatous hamartoma ) , and capillary hemangioma . crescent - shaped cleft like spaces were seen around the lobules [ figures 2 and 3 ] . based on the clinical findings and characteristic histology , a diagnosis of tufted angioma was made . after discussion about the possible modalities of treatment and the chance of spontaneous regression , the parents preferred regular follow - up without any active intervention and the child was kept under observation . histopathology showing well - circumscribed poorly - canalized capillary lobules in the dermis with crescent - shaped spaces around them . h and e , 100 showing well - defined capillary tufts surrounded by crescent - shaped clefts . ta was described for the first time by wilson jones in 1976 as an acquired vascular proliferation of peculiar histological characteristics and reports of additional cases had helped better characterization of this clinicopathologic entity . it commonly presents in infancy or early childhood , though adult - onset cases have been reported also . ta usually presents as a macule , papule or plaque over the upper trunk , neck and proximal part of the limbs ; involvement of other locations like face , oral mucosa and lip is also known . ta is a sporadic disease with more than half of the cases occurring during the first 5 years of life . hyperhidrosis , as in our case , and hypertrichosis can also occur over the lesion . eccrine sweat gland elements however were not seen to be increased in the histopathology of our patient . ta should be differentiated from kaposiform hemangioendothelioma , juvenile capillary , or strawberry angioma , haemangiopericytoma , glomeruloid haemangioma , or pyogenic granuloma . ta can however be diagnosed by the distinctive histopathological pattern characterized by the vascular tufts of densely packed capillaries , randomly scattered throughout the dermis in a so called cannonball configuration . there are crescentic spaces surrounding the vascular tufts and lymphatic - like spaces within the tumor stroma . immunohistochemical stains show strong positivity for ulex uropaeus i lectin and en4 and unlike infantile hemangioma , negative staining for glut 1 . ta , like kaposiform hemangioendothelioma , may be associated with the kasabach - merritt syndrome ( kms ) . physicians should look for the appearance of petechiae or ecchymotic patches and if they occur , a complete hemogram ( including a platelet count ) , prothrombin time and/or activated partial thromboplastin time and full screening for disseminated intravascular coagulation should be ordered . common association with kms , morphologic similarity , association in the same patient , and common expression of lymphatic markers had led to the suggestion that ta may be a minor form of kaposiform hemangioendothelioma or part of a spectrum of the same condition . ta usually pursue a persistent course , but spontaneous regression may occur in a proportion of cases . different modalities of treatment including complete surgical excision , cryosurgery , and radiotherapy had been tried for ta . pulsed dye laser has also been reported as an effective option for treatment of ta . embolization and vincristine are found to be effective in patients having kms . in conclusion , we have reported a rare case of multiple tufted angiomas with annular morphology in a child . the possibility of this tumor should be kept in mind while dealing with patients having lesions of similar morphology . we described a boy who had multifocal lesions with large annular plaques as well as papules and nodules .

tufted angioma ( ta ) is a localized benign hamartomatous vascular proliferation usually presenting in the childhood as an erythematous plaque . we report here a rare case of multifocal ta in an 8-year - old boy who presented which two large annular lesions as well as multiple papules and nodules on the back for the duration of 4 years . histology showed typical well circumscribed poorly canalized vascular lobules with cannon ball configuration .

inflammatory macular edema represents one of the main causes of significant vision loss in patients with uveitis , as a result of the breakdown of the blood retinal barrier by inflammatory mediators such as tumor necrosis factor - alpha and interleukin-1beta.1 in an effort to intercept the circulation of these mediators , corticosteroids have been used in variable delivery forms ( oral , intravitreal , sub - tenon s administration ) as a treatment modality for macular edema on the background of various types of chronic posterior uveitis . the repeated administration nature of periocular and intravitreal steroid injections as well as the increased incidence of side effects associated both with topically and systemically administered corticosteroids24 led to the development of slow - release therapeutic modalities . based on a phase iii study showing that the 34-week risk of uveitic recurrence fell significantly from 51.4% to 6.1% and visual acuity improved significantly,5,6 the food and drug administration approved an intravitreal fluocinolone acetonide ( fa ) implant that could deliver a sustained dose of corticosteroid ( retisert ; bausch & lomb incorporated , bridgewater , nj , usa ) for the treatment of the posterior uveitis . since 2005 , the use of fa implant gained popularity among ophthalmologists . nonetheless , the identification and management of possible intraoperative or postoperative complications associated with its use remains an ongoing process . the purpose of the present work is to report the unusual but serious postoperative complication associated with the implantation of retisert , which to the best of our knowledge has never been reported before , and describe the surgical management of scleral melt at the site of the retisert implantation in a patient with posterior uveitis on the background of psoriatic arthritis . a 42-year - old caucasian woman was referred to our department complaining of sudden vision loss , watery discharge from her right eye ( re ) , and pain . she had a complex past ocular history that included the implantation of retisert in her re to treat persistent uveitis - associated cystoid macular edema on the background of psoriatic arthritis 18 months earlier . in addition , according to her notes , she had undergone combined phacoemulsification and vitrectomy with epiretinal membrane peeling 2 years before the fa implant . one year after the retisert implantation , she underwent right trabeculectomy to treat persistently high intraocular pressure . on examination , the intraocular pressure ( iop ) was 2 mmhg , the anterior chamber was flat , and the visual acuity was counting fingers in the re . an anterior segment examination revealed scleral melt with active leaking ( positive seidel test ) at the site of the fa implant . intraoperatively , an anterior chamber maintainer was used and surgical exploration confirmed significant scleral melt at the site of implantation with leaking aqueous humor ( figure 1 ) . a scleral patch graft was sutured over the leaking sclerotomy . on the following day , the iop was 9 mmhg and the fundus examination revealed that the fa implant had detached from the scleral sutures and was free floating in the vitreous cavity . three weeks later , the iop was 18 mmhg , the visual acuity recovered to 20/30 , and the patch graft was in good position ( figure 2 ) . benefits and risks of vitrectomy to remove the retisert implant were discussed with the patient ; however , she decided against surgery . two years later , visual acuity remained 20/30 with no recurrence of the cystoid macular edema , and iop within normal limits , without additional medication . fa has a high potency , a low solubility , and a very short duration of action in the systemic circulation , enabling the steroid pellet to be small and reducing the risk of systemic side effects . the implant consists of a tablet encased in a silicone elastomer cup containing a release orifice and a polyvinyl alcohol membrane positioned between the tablet and the orifice . the silicone elastomer cup assembly is attached to a polyvinyl alcohol suture tab with silicone adhesive , which is supported to the sclera with sutures . the most common side effects of retisert are cataract formation ( all patients require cataract surgery within 3 years ) and significantly raised ocular pressure ( 40% of patients require trabeculectomy surgery ) . more rare side effects are vitreous hemorrhage , retinal detachment , vitreous bands , scleral thinning over the implant , and hypotony ( iop < 6 mmhg in 9.4% of implanted eyes).2,69 scleral melt has not been reported as a possible complication of fa implant . in a study aiming to evaluate whether intravitreal fa implantation ( retisert ) leads to scleral thinning , taban et al10 reported that fa implant appears to lead to overall statistically nonsignificant scleral thinning with few exceptions . in our case , significant scleral melt developed 18 months after the implantation of fa implant , which to the best of our knowledge has never been reported before . of course , the patient had previously undergone vitrectomy with epiretinal membrane peel before fa implant as well as a trabeculectomy post - retisert implantation . it is possible that these procedures could represent an additional factor for the significant scleral melt observed in our patient , although no significant inflammation or infection had been recorded post - vitrectomy or post - trabeculectomy . no adverse events were observed to be associated with the presence of the free - floating implant in the vitreous cavity .

intravitreal fluocinolone acetonide implant ( retisert ) has a high potency , a low solubility , and a very short duration of action in the systemic circulation , enabling the steroid pellet to be small and reducing the risk of systemic side effects . scleral melt has not been reported as a possible complication of retisert implant . the authors describe the occurrence of scleral melt 18 months after the implantation of fluocinolone acetonide implant in a 42-year - old caucasian woman . to the authors knowledge , this is the first report of this possible complication .

an operating microscope ( om ) has been considered as the mainstay in modern neurosurgery . it produces magnified images on the retina stereoscopically while providing detailed views of surgical anatomy . during the last two decades , neuroendoscopes are increasingly used in neurosurgery for intraventricular lesions , spine , hematoma and predominantly for trans - sphenoidal skull base surgery . an endoscope is sometimes used as an adjunct to microsurgery with om . . an endoscope can be useful by means of providing a better overview of the operating field and also revealing detailed structures with fine illumination . surgeons visualize the operative field from a display connected to the camera with usage of an endoscope . on the other hand , compared with om , the target is viewed only through right and left eyepieces . in 2008 , an exoscope system i.e. the video telescope operating monitor ( vitom ) was introduced as an alternative to both om and endoscope . the exoscope serves for observing and illuminating an object field on a patient from a position set apart from the patient s body . it enables surgeons to complete the operation under assistance by visualizing magnified images with high resolution on a display4,5 ) . therefore stereopsis was required to improve hand and eye coordination for microsurgical procedures with usage of the exoscope . subsequently novel three - dimensional and high - definition operating scopes have been developed according to recent high - tech innovations in a digital surgical technology . the standard neuroendoscope can only provide a short focal distance of approximately 3 to 20 mm . therefore , vitom allows abundant space to insert and manipulate the instruments according to this specification ( table 1 ) . usually the vitom is placed at regular interval of 25 cm from the operative field at first . an illustrative case of spinal lipoma surgery with usage of vitom was shown on fig . the main manipulations in this surgery were as follows ; drilling the vertebral arches , cutting dura and arachnoid membrane with scissors , making suspending stitches , separating adherent arachnoid , resection of the lipoma along the white plane , forming circular arc by sawing the pia matter to make a neural cord and closure of dura at last . these operative techniques were completed under 2d motion images with a visual perception through dynamic cue and stereoscopically viewing corresponding to the motion parallax . but lacking the stereoscopic vision made it difficult to manipulate required hand - eye coordination such as taking hold the needle and stitch up . according to my clinical experiences , three - dimensional ( 3d ) motion images must be necessary in a case with complete resection of deep seated lesions or vascular anastomosis for exoscopic surgery . the emphasizing advantages of exoscope were regarded as the wide field of view ( fov ) and deep focus . vitom provides the ability to maintain 35 mm depth of field ( dof ) under 50 mm fov . it minimized the need for repositioning and refocusing during the procedure . on the other hand , only 50 mm fov is possible under minimum wd , however , less than 20 mm fov is easily available under 200 mm wd with om ( table 1 ) . from this point of view , further refinements in high resolution imaging under strong magnification , such as digital zooming would be a welcome to the vitom . in the field of laparoscopic surgery , 3d laparoscopes with various mechanical designs are currently used successfully . those prevent signs of fatigue while shortening the operating time and facilitate various procedures inside the body , especially in performing precise suturing . 3d endoscope provides enhancing subject depth perception and spatial orientation . according to the recent reports , 3d images improve surgical dexterity in the field of neuroendoscope3,10 ) . for example , clinical application of 3d - neuroendoscope for trans - sphenoidal surgery is regarded as an effective assistive technique and supports the feasibility and safety9,10 ) . surgeons sometimes observe an intracranial object field from a position set apart from the sphenoid sinus during this procedure . vsiii system ( visionsense , philadelphia , pa , usa ) is one of the valuable one . it is based on insect - eye technology , which involves the incorporation of a single objective lens that splits light along two paths , reconstructing a 3d image9 ) . on the other hand , it incorporates information from two distinctive perspectives to render a single 3d view , similar to human vision with binocular depth perception . exoscopic microsurgery with usage of the einstein vision , 3d and high - definition ( hd ) laparoscope system which is designed based on dual optical technology . they concluded that the image quality was found to equal to that of the om , but suitability for minimally invasive neurosurgical operations is inadequate . yoshimoto et al.10 ) reported their clinical experience of endonasal surgery with usage of dual optical channel 3d endoscope ( developed by shinko optical corporation and commercialized by machida endoscope corporation , tokyo , japan ) and compared stereoscopic images with vsiii system . according to that , the stereoscopic effect of dual optical channel 3d endoscope is stronger . in other words , dual optical channel 3d endoscope exhibits greater magnitude of binocular disparity , which is translated into the sense of extrusion and depth of structures . in 2014 , a novel 3d and hd flexible scope called 3d - eye - flex was developed to visualize the operative field as a 3d digital image and support more accurate microsurgery6 ) . it was introduced with an enhanced 3d - hd laparo - thoraco videoscope system ( ltf- y009 , olympus medical systems ) . 3d - eye - flex has two miniature - sized charge coupled device ( ccd ) chips at the distal end of the scope . consequently , regardless of rigid or flexible , placing the imaging device at the tip has made on site processing of images without interruption possible , while maintaining consistent image quality . a 15 mm - long rigid 3d and hd scope with a 15 mm outer diameter is attached to a 615 mm - long flexible bellows . the focus distance , which is the same as the wd , is 18100 mm . the illumination is not as bright as that of om , however , the ccds help to enhance the image . a circular polarizing filter system is used for the 3d display to deliver life - like images ( fig . exoscope , an alternative to om , by means of capturing the 3d magnified images using digital signals from the outside of the body . the wide angle of view and large dof inherent in the endoscope should be emphasized as advantages just like vitom system . the large dof of 3d - eye - flex drastically minimizes the need for repositioning and refocusing during a surgical procedure . moreover , neurosurgeons feel more comfortable when using stereoscopic vision , especially in cases of deep seated lesions . on the other hand , placing the scope close to the operative area should be required for magnifying objects . it is more likely to be stained by blood or bone dust , fogging the lens and narrowing operative space . as described above , recently developed operative scopes visualize the operative field as digital images and make it possible to verify the images according to application . for example , narrow - band imaging ( nbi ) while changing the light wavelength , i.e. autofluorescence , is easily applicable with 3d - eye - flex , and can be integrated with the information obtained from white light7 ) . an optical color separation filter narrows the bandwidth for spectral transmittance , lets only two narrow wavelengths through . these two specific wavelengths are strongly absorbed by hemoglobin and allow a better understanding of superficial and subependymal vasculature in the ventricle ( fig . 4 ) . in another example , a fluorescent dye injected into the body leaks out of the tumor blood vessels due to the disrupted blood - brain barrier . it is excited with an ordinary light wavelength and the yellow color - stained tumor is visible even to the naked eye . with further refinement , an ultra - high magnified image captured by endo - cytoscopy may be possible . currently these images of the operative field are projected onto a display adjacent to navigation images or functional images . it may be coregistered on the identical display in the near future . in state - of - the - art neurosurgery , neurosurgeons could highly benefit from a new surgeon s eye that visualizes the operative field with integration of the medical information received by the senses and interpreted by surgeon s brain on demand . the novel operative scopes including exoscope system have potential for being developed to this new application . it will set the stage for the next generation in digital image based neurosurgery .

an exoscope , high - definition video telescope operating monitor system to perform microsurgery has recently been proposed an alternative to the operating microscope . it enables surgeons to complete the operation assistance by visualizing magnified images on a display . the strong points of exoscope are the wide field of view and deep focus . it minimized the need for repositioning and refocusing during the procedure . on the other hand , limitation of magnifying object was an emphasizing weak point . the procedures are performed under 2d motion images with a visual perception through dynamic cue and stereoscopically viewing corresponding to the motion parallax . nevertheless , stereopsis is required to improve hand and eye coordination for high precision works . consequently novel 3d high - definition operating scopes with various mechanical designs have been developed according to recent high - tech innovations in a digital surgical technology . it will set the stage for the next generation in digital image based neurosurgery .

geolocation and remote sensing technologies are increasingly being applied to the mapping and spatial analysis of infectious diseases , including lymphatic filariasis and malaria . for such maps to reflect the real pattern of infection or disease , lymphatic filariasis and malaria are both currently subject to renewed control programmes , and share anopheline vectors in some parts of the world . filariasis is being targeted for elimination , but reduction in its infection intensity could conceivably , via the removal of infection - induced vector mortality , lead to more efficient transmission of malaria . accurate mapping of the two infections can help monitor their control , including the detection of any unwanted interactions . here , we present spatial analysis of both parasites in the same area of papua new guinea , using a recently developed technique which estimates the scale of variation , taking into account the typically highly skewed distribution of parasite counts . in a rural area of the east sepik province , cross - sectional parasitological surveys were done of the population aged over five years , as part of a trial of diethylcarbamazine ( dec ) plus ivermectin versus dec alone against lymphatic filariasis . although , with regard to malaria , the lower age threshold is a limitation , in the nearby wosera area , peak prevalence was not reached till after five years . wuchereria bancrofti microfilariae were counted microscopically on nuclepore filters , through which 1 ml of night - collected blood had been passed . anopheles mosquitoes , predominantly anopheles punctulatus s.s . , are the vectors of filariasis in the area . villages are divided into subunits , which we call hamlets , distinguished by names in the local languages . these were mapped with a hand - held trimble ensign global positioning system ( gps ) machine . in the 1994 survey , immediately before the first round of treatment , blood samples were obtained from 2,219 people in 149 hamlets . hamlets whose distance to their nearest neighbour was , due to gps inaccuracy , measured as less than 10 m were combined with their nearest neighbour . there were two such instances , so reducing the total number of hamlets to 147 . as described elsewhere , spatial structure in the infection densities was fitted by a negative binomial model . the mean density is fitted as a log - linear function of age , sex , and the hamlet mean . in turn , the hamlet means are given a spatial structure , with closer hamlets being more highly correlated . specifically , hamlet i adds a ' hamlet effect ' ui to the logarithm of the mean density . when exponentiated , these are similar to standardized mortality ratios ( smrs ) although relate to parasite densities rather than death rates , so can be called standardized parasite density ratios . these age- and sex - adjusted hamlet effect uil have a covariance matrix ( 1/)exp(-dil/ ) , where dil is the distance between hamlet i and l. the parameter measures the scale of spatial correlation . more specifically , loge2 is the distance over which the correlation reduces by half , which we call the ' half - distance ' . the process can also be thought of a smoothing process of the raw hamlet means , adjusting for age and sex , and with a large spatial scale ( ) corresponding to a greater degree of smoothing . the model was fitted by programs written in the c and fortran languages , and checked in terms of ability to represent the spatial variability , and robustness to distributional assumptions . at the individual level , the mean pre - treatment microfilaraemia density ( including zeros ) increased with age , till reaching 1591 mf / ml in the 4049 year age group , then flattening out . the mean p. falciparum density was 18 asexuals per 200 white cells in those aged 510 years , decreasing to below 2 for ages over 30 years . at the hamlet level , the median of the crude hamlet - specific pre - treatment mean microfilarial densities was 552 mf / ml , range 04625 . for p. falciparum , the median was 2.2 asexual parasites per 200 white cells , range 0113 . the figure shows the spatial variation in the pre - treatment density of both parasites in this area , estimated from the model , taking into account age and sex effects , and spatial correlation . w. bancrofti had an estimated half - distance of 1.7 km ( = 2.41 , = 1.79 ) . p. falciparum showed virtually no spatial correlation , the half - distance being just 14 m ( = 0.0208 , = 1.13 ) , around the resolution limit of the gps . spatial variation of a ) w. bancrofti and b ) p. falciparum in parts of urim and urat census districts , east sepik province . the scale is in kilometres with an arbitrary origin near the centre of the study area ( 142.7e , 3.6s ) . each hexagon represents one hamlet , with the shading showing the quartile of the standardized parasite density ratio . for w. bancrofti , the 0 , 25 , 50 , 75 and 100th percentiles are 0.27 , 0.56 , 1.02 , 1.71 and 4.3 respectively . for p. falciparum the curve plotted against the vertical axis shows the rate at which correlation in mean parasite density decays with distance . the solid lines in the body of the map show unpaved roads , and the dashed line indicates the division of villages between the two census districts . one year after the first round of mass treatment with anti - filarial drugs ( coverage 88% ) , all 14 randomized clusters showed a reduction in williams mean w. bancrofti density , ranging from 47 to 96% , mean 80% . all 14 clusters showed an increase in williams mean p. falciparum , the increases ranging from 2 to 255% , mean 91% . however , although dec+ivermectin was more effective against w. bancrofti , no tendency was seen for those clusters to have larger increases in p. falciparum : in 3 of the 7 pairs the dec+ivermectin cluster had the larger increase , with 4 having the opposite tendency . to further investigate the possibility that this increase was due to the treatment , the results of the spatial models were put into a hamlet - level analysis : an ' ecological ' analysis in epidemiological terms . the difference in the post- and pre - treatment hamlet effects was calculated for both filariasis and malaria , and a linear relation tested using the pearson correlation coefficient . there was negligible correlation between the changes in the densities of the two infections ( r = 0.026 , p = 0.75 ) . the world health organization methodology of ragfil ( rapid assessment of the geographical distribution of bancroftian filariasis ) is based on a 50 50 km grid . gyapong et al . have compared this to a finer 25 km grid in ghana , with both leading to operationally similar conclusions . when extended to three other countries of west africa , the method showed filariasis to have an unexpectedly wide geographical distribution . the current results suggest that , at the opposite end of the spatial scale , it may be possible for foci to persist within the interstices of a 50 50 km grid , or even a 25 25 km one ; a conclusion similar to that reached by srividya et al . in india . however , the overall importance of any such effects will also depend on the relative magnitudes of variation at different scales , which we are unable to measure beyond the extent of our current study area . the need for accurate geographical monitoring may increase if the current elimination campaign reduces filariasis over a wide scale and proceeds from an ' attack ' to a ' consolidation ' phase ( to borrow malaria eradication terminology ) . for example , thompson et al . , found the risk of malaria varying by a factor of 6 over 500 m . however , the scale of variation found in the current study was still smaller than expected , with even the closest hamlets showing little correlation . the much smaller scale of variation of malaria is probably related to its rapid variation over time . by comparison , the risk of acquiring w. bancrofti infection per mosquito bite seems to be much smaller , but infections can last much longer . a single cross - sectional survey therefore reflects a longer - term aggregate of filariasis exposure history . our estimation of the hamlet effects can be seen as a smoothing method , in which the degree of smoothing is determined by the data . in this example , the west - east trend in filariasis density was not easily discernible in the raw data , while the low spatial correlation of malaria meant that the smoothed map is similar to the crude one . any pattern presumably reflects spatial variation in factors which affect the parasite , vector or host , but which are not included in the model . in the current study , such factors are likely to include those related to vector density , such as distance to breeding sites , but this information is not available for the whole study area , and the lack of pattern in malaria infection suggests that other factors must also be involved . we view the technique as potentially useful in identifying such factors , as well as identifying ' hot spots ' of infection . our method takes account of the extreme skewness shown by most parasite distributions , which can cause problems even at the exploratory stage of analysis . for example , we found that using the common log(x+1 ) transformation to plot the hamlet ' geometric means ' induced a spurious spatial correlation in malaria infection . excess mosquito mortality caused by w. bancrofti would make it feasible for filariasis control to enhance malaria transmission . an ' ecological ' analysis did not show such an effect in this study , but monitoring should continue in those areas where anopheles are vectors of both infections . for the elimination of filariasis , mapping at small as well as large scales will be necessary , including urban areas , especially as efforts proceed beyond the ' attack ' phase . dec diethylcarbamazine gps global positioning system ragfil rapid assessment of the geographical distribution of bancroftian filariasis smr standardized mortality ratio the work originated in a drug trial of which james kazura and michael alpers were the co - principal investigators , and which was led in the field by phil hyun and zachary dimber . neal alexander worked on the drug trial and , for this paper , made the gps readings and wrote the first draft . moses bockarie also contributed to the trial , including ensuring that the blood slides were read . the spatial model was initially developed by neal alexander under the supervision of bryan grenfell . the model was finalized by neal alexander , rana moyeed and julian stander , and fitted by programs written by rana moyeed and julian stander . the drug trial was supported financially by the world health organization ( grant number tdr 910466 ) and the government of papua new guinea . julian stander was partially supported by the european union tmr network erb - fmrx - ct96 - 0095 . bryan grenfell was supported by the wellcome trust and the biotechnology and biological sciences research council .

the spatial variation of wuchereria bancrofti and plasmodium falciparum infection densities was measured in a rural area of papua new guinea where they share anopheline vectors . the spatial correlation of w. bancrofti was found to reduce by half over an estimated distance of 1.7 km , much smaller than the 50 km grid used by the world health organization rapid mapping method . for p. falciparum , negligible spatial correlation was found . after mass treatment with anti - filarial drugs , there was negligible correlation between the changes in the densities of the two parasites .

cutaneous paraneoplastic syndromes include acanthosis nigricans , the sign of leser - trlat , eruptive acrochordons , acquired ichthyosis , erythroderma , palmoplantar hyperkeratosis , acquired hypertrichosis lanuginosa , erythema gyratum repens , necrolytic migratory erythema , bazex 's syndrome and dermatomyositis . the presence of either syndrome in patients warrants evaluation for a possible underlying malignancy . here we report the case of a 79-year - old man , who developed numerous several centimeter - large seborrheic keratoses on his chest and back within the time period of one year . workup led to the diagnosis of colonic adenocarcinoma , underscoring the paraneoplastic etiology of the seborrheic keratoses in this patient . a 79-year - old man with a previous diagnosis of chronic lymphocytic leukemia was seen for preoperative evaluation prior to elective right peripatellar bursectomy after having failed antibiotic treatment . on physical examination numerous seborrheic keratoses in a christmas tree pattern were noted on his chest and back ( fig . the patient reported that the lesions had appeared and advanced within the past twelve months on his trunk . he was seen by a dermatologist , who suggested performing endoscopies of the upper and lower gastrointestinal tract . the patient had not noted clinical symptoms otherwise suggestive of colon cancer , such as unintentional weight loss or recent change of bowel habits . the clinical presentation of the seborrheic keratoses in this patient was found to be consistent with the sign of leser - trlat . leser - trlat is a rare dermatologic finding named after two surgeons , the german edmund leser ( 18281916 ) and the french ulysee trlat ( 18271890 ) . however , the first descriptions of patients with characteristic signs of leser - trlat were published in 1900 and 1901 by the german dermatologist eugen hollnder . the leser - trlat sign is characterized by the sudden onset of multiple seborrheic keratoses or an unusually rapid increase in size and number of preexisting seborrheic keratoses , occasionally on an inflammatory base . it is commonly associated with malignancies , primarily gastrointestinal adenocarcinomas [ 5 , 6 ] , but also squamous cell carcinomas , leukemias and lymphomas . although patients with nonmalignant conditions , such as pregnancy , hiv infection or after having received heart transplantation , can also develop seborrheic keratoses of florid eruption , the term leser - trlat usually implies paraneoplasia . the significance of this sign has been debated in the medical literature , as leser - trlat is observed primarily in elderly individuals , who are statistically at higher risk for developing both seborrheic keratoses as well as various malignancies . therefore , accurate diagnosis is linked to the rapidity of onset of seborrheic keratoses , and to the growth behavior of previously noted seborrheic keratoses . only rarely has leser - trlat been reported in younger patients . the seborrheic keratoses seen in leser - trlat differ neither morphologically nor histologically from commonly seen seborrheic keratoses . they are found predominantly on back and chest of patients , and there is no predilection for patients gender or ethnic / ancestral background . the most prevalent clinical symptom is pruritus , seen in 43% of malignant cases [ 12 , 13 ] . in approximately 20% of cases acanthosis nigricans is also present , either at the time of cancer diagnosis or it develops subsequently . while the pathogenesis of this condition is unclear and remains to be elucidated , due to the proliferative nature of cutaneous paraneoplasias , a possible pathogenic role of epidermal growth factor and alpha - transforming growth factor in the development of the seborrheic keratoses associated with malignancies has been hypothesized and reported . on rare occasions , skin manifestations similar to the leser - trlat sign can be mimicked by malignant melanoma , thus justifying excision biopsies and histologic examinations of suspicious lesions in distinct cases . florid eruption or abnormally fast growth of seborrheic keratoses especially in elderly patients should always raise the suspicion for an underlying malignant disease , in particular for gastrointestinal adenocarcinomas . performing an endoscopic evaluation of the gastrointestinal tract of affected patients

we report the case of a 79-year - old caucasian man , who developed numerous pruritic seborrheic keratoses on his chest and back within one year . an underlying malignant disease was suspected . upper and lower endoscopies were performed and the patient was diagnosed with adenocarcinoma of the ascending colon . we discuss the clinical significance of his cutaneous symptoms / signs , and review the medical literature on the paraneoplastic sign of leser - trlat .

misdiagnosis of bipolar disorder is a potentially serious problem for patients , which sometimes leads to inappropriate treatment.1 however , it is not unusual for bipolar disorder to be misdiagnosed as a major depressive disorder.2 previous studies have shown that the proportion of cases of bipolar disorder misdiagnosed as a major depressive disorder is 20.8%40%.24 nevertheless , there are few biomarkers for accurate diagnosis . if patients become depressive for the first time and have never experienced a manic episode , it is difficult to determine whether that depressive episode is unipolar or bipolar depression , and the risk of a manic switch is unknown . near - infrared spectroscopy ( nirs ) is a noninvasive and useful method that uses near - infrared light to measure hemoglobin concentration changes in the cortical surface area . although changes in the nirs signals measured on the forehead during the word fluency task may be partially associated with changes in skin blood flow,5 the changes in oxygenated hemoglobin ( [ oxyhb ] ) are associated with changes in the regional cerebral blood volume . nirs enables the assessment of brain function , and recent studies have shown that the frontal hemodynamic patterns detected by nirs can be a biomarker for the diagnosis of major psychiatric disorders.6,7 in the present case , nirs during the word fluency task was measured during the clinical course of bipolar disorder . in brief , [ oxyhb ] and deoxygenated hemoglobin ( [ deoxyhb ] ) were measured with a 52-channel nirs machine ( hitachi etg-4000 ; hitachi medical corporation , tokyo , japan ) at two wavelengths of near - infrared light ( 695 and 830 nm ) , the absorption of which was measured , and [ oxyhb ] and [ deoxyhb ] were calculated as previously described.8 the distance between pairs of source - detector probes was set at 3.0 cm and each measured area between pairs of source detector probes was defined as a channel . the probes of the nirs machine were fixed with 3 11 thermoplastic shells , with the lowest probes located along the fp1-fp2 line according to the international 1020 system used in electroencephalography . we used the word fluency task because it is easy to understand and execute , and it is also an executive task that produces distinct differences in performance and neuroimaging data among each diagnostic group of psychiatric disorders.7 additionally , plasma levels of homovanillic acid ( hva ) , a dopamine metabolite , and 3-methoxy-4hydroxyphenylglycol ( mhpg ) , a noradrenaline metabolite , were measured longitudinally using high performance liquid chromatography . in our hospital , we measured both plasma levels of monoamine metabolites ( every 3 weeks in principle ) and nirs ( before and after the treatment ) in psychiatric inpatients with mood disorders to investigate the association between plasma monoamine metabolites and nirs signals . this protocol was approved by the ethics committee of fukushima medical university , and the patient consented to participate after having been informed of the purpose of the study . the patient was a 22-year - old man who had no history of psychiatric illness . he was admitted to our hospital due to major depression that was diagnosed according to the diagnostic and statistical manual for mental disorders , fourth edition , with moderate sadness , agitation , retardation , and difficulty in concentrating . we treated the patient with paroxetine and lorazepam for about 4 weeks , but treatment was not successful . on day 4 , his montgomery sberg depression rating scale ( madrs ) score was 44 , and his plasma levels of hva and mhpg were 4.6 ng / ml and 1.9 ng / ml , respectively . figure 2 shows the waveform of [ oxyhb ] during the cognitive activation of the word fluency task . nirs signal changes were measured during a 10 second pretask baseline period , a 60 second task period , and a 55 second posttask baseline period . the initial syllables assigned were changed every 20 seconds ( /a/ , /ka/ , and /sa/ , respectively ) during the 60 second task period . during the task period , the patient was instructed to generate as many japanese words beginning with the designated syllable as possible . in the pretask and the posttask baseline periods , the patient was instructed to repeat a train of syllables ( /a/ , /i/ , /u/ , /e/ , and /o/ ) . he sat on a chair in a room with daylight with his eyes open throughout the measurements . we focused on increases in [ oxyhb ] , because this appears to reflect task - related cortical activation more directly than decreases in [ deoxyhb].7 we defined the patterns of nirs waveforms using the grand average waveforms in the frontal region ( ch 2528 , ch 3638 , and ch 4649 ; figure 3 ) and two simple visual indices,7 integral value , and centroid value . the integral value describes the size of the hemodynamic response during the 60 second activation task period , whereas the centroid value serves as an index of time course changes throughout the task , with periods representing the timing of the hemodynamic response.7 a recent study reported that the optimal threshold of the centroid value of the frontal region between major depressive disorder and two other disorders ( schizophrenia and bipolar disorder ) is 54 seconds ( major depressive disorder < other 2 disorders).7 on day 4 , the centroid value of the grand average in the central region was 68.6 seconds ( figure 2 ) , and the nirs waveforms showed an [ oxyhb ] reincrease in the posttask period ( ch 34 , 35 , 36 , 39 , 45 , 46 , 47 , and 49 ; figure 2 ) , which is characteristic of schizophrenia.6,7,911 on day 25 , his madrs score was 40 , his plasma hva level was markedly higher at 49.3 ng / ml , and his plasma mhpg level was 1.6 ng / ml . on day 27 , he was voluntarily discharged from the hospital , but was still in a depressive state . on day 30 , 3 days after leaving the hospital , he became manic and was readmitted to our hospital . he was in a state of psychotic mania with elevated mood , grandiosity , aggression , auditory hallucination , and thought broadcast , with a young mania rating scale ( ymrs ) score of 48 . we subsequently treated him with lithium , risperidone , and zotepine for approximately 3 weeks , and his manic state improved . on day 46 , his ymrs score was 29 , and plasma levels of hva and mhpg were 17 ng / ml and 1.3 ng / ml , respectively . however , he refused drugs because of extrapyramidal symptoms and became manic with psychotic symptoms again . therefore , we tried a combination of lithium , olanzapine , and zotepine , and the treatment was successful . on day 77 , the nirs waveforms turned to a negative pattern ( figure 2 ) , which was defined by an integral value of the grand average in the central region < 0 , whereas there were [ oxyhb ] reincreases in the posttask period ( ch 33 , 41 , 42 , 43 , 44 , 51 , and 52 ) . on day 99 , his ymrs score decreased to 3 , and his plasma levels of hva and mhpg were 8.7 ng / ml and 1.9 ng / ml , respectively . nine months later , he was off medication , became manic again , and was admitted to another psychiatric hospital . to the best of our knowledge , this is the first case report to measure both nirs and plasma levels of monoamine metabolites in a patient with bipolar disorder , although the clinical course in this patient was not usual as the mania occurred within the first weeks of the initiation of serotonin selective reuptake inhibitor ( ssri ) treatment . in this case , it was difficult to diagnose bipolar depression from only clinical symptoms at his first admission . we could not predict the subsequent manic switch with psychotic features , which was likely caused by paroxetine . however , the results of nirs on day 4 showed a pattern of schizophrenia , characterized by a smaller [ oxyhb ] increase during the first half of the task and an [ oxyhb ] reincrease in the posttask period,4,911 but not a unipolar depression pattern , which is characterized by only a smaller [ oxyhb ] increase during the first half of the period.4,9,12,13 care must be taken to interpret these findings as patterns of diseases because of the small number of studies . an [ oxyhb ] reincrease in the posttask period is considered as inefficient activation of the prefrontal cortex,4,9,11 which is one of the quantitative abnormalities in schizophrenia.14 these results may have predicted a possible risk of a manic switch in this patient . a recent study7 reported that the frontal hemodynamic patterns detected by nirs accurately distinguished between patients with major depressive disorder and those with bipolar disorder or schizophrenia with depressive symptoms . although the clinical status of bipolar depression may be different from that of unipolar depression,1 it is not easy to clearly distinguish without a previous manic episode . in fact , most bipolar disorder patients with depressive symptoms are initially diagnosed as having major depression.2 because there are few biomarkers for diagnosis , nirs findings may help for distinguishing unipolar and bipolar disorders . however , nirs signals changed after treatment with antipsychotics and lithium in this patient . although it is believed that nirs waveforms are a possible trait marker , nirs signals may change with the state or the medication . interestingly , nirs findings in this case showed a pattern of schizophrenia , not a pattern of bipolar disorder , which is characterized by a smaller [ oxyhb ] increase during the early period , and larger [ oxyhb ] increase during the late period of this task.15 this result is consistent with a manic episode in this case that included psychotic symptoms such as hallucination and thought broadcast . furthermore , 5 days before the manic switch , the patient s plasma hva level was almost ten times higher than just after admission . because the hva level change occurred in tandem with the manic symptoms during the clinical course , it is estimated that the manic episode in this case was associated with dopaminergic function . plasma hva levels have been considered as a possible indicator in the treatment of schizophrenia16,17 and bipolar disorder.18,19 furthermore , because ssris act on dopaminergic and serotonergic neural systems,20 the increase in the plasma hva level in this patient may have been induced by paroxetine . a previous study reported that psychosis or mania induced by ssris showed a pattern of increased plasma hva levels.21 this is consistent with our findings of the changes in plasma hva levels in this patient . taken together , the nirs findings in this patient may be based on dopaminergic dysfunction . however , the changes in the nirs may not be directly associated with the changes in plasma hva levels , because nirs findings are based on frontal brain functions , whereas plasma hva levels are related to psychotic symptoms,22 which seem to be a reflection of the mesolimbic dopamine system . in this case , nirs findings in a depressive state may predict the possible risk for a manic switch . longitudinal monitoring of plasma hva levels may be useful in the treatment of bipolar disorder , in particular in patients with psychotic symptoms like this case .

misdiagnosis of bipolar disorder is a serious , but not unusual problem for patients . nevertheless , there are few biomarkers for distinguishing unipolar and bipolar disorder . near - infrared spectroscopy ( nirs ) is a noninvasive and useful method for the measurement of hemoglobin concentration changes in the cortical surface area , which enables the assessment of brain function . we measured nirs and plasma monoamine metabolite levels in a patient with bipolar disorder . a 22-year - old man was admitted due to major depression . at admission , nirs findings showed oxygenated hemoglobin reincrease in the posttask period , which is characteristic of schizophrenia . after treatment with paroxetine , he became manic with psychotic symptoms . his plasma level of homovanillic acid just before the manic switch was ten times higher than that just after paroxetine initiation . treatment with lithium and antipsychotics was successful , and plasma homovanillic acid decreased after treatment . in this case , the nirs findings may predict a possible risk of a manic switch , which is likely induced by paroxetine . nirs may be able to help distinguish unipolar and bipolar disorder in clinical settings .

malakoplakia is an uncommon but distinctive type of chronic granulomatous inflammation that is characterized histologically by the presence of sheets of histiocytes with granular cytoplasm ( von hansemann cells ) admixed with intracellular and extracellular basophilic laminated inclusions ( michaelis - gutmann bodies ) . the present case , however , is the first case of epididymal malacoplakia without concurrent involvement of the testis . although the exact etiology of malakoplakia remains poorly understood , it is commonly associated with microbial infections and states of diminished immune response . here we report an unusual case of malakoplakia that involved the epididymis in a 61-year - old man with a scrotal mass . a 61-year - old man presented with a painful mass of his left epididymis for several months . ultrasonography of the left epididymis revealed a mass lesion of mixed echotexture in the epididymal tail ( fig . histopathology showed an epididymal mass comprising sheets of histiocytes with granular eosinophilic cytoplasm ( fig . many of the histiocytes contained small round to oval targetoid structures that were morphologically consistent with michaelis - gutmann bodies . the patient 's postoperative recovery was uneventful and the surgical outcome has been satisfactory for 8 months . malakoplakia , derived from the greek adjective malakos ( soft ) and plaka ( plaque ) , was first described in 1902 by michaelis and gutmann and was clearly explained by mcclue in his review . epididymal malakoplakia was first described in 1968 by green , and there have been five reports of this condition in korea . malakoplakia , which typically involves the urinary tract , is an uncommon form of chronic inflammation caused by chronic infections and characterized by accumulation of macrophages . it has also been found in various sites such as the gastrointestinal tract , pancreas , liver , lymph nodes , skin , respiratory tract , adrenal gland , vagina , and brain . malacoplakia is characterized histologically by the presence of michaelis - gutmann bodies contained within von hansemann macrophages . special stains such as periodic acid schiff and von kossa for calcium can be particularly helpful in highlighting the michaelis - gutmann bodies when these are obscured within dense lymphohistiocytic infiltrate . the etiology of malakoplakia has not been fully elucidated . coliform bacteria , particularly e. coli , have been isolated from the involved sites of genitourinary malakoplakia in more than two - thirds of patients . another potential contributing factor to the development of malakoplakia is an impaired immune response . in a review by long and althausen , approximately 40% of malakoplakia cases that did not involve the urinary tract were associated with immunosuppression . the ability of phagocytes to completely digest bacteria is impaired in malakoplakia , which is thought to be related to low levels of intracellular cyclic guanosine monophosphate ( cgmp ) and diminished release of b - glucuronidase . this would explain the successful treatment of a case with the cholinergic agonist bethanechol chloride , which acts by increasing the levels of cgmp . the treatment options for malakoplakia include two main approaches : the administration of antibiotics and surgical excision , depending on the site and extent of involvement . antibiotics that can penetrate the cell membrane and concentrate in macrophages are associated with a high cure rate . treatment with trimethoprim - sulfamethoxazole may be helpful because of the ability of trimethoprim to enhance the killing of viable undigested microorganisms inside malakoplakic macrophages . also , because ciprofloxacin penetrates well into macrophages , this drug has been found to be particularly useful in patients with advanced malakoplakia . in addition to these agents , bethanechol is believed to enhance phagocytic bactericidal activity by increasing cgmp levels . if conservative treatment fails to control and diminish the malakoplakia , which is the most likely situation according to most investigators , surgical resection is needed . close follow - up of these patients is needed because multiple locations can be affected . in our case , considering the involvement of the epididymis in our patient , who had no fever and negative results on urinalysis and urine culture , excision of the epididymal mass was the best option without antibiotic therapy , and this treatment led to a satisfactory outcome .

malacoplakia is a chronic inflammatory disease . the disease mainly affects the urinary bladder , although involvement of extravesical sites is increasingly being documented . most frequently involved is the urinary tract , particularly the urinary bladder , although the testis , epididymis , lungs , bone , colon , prostate , female genital organs , and retroperitoneum can also be involved . here we report the case of a 61-year - old man with a scrotal mass with histology that was specific for malacoplakia of the epididymis . the histologic workup demonstrated extensive involvement of the epididymis by diffuse infiltrates of large histiocytes with eosinophilic granular cytoplasm and numerous michaelis - gutmann bodies , which were diagnostic of malakoplakia . this is the first case of epididymal malacoplakia in our country and the first case of epididymal malacoplakia without concurrent involvement of the testis . there have been few reports of this condition worldwide .