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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 . |
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