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in vivo bioluminescence imaging ( bli ) is a technology that is frequently used in the study of animal tumor models . it has been successfully used to follow many different types of tumors , such as prostate , breast , colon , ovarian , and lung cancers [ 28 ] . the in vivo bli method is based on the action of luciferase on luciferin which produces light emission within the xenograft [ 9 , 10 ] . the light - producing reaction requires molecular oxygen and atp for the oxidation of luciferin to oxyluciferin . the light produced is transmitted through tissue and detected by a sensitive charge - coupled device ( ccd ) camera ; the acquired data can be presented as qualitative pseudocolor images or as quantitative photon counts . a significant advantage of in vivo bli is the ability to noninvasively obtain several data points from the same group of animals by repeated monitoring . in addition , the sensitivity of in vivo bli permits the detection of very small tumors or metastases [ 8 , 11 ] . a major concern is that solid tumors frequently outgrow their oxygen supply and can develop central hypoxia . alternatively , tumor hypoxia can develop as a result of treatment . in these settings , oxygen available for the bli reaction could be reduced to limiting levels , which would result in a reduced bli signal ( bls ) and underestimation of the actual tumor size . in the process of developing an in vivo bli - based mouse model of u87 glioma cells for evaluation of radiotherapy , we noted that these solid tumors frequently become transiently or chronically hypoxic and that , in this situation , tumor growth determined by bli may be an underestimate . we therefore present the effect of oxygen , hypoxia , ph , and cellular viability on the bls in this model . the in vitro and in vivo results indicate that the development of hypoxia or ph changes could impact the use of bli in quantitative studies of tumor growth and treatment response . u87 human malignant glioma cells were obtained from atcc ( manassas , va ) and were transfected with the cdna encoding firefly luciferase to produce u87-luc cells . these were maintained in dmem medium ( invitrogen , grand island , ny ) supplemented with 10% fetal bovine serum ( jrh biosciences , lenexa , ks ) and 1% penicillin / streptomycin ( invitrogen ) . five million u87-luc cells in 100 l pbs were injected subcutaneously in the dorsal side of the upper hind limb of female mice using insulin syringe . xenografts were allowed to grow for 10 days when the initial measurement was made with calipers and with bli . tumor volume measurements were calculated using the formula for an oblong sphere : volume = ( width length ) . the mice were handled in accordance with iacuc guidelines ; experiments were approved by the institutional committee for animal research . bli was performed using the ivis-200 imaging system ( xenogen corporation , berkeley , ca ) . mice were anesthetized by inhalation of 2% isoflurane ( abbott laboratories , chicago , il ) . each set of mice were positioned in the special imaging chamber and injected subcutaneously ( dorsal midline ) with 150 mg / kg d - luciferin ( xenogen ; perkinelmer , waltham , ma ) in approximately 200 l . the luminescent camera was set to 1 min exposure , medium binning , f/1 , blocked excitation filter , and open emission filter . the photographic camera was set to 2 s exposure , medium binning , and f/8 . the field of view was set at 22 cm distance to image up to 5 mice simultaneously or 412.9 cm to view plates and tubes . images were acquired in sequence at 1 min intervals ( 60 s exposure , no time delay ) for 30 min . the intensity of bls in the luminescent area of the tumor , which is also described as the region of interest ( roi ) , bls was plotted as photon / sec / m against time as an indicator of tumor burden . a nude mouse with bilateral thigh u87-luc xenografts underwent bli as described above . while under the same general anesthesia , a rubber band was firmly tightened around the right thigh proximal to the tumor . 2 min after application of the band , bls was collected for 1 min . the band was then removed ; 2 min later , bls was collected again for 1 min . a nude mouse with right thigh u87-luc xenografts was kept in a hypoxia chamber ( bactrox , shel lab , sheldon manufacturing inc . , the mouse was then put into a sealed transparent bag and transferred to the imaging chamber ; bli was performed as described above . bli was performed before and after 1 ml air was injected into the tumor using an insulin syringe . mansfield , oh ) , which consumes oxygen directly , was used to induce acute hypoxia in the tissue culture media ( final concentration 50250 mu / ml ) . figure 1 compares the growth of u87-luc flank xenografts when measured by calipers ( figure 1(a ) ) or bli ( figure 1(b ) ) and allowed to grow to a large size . the two evaluations of tumor volume were similar through day 17 , but subsequently a drastic reduction in bls was noted while volume calculated using caliper measurements continued to increase . as shown in figure 1(c ) , the fold change in bls on day 21 relative to day 17 was dependent on tumor size . specifically , tumors that had the weakest bls on day 17 ( lower tertile ) demonstrated , on average , a 38.7% increase in bls on day 21 . conversely , tumors with the most intense bls on day 17 ( upper tertile ) showed an average of 55.8% reduction in bls on day 21 . regardless of tumor size on day 21 , maximal bls intensity always occurred at the center of the tumor . additionally , some tumors were removed and sectioned immediately after euthanasia ; these did not show any gross evidence of central necrosis . these findings suggest that the reduction in bls on day 21 was not a result of central tumor necrosis . thus , the correlation of change in bls with tumor size suggests that the bls is impacted by physiologic tumor changes that correlate with increasing size , such as hypoxia and/or ph change . in order to investigate this phenomenon , we performed a series of studies using bli on cultured cells in vitro . it is well established that bls intensity correlates with cell number . to demonstrate this for u87-luc cells , aliquots pelleted in conical tubes were assessed by bli ( figure 2(a ) ) . intensity of the bls correlated with total cell number ( figure 2(b ) ) . to test the effect of viability on signal generation , equal volumes of either healthy , viable or sonicated cells sonicated cells showed no light emission indicating that only intact cells can produce bls ( figure 2(c ) ) . in order to investigate the effect of hypoxia on bls from cultured cells , oxyrase is a mixture of membrane monooxygenases and dioxygenases that removes dissolved oxygen rapidly from aqueous and semisolid environments [ 15 , 16 ] . u87-luc cell pellets and monolayers were exposed to oxyrase for 5 min to induce acute hypoxia . this reduction was reversed by reoxygenation ( figures 3(b ) and 3(c ) ) , which was performed by bubbling air through the media . to evaluate the effect of chronic hypoxia on bli in vitro , u87-luc cells were grown in either a normoxic or hypoxic environment for 5 days ( figure 4(a ) ) and bli was performed at 1 , 3 , and 5 days . cells grown in hypoxia showed statistically significant reduction in bls compared to cells grown in normoxia ( figure 4(b ) ) . while bls was substantially reduced after 3 and 5 d in hypoxia , cell number also decreased ; however , the reduction in bls was much greater than the decrease in cell number , 25-fold versus 5-fold , respectively , suggesting a direct effect of hypoxia on the bls ( figure 4(c ) ) . at 5 min after reoxygenation , intensity of the bls had quadrupled ( p < 0.05 ) and it continued to dramatically increase for 24 h after reoxygenation ( figure 4(d ) ) . the rapid early increase in bls with re - oxygenation is not attributable to proliferation and represents the reversible impact of hypoxia on the luciferase reaction resulting in reduced light emission . thus , the cell number is underestimated by the light emission under hypoxic conditions . at 24 h after re - oxygenation , further recovery of the bls was noted and is likely attributable to both increased oxygen availability leading to correction of the bls and also to proliferation in response to normoxia . hypoxia and acidosis may coexist in solid tumors , and many cellular processes are ph dependent , including enzymatic activity and cell proliferation . in general , tumors are more acidic than normal tissues with median ph values of about 7.0 in tumors and 7.5 in normal tissues [ 1820 ] , and considerable variation in tissue ph at different regions of the same tumor has been observed . bls was maximal between ph 6 and ph 8 , with a gradual decrease in bls as the ph increased across this range . in order to demonstrate the effect of acute ischemia on in vivo bli , a tourniquet was applied on the leg of a nude mouse proximal to an established u87-luc thigh xenograft . bli performed 2 min after placement of the tourniquet demonstrated substantially reduced bls on the side of the tourniquet with stable bls on the contralateral side . within 2 min after releasing the tourniquet and restoring blood flow to the tumor , a strong bls was present ; the bls was greater after reperfusion than prior to tourniquet placement ( figure 6(a ) ) . thus , acute ischemia results in underestimation of tumor size by bli in an in vivo thigh xenograft tumor model . while the decreased blood flow following tourniquet placement undoubtedly leads to reduced substrate delivery to the tumor , adequate substrate was present to produce a strong bls immediately prior to tourniquet placement ( figure 6(a ) ) . thus , the dramatic reduction in bls following tourniquet placement is predominantly due to reduced oxygen tension in the tumor . this concept is supported by the finding that augmentation of tumor blood flow can enhance the bls . figure 6(b ) shows the bls over time of u87-luc thigh xenografts . at 30 min with declining bls , the mice were given an intraperitoneal injection of nicotinamide , a peripheral vasodilator that increases tissue perfusion . immediately after injection , bls increased in all tumors , indicating that blood flow augmentation increases bls . to further evaluate the significance of substrate delivery versus oxygenation , bli was performed in a systemically hypoxic mouse , a dead mouse , and a dead mouse after intratumoral air injection . after 10 min in the hypoxia chamber , the bls was completely abolished ( figure 7(b ) ) . when luciferin was injected prior to termination , the postmortem mice exhibited no bls ( figure 7(c ) ) . however , direct injection of air into the tumor resulted in a strong bls similar to the premortem tumor . this demonstrates that , despite the lack of active perfusion and continuous substrate delivery that occurs in the post - mortem state , a bls could still be generated by manual oxygenation . this suggests that a decrease in the bls of hypoperfused tumors is not solely due to reduced substrate availability and that hypoxia plays an important role in reducing the bls . based on the previous data , tumors or treatments that involve hypoxia , hypoperfusion , or substantial ph changes may yield unreliable data when assessed by bli it is assumed that the bls will increase as the tumor volume increases , but this relationship may not hold in the setting of hypoxia . in certain cases , for example , when solid tumors necrose centrally in response to therapy , the bli signal will fall due to the hypoxia and necrosis , consistent with the death of a portion of the tumor despite the overall external tumor size continuing to enlarge as measured by calipers . in these cases , bli may be more representative of treatment effect and caliper measurements may be misleading . unfortunately , tumors that are simply hypoxic may also appear smaller by bli , despite being adapted to grow at low oxygen tension . tissue necrosis and death also affect the optical properties of tissues and thus affect scattering and absorption of light , which may additionally impact the interpretation of bli . the use of bli in xenografts provides a convenient method for non - invasive monitoring of in vivo tumors ; this is particularly useful when tumors are not accessible to calipers . many solid tumors undergo a certain degree of hypoxia and ph changes with growth and/or treatment , which can significantly reduce the bls . thus , caution should be used in interpretation of bli results when tumor hypoxia is present .

bioluminescence imaging ( bli ) is a relatively new noninvasive technology used for quantitative assessment of tumor growth and therapeutic effect in living animal models . bli involves the generation of light by luciferase - expressing cells following administration of the substrate luciferin in the presence of oxygen and atp . in the present study , the effects of hypoxia , hypoperfusion , and ph on bli signal ( bls ) intensity were evaluated in vitro using cultured cells and in vivo using a xenograft model in nude mice . the intensity of the bls was significantly reduced in the presence of acute and chronic hypoxia . changes in cell density , viability , and ph also affected bls . although bli is a convenient non - invasive tool for tumor assessment , these factors should be considered when interpreting bls intensity , especially in solid tumors that could be hypoxic due to rapid growth , inadequate blood supply , and/or treatment .

the most commonly administered psychometric screening assessment for cognitive functioning is the mini - mental state examination ( mmse ) . a large amount of medical literature has been published on the relative sensitivity of mmse in identifying overt dementia . however , its utility has been seen to have decreased when patients with mild cognitive decline are assessed . importantly , use of mmse has been constrained by demographic variables , with scores decreasing with advanced age and lower levels of education . therefore , routine screening of high - risk elderly people for early cognitive impairment using mmse may be , therefore , constrained . however , identifying cognitive dysfunction in individuals at risk for dementia , as early as possible , is desirable so that appropriate treatment strategies can be implemented earlier in the course of the disease . the fact that 10 warning signs are elicited from attendants / caregivers eliminates the constraints of education . the key , however , will lie in its ( 10 warning sign ) ability to screen individuals with cognitive impairment . we conducted a post - hoc analysis of the data from a study conducted by us on prevalence of dementia in selected geographical areas of himachal pradesh , wherein we had used both 10 warning signs and hindi mental state examination ( hmse ) and its bharmouri mental state examination ( bmse ) ; modifications of mmse in the first phase of a two - phase study to estimate the prevalence of dementia . the purpose of this analysis was to explore the feasibility of using 10 warning signs as a questionnaire to screen individuals with cognitive impairment largely illiterate the elderly indian population . for this purpose , a comparative analysis between hmse / bmse and 10 warning signs was used . the data used for analysis in the present study were obtained from a study conducted on the elderly population ( 60 years and above ) from selected geographical areas ( migrant , urban , rural , and tribal ) of himachal pradesh state in the north - west india and published elsewhere . a brief description of the source study is given here : this cross - sectional study was conducted in two phases : ( 1 ) a screening phase and ( 2 ) a clinical phase . the screening phase includes details on participant 's age , sex , and educational status . during this process of seeking information on participant 's details , a hindi version of cognitive screen ( hmse ) was used in the urban , rural , and migrant population . for the tribal population , a modified ( bharmouri ) version , referred as bmse of cognitive screen a score below 24 ( out of a possible score of 30 ) on cognitive screen was considered as a suspect case of dementia and was evaluated for clinical diagnosis . the clinical evaluation was carried out by a psychiatrist with the help from an internist and two public health specialists . after clinical , the study participants were classified as normal or demented . for the purpose of this post - hoc analysis , the data of all 2000 participants was analyzed . the analysis focused on a comparative assessment of 10 warning signs and hmse / bmse . the screening phase includes details on participant 's age , sex , and educational status . during this process of seeking information on participant 's details , a hindi version of cognitive screen ( hmse ) was used in the urban , rural , and migrant population . for the tribal population , a modified ( bharmouri ) version , referred as bmse of cognitive screen a score below 24 ( out of a possible score of 30 ) on cognitive screen was considered as a suspect case of dementia and was evaluated for clinical diagnosis . the clinical evaluation was carried out by a psychiatrist with the help from an internist and two public health specialists . after clinical , the study participants were classified as normal or demented . for the purpose of this post - hoc analysis , the data of all 2000 participants was analyzed . the analysis focused on a comparative assessment of 10 warning signs and hmse / bmse . table 1 provides details on the correlation between scores on 10 warning signs screen and scores on hmse / bmse . it is seen from table 1 and figure 1 that there is a clear cut negative correlation between scores on 10 warning signs screen and the scores hmse / bmse scale . as the scores on 10 warning signs screen , the scores on hmse / bmse fall both pointing to identification of the same clinical diagnosis i.e. dementia . the value of pearson correlation coefficient at 2.52 was found to be statistically highly significant [ table 1 ] . a high statistically significant points to a strong association between scores on 10 warning signs screen and the scores on hmse / bmse indicating the utility of 10 warning signs in assessment of cognitive impairment in elderly . correlation of 10 question screening score and hmse / bmse score among 2000 elderly evaluated for cognitive impairment correlation of 10 question screening score and hindi mental state examination / bharmouri mental state examination score among 2000 elderly evaluated for cognitive impairment the current study was conducted with the aim to explore the utility of using 10 warning signs as a screening instrument to identify cognitive impairment in largely illiterate indian population . it has been observed that it may be difficult for elderly illiterate to navigate through various components of the mental state examination . this is not the same with 10 warning sign wherein assessment is dependent on details provided by caregivers who necessarily need not be illiterate or elderly . further in diagnosing mild dementia , reliable information obtained from caregivers about minor cognitive changes in a person suspected of dementia may be more important than quantitative assessment , which can be insensitive to mild impairment . furthermore , the fact that family members are likely to be aware of signs and symptoms of possible dementia that may not be readily apparent to clinical staff . important use of 10 warning signs screen will make assessment of cognitive impairment easier in patients with a comorbid condition like visual or auditory impairment . ten warning signs screen can be an important screening total for assessment of cognitive impairment in the elderly indians .

introduction : routine screening of high - risk elderly people for early cognitive impairment using mini - mental state examination ( mmse ) and its modifications may be constrained by demographic and other variables . warning signs ( as reported by family / caregivers ) may be a useful alternative . the present data analysis was carried out with the aim to identify the role of 10 warning signs screen as an alternative tool for screening for cognitive impairment among elderly.materials and methods : for the purpose of this analysis ( correlation ) , data available with us from a study conducted on the elderly population ( 60 years and above ) from selected geographical areas ( migrant , urban , rural , and tribal ) of himachal pradesh was used.results:a high statistically significant was found between scores on 10 warning signs screen and hindi mental state examination / bharmouri mental state examination ( modifications of mmse).conclusions : ten warning signs screen can be an important screening total for assessment of cognitive impairment in the elderly indians .

a 66-year - old healthy man was referred from a private dental clinic for evaluation of a multilocular radiolucency at the left molar region of the mandible . panoramic radiograph revealed a well - defined multilocular radiolucent area under the mandibular canal at the distal root of the second molar tooth ( fig . the lesion showed three lobulated radiolucencies with radiopaque margins in the region of the submandibular gland fossa . on clinical examination axial cbct images showed a lingual bony defect located at the lingual side of the mandibular canal ( fig . 2 ) . coronal cbct images showed a lobulated bony defect below the mandibular canal ( fig . the maximum mesiodistal length of the defect was 14.16 mm , and the height was 7.38 mm . the maximum buccolingual length of the defect was 4.44 mm , not showing the expansion or thinning of the buccal cortical bone . parasagittal cbct images showed three lobulated radiolucencies with radiopaque margins between the mandibular canal and the inferior border of the mandible ( fig . reformatted cbct images revealed a bony defect extending from the medial surface of the mandible ( fig . developmental salivary gland defect is typically asymptomatic and next to impossible to palpate , and is generally found incidentally during radiographic examination of the area . in a recent review of a large number of cases , males predominated over females at a ratio of 6.1 : 1 , with a peak incidence in the fifth and sixth decades of life.4 many other terms have been used for this defect including lingual salivary gland depression , stafne bone cavity , stafne cyst , static bone cavity , and idiopathic bone cavity.2,5 - 8 on panoramic radiograph , the defect appears as a circular or ovoid , well - defined radiolucency that ranges in diameter from 1 to 3 cm . the margins of the radiolucent defect are well - defined by a dense sclerotic radiopaque margin of variable width , which is usually thicker on the superior aspect . characteristically , it is situated just above or at the inferior border of the mandible , between the area of the first molar and the mandibular angle , and always inferior to the mandibular canal . in this case the defect , however , was located at the characteristic region . in recent years , computed tomography ( ct ) , cbct , and magnetic resonance imaging ( mri ) have been shown to be diagnostically valuable in addition to panoramic radiographs . mri , with its enhanced definition of adjacent soft tissue , may reveal the occurrence of soft tissue extending into the defect.2 advanced radiological assessment using cbct is usually sufficient to achieve a final diagnosis of a developmental salivary gland defect and to avoid surgical treatment , which would be an unnecessary option in the management of a developmental salivary gland defect except for symptomatic or other concomitant pathologies . individual developmental salivary gland defects having been followed for some years with periodic radiographic examinations showed no changes in size or shape of the defects over time . periodic radiographic examination is recommended to document the static nature of the lesion .

developmental salivary gland defect is a bone depression on the lingual surface of the mandible containing salivary gland or fatty soft tissue . the most common location is within the submandibular gland fossa and often close to the inferior border of the mandible . this defect is asymptomatic and generally discovered only incidentally during radiographic examination of the area . this defect also appears as a well - defined , corticated , unilocular radiolucency below the mandibular canal . although it is not uncommon for this defect to appear as a round or ovoid radiolucency , multilocular radiolucency of these defects is relatively rare . this report presents a case of a developmental salivary gland defect with multilocular radiolucency in a male patient .

in recent years , one - dimensional ( 1d ) nanostructured materials have attracted great interest due to their superior performance in applications such as electronics , optoelectronics , energy storage and conversion , sensing and drug delivery . up to now , lots of approaches have been reported to synthesize 1d nanostructures , such as laser ablation , chemical vapor deposition ( cvd ) , thermal evaporation , hydrothermal / solvethermal process , chemical reaction , template / precursor - directed methods , and so on [ 2 - 9 ] . more recently , current existing 1d nanostructures have been considered as useful precursors to generate other 1d nanostructures that might be difficult to directly synthesize as uniform samples [ 10 - 15 ] . for example , wang and qi reported the synthesis of ag2s , ag2se , and ag nanofibers by using ag2c2o4 as a general precursor , employing both anioic exchange and redox reactions . fe3o4 nanotubes have been prepared by epitaxial coating of fe3o4 layer on mgo nanowires and subsequently wet - chemical etching . single - crystalline znal2o4 spinel nanotubes could be fabricated through a spinel - forming interfacial solid - state reaction of core more recently , we have used carbon nanotubes as templates to synthesize metal oxide and composite nanotubes via layer - by - layer technique . as typical anisotropic magnetic nanomaterials , 1d iron oxide nanostructures are of great interest because of their interesting magnetic properties caused by shape anisotropy [ 16 - 18 ] . however , it is difficult for magnetic iron oxides to form 1d nanostructures due to their spinel crystal . recently , great efforts have been made to synthesize 1d iron oxides nanostructures by means such as oxidation of iron plates , utilization of various templates and surfactant - assisted hydrothermal and solvothermal . however , it remains challenge to selective synthesize 1d iron oxides nanostructures with controllable morphology . herein , as precursors , fec2o42h2o nanowires were synthesized by a simple microemulsion - based method . ultralong and uniform -fe2o3 and fe3o4 nanowires could be selectively fabricated by annealing of fec2o42h2o nanowires under different temperatures and atmospheres . co3o4 nanowires were also prepared to confirm the versatility of the method for metal oxide nanowires . the experiment details were as follows : 2.5 g ctab ( cetyltrimethylammonium bromide ) was dissolved into a mixture of 75 ml of cyclohexane and 2.5 ml of n - pentanol . after 20 min of stirring , 3.75 ml of 0.1 m h2c2o4 aqueous solution was introduced into the above resulting solution , and the mixture was stirred for an additional 25 min . finally , 1.25 ml of 0.1 m feso4 was added to the above microemulsion and stirred for 24 h at room temperature . after the reaction was completed , the resulting products were centrifugalized , washed with deionized water and ethanol to remove the ions possibly remaining in the final product , and finally dried at 80c in air . the obtained powders were annealed under o2 ( 550/700c ) and ar / h2 ( 400c ) , respectively . the obtained samples were characterized by x - ray powder diffraction ( xrd ) using a rigaku d / max - ga x - ray diffractometer with graphite monochromatized cu k radiation ( = 1.54178 ) . the morphology and structure of the samples were examined by field emission scanning electron microscopy ( fesem , hitachi s-4800 ) , transmission electron microscopy ( tem , jem-200 cx , 160 kv ) and high - resolution transmission electron microscopy ( hrtem , jeol jem-2010 ) with an energy - dispersive x - ray spectrometer ( edx ) . the infrared ( ir ) spectra were measured with a nicolet nexus ftir 670 spectrophotometer . figure 1 shows the x - ray diffraction ( xrd ) patterns of the precursors and the subsequent products after annealing processes . it can be seen that all the peaks of the precursors can be assigned to pure ferrous oxalate dehydrate ( fec2o42h2o ) ( jcpds : 72 - 1305 ) . when the precursors were annealed in air at 550/700c , all the diffraction peaks of the products can be readily indexed to the pure rhombohedral phase of -fe2o3 ( jcpds : 33 - 0664 ) . when the precursors were annealed in ar / h2 ( 5% h2 ) at 400c , all the diffraction peaks of the products can be readily indexed to a pure cubic phase of fe3o4 ( jcpds : 65 - 3107 ) . the results of xrd demonstrate that fec2o42h2o can be transformed to -fe2o3 and fe3o4 during the annealing processes under different atmosphere . xrd patterns of as - synthesized products the fec2o42h2o nanowires used as the precursors for the synthesis of -fe2o3 and fe3o4 nanowires were prepared by a simple microemulsion - based method . figure 2 shows the sem and the tem images of the as - synthesized fec2o42h2o nanostructures . as observed , the obtained fec2o42h2o nanostructure exhibits the morphology of the nanowires with the diameter of about 100 nm and the length of tens of micrometers . moreover , the surface of the fec2o42h2o nanowires seems smooth , and no defects can be observed . when the fec2o42h2o nanowires were annealed in air at 550c , porous -fe2o3 nanowires were fabricated . figure 3 shows the sem , tem , and hrtem images of the as - synthesized -fe2o3 nanowires . it can be seen that the as - synthesized -fe2o3 nanowires retain the morphology of the fec2o42h2o nanowires ( fig . however , many nanopores with diameters of about 1030 nm appear because of the release of co2 from fec2o42h2o during the heat treatments , resulting in the porous nanowires ( fig . such the porous nanowires may exhibit superior performance in li - battery and gas sensors because of the large surface area . as can be seen , two nanocrystals connect together with a grain boundary between them . there are two kinds of lattice fringes with lattice spacings of about 0.37 and 0.25 nm , corresponding to the { 1012 } plane and { 1120 } plane of -fe2o3 , respectively , which indicates their polycrystalline nature . figure 4 shows the sem and the tem images of the products when the annealing temperature was raised up to 700c . compared with the products following a 500c annealing process , this sample shows a similar morphology of nanowires but the nanocrystals that composed of nanowires shows better fusion between them due to the higher annealing temperature . figure 5 shows the morphology and the structure characterizations of the products when the fec2o42h2o nanowires were annealed in ar / h2 ( 5% h2 ) at 400c . the sem and the tem images indicate that the as - synthesized products show the morphology of nanowires , which retains the morphology of the precursors ( fig . however , the diameters of the nanocrystals and the nanopores that composed of the nanowires are about 5 and 2 nm ( fig . 5e , 5f ) , respectively , which are smaller than the -fe2o3 nanowires due to the lower annealing temperature . the lattice fringe with a lattice spacing of 0.25 nm corresponds to the { 311 } plane of fe3o4 ( fig . 5f ) . sem images ( a ) , ( b ) and tem images ( c ) , ( d ) of fec2o4 nanowires morphological and structural characterization of fe2o3 nanowires synthesized at 550c : a , b sem images ; c e tem images ; f hrtem images sem images ( a ) , ( b ) and tem images ( c ) , ( d ) of fe2o3 nanowires synthesized at 700c morphological and structural characterization of fe3o4 nanowires : a , b sem images ; c e tem images ; f hrtem images ir analysis was employed to further confirm the transformation from fec2o42h2o nanowires to -fe2o3 and fe3o4 nanowires during the thermal treatments . as can be seen from fig . 6a , the peaks at 3,358 , 1,629 , 1,318 , and 496 cm are attributed to o h , c = o , c o , and fe o functional groups , respectively , indicating the formation of fec2o42h2o . in order to clarify the difference of ir spectra between fe2o3 and fe3o4 , it can be seen that there is only one peak at 574 cm for fe3o4 , while -fe2o3 shows two or three peaks which is related with its structure and size . in addition , -fe2o3 also exhibit three peaks between 500 and 700 cm , which is different from fe3o4 . the ir analysis combined with tem images and xrd pattern can confirm the synthesis of fe3o4 nanowires . ftir spectra of as - synthesized products as a result , ultralong and uniform -fe2o3 and fe3o4 nanowires were selectively synthesized by the annealing of fec2o42h2o nanowires under different temperatures and atmosphere . as can be seen , when two microemulsion solutions containing feso4 and h2c2o4 are mixed , fec2o4 nucleation and irreversible micellar fusion may be coincident . during the nucleation , the surfactant molecules of side surfaces of the cylindrical droplets may adsorb on surface planes of the formed fec2o4 nucleus , which may result in the one - dimensional growth of fec2o4 . finally , -fe2o3 and fe3o4 nanowires can be obtained after the calcinations of fec2o4 nanowires under different conditions . the morphology , the structure , and the phase of as - synthesized products could be determined by the precursors and the annealing conditions . schematic illustrations for lbl synthesis of -fe2o3 and fe3o4 nanowires based on the above - mentioned analysis , the mechanism for the formation of -fe2o3 and fe3o4 nanowires can act as a guideline for the synthesis of the other metal oxide nanowires . it can be seen that porous co3o4 nanowires with diameters of about 200 nm and lengths of several micrometers can be obtained by the calcinations of coc2o4 nanowires , which confirms the versatility of the microemulsion - based method . a sem image of coc2o4 nanowires ; b sem image of co3o4 nanowires ; c tem image of co3o4 nanowires ; d xrd of co3o4 nanowires in summary , we have developed a microemulsion - based method in combination of the calcinations to selectively synthesize -fe2o3 and fe3o4 nanowires with the diameter of about 100 nm and the length of tens of micrometers . the fec2o42h2o nanowires used as the precursors were prepared by a simple microemulsion - based method . -fe2o3 and fe3o4 nanowires can be synthesized by the calcinations of fec2o42h2o nanowires under air and h2/ar at different temperatures , respectively . moreover , it is believed that the approach presented here can be extended to synthesize other 1d metal oxide nanostructures . co3o4 nanowires have been fabricated to confirm the versatility of the method for metal oxide nanowires . 2007aa02z476 ) , nsfc ( no . 50802086 ) , china postdoctoral science foundation funded project ( no . 20090461350 ) . this article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited . this article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited .

hematite ( -fe2o3 ) and magnetite ( fe3o4 ) nanowires with the diameter of about 100 nm and the length of tens of micrometers have been selectively synthesized by a microemulsion - based method in combination of the calcinations under different atmosphere . the effects of the precursors , annealing temperature , and atmosphere on the morphology and the structure of the products have been investigated . moreover , co3o4 nanowires have been fabricated to confirm the versatility of the method for metal oxide nanowires .

mice are naturally nocturnal animals ( mclennan and taylor - jeffs , 2004 ; refinetti , 2004 ) which tend to be active after dark and rest during the day ( arakawa et al . , 2007 ; , 1994 ; panksepp and lahvis , 2007 ; terranova et al . , 1998 ) . the dark and light phases are sometimes referred to as active phase and inactive phase , respectively , reflecting the nocturnal nature of the mouse ( arakawa et al . , 2007 ) . numerous studies have described circadian variations in physiological processes ( arraj and lemmer , 2006 ; castillo et al . , 2005 ; kohsaka et al . , 2007 ; li et al . , 2006 ; refinetti , 2007 ) , circulating hormones ( li et al . , 2006 ; malisch et al . , 2002 ) , wheel running activities ( kopp , 2001 ; kriegsfeld et al . , 2008 ; meng et al . , 2008 ; valentinuzzi et al . , 2000 ) , cognitive performances ( chaudhury and colwell , 2002 ; eckel - mahan et al . , 2008 ; roedel et al . , 2006 ; valentinuzzi et al . , 2004 ) and social behaviors ( arakawa et al . , 2007 ; van loo et al . , 2004 ) in laboratory rats and mice . a recent study by arakawa et al . ( 2007 ) provides a useful description of spontaneous social behaviors of inbred mice in a laboratory environment across the circadian cycle . groups of 3 - 4 c57bl/6j ( b6 ) mice were placed in a semi - natural living environment a large apparatus built to resemble the burrow systems in which small rodent species dwell in the wild . spontaneous social behaviors were recorded in both light and dark phases for 2 weeks and scored from the videotapes afterwards . time sampling results showed that mice exhibit more social approach towards other animals in the dark phase and more huddling during the light hours . this study confirmed that standard laboratory inbred mice , like wild - dwelling mice , prefer to engage in social activities in the dark phase . another important implication from this study is that sociability might be an enduring trait that manifests differently in opposite phases . active approach may be the major social behavior in the dark phase , while inactive huddling predominates as a reflection of sociability in the light phase . although most people are aware of the fact that mice are nocturnal , many researchers conduct behavioral tests in the light phase because of practical difficulties . as such , the current literature on mouse social behaviors consists of studies done in both phases . as shown in table 1 , while dark phase experiments continue to contribute to our current knowledge of mouse social behaviors ( arakawa et al . , 2008a , b ; bluthe et al . , 1993 ; cheh et al . , 2006 ; clipperton et al . , 2008 ; d'amato , 1998 ; daza - losada et al . , 2008 ; gomez et al . , 2008 ; kurian et al . mcnaughton et al . , 2008 ; panksepp and lahvis , 2007 ; panksepp et al . , 2007 ; , 2008b ; torres et al . , 2005 ; yang et al . , 2007b ) , light phase experiments have also been producing remarkable findings on genetic , neuroanatomical , and environmental factors that are important for mouse social behaviors ( babovic et al . , 2008 ; bielsky et al . , 2004 , 2005 ; dluzen and kreutzberg , 1993 ; egashira et al . , 2007 ; ehninger et al . , 2008 ; fairless et al . , 2008 ; ferguson et al . , 2001 ; jamain et al . , 2008 ; koh et al . , 2008 ; lee et al . , 2008 ; long et al . , 2004 ; moretti et al . , 2005 ; moy et al . , 2007 , 2008 ; , 2008 ; refinetti , 2004 ; ryan et al . , 2008 ; scattoni et al . , 2008a ; scearce - levie et al . , , 2008 ; winslow and camacho , 1995 ; wrenn et al . , 2004 ) . a prevailing concern is that social scores obtained from experiments done in opposite phases may not be comparable . to address this concern , we compared social scores reported in light and dark phase studies . in the social recognition test , the subject is presented with a novel mouse for multiple short trials separated by 2030 min intervals . in a dark phase studies , the baseline sniff time was approximately 120 s in dba/2 mice tested in a 4-min trial ( bluthe et al . , 1993 ) and 150 s in wild type mice tested in a 5-min trial ( choleris et al . , 2003 ) in light phase experiments , the baseline sniff time was approximately 90 s in cd-1 mice tested in a 2-min trial ( dluzen and kreutzberg , 1993 ) and 60 s in 129x1/svj mice tested in a 90-s trial ( scearce - levie et al . , 2008 ) . significant reductions in sniff time towards the re - introduced stimulus mouse was found in mice tested in both phase ( bluthe et al . , 1993 ; choleris et al . , 2003 ; dluzen and kreutzberg , 1993 ; scearce - levie et al . , 2008 ) . moreover , in a study that directly compared the social recognition test done in opposite phases , phase effect was not significantly different between light and dark phases for the level of social sniffing , and similar strain differences were found in both phases ( hossain et al . , 2004 ) . taken together , these findings supports the interpretation that mice tested in both circadian phases exhibit comparable levels of active social investigation ( i.e. social sniff ) towards novel social stimuli , and that light phase testing can be used to evaluate social recognition / memory . in our three - chambered social approach test ( chadman et al . , 2008 ; crawley et al . , 2007 ; mcfarlane et al . , 2008 ; moy et al . , 2004 , 2007 , 2008 ; nadler et al . , 2004 ; ryan et al . , 2008 ; stack et al . , 2008 ; yang et al . , 2007a , b ) , more time spent in the chamber containing a novel mouse than in the chamber containing a novel object indicates the presence of sociability ( i.e. greater interest in interacting with a novel conspecific than with a novel inanimate object ) . studies published since the invention of this task have consistently showed high sociability in b6 mice . interestingly , both light phase studies ( moy et al . , 2007 , 2008 ; ryan et al . , 2008 ) and dark phase experiments ( mcfarlane et al . , 2008 ; yang et al . , 2007b ) showed that b6 mice spend around 300 s in the chamber containing the novel mouse and about 200 s in the chamber containing the novel objects in a 600-s test session , indicating that social approach scores are similar in animals tested in opposite phases , as described in more detail below . taken together , evidence summarized above indicates that the levels of social behaviors are actually quite similar between light and dark phase studies . the standard daytime working hours of humans overlap with the inactive phase of mice . the large body of literature documenting murine nocturnality has led many investigators to believe that dark phase mouse behaviors are more analogous to daytime human behaviors and that dark phase testing promises superior outcomes as compared to light phase testing ( hossain et al . , 2004 ) . while there is no doubt that dark phase testing is ethologically correct and theoretically ideal , this approach generates a number of practical difficulties . first , dark phase testing , which commonly requires reversing or shifting the light / dark cycles ( blanchard et al . , 2005 ; yang et al . , 2007a ) , can not be easily accommodated in many research facilities . many researchers have to share animal housing rooms with several other investigators who may not want to reverse the ld cycle . subjects waiting to be tested can be held in communal acclimating room or even in the hallway outside the experimental room . dark phase testing , which requires dedicated dark rooms for acclimating subjects and/or mice used as novel social stimuli , is simply not practical for researchers with tight experimental space ( not an uncommon situation ) . cages need to be covered with light - proof materials when transferring animals between rooms and whenever the door is opened . the red light generated from commonly used incandescent red light bulbs is less than ideal for human visual perception ( mclennan and taylor - jeffs , 2004 ) , making it difficult to perform tasks that require visual acuity , e.g. identifying animals ( by tattoos or ear tags ) , live scoring behaviors , and taking notes . also , catching escaped animals in a dark room can be quite difficult . in experiments in which the some subjects are hyperactive or irritable , this problem could cause frequent interruptions to the experiment and unnecessary disruptions to the subjects . high sociability in b6 mice and low sociability in btbr mice have been consistently reported in a number of recent studies ( mcfarlane et al . , 2008 ; , 2007a , b ) , some of which were done in the light phase ( moy et al . , 2007 , 2008 ) and others in the dark phase ( mcfarlane et al . , 2008 ; yang et al . , two questions arise : ( 1 ) in the three - chambered social approach apparatus , would mice be more interested in interacting with the novel mouse in dark phase than in the light phase ? ( 2 ) would testing social approach behaviors in opposite circadian phases yield quantitatively different outcomes ? we addressed these questions in the primary publication ( yang et al . , 2007a ) . social approach scores were compared between two cohorts of b6 and btbr males , one cohort raised in a conventional 12:12 light / dark cycle ( lights on at 6:00 a.m. ) and tested in the light phase , under fluorescent light , and the other cohort raised in the reversed 12:12 light / dark cycles ( lights on at 9:00 p.m. ) and tested in the dark phase , under incandescent red light illumination . b6 tested in the light phase spent as much time in the chamber with the novel mouse as b6 tested in the dark phase , and displayed similar time spent sniffing the novel mouse . moreover , qualitatively and quantitatively similar strain differences in chamber time and sniff time were found in both phases , indicating that testing sociability in the light phase produced results highly comparable to dark phase experiments . , 2007a ) described a series of five experiments to test whether circadian phase affect the expression of social behaviors in mice bearing mutations of the vasopressin receptor subtype 1b gene ( avpr1b ) . in addition , we assessed the extent to which results of the social approach task are replicable in our laboratory . two cohorts of avpr1b mice were tested in the light phase and three cohorts in the dark phase . one light phase experiment reported genotype differences in chamber time but not in sniff time . the second light phase experiment and all three dark phase experiments found no genotype differences in either chamber time or sniff time . thus , as in the b6 vs. btbr experiments , similar levels of chamber time and sniff time were found in avpr1b mice tested in the two circadian phases , as well as across cohorts . these highly consistent results from the avpr1b experiments indicate that circadian phase is not likely to affect the outcome of a genetic study . the last part of our study ( yang et al . , 2007a ) compared juvenile play behaviors of apvr1b mice tested in the two circadian phases . to increase the motivation of social interaction , pups were taken from the home cage and isolated in clean cages for 1 h before the play test . two non - sibling pups were then placed in a novel area ( noldus phenotyper observer 3000 chamber , noldus , leesburg , virginia ) and allowed to interact freely for 30 min . juvenile avpr1b of all genotypes tested in the two circadian phases exhibited similar levels of active social investigation and play soliciting behaviors , indicating that light phase testing is acceptable for studying juvenile social behaviors as well ( yang et al . , 2007a ) . taken together , our findings demonstrate that mice can actively perform the social approach task in the light phase , and that results from light and dark phases are comparable . with a substantial body of literature clearly showing circadian variations in social behaviors in rodents , how does one explain the similar levels of sociability in mice tested in opposite phases , and the fact that many light phase studies have yielded meaningful results ? field studies have shown that many species of nocturnal rodents are able to adjust their activities according to non - photic factors including predation and conspecific competition ( daily and ehrlich , 1996 ; mistlberger and skene , 2004 ; mrosovsky , 2003 ; shkolnik , 1971 ) . for laboratory mice , human activities in the vivarium and test facility may act analogously as circadian entrainers . in standard commercial and research facilities , routine cleaning , feeding , cage changing , and inspection of mice are conducted during the light phase . it is probable that animals that are better at adapting to such daily disruption have enjoyed reproductive success superior to those individuals who were unable to adapt well . consequently , modern laboratory mouse colonies might largely consist of animals that have evolved to be able to adjust physiologically and behaviorally to the demands of the vivarium environment . further , the ethological importance of investigating a novel conspecific may override the tendency of mice to sleep during the light phase . thus , social interaction assays may be among the least sensitive to circadian phase , at least for laboratory mice . the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest .

the rich repertoire of mouse social behaviors makes it possible to use mouse models to study neurodevelopmental disorders characterized by social deficits . the fact that mice are naturally nocturnal animals raises a critical question of whether behavioral experiments should be strictly conducted in the dark phase and whether light phase testing is a major methodologically mistake . although mouse social tasks have been performed in both phases in different laboratories , there seems to be no general consensus on whether testing phase is a critical factor or not . a recent study from our group showed remarkably similar social scores obtained from inbred mice tested in the light and the dark phase , providing evidence that light phase testing could yield reliable results as robust as dark phase testing for the sociability test . here we offer a comprehensive review on mouse social behaviors measured in light and dark phases and explain why it is reasonable to test laboratory mice in experimental social tasks in the light phase .

celiac disease ( cd ) is a disorder of the small intestine known by mucosal inflammation , villous atrophy , and crypt hyperplasia , which appear upon exposure to dietary gluten and improve after withdrawal of gluten from the diet . however , the serologic tests for celiac disease and the common use of upper endoscopy have complicated the definition . these tests have identified patients who may be involved in the disease but have variable degrees of histop - athologic symptoms and changes . no definite single test can lead to a definite diagnosis of celiac disease for every individual . so , the most important step in diagnosis as a general rule is using serologic tests . the specific tests like iga anti - tissue transglutaminase and iga endomysial antibody can be recom - mended [ 2 , 3 ] . patients with a positive iga endomysial or transglutaminase antibody test should undergo a small bowel biopsy . the exact minimal number is uncertain ; however , some experts believe that at least four should be obtained . the duodenal mucosa may be atrophic with loss of folds , contain visible fissures , have nodular appearance or scalloped folds , but such findings are not universally acceptable and may be seen with some other disorders . the diagnosis is usually established if there is a correlation between the serologic results and the biopsy findings . tissue transglutaminase is a ubiquitous intracellular enzyme released by inflammatory and endothelial cells and fibroblasts in response to mechanical irritation or inflammation . once it has been secreted , it cross - links glutamine - rich proteins like gluten proteins from wheat . however , it can also deamidate glutamine residues in gluten to glutamic acid . deamidation causes a negative charge in gluten peptides , which increases their binding to hla - dq2 and dq8 , which potentiates their capacity to stimulate t - cells [ 6 , 7 ] . in addition to activation of pathogenic t cells , innate responses to gliadin are also involved in the immune response , and perhaps even necessary to trigger the gliadin - specific ( adaptive ) t - cell response in genetically potential individuals . pattern recognition to provide an early response to stimuli such as rna , dna , lipopolysaccharide , or viral proteins , in contrast to the adaptive immune system , which depends on hla - presentation and t - cell recognition and expansion . in celiac disease , certain cereal peptides can apparently initiate innate immune responses in macrophages , monocytes , dendritic cells , and intestinal epithelia via yet unknown receptors and mechanisms [ 8 , 9 ] in the immune system . when t - cells are stimulated , two types of t - cells are produced . one type is t - helper and the other one is memory t - cell . therefore , every time gluten enters the body of celiac patients , memory t - cells will be activated and trigger innate immune response . this study tries to answer this question whether the immune response starts if gluten enters the body of celiac patients through skin and whether gluten skin patch test can be used for celiac disease diagnosis . a patch test is based on the principle of a type iv ( delayed ) hypersensitivity reaction . this is where a substance is recognized by immune cells in the skin known as antigen - presenting cells ( apcs ) . the apc moves down the lymphatic system to a lymph node where it presents antigen to t - cells . if the t - cell identifies the substance as a threat , it sends out all types of immune cells including more of its own type to where the antigen has entered the skin . patch test is the gold standard of food allergy diagnosis , and celiac disease is one of the non - ige mediated types of food allergy . when gluten comes into contact with the skin of a celiac patient ( through patch test ) , tissue transglutaminase in skin cells can transmute gluten to glutamic acid , and apcs move down to the lymphatic node ( where there are gluten - specific memory t - cells ) and present gluten as an antigen to t - cells , the immune system is thus activated and produces hypersensitivity reaction type iv . therefore , it can be stated that skin patch test can be considered as a method for diagnosis of celiac disease . in this study , we try to determine the effectiveness of patch test in diagnosis of celiac disease compared to that of biopsy . this study was carried out in al - zahra university hospital affiliated with isfahan university of medical sciences , isfahan , iran . we collected comprehensive clinical and histological data of all patients suspected of celiac disease undergoing endoscopy from november 2005 until june 2009 . the patients were divided into two groups , the case group and the control group . in the case group , there were 30 patients with typical celiac disease criteria ; they had symptoms of celiac disease , positive serologic test results , villous atrophy in biopsy , and their symptom resolved subsequently on a gluten - free diet . in the control group , we investigated whether these patients suffered from dyspepsia or had intestinal diseases other than celiac disease , such as gerd , h. pylori infection , or gastroenteritis . all patients in the control group had normal villous architecture . in this study , we used viaskin , which is a type of gluten patch test produced by dbv technology , france . viaskin has a polymer plate containing gluten , with positive and negative poles ( the negative pole is placed on the skin of patient . when viaskin is placed on the skin , the gluten in the polymer plate is solved by natural moisture of the skin and absorbed , as a result of which the immune system is activated . in this study , we placed both gluten patch test and placebo patch test on the skin between scapulas of the patient . after 48 hours , we removed both patch tests and reported the responses twice ; after 48 hours and 96 hours . the result of patch tests had five grades : grade 0 meant no reaction , grade i : mild erythema , grade ii : severe erythema , grade iii : erythema and eventually papules or only papules , and grade iv meant erythema , vesicles , and pustules . four patients in the case group and eight patients in the control group who showed irritation reactions were withdrawn from this study . in order to determine the diagnostic value of gluten patch test , once we chose grade 0 as negative response and once grade 0 and i as negative response . we determined sensitivity , specificity , positive predictive value ( ppv ) , and negative predictive value ( npv ) of gluten patch test both after 48 and 96 hours . statistical differences between the study groups were evaluated using spearman 's test , mann whitney test , or chi square test , as appropriate . sensitivity and specificity , positive predictive value ( ppv ) , and negative predictive value ( npv ) of gluten patch test in detecting celiac disease were determined . median age of control group was 9.08 ( range : 316 ) and in control group was 11.27 ( range : 431 ) . twelve patients ( 40 ) in case group and 15 patients ( 55.6% ) in control group were females . the values for gluten patch test after 48 hours and 96 hours are shown in table 2 . the best results were obtained when we reported the responses of gluten patch test after 96 hours , in which sensitivity 95% , specificity 8% , ppv 67% , and npv 43% were reported . therefore , gluten patch test is not efficient in screening celiac disease . primary reason for endoscopy and small intestine biopsy in study and control groups in this study , we compared responses to gluten patch test with severity of villous atrophy in patients with celiac disease ( partial atrophy of villus was considered as mild and marsh iiic was of the greatest severity ) , spearman 's test showed that there is a direct relationship between gpt response after 48 h and severity of villous atrophy ( r=0.26 p=0.04 ) ; for example , we can say patients with marsh iiic will show a higher grade of gpt after 48 h than patients with partial atrophy , but there is no relationship between response to gpt after 96 and severity of villous atrophy . there is an inverse relationship between patients age and response to gpt after 96 h ( confirmed by spearman 's test results : r=0.25 , p=0.04 ) . this means that after 96 hours , older patients will show a lower grade of gpt response than younger patients . but there is no relationship between age and response to gpt after 48 h. the value for gluten patch test in diagnosis of celiac disease in comparison with small intestine biopsy gpt : gluten patch test ; npv : negative predictive value ; ppv : positive predictive value in 30 patients with celiac disease , six patients discontinued gluten - free diet . there was no relationship between response to gpt and continuing gluten - free diet ( confirmed by chi - square test results , p=0.16 ) . in this study , there was a direct relationship between serology test results ( anti t - tg igg , anti gliadin iga ) of cd patients and responses to gpt after 96 hours ( by mann we can therefore say there is a relationship between negative anti gliadin iga and negative anti t - tg igg on the one hand and grade 0 in gluten patch test after 96 h on the other hand . but there is no relationship between results of these serology tests with results of gpt after 48 hours , and there is no relationship between the results of other serology tests ( anti endomysial ab iga , igg , anti gliadin ab igg , anti t - tg iga ) and responses to gpt . for the first time , the diagnostic value of gluten patch test for celiac disease was investigated in this study . different studies have shown that skin patch test is a reliable test for diagnosis of food allergy and delayed hypersensitivity reaction [ 13 , 14 ] and useful to diagnose both mediated and non - mediated ige reactions . several studies have shown that skin patch test is sensitive in diagnosis of food allergies associated with atopic dermatitis , particularly in young children [ 16 , 17 ] . in a study , specificity of skin patch test in diagnosis of cow milk allergy was determined to be 95% and for hen eggs to be100% . in 46 patients with allergic eosinophilic esophagitis , the sensitivity of both skin patch test and skin prick test were 97% and specificity of both was 5% in diagnosis of foods that cause aee . in another study on 19 patients with food protein - induced entrocolitis syndrome ( fpies ) , sensitivity of skin patch test was shown to be 10% and its specificity to be 71% in diagnosis of foods associated with fpies . all the studies showed that skin patch test is useful for food allergy diagnosis and because celiac disease is a food allergy and is a type of non - ige mediated reaction , it was expected that gluten patch test could be an effective test in diagnosis of celiac disease . however , this study showed that gluten patch test can not be such an efficient test in screening of celiac disease . nevertheless , the gluten patch test can be useful in diagnosis of cd when employed with clinical symptoms , serology test , and biopsy of small intestine . we should doubt our diagnosis if a patient with cd shows positive response to gpt after 96 h. regarding the value of this study , we should doubt the statement that cd is a kind of food allergy ; perhaps it is better to present celiac disease as an autoimmune disease . this hypothesis is reinforced by association of celiac disease with other autoimmune diseases such as diabetes type i [ 21 , 22 ] , selective iga deficiency [ 23 , 24 ] , autoimmune thyroid disease [ 25 , 26 ] , and autoimmune myocarditis [ 27 , 28 ] . in this hypothesis , in cd patients , gluten is probably similar to epithelium of small intestine and when patients use gluten , the autoimmune system will be activated . this study showed that there is a direct relationship between severity of villous atrophy in cd patients and the response to gluten patch test after 48 h. is the grade of villous atrophy predictable by the grade of gluten patch test result after 48 hours ? there is a direct relationship between gluten patch test results after 96 h and anti gliadin iga and anti t - tg igg results . will gluten patch test after 96 h be able to be replaced with anti gliadin iga and anti t - tg igg ?

objectiveceliac disease is an intestinal disorder identified by mucus inflammation , villous atrophy and crypt hyperplasia . this disorder can be controlled by elimination of gluten from daily diet . patients with celiac disease are at greater risk of gastrointestinal malignancy and non - hodgkin lymphoma than are the general population . this study tries to present the value of gluten patch test for diagnosis of celiac disease.methodsin this investigation , the study population was divided into case and control groups . the case group consisted of patients with celiac disease . the control group were patients involved in celiac disease but suffering from other gastrointestinal disorders . both gluten patch and placebo patch were attached to the skin between the scapulas . the results were read twice : 48 hours and 96 hours after the patch was applied . patients who showed irritation reactions were withdrawn from this study . the results were analysed by spss software , spearman 's test , chi square , and mann whitney tests.findingsthe value obtained from the gluten patch test after 96 hours are as follows : specification at 95% , sensitivity at 8% , positive prediction value at 67% , and negative prediction value at 43%.conclusionit can be concluded that the gluten patch test is not an efficient test for screening of celiac disease , however , it can be useful for diagnosis of celiac disease if employed and studied with clinical symptoms and serologic and biopsy tests . furthermore , we should doubt our judgment if the result of gluten patch test for the patient with celiac disease is positive .

nineteen of 63 patients , operated in a high - volume cataract surgery setting at a nearby hospital were referred to us with acute onset of redness and decreased vision . at admission , all patients underwent slit - lamp examination , applanation tonometry , dilated fundus evaluation and b - scan ultrasonography . our cohort comprised the last few cases operated on day 2 and almost all patients from day 3 of the surgical " camp " . all patients had undergone sutureless manual small - incision cataract extraction with single - piece polymethylmethacrylate intraocular lens ( iol ) implantation . of these , one was left aphakic while the other had the iol implanted in the ciliary sulcus . all patients were on topical gentamycin 0.3% six - hourly , topical prednisolone acetate 1% hourly , homatropine 2% drops three times daily and oral ciprofloxacin 500 mg twice daily . at presentation [ table 1 ] , lid edema , gross corneal edema with severe exudative reaction was seen in all cases [ figs 1 and 2 ] . relative afferent pupillary defect was noted in all the nine patients who had inaccurate projection of rays . b - scan ultrasonography at admission revealed anterior to mid - vitreous echoes in all patients at 60% gain . diagnostic vitreous tap was done in three patients ; one representing those with hypopyon , one without hypopyon and one with severe pain . eighteen patients were given intravitreal injections of vancomycin ( 1.0 mg / 0.1 ml saline ) and ceftazidime ( 2.25 mg / 0.1 ml saline ) . topical ciprofloxacin ( 0.3% ) hourly , dexamethasone - chloramphenicol combination hourly and atropine sulphate 1% three times daily were started . oral acetazolamide 250 mg six - hourly , anti - diabetic and anti - hypertensive medication were used as required . vitrectomy could not be performed in any patient due to corneal edema and severe anterior chamber exudative reaction . all three vitreous samples revealed gram - negative bacilli on smear and profuse growth on culture . susceptibility testing ( as per the clinical laboratory standards institute)4 revealed identical sensitivity patterns in all three samples . it was resistant to penicillin , vancomycin , gentamicin , norfloxacin , ciprofloxacin , tetracyclin , chloramphenicol , lomifloxacin , ofloxacin and tobramycin and sensitive to ceftazidime , cefotaxime , imipenem and meropenem . sixteen patients received four doses , two patients refused the last two doses and one patient refused all surgical intervention . following the sensitivity report , only ceftazidime was given as the third and fourth doses . in poor responders and those patients who developed corneal infiltrates , the other two resulted in autoevisceration , one a newly detected diabetic who allowed only two intravitreal injections and the other who refused any surgical intervention . five out of 19 eyes regained 20/200 or better vision [ table 1 ] within 18 days even without vitrectomy . pseudomonas is the commonest gram - negative causative organism.5,6 successful management depends on rapid recognition and prompt intervention.7 vitreous tap for smear and culture , followed by immediate intravitreal administration of broad - spectrum antibiotics and , a vitrectomy if indicated is the current standard of care . although most patients in this series qualified for immediate vitrectomy according to the endophthalmitis vitrectomy study protocol,8 this was deferred due to severe stromal edema obscuring the view . high - volume surgery still has a role in reducing the cataract load in india.9 when endophthalmitis occurs in these settings , every effort should be made to trace the source of infection . ideally , the efficacy of the sterilizer using test strips , sterility of the air using settle plates and culturing of the swabs , instruments and remaining fluids should be done . in another series of endophthalmitis caused by entrobacter species , inadvertent use of unsterilized swabs was found to be responsible.2 investigation into the outbreak however , could not be done fully as the patients came from an independent center . only unopened containers from the batch of viscoelastic and intraocular fluids used for the surgeries were provided for culture . the causative organism , enterobacter amnigenus isolated in our series , is an environmental pathogen10 and normally results in infection only if inoculated in high doses . the patients were absorbed into the referral system of the neighboring state to which they belonged and could not be subsequently followed up by us . the similar clinical presentation and the fact that all three samples grew the same rare organism , of identical subtype and identical sensitivity patterns , strongly suggests that this organism was responsible for the entire epidemic . as highlighted by this report , investigating outbreaks of endophthalmitis even in a high - volume surgical setup thus becomes important from the diagnostic , therapeutic and public health point of view .

we report a case series of endophthalmitis by an organism hitherto not reported in the eye . nineteen of 63 cataract patients operated in a high - volume setup were urgently referred to us with acute onset of decreased vision one to two days following cataract surgery . all patients had clinical evidence of acute endophthalmitis with severe anterior chamber exudative reaction . vitreous tap was done in three representative patients and repeated intravitreal injections were given as per established protocol . the vitreous sample from all three patients grew enterobacter amnigenus biogroup ii , a gram - negative bacillus which , to the best of our knowledge , has never been reported in the eye . with prompt and accurate microbiological support , it was possible to salvage 17 of these eyes without performing vitrectomy . six eyes regained 6/200 or better vision .

situs inversus totalis , a congenital anomaly present in approximately 0.01% of the population , results in complete mirror - image reversal of all the thoracic and abdominal organs . the laparoscopic literature has several reports of successful bariatric procedures in patients with situs inversus despite the extremely low prevalence of this condition.[13 ] while several equivalent alternatives are available in the bariatric algorithm , more recently the laparoscopic sleeve gastrectomy ( sg ) has been gaining traction as an effective means of weight loss in patients with morbid obesity.[47 ] a 39-year - old woman who had previously undergone an open gastric banding procedure 20 months earlier for morbid obesity presented with increased weight gain . her weight at presentation was 106 kg ( body mass index 42 kg / m ) , a percentage excess weight loss ( ewl ) of only 1.9% . her medical history was significant for hypertension , noninsulin - dependent diabetes mellitus , hypothyroidism , obstructive sleep apnea , and situs inversus totalis . the presence of situs inversus was initially discovered during her first weight loss operation and confirmed by computed tomography of the abdomen [ figure 1 ] . the operating surgeon began the case laparoscopically , but upon recognizing the altered anatomy made the decision to convert to an open gastric band placement . given the failure of this first procedure to produce meaningful weight loss , the patient was scheduled for laparoscopic removal of the gastric band with concurrent sg . coronal computed tomographic scan of the abdomen and pelvis with oral and intravenous contrast demonstrating the mirror - image anatomy . panel a displays a cross - section of the band in its position on the right side of the abdomen . panel b further demonstrates the altered anatomy with left - sided liver and right - sided stomach the patient was positioned supine on the operating room table . secondary to the presence of situs inversus , the veress needle was placed in the right upper quadrant to avoid the liver . a 12-mm trocar was placed five fingerbreadths above the umbilicus , just to the right of midline . next , a 5-mm trocar was placed in the left lower quadrant approximately two fingerbreadths below the umbilicus in the midclavicular line . a 12-mm port was then placed under direct vision in the left midclavicular line approximately five fingerbreadths above the umbilicus . a 12-mm port was placed in the right upper quadrant in the midclavicular line , and a 5-mm port was placed in the right upper quadrant one fingerbreadth below the costal margin in the midaxillary line [ figure 2 ] . exploration revealed extensive adhesions as a result of her previous open procedures . at this point , the stomach was identified and noted to be severely adhered to the liver , which was , in turn , adherent to the abdominal wall . the stomach was mobilized , the band was identified , and the band buckle was cut and removed . the previous fundoplication was taken down using a 3.5-mm depth 45-mm length stapler , and the greater curvature and short gastric vessels were divided using a harmonic scalpel . after performing the dissection all the way to the angle of his and exposing the left crux of the diaphragm , a 34-french bougie was placed into the stomach with the tip of the bougie sitting in the proximal duodenum . the formation of the gastric sleeve with a 4.8-mm depth 45-mm length stapler was started from a point 5 cm proximal to the pylorus muscle and directed toward the angle of his [ figure 3 ] . eight total firings were used , thus dividing the stomach completely and forming a gastric tube over the 34-french bougie . at the most proximal aspect of the stomach , several dense adhesions to the diaphragm were encountered and eventually taken down . following the formation of the gastric tube , the staple line was oversewn with 2 - 0 absorbable suture using an endo stitch ( covidien inc . , after submerging the gastric tube underwater , air was pumped into the scope , and subsequently no leak was appreciated . before removal of the last trocar , the detached stomach was placed into a specimen retrieval bag and removed from the peritoneal cavity via the 12-mm port in the right upper quadrant . the same trocar site was slightly extended to allow for removal of the port and band . finally , a jackson pratt drain was placed by the sleeve for surveillance purposes . novel port placement ( copyright sages 2010 , soper nj , swanstrom ll , eubanks ws , eds . mastery of endoscopic and laparoscopic surgery ) intraoperative image ( white arrow indicates the angle of his ; blue arrows indicate several gastrohepatic adhesions , and black arrows indicate the greater curvature of the stomach ) the postoperative course was complicated by a leak resulting in a 3.9 2.8 cm collection in the gastrosplenic ligament adjacent to the surgical suture line [ figure 4 ] . a jackson pratt drain was left alongside the sg at the time of surgery as this is the surgeons protocol for revisional surgery . the patient underwent an upper endoscopy and placement of a 12-cm removable polyflex stent ( boston scientific inc . , natick , ma ) for management of the leak [ figure 5 ] . over the next few weeks further imaging demonstrated interval migration of the stent into the stomach with no change in the size or location of the perigastric collection [ figure 6 ] . the patient was managed conservatively despite the stent movement and had eventual resolution of her symptoms . the stent was subsequently removed without any complications . currently , the patient is 2 years out from the laparoscopic sg . postoperative upper gi series demonstrating extravasation of contrast at the most proximal aspect of the staple line completion radiograph following endoscopic placement of a removable stent across the anastamotic leak site coronal computed tomographic scan of the abdomen and pelvis with oral and intravenous contrast demonstrating complete migration of the stent into the body of the stomach secondary to the presence of situs inversus , the veress needle was placed in the right upper quadrant to avoid the liver . a 12-mm trocar was placed five fingerbreadths above the umbilicus , just to the right of midline . next , a 5-mm trocar was placed in the left lower quadrant approximately two fingerbreadths below the umbilicus in the midclavicular line . a 12-mm port was then placed under direct vision in the left midclavicular line approximately five fingerbreadths above the umbilicus . a 12-mm port was placed in the right upper quadrant in the midclavicular line , and a 5-mm port was placed in the right upper quadrant one fingerbreadth below the costal margin in the midaxillary line [ figure 2 ] . exploration revealed extensive adhesions as a result of her previous open procedures . at this point , the stomach was identified and noted to be severely adhered to the liver , which was , in turn , adherent to the abdominal wall . the stomach was mobilized , the band was identified , and the band buckle was cut and removed . the previous fundoplication was taken down using a 3.5-mm depth 45-mm length stapler , and the greater curvature and short gastric vessels were divided using a harmonic scalpel . after performing the dissection all the way to the angle of his and exposing the left crux of the diaphragm , a 34-french bougie was placed into the stomach with the tip of the bougie sitting in the proximal duodenum . the formation of the gastric sleeve with a 4.8-mm depth 45-mm length stapler was started from a point 5 cm proximal to the pylorus muscle and directed toward the angle of his [ figure 3 ] . eight total firings were used , thus dividing the stomach completely and forming a gastric tube over the 34-french bougie . at the most proximal aspect of the stomach , several dense adhesions to the diaphragm were encountered and eventually taken down . following the formation of the gastric tube , the staple line was oversewn with 2 - 0 absorbable suture using an endo stitch ( covidien inc . , after submerging the gastric tube underwater , air was pumped into the scope , and subsequently no leak was appreciated . before removal of the last trocar , the detached stomach was placed into a specimen retrieval bag and removed from the peritoneal cavity via the 12-mm port in the right upper quadrant . the same trocar site was slightly extended to allow for removal of the port and band . finally , a jackson pratt drain was placed by the sleeve for surveillance purposes . novel port placement ( copyright sages 2010 , soper nj , swanstrom ll , eubanks ws , eds . mastery of endoscopic and laparoscopic surgery ) intraoperative image ( white arrow indicates the angle of his ; blue arrows indicate several gastrohepatic adhesions , and black arrows indicate the greater curvature of the stomach ) the postoperative course was complicated by a leak resulting in a 3.9 2.8 cm collection in the gastrosplenic ligament adjacent to the surgical suture line [ figure 4 ] . a jackson pratt drain was left alongside the sg at the time of surgery as this is the surgeons protocol for revisional surgery . the patient underwent an upper endoscopy and placement of a 12-cm removable polyflex stent ( boston scientific inc . , natick , ma ) for management of the leak [ figure 5 ] . over the next few weeks further imaging demonstrated interval migration of the stent into the stomach with no change in the size or location of the perigastric collection [ figure 6 ] . the patient was managed conservatively despite the stent movement and had eventual resolution of her symptoms . postoperative upper gi series demonstrating extravasation of contrast at the most proximal aspect of the staple line completion radiograph following endoscopic placement of a removable stent across the anastamotic leak site coronal computed tomographic scan of the abdomen and pelvis with oral and intravenous contrast demonstrating complete migration of the stent into the body of the stomach to our knowledge , this is the first published report of a laparoscopic sg after open gastric banding in a patient with situs inversus totalis . however , modifications in the standard trocar placement can help make the procedure more technically feasible . awareness of the inherited condition before undertaking the operation allows for advanced planning and preparation . in this case , the history of prior open gastric banding made the operation especially tricky , primarily due to the numerous adhesions encountered . revisional surgery is always difficult , but when performed in a patient with situs inversus may be even more challenging . after encountering the initial disorientation , experienced we believe the postoperative leak occurred secondary to the difficult dissection around the gastric fundus , independent of the altered anatomy . these anastamotic leaks can be classified as early or late , depending on how soon postoperatively they occur . in the early period ( <3 days ) , many advocate primary repair . washout and drainage is also an excellent alternative in patients with severe inflammation , signs of sepsis , or hemodynamic instability . the endoscopic placement of polyester or nitinol covered stents is a fairly recent innovation , allowing patients to be maintained on oral enteral nutrition . there have been several reports in the literature supporting their use in both early and late leaks.[911 ] the accepted leak rate for sg is 1.6% at the esophagogastric junction and 0.8% at lower points along the staple line . laparoscopic vertical sg after open gastric banding in a patient with situs inversus can be performed safely by experienced laparoscopic surgeons . while our case yielded a good result , other similar cases are needed to establish the reproducibility and long - term efficacy of the procedure .

while several equivalent alternatives are available in the bariatric algorithm , more recently the laparoscopic sleeve gastrectomy ( sg ) has been gaining traction as an effective means of weight loss in patients with morbid obesity . we present the case of a 39-year - old woman with situs inversus totalis , who was taken to the operating room for laparoscopic sg . the patient had previously undergone a failed open gastric banding procedure 20 months earlier . awareness of the inherited condition before performing the operation allows for advanced planning and preparation . subsequent modifications to the standard trocar placement help make the procedure more technically feasible . to our knowledge , this is the first published report of a laparoscopic sg after open gastric banding in a patient with situs inversus totalis . after encountering the initial disorientation , we believe experienced laparoscopic surgeons can perform this procedure successfully and safely .

ewing 's sarcoma ( es ) was first described as an osteolytic bone tumor composed of malignant , small round cells by james ewing in 1921 . extraosseous ewing 's sarcoma was first described by tefft in 1969 ; it is a rare , malignant mesenchymal tumor similar to intraosseous es . since its characterization in 1980s , this tumor has increasingly been reported from diverse sites including the oral cavity , salivary glands , subcutis , lung , heart , pericardium , biliary tract , kidney , urinary bladder , uterine corpus and cervix , gonads , pancreas , vagina , rectovaginal septum , prostate , esophagus , and stomach . to the best of our knowledge , no reports of its occurrence in the lesser sac have been documented in the literature . a 47-year - old woman presented with a short history of abdominal pain of 15 days duration . physical examination revealed an epigastric mass measuring 7 8 cm , which was firm in consistency and moving with respiration . examination suggested a large , well - defined , heterogenously enhancing mass measuring 12 15 cm with an epicenter in the lesser sac and loss of fat planes with the body and part of the tail of the pancreas and posterior wall of stomach . the possibility of an exophytic pancreatic mass or exophytic gastrointestinal stromal tumor ( gist ) from the posterolateral wall of the stomach was proposed ( fig . 1 ) . the patient underwent an exploratory laparotomy , which showed a tumor in the lesser sac abutting the left dome of the diaphragm dorsally , the splenic hilum to the left , the transverse mesocolon inferiorly , and the posterior wall of stomach anteriorly . the tumor extended posterior to the stomach and was firmly adherent to the pancreatic tissue . excision of the tumor with a distal pancreatectomy and splenectomy was performed and the specimen was received in our laboratory for histopathological examination and diagnosis . grossly , the tumor was well - circumscribed , partly encapsulated , measured 10 15 cm , and weighed 830 g. the tail of the pancreas was compressed by the tumor and was identified near the splenic hilum . cut section of the mass showed a grey tan hemorrhagic tumor with large areas of necrosis ( corresponded to the cystic changes seen on ct ) ( fig . 2 ) . microscopy revealed a fairly well - circumscribed tumor with a fibrous pseudocapsule composed of sheets of small round cells with enlarged round to oval nuclei , fine stippled chromatin , and moderately clear to amphophilic cytoplasm , which was periodic acid - schiff stain positive . geographic areas of necrosis with focal peritheliomatous proliferation of tumor cells around the blood vessels , increased mitosis , prominent apoptosis , and nuclear moulding were noted . in some areas , peripherally compressed pancreatic tissue was seen and no tumor infiltration was discerned ( figs . 3 and 4 ) . the tumor cells were cd99 positive , while cytokeratin ( ck ) , desmin , synaptophysin ( syp ) , and chromogranin ( chr ) were negative ( fig . a final diagnosis of extraosseous ewing 's sarcoma / primitive neuroectodermal tumor ( es / pnet ) of the lesser sac was made . she was scheduled for alternating ie ( ifosfamide and etoposide ) and vac ( vincristine , adriamycin , and cyclophosphamide ) chemotherapy . currently , the patient has completed two cycles of chemotherapy with no further complaints and is receiving regular follow - up care . es and pnet are characterized by the same cytogenetic alterations ( t(11;22 ) ( q24;q12 ) which forms ewsr1-fli1 fusion product ) and comparable morphologic and immunophenotypic features . they are hence classified under the same group of lesions - the es / pnet family of tumors . in their extensive review on ectopic tumors , wick and nappi attributed the origin of these tumors to ectopic neural and neuroectodermal proliferations . they further suggested that although neural tissues are ubiquitously distributed throughout the body , the occurrence of tumors related to this lineage is extremely uncommon in some topographic sites . es / pnet is a poorly differentiated tumor that is integrated in the morphologic category of ' small round cell ' tumors . the various entities that have ' small round cell ' morphology occurring at this site are lymphoma , pancreatic endocrine tumor ( pet ) , pancreatoblastoma , extra - renal wilm 's tumor , extra - adrenal neuroblastoma , hepatoblastoma , rhabdomyosarcoma , desmoplastic small round cell tumor ( dsrct ) , and visceral small cell neuroendocrine carcinoma ( scnc ) . specifically , there is a broad spectrum of tumors having a similar morphology that includes sheets of small , round blue cells . this problem is markedly enhanced when the tumor site of origin is uncertain , as observed in the present case . differential diagnoses of dsrct , scnc , pet , and pancreatoblastoma were entertained based on histomorphology in this case . dsrct 's are usually multicentric tumors involving the peritoneal cavity , although extraperitoneal neoplasms have been described . the cellular phase does not have much desmoplasia and can resemble soft tissue es . since the tumor cells were negative for ck and desmin , dsrct was ruled out . cell to cell molding was noted in the present case , which is usually seen in scnc . since the cells were negative for syp and chr , small cell neuroendocrine carcinoma and malignant pet were ruled out . pancreatoblastomas are rare in adults and microscopically show islands of squamoid morules amongst the neoplastic cells , which was not observed in this case . strong membrane positivity for cd99 was observed in all of the cells confirming the diagnosis of extraosseous es / pnet . unlike intraosseous es , the radiologic findings of extraosseous lesions are non - specific . in the present case , this confusion may be partly due to the unanticipated occurrence of the tumor in a previously undescribed site . in conclusion , extraosseus es / pnets are malignant , highly aggressive tumors , with a poor patient outcome . even though it is rare , this entity should be considered in the differential diagnosis of intraabdominal , extraintestinal masses .

extraosseous ewing 's sarcoma / primitive neuroectodermal tumor ( es / pnet ) is an uncommon , aggressive , and malignant tumor with a poor patient outcome . its occurrence in the lesser sac is a rare event and to the best of our knowledge , has not been previously described . the present case was clinically and radiologically misdiagnosed as a pancreatic tumor / gastrointestinal stromal tumor . histopathology revealed a tumor with " small round cells " that were positive for cd99 , confirming the diagnosis of es / pnet . this report highlights the importance of considering ewing 's sarcoma in the differential diagnosis of intraabdominal , extraintestinal masses .

primary squamous cell carcinomas ( scc ) of the breast are exceedingly uncommon lesions , since they occur in less than 0.074% of all primary invasive breast carcinomas . we should exclude an epidermal origin , especially from the nipple region and the possibility of metastatic infiltration of the breast by an scc from a different location and to classify the breast tumor as a primary scc . also , differential diagnosis must include other primary carcinomas in which squamous metaplasia are found . prognosis and treatment of this disease a 45-year - old woman was admitted with complaint of lump in the left breast for 3 months . physical examination revealed a hard , tender lump of size 8 7 cm in upper and outer quadrant in the left breast . chest radiograph , ultrasonography of the abdomen , computed tomography of the thorax , and gynecological examination were performed . on fine needle aspiration cytology carcinoma of the breast was diagnosed . according to all these findings , the patient underwent modified radical mastectomy with axillary lymph node clearance was performed [ figure 1 ] . gross operative picture of the left breast showing axillary lymph nodes on microscopic examination , tumoral structure composed of large hyperchromatic nuclei with abundant cytoplasm , along with multiple foci of keratin pearl in different sizes and marked increase in mitotic activity [ figures 2 and 3 ] was observed . there was no origin from the surface epithelium and no different tumoral components were seen . the patient was started with adjuvant 6 cycles of cap ( cyclophosphamide , adriamycin , and cisplatinum ) chemotherapy . the patient is alive and disease - free , 8 months follow - up after the diagnosis . malignant squamous cells in trabeculae arrangement forming keratin pearls in the center ( 100 , h and e , 200 ) histopathology showing squamous cells arranged in whorls with centrally keratin pearl formation ( 100 , h and e , 200 ) scc is a well - known malignancy of the skin and other organs surrounded with squamous cells such as the esophagus and the anus . primary scc is an extremely rare malignancy and is believed to originate from the epithelium of the mammary ducts but tumor may also arise from foci of squamous metaplasia within a pre - existing adenocarcinoma of the breast . there are few reported cases of primary scc with origin from the capsules surrounding the silicone breast prostheses . according to our search in the world literature , the incidence of the primary scc among all the breast carcinomas is approximately between of 0.1% to less than 0.04% . primary scc of the breast is defined when more than 90% of the malignant cells are of the squamous cell type without any relation with the skin and there is no primary location elsewhere in the body . classically metaplastic tumors are mainly divided into two types : firstly tumors with squamous metaplasia , and secondly tumors with heterologus components . morphologically these tumors are of five subtypes : ( a ) matrix - producing carcinoma , ( b ) spindle cell carcinoma , ( c ) carcinosarcoma , ( d ) squamous cell carcinoma of ductal origin , and ( e ) metaplastic carcinoma with osteoclastic giant cells . breast carcinoma arises from the mammary glandular epithelium , the phenotypic expression of squamous differentiation in breast cancer is considered a form of metaplastic carcinoma . scc can occur from 29 years to 90 years of age in adult women , with a median of 52 years of age . primary tumors tend to be relatively large ranging from 2 to 5 cm and enlarged over a period of 2 to 3 weeks or in some cases for as long as 18 months . about two - thirds of these tumors are cystic or have a cystic component with central necrosis . axillary lymph node metastasis occurs rarely which is usually associated with metaplastic scc arising in an invasive ductal carcinoma . but some thought that scc of the breast can be presented with aggressive course along with outcome comparable to poorly differentiated breast adenocarcinoma . patient should get cisplatinum - based chemotherapy regimen with diagnosis of scc , as documented by dejager et al . most of the scc are radiosensitive and primary scc of the breast of small in size could be treated with lumpectomy with axillary clearance followed by radiotherapy . treatment should be based on the pathological features of the tumor rather than the age of the patient , but very young women have excessive risk of local recurrence and dying , as compared to their middle - aged counterparts , even if diagnosed early and receiving an intense treatment . after correction for stage , tumor characteristics , and treatment , age is an independent risk factor for death in women less than 34 years of age , in breast carcinoma . menes et al . recommended a selective approach like sentinel node biopsy , because lymph node involvement plays a lesser prognostic and therapeutic role in this disease . the diagnosis of primary scc of the breast can only be made in the absence of an associated primary scc in a second site and in the absence of skin involvement . the prognosis of the pure scc of the breast and proper approach for the treatment is still in doubt . surgical and medical treatment of scc of the breast should be started to fit its distinct biologic characteristics . scc is reported to result in less lymphatic spread than adenocarcinomas . in 10 to 30% of cases , on other side , distant metastasis may be seen in about 30% of the patients . it is recommended to give patients similar adjuvant therapy but the radiosensitivity of sccs is uncertain . it may be prudent to initiate adjuvant radiation therapy earlier than usual for breast cancer because of the tendency for locoregional relapse . breast scc is an extremely aggressive disease associated with frequent locoregional and distant relapses and resultant deaths .

in females , the most common cancer is breast carcinoma in which squamous cell carcinoma ( scc ) is a rare type of malignancy . histologically , infiltrating ductal carcinoma is the most common type and lobular , mucinous , and medullary types have lower incidence . pure scc of the breast can originate from the skin , nipple , or epithelium of a deep - seated dermoid cyst or squamous metaplasia on chronic inflammation background . we are reporting a rare case of primary scc of the breast in a 45-year - old female . in follow - up of 8 months , patient is doing well . we discussed our approach for treatment with review of the literature . we have treated this patient successfully with surgical and adjuvant chemotherapy .

a female gender assignment is easy , but as they are genetically males , a male gender assignment is appropriate . a 2-year - old child was referred with an absent phallus , well - developed scrotum , and normally descended testicles [ figure 1 ] . in neonatal period , the baby was passing urine from the anus and after 1 week developed sepsis and renal failure . a grossly pyonephrotic single kidney on the right side on ultrasound and computed tomography ( ct ) scan , prompted for an emergency pyelostomy and colostomy ( done at another center ) . the baby recovered from sepsis but was lost to follow - up . when presented to our center at 2 years of age , the child was thriving well , phenotypically a boy ( without a phallus ) with a 46 xy karyotype and had no dysmorphic features . he had a well - functioning left iliac colostomy , and the pyelostomy was draining clear urine . the child was evaluated with a plan for phallic reconstruction along with closure of pyelostomy and colostomy before he reached school age . the renal parameters were within normal limits and renal tract ultrasound showed , a grossly hydronephrotic right kidney with thin cortex and an absent left kidney . a ct urogram and magnetic resonance urogram showed crossed fused ectopic kidney on the right side with grossly hydronephrotic lower unit ( crossed kidney from left ) . the pyelostomy was draining the upper unit of fused kidney with normal parenchyma and showed that the ureters were normal . a single functioning kidney was imaged on tc-99 m dimercaptosuccinic acid ( dmsa ) scan on the right side , and a pyelostogram visualized a dilated pelvis with mildly dilated ureter draining into bladder . to further characterize the defect an examination under anesthesia , revealed a small fistula opening into anterior wall of lower rectum at its junction with anal canal which could not be cannulated . a cystogram done through a suprapubic puncture showed good sized bladder with bilateral grade 1 reflux and the proximal portion of urethra ( 1 cm ) was imaged draining into rectum . a scrotal phalloplasty was performed [ figure 2 ] according to the technique described by bajpai with creation of perineal urethrostomy . the pyelostomy was formally closed after 6 months , and the non - functioning hydronephrotic kidney was left undisturbed . , a buccal musosal tube was created and inserted into the perineum and tunneled to exit at the tip of neophallus [ figure 2 ] with a view to connect the 2 ends at a later date . on exploration after 6 months , the buccal tube had shrunk in size causing tethering and lead to an apparent reduction in size of neophallus . the child started schooling at 4 years , is continent and has been mingling with peers at school with no issues of gender discordance . a 2-year - old boy with absent penis . a pyelostomy and colostomy were done in neonatal period for urinary sepsis steps of scrotal phalloplasty ( bajpai technique ) . ( d ) a tunneler ( urethral dilator ) is used to create a tunnel from just anterior to perineal urethrostomy , which would exit at tip of penis . a preformed buccal mucosal tube is drawn into this tunnel and anchored ( not shown in this figure ) the urethra opens at any point along perineal midline raphe , but most commonly opens on to anterior wall of anal verge . in our case , the urethra opened at the superior most part of anal column . skoog and belman , classified aphallia based on the urethral opening in relation to anal sphincter as postsphincteric , presphincteric ( prostatorectal fistula ) , and urethral atresia . on reviewing 60 reports of aphallia , they found that the more proximal the urethral meatus , the greater the likelihood of neonatal death and the higher the incidence of other anomalies . sixty percent of patients had a postsphincteric meatus located on a peculiar appendage at the anal verge . this group had the highest survival rate ( 87% ) and the lowest incidence of other anomalies ( 1.2/patient ) . twenty - eight percent had presphincteric urethral communications ( 36% mortality ) , and 12% had urethral atresia and a vesicorectal fistula for drainage ( 100% mortality ) . the ectopic lower unit in the index case was grossly hydronephrotic with no function on dmsa scan . the management of aphallia is a challenge , and many have been assigned a female gender which can possibly result in subsequent gender dysphoria . although the role of androgen imprinting prenatally and its long - term psychologic effects are difficult to analyze in a child , a male gender assignment seems to be appropriate . the sexual orientation of these children can only be defined when they reach an appropriate age when they are free to choose the appropriate surgical correction to suit their need . scrotal phalloplasty as described by bajpai , gives excellent cosmetic result and in our index case , it looks essentially like a normal penis and alternative skin flap based phalloplasty are also reported . as the neophallus lacks erectile tissue ( corpora ) , a penile prosthesis ( inflatable ) can be inserted at adolescence ( at around 15 years of age ) . to accommodate the prosthesis , a male gender assignment is appropriate for the rare boys born with aphallia . with the refinements in technology in medical and allied field growing rapidly , these children should have numerous options to choose from to suit their livelihood as they mature .

a 2-year - old male child presented to us with aphallia . at birth , he was passing urine from the anus and had undergone emergency colostomy and pyelostomy for urinary sepsis at 1 week of life . after a complete evaluation , the child underwent perineal urethrostomy and scrotal phalloplasty followed by buccal mucosal tube urethroplasty in the second stage , which was completed before the child started schooling .

bronchobiliary fistula ( bbf ) , an uncommon complication of radiofrequency ablation ( rfa ) , is due to abnormal communications between the biliary tract and bronchial trees . in addition , it may be presented as a complication of either hepatic abscess , hydatid disease of the liver , hepatic malignancy , trauma , or liver surgery.1,2 the optimal management of bbf is still controversial and is often associated with high morbidity and mortality rates . although bbf has traditionally been treated surgically , nonsurgical interventional management such as endoscopic drainage or percutaneous abscess drainage have recently been suggested as the first therapeutic option.3 if the nonsurgical treatment of bbf fails , surgical exploration is inevitable . herein , we describe a case of bbf due to rfa for recurring hepatocellular carcinoma which was successfully treated with surgical resection and drainage . a 52-year - old woman was treated with percutaneous rfa for recurrent hepatocellular carcinoma ( hcc ) at segment 7 . her past medical history revealed that she had undergone central bisectionectomy for a 5-cm hcc , which was located between segments 4 and 8 , seven years ago . from august 2007 to may 2009 , after the operation , she had been treated with transarterial chemoembolization for a total of six times due to a recurrent hcc at her remnant liver segments . when the seventh recurrence was detected by follow - up liver computed tomography ( ct ) , rfa was performed percutaneously under ultrasonographic guidance in the 3.5-cm viable tumor of segment 7 , located in the liver dome and close to the diaphragm . after rfa , the total bilirubin level gradually increased without any other symptoms , and a level of 10.9 mg / dl was measured 5 days post - rfa . a liver ct was performed thereafter , and showed obstructions of the entire right portal flow with right bile duct dilatation and decreased perfusions of the atrophic right posterior section . endoscopic retrograde cholangiopancreatography ( ercp ) was performed and showed structure of the common hepatic ducts and dilatation of both intrahepatic ducts ( fig . endoscopic retrograde biliary drainage ( erbd ) was performed , and two plastic stents ( pigtail stents with 7-french and 10-cm length ) were inserted in the right and left bile ducts , respectively . the decreased level of total bilirubin was confirmed three days after stent insertions , and the patient was discharged without symptoms on that same day . the patient was then admitted through the emergency room 25 days later due to high fever ( 38.3 ) with no other symptoms . abdominal ct showed that the rfa zone had changed to an abscess pocket with small air bubbles . the patient was empirically treated with antibiotics for ten days and discharged with mild coughing according to the decreasing abscess cavities . the patient revisited the emergency room two days after discharge , i.e. , 41 days after the erbd was performed , presenting with a persistent cough producing yellow - green sputum and dyspnea with high - grade fever of more than 38. coughing increased when lying down and improved when sitting upright . blood test exhibited mild liver dysfunction , inflammatory reaction ( white blood cell counts 23.11,000/l , normal range , 3.2 - 8.61,000/l ; c - reactive protein 12.2 mg / dl , normal range 0.3 mg / dl ) , and hypoxemia , where the sputum analysis revealed a total bilirubin level of 3.1 mg / dl . a chest x - ray and abdominal ct demonstrated localized pneumonia in the lower right lobe of the lung and appeared as a consolidation . an abscess pocket in the right basal lung showed a fistula from an abscess cavity in the liver to the lower right lobe of the lung ( fig . 2 ) . surgical treatment was determined because the patient gradually aggravated with uncontrolled septic shock , and it was impossible to access the abscess pocket for drainage percutaneously or endoscopically due to the location . right posterior sectionectomy of the liver , a combined resection of the diaphragm and drainage of lung abscess with tube thoracostomy were all performed . the abscess cavity of the right posterior section contained bile - stained necrotic materials , and was communicated with an abscess in the right basal lung through a pinpoint perforation of the inflamed diaphragm . apart from localized visceral pleural damages , the lower right lobe appeared to be healthy and capable of full expansion . the diaphragmatic defect measured 10 cm in the largest diameter and closed primarily around the muscle . the right and left bile ducts around an abscess of the rfa zone were disrupted , and thus , a biliary reconstruction to the left lateral section by roux - en - y hepaticojejunostomy was required ( fig . the operative time was 460 minutes , and the amount of blood loss was 760 ml . no postoperative complications occurred , and nine days after surgery , the patient was discharged with symptomatic improvements . a 2-months follow - up chest x - ray demonstrated that the pleural effusion and pneumonic consolidation in the right basal lung were obliterated ( fig . 4 ) . clinical follow - ups continued for eight months without any further complaints . bbf was first reported by peacock in a patient with hydatid disease of the liver.4 rfa is one of a variety of causes for acquired bbf . in hepatocellular carcinoma , the use of rfa increased as an alternative or adjuvant treatment of surgical resection . as a result pathogenesis of rfa - related bbf probably results from diaphragmatic thermal injuries and intrahepatic biloma formations . in our patients , these causes seem to be the main factors for the development of the bbf . the developmental steps of the bbf occurring after rfa can be assumed as follows : collateral thermal injury of the diaphragm ; biloma formation around the ablative zone ; development of diaphragmatic defect with increased pressures due to a growing biloma ; rupture of the biloma into the diaphragmatic defect ; development of bilious pleural effusion and basal pneumonia ; and formation of a fistula between the diaphragmatic defect and injured terminal bronchioles.5 moreover , biliary tract injury during rfa causes biliary stenosis and cholangitis , which consequently requires erbd for our patients . even after the biliary decompression was achieved with erbd , bbf developed gradually due to thermal injuries of the diaphragm . bilioptysis defined productive coughs of bile - tinged sputum in nearly all the reported cases.2 the presence of bile in the sputum can be easily identified by using biochemical analysis of the sputum for bilirubin . other symptoms and signs include orthopnea , chest pain , fever , jaundice and abdominal pain . diagnosis can be confirmed by imaging procedures such as the hepatobiliary imino - diacetic ( hida ) scan , percutaneous transhepatic cholangiography ( ptc ) , ercp , ct or the magnetic resonance cholangiopancreatography ( mrcp).2 in this case , abdominal ct was performed when patients had symptoms such as bilioptysis , and showed fistula tracts between the biliary system and bronchial tree through the diaphragm . there is still no consensus on the optimal treatments of bbf . generally , there are two treatment options for bbf , such as operative procedures and nonsurgical interventions . surgical treatments have traditionally been performed with two - fold principles : first , to relieve any biliary obstructions and permit continuous free drainage of bile into the digestive tract usually through the creation of roux - en - y hepaticojejunostomy ; and second , to drain all abscesses and to excise the fistula tract together with the diseased lung segment or to completely obliterate the fistula tract.3,6 in this case , liver resection was performed due to disruptions of the bile duct wall and liver abscess , and thus , the abscess drainage of the lung was performed without resections of lung parenchyma . however , surgery for bbf in a patient , who has undergone liver resections and who is in a state of sepsis , could add to the negative sentiments for retrieval.3,7 nonsurgical treatments such as radiological and endoscopic interventions , which are less riskier than surgery , have been recently highlighted . in the previous cases , patients with bbf following rfa which are complicated by biloma or liver abscess successfully underwent external drainages with or without endoscopic drainage.5,8 there are reports on successful treatments of endoscopic nasobiliary drainage or endoscopic sphincterotomy in all cases.1 embolization of the bbf tract using cyanoacrylate glue through bronchoscopy has been reported as an alternative nonsurgical approach.9 however , these less invasive interventions usually involve long - term drainage maintenances with antibiotics after symptom improvements for complete remissions of the bbf and repeated for radiological manipulations.3,10 although the operative procedure for bbf may be complex with significant morbidity and mortality , surgery is ultimately considered in cases where the nonsurgical interventional techniques have failed or when there are complications from the underlying diseases , similar to our patient who had impossible accesses to the abscess pockets , uncontrolled sepsis , and progressions of pneumonic consolidation . in summary , a definite procedure such as surgery for bbf should be considered aggressively when the non - invasive interventions fail .

bronchobiliary fistula ( bbf ) is a rare complication of radiofrequency ablation ( rfa ) , in which there is abnormal communications between the biliary tract and the bronchial trees . surgery should only be considered for bbf when non - invasive interventions have failed . in this report , we describe the surgical management for bbf when complicated by an abscess that was encountered after rfa in a 52-year - old woman with recurrent hepatocellular carcinoma ( hcc ) . she had previously undergone central bisectionectomy of hcc 7 years ago , and had been treated with a sixth transarterial chemoembolization and first rfa for recurrent hcc after the operation . after the liver abscess and bbf occurred in the posterior section of the liver , she received posterior sectionectomy and hepaticojejunostomy , drainage of the lung abscess , diaphragmatic resection and repair because it was impossible to drain the abscess radiologically . symptomatic improvements were being achieved through operative treatments where pleural effusion and pneumonic consolidation was obliterated on a 2-months follow - up image .

human papillomaviruses ( hpvs ) are small , non - enveloped dna viruses ( 1 ) . hpv infection is associated with more than 90% of all the cases of cervical cancer , which is the second leading cause of cancer death among women worldwide 1 . , 2 .. hpvs have been classified into more than 100 types based on the nucleotide sequence homology of a single molecule of 8-kb double - stranded circular dna . each hpv type has different specificity for infection of skin or mucosa ( 3 ) . hpv virion ( 5560 nm in diameter ) is contained within an icosahedral capsid , which comprises l1 major and l2 minor capsid proteins ( 4 ) . l1 proteins form pentamers ( capsomeres ) , and 72 capsomeres assemble into a t-7d icosahedral lattice 5 . l2 proteins interact with l1 pentamers ( 5 ) . the molar ratio of l1 and l2 proteins is estimated to be 30:1 7 . , 8 .. l1 proteins can self - assemble into virus - like particles , which have the similar size , shape , and conformational epitope to native virion capsid proteins , although l2 proteins increase the efficiency of dna encapsidation by at least 50 folds 8 . , 9 . , 10 .. hpvs infect basal cells of epithelium through microlesions and replicate only in the differentiating cells . these cells are difficult to culture in vitro ; hence , no tissue culture system for the large - scale propagation of hpv virions in vitro is available at present . the study of these viral structural proteins is behind that of the oncoproteins of their counterfeits . consequently , little is known about the cellular and viral factors that control the switch and process of papillomavirus genome replication and viral protein expression . many events in the papillomavirus life cycle have not been elucidated , and particularly the nuclear transport process of the viral genome and structural proteins is poorly understood . however , at present the knowledge of l1 proteins of hpvs is understood at the molecular level in a certain extent . during the virus life cycle , l1 proteins seem to enter the nuclei of host cells twice . in the initial stage of hpv infection , immediately after the virions infect the undifferentiated proliferating epithelial cells , l1 proteins together with the viral genome are transported into the nuclei of proliferating epithelial cells . during the late stage of hpv infection , the newly synthesized l1 proteins in cytoplasm are transported into the nuclei of terminally differentiated keratinocytes to package the replicated hpv genomic dnas and assemble into infectious virions , together with l2 proteins ( 11 ) . this would suggest that the nuclear import of l1 proteins plays a very important role in hpv infection and production . the ability of the virus importing into the nucleus is determined by the nuclear localization signal ( nls ) in the c - terminal of hpv l1 proteins , so it is important to investigate the nlss of hpvs . to date , more than 120 hpv types have been isolated and partially characterized , and about 100 distinct hpv types have been identified and fully sequenced . the fact means that it is very difficult and unpractical to identify the nlss of all hpv types by experiments . in this paper , we attempt to analyze and predict the nlss of 107 types of hpv l1 proteins by bioinformatic analysis . the full sequences of 107 types of hpv l1 proteins were obtained from available databases ( see materials and methods ) . out of the 107 types , the nlss of 39 types were predicted by predictnls software ( http://cubic.bioc.columbia.edu/predictnls/ ) . among them , 35 types contain bipartite nlss , where the two tight clusters of basic residues ( one is krkr , krkrk , krkkrk , the other is kr , rkr , krk ) are preceded , with a spacer of 1014 amino acids . the other four types ( hpv22 , hpv34 , hpv48 , and hpv73 ) were predicted to contain monopartite nlss , where these arginines and/or lysines form a tight cluster of basic residues as typified by the simian virus 40 large t antigen ( sv40 t ) . the nlss of the remaining hpv types were predicted according to the characteristics and the homology of the already predicted nlss as well as the general rule of nlss . according to the result , the nlss of 107 types of hpv l1 proteins were classified into 15 categories ( table 1 ) , among which the categories xiv and xv contain monopartite nlss . in addition , the nlss of hpv l1 proteins 1 , 6 , 11 , 16 , 31 , 33 , 35 , and 45 can also be obtained from the literature 12 . in eukaryotic cells , the nucleus has a highly specialized structure that participates in the regulation of cell processes , including the regulation of cell cycle and the induction of antiviral responses ( 16 ) . the nuclear pore complex ( npc ) has a large supramolecular structure with a mass of 125 kda in vertebrates , which is embedded in nuclear envelope as the only gateway between nucleus and cytoplasm 17 . , 18 . , 19 . , 20 .. over the past years , a consensus model of the three - dimensional ( 3d ) architecture of npc shows that it is composed of an eight - fold symmetric central framework ( 21 ) . in the course of biological evolution , npc keeps a very high homology in eukaryotic cells , sharing a similar nuclear transport mechanism 19 . , 20 .. the nuclear import of proteins typically requires the presence of nlss , which are characteristically rich in basic amino acids 22 . , 23 . , 24 .. nls motifs play a key role in the nuclear transport mechanism . in order to enter into nucleus , the transport of proteins with a molecular weight ( mw ) at 4560 kda must be made through npc via an nls or be associated with another protein via a piggyback mechanism , whereas the nuclear import of small proteins ( mw<40 kda ) cross npc via passive diffusion 25 . , 26 . , 27 .. nlss are subsequently found in numerous viral and nuclear proteins of eukaryotic cells . at present the first category includes the monopartite ( single type ) nlss that contain 35 basic amino acids with the weak consensus lys - arg / lys - x - arg / lys residues preceded by a helix - breaking residue , which are similar to the sv40 t nls ( pkkkrkv ) ( 28 ) . the second category includes the bipartite nlss that contain two clusters of basic regions of 34 residues with a basic dipeptide upstream from a simple basic sequence , each separated by approximately 10 amino acids , which are similar to the nucleoplasmin nls ( krpaatkkagqakkkkldk ) 29 . , 30 .. the sequences ( pkkkrkv and krpaatkkagqakkkkldk ) found in sv40 t and nucleoplasmin are prototypes for monopartite and bipartite nlss , now known to be present in many , probably thousands of different proteins . nlss are capable of directing a non - karyophilic protein into nucleus when conjugated genetically or chemically . however , not all experimentally known nlss comply with the above rules 31 . , 32 . , 33 .. several other nls sequences have been identified , which are quite different from classical nlss , such as the nlss discovered in hnrnp proteins , ribosomal proteins , and usnrnps 34 . , 37 .. recent studies have identified several proteins that contain more than one nls , including the nuclear factor 1-a ( 38 ) , the cell division control protein mcm10 ( 39 ) , the herpes simplex virus gene product icp22 ( 40 ) , the hiv preintegration complex ( 41 ) , the epstein - barr virus dnase ( 42 ) , the papillomavirus oncoprotein e6 ( 43 ) , brca2 ( 44 ) , and rep68/78 proteins ( 45 ) . the enzyme 5-lipoxygenase ( 5-lo ) has three nlss that contain dispersed basic residues , unlike the tight cluster of basic residues of the classical sv40 t nls ( 46 ) . one explanation is that multiple nlss may cooperate with one another and allow more efficient nuclear import or share an alternative entry mechanism in the nuclear import , affording redundancy in proteins that require successful nuclear import , as in cell cycle proteins or viral integration proteins 42 . , 47 .. traditionally , in order to identify an nls experimentally , both of the facts should be considered routinely . firstly , the candidate should be deleted to disrupt the nuclear import of the nls ; secondly , a non - nuclear protein will be imported into the nucleus if fused to the nls ( 48 ) . it is very difficult and unpractical to identify the nls motifs of more than 120 types of hpvs by experiments . bioinformatic techniques perhaps could be applied to analyze and predict new nlss , which would remedy this situation . the method comprises two steps : ( 1 ) data collection : collect experimental nls motifs from literature , and extend the motifs through close homologues ; ( 2 ) generalization : refine the motifs found by shortening ( for those too specific ) or lengthening ( for those not specific enough ) , and test the new motifs conceptually similar to the known motifs found in nuclear protein families . the crucial component of both steps is to accept motifs if not found in non - nuclear proteins . therefore , it is feasible to discover new nlss in hpv l1 proteins by comparing the homologues of different types . according to cokol s method , we analyzed the hpv l1 protein sequences for the confirmation of nlss using predictnls software . out of the 107 types of hpv l1 proteins , the nlss of 39 types were predicted by predictnls . applying psortii and predictnls in general , two naturally evolved proteins with more than 30% identical residues could share similar 3d structures ( 50 ) . it is possible to infer nlss by comparing the homologues of more than one protein . due to the high homology of the nlss among the l1 proteins of all hpv types , we subsequently found similar sequences in the c - terminal of all the remaining 68 types of hpv l1 proteins , which were similar to the nlss already predicted by predictnls and collected in experimental data . according to the consensus rule of nlss and the high homologues , the nlss of 107 types of hpv l1 proteins were classified into 15 categories ( table 1 ) . among them , the categories i to xiii contain classical bipartite nlss , while the categories xiv and xv contain classical monopartite nlss . however , the nlss predicted in this paper have been proved with few experimental data . the cluster of basic residues rrr in the upstream of the bipartite nls ( rrrptigprkrpaast - stastasrpakrvrirskk ) of hpv45 has been proved certainly to have the nuclear localization ability ( 13 ) . the discontinuous basic amino acids k and r in the upstream of the nlss of 107 types of hpv l1 proteins perhaps also possess the ability of nuclear localization . at the same time , the nls of hpv33 was proposed to be bipartite , while the experimental result proved that hpv33 possibly contains a monopartite nls ( 52 ) . on the other hand , while the experimental results proved that many types of hpv l1 proteins ( for example , hpv1 , 6 , 31 , 33 , and 35 ) contain nlss , they can not be found by predictnls . whereas , it is not all the clusters of basic residues of predicted nlss that have the nuclear localization ability , such as the nls of the il1 53 . therefore , it is surely worth amending and supplementing the classification . in conclusion , this classification would play an important role in the study of the nlss of hpv l1 proteins . the results of this paper suggested that the different hpv types classified in the same category could share the similar or the same nucleocytoplasmic transport pathway . the nlss in the same category would be used as a common realistic and feasible target for preventing and treating different types of hpv infection . the results also showed that bioinformatic technology could be used to analyze and predict the nlss of proteins . the hpv l1 protein sequences were searched from the following databases : http://cubic.bioc.columbia.edu/db/ http://www.ncbi.nlm.nih.gov/ http://www.stdgen.lanl.gov/stdgen/virus/ http://ca.expasy.org/ firstly , the initial sets from the literature for experimentally determined nlss were collected . secondly , entrez , blast , and dnaclub software tools were used to analyze the homology of all types of hpv l1 protein sequences obtained . the useful web server ( predictnls ) for identifying potential nlss in protein sequences is available at http://cubic.bioc.columbia.edu/predictnls/ and was used to analyze and predict the nlss of hpv l1 proteins . according to the characteristics and the homology of the nlss predicted by predictnls , as well as the general rule of nlss , the hpv l1 proteins were classified into 15 categories . the program also allows experimentalists to test the accuracy and coverage for new nls motifs that they may find or suspect . this feature has already helped to experimentally unravel a novel nls in the hairless protein ( 55 ) .

in this study , 107 types of human papillomavirus ( hpv ) l1 protein sequences were obtained from available databases , and the nuclear localization signals ( nlss ) of these hpv l1 proteins were analyzed and predicted by bioinformatic analysis . out of the 107 types , the nlss of 39 types were predicted by predictnls software ( 35 types of bipartite nlss and 4 types of monopartite nlss ) . the nlss of the remaining hpv types were predicted according to the characteristics and the homology of the already predicted nlss as well as the general rule of nlss . according to the result , the nlss of 107 types of hpv l1 proteins were classified into 15 categories . the different types of hpv l1 proteins in the same nls category could share the similar or the same nucleocytoplasmic transport pathway . they might be used as the same target to prevent and treat different types of hpv infection . the results also showed that bioinformatic technology could be used to analyze and predict nlss of proteins .

multiple sclerosis ( ms ) is a chronic autoimmune disease that causes deterioration of the myelin sheath leading to a myriad of neurological symptoms . there is still no understanding of what causes ms or a cure for the disease . fingolimod is an immunomodulatory drug that has recently been approved for the treatment of ms . it was the first oral medication approved for the treatment of ms , most notably for relapsing - remitting ms ( rrms ) . it is the first sphingosine 1-phosphate ( s1p ) receptor modulator to be approved as a medication for any disease . sphingolipids are a class of signaling molecules that are most densely expressed in the brain . fingolimod acts by agonizing the s1p1 receptor and producing a subsequent down - regulation of the receptor 's expression . when fingolimod is used , this function is interrupted thereby preventing some lymphocytes from entering the central nervous system ( cns ) . fingolimod also has the ability to cross the blood - brain barrier ( bbb ) , which allows it to directly affect the cns . the most exciting aspect of fingolimod may not be in its action but in its mode of administration . there are currently only three oral medications on the market for treating ms , including fingolimod . the drug has been able to produce remission in patients with severe rrms and some cases ease of nonremitting forms of ms . these cardiovascular effects are most likely caused by the down - regulation of s1p1 receptor function fingolimod causes . sphingolipids have been indicated as cardiovascular protectants that promote a regular heart rate . in rare cases cardiovascular side - effects may be more common in patient populations than suggested by clinical trials . in a phase iii trial , one woman died who did not have varicella - zoster virus ( vzv ) antibodies due to a lack of being immunized or previously having the chickenpox . when she contracted a primary infection while on fingolimod the results were deadly . in certain rare cases , patients on fingolimod developed aggressive skin cancer after the drug suppressed their immune function . the increased risk for skin cancer is also common with other immunomodulating ms therapies . the most common side - effects include fatigue , headache , back pain , diarrhea , and flu - like symptoms . this is the first study , to our knowledge , that will investigate the effect fingolimod administration has on a patient 's platelet ( plt ) count . most studies , both experimental and observational , cite fingolimod 's ability to produce lymphopenia , or a low lymphocyte count . in vitro , fingolimod increased populations of regulatory t cell populations , further supporting the claim that the drug actively suppresses immune function . there have also been studies citing a decrease in these regulatory t cells after application of fingolimod , or no significant change . investigating the effect fingolimod has on plt count in the ms population is important to deduce what health risks the drug poses for long - term usage . this quasi - experimental study was performed on 80 patients who were diagnosed with definite ms ( 15 men and 65 women ) . the study population of this investigation was selected from the isfahan multiple sclerosis society ( imss ) , the only referral system in isfahan . the severity of the patient 's disability was assessed using the expanded disability status scale . other clinical characteristics and paraclinical features were obtained using patient recall , the imss , and taking patient histories . in addition to giving an explanation about the study , written informed consent was obtained from all ms patients who were included in the study before initiation of the study procedure . the ethnical institutional committee of kashan university of medical sciences also approved this study 's protocol . before initiating fingolimod treatment of the ms patients , 3 ml of venous blood were collected from all subjects using routine venipuncture method and was stored in tubes containing edta as an anticoagulant . since the time of blood sampling ( day or night ) and physical activity can considerably affect the individual level of plts , all blood samples were collected in the morning without previous physical activity . the plt counts were determined using an automated cell counter within 24 h after collection . the cell count was done at the immunology laboratory of isfahan university of medical sciences . patients who have never had the chickenpox and never received the varicella vaccine were immunized with it 1-month prior to starting fingolimod therapy . in order to ensure that the antibodies for vzv were present in the patient 's blood , serology testing for varicella one month after beginning fingolimod therapy , all cases were called back to the imss and 3 ml blood samples were again obtained . again , other clinical features and paraclinical characteristics were obtained using a questionnaire required of all participants . statistical analysis was performed using spss for hardware ( version 20 , ibm , chicago , il ) . furthermore , paired sample t - test and independent sample t - test was used for other statistical analysis . all tests were two - tailed , and p < 0.05 was considered as a significant threshold . this quasi - experimental study was performed on 80 patients who were diagnosed with definite ms ( 15 men and 65 women ) . the study population of this investigation was selected from the isfahan multiple sclerosis society ( imss ) , the only referral system in isfahan . the severity of the patient 's disability was assessed using the expanded disability status scale . other clinical characteristics and paraclinical features were obtained using patient recall , the imss , and taking patient histories . in addition to giving an explanation about the study , written informed consent was obtained from all ms patients who were included in the study before initiation of the study procedure . the ethnical institutional committee of kashan university of medical sciences also approved this study 's protocol . before initiating fingolimod treatment of the ms patients , 3 ml of venous blood were collected from all subjects using routine venipuncture method and was stored in tubes containing edta as an anticoagulant . since the time of blood sampling ( day or night ) and physical activity can considerably affect the individual level of plts , all blood samples were collected in the morning without previous physical activity . the plt counts were determined using an automated cell counter within 24 h after collection . the cell count was done at the immunology laboratory of isfahan university of medical sciences . patients who have never had the chickenpox and never received the varicella vaccine were immunized with it 1-month prior to starting fingolimod therapy . in order to ensure that the antibodies for vzv were present in the patient 's blood , serology testing for varicella immunoglobulin g was done . after the first blood sampling , fingolimod treatment was immediately initiated . one month after beginning fingolimod therapy , all cases were called back to the imss and 3 ml blood samples were again obtained . again , other clinical features and paraclinical characteristics were obtained using a questionnaire required of all participants . statistical analysis was performed using spss for hardware ( version 20 , ibm , chicago , il ) . furthermore , paired sample t - test and independent sample t - test was used for other statistical analysis . all tests were two - tailed , and p < 0.05 was considered as a significant threshold . a total of 80 ms patients ( 15 men and 65 women ) with a mean age of 32.65 8.12 and the average age at onset of 29.68 7.94 were enrolled in this study . however , during the study 14 of them were excluded due to treatment - related complications , including cardiovascular , hepatic , gastrointestinal , hematologic , and dermatologic complications . all of the patients were diagnosed as cases of rrms according to the mcdonald 's criteria . clinical and paraclinical features of rrms patients the mean level of plts before initiation of fingolimod therapy ( plt1 ) among these ms patients was 256.53 66.26 . after 1-month of fingolimod treatment the plt level yielded an average of 229.96 49.67 ( plt2 ) . this number is significantly lower than the average plt count before treatment ( p < 0.01 ) . before initiation of treatment , the average plt counts for men and women were 229.81 53.54 and 261.87 67.67 , respectively . after 1-month of follow - up the level of plt reached 198.27 35.76 and 236.30 49.88 among men and women respectively . this shows a statistically significantly decreased level of plts circulating in both men and women . this reduction was more considerable among women ( p = 0.03 in men , p < 0.01 in women ) [ table 2 ] . our data showed that the vast of majority of the cases had decreased plt count after 1-month of treatment with fingolimod . plt count before and after treatment with fingolimod prior to the treatment , there was no significant difference between women and men relating to their plt count ( p = 0.14 ) , whereas after 1-month of beginning of the treatment , the plt count of women was significantly higher than that of men ( p = 0.01 ) . we did not have any patients , whose plt count dropped below the reference limit . our results show a statistically significant decrease in plt levels for patients taking fingolimod oral medication for 1-month . plt counts were decreased in the entire cohort and in both males and females separately . although these average levels did not drop below the normal range for adults , it should be noted that these levels are after only a month of treatment . further investigation will need to be done to determine what the long - term effects are taking fingolimod . while we do not have any other references to compare these results to , we do have a vast expanse of knowledge about the health risks fingolimod treatment poses . there is a significant lack of knowledge about what the long - term effects of taking fingolimod might be for different patient profiles . there is a dose - dependent relationship between fingolimod and adverse reactions to the drug . most severely , fingolimod users experience herpes zoster infections and cardiovascular effects including bradycardia . in an interesting study , they found that the treatment had no significant effect on plt function . besides the obvious health risks a continually decreasing plt count suggests such as an increased risk of bleeding , this information is crucial to understanding the function of sphingosine receptor for s1p . a decreased level of blood plasma s1p has been demonstrated after the myocardial infraction in rats . aspirin is an anti - plt drug that is often given to patients who have experienced negative cerebrovascular events . while a low - dose of aspirin might produce increased levels of s1p in the blood plasma , a higher dose can cause lowered levels of circulating s1p . if patients are experiencing cardiovascular symptoms from taking the drug , aspirin may be an option for treatment that could interfere with fingolimod 's effectiveness . the decrease in plt count in these patients , however , may be a positive force for protecting against ms . recent studies suggest plts as a sort of neuroinflammatory instigator that uses a compromised bbb to recruit and activate immune pro - inflammatory cells . in the mouse model for ms , experimental autoimmune encephalitis and in humans , plts were found in brain lesions suggesting this critical role plts have in neuroinflammation . however , it suggests that fingolimod 's effects may not be completely reliant on reducing classic autoimmune cells , such as lymphocytes . if so , this suggests that further treatments for autoimmune diseases such as ms could rely only on lowering plt counts to produce minimal side - effects for maximum gain . by avoiding the targeting of lymphocytes , many extreme side - effects such as rampant skin cancer and herpetical infections might be avoided . although ocwieja et al . , has earlier investigated the role of fingolimod in plt count , there is not many evidence with regard to the possible mechanisms that may have impact on the plt count and function , therefore , decreased plt count after fingolimod therapy that has been found in our study can show importance of investigating possible underlying mechanisms in future studies . the role plts have in ms and in fingolimod treatment needs to be further investigated in humans in order to elucidate these further treatment options . this is an area that has not been investigated previously in regards to fingolimod 's possible long - term effects on patient health . however , this study was only done 1-month after fingolimod treatment was initiated and as a limitation had no control group . further analysis of long - term users will need to be done in order to investigate how drastic the plt depletion is . our results also suggest that fingolimod 's effectiveness may lie in its ability to reduce plts in ms patients . this is an important step forward in treatment options for ms and other autoimmune diseases . if plts can be directly indicated in autoimmune pathogenesis , then perhaps they can be used as a primary target in treating these diseases .

background : while many studies have previously focused on fingolimod 's effect on immune cells , the effect it has on circulating and local central nervous system platelets ( plts ) has not yet been investigated . this study will elucidate what effects fingolimod treatment has on multiple sclerosis ( ms ) patients plasma plt levels . in addition , it will propose possible reasoning for these effects and suggest further investigation into this topic.methods:this quasi - experimental study used patients from the isfahan multiple sclerosis society to produce a subject pool of 80 patients , including 14 patients who ceased fingolimod use due to complications . the patients had their blood analyzed to determine plt levels both 1-month prior to fingolimod treatment and 1-month after fingolimod treatment had been started.results:the mean level of plts before initiation of fingolimod therapy ( plt1 ) among these ms patients was 256.53 66.26 . after 1-month of fingolimod treatment , the plt level yielded an average of 229.96 49.67 ( plt2 ) . this number is significantly lower than the average plt count before treatment ( p < 0.01).conclusions : ms patients taking oral fingolimod treatment may be at risk for side - effects caused by low plt levels . this may not be a factor for patients with higher or normal plt levels . however , a patient with naturally low plt levels may experience a drop below the normal level and be at risk for excessive bleeding . in addition to these possible harmful side - effects , the decreased plt population may pose positive effects for ms patients .

diabetes definition - diabetes is a disease which is caused by the inadequate production of insulin by the body or by the body not being able to properly use the insulin that is produced thereby resulting in hyperglycaemia ( high blood glucose levels ) ( 1 ) . almost 10 % of the adult population of pakistan suffers from diabetes mellitus ( 1 ) . diabetes mellitus plays an instrumental role in causing diseases like hypertension , cardiovascular diseases , diseases of skin appendages and gangrene ( 2 ) . other serious complications include retinopathy , neuropathy , nephropathy , and lower - extremity amputations ( 1 , 2 ) . proper management requires patients to be aware of the nature of the disease , its risk factors , its treatment and its complications ( 3 , 4 ) . diabetes mellitus along with its complications contribute a significant amount of burden on the society . this has resulted in a less efficient workforce and a huge economic burden on pakistan ( 5 ) . this study was conducted to assess the level of awareness among the diabetics of rural and urban populations of pakistan . the aim of this study was to find out the areas which need more attention in terms of resources and planning . this cross - sectional survey was conducted in july 2004 on randomly chosen diabetic patients of both rural and urban areas . the rural areas included habibabad , haveli koranga and baba kanwal ( all of which lie in punjab province ) . it contained true / false type of questions which were aimed to assess the awareness of diabetes mellitus in relation to its definition , types , causes , symptoms , control , management , treatment , complications and its relation to other diseases . a few examples of the questions asked are as follows : 1 ) to the best of your knowledge is diabetes a communicable disease true / false ? 2 ) to the best of your knowledge does diabetes have anything to do with insulin true / false ? 3 ) to the best of your knowledge does obesity have any relation to a person developing diabetes true / false ? apart from such questions the questionnaire also gathered data about sex , level of education and socio - economic status . all the surveys were administered in the presence of at least one of the authors . urban diabetic patients were surveyed in hospitals , schools , universities and their residences whereas rural diabetic patients were surveyed largely at village meetings ( chopaals ) . the majority of the population answered 610 questions correctly out of a total of 25 questions asked . similarly , 120 urban diabetic patients were asked the same 25 questions . in this case , the majority of diabetic patients gave 1620 answers correctly as shown in figure 1 . the mean awareness among the rural population was 13 ( sd 2 ) correct answers out of a possible 25 . in the case of the urban diabetic patients , the mean awareness was 18 ( sd 2 ) correct answers . out of the 120 urban diabetic patients surveyed , 71 were males and 49 were female . in comparison the data was also collected and tabulated ( table 1 ) based on the level of education of each participant . it was determined that that in the rural cohort , almost half of the participants had never gone to school at all ; comparatively , a quarter of the urban participants had no formal education . in the present study , we have sought to determine the awareness level of both urban and rural diabetic patients about the disease . the strategy of this study was to prepare a questionnaire that would test the basic knowledge of diabetes mellitus , its definition , types , causes , symptoms , complications , management , treatment and relation to other diseases . this survey was administered to both rural and urban diabetic patients . our study shows that the urban diabetic patients are much more educated about diabetes when compared with the rural diabetic patients . upon reviewing the answers to certain questions desi ghee ( a condiment high in cholesterol and saturated fatty acids ) instead of cooking oil among both the rural and urban diabetic patients . one other finding which was prevalent among rural diabetic patients was their preference to consult hakeems ( muslim physicians ) over doctors when it came to diabetes . one factor which was observed to play a role in improving awareness was the level of education attained . a well - educated person had a much higher awareness level than a person who had received no education whatsoever . as a result , we want future studies to look into this factor , and assess to what extent this factor plays a role . female diabetic patients were found to be far less aware of diabetes mellitus when compared with the males . one reason for this finding could be the low female literacy rate in pakistan ( 6 ) . again , it emphasizes that future studies should be carried out to determine the link between education and diabetes awareness . the link between awareness and socio - economic status is another factor that should be studied more deeply . it was observed during our study that diabetics belonging to poor socioeconomic status were less aware than those belonging to the higher class . while conducting this research , the authors have inculcated ideas on how to improve awareness about diabetes mellitus . in the short run , the authors believe that increasing the level of awareness among village elders in india and pakistan would be a very potent strategy . the organization in rural areas is such that all people are required to meet on a weekly or monthly basis at meetings known as chopaals , where the village elders dispense their experiences . in making the elders more aware , the trickling effect may make the general rural population more aware about diabetes mellitus . another strategy is to make the hakeems in the rural population more informed about the population s level of awareness , and help guide them to increase the awareness of their patients . the common rural citizen has a lot of fears concerning doctors and allopathic medication . as a result , increasing the level of awareness of the hakeems could to some extent help the general population as well . however , in the long run improving education standards and socioeconomic status is no doubt the cornerstone in enhancing diabetes mellitus awareness . in conclusion , our study has provided direct evidence that urban diabetic patients are more aware than rural diabetic patients about diabetes mellitus . we have provided some discussion with regards to other factors that determine the awareness level of diabetes mellitus .

a questionnaire - based cross - sectional study was carried out to assess the awareness of diabetes mellitus among rural and urban diabetics . after analyzing the awareness level of both populations , the urban diabetics were found to be more educated about diabetes . a 25-question survey was used to judge the awareness level of diabetes mellitus . a total of 240 diabetics were surveyed , 120 each from rural and urban areas . the mean awareness among the rural population was 13 ( sd 2 ) correct answers out of a possible 25 . similarly , in the case of the urban diabetics the mean awareness was 18 ( sd 2 ) correct answers . the survey was conducted on randomly chosen diabetics belonging to lahore and faisalabad , ( urban areas ) , as well as habibabad , haveli koranga and baba kanwal ( rural areas ) . the results emphasize the interrelation between demography and awareness of diabetes mellitus . the rural diabetics are far less knowledgeable about diabetes mellitus , its management and its complications . thus , there is an urgent need to improve the awareness level of diabetes mellitus in rural areas . doing so will give rise to a healthier workforce and a lessened economic burden on pakistan .

the recently recognized escherichia coli clonal group a ( cga ) accounts for up to 50% of trimethoprim - sulfamethoxazole ( tmp - smz)resistant e. coli from u.s . available data show cga to exhibit a stereotypical virulence factor ( vf ) profile and a conserved multidrug antimicrobial resistance phenotype , i.e. , to ampicillin , chloramphenicol , streptomycin , sulfonamides , tetracycline , and trimethoprim ( acssuttp ) , which is conjugally transferable on a large plasmid ( 1,2 ) . together with cga s unusual o antigens ( o11 , o17 , o73 , and o77 ) , these findings suggested that cga represents a newly emerged virulent clonal group ( 1,2 ) . cga s homogeneity across geographic locales , and the indistinguishable pulsed - field gel electrophoresis ( pfge ) profiles of clustered cga isolates within 1 community ( 1 ) , suggested recent and possibly ongoing dissemination , a novel paradigm for extraintestinal pathogenic e. coli ( expec ) ( 4 ) . to date , cga has been studied only within the united states , predominantly among women with uncomplicated urinary tract infections ( uti ) . its occurrence in some locales has been questioned ( 5 ) , and its antimicrobial susceptibility profile has been assessed for only 12 drugs ( 1,2,6 ) . accordingly , we sought to more fully define the global distribution , host range , virulence characteristics , and resistance phenotypes of cga . , 10 non - u.s . ) each provided approximately 25 consecutive tmp - smz resistant and tmp - smz susceptible e. coli isolates , except for 2 that provided resistant isolates only ( table 1 ) . isolates were distributed by specimen type ( urine / other ) and source ( inpatient / outpatient ) . antimicrobial drug resistant and susceptible isolates were collected approximately concurrently in 2001 from each site , except london ( 1999 ) ( 7 ) and columbus ( 1999 and 2002 ) . when available , data regarding specimen type and host gender , age , and inpatient / outpatient status were provided . * isolates were collected in 2001 for all sites except london , england ( 1999 ) , and columbus , ohio ( 1999 for susceptible isolates and part of resistant isolates ; 2002 for remaining resistant isolates ) . eighteen centers contributed both susceptible and resistant isolates ( total , 47 to 100 isolates each ; median , 55 ) . two centers contributed only resistant isolates ( chicago , il : 24 isolates ; england : 46 isolates ) . specimen type was known for 55 of the cga isolates and was urine for 42 , nonurine for 13 ( 10 blood , 1 tracheal aspirate , 1 fecal , 1 unspecified nonurine ) . phylogenetic group ( a , b1 , b2 , or d ) was defined by triplex polymerase chain reaction ( pcr ) ( 8) . group d isolates were defined as cga if by random amplified polymorphic dna ( rapd ) analysis they resembled cga controls with primers 1254 and 1290 , or with one of these plus 2 of primers 1247 , 1281 , or 1283 ( 2 ) . cga isolates and ( 2:1 ) geographically matched controls selected randomly based on the local tmp - smz resistance prevalence were tested for 35 expec - associated virulence markers and 13 papa alleles by pcr ( 2 ) . isolates were defined as expec if positive for > 2 of papa and/or papc , sfa / foc , afa / dra , iuta , and kpsm ( 10 ) . the aggregate virulence score was the number of different virulence markers detected in an isolate , adjusted for multiple detection of certain operons . o typing was carried out by the e. coli reference center ( university park , pa ) . o antigens o1 , o2 , o4 , o6 , o7 , o16 , o18 , o25 , and o75 were considered uti - associated ( o - uti ) ( 10 ) . susceptibility testing of the isolates to 30 drugs was carried out by broth microdilution ( 11 ) or disk diffusion ( nitrofurantoin ) ( 11 ) , by using e. coli atcc 25299 for reference and national committee for clinical laboratory standards ( nccls)specified interpretative criteria ( 12 ) , except for kanamycin , spectinomycin , and streptomycin ( resistant at mics of > 25 mg / l , > 128 mg / l , and > 8 mg / l , respectively ) . the aggregate resistance score was the number of different agents to which an isolate exhibited resistance . statistical analysis used a fisher exact or a chi - square test for comparisons of proportions and the mann - whitney u test for comparisons of scores . multiple variables were assessed as predictors of selected outcomes by multivariate logistic regression or multiple linear regression . the 1,102 clinical e. coli isolates were divided evenly by u.s . and non - u.s . overall , phylogenetic group b2 predominated ( 44% ) , followed by group d ( 27% ) . than non - u.s . isolates ( 34% vs. 21% : p < 0.001 ) . tmp - smz resistant isolates exhibited significant shifts from group b2 toward groups a , d , or both . the nearly 2-fold greater prevalence of group d among tmp - smz - resistant isolates reversed , for u.s . * ecor , e. coli reference tmp - smz , trimethoprim - sulfamethoxazole . ( by fisher exact test ) for comparison of susceptible and resistant isolates are shown when < 0.05 . for prevalence of group b2 ( versus group d ) within same column ; p 0.01 , mcnemar s test . resistant isolates ; p < 0.001 ( fisher exact test ) . by rapd analysis , 23% of group d isolates ( 6% overall ) represented cga ( table 2 ) . cga was strongly associated with tmp - smz resistance ( 10% of resistant isolates , 1.7% of susceptible : p < 0.001 ) and a u.s . tmp - smz resistant isolates and 5% of those from abroad ( p < 0.001 ) , but for a similarly low proportion of u.s . according to multivariate logistic regression analysis , after accounting for tmp - smz resistance and u.s . origin , none of the other source variables ( specimen type and host gender , age , and inpatient / outpatient status ) was significantly associated with cga status or appreciably altered the association of tmp - smz resistance or u.s . cga occurred in all but 3 locales ( 110 isolates per locale ) , accounting for up to 29% of local resistant isolates ( median , 9.5% ) ( table 1 ) . cga was highly prevalent ( 20%25% ) among resistant isolates from the 3 pediatric centers ( columbus , houston , and toulouse ) and the veterans hospital ( tucson ) . cga accounted for 29% of the ostensibly nonclonal ( 5 ) tmp - smz resistant isolates from chicago . consistent with this , xbai pfge profiles of 6 chicago and 2 reference cga isolates were highly similar ( figure 1 ) . xbai pulsed - field gel electrophoresis profiles of escherichia coli clonal group a ( cga ) isolates and e. coli o157:h7 . six cga isolates from chicago , il ( a series identifiers ; lanes 1 , 3 , 4 , 5 , 7 , and 8) exhibit similar profiles to reference cga isolates seq102 ( from california ; lane 2 ) and umn26 ( from minnesota ; lane 6 ) ( 1 ) . cga isolates differed significantly from controls , according to almost all characteristics analyzed ; they were significantly enriched with the o11 , o17 , and o77 antigens , certain vfs ( f16 papa allele , papahcefg , papg allele ii , iha , iuta , kpsm ii , trat , and ompt ) , and expec status , but lacked other traits ( figure 2 ) . aggregate virulence scores were similar for cga and controls ( medians , 8.0 ) but were less diverse for cga ( range 59 , vs. 113 ) . virulence traits ( top ) and antimicrobial resistance phenotypes ( bottom ) of escherichia coli clonal group a ( cga ) isolates versus non - cga controls . percent of isolates positive for each virulence trait ( top ) or resistance phenotype ( bottom ) is shown by pink bars to left of midline ( for cga ) or blue bars to right of midline ( for controls ) . no isolates were positive for bmae ( m fimbriae ) , or resistant to amikacin , aztreonam , cefepime , ceftazidime , ertapenem , imipenem - cilistatin , nitrofurantoin , piperacillin - tazobactam , or ticarcillin - clavulanate . p value symbols at right of each chart , from fisher exact test or test , are for significant differences between cga and non - cga . * , p < 0.05 ; * * , p 0.01 ; * * * , p 0.001 . by multivariate logistic regression , both cga status and phylogenetic group b2 were significant independent predictors of expec status , with cga exhibiting an odds ratio ( or ) of 21.9 ( 95% confidence interval [ ci ] , 6.178.2 ; p < 0.001 ) , and group b2 an or of 2.4 ( ci , 1.73.4 ; p < 0.001 ) . additionally , by multiple linear regression , cga status ( standardized regression coefficient [ ] = 0.57 ; p < 0.001 ) and group b2 status ( = 0.596 ; p < 0.001 ) predicted vf score better than did o - uti ( = 0.32 ; p = 0.002 ) . antimicrobial resistance phenotypes were compared between cga isolates and a subset of the controls , which had been selected to provide an unbiased distribution of tmp - smz resistance ( figure 2 ) . cga exhibited a higher prevalence of resistance to 10 individual drugs , any drug , and acssuttp , whereas controls exhibited a low but measurable prevalence of resistance to 7 drugs to which all cga isolates were susceptible . accordingly , resistance scores were significantly higher for cga than controls ( median 8.0 [ range 111 ] vs. 5.5 [ range 015 ] ; p = 0.001 ) . 520/9,880 mg / l ; 61% of resistant isolates had mics > 520/9,880 mg / l . cga accounted for 67% of this highly resistant population ( p = 0.01 vs. controls ) . the u.s . and non - u.s . cga isolates exhibited only 2 statistically significant differences for vf profiles , o antigens , and resistance phenotypes , with iron ( p = 0.03 ) and absence of ompt ( p = 0.008 ) associated with non - u.s . we found that the recently described e. coli cga is globally but heterogeneously distributed and more prevalent within the united states than abroad . clonal group a affects diverse host populations ( including inpatients , outpatients , adults , children , men , and women ) , infects urinary tract and nonurinary tract sites , is strongly associated with tmp - smz resistance ( including high - level resistance ) , and exhibits a robust virulence profile suggesting enhanced extraintestinal virulence . this combination of resistance and virulence may account for cga s recent emergence as a broadly disseminated epidemic clone however , it also could reflect more rapid clonal expansion within the united states due to enhanced dissemination or more favorable conditions for outgrowth , including possibly less competition from other potential occupants of the same niche(s ) . the variable prevalence of cga among even closely situated locales , both within the united states and abroad , might reflect true geographic heterogeneity , versus locale - specific differences in patient populations , selection criteria , and collection intervals . studies that compare well - defined , homogeneous , concurrent populations from different locales are needed . the new evidence of cga as a prominent tmp - smz resistant pathogen among children and veterans extends the known host range of cga , consistent with a recent report of cga as a community - wide tmp - smz - resistant pathogen in denver , colorado ( 6 ) . this finding illustrates cga s pathogenic versatility . that 29% of the tmp - smz resistant isolates from chicago , illinois , proved to be cga and resembled reference cga isolates by pfge , despite a previous pfge - based assessment of nonclonality ( 5 ) , illustrates the limitations of conventional pfge analysis as a screen for cga . we have developed a cga - specific pcr assay , based on a single nucleotide polymorphism within fumc , to provide improved screening for cga ( 15 ) . cga s robust , highly homogeneous consensus vf profile ( f16 papa allele , papg allele ii , iuta , kpsm ii , trat , and ompt ) suggests considerable extraintestinal virulence potential , an inference supported by experimental data indicating that cga is able to compete successfully with classic group b2-derived pathogens in a mouse uti model ( j.r . determination of which vfs of cga contribute most to pathogenicity may identify future targets for preventive interventions . in our study , antimicrobial resistance was more extensive and , with tmp - smz , more potent for cga than controls . conceivably , high - level tmp - smz resistance could allow cga to out - compete even other tmp - smz resistant strains . cga s resistance involved primarily older agents , whereas fluoroquinolone and cephalosporin resistance was confined to controls . however , the emergence of fluoroquinolone resistance within the closely related o15:k52:h1 clonal group ( 2,13 ) suggests that this potential exists also for cga . the study s strengths include large population , broad geographic sampling , matching of cga and control isolates , and extensive range of traits analyzed . limitations include the heterogeneous inclusion criteria , gaps in global surveillance , possible type i errors from multiple comparisons , and limited sampling per locale . in summary , we found cga to be a globally disseminated , multidrug - resistant clonal group of pathogenic e. coli with a broad range of human hosts . although more prevalent within the united states than abroad , cga exhibits characteristic o antigens , resistance markers , and virulence traits wherever encountered . further study is needed of the origins , virulence mechanisms , geographic distribution , clinical associations , and modes of dissemination of cga .

among 1,102 recent escherichia coli clinical isolates , clonal group a was identified in 17 of 20 ( u.s . and non - u.s . ) geographic locales , mainly among u.s . isolates ( 9% vs. 3% ; p < 0.001 ) and those resistant to trimethoprim - sulfamethoxazole ( 10% vs. 1.7% ; p < 0.001 ) . the extensive antimicrobial resistance and virulence profiles of clonal group a may underlie its recent widespread emergence .

foreign body ingestion does not usually necessitate aggressive surgical interventions as most foreign bodies pass through the gastrointestinal tract without causing harm . nonetheless , gastrointestinal perforation remains a potential major complication of foreign body ingestion reported to occur in around 1% of cases . dietary foreign body ingestion such as fish bones , chicken bones and shell fragments causing gastrointestinal perforations have been reported . surgical intervention aiming to remove the offending foreign body and to restore gastrointestinal continuity remains the mainstay of management . this case represents early diagnosis followed by successful endoscopic management of gastric perforation caused by an ingested chicken bone , potentially avoiding more invasive surgical interventions . a 68 year old complained of a 2-day history of a non - remitting localized epigastric pain associated with anorexia and night time sweating . the patient denied any difficulty swallowing , lasting heartburn , nausea , vomiting or recent changes in bowel habits or having similar pain episodes in the past . the patient was otherwise known for hypertension , coronary artery disease and a recent cerebrovascular accident on appropriate medications including aspirin and plavix . the patient was febrile at 38.1 c while the rest of his vital signs were within normal limits . his abdominal exam revealed a well localized area of tenderness in the epigastric region associated with voluntary guarding . initial laboratory investigations were unremarkable except for a markedly elevated white blood cell count to 23.9 10 . an ultrasound of the liver ruled out the presence of biliary diseases that can explain the patient s signs and symptoms . a ct scan of the abdomen revealed the presence of a radiopaque elongated structure that penetrates through the full thickness of the gastric wall , close to the pylorus , reaching the head of the pancreas with surrounding inflammatory changes ( fig . 1 ) . although there was no evidence of extra - luminal air , free fluid was noted to surround the head of the pancreas extending to gerota s fascia on the right side . the findings seen on radiologic imaging were discussed with the patient as well as the therapeutic options that can be offered . these therapeutic options included laparoscopic versus open exploration of the abdomen with planned removal of the foreign body and closure of the gastrointestinal defect . a trial of endoscopic removal of the foreign body was also offered acknowledging that outcomes can not be guaranteed given the uncommonness of the situation . the patient willingly consented for an endoscopic trial prior to a more invasive surgical intervention understanding the risks and benefits of his choice . the patient had been started on broad - spectrum antibiotics besides an intravenous continuous infusion of pantoprazole and he was shortly wheeled to the operating room . in the operating room , the patient was given intravenous sedation with 2.5 mg of midazolam after applying topical lidocaine to the back of the throat . the gastroscope was introduced under direct visualization with minimal inflation of air and advanced carefully . the chicken bone was then clearly seen penetrating the gastric wall in the prepyloric area with surrounding inflammation and swelling of the gastric mucosa ( fig . initially , we tried retrieving the chicken bone by encircling its blunt end leaving the sharp end to trail to minimize the chance of oesophageal injury . however , due to the structure of the bone , the bone kept on retaining a certain angulation . we then decided to encircle the sharp end with the snare device putting it in close proximity to the gastroscope s camera . using this method the chicken bone was 4.8 cm long with a rounded blunt end which tapers down to a more pointed end ( fig . the oesophagus and stomach were re - examined by the gastroscope ensuring the absence of iatrogenic injuries . the site of perforation was clipped using an endoscopic metallic clip ( figs . 4 and 5 ) . the next day , the patient reported no pain and was allowed to drink then was rapidly progressed to full diet . his epigastric tenderness dissipated and his white cell count dropped dramatically reaching 9.1 10 by the second day . the patient was discharged home with a 10 day course of oral antibiotics and pantoprazole . it has long been observed that foreign body related perforations occurring in the stomach , duodenum and large intestine tend to follow a subtle clinical course leading to their delayed presentation , diagnosis and subsequent management . this phenomenon is thought to be due to the characteristic thick muscular wall of these hallow organs and the presence of surrounding omentum and solid organs . consequently , a more gradual perforation occurs coupled by a simultaneous sealing effect from nearby tissue eventually yielding in most cases intra - abdominal abscesses . hence , having a high degree of suspicion can aid in reaching an early diagnosis and instilling appropriate management . endoscopic procedures have played a major rule in retrieval of ingested foreign bodies that can potentially lead to gastrointestinal complications if left unattended . yet the rule of endoscopic management when perforations occur is not well defined but is certainly gaining recognition . similar to the presented case , two reported cases have demonstrated successful endoscopic management of gastric perforation caused by ingested chicken bone . the main culprit in successful endoscopic management seem to be related to early diagnosis prior to the development of intra - abdominal abscesses . high degree of suspicion is important in diagnosing foreign body related gastrointestinal complications as the clinical presentation can be elusive . early diagnosis allows for the utilization of less invasive therapeutic interventions , subsequently leading to faster recovery . in the right context , both authors contributed in the clinical care of the patient and subsequent follow up as well as writing up the case report .

highlightswe discuss a case of gastric perforation caused by a sharp chicken bone ingestion.early diagnosis lead to successful minimally invasive management using an endoscopic approach.high degree of suspicion is important in diagnosing foreign body related gastrointestinal complications as the clinical presentation can be elusive.early diagnosis can allow the utilization of less invasive therapeutic interventions , subsequently leading to faster recovery.in the right context , therapeutic endoscopy can help to avoid more aggressive surgical interventions .

sepsis , the host response to infection , involves a series of clinical , haematological , inflammatory and metabolic responses that can ultimately lead to organ failure ( 1 ) . insulin resistance generally refers to resistance to the metabolic effects of insulin , including the suppressive effects of insulin on endogenous glucose production , the stimulatory effects of insulin on peripheral ( predominantly skeletal muscle ) glucose uptake and glycogen synthesis and the inhibitory effects of insulin on adipose tissue lipolysis ( 2 ) . sepsis is an insulin resistance state and the degree of insulin resistance is directly proportional to the severity of stress response ( 3 ) . multi organ dysfunction syndrome ( mods ) as per the definition proposed by a consensus conference committee in 1992 , fever or hypothermia , leucocytosis or leukopenia , tachypnea and tachycardia are the cardinal signs of systemic response often called as systemic inflammatory response syndrome ( sirs ) ( 4 ) . sepsis is defined as sirs due to known infectious aetiology . when sepsis is associated with dysfunction of organs e.g. distant from the site of infection , the patient has severe sepsis . severe sepsis may be accompanied with hypotension or evidence of hypo - perfusion . when hypotension can not be corrected by infusing fluids , the diagnosis is septic shock . refractory septic shock is defined as septic shock that lasts for > 1 h and does not respond to fluid or pressure administration , and multiple organ dysfunction syndrome is the dysfunction of more than one organ , requiring intervention to maintain homeostasis . as sepsis progresses to septic shock and mods , sepsis is usually reversible whereas patients with septic shock and mods , often succumb despite aggressive therapy ( 5 ) . the metabolic response to critical illness includes stimulation of the hypothalamic - pituitary - adrenal axis , resulting in increased levels of growth hormone , prolactin and acth level which stimulates excess of cortisol production from the adrenal cortex . catecholamine , both endogenous and exogenous ( given to maintain circulation ) , also contribute to the hyperglycemia during critical illness . mediators of systemic inflammatory response such as interleukin-1 ( il-1 ) and tumor necrosis factor alpha ( tnf- ) , cause hyperglycemia and peripheral insulin resistance by inducing the release of stress hormones . they also alter insulin receptor signaling pathway in the target cells and create insulin resistance ( 6 - 8 ) . mild hyperglycemia in critically ill patients can also be harmful since it acts as procoagulant , induces apoptosis , impairs neutrophils function , increases risk of infection , impairs wound healing and is associated with increased mortality even after adjusting for severity of illness ( 1 , 9 ) . the aim of the study is to define the insulin resistance ( ir ) and to compare ir and amount of insulin with infectious complication among neurosurgical intensive care ( nsic ) patients in mother theresa university hospital center ( mtuhc ) in tirana albania . 154 patients with infectious complication among neurosurgical intensive care patients in mtuhc , were selected and randomized in two groups according to early versus late nutrition . finally 73 ( 47% ) patients were randomly assigned to early nutrition group and 81 ( 53% ) to late nutrition group . the data included age , gender , length of stay , white blood account , glycemia was measured every hour , amount of insulin used per patients measured as units per day , sirs complications , body mass index ( bmi ) , body temperature , cardiac and respiratory frequencies , blood pressure . blood , urine , cerebrospinal liquor ( csl ) and bronchial secretions bacteriological examinations were also performed . we define the insulin resistance as need of 200 or more units of insulin per day to control blood sugar levels ( 10 ) . the level of glycemia was maintained between 80 - 110 mg / dl based ( tight glycaemic control protocol ) ( 11 ) . in the early nutrition group the nutrition begun within the first 72 hours after admission in icu and in the late nutrition group the nutrition begun more than 72 hours after admission . all groups were given the same nutrition : fresubine ( enteral ) and cabiven ( parenetral ) . the difference between two groups it the time when nutrition begun ( 11 , 12 ) . european society of parenteral and enteral nutrition ( espen ) guidelines were used for nutrition in icu . during the acute and initial phase of critical illness an exogenous energy supply in excess of 20 - 25kcal / kg bw / day may be associated with a less favorable outcome . during recovery ( anabolic flow phase ) , the aim should be to provide 2530 total cal / kg bw / day ( 12,13 ) . all patients receiving less than their targeted enteral feeding after 2 days should be considered for supplementary parenteral nutrition ( 13 , 14 ) . for our purposes , average and standard deviation for age , bmi , length of stay , amount of insulin per day ( unit / day ) , amount of calories per kg / weight per day used were calculated and reported . the analysis of covariance ( anova ) was used to compare the average amount of insulin between two groups . for our purposes , average and standard deviation for age , bmi , length of stay , amount of insulin per day ( unit / day ) , amount of calories per kg / weight per day used were calculated and reported . the analysis of covariance ( anova ) was used to compare the average amount of insulin between two groups . out of 154 patients selected in our study , 73 ( 47% ) were assigned to the early nutrition group and 81 patients ( 53% ) to the late nutrition group . table 1 shows the bmi after 7 days in late nutrition group is lower than the early nutrition group ( p=0.04 ) due to probably serious complications . comparing other variables did not find reveal any statistical difference between the two groups ( p>0.05 ) . statistical significance p0.05 table 2 shows that there are no statistical differences between two groups regarding all categorical variables . statistical significance p0.05 average insulin value was 12 ( 8.7 ) ui among early nutrition group and 23.8 ( 12.9 ) among late nutrition group , with statistical significance difference ( p<0.01 ) ( figure 1 ) . insulin amount ( u / day ) according to nutritional way ( early vs late nutrition ) . we had no patient in early nutrition group who developed insulin resistance but among the patients of late nutrition group , six of them ( 7.4% ) developed insulin resistance . we noted that with sirs was present in 45 ( 68.6% ) patients of early nutrition group and 11 ( 13.6 ) patients of late nutrition group ( p<0.01 ) ( figure 2 ) . sepsis had developed in 19 ( 26.0% ) patients in early nutrition group and 58 ( 65.4% ) patients in late nutrition group ( p<0.01 ) . moreover , septic shock had developed in 2 ( 2.7% ) patients of early nutrition group and 12 ( 14.8% ) patients of late nutrition group ( p=0.01 ) . finally , mods was present in 2 ( 2.7% ) patients of early nutrition group and 5 ( 6.2% ) patients of late nutrition group ( p<0.01 ) ( figure 2 ) . it is the first study evaluating insulin resistance in our intensive care unit and in the field of intensive care in albania . all the patient were not diabetics nor did they present with infectious problems and we think that in this contingent of patients it is feasible to exactly define the role of insulin and the effects of early and late nutrition on infectious problems ( sirs and its complications ) , through an experimental study design . in our study we included patients that stayed 7 days or more in our icu in order to better distinguish the influence of nutrition way ( early vs. late ) and to study appropriately evaluate the insulin resistance among them . sepsis was the most frequent complication among our patients ( 50% ) compare with other complications ( p<0.01 ) . among the icu patients and especially among septic patients hyperglycemia is a very frequent phenomenon . this hyperglycemia is due to increasing level of counter regulatory hormones of glucose metabolism ( cortisol , glucagon ) as well as increasing level of catecholamine . important role is also played by insulin resistance and for this reason we have implemented the tight glycaemic control protocol , maintaining the blood sugar at levels 80 110 mg / dl ( 12 ) . we found in our study that the average amount of insulin per day in order to maintain the glycemia levels above mentioned levels was higher in the late nutrition group than in the early nutrition group ( p<0.01 ) . we think that this is due to less severe infective complications that were found in this group . about the insulin resistance we did nt found any patient with insulin resistance in early nutrition group compared with 6 ( 7.4% ) patients in the late nutrition group . this is according to the definition of insulin resistance that we use in our study ( 10 ) . from this study we concluded that the insulin resistance developed more commonly in neurosurgical icu patients that received late nutrition compared to receiving early nutrition . this is associated with the high rate of infectious complications and severity of the infections in these patients .

background : systemic inflammatory response syndrome ( sirs ) is a common complication in neurosurgical diseases in intensive care unit ( icu ) . because of associated insulin resistance ( ir ) the icu is in dilemma in which stage to start the nutrition to patients and what is the amount of insulin unit to control the hyperglycemia.aim:to define the ir and to compare ir and amount of insulin among icu patients in mother theresa university hospital center ( mtuhc ) in tirana albania.methods:154 patients with neurosurgical disease and sirs complications were randomized in two groups : early nutrition 73 patients ( 47% ) and late nutrition 81 ( 53% ) and compared for a number of variables.results:there was no statistical age and gender difference between the two groups ( p>0.05 ) . the amount of insulin units to control the level of glycemia ( 80 - 110 mg / dc ) was 12.87 unit per day in early nutrition and 23.8 12.9 units in late nutrition group ( p<0.01 ) . no patient in early nutrition group but six ( 7.4% ) patients in late nutrition group developed insulin resistance ( p=0.03).conclusions : the ir due to the infection complications is higher among late than early nutrition group . therefore , we suggest that in neurosurgical icu it would be better to start the nutrition within 72 hours .

saliva is an oral fluid that has been used as a diagnostic tool in medicine and dentistry . the source of the specimen that can be used for salivary markers are whole saliva , gingival crevicular fluid ( gcf ) and plaque . among these , enzymes released from the host can be easily obtained within the oral cavity either from gcf or from the whole saliva . several enzymes evaluated for the early diagnosis of periodontal disease are lactate dehydrogenase , alkaline phosphatase ( alp ) , acid phosphatase , aspartate aminotransferase and alanine aminotransferase . sampling technique for gcf collection is a time - consuming process and is a difficult procedure . this was first recognized by ishikawa and cimasoni , who demonstrated a level of alp enzyme in gcf and showed a significant correlation between alp concentration in gcf and pocket depth . so easy , non - invasive , less time - consuming , chairside technique like salivary - alp ( s - alp ) analysis from saliva samples was preferred in our study . the by - products of cigarette smoking such as carbon monoxide , hydrogen cyanide and benzopyrene are toxic . cigarette smoking is known to be one of the major causes of various health disorders . these toxic components can predispose to different systemic disorders , such as cardiac diseases , cancers , precancerous lesions and pulmonary disorders . the salivary antioxidant system plays a very important role in the anti - carcinogenic capacity of saliva and includes various enzymes and molecules , such as uric acid , peroxidase ( 02 ) system and phosphatases . diabetes is one of the systemic disorders that has adverse effects on various human organic systems leading to nephropathy , delayed wound healing , etc . intracellular enzymes are increasingly released from the damaged cells of periodontal tissues due to diabetes into the gcf and saliva . s - alp is one of the sensitive markers for the early detection of oral carcinoma . salivary diagnosis can be performed in all the dental institutions to assess the malignant risk potential of potentially malignant disorders and thus quality of life of patients can be improved . based on these reviews , this study is conducted to evaluate the role of s - alp in three groups which includes diabetics , smokers , and diabetics who smoke . the study included a total of 40 patients between the age group of 30 and 50 years who visited our department . group a included 10 smokers who were diabetic , six among them were diagnosed with leukoplakia . group b included 10 smokers who were nondiabetic , two among them were associated with leukoplakia . patients with systemic diseases such as pagets , renal failures and liver cirrhosis where there will be raise in alp were all excluded from the study . patients who were diagnosed with periodontitis clinically based on probing depth , bleeding gums and radiographical bone loss were excluded from the study . ethical clearance was obtained from the institutional review board and consent forms from patients were also taken . a volume of 5 ml of unstimulated saliva samples were collected in sample container from all the participants . subjects were instructed not to take food for 2 h prior to saliva collection . after rinsing the mouth , patients were asked to collect saliva in the floor of the mouth and then spit into a sample container . the sample the resultant supernatant saliva was separated , 20 l of the sample was mixed with 1000 l of erba mannheim kit alp reagent for the estimation of s - alp levels in auto - analyzer . this was based on kinetic method recommended by international federation of clinical chemistry [ figures 1 and 2 ] . the sample mixed with reagent alkaline phosphatase reagent sample collected in test tubes testing the sample in analyzer salivary alkaline phosphatase values assessed in auto analyzer one - way anova was performed to compare data among all groups and found that results were statistically significant with increased activity of alp levels in saliva from smokers with diabetes group when compared to control , diabetics and smokers . according to some studies , in diabetic patients , there will be raise in s - alp levels due to bone loss . in our study , smokers had significant raise in s - alp levels when compared to diabetic and control groups . three cases were diagnosed as homogenous leukoplakia , of three cases two patients were using bidi and one patient was using cigarette with oral medication for diabetes . duration of smoking ranging from 15 to 40 years exhibiting higher levels of s - alp ( 74.48 /l ) when compared to smokers without oral lesions ( 27.81 /l ) [ tables 13 ] , figure 5 . mean s - alp levels in each group and there comparisions comparisons between the groups showing mean s - alp levels clinical details , habit durations of premalignant lesions with s - alp level increasing significantly among 20 diabetic patients in both groups c and d , 19 were on oral medication and only one person was not using any medication showing high s - alp level irrespective of duration . interest in using saliva as a diagnostic medium has been increasing in the last 10 years . salivary components for diagnosis include enzymes , immunoglobulins , hormones of host origin , bacteria and bacterial products , ions and volatile compounds . enzymes in saliva have been studied as markers of periodontal disease and these are derived from cells in the salivary glands , macrophages from gingival sulcus or pockets , polymorphonuclear ( pmns ) leukocytes , epithelial cells from oral cavity and microorganisms . alp is a membrane - bound glycoprotein found on most cell membranes in the body and physiologically occurs during bone formation in developmental stages . it is produced by many cells within the periodontal environment , the principal source being pmns leukocytes , bacterial fibroblast and osteoblast activity which is disturbed due to diabetes , smoking , etc . alp is one of the potentially powerful markers of periodontal disease activity and alp levels increases in periodontal diseases . thus , we excluded periodontal disease patients who were diagnosed clinically and radiographically with pockets and bone loss . this is to avoid false positive results and to evaluate alp diagnosing sensitivity in diabetes and smoking alone . toxic products due to smoking levels depend on the balance between their rates of production and their rates of clearance by the endogenous antioxidant systems , including superoxide dismutase ( sod ) , catalase ( cat ) , the glutathione ( gsh ) redox cycling enzymes , gsh - px , reductase and gsh itself . one of the principal reactive oxygen species produced in aerobic organisms is o2 , which is highly cytotoxic . with the cytotoxicity of this oxidant , exposure to cigarette smoke results in increased levels of antioxidant enzymes , such as cat , copper / zinc sod , px and gsh - px . cat , px , or gsh - px can , in turn , convert h2o2 to molecular oxygen and water . under physiologic conditions , the imbalance between the formation of free oxygen radicals and inactivation of these species by antioxidant is capable of causing damage to various cellular and extracellular constituents . at the same time , s - alp evaluation which is altered due to antioxidant imbalances can act as alarm in smokers and diabetics . this study showed higher s - alp levels in diabetics , smokers than controls , explaining the cellular metabolic alterations . furthermore , s - alp levels in smokers with diabetics group significantly proposes there exists some role between salivary enzymes and harmful habits like smoking to which diabetes shows additive destructive behavior . noticeable raise of s - alp in premalignant disorders observed in sample explains that premalignancy related adverse effects can also be analyzed by simple sialodiagnosis . further studies on large populations are needed to confirm the reliability of these parameters and to determine their effect systemically due to smoking , premalignancy and malignancy . on the basis of the results of this study , it can be concluded that the s - alp enzyme was significantly greater in diabetes mellitus , smokers and subjects with potentially malignant disorders without any periodontitis compared to systemically healthy individuals . we emphasize that screening of premalignancies and malignant lesions can be made by measuring the s - alp levels .

background : alkaline phosphatase ( alp ) is a hydrolase intracellular enzyme participating in the metabolic processes of cells . rise in salivary alp ( s - alp ) levels reflects inflammation and destruction of healthy tissues suggesting it as a clinical biomarker . s - alp is used in analyzing the severity of the disease occurrence in smokers and nonsmokers who are diabetic and nondiabetic . s - alp levels are analyzed using autoanalyzer in 40 patients who visited our department.aims and objectives : to determine the levels of s - alp in diagnosing potentially malignant conditions and debilitating diseases in early stages of inflammation and altered cellular metabolism.materials and methods : the study groups include : ( 1 ) group a - 10 smokers who are diabetic . ( 2 ) group b - 10 smokers who are nondiabetic . ( 3 ) group c - 10 nonsmokers who are diabetic . ( 4 ) group d - 10 nonsmokers and nondiabetic as control . unstimulated saliva samples are collected and run in auto - analyzer with alp enzyme reagent to analyze alp levels . comparison is made between all the four groups.results:results were statistically significant with increased activity of alp levels in saliva from group a when compared to group d. the results are group a > group b > group c > group d. the results also revealed significant raise in levels of alp levels in saliva from smokers when compared to diabetes . thus explaining adverse effects of smoking.conclusion:s-alp can be considered to be the biomarker for evaluating adverse effects of smoking , diabetes and other debilitating diseases in early stages .

moreover , its diagnosis is delayed partly due to prior surgical history coupled with low index of suspicion ; hence , the rate of perforation for stump appendicitis approaches 70% . for our knowledge , no study in literature had described about laparoscopic completion appendectomy for residual tip appendicitis . here , we present a case of residual tip appendicitis diagnosed 3 months after the index surgery and underwent successful completion appendectomy . a 13-year - old boy who underwent laparoscopic surgery , probably appendectomy 3 months ago for acute appendicitis was referred for episodic pain in lower abdomen over last 1 month that had been treated with trial of antibiotics and analgesics . there were waxing and waning of these symptoms over the mentioned duration . this episode was sudden in onset , severe in intensity associated with two episodes of non - bilious vomiting and high - grade fever which brought this patient to us . on examination , a clinical diagnosis of residual appendicitis was made , and empirical broad spectrum antibiotics were started . an ultrasound abdomen was performed , which revealed the presence of inflamed noncompressible , non - peristaltic , tubular structure about 2.5 cm in length and 1.2 cm in diameter located in paracaecal region with a collection of viscous fluid of around 50cc . findings were confirmed by doing a contrast enhanced computed tomography ( cect ) [ figure 1 ] . laparoscopy revealed intraperitoneal adhesions in right iliac fossa with purulent collection about 50cc . following careful adhesiolysis , the inflamed residual tip of appendix of size 4 cm laying in paracaecal position was confirmed . we observed the presence of intact blood supply [ figure 2 ] to this portion from adjoining colonic wall , which probably has maintained the viability and thus persistent inflammation . post - operative recovery was uneventful ; the patient was discharged on the 3 post - operative day . axial section ct abdomen and pelvis : arrow showing residual tip of appendix black arrow : residual appendix . stump appendicitis is an acute inflammation of the residual appendicular stump which is usually an under - reported , delayed complication of an appendectomy . rose in 1945 was the first to describe stump appendicitis . there are 37 cases of residual stump appendicitis which had been reported in the published literature , but no study in english literature had mentioned about residual tip appendicitis . the reported interval between surgery and presentation of stump appendicitis varies between few weeks to many years . this patient presented to us after 3 months of laparoscopic appendectomy . in the last two decades , with the introduction of laparoscopic appendectomy , the incidence of stump appendicitis had increased , which has been reported in many previous studies . the possible causes could be due to initial improper surgical technique or may be contributed by relative increase in number of laparoscopic appendectomies . however , the most recent review by liang et al . revealed that incidence of stump appendicitis after standardised laparoscopic appendectomy is less than half as compared to open technique . there is a high morbidity rate for stump appendicitis in comparison to the initial episode , due to a combination of delayed diagnosis and high rate of stump - related complications . pre - operative diagnosis of stump appendicitis is difficult because of prior surgical history of appendectomy which usually leads to exclusion of appendicular pathology as differential diagnosis unless a high index of suspicion is exercised . although ultrasound abdomen can be informatory , the confirmation is usually obtained by cross - sectional imaging studies . cect features of stump appendicitis can include distended appendiceal stump , pericaecal inflammatory changes , abscess formation , fluid in the right paracolic gutter , caecal wall thickening and sometimes an ileocaecal mass . diagnostic laparoscopy is useful in some doubtful cases with persistent abdominal symptoms after ruling out other pathologies by doing extensive imaging . the completion appendectomy is the treatment of choice for stump appendicitis , most commonly done as an open operation but a successful laparoscopic approach also had been reported in literature . it is recognised that long appendiceal stump and improper identification of stump during appendectomy is the main risk factor for residual appendix . in our case , during previous surgery , stump removal was complete , but the terminal portion of tip of appendix was left behind . usually , a residual tip will not manifest as it would get sloughed off in view of ischemia , but in certain cases like ours , it can acquire the blood supply from adjacent organs , especially in areas like retrocaecal , paracaecal or sub hepatic locations . if the residual tip is left intact incidentally in such location during an initial appendectomy , it can manifest itself as described above . mangi and berger have suggested that the incidence of stump appendicitis can be decreased by proper identification of the base of the appendix and by leaving an appendiceal stump of <3 mm long . stump appendicitis should be included in differential diagnosis of right - sided abdominal pain , especially with prior history of appendectomy . clinicians should exercise a high index of suspicion in such cases to avoid morbidity due to delayed diagnosis . diagnostic laparoscopy can be an important evaluation tool in armamentarium of a surgeon which can contribute for precise diagnosis as well as a therapy . we authors hereby would like to emphasise the importance of complete removal of appendix not only stump part but also tip , especially in certain locations such as paracaecal , retrocaecal and subhepatic .

appendectomy is one of the most common emergency surgical procedures . stump appendicitis is well - recognised entity has been described in the literature . still , with recent advance in imaging technique , it remains as a clinical challenge for diagnosis and effective treatment . we present a case of 13-year - old boy who underwent laparoscopic appendectomy 3 months back and presented to us with acute abdomen associated with vomiting and fever . imaging revealed the presence of a tubular residual inflamed tip of the appendix of size 4 cm laying in paracaecal position with approximately 50cc purulent collection around it . subsequently , the patient underwent successful laparoscopic completion appendectomy with uneventful postoperative recovery . histopathological examination confirmed that resected structure as an inflammatory residual appendix . for our knowledge , after an extensive search of english literature , no study had described about laparoscopic completion appendectomy for residual tip appendicitis . we authors hereby would like to emphasise the importance of complete removal of appendix not only stump part but also tip , especially in certain locations such as paracaecal , retrocaecal and subhepatic . laparoscopy can be an option for the management of these patients , in selected cases , and with available expertise .

despite the reduction in mortality from cardiovascular diseases over the past decade , these disorders are the leading cause of mortality or disability of individuals . generally speaking , in patients with chronic coronary heart problems , curing the disease is deemed as an unrealistic and unattainable goal , since it is debilitating and progressive and many external and internal factors affect its exacerbation or improvement . naturally , these characteristics affect the quality of life of patients and noticing such an important indicator is a main objective of therapy and care . although common assessment methods of patients improvement such as clinical examinations , laboratory investigations , and advanced imaging techniques provide important information about disease , they are not enough in a holistic view to the patient . from this view , diseases can not be separated from personal and social characteristics of patients . extending and centralizing measuring patients quality of life is not only a tool to evaluate the effectiveness of therapeutic interventions , but also a method to analyze the cost - effectiveness of these interventions . being a vast concept , quality of life does not have a unified definition . in recent years the advancement of technology in medicine mostly has forgotten the comprehensive focus on the needs of people . health - related quality of life , along with therapeutic interventions , focus on feeling well and life satisfaction ; so , the quality of life concept is beyond health , though health dependent . the world health organization ( who ) suggests four dimensions for quality of life : physical health including pain and discomfort , sleep , rest , and ability to do everyday workspsychological health including appearance , positive and negative feelings , memory , focus , and self - confidencesocial relationships including personal relationships , social support , and sexual relationshipsenvironment including financing , home environment , access to information , participation in social activities , and commutation facilities . physical health including pain and discomfort , sleep , rest , and ability to do everyday works psychological health including appearance , positive and negative feelings , memory , focus , and self - confidence social relationships including personal relationships , social support , and sexual relationships environment including financing , home environment , access to information , participation in social activities , and commutation facilities . the us agency for healthcare research and quality ( ahrq ) reports about the importance of secondary prevention for cardiovascular patients : annually , more than 2 million new coronary patients in the us need care and rehabilitation programs , since investigations show that follow - up cares lead to increase of ability , decrease of pain , anxiety , heart failure , increase of social and family interactions , and finally improvement of quality of life in these patients . quality of life assessment , especially with chronic diseases , is of great importance since in these diseases , not only physical health but also psychological and social health are seriously threatened and most patients live their lives hopelessly . cardiovascular diseases are generally categorized as chronic diseases and therefore the assessment of these patients quality of life is of great importance for therapeutic decision making . paying attention to secondary preventions in holistic view structure and achieving improvements of patients lives necessarily require new methods along with common therapies , methods which are generally developing in the field of alternative medicine and at the same time being assessed in different communities . a research investigated the effect of cognitive - behavioral therapies and drug therapy on anxiety disorders in comparison with drug therapy for 232 patients in two groups and showed that combination therapy ( cognitive - behavioral therapy together with drug therapy ) significantly reduced anxiety symptoms in these patients and improved their performance and quality of life . such therapeutic interventions are not so widespread in our community and the training contents of these interventions are not adapted to our culture . also , their efficiency is not studied comprehensively through scientific methods . this study is one of the first works done in this domain in iranian community , which attempts to investigate the effects of cognitive - behavioral trainings on the quality of life of cardiovascular patients . two - group pretest , post - test design was used in this quasi - experimental research . the sample consisted of 56 coronary heart patients who were randomly selected from chamran hospital 's heart and training center and isfahan cardiovascular research center . data were collected using macnew quality of life questionnaire designed exclusively to assess cardiac patients quality of life . it includes 27 questions and assesses cardiac patients quality of life at three subscales : emotional functioning , physical and social functioning , and quality of life of cardiac patients . fourteen questions are about physical functioning , 14 questions are about emotional functioning , and 13 questions are about social functioning . questions were allocated such that each question could be in one , two , or all three domains . therefore , one 's score in physical functioning equals to the mean score of 14 questions in the same domain , in emotional functioning it equals to the mean score of 14 in this domain , and in social functioning , it equals to the mean score of 13 questions in this domain . each question has a 7-scale response criteria and a subject 's response to each of these seven propositions shows his or her stance on a continuum from the highest score is 7 and the lowest score is 1 in each domain , showing high quality of life and low quality of life , respectively . this questionnaire has been standardized for cardiac patients in isfahan city by yousefi and jafari in 2004 . the reliability of the questionnaire used in this study was calculated as 0.94 through cronbach 's alpha . the training content designed for the experiment group included eight 2-hour group sessions which were held weekly . it was designed based on the topics of two books , namely cognitive therapy in groups : guidelines and resources for practice and the trainers questionnaire kit , related literature , identification of specific problems of cardiovascular patients , and religious and cultural bases of the society . this training content included 10 general goals : informing patients about anxiety disorders and related issuesfamiliarity with the logic of cognitive - behavioral traininghelping subjects to identify negative automatic behaviors and thoughtattending one 's own feelings and replacing negative automatic thoughts with logical thoughtsrelaxation techniquesmethods of effective communicationtechniques of systematic desensitizationgroup assertiveness techniquesclarifying the relationship between thoughts and mood statesto stop thinking for dealing with negative thoughts informing patients about anxiety disorders and related issues familiarity with the logic of cognitive - behavioral training helping subjects to identify negative automatic behaviors and thought attending one 's own feelings and replacing negative automatic thoughts with logical thoughts relaxation techniques methods of effective communication techniques of systematic desensitization group assertiveness techniques clarifying the relationship between thoughts and mood states to stop thinking for dealing with negative thoughts each session had specified goals and homework corresponding to the received training . experiment group subjects answered the pre - test questionnaire before the training and the post - test questionnaire 3 weeks after completing the training . control group subjects did not receive any training but were told that they would be called for a training course . the collected data were analyzed in spss software by using independent t - test to compare the age of patients and the duration of their disease , kolmogorov simonov ( ks ) test to investigate the score normality of two groups for quality of life scale and its three subscales in pre - test and post - test , and covariance analysis ( ancova ) test to compare the mean of quality of life of two groups with controlling the scores of pre - test . the criterion to reject the null hypothesis score normalcy of both groups at quality of life scale and its three subscales in pre - test and post - test was investigated and supported by ks test ( 0.5 ) . frequency of gender , marital status , risk factors , financial situation , job stress , and education were compared in the two groups by chi - square test , which did not show significant differences . the age of patients and duration of their disease in both the groups were compared through independent t - test which did not show significant differences with scores ( t = 1.025 and 1.24 , respectively ) [ table 1 ] . mean and standard deviation of scores of subjects of both the groups before and after intervention in order to eliminate the possible effects of pre - testing , quality of life ( dependent variable ) was analyzed by ancova . results of ancova test , the effect of cognitive - behavioral trainings on the dependent variable of macnew quality of life and its subscales results showed that eliminating the possible effects of pre - testing , cognitive - behavioral trainings had significant effect in three quality of life subscales and the total score of quality of life with p<0.0001 . this study aimed at investigating the effect of cognitive - behavioral training on quality of life improvement of cardiovascular patients . as shown by the results , the size effect and high statistical power of the test indicate that with current sample size , cognitive - behavioral trainings had a significant and determinant effect on the improvement of cardiovascular patients quality of life . in this research , no change was made in the drugs received by experiment and control groups , but studies which compared the effect of cognitive - behavioral trainings with that of drug therapy show that besides reducing anxiety and improving quality of life of cardiovascular patients , cognitive - behavioral trainings also lead to lowering drug use . the effect of cognitive - behavioral trainings on improving the quality of life has been investigated extensively and is the research still continues . a study found that cognitive - behavioral trainings are effective in increasing the quality of life of anxious patients . there is also convincing evidence that anxiety is a predisposing risk factor in developing coronary heart disease ( chd ) . but implementing other psychotherapy techniques such as relaxation , meditation , and biofeedback through lowering blood pressure reduce the vasoconstriction and improve the heart function and quality of life . other researches which investigated the effect of cognitive - behavioral trainings found these interventions effective , especially in secondary prevention . with gradual development in holistic view toward treatment of patients and its relative popularity among experts , methods appropriate with the view the psychological method is being widely used as one of the effective methods in alternative medicine , especially in the treatment of chronic diseases . in this regard , the results of this study and other similar studies in the world will make cognitive - behavioral training as an inseparable part of treatment protocol for chronic patients in general and cardiovascular patients in particular . it seems that there is a close relation between one 's perceptions of himself , his confidence , the ability to arouse positive feelings and resist negative feelings , positive view of himself , his world and the future and being realistic , and coping with chronic diseases especially with cardiovascular diseases . if these factors become reinforced on patients , they will have significant effects on feelings about recovery , life satisfaction , being less panic and anxious , and consequently on improvement in quality of life . given the fact that the present research is one of the early efforts in iran , its feasibility and results indicate the research 's functionality . it needs to be mentioned that the investigated domain has not reached the status of saturation research yet . other topics and domains also need to be investigated extensively , such as durability of the effects of cognitive - behavioral trainings , balance between cognitive - behavioral trainings and drug use , interactions between physicians and behavioral scientist whilst visiting patients , ensuring when patients reach the ability to control their feelings . prospective longitudinal studies together with larger sample size and more variables can have useful and practical results which will compensate the shortage of research in this domain . results of researches such as the present research will lead to more wisely adopting effective methods of complementary medicine by health and medical education authorities and to reinforce the holistic view ; consequently , both medical education programs and treatment protocols will undergo significant changes in the future .

background : considering the significance of quality of life in chronic diseases and the role of education in its improvement , this study was performed to investigate the effect of cognitive - behavioral therapy on improving the quality of life of cardiovascular patients in isfahan city.materials and methods : in this experimental study , 56 patients , who referred to chamran hospital and isfahan cardiovascular research center , were randomly selected and assigned to two groups , i.e. experiment and control . the experiment group was trained in eight sessions , each session taking 2 hours . both groups received macnew quality of life questionnaire before and 2 weeks after treatment . some demographic data were also gathered along with the questionnaire . data were analyzed by spss software using statistical tests such as independent t - test , chi - square , and analysis of covariance.results:observing the possible effect of pre - test , cognitive - behavioral therapy had a significant effect on the total score of quality of life and its three subscales.conclusion:it seems that along with other medical therapies , making use of cognitive - behavioral intervention is an appropriate method for improving the quality of life of cardiovascular patients .

research suggests some 8% of tumors from the cerebellopontine angle ( cpa ) are meningioma 's . as these tumors grow and involve the cpa , their clinical manifestations mimic those commonly seen in patients with ascoustic neuroma . however , a few cases were reported of meningiomas inducing vertiginous sensations where the meningioma does not occupy the internal auditory meatus , but surrounds the region of the endolymphatic sac . coelho et al . presented 3 cases of posterior fossa meningiomas with mnire's - like symptoms . in their report , the posterior fossa meningioma 's were limited to the dura overlying the endolymphatic sac ; not in the region of internal auditory meatus . this suggests that posterior fossa meningiomas around the endolymphatic sac could produce vertiginous sensations by inducing endolymphatic hydrops . in this article , we describe one case of a posterior fossa meningioma with recurrent vertigo and headache . a 44-year - old woman presented with several - years history of episodic vertigo lasting from several minutes up to several hours and was accompanied by headache . she did not complain of hearing loss , tinnitus , otalgia , otorrhea , or facial palsy . she had no other significant medical history . a complete otolaryngologic examination including flexible nasopharyngoscopy and neurologic tests suggested the autonomic system was normal . over the years , the severity has increased in the episodes . just before seeking help at our hospital we performed a pure - tone audiogram , vestibular function tests , rotation test , electrocochleography ( ecog ) , vestibular evoked myogenic potential , computer tomography ( ct ) , and magnetic resonance imaging ( mri ) . her pure - tone audiogram proved to be normal , but the caloric test indicated a left canal paralysis of 72% and right directional preponderance of 30% . the cochlear summating potential to auditory nerve action potential ratio ( sp / ap ratio ) of the electrocochleogram was 0.29 - 0.16 . a temporal bone ct scan was performed that revealed a 1.51.0 cm round , bony defect at the left posterior petrous ridge ( fig . a contrast - enhanced mri scan confirmed that a broad - band 1.51.0 cm mass was attached to the left posterior petrous ridge . intraoperatively , the tumor was found to be attached to the dura overlying the endolymphatic sac ( fig . 3 ) . since there was no evidence that the tumor and 8th nerve were in contact , the tumor and surrounding dura were excised . the dural defect was patched with temporalis fascia , and the mastoid cavity was packed using abdominal fat grafts . there were no significant postoperative symptoms or relapse and the patient no longer complains of dizziness following surgery . at 1 year approximately 8 - 12% are located in the posterior cranial fossa [ 4 , 5 ] . the most common sites of origin , in descending order , are the parasagittal region , falx , convexit , olfactory groove , tuburculum sellae , sphenoid ridge , anterior petrous face , posterior petrous face , and so on . meningiomas of the posterior cranial fossa compose 5% to 8% of all intracranial meningiomas and around 10% to 15% of cpa tumors . the clinical manifestations of meningiomas of the cpa are similar to those of acoustic neuromas , and it is often difficult to differentiate these two entities by their clinical presentations . progressive hearing loss , tinnitus , disequilibrium , and other cranial nerve function abnormalities are common to both lesions . however , the onset of clinical manifestations of posterior petrous meningioma are often insidious , although it is dependent on the site of origin . due to the fact that meningiomas grow insidiously , neurological findings are absent in the majority of cases until the tumor becomes relatively large . in the case of meningiomas in the iac or posterior petrous area , the initial symptoms are frequently otologic such as hearing loss or vertigo . in 1996 , friedman et al . cmejrek and megerian described 3 patients with mnire's - like symptomatology who were diagnosed as having a meningioma affecting the endolymphatic sac . coelho et al . presented 3 cases of posterior fossa meningiomas with mnire's - like symptoms . arachnoid cysts in the posterior fossa have also been reported to cause mnire's - like symtoms . described a posterior fossa arachnoid cyst in a 40-year - old man with unilateral tinnitus , constant lightheadedness , disequilibrium , and occasional vertigo . described one of three study cases of posterior fossa arachnoid cyst in which the patient exhibited classic symptoms of mnire 's disease . in our case , the patient presented with only episodic vertigo and headache without fluctuating hearing loss , tinnitus , or dizziness because of a very small sized tumor . the mechanism by which a posterior petrous meningioma results in mnire's - like symptoms remains unknown . however , some authors described the intimate involvement of these tumors with the endolymphatic sac . the subsequent dysfunctions of the sac resulting from local invasion , compression by local hyperostosis , or changes in the microcirculation lead to aberrant endolymphatic homeostasis and subsequent hydrops . direct tumor invasion or hyperostotic compression of the endolymphatic system leading to hydrops has been well described in the guinea pig model . however , the difficulty of detecting hydrops in human subjects has made it difficult to verify , with any certainty , a cause - and - effect relationship between endolymphatic obstruction and hydrops . recently , several cases support the concept that obstruction of the endolymphatic sac and duct by a tumor can produce mnire's - like symptoms ; possibly via the production of endolymphatic hydrops , similar to observations in the guinea pig . friedman et al . noted that a tumor in the region of the endolymphatic sac causes endolymphatic hydrops and that the resultant endolymphatic hydrops trigger mnire's - like symptoms . preserved hearing , in this case , was explained as non - invasion of the internal acoustic canal , or spread into the endolymphatic sac . this concept is supported by 2 cases of mnire's - like symtoms reported by cmejrek and megerian in which endolymphatic sac compression resulted in ecog changes suggestive of hydrops . described normalization of an elevated sp / ap ratio on ecog tests after removal of a posterior fossa meningioma . although our case has not presented fluctuating hearing loss or a change of sp / ap ratio , the case has provided further evidence to support the concept that endolymphatic hydrops represents the pathophysiologic mechanism in the production of mnire 's symptomatology . this approach , familiar to neuro - otologists , provides adequate exposure for smaller tumors , including petrous ridge meningioma . if wider exposure is needed , hearing preservation action should be undertaken with the retrosigmoid approach . , the patient 's small - sized tumor was removed through a transmastoid approach and the remaining mastoid cavity was plugged with fat to prevent a postoperative cerebrospinal fluid leakage . in summary , a meningioma presenting mnire 's symptoms is very rare , but it is worthy of diagnostic consideration even in those patients with typical or atypical mnire 's disease . once diagnosed , clinicians should consider the surgical removal of tumors to facilitate the complete resolution of symptoms . in our case , the mechanisms of recurrent vertigo were the repeated injuries of vestibular system by the invasion of endolymphatic sac or mechanical obstruction of endolymphatic sac from tumor .

meningioma 's account for around 15% of all primary brain tumors with some 10% of meningiomas arising in the posterior fossa . in rare cases , a meningioma can form around the endolymphatic sac . when formed in the posterior fossa , meningioma tumors can produce vague , non - specific vertiginous symptoms . research has observed that a subset of these lesions could produce symptoms indistinguishable from those of meniere 's disease . therefore , we described the clinical features of a case of posterior petrous meningioma with recurrent vertigo as well as the substantial resolution of symptoms after tumor removal via transmastoid approach .

the cumulative lifetime incidence of epilepsy is 3% while more than half of cases begin in childhood . parents of epileptic children often ask if there is any relationship between specific foods in a usual daily diet and amelioration or exacerbation of seizure attacks . the oldest recommendation which we have is by avicenna , the great iranian physician of nearly 1000 years ago , who believed and recommended that epileptic patients should avoid excessive eating and also avoid some foods such as beef , mutton , fish , milk , onion , garlic , celery , radish , turnip , cauliflower , carrot , broad beans and lentils . reviewing literature we can find reports of reduction of seizure threshold in rats by excess dietary amino acids , induction of convulsive disorders in rats by monosodium glutamate , occurrence of generalized convulsions after consumption of a large amount of gingko nuts , and induction of seizures and refractory status epilepticus due to star fruit intoxication in patients with chronic renal disease . although there is no randomized controlled trial to prove correlation between foods and epilepsy or to recommend specific dietary restriction for children suffering epilepsy , a few studies have tried to evaluate beliefs and experiences of people about this relationship . another thing which we should consider is the attitude of our community to different types of foods according to traditional medicine in which food substances are divided into three groups as follows : foods with cold nature , foods with moderate nature , and foods with warm nature . there is no published study to evaluate attitude of people to relation of epilepsy with these food groups . therefore , regarding to importance of this subject and specific attitude of our families to different kinds of foods based on traditional medicine , we designed this study . alternative medicine including herbal medicine , homeopathy , acupuncture and other approaches become increasingly popular in the world ; but there is limited conclusive evidence about efficacy of these methods on epilepsy , moreover the situation of these treatments for epilepsy in iran is not so clear , hence , as our next goal in the study , we tried to ask the attitude of parents of children with epilepsy toward the role of these approaches on seizure control . undoubtedly this is important because sometimes these treatments are used by families without informing the physician while there are possible risks of prescription of these treatments without any scientific evidence . we carried out a cross - sectional study with analytic aspect at outpatient clinics of children 's medical center , affiliated to tehran university of medical sciences ( tums ) , iran , in 2008 ( from january to december ) . these clinics are one of the main referral centers for children suffering from epilepsy from all over the country . applying convenient sampling , we selected the patients with epilepsy ( idiopathic or symptomatic ) rather than children affected by seizures with fever or metabolic disorders . patients were taking antiepileptic drugs . to assess parents attitudes toward the relation of foods and alternative medicine with epilepsy the questionnaire also asked their idea about effect of three main food groups according to traditional medicine ( foods with cold , moderate or warm nature ) and effect of alternative medicine on epilepsy . they were requested to select one of the following options : the item improves diseaseit has no effect on diseaseit precipitates diseasehaving no idea . the item improves disease it has no effect on disease it precipitates disease validity of questionnaire was approved by expert panel . to analyze reliability of questionnaire we determined cronbachs alpha for assessing the relationships , p value less than 0.05 was considered significant . to evaluate negative attitude to each group of foods ( i.e. , cold , moderate or warm nature ) at level of 25% , with acceptable difference of 7% the questionnaire also included demographic information of patients and the family such as educational level of parents , average monthly income of family , patients age and sex , familys religion and residence city . after taking verbal informed consent from parents of children with epilepsy , we gathered the information via personal interviews . they were from different parts of iran , so , cultural factors seemed to be different . the age of epileptic children varied from 1 to 14 years [ mean ( sd ) age : 5.9 ( 3.1 ) ] . educational levels of epileptic children 's parents while only one of the fathers was epileptic ( 0.7% ) , history of epilepsy was positive in 13 ( 8.6% ) of mothers . average monthly income of family ranged from $ 55.6 to $ 1111.1 [ mean ( sd ) income : 420.7 ( 207.4 ) ] in general , 59 ( 39.1% ) of participants [ confidence interval ( ci)95% : 31.3 - 46.9 ] believed that foods had no effect on epilepsy . 51 ( 33.8% ) cases [ ci95% : 26.2 - 41.3 ] said that foods might have negative or positive effect on epilepsy . 41 ( 27.1% ) of them [ ci95% : 20.1 - 34.2 ] had no idea . in other words , 100 ( 66.2% ) believed that food does not improve or precipitate seizures . the attitude of parents to relation of each group of three above mentioned traditional dietetic groups based on traditional medicine is seen in table 2 . as illustrated in the table , the most negative attitude was related to foods with cold nature , while the most positive attitude was toward foods with warm nature . parents attitude to food groups of traditional medicine parents believed that foods with moderate nature do not ameliorate or exacerbate epilepsy . about following substances , participants either had no idea or said that they have no effect on epilepsy : mulberry , beetroot , celery , saffron , ergot of rye , cow 's brain and sheep 's brain . following were recognized by our participants as the most aggravating food substances ( numbers and percentages are seen in parentheses ) : cucumber ( 37 , 24.5% ) , sour yoghurt ( 30 , 19.9% ) , broad bean ( 24 , 15.9% ) , watermelon ( 23 , 15.2% ) , vinegar ( 21 , 13.9% ) , sweet yoghurt ( 20 , 13.2% ) , lemon juice ( 19 , 12.6% ) , verjuice ( 19 , 12.6% ) , hot pepper ( 19 , 12.6% ) , and churned sour milk ( 19 , 12.6% ) . following food substances were recognized by participants as the most ameliorating substances ( numbers and percentages are seen in parentheses ) : honey ( 31 , 20.5% ) , sugar ( 27 , 17.9% ) , ripe dates ( 23 , 15.2% ) , lentil ( 18 , 11.9% ) , walnut ( 18 , 11.9% ) , sesame ( 15 , 9.9% ) , and sheep 's milk ( 15 , 9.9% ) . other substances were reported either ameliorating or aggravating or both ( of course , by different people ) at lower percents . we also evaluated participants attitude considering any food substance in related group of food guide pyramid . the average of attitude scores is illustrated in table 3 , using previously mentioned scoring . as seen in this table , none of parents believed that food substances belonged to " bread and corns " group might precipitate epilepsy . mean attitude scores to " vegetables and fruits " and " milk and dairy products " groups was below zero indicating that on the average , participants believed that these groups aggravate epilepsy . parents ' attitude scores regarding food pyramid groups sd : standard deviation to see if educational levels of parents , family income and history of epilepsy in family , affect parents attitude to food - epilepsy relation , we analyzed our data based on these variables . the only statistically significant difference was seen based on educational levels of fathers . in other words , 16 of 24 ( 66.7% ) families in which fathers had educational levels above high school graduation , believed in food - epilepsy relation ; while 35 of 127 ( 27.5% ) families in which fathers had lower educational levels believed in such relation ( p<0.001 ) . there were no significant differences between different subgroups considering mothers ' educational levels , history of epilepsy in family and monthly income of the family looking at this table , it is obvious that the majority of participants had no idea about the efficacy of alternative approaches to epilepsy . moreover , among different types of alternative medicine , the most positive attitude was to herbal medicine . the oldest recommendation which we have is by avicenna , who believed and recommended that epileptic patients should avoid excessive eating , foods with cold nature and also some foods such as beef , mutton , fish , milk , onion , garlic , celery , radish , turnip , cauliflower , carrot , broad beans and lentils . he also advised the main daily meal to be divided into three parts , one - third for lunch and two - thirds for dinner . of course , he was one of the greatest physicians of traditional medicine and has mentioned some other characteristics of food substances in his book . therefore , it seems that he believed in different factors which affect food - epilepsy relation . however , to design a clinical controlled study to evaluate the effects of different foodstuffs on epilepsy in children is not so easy ; perhaps this is why researchers just have tried to evaluate people 's attitudes and experiences . in a published study in fars province , iran , among 125 families of epileptic children personal confirmatory experiences with seizures after consumption of certain food materials were reported by 31.2% of families . dairy products , sour foods , fruits and vegetables were the most common foods reported to be responsible . in another study from the same province , among 250 health care workers participated , 58.4% believed there existed a relationship between consumption of specific foods and occurrence of seizures . dairy products , sour foods , food additives , meats , fish , fruits and vegetables were the most common foods reported to be responsible for occurrence of seizures according to their experiences . a more recent study carried out in america , showed that only 5.7% of epileptic patients ( with an average age of 40.316 ) believed in such a relationship . therefore it could be due to the cultural diversity . comparing these data with our results showing only 33.8% of participants believed that foods had positive or negative effect on epilepsy , is in favor of this idea that relation of foods and epilepsy may be more culturally based than being a fact . however , it is clear that we have evaluated just parents ' attitude and our results ca n't prove or disprove food - epilepsy relation by itself . considering results of our study , the most negative attitude was directed at foods with cold nature ; obviously this result is consistent with avicenna 's belief . as mentioned before , participants believed that vegetables , fruits and dairy products were the most aggravating food groups . the analysis of parents ' attitude based on educational levels revealed that fathers ' educational level had influenced parents ' attitude ; in a way that educational levels higher than high school had made them believe more in food - epilepsy relation . this result is inconsistent with the result of previously published study from iran in which well educated ( above high school ) families believed less in such relation than low educated ( below high school ) families ( 40% versus 62.4% ) . a possible reason for such disagreement is that we have no scientific evidence about relation between daily diet and epilepsy . in other words , increasing educational level in different fields can not have the same influence on parents ' attitudes toward food - epilepsy relation . anyway , this disagreement shows that people 's attitude to this subject ca n't be anticipated based on their educational level . it is worthwhile to have a look on possible causes of food - epilepsy relation . reviewing literature we find that lowering seizure threshold , food - drug interaction , deficiency of some vitamins ( e.g. thiamin ) and allergic reaction to foods ( as allergens ) have been mentioned so far . however , regarding results of studies indicating food - epilepsy relationship and results of our study and similar studies , it seems that specific foods may precipitate seizures in specific settings . in other words , in contrast , such a belief results from cultural factors . finally , we suggest designing further clinical controlled prospective studies , regarding different aspects of this subject , to prove or disprove food - epilepsy relation . our data showed that just 10.6% of participants believed that alternative medicine ( in general ) may be beneficial in children with epilepsy . this indicates that our participants were not interested in these approaches ; perhaps because they have referred to a conventional medicine center otherwise they would have referred to alternative medicine centers . however , more than half of participants ( 55% ) had no idea on this subject ; therefore , we think that educational programs by experts are needed to make people familiar with available facts in this field ; at the same time , to carry out randomized clinical trials is really needed to clarify more facts . compared with previous published study from iran , parents of epileptic children believed less in food - epilepsy relation . majority of parents either believed that foods had no effect on epilepsy or had no idea . however , among those who believed in food - epilepsy relation , the most negative attitude was directed at foods with cold nature . moreover , these parents believed that vegetables , fruits and dairy products were the most aggravating food groups ( similar to previous studies from iran ) . more than half of parents had no idea about efficacy of alternative medicine to epilepsy .

objectiveparents of epileptic children are willing to know if specific foods precipitate or aggravate their kids ' seizures . nonetheless conclusive data are limited . alternative medicine has become a popular approach to many diseases in the world and there are limited data about this approach to epilepsy in iran . we tried to evaluate attitude of parents of epileptic children to food - epilepsy relationship and alternative therapeutic approach to epilepsy.methodswe carried out a cross - sectional study with analytic aspect at children 's medical center , tehran , iran in 2008 , by asking the parents of epileptic children to fill out a valid and excellently reliable questionnaire . we collected parents attitude and analyzed it using spss software.findingsone-hundred and fifty one families participated in the study . fifty - nine of participants ( 39.1% ) believed that foods had no effect on epilepsy . fifty one cases ( 33.8% ) said that foods might have negative or positive effect on epilepsy and 27.1% ( 41 cases ) had no idea . higher percent of parents believed in food - epilepsy relation in cases that fathers had educational levels above high school graduation . sixteen cases ( 10.6% ) said that alternative medicine might improve epilepsy and 55% had no idea about efficacy of this approach to epilepsy.conclusioncompared with previous published study from iran , parents of epileptic children believed less in food - epilepsy relation . majority of parents either believed that foods had no effect on epilepsy or had no idea . more than half of parents had no idea about efficacy of alternative medicine to epilepsy . only a few of them believed in ameliorating effects of alternative medicine on epilepsy .

the combined incidence is reported to be 0.03 per 100,000 persons in the united states . the myxoid variant of chondrosarcoma of bony origin is an uncommon entity and its location in the skull is rarer still with incidence as low as 0.16% , including those arising from its coverings , supporting tissues , and cranial bones . this tumor occurs mainly in the spheno - occipital region . because of the similarity to chordoma , the synonym for it is chordoid sarcoma or parachordoma , and indeed , it is misdiagnosed frequently as such . it is essential to distinguish myxoid chondrosarcoma from chordoma and especially its chondroid variant , as it has a better prognosis when compared to the latter . a 48-year - old female presented with headache and sixth cranial nerve palsy since six months and vomiting since 20 days . computed tomography scan ( ct scan ) showed a lobular lesion measuring 3.93.0 cm with calcific specks in the medial temporal region involving the left greater wing and body of the sphenoid bone along with the petrous part of the temporal bone . magnetic resonance imaging ( mri ) showed a t2 hyperintense lesion involving the clivus , petrous temporal bone , and sphenoid bone on the left side . this lesion was hypointense on t1- weighted image [ figure 1a ] and enhancing heterogeneously in postcontrast ( gadolinium ) study [ figure 1b ] . as the lesion was in midline and contained calcified matrix , a provisional diagnosis of chordoma was made . perioperatively , the tumor was noted to be of extradural location , and was soft and suckable . the excised tissue comprised multiple irregular , glistening , soft lesional fragments of 0.4 to 0.8 cm with focal gritty areas of calcification . ( a ) t1-weighted axial image : lesion is hypointense on t1-weighted image ( b ) postcontrast t1-weighted axial image : shows heterogeneous enhancement of the lesion fragmented tissue samples from the mass were fixed in 10% formalin , routinely processed for paraffin embedding , and stained with hematoxylin and eosin . the histological sections revealed the lobular lesional component [ figure 2 ] comprising large cells with round to mildly pleomorphic vesicular nuclei and abundant vacuolated cytoplasm lying on a mucomyxoid background [ figure 3 ] . these were associated with conspicuous cartilaginous areas having the presence of uni to multinucleated lacunae , foci of dystrophic calcification and intervening fibrocollagenous tissue with proliferating congested capillaries , separating the lobules . a histological diagnosis of myxoid variant of chondrosarcoma was made . to rule out the clinical and radiological suspicion of chordoma and to affirm the hematoxylin and eosin diagnosis , the help of immunohistochemistry was sought . the immunohistochemical positivity of the tumor component for the s100 protein and vimentin [ figure 4 ] and negativity for the epithelial membrane antigen ( ema ) and cytokeratin ( ck)favored the diagnosis of myxoid variant of chondrosarcoma over chondroid chordoma . lobular arrangement of tumor cells separated by fibrous septae [ hematoxylin and eosin 100 ] large bubbly - looking tumor cells with stellate - shaped nucleus and abundant vacuolated cytoplasm ( physaliphorous - like cells ) [ hematoxylin and eosin 400 ] cytoplasmic positivity for vimentin [ immunohistochemistry 400 ] fragmented tissue samples from the mass were fixed in 10% formalin , routinely processed for paraffin embedding , and stained with hematoxylin and eosin . the histological sections revealed the lobular lesional component [ figure 2 ] comprising large cells with round to mildly pleomorphic vesicular nuclei and abundant vacuolated cytoplasm lying on a mucomyxoid background [ figure 3 ] . these were associated with conspicuous cartilaginous areas having the presence of uni to multinucleated lacunae , foci of dystrophic calcification and intervening fibrocollagenous tissue with proliferating congested capillaries , separating the lobules . a histological diagnosis of myxoid variant of chondrosarcoma was made . to rule out the clinical and radiological suspicion of chordoma and to affirm the hematoxylin and eosin diagnosis , the immunohistochemical positivity of the tumor component for the s100 protein and vimentin [ figure 4 ] and negativity for the epithelial membrane antigen ( ema ) and cytokeratin ( ck)favored the diagnosis of myxoid variant of chondrosarcoma over chondroid chordoma . lobular arrangement of tumor cells separated by fibrous septae [ hematoxylin and eosin 100 ] large bubbly - looking tumor cells with stellate - shaped nucleus and abundant vacuolated cytoplasm ( physaliphorous - like cells ) [ hematoxylin and eosin 400 ] cytoplasmic positivity for vimentin [ immunohistochemistry 400 ] extraskeletal myxoid chondrosarcoma ( emc ) was first described in 1953 by stout and verner , who reported a small series of morphologically similar appearing cases , all of which arose in the extremities of adults . however , in 1972 , enzinger and shiraki , in a series of 34 cases , first established emc or chordoid sarcoma as a distinct clinicopathologic entity . despite numerous additional case reports and series of extraskeletal chordoid sarcoma , only a few case reports of its skeletal counterpart , smc ( smc : skeletal myxoid chondrosarcoma ) are found in the literature . are smc and emc the same entity arising in two different locations , or are they two separate entities ? in a systematic attempt to answer the question , antonescu et al . performed a comparative clinicopathologic , ultrastructural , and molecular study of smc and emc . the gender distribution was identical in both groups and the mean age was slightly higher for emc patients [ 55 vs 45 years ] . electron microscopy revealed intracisternal microtubules and prominent mitochondria in emc cases and only inconspicuous organelles in smc . molecular analysis for the ews - chn fusion rna resulting from the t ( 9;22 ) was detected in emc cases only . the conclusion drawn was that although similar light microscopic features are noted in emc and smc , fundamental differences are present at the ultrastructural and molecular levels , suggesting that emc and smc represent two distinct entities in the chondrosarcoma family of tumors . chordoma is a slow - growing malignant neoplasm arising from ectodermally derived notochordal remnants and accounts for less than 5% of primary bone tumors . morphologically , chordoma is composed of large cohesive cells with abundant , bubbly eosinophilic cytoplasm , known as physaliphorous cells. hyaline cartilage is rarely observed except in the variant located in spheno - occipital region , the so - called chondroid chordoma . based solely on microscopic features , distinction between chordoid sarcoma and chordoma may be difficult as the vacuolated areas of chordoid sarcoma may closely resemble those observed in chordoma . however , diagnostic physaliphorous cells are absent in chordoid sarcoma in contrast to chordoma , and cytoplasmic vacuolation tends to be focal rather than diffuse . further , although both the lesions are multilobated , this feature tends to be more distinct in chordoid sarcoma . in 1973 , heffelfinger et al . , for the first time described a chordoma with cartilaginous differentiation and named it the chondroid variant of chordoma which later on gained support from the immunohistochemical study by rosenberg et al . , who demonstrated positivity for epithelial and mesenchymal markers ( i.e. , ema , ck , s100 protein , and vimentin ) in both chordoma and its chondroid variant while differentiating the myxoid variant of chondrosarcoma which displayed positivity only for the mesenchymal markers ( i.e. , s100 protein and vimentin ) . for diagnosing cases without classical histology , that is , myxoid chondrosarcoma with atypical morphological features , apart from immunohistochemistical study , fish ( fish : fluorescent in situ hybridization ) analysis using ewsr1 and nr4a3 probes has been proposed by noguchi et al . in their study comprising 18 cases of emc , the positive results of 72% for ewsr1 and 61% for nr4a3 gene rearrangements led to the conclusion that fish analysis of formalin - fixed , paraffin - embedded specimens for the said new probes is useful , convenient , and may provide an ancillary method for diagnosis , especially in difficult cases . remnants of primitive notochord at the spheno - occipital synchondrosis gives rise to skull chordomas whereas chondrosarcomas take origin from the embryonic rest of the cartilaginous matrix of the cranium or primitive mesenchymal cells . chondrosarcomas usually begin laterally ( i.e. , from the spheno - occiput region ) and grow into the midline to involve the clivus , whereas chordomas behave vice versa . in an immunohistochemical study to predict clinical outcome , heyse et al . compared three isoforms of cd44 and came up with the conclusion that overexpression of cd44s correlated significantly with metastatic potential and poorer survival of patients with chondrosarcoma , which may serve as a prognostic marker independent of grading and other covariates . nguyen et al . proposed adjuvant radiation therapy after maximal surgical resection of the tumor . after comparing with other forms of radiation therapy , they advocated proton beam therapy as a better tool used to increase the dose delivered to the tumor while elegantly sparing dosing to adjacent critical normal structures . to conclude , although the myxoid variant of chondrosarcoma and chondroid chordoma are similar in several aspects , they differ in their origin and clinical outcome . skull base myxoid chondrosarcoma carries a markedly more favorable outcome with minimal recurrence and excellent long - term control , whereas chordomas including its chondroid variant demonstrate an aggressive clinical course and have a uniformly poor outcome after disease recurrence . radiotherapy is usually recommended following surgery in chordoma , whereas resection of the tumor suffices in the myxoid variant of chondrosarcoma . our patient underwent surgical excision of the tumor without any radiotherapy and is doing well in the postoperative one - year period . although a few cases of myxoid chondrosarcoma of the sphenoid bone have been described in literature , our case adds to the existing literature emphasizing the importance of immunohistochemistry in arriving at a final diagnosis .

the myxoid variant of chondrosarcoma is usually seen in soft tissues where it is known as chordoid sarcoma or parachordoma . rarely , it involves bone and when it does , cranial bones are the preferred location . this tumor is frequently amalgamated with the chondroid variant of chordoma , especially when the lesion occurs in the sphenoid bone / spheno - occipital region , because of their similar clinical presentations , anatomical locations , radiological findings , and mistaken histopathological features . it is essential to distinguish myxoid chondrosarcoma from the chondroid variant of chordoma , because of the different treatment protocol and prognostic importance . we present such a location - based diagnostic dilemma , solved successfully with ancillary immunohistochemistry .

walter kennedy chosen the term nocebo ( latin for i will harm ) as the counterpart of placebo . this term was introduced a few years after henry beecher published his paper on the placebo effect . most clinical studies explored the beneficial effects of nutraceuticals and ignored their nocebo effects , the seeds / oil of nigella sativa has anti - inflammatory , analgesic , antipyretic , antimicrobial , hypotensive , hypoglycemic , antiepileptic and antineoplastic activity [ 4 - 7 ] . garlic , considered either food or herbal medicine , possesses antimutagenic and antiproliferative properties that can be used in anticancer interventions , hypoglycemic [ 8 - 10 ] . coenzyme q10 ( coq10 ) is an essential electron carrier in the mitochondrial respiratory chain and an important antioxidant . it exerts a beneficial effect on cognitive , digestive , cardiovascular and immune systems , and modulates inflammatory and degenerative processes in the body [ 11 - 13 ] . nutraceuticals derived from such spices as turmeric , red pepper , black pepper , licorice , clove , ginger , garlic , coriander , and cinnamon target inflammatory pathways , thereby may prevent neurodegenerative diseases e.g. , parkinson s disease . on the other hand , most clinical studies ignored the subtle central effect of the nutraceuticals , therefore the aim of this study is to show the nocebo effects of the nutraceuticals notably black cumin , garlic and coq10 on the integrative function of central nervous system and psychomotor performance in human using leeds battery testing . this is a randomized , controlled , double - blind , prospective study conducted in the department of pharmacology , college of medicine , al - mustansiriya university , baghdad , iraq in february 2013 . they were randomly chosen from college medical students , aged ranges between 19 and 24 years ( mean age 21 years ) . all participants were in good health , without any significant clinical history of physical or mental illness and not taking any concomitant medication that was likely to interfere with the study . the study was approved by local scientific committee of the institution and written informed consent was obtained from all participants . prior to the study participants were trained to perform the psychomotor performance tests and practiced on three separate occasions to exclude any learning bias . then , they were randomly assigned equally to one of the following groups : group a : received single dose of n. sativa oil ( 500 ml capsule , sehapharma , egypt ) . group b : received single dose of garlic ( 500 mg capsule , private label nutraceuticals , usa ) . group c : received single dose of coq10 ( 120 mg capsule , maritzmayer laboratories , usa ) . group d : received a single dose of matching oral placebo ( 300 mg starch capsule ) . all participants in the above 4 groups were subjected to leeds battery psychomotor instrument before and after 3 h of taking the corresponding interventional agent ( nutraceuticals or placebo ) in order to assess their pre- and post - treatment psychomotor performance in term of choice reaction time ( crt ) , critical flicker fusion ( cff ) and total reaction time ( trt ) . it is well - known that crt can be used to assess the sensory - motor alertness through measuring the speed of recognition and motor responding to particular sensory stimulus . in the present study , by using leeds psychomotor tester , the participants instructed to respond to the bright red light that illuminated in one of six position in random way by pressing the button where the light presented . it s important to mention that the mean of 9 consecutive presentations is recorded as a response measure of three components of reaction time : recognition , motor , and trt . the recognition reaction time ( rrt ) represent the time spent between red light illumination in the leeds psychomotor device and the beginning of participant responding toward that light ( motor action ) , manifested by lifting of their finger from specific site ( start button ) . the motor reaction time ( mrt ) represented by the time spent from the start of motor action to the end of it i.e. , the time through which the finger of the participant moves from start button to the response button . the cff task assessed the integrative capacity of the central nervous system ( cns ) and , more specifically , the ability to discriminate discrete bits of sensory information . in this , the participants are asked to concentrate on 4 illuminated points and to response to the changes in illumination in these points from flickering to fusion and vice versa . individual thresholds are determined by the psychophysical method of limits on 3 ascending ( flicker to fusion ) and 3 descending ( fusion to flicker ) scales . a decrease in the cff threshold is indicative of a reduction in the overall integrative activity of the cns . all data were analyzed using the statistical package of social sciences ( spss ) version 15 for windows program on the computer . table 1 shows that the neither placebo nor nutraceuticals exerted a significant effect on trt . the rrt is insignificantly reduced by 2.77% ( placebo ) , 5.83% ( n. sativa ) , 7.21% ( garlic ) and 12.64% ( coq10 ) from the pretreatment values [ table 1 ] . nutraceuticals adversely affect the mrt to reach the significant level in subjects pretreated with garlic [ table 1 ] . placebo treatment reduced the mrt by 1.4% while the nutraceutical preparations prolonged the mrt by 12.22% ( n sativa ) , 30% ( garlic ) and 8.82% ( coq10 ) . placebo and nocebo effects of nutraceuticals preparations integrative activity of central nervous assessed by measuring the cff threshold ; ascending and descending components remained stable with placebo pretreatment and nutraceuticals [ table 2 ] . the results of this study show that garlic produces nocebo effect on the motor component of reaction time while n. sativa and coq10 produce placebo effect . all the nutraceuticals produce placebo like effect on the integrative activity of the cns . the effects of n. sativa on the brain were extensively done on small animals and in vitro utilizing cell lines . these studies showed that n. sativa exert antiepileptic , anxiolytic , and cerebral protection against ischemia and reperfusion injury [ 16 - 19 ] . this study shows that n. sativa does not produce any effect on the healthy human brain in term of psychomotor performance or integration activity of cns , i.e. ; it is a safe nutraceutical . the neuroprotective effect of garlic was extensively studied in different experimental models of cerebral ischemia and neurodegenerative diseases [ 20 - 22 ] . this study demonstrates the nocebo effect rather than the beneficial effect on the psychomotor function in the healthy human . therefore , the garlic nutraceutical should prescribe with caution in conditions associated with impaired psychomotor performance , e.g. , elderly age group or in concomitant use with cns depressant agents , e.g. , alcohol or antihistamines . coq10 protects the neurons from degenerative changes , e.g. , parkinson s disease , huntington s chorea , optic nerve atrophy and it exerts a beneficial effect in the management of headache including migraine [ 25 - 27 ] . in this study , short term therapy and one dose testing of each nutraceutical are the limitations of the study .

background : herbal medicines are often perceived by the general public as a soft alternative to western medicine , but the use of these substances can be risky since they can induce nocebo effect.aim:the aim was to evaluate the nocebo effects of nigella sativa oil , garlic and coenzyme q10 ( coq10 ) on the integrative function of the central nervous system and psychomotor performance.materials and methods : this is a randomized , double - blind , controlled , and prospective study conducted in the department of pharmacology , college of medicine , al - mustansiriya university , baghdad , iraq during february 2013 . a total of 160 medical students participated in this study were randomly assigned equally to one of the following groups : group a : received single dose of n. sativa oil ( 500 ml capsule ) ; group b : received single dose of garlic ( 500 mg capsule ) ; group c : received single dose of coq10 ( 120 mg capsule ) and ; group d : received single dose of matching oral placebo ( 300 mg starch capsule ) . for all participants , reaction time and flicker fusion threshold were measured by the leeds psychomotor performance test battery before and after 3 h of taking the drugsresults : neither placebo nor nutraceuticals exerted significant effect on total reaction time . although the recognition reaction time is insignificantly reduced by 2.77% ( placebo ) , 5.83% ( nigella sativa ) , 7.21% ( garlic ) and 12.64% ( coq10 ) from the pretreatment values , they are adversely affect the motor reaction time to reach the significant level in subjects pretreated with garlic ( p = 0.02).conclusion : nutraceuticals are not free from nocebo effect on psychomotor performance .

treatment of metastatic tumours of proximal femur usually used to be either palliative in the form of radiotherapy and chemotherapy or a very radical in form of hemipelvectomy and hip disarticulation . both forms of treatment were associated with dismal outcomes . now with the technological advancement and refinement in surgeries a custom made hip prosthesis offers a much better treatment option to the surgeon and a good quality life to the patient . we are presenting a case of metastatic adenocarcinoma of upper end of left femur with pathological fracture with a small primary in right lung treated with custom made hip prosthesis . patient received chemotherapy for primary lesion and is doing well at 11 months of follow up . this case is being presented on account of its unusual presentation and to give emphasis that in spite of metastatic disease , patient can be considered for limb salvage and megaprosthesis to improve his / her quality of life . this can be considered provided patient s general condition permits and if only a single solitary metastasis is present . a single space occupying mass in an adult is much more likely to be a focus of metastatic carcinoma . in females , the breasts and lungs are the most common primary disease sites ; approximately 80% of cancers that spread to bone arise in these locations . in males , cancers of the prostate and the remaining 20% of primary disease sites in patients of both sexes are the kidney , gastrointestinal tract and thyroid as well as sites of unknown origin . metastatic bone tumors are much more common than primary tumors and proximal femur is the most common site of involvement in the appendicular skeleton . pain , pathological fractures and hypercalcemia are the major sources of morbidity with bone metastasis . treatment goals aim to preserve function of the lower limb , eliminate pain and improve the quality of remaining life . an assessment of the risk of pathological fracture must be made by an experienced orthopaedic surgeon . lesions that do not represent a risk for fracture may be treated with radiation or by appropriate chemotherapy directed at the primary tumor . lesions that are regarded as a risk for pathologic fracture should be surgically stabilized on an elective basis before a fracture occurs . the goals of surgery are to preserve stability and function of the musculoskeletal system as well as to alleviate pain . patients who were candidates for extensive femoral resection because of malignant tumor were long considered a high - risk group for limb - sparing procedures because of the extent of bone and soft - tissue resection , as well as the use of adjuvant chemotherapy and radiation therapy . hip disarticulation or hemipelvectomy was therefore the classic treatment for patients with large lesions of the proximal or mid femur . the limb salvage surgery as a palliative treatment will provide more psychological benefit not only to the patient but also to relatives and will increase self confidence so that the quality of life is better for the expected duration of survival . a 65 years old female presented in september 2010 , to our department with chief complaints of severe pain and swelling in left thigh since last 2 years . she was unable to walk and had loss of appetite since 1 years . according to the patient she was apparently asymptomatic 2 years back when she developed pain in left thigh . it was constant in nature and was present even at rest , dull aching type aggravated by hip movements . it was also associated with swelling over the upper part of thigh . for the above complaints patient took some local treatment but was not relieved . after six months patient was unable to bear weight even partially and was completely bed ridden . she was not having any complaint of cough , fever , haemoptysis or hoarseness of voice , difficulty in swallowing for solids or liquids . patient was having a history of intermittent pain in right side of middle chest , which used to relieve on taking non steroidal antiinflammatory drugs . there was no history of any gastrointestinal upset or urinary problem , any breast lump , trauma syphilis , leprosy , diabetes and hypertension . on examination there was a 10 cm 5 cm swelling over antero - lateral aspect of upper part of left thigh . the swelling was diffuse , hard , localized to upper part of thigh , immobile , non - translucent , non - illuminant , non - fluctuant , non - pulsatile and fixed to the bone . plain radiographs of the affected part showed ill - defined osteolytic permeative pattern or moth eaten type of lesion with destruction of bone involving the diaphyseal and metaphyseal region of proximal femur and extension into the soft tissues ( fig . pre - operative radiograph of the patient showing permeative pattern or moth eaten type of lesion seen over the metadiaphyseal region of left femur with pathological fracture . there was pathological fracture of femur at the distal margin of the tumor lesion with no periosteal new bone formation . magnetic resonance imaging revealed a large expansile intramedullary osteogenic hypo intense vascular primary mitotic lesion of upper metadiaphyseal aspect of left femur with extra osseous extension of soft tissue in anterior and lateral myofascial compartment without any involvement of adjacent hip joint or neurovascular bundle . contrast enhanced computed tomography scan of thorax was done to know about the nature of ill - defined opacity and it revealed a lobulated soft tissue density mass lesion measuring 2630 mm noted in apical segment of right lower lobe . 2 ) . contrast enhanced ct scan of thorax - showing mass lesion in the apical segment of right lower lobe . fluoroscopic guided needle biopsy of the femoral lesion revealed it to be a metastatic adenocarcinoma . as patient was symptomatic due to metastatic lesion but not due to primary lesion so priority was given to metastatic site . the patient was planned for surgery , but as tumor was very vascular so to reduce the risk of bleeding at the time of surgery pre - operatively radiotherapy was planned . palliative radiotherapy was given at a dose of 30 gy in10 fractions in 2 weeks with cobalt 60 in department of radiotherapy of our institution to relive pain and to reduce vascularization of tumor . 3 weeks after the completion of radiotherapy , hip was exposed by the postero - lateral approach extending the incision more distally . 17 cm of the affected bone including the head of the femur was resected out ( fig . the cut muscles were tied at the ports at the upper end of the prosthesis . stitches were removed on 12th post - operative day and patient was allowed to walk with the help of walker . intraoperative specimen of tumour excision with wide local excision of the tumour done after operative procedure for bone lesion patient was planned for chemotherapy and radiotherapy for primary lung lesion . gemcitabine and cisplatin intravenous on day 1 and day 8 , q-3wks followed by radical dose of loco - regional radiotherapy ( 60 gy/30 fractions ) . she has completed 11 months of follow up and is totally asymptomatic , pain free and walks independently with support ( fig . typically multifocal but renal and thyroid carcinomas are notorious for producing only a solitary lesion . in our case patient presented with pathological fracture due to a solitary secondary bony lesion with incidental diagnosed lung primary . an assessment of the risk of pathological fracture must be made by an experienced orthopaedic surgeon . lesions without a risk for fracture should be treated with radiation or by appropriate chemotherapy directed at the tumour . lesions with a risk for pathologic fracture should be surgically stabilized before a fracture occurs . the goals of surgery are to preserve stability and function of the musculoskeletal system as well as alleviate pain . when any patient presents with metastatic disease our intent of treatment is changed from radical to palliative ; but in this case our intent of treatment was curative , because primary was a small lesion and only a single metastasis was present though patient was having pathological fracture but keeping in mind good general condition of the patient and no other metastatic lesion elsewhere , we started our treatment with radical intent . our patient had a good general condition and life expectancy ; she was only rendered immobile due to the pathological fracture . there are various possible constructive options to treat femoral bone loss are long - stem cemented or press - fit stems , impaction allografting , resection arthroplasty , allograft - prosthetic composite ( apc ) and proximal femoral mega prosthesis . most of patients with metastatic lesions to the proximal femur respond well to radiation therapy . of the 510% of these patients who require surgery , the most common reason is pathologic fracture , followed by tumor progression and intractable pain . hip disarticulation or hemipelvectomy was therefore the classic treatment for patients with large lesions of the proximal or mid femur . improved survival of patients with musculoskeletal malignancies , refinements in surgical technique and developments in bioengineering , has allowed the execution of limb - sparing surgeries in these extreme situations . as a result , proximal and total femur resection have become surgical options in the treatment of primary bone sarcomas and metastatic bone disease . expecting a favorable outcome and to improve the quality of life of the patient we went for a limb salvage surgery in form of custom made hip prosthesis despite of it being a metastatic tumor . the justification for using proximal femoral replacement surgery with a one year mortality of 65% is debatable . wedin et al reported 30% one year , 10% two years and 7% three years patient survival following surgery for proximal femoral metastases while chandrasekhar et al reported 35% , 20% and 10% as respective figures . in our case patient is fine at almost one year of follow - up and longer follow up will be needed to further comment of survival in long bones , the most common site for metastases is the proximal femur . for lesions involving this region , osteosynthetic devices frequently fail , and for this reason , endoprosthetic reconstruction may be the optimal choice for treatment . despite the metastatic lesion from lung primary limb salvage by using custom mega prosthesis is a good option in the management of these patients . although the survival rate remains grim , the patients can benefit from an improved quality of life . moreover , the psychosocial morbidity associated with disfiguring amputations can be avoided by extending the realms . high cost is a constraint a palliative megaprosthetic replacement is a good option in cases of pathological fractures secondary to metastatic adenocarcinoma . this will improve the patients quality of life for the remaining years , however cost is a constraint .

introduction : bone is the third most common site of metastatic disease . treatment of metastatic tumours of proximal femur usually used to be either palliative in the form of radiotherapy and chemotherapy or a very radical in form of hemipelvectomy and hip disarticulation . both forms of treatment were associated with dismal outcomes . now with the technological advancement and refinement in surgeries a custom made hip prosthesis offers a much better treatment option to the surgeon and a good quality life to the patient.case presentation : we are presenting a case of metastatic adenocarcinoma of upper end of left femur with pathological fracture with a small primary in right lung treated with custom made hip prosthesis . patient received chemotherapy for primary lesion and is doing well at 11 months of follow up.conclusion:this case is being presented on account of its unusual presentation and to give emphasis that in spite of metastatic disease , patient can be considered for limb salvage and megaprosthesis to improve his / her quality of life . this can be considered provided patient s general condition permits and if only a single solitary metastasis is present .

eighty - eight eyes of 88 healthy adult volunteers ( 40 males and 48 females ) were included in this study . the study was conducted in accordance with the tenets of the declaration of helsinki and was approved by an institutional review board . the participants had to be at least 18 years of age and able to comply with the lens wearing and clinical trial visits scheduled as directed by the investigator . normal , and they should not have conditions that would prevent them wearing cls safely . the corrected vision had to be 20/40 or better in each eye with spherical cls . exclusion criteria include any current ocular disease , history of ocular surgery , ocular hypertension or any evidence of corneal pathology such as keratoconus . all subjects underwent a comprehensive examination including visual acuity measurement , with anterior and posterior segment evaluation . it measures iop using an air puff and without any physical contact with the eye . during the air puff , a 9 mm slit through the apex illuminates the eye , and a built - in high - speed camera records the movement of the eye at 4330 images / s . the camera uses a sequence of 140 scheimpflug images of the cornea , which are analyzed by a built - in computer . the shape of the cornea changes from the normal convex surface to a concave surface . the device then calculates the time required to applanate the cornea with the air puff . for each patient , three consecutive measurements with the corvis st were performed by a single examiner , under the same conditions first without and then after 15 min of wearing a cl . all of the worn cls were discarded immediately following removal . to minimize diurnal variation , all measurements were done during the same session at the same time of the day ( 11 am 1 h ) . in this study , 0.50 ds cls ( dailies , alcon , tx , 69% water , 8.7 mm base curve , 14 mm diameter , center thickness 0.10 mm ) were used . the repeatability of iop measurement using the corvis st with and without cl was evaluated using pearson 's correlation analysis . bland - altman plotting was used to assess the limits of agreement between the measurements with and without cls . the repeatability of iop measurement using the corvis st with and without cl was evaluated using pearson 's correlation analysis . bland - altman plotting was used to assess the limits of agreement between the measurements with and without cls . this study evaluated 88 healthy eyes of 88 participants . there were 40 males and 48 females with a mean ( standard deviation [ sd ] ) age of 25 4 years ( range 2035 years ) . the average iops measured by the corvis st with and without cl were 13.79 2.54 and 13.80 2.70 mm of hg respectively [ table 1 ] . the mean difference was 0.01 0.16 ( 95% confidence interval [ ci ] , + 1.97 to 2.00 ) mm hg . statistical analysis via paired t - test found no statistical difference between the two groups ( p = 0.15 ) . iop measured by corvis st there was a good correlation between iop measured with and without cl ( r = 0.93 , p < 0.001 ) . intra - examiner repeatability of iop measurement with and without cls is shown in table 2 . the correlation was good for consecutive measurements of iop ranging 0.950.99 ( p < 0.001 for all correlations ) . 1 shows the limits of agreement between iop measurements with and without cls in a bland - altman plot . levene 's test confirmed that the presence of cl does not significantly affect the repeatability of iop measurements ( f = 0.45 , p = 0.141 ) . bland - altman plot showing agreement between the intraocular pressure measured by corvis st with and without contact lenses . 2 shows the box plot of iop measurements by the corvis st with and without cls . the plots indicate similar distributions and inter - quartile range on both sides of the medians . we investigated the difference in iop measured using the corvis st tonometer on healthy eyes with and without cl . recent studies have confirmed that the corvis st tonometer provides reliable and reproducible iop measurements without the need for either local anesthesia or fluorescein staining . in addition , variation in central corneal thickness seems to have little or no influence on iop measurements by the corvis st . previous studies have shown that the use of soft cls does not affect iop when measured by the topcon or nidek air puff noncontact tonometer . however , ogbuehi found that measuring iop through soft cls resulted in consistent and significant differences measurements . insler and robbins found that the difference in iop measured by nct with and without soft cls was higher in hyperopic lenses than in myopic lenses and that the power of the soft cl was a predictor of iop difference . in addition , the water content of the cl also contributes to the iop measurement . however , this effect is negligible when there is a high water content lens or a power of < 3.00 ds . low minus powered silicone hydrogel lenses are also reported to have a negligible effect on the iop . found a good correlation between iop measured through hydrogel and silicone hydrogel cls . while comparing iop in 40 normal eyes with and without a low powered minus cl , lim et al . found that tonopen consistently determined higher readings than gat we found a negligible difference between iop measurements with and without cls in our study , in addition , the difference we found , was lower than the difference in previous studies using applanation tonometry . nosch et al . , in their study comparing iop readings over a thin hydrogel cl with dct , found that a thin cl does not affect iop measurements , which corroborates our findings . we found a mean difference sd ( 95% ci ) in iop measurement without and with cls of 0.01 0.16 mm of hg , which was statistically not significant . our results are in agreement with a similar previous study conducted in glaucomatous patients that found a mean difference of 0.57 2.3 mm hg ( 95% ci , 1.50.3 ] . although previous studies have found that noncontact tonometry can be influenced by the central corneal thickness , we did not evaluate implications of varying corneal thickness and the central thickness of cls on iop measured by the corvis st . in addition , we did not measure iop through silicone hydrogel cls , which are the most frequently used extended wear therapeutic lens . in summary , our results have shown that the iop measurements in healthy eyes by the corvis st were not affected by soft cls and were reproducible . the device could , therefore , be an invaluable useful tool in the pre- and post - operative iop measurement in patients undergoing refractive surgery . it may prove to be invaluable in those cases where measuring iop over a cl is necessary , such as in patients with bandage cls . patients with corneal pathology such bullous keratopathy , abrasions or ulcers could benefit from iop measurements over a cl as the cl would serve as a buffer and hence protect the cornea . furthermore , the use of anesthetic drops can be avoided , making further corneal evaluation possible . additional studies are needed to evaluate the accuracy of the corvis st readings over different cl powers and in diseases like glaucoma . although previous studies have found that noncontact tonometry can be influenced by the central corneal thickness , we did not evaluate implications of varying corneal thickness and the central thickness of cls on iop measured by the corvis st . in addition , we did not measure iop through silicone hydrogel cls , which are the most frequently used extended wear therapeutic lens . in summary , our results have shown that the iop measurements in healthy eyes by the corvis st were not affected by soft cls and were reproducible . the device could , therefore , be an invaluable useful tool in the pre- and post - operative iop measurement in patients undergoing refractive surgery . it may prove to be invaluable in those cases where measuring iop over a cl is necessary , such as in patients with bandage cls . patients with corneal pathology such bullous keratopathy , abrasions or ulcers could benefit from iop measurements over a cl as the cl would serve as a buffer and hence protect the cornea . furthermore , the use of anesthetic drops can be avoided , making further corneal evaluation possible . additional studies are needed to evaluate the accuracy of the corvis st readings over different cl powers and in diseases like glaucoma .

objectives : the objective was to determine the repeatability of intraocular pressure ( iop ) measurements made through a soft contact lens ( cl ) using the scheimpflug noncontact tonometry in healthy subjects.methods:this prospective , randomized , single - center study included one eye of 88 subjects ( 40 male and 48 female ) . only participants without glaucoma or any other ocular pathology were included in this study . three consecutive iop measurements by the scheimpflug noncontact tonometry were performed with and without daily disposable hydrogel cls ( 0.50 ds ) ( dailies - nelfilcon a , 69% water , 8.7 mm base curve , 14 mm diameter , center thickness 0.10 mm ) by a single operator . to avoid any bias arising from diurnal variation , all measurements were made at a similar time of day ( 11 am 1 h ) . the repeatability of iop measurements using the scheimpflug noncontact tonometry with and without cls was evaluated using pearson 's correlation analysis . bland - altman plotting was used to assess the limits of agreement between the measurements with and without cls.results:the mean ( standard deviation ) iops with and without cl were 13.80 2.70 and 13.79 2.54 mm of hg respectively . the mean difference was 0.01 0.16 ( 95% confidence interval , + 1.97 to 2.00 ) mm hg . statistical analysis via paired t - test showed no statistical difference between the two groups with ( p = 0.15 ) . a good correlation was found for iop measurements with and without cl ( r = 0.93 , p < 0.001 ) . good test - retest reliability was found when iop was measured with and without cl.conclusion:there was no significant difference between iop measured with and without cls by scheimpflug noncontact tonometry .

soma ( carisoprodol ) is a commonly prescribed , centrally acting skeletal muscle relaxant that inhibits interneuronal transmission in the descending reticular formation and spinal cord . a few case reports have now been reported in the literature suggesting the addiction potential of carisoprodol . a 57-year - old chronic alcoholic , diabetic , hypertensive , hypothyroid male was admitted to a tertiary hospital for bilateral knee replacement . his daily medications included losartan ( 50 mg ) , metformin ( 1 g ) and eltroxin ( 0.75 mg ) for the last 2 years . gradually , he also developed visual hallucinations , restlessness , insomnia , and profuse sweating . with the possibility of metabolic disturbance was given in escalating doses ( 15 mg / day ) . in spite of treatment with haloperidol and zolpidem his condition worsened and was shifted to the critical care unit for assessment of need of mechanical ventilation . in the intensive care unit ( icu ) , his pulse rate was 112/min , blood pressure of 128/74 mmhg , respiratory rate of 30/min , temperature 101f and spo294% on oxygen supplementation . his general condition kept on deteriorating with increasing tachypnoea up to 40/min , tachycardia ( 130/min ) , and worsening delirium ( detected using the confusion assessment method - cam score ) . laboratory investigations showed an elevated white blood cell count ( 19,000/mm ) , creatinine phosphokinase -11560 units / dl , ( mb isoenzyme 45 units / dl ) , serum glutamic oxaloacetic transaminase -238 units / dl , serum glutamic pyruvic transaminase -154 units / dl and lactate dehydrogenase-124 units / dl , blood urea-45 mg / dl . urine analysis , serum electrolytes , chest roentgenogram , electrocardiography , computed tomography head , drug screen , blood cultures , lumbar puncture , and thyroid profile were all unremarkable . the other differential diagnoses considered in the icu were an infectious pathology , pulmonary embolism , alcohol withdrawal or nms . the whole case was re - evaluated , and it was revealed that the patient was consuming soma to alleviate his knee pain . over time , he became dependent and consumed double the indicated dose ( 6 - 7 tablets ) daily since last 10 years . due to the presence of a generalized rigidity , high - grade fever , fluctuations in sensorium , autonomic dysfunction , distal myoclonus , and marked elevated creatine phosphokinase ( cpk ) possibility of possible nms was considered and he was started on baclofen ( 30 mg / day ) and lorazepam ( 6 mg / day ) . over the next 48 h , he was calm and oriented though sedated . in the next two days , myoclonus and rigidity disappeared , cpk levels dramatically declined ( 189 mg / dl ) , and his condition completely stabilized . soma ( carisoprodol ) is n - isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate ; and is routinely used in primary care settings for the treatment of musculo - skeletal disorders associated with muscle spasms and back pain . it exerts its effect through central sedation and has an indirect agonist effect on the gamma - aminobutyric acid - a receptors . it is accepted that therapeutic effects of carisoprodol and its abuse potential are due to its conversion to meprobamate . half - life of carisoprodol and pharmacologically active metabolite , meprobamate is 2 - 3 h and 11 h , respectively , but may increase to 48 h with chronic use . to the best of our knowledge , there are only five case reports reported till date . withdrawal symptoms have occurred when intake of 700 - 2100 mg / day of carisoprodol was suddenly stopped after 9 months . propose that carisoprodol withdrawal may have precipitated nms when daily intake of large doses was abruptly stopped in this case . this diagnosis was supported by clinical features and laboratory parameters with complete resolution of the syndrome after institution of treatment and normalization of laboratory parameters . long - term consumption of heavy doses induces neural adaptation to their presence and rebound resurgence of neural electrical activity occurs after its sudden withdrawal . the rebound leads to symptoms ranging from anxiety , jitteriness to delirium , depending on the severity of withdrawal and degree of neuronal hyperactivity . the typical meprobamate withdrawal syndrome may involve various degrees of insomnia , vomiting , tremors , muscle twitching , overt anxiety , anorexia , ataxia , and bizarre behavior . he had insomnia , delirium , hallucinations , and cold sweating after 48 h of drug cessation with associated features like fever , rigidity , myoclonus , and high cpk levels . in our patient , as he developed respiratory distress , pulmonary embolism in the setting of postoperative period was a differential . when he developed fever , muscular rigidity , leukocytosis , altered consciousness , and elevated ck levels diagnosis of nms was considered . our patient had possible nms as there were clinical features to suggest the syndrome and normalization of the laboratory parameters after start of specific treatment . however , in our patient , it was the cessation of soma abuse which led to nms as the symptoms appeared prior to administration of haloperidol . as dantrolene was not readily available baclofen it resolved the rigidity in few hours with improvement in sensorium , general condition , and ck levels . our patient was addicted to soma , and sudden withdrawal may have precipitated nms in the postoperative period which was successfully managed with supportive therapy and specific treatment with baclofen and benzodiazepine . thus , clinicians should exercise high degree of suspicion in managing postoperative psychosis and nms .

soma ( carisoprodol ) is n - isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate ; a commonly prescribed , centrally acting skeletal muscle relaxant . neuroleptic malignant syndrome ( nms ) is a potentially life - threatening adverse effect of antipsychotic agents . although diagnostic criteria for nms have been established , it should be recognized that atypical presentations occur and more flexible diagnostic criteria than currently mandated , may be warranted . we wish to report a postoperative case of bilateral knee replacement who presented with carisoprodol ( soma ) withdrawal resembling nms that was a diagnostic dilemma . subsequently , it was successfully treated with oral baclofen in absence of sodium dantrolene .

a synchronous cancer of squamous cell origin found in the esophagus and stomach is very rare among gastrointestinal cancers . squamous cell carcinomas take up 38% of all esophageal cancers , and it is common in esophagus , but not in stomach.1,2 less than 100 cases were reported until now.3 a synchronous presentation of squamous cell carcinoma in the esophagus and stomach is so rare that it has not been reported in korea , yet . therefore , making an accurate diagnosis is crucial in order to plan treatment for the synchronous cancer . we have experienced a squamous cell carcinoma of esophagus and stomach and therein report this case to demonstrate that the cancer can be treated through accurate diagnosis , effective surgery and combination of chemoradiation therapy . a 57 year old male was admitted to the department of oncology complaining of dyspepsia for 2 months and sudden onset of hematemesis . he underwent endoscopy and computed tomography ( ct ) and was diagnosed with esophageal cancer and stomach cancer . he had a history of complete atrioventricular block and had a pacemaker implemented in 1992 . he had diabetes mellitus and his social history was significant for drinking a bottle of alcohol daily and smoking one pack of cigarettes for 30 years . his blood pressure was 120/80 mm hg , pulse 60/min , respiration 20/min , body temperature 36.5. his skin was dry and warm , with pale icterus and dry tongue . his lungs were clear to auscultation and his heart was regular without murmur or rubs . the complete blood count showed white blood cell count 9,610/mm , hb 10.4 g / dl , plt 28410/mm . his blood chemistry was normal , with tumor markers carcinoembryonic antigen ( cea ) 2.22 ng / ml and squamous cell carcinoma antigen ( scc ag ) 2.2 g / l . on ct , there was an ulcerofungating mass from the pylorus of the stomach to lower esophagus . the stomach lesion was abutting the tail of the pancreas and the diaphragm on ct ( fig . 1 ) . the positron emission tomography - computed tomography ( pet - ct ) showed no distant metastasis other than suspicious cancerous lesion in stomach and esophagus . the endoscopic finding revealed an irregular shaped lesion with decreased vascular marking from 31 to 39 cm from upper incisor . the main cancer lesion in the esophagus was 35 cm from ui with serosa invasion and local lymph node metastasis . 2 ) . the stomach lesion was bormann iii shaped , moderately - differentiated squamous cell carcinoma , with serosa exposure and local lymph node invasion by 9 mm ( fig . 3 ) . according to above findings , the stomach lesion was resectable and he underwent total gastrectomy and esophagoduodenostomy.4 the operative findings showed a 66 cm sizedulcerofungating mass in the lesser curvature of the stomach that invaded soft tissue of the pancreas ( fig . postoperative findings demonstrated a squamous cell carcinoma of the stomach , pt4n2m0 with serosa invasion , 4 out of 41 local lymph nodes metastasis with perineurovascular invasion . the pathologic finding showed that the proximal resection margin of the gastric lesion was negative . this suggests the squamous cell carcinoma of the stomach was not a direct extension from squamous cell carcinoma of esophagus . the patient was in good condition after the surgery , and underwent combination chemoradiotherapy ( 5-fluorouracil / cisplatin : 5fu 1 g / m per day on the first 4 days of weeks 1 , 5 , 8 , and 11th weeks , cisplatin 75 mg / m on first days of 1 , 5 , 8 , 11th weeks , radiotherapy 2.0 gy for 5 days a week ) . there have been a few reports on the double primary cancers consisting of esophageal squamous cell carcinomas and gastric adenocarcinomas , but squamous cell carcinoma of stomach is a rare finding as described in this report . recently , there has been increasing incidence of esophageal cancers associated with barrett 's esophagus . adenocarcinomas increased by six - fold from 1975 to 2001 , while 97 percent of adenocarcinoma arising from esophagogastric junction is associated with barrett 's esophagus.5,6 the prevalence of squamous cell carcinoma is on the decline , but still common in asia in association with smoking and alcohol consumption.7,8 the metastasis of esophageal cancer occurs commonly through lymphatic systems , and intramural metastasis plays an important role in tumor distribution . intramural metastasis is known to have a poor prognosis . among 1,259 patients who received surgical resection of esophageal cancers , 93 ( 7.4% ) these metastatic lesions looked similar to gastric submucosal tumor , which suggested that metastasis occurred through lymphatic systems.9 to diagnosis a synchronous cancer , three conditions should be satisfied . first of all , cancer lesions should be located apart from each other , and should not be contiguous . , the postoperative pathologic findings showed that the proximal resection margin of the gastric lesion was negative , which implies that two lesions were located separately . that is , the cancer originates from two lesions ; one from the lower esophagus and the other from the gastric fundus . moreover , the fact that the level of differentiation was different in two lesions suggests that they arise from different origins . valduga et al.10 reported a synchronous cancer with undifferentiated squamous cell carcinoma of stomach and well - differentiated squamous cell carcinoma of esophagus . in this regard , the main lesion of the synchronous cancer occurred from the fundus of the stomach reaching the esophagogastric junction , and the lower esophagus . squamous cell carcinoma mainly occurs in the mid to lower esophagus , and it is not uncommon to have other accompanying cancerous lesions . suzuki et al.11 reported that the most common lesion is the stomach ( 59.6% ) , and then colon and rectum ( 12.3% ) in the order of frequency . also , it has been reported that the mortality from the accompanying cancerous lesions is higher than the mortality from the esophageal cancer itself.12 therefore , it is important to consider the possibility of other existing cancers other than the esophagus . since the only curative treatment of esophageal cancer or gastric fundus cancer is surgical resection , it is imperative that we examine the possible metastatic lesions thoroughly before deciding the operation . until now , the standard therapy of advanced esophageal cancer is combined modality therapy : 50 gy in 25 fractions over 5 weeks , plus cisplatin intravenously on the first day of weeks 1 , 5 , 8 , and 11 , and fluorouracil , 1 g / m per day by continuous infusion on the first 4 days of weeks 1 , 5 , 8 , and 11 . in a randomized trial , combined therapy increased the survival of patients who have squamous cell or adenocarcinoma of the esophagus , compared with radiotherapy alone.13,14 in this case , we demonstrated the synchronous cancer of squamous cell origin in the esophagus and stomach . esophageal cancer tends to spread axially , up and down the length of the organ and to regional lymphatics , producing morbidity and mortality . therefore , when making a diagnosis , staging a cancer and evaluating treatment response , we should be aware that there may be potential cancer lesions other than the esophagus . through prudent diagnosis and treatment plan , complete resection of the tumor burden and chemoradiation therapy for

synchronous esophageal and gastric cancers with the pathologic features of a squamous cell carcinoma are extremely rare . a 57-year - old male visited our hospital with a history of hematemesis and was diagnosed with a synchronous cancer . he underwent a staging work - up , and the resectable lesion in the stomach was operated on following radiologic and endoscopic evaluations . the pathologic examination revealed a synchronous cancer consisting of squamous cell carcinoma in the distal esophagus and the cardia of the stomach . we report a case of a synchronous cancer that was successfully treated by surgical resection followed by concurrent chemoradiotherapy . we also discuss the hypothesis regarding the origin and presentation of the synchronous cancer and highlight the importance of careful surveillance by physicians at the time of diagnosis .

pirfenidone is an anti - fibrotic agent that has been approved for idiopathic pulmonary fibrosis ( ipf ) in europe , japan and india so far . there are scarce reports of its use in other fibrotic lung diseases , particularly other interstitial lung disease ( ild ) associated with known causes like systemic sclerosis ( ssc ) . we report the case of a patient with long - standing ssc - ild who showed symptomatic and functional improvement after pirfenidone treatment . our patient is a 44-year - old lady who was diagnosed with systemic sclerosis ( ssc ) 15 years ago with tightening of facial skin , thickening of skin over the fingers and pitting of finger tips . as per the 1980 american college of rheumatology guidelines for diagnosing systemic sclerosis , the patient was diagnosed as having ssc ( 1 major and 2 minor criteria ) . in 2006 , she presented with worsening breathlessness . in 2006 , she was also diagnosed to have systemic sclerosis - interstitial lung disease ( ssc - ild ) on the basis of bibasal crackles and an hrct scan of the chest which was suggestive of a non - specific interstitial pneumonia ( nsip ) pattern . despite treatment with corticosteroids , cyclophosphamide and azathioprine for 5 years her lung function gradually worsened as shown in table 1 and figure 1 . the six minute walk distance ( 6mwd ) also declined from 350 m in 2006 to 200 m in january 2011 . the oxygen desaturation also increased with the oxygen saturation at the end of the 6 minutes walk dropping from 91% in 2006 to 85% in january 2011 . treatment , and after discussion with the patient about off - label use of the drug , other treatments were stopped and pirfenidone ( 200 mg three times a day ) was commenced as a compassionate use in march 2011 . treatment was well tolerated and lung function stabilized over the next year ( forced vital capacity ( fvc ) 45% , diffusing capacity of lung for carbon monoxide ( dlco ) 27% predicted ) . after 20 months of pirfenidone therapy , the patient was less symptomatic with improved effort tolerance and lung function showed a trend towards improvement ( fvc 58% and dlco 54% predicted ) [ ref table 1 and figure 1 ] . the oxygen saturation at the end of six minutes ' walk also improved to 90% . serial two - dimensional echocardiography over the past 6 years did not suggest the presence of pulmonary hypertension . fvc and dlco before and after starting pirfenidone lung function as measured by % predicted fvc ( dotted line ) and dlco ( solid line ) -yearly measurements pre - pirfenidone hrct chest image 2008 pre - pirfenidone hrct chest image 2010 post - pirfenidone hrct chest image 2012 pulmonary fibrosis is the most common cause of mortality in patients with ssc surpassing scleroderma renal crisis , which has become a rarity following the advent of angiotensin - converting - enzyme ( ace ) inhibitors . a number of pro - inflammatory and pro - fibrotic extracellular mediators which have been implicated in the pathogenesis of ipf may also play a role in ssc - ild . the pivotal mediator of fibrosis is the multifunctional cytokine transforming growth factor - beta ( tgf- ) . substantial evidence implicates tgf- , along with platelet - derived growth factors , endothelin 1 and cytokines , in the pathogenesis of ssc . hence , targeting the tgf- activated pathway may be a rational strategy in the treatment of ssc - ild . pirfenidone , which has known anti - inflammatory , anti - fibrogenic and antioxidant properties , has been shown to reduce fibroblast proliferation and inhibit tgf--stimulated collagen production . we describe here an ssc - ild patient , who clearly showed a reversal in lung function deterioration after initiation of pirfenidone . miura and colleagues reported improvement of lung function after pirfenidone treatment in three japanese patients with ssc - ild . nagai and colleagues also showed that pirfenidone had a stabilizing effect on the course of 10 patients with chronic progressive pulmonary fibrosis , 2 of which were ssc - ild cases . the capacity trials showed that 2403 mg / day of pirfenidone was the most effective although a smaller dose of 1197 mg / day also slowed the decline in fvc . in nagai 's study the dose of pirfenidone used was about 40 mg / kg / day . in our patient , we used a lower dose of pirfenidone of 200 mg three times a day and continued the same without increasing as the patient had stabilized clinically and functionally on that dose . the above - mentioned reports , together with the present one , suggest that pirfenidone should be investigated in properly designed prospective trials as a treatment for patients with progressive ssc - ild .

pirfenidone is an anti - fibrotic drug which has been approved for the management of patients with idiopathic pulmonary fibrosis ( ipf ) . however , its role in interstitial lung disease ( ild ) due to other causes such as systemic sclerosis ( ssc ) is not clear . we present a case of a patient with ssc associated ild who showed a subjective as well as objective improvement in lung function with pirfenidone .

perfect crystal x - ray and neutron interferometry has a long history [ 13 ] , but an interesting feature of crystal interferometers , namely their extreme angular sensitivity , has been exploited only by intensity measurements but not yet by phase measurements . only recently , the machining of large - scale crystal interferometers , specially designed , opened novel applications in neutron optics and fundamental physics . the interferometer of mach zehnder type has been cut with two additional lamellas l1 and l2 in the middle ( fig . 1 ) , which can be used for the measurement of crystal phases due to dynamical diffraction . we refer to this phase as laue phase because the underlying diffraction process is known as laue transmission in crystallography . due to the large interferometer dimensions , different prism configurations can be employed for coherent beam deflection with smoothly tunable deflection angles . it turns out that the laue phase is extremely sensitive to beam deflections in front of the crystal lamellas ( section 2 ) , which become detectable with the new interferometer setup ( section 3 ) . after the first successful tests and phase measurements new applications can be envisaged , like the nice idea presented by ioffe et al . for measuring the neutron electron scattering length , or a proposal made by greene et al . for testing a hypothetical short - range interaction ( section 4 ) . a distinct phase shift is generated when the neutron wave passes a perfect crystal plate close to the bragg condition . in the following , we are considering only the diffracted wave in forward direction . the laue phase is then defined as the argument of the complex transmission amplitude ( t ) as shown in fig . 2.(1)laue(y)arg{t(y)}y=sin2be/|vhkl| . the parameters y and =b describe the beam deviation from the bragg angle b , e the neutron energy and |vhkl| the crystal potential . the laue phase in an analytical form reads(2)laue(y)=laue(0)ahy+arctan{y1+y2tan[ah1+y2]}. at certain positions of , the arctan term induces a distinct fine - structure to the phase which is extremely sensitive to the pendellsung length h . the pendellsung length is an important parameter in crystal optics because it contains important quantities like the atomic scattering length ( batom ) and the debye waller factor ( w)(3)ahd/hh=n2dlnbatom(q)ew(q)tanbbatom and w depend on the momentum transfer ( q=2n / dl ) ; n denotes the atomic density , dl the lattices spacing and n the order of reflection . it turns out that the slope of the laue phase , and hence the angular resolution , reaches its maximum in the vicinity of the bragg condition =b0 . there laue increases linearly with and the angular resolution is determined by the geometric ratio of thickness ( d ) and lattice spacing ( dl)(4a)laue()laue(0)+nddl+o(3)or alternatively it can be written as a function of momentum transfer(4b)laue()laue(0)+qd2+o(3 ) . higher order reflections ( nh , nk , nl ) , or equivalently larger momentum transfers , are therefore more sensitive to beam deflections ( fig . first measurements of the laue phase have been performed at an instrument ill - s18 with the configuration shown in fig . the fine - tuning of beam deflection was achieved with a simultaneous rotation of four aluminium prisms about the axis ( fig . the averaging of the laue phase over the angular distribution slightly reduces the instrumental resolution yielding an angular sensitivity of(5)()8.50.001(440)and()60.001(220)near the bragg condition . 4b is a compromise because further experiments are intended , in which the two - loop feature becomes essential . the angular sensitivity would further be enhanced by machining a new interferometer with thicker lamellas , for example l1=l2=15 mm as sketched in fig . 4c , and by generating two opposite beam deflections . assuming a realistic phase resolution of 0.11 and considering all possible improvements an angular resolution of 10 s of arc ( 510 rad ) seems feasible . another method for achieving high angular sensitivity can be realized with the same interferometer crystal in the non - interfering arrangement . then the angular sensitivity depends again on the geometric ratio dl / d , but it can be expected that the high phase resolution makes the interference method favorable over the analysis of rocking curve widths . as primary goal , the accuracy of laue phase measurements has to be improved , in particular at angular positions , where deviations from the linear behavior are expected ( see the pendellsung - structures in the phase plot in fig . 5 ) . such nonlinear structures reveal a pronounced sensitivity to the pendellsung length and the parameters therein , namely the atomic scattering length and the debye waller factor . according to a proposal by greene et al . , the atomic scattering length comprises three contributions , the dominant nuclear scattering length ( bn ) , the neutron electron scattering length ( bne ) , and a hypothetical short - range interaction ( bg)(6)batom(q)=bnz[1f(q)]bne+fg(q)bg . the bne and bg terms become distinguishable by their different q - dependence of the form factors f , fg . a precise measurement of batom at several reflections would allow separating the different contributions . a short - range interaction would modify the silicon scattering length , with the effective range parameter ( s ) as dominant parameter ( bgs2 ) . corrections to newton s law of gravity are mainly expected at submillimeter , even at nuclear length scales . the most common assumption consists in a modified potential according to(7)v(r)=gmmr(1+er/s),where g is the gravitational constant , m and m are the interacting masses and characterizes the strength of the correction . one now has to find constraints for over a wide range of s ( e.g. =10 , s=1 f220bg=1.410 fm ) . especially in the range s<100 nm , the constraints for are still very weak , as most methods are not sensitive to this region . interferometers with long beam paths become increasingly sensitive to the coriolis force due to earth s rotation . this causes an additional , wavelength - dependent , beam deflection and an offset to the laue phase as shown in fig . experimentally a phase offset of approximately 50 has been obtained for the ( 2 2 0 ) reflection , and accordingly 25 offset for the ( 4 4 0 ) reflection . the coriolis deflection can be compensated by inserting suitable wedges in both interfering beams , whereby the visibility maximum is restored . another , much larger coriolis phase arises due to the interferometer s large enclosed beam area ( a=area vector perpendicular to the enclosed beam , see table 1 ) . this so - called sagnac phase depends on the product a ( =earth s rotation vector ) ; it is wavelength - independent and becomes larger than 900 considering the present beam orientation at instrument s18 . the sagnac phase becomes crucial in gravitation experiments , where it has to be eliminated experimentally by an interleaved scanning procedure . it turns out that perfect crystal interferometers are extremely sensitive to beam deviations close to the bragg condition . by further evolving the interferometer design an angular resolution of the order of 10 s of arc and momentum resolution q210 nm becomes attainable . large crystal interferometers consisting of six or more beam splitters open new application fields like the precise measurement of the laue phase and associated fundamental quantities like the neutron electron scattering length or the recently derived short - range interaction scattering length . improving the angular sensitivity and

the currently largest perfect - crystal neutron interferometer with six beam splitters and two interference loops offers novel applications in neutron interferometry . the two additional lamellas can be used for quantitative measurements of a phase shift due to crystal diffraction in the vicinity of a bragg condition . the arising phase , referred to as laue phase , reveals an extreme angular sensitivity , which allows the detection of beam deflections of the order of 106 s of arc . furthermore , a precise measurement of the laue phase at different reflections might constitute an interesting opportunity for the extraction of fundamental quantities like the neutron electron scattering length , gravitational short - range interactions in the sub - micron range and the debye waller factor . for that purpose several harmonics can be utilized at the interferometer instrument ill - s18 .

guillain - barr syndrome ( gbs ) is an acute inflammatory demyelinating polyneuropathy , an autoimmune disease affecting the peripheral nervous system that is usually triggered by an acute infectious process and is an important cause of acute neuromuscular paralysis9,13 ) . in typical cases , the first symptoms of gbs are pain , numbness , paresthesia , and weakness in the limbs3 ) . the weakness may initially be proximal , distal , or a combination of both and rapidly progressive3 ) . lumbar spinal stenosis , which is prevalent in elderly population , is one of the causes of cauda equina syndrome in elderly12 ) . in a typical patient with gbs , however , in patients with asymmetric weakness , in those with weakness only in the lower extremities , in those with normoreflexia , or in those with symptomatic lumbar spinal stenosis , the diagnosis of gbs as a cause of cauda equina syndrome is challenging . here , we report on a case of cauda equina syndrome resulting from gbs in 74-year - old patient with symptomatic lumbar spinal stenosis and discuss the differential diagnosis of these two diseases . a74-year - old previously healthy woman presented to the emergency department with low back pain , bilateral numbness and weakness in the lower extremities . her symptoms had begun after riding in a car for 4 hours 1 day before and become worse . she had been treated for symptomatic lumbar spinal stenosis with medication and physiotherapy for 1 month . physical examination revealed paresis of the left lower extremity with strength of 4/5 and of the right lower extremity with strength of 4+/5 . deep tendon reflexes including biceps jerk , knee jerk and ankle jerk were all hypoactive , and the babinski sign was negative . magnetic resonance imaging ( mri ) of the lumbar spine revealed spinal stenosis at the levels l2-l3 , l3-l4 , and l4-l5 , and disc protrusion was suspected at the l3-l4 level ( fig . initially she was managed with pain control and regular neurological assessment , but her pain and weakness got worse over the next 3 days . she became unable to stand without assistance with strength of 3/5 in the left lower extremity and of the right lower extremity with strength of 4/5 . we suspected pain and paraparesis resulting from causes other than the lumbar spinal stenosis because of the rapidly progressive motor weakness . electromyography ( emg ) and nerve conduction study ( ncs ) 4 days after the onset of weakness of the lower extremities . two days after the initial emg and ncs , she complaint of voiding difficulty and there was 600 cc of post - voiding residual urine in the bladder . however ncs repeat examination at that time again revealed no evidence of peripheral neuropathy . under the impression of cauda equina syndrome due to lumbar spinal stenosis with disc herniation , the patient underwent emergency operation with decompression of the three narrow levels however , her weakness and urinary retention remained unchanged postoperatively , and in addition , bilateral facial palsy , which was more severe in the left side , occurred 5 days after the operation . after referral to the department of neurology for the facial palsy , gbs was taken into consideration as main diagnosis . electrodiagnostic evaluation , which was performed approximately 2 weeks from the onset of symptoms , presented electrodiagnostic findings suggestive of gbs . owing to postoperative wound problems at lumbar region , and refusal of the patient to further invasive procedures , lumbar spinal cerebrospinal fluid ( csf ) tapping , treatment was initiated solely under impression of gbs by clinical features , clinical course , and results from electrodiagnostic study . she took intravenous immunoglobulin in a regimen of 0.4 g / kg daily for 5 consecutive days . three weeks after the onset of symptoms , her weakness began to improve and she could walk with assistance at 5 weeks after the onset of weakness . one year after the onset of symptoms , her pain and weakness were much improved , urination was nearly normal , and no facial palsy was found . she could walk without assistance , but limping and numbness on the lower extremities remained . gbs has remained a descriptive diagnosis of a disorder for which there are no specific diagnostic tests13 ) . the combination of rapidly progressive symmetrical weakness in the arms and legs with or without sensory disturbances , hypoflexia or areflexia , in the absence of a csf cellular reaction , remain the hallmarks for the clinical diagnosis of gbs13 ) . in typical cases , the first symptoms are pain , numbness , paresthesia , or weakness in the limbs3 ) . pain was reported in the 2 weeks preceding weakness in 36% of patients , and 66% reported pain in first 3 weeks10 ) . the most frequent location of pain was the extremities , less often low back or back10 ) . the most frequent pattern of pain was muscle pain , less often painful paresthesia or radicular pain10 ) . the weakness may initially be proximal , distal , or a combination of both , rapidly progressive , bilateral , and relatively symmetric3,13 ) . however , atypical cases have been reported , in which the patients presented with asymmetric weakness , unilateral fascial palsy , normorelexia , or hyperreflexia2,7,15 ) . the diagnosis of gbs itself is usually not difficult for the neurologist , but can be challenging for the physician of first contact who may not have seen a case3 ) . in a typical patient with gbs , however , in atypical patients , clinical manifestations of gbs can vary and the diagnosis of gbs may be challenging even to the neurologist . a thorough medical assessment may be needed to exclude ' ' mimic disorders"9,13 ) . in such cases ncs and emg play a very important role in diagnosis , subtype classification , and confirmation that the disease is a peripheral neuropathy , but in up to 13% of cases the initial ncs are normal3,9 ) . in these cases , retesting in 1 to 2 weeks might be required to confirm the diagnosis3,9 ) . in the present case , initial and repeated electrodiagnostic test did not suggest gbs , but the tests were performed too early , that is within 1 week after the onset of symptoms . in addition to ncs and emg , csf analysis may confirm a diagnosis of gbs9 ) . csf protein concentrations in patients with gbs are often normal in the first week , but increased in more than 90% of the patients at the end of the second week13 ) . therefore , neither of these tests is highly sensitive early in the course of the disease8 ) . we did not examine csf because we did not consider the possibility of gbs initially . however , even if diagnosis with gbs was considered and subsequent csf evaluation was performed at the time of arrival at the emergency department or on admission , gbs would not have been accurately diagnosed due to the fact that csf profiles are usually normal in the early stage of gbs . in the present case , lower extremity weakness was not improved following surgery , and in addition , although asymmetric , bilateral facial palsy developed . after referral to the department of neurology for the facial palsy , gbs was taken into consideration as main diagnosis . electrodiagnostic evaluation , which was performed approximately 2 weeks from the onset of symptoms , presented electrodiagnostic findings suggestive of gbs . owing to postoperative wound problems at lumbar region , and refusal of the patient to invasive procedures including lumbar spinal csf tapping , treatment was initiated solely under impression of gbs by clinical features , clinical course , and results from electrodiagnostic study . some authors suggested spinal mri is a sensitive diagnostic test and should be considered an additional diagnostic tool8,14 ) . spinal mri with gadolinium frequently indicates enhancement of the spinal nerve roots early in the course of pediatric gbs , and aids clinicians in establishing a diagnosis early in the course of the disease , when other diagnostic tests may still produce normal results8 ) . however , in patients with lumbar spinal stenosis , enhancement of compressed nerve roots can be visualized in mri and this enhancement is thought to reflect either obstructed periradicular veins , indicating venous stasis , intraradicular edema , or breakdown of the blood - nerve barrier , a sign of chronic compressive radiculitis1,6,11 ) . in the present case , enhancement of the cauda equina was found in the mri of the lumbar spine , but we thought it resulted from compressed nerve roots in lumbar spinal stenosis rather than gbs . we could find no report on the differences in enhancement patterns in the mri between gbs and lumbar spinal stenosis . the classic clinical presentation of cauda equina syndrome is characterized by low back pain , bilateral sciatica , saddle anesthesia , weakness of lower extremities that may progress to paraplegia , bowel and bladder dysfunction , and impairment of the ankle jerk12 ) . although evaluating a patient with back pain who present with " classic " cauda equina syndrome typically does not present a diagnostic challenge , evaluating a patient with back pain who has early and incomplete signs and symptoms of cauda equina syndrome are difficult problems12 ) . symptoms and signs of gbs and cauda equina syndrome resulting from lumbar spinal stenosis are similar in many ways . thus , the diagnosis of gbs can be difficult , particularly in patients with pre - existing symptomatic lumbar spinal stenosis who presented with low back pain , asymmetric weakness of the lower extrimities , bilateral numbness or paresthesia in the lower extrimities , and urinary retention as in our patient . but , lumbar spinal stenosis per se is seldom a cause of the cauda equina syndrome and is only found in exceptional cases in spite of the fact that this disease causes a compression of the dura5,11 ) . in one study of 163 patients with lumbar spinal stenosis in southern sweden in the period 1982 - 1991 , an annual incidence of lumbar spinal stenosis of about 50 cases per million inhabitants was found . during this 10-year period , in another study , 340 cases of lumbar spinal stenosis were diagnosed in a county in denmark in the period 1996 - 2000 . during a 5-year period , only one patient with acute cauda equina syndrome in patients with lumbar spinal stenosis was diagnosed5 ) . while a disc herniation in a narrow spinal canal may start the cauda equina syndrome , sudden onset of a cauda equina syndrome resulting from a large herniated disc is different from the insidious onset of a cauda equina syndrome from lumbar spinal stenosis5,12 ) . in the present case , disc herniation at the l3-l4 level was found in the mri of the lumbar spine . we thought the pain , progressive paraparesis , and urinary retention resulted from the disc herniation with underlying lumbar spinal stenosis because no other causes were found on the electrodiagnostic study . but in retrospect , the patient presented with rapidly progressive paraparesis and this was more suggestive of gbs rather than lumbar spinal stenosis . atypical symptoms and signs of gbs can be confused with those of lumbar spinal stenosis . careful observation of the clinical course and the awareness and suspicion of a possibility of gbs are essential for the proper management and for avoiding unnecessary surgery for lumbar spinal stenosis .

guillain - barr syndrome ( gbs ) is an acute inflammatory demyelinating polyneuropathy . in typical cases , the first symptoms of gbs are pain , numbness , paresthesia , weakness in the limbs . autonomic involvement is common and causes urinary retention and ileus . much of these symptoms overlap with those of lumbar spinal stenosis . therefore , correct diagnosis of gbs in a patient with symptomatic lumbar spinal stenosis or in a patient with atypical manifestations of gbs can be difficult , especially early in the course of gbs . here , we report on a case of atypical gbs in a 74-year - old previously healthy patient with lumbar spinal stenosis and discuss the differential diagnosis of the gbs and lumbar spinal stenosis .

adenoid cystic carcinoma ( acc ) is a malignant tumor which develops in areas with secretory glands , most commonly in the head and neck region . the name cylindroma originated from the specific appearance of the tumor cells with cylindrical pseudolumina or pseudospaces . primary acc ( pacc ) of the skin is a rare tumor first described by boggio in 1975 , of which fewer than 70 cases have so far been studied in detail and reported in the english literature . pacc has a low potential for distant metastases but has a very aggressive infiltrative growth pattern , frequent perineural invasion , and a high risk of local recurrence after excision . the high risk of local recurrence after surgery suggests that postoperative radiotherapy should be administered . in 1991 , a 43-year - old woman presented to the dermatologist with a 10-year history of an enlarging nodule in the right axilla . in the previous couple of years , there were several episodes of inflammation . a wide excision was performed , and the histological result showed acc of the skin . macroscopically , the tumor nodule was solid and covered with connective tissue . in 1996 , radiotherapy was offered and performed with 44 gy administered . in 2000 , a local recurrence was suspected in the area of the previous surgical treatments , but postexcision histology showed connective tissue only . in 2006 and 2010 , excisions were made after local recurrences of tumor formation in the operative cicatrix , which were diagnosed as acc . all of the laboratory and imaging tests during the 24-year history of the disease were within normal ranges , and no metastatic disease was diagnosed . in march 2015 , once again , growth in the postoperative cicatrix in the right axilla appeared . 1 ) , with the tumor cells arranged in multiple variously sized lobules . they showed an overall cribriform appearance of the tumor ( fig . the chest ct scan showed no pulmonary metastases , and the patient was offered an active follow - up . pacc of the skin is a rare tumor with fewer than 70 cases reported in the english literature . it equally affects males and females , with a slight prevalence in females ( 54% ) [ 7 , 8 , 9 ] . in 44% of the cases , there was a documented local recurrence with a follow - up period of 58 months . metastases in other organs are rare and , in the event that they occur , the lung and lymph nodes are commonly affected sites . the reported patient presented with pacc of the skin , first diagnosed in 1991 , with four histologically confirmed local recurrences . there were no detailed case reports in the accessible literature on such series of local recurrences , only reports on a high risk of such recurrences . all four recurrences were surgically treated ; after the second one , a decision for radiotherapy was made , and the latter was administered at a dose of 44 gy . the last local recurrence we described was diagnosed in march 2015 and was treated only surgically . acc of the skin most often presents a treatment challenge due to the rarity of the lesion . surgical resection is a primary treatment , usually followed by radiotherapy ; chemotherapy is used in select cases . wide excision is the most common surgical technique , which was performed in the reported patient as well . xu et al . reported 7 cases treated with mohs micrographic surgery without local recurrences during the follow - up period . nevertheless , the authors admit that the limited number of cases and the insufficient follow - up period do not allow drawing a definitive conclusion on the superiority of mohs micrographic surgery over wide local excision . there are no studies in the literature indicating the best surgical approach , and there are no sufficient follow - up data in cases with multiple local recurrences either . again , because of the rarity of pacc of the skin , there are no studies in the literature about the efficacy of radiotherapy and chemotherapy . nevertheless , there are a few reports debating that radiotherapy in pacc of the skin can help in achieving locoregional control when given postoperatively . cisplatin - containing regimens ( cisplatin and 5-fluorouracil , cisplatin and anthracyclines , cisplatin and vinorelbine ) showed some response in isolated cases [ 12 , 13 , 14 ] . the reported patient presented with pacc of the skin , with multiple local recurrences treated with wide local excisions and radiotherapy , and without imaging evidence of metastatic disease . after the last local recurrence , the patient was offered an active follow - up , the decision being based on the long disease - free intervals between the local recurrences . surgery remains a possible future option for treatment , as the localization of the tumor allows further excision in case of recurrences . chemotherapy is not curative and could be reserved for metastatic disease , whereas radiotherapy could be used for future local control . the corresponding author acknowledges that he is responsible for complying with ethical requirements and declares that the patient was correctly informed and written informed consent was obtained ; the confidentiality of the patient was strictly preserved ; the patient was informed about the submission of the manuscript and will be acquainted when the article is published , and the principal of the complex cancer center , plovdiv , was informed and the manuscript was written according to the ethical codex of the institution .

primary adenoid cystic carcinoma ( pacc ) of the skin is a rare tumor with fewer than 70 cases studied in detail in the english literature . this type of tumor shows a prolonged course and a growth pattern usually manifested by multiple local recurrences and has a low potential for distant metastases . the most important modality for primary treatment is surgical resection followed by radiotherapy . we report a woman aged 43 years at the time of diagnosis , who presented with a slow - growing nodule in the right axilla without lymph node enlargement . a wide local excision was performed , and the histology revealed an adenoid cystic carcinoma . during the next 24 years , another four local recurrences were excised ( the last one in 2015 ) and confirmed histologically to be adenoid cystic carcinoma . the patient was given 44 gy of radiotherapy after the second surgery in 1996 . pacc of the skin is a rare tumor with insufficient data concerning the efficacy of the surgical technique and chemotherapy and radiotherapy treatment , even more so in the case of multiple recurrences . after the last recurrence , the patient was offered an active follow - up based on the long tumor - free intervals in the past and because the site of the primary tumor allowed further surgical excisions in future recurrences .

a 56-year - old male , 168 cm tall and weighing 71 kg , with a traumatic right rotator cuff injury , was scheduled for arthroscopic reconstruction surgery under general anesthesia . this patient had a history of diabetes mellitus and was taking oral hypoglycemic agents and insulin . for several years , he experienced recurrent episodes of severe left ocular pain and increased iop , which later resolved . on close ophthalmic examination , there was mild epithelial edema of the cornea with a few keratic precipitates , and his cup / disc ratio was 0.5 with no visual field change . during the acute crisis period , the measured iop in his left eye was above 30 mmhg and the iop in his right eye was 13 mmhg . his symptoms were relieved after applying eye drops containing dorzolamide , a carbonic anhydrase inhibitor , and prednisolone acetate , but frequently recurred . three weeks before his scheduled surgery , the iop in his left eye rose again and he became extremely anxious about the operation . after consultation with an ophthalmologist , we decided to measure the patient 's iop intraoperatively using portable tonometry , and obtained informed consent from the patient for this perioperative risk . preoperative laboratory findings , including hemoglobin concentration , liver function and coagulation tests , and arterial blood gas analysis , were normal , as were chest x - rays . the patient had a left axis deviation and an incomplete right fascicular block on electrocardiography and a mild restrictive pattern on pulmonary function test without any significant symptoms . in the morning of the day of surgery , the patient received 7.5 mg of midazolam per os . before entering the operating room , his vital signs were stable , with a blood pressure of 133/75 mmhg , a heart rate of 82 beats per min , and an oxygen saturation of 99% . two drops of 0.5% proparacaine hydrochloride were applied to each eye , and iop was measured by portable tonometry ( tono - pen avia , ametek , ny , usa ) ( fig . initially , iop was 19 mmhg in his left eye and 16 mmhg in his right eye . a 20-gauge catheter was inserted into his left radial artery to monitor continuous arterial pressure . anesthesia was induced with propofol 100 mg , lidocaine 75 mg , rocuronium 50 mg , and a supplemental dose of fentanyl 100 g , and ventilation was controlled to maintain end tidal carbon dioxide at 35 5 mmhg . anesthesia was maintained with 2 - 2.5% sevoflurane in an oxygen - air mixture ( fio2 0.5 ) . immediately after tracheal intubation , iop increased to 23 mmhg in his left eye and 21 mmhg in his right eye , but decreased within 5 min to 14 mmhg and 12 mmhg , respectively . initial arterial blood gas analysis showed an hct of 39% , a ph of 7.48 , a paco2 of 34 mmhg , and a pao2 of 240 mmhg . after changing the patient 's position to left lateral decubitus , the iop was 15 mmhg in his left eye and 14 mmhg in his right side , but increased to 20 mmhg and 14 mmhg , respectively , after skin incision and arthroscopic insertion . the concentration of inhaled sevoflurane was adjusted in response to instantaneous iop variation , and the occurrence of iop surge was closely monitored . during the 210 min operation , the patient 's vital signs remained stable and no adverse event occurred . serial measurements by portable tonometry showed that his iop remained within an acceptable range throughout the entire perioperative period ( fig . posner - schlossman syndrome is an uncommon ocular hypertensive disorder , with a mean annual incidence of 0.4 per 100,000 population and a mean annual prevalence of 1.9 per 100,000 . its symptoms include blurred vision and/or ocular pain , which frequently subside in days to weeks . moreover , posner - schlossman syndrome is associated with anterior uveitis and usually recurs periodically . although its pathogenic mechanism is unclear , it has been associated with herpes simplex virus , cytomegalovirus infection , and autonomic dysfunction , and has been suggested as a variation of developmental glaucoma . posner - schlossman syndrome may be related to primary open - angle glaucoma and non - arteritic anterior optic neuropathy , which cause ischemic optic disc changes . because an acute increase in iop , to over 40 mmhg ( normal 10 - 21 mmhg ) , may be present for several days prior to the manifestations of symptoms , control of iop during this period is critical . partial or total blindness after non - ophthalmic surgery has been reported in patients who experience an increase in iop beyond the normal range . although our patient was in a relapsed phase of posner - schlossman syndrome and his iop was within the normal range at the time of surgery , attention is warranted during surgery because some of these patients have atypical presentation , with elevated iop between attacks . most anesthetic drugs and opioids lower iop , and intravenous anesthetics such as propofol , thiopental , and etomidate reduce iop surge . propofol , administered in a continuous intravenous manner , reduces iop regardless of changes in blood pressure and heart rate . propofol seems to be a better anesthetic choice in these patients , as it protects against iop , even in patients in the trendelenburg position , possibly due to a sympatholytic effect . over the relatively short period of most operations , changes in iop in patients anesthetized with propofol and sevoflurane vecuronium bromide , at a concentration of 0.1 mg / kg , reduces iop 22.6% , by indirectly lowering central venous pressure and venous pooling . by contrast , succinylcholine increases iop by direct contraction of the orbital smooth muscle , hindering aqueous outflow . although topical application of a carbonic anhydrase inhibitor , a beta - blocker , an alpha - adrenoceptor agonist , or a prostaglandin analogue can be used to treat acute ocular hypertension , the benefit of these drugs must outweigh the risks of possible systemic adverse effects . factors other than anesthetic drugs can alter iop . manipulations that increase iop include use of a laryngoscope , tracheal intubation , insertion of a laryngeal mask into the airway , hypoxia , hypercarbia , and patient position . hypoxia , hypercarbia , and coughing reflex during airway maneuvers may increase central venous pressure , resulting in an increase in iop . patient position may also affect iop ; for example , in the trendelenburg position with pneumoperitonium , the iop may increase due to increased systemic blood pressure , partial pressure of end tidal carbon dioxide , or endobronchial pressure . in a steeper trendelenburg position , greater than 30 degrees of bed tilting , optic hypoperfusion caused by the compartment syndrome of the optic nerve may lead to postoperative visual loss . to manage the iop surge , it is necessary to avoid venous pooling of the orbit by relieving the patient from the deep head down position , placing the orbit above the level of the heart . maintaining ocular perfusion pressure , calculated by subtracting iop from mean arterial pressure , above the iop can prevent hypoperfusion , which may lead to optic ischemia in a closed compartment . the increases in iop during intubation and emergence from anesthesia may be prevented by minimizing sympathetic stimulation and cough reflexes , and by maintaining patient hemodynamic variables within acceptable ranges . patients who experience a sudden iop surge should be kept in the reverse trendelenburg position and treated with ophthalmic beta - blockers such as timol eye drops . tonopen is a light - weight portable device with a small diameter tip that has an accuracy equal to that of the goldmann applanation tonometer , considered the gold standard for measuring iop . although measurements using the tonopen and goldmann applanation tonometers can differ more than 5 mmhg in approximately 7 - 8% of eyes , tonopen measurements are within 3 mmhg of goldmann measurements in > 80% of eyes . a statistical confidence indicator is shown on the screen as a percentage , thus indicating the accuracy of the measurement . we monitored iop in our patient at regular intervals and during maneuvers such as intubation and position change to maintain iop at constant levels . a portable tonometer can therefore provide point - of - care monitoring of iop during general anesthesia . in conclusion , patients with posner - schlossman syndrome can experience adverse events related to visual function upon undergoing non - ophthalmic surgery under general anesthesia . serial measurements of perioperative iop will provide clinical information useful for the safety of these patients .

a 56-year - old man with a rotator cuff injury , scheduled for arthroscopic reconstruction surgery , had a history of recurrent symptoms of eyeball pain and blurred vision for several years . after close examination , he was diagnosed with posner - schlossman syndrome . three weeks before the scheduled surgery , his intraocular pressure ( iop ) increased ( > 30 mmhg ) and he became extremely anxious about the surgery . we monitored his iop intraoperatively and successfully completed general anesthesia without any sequelae . as posner - schlossman syndrome can present with severe complications that may lead to postoperative visual loss , intraoperative monitoring of intraocular monitoring and careful anesthetic management are crucial to protect vision .

but , these days , with advanced technology , brain receptors have been mapped . in 1957 , kuhn reported that imipramine has antidepressant properties . this was followed by other tricyclics such as amitriptyline , nortriptyline , doxepine , etc . and , later on , the selective serotonin reuptake inhibitor , i.e. fluvoxamine , fluoxetine , sertraline , etc . however , to date , the mechanism of action of these antidepressant drugs is yet to be precisely known . today , many antidepressants are available but they often cause adverse effects , particularly psychomotor and cognitive . this leads to patient maladjustment and may impair psychomotor performance , which plays important role in driving and operating complex machinery . therefore , it is desirable to develop antidepressant drugs with a minimal effect on these functions so that the patient 's productivity or social adjustment are not hampered . fluvoxamine is a newer antidepressant and hence the present study was planned to investigate its effect on psychomotor functions and compare with nortriptyline and record their adverse reactions . a total of 26 healthy volunteers , 20 males and six females , of age group -30 years with informed consent were included in this double - blind , placebocontrolled , crossover study . a single oral dose of fluvoxamine 50 mg , nortriptyline 50 mg and placebo was administered following a latin square design . the parameters were tested at 0 , 2 and 4 h. before the study volunteers received training till a performance plateau was reached . six - digit cancellation test ( 6dct ) : volunteers were required to cancel as many target digits as possible in a sheet consisting of 1,200 randomized digits in 3 min . digit symbol substitution test ( dsst ) : volunteers were required to insert the corresponding symbol in the space above each digit in a sheet consisting of 200 randomized digits in 2 min . critical flicker fusion test ( cfft ) : it is a reliable psychometric test as there is no learning curve effect . the apparatus consists of a viewing tube at the end of which a red circle of light flickers at the rate of 550 cycles / s . the critical fusion frequency was determined by increasing the frequency from 5 hz till a steady light source was seen and the critical flicker frequency by decreasing the frequency from 50 hz till flickering was seen . arithmetic ability test ( aa ) : the subjects had to solve simple mathematical problems , i.e. addition , subtraction , multiplication and division ( five of each ) within 2 min . this was tested by steadiness tester , which consists of holes of different size sand subjects had to insert stylus into the hole without touching its sides . the volunteers were asked to indicate the state of their current feeling by marking on a 100 mm horizontal line . the opposite mood - related adjectives at each end were as follows : wide awake - extreme sleepyalert - dullactive - tired wide awake - extreme sleepy volunteers marked their subjectively felt side effects on a sheet . the tests used were anova followed by post - hoc newman - keuls multiple comparison test . six - digit cancellation test ( 6dct ) : volunteers were required to cancel as many target digits as possible in a sheet consisting of 1,200 randomized digits in 3 min . digit symbol substitution test ( dsst ) : volunteers were required to insert the corresponding symbol in the space above each digit in a sheet consisting of 200 randomized digits in 2 min . critical flicker fusion test ( cfft ) : it is a reliable psychometric test as there is no learning curve effect . the apparatus consists of a viewing tube at the end of which a red circle of light flickers at the rate of 550 cycles / s . the critical fusion frequency was determined by increasing the frequency from 5 hz till a steady light source was seen and the critical flicker frequency by decreasing the frequency from 50 hz till flickering was seen . arithmetic ability test ( aa ) : the subjects had to solve simple mathematical problems , i.e. addition , subtraction , multiplication and division ( five of each ) within 2 min . six - digit cancellation test ( 6dct ) : volunteers were required to cancel as many target digits as possible in a sheet consisting of 1,200 randomized digits in 3 min . digit symbol substitution test ( dsst ) : volunteers were required to insert the corresponding symbol in the space above each digit in a sheet consisting of 200 randomized digits in 2 min . critical flicker fusion test ( cfft ) : it is a reliable psychometric test as there is no learning curve effect . the apparatus consists of a viewing tube at the end of which a red circle of light flickers at the rate of 550 cycles / s . the critical fusion frequency was determined by increasing the frequency from 5 hz till a steady light source was seen and the critical flicker frequency by decreasing the frequency from 50 hz till flickering was seen . arithmetic ability test ( aa ) : the subjects had to solve simple mathematical problems , i.e. addition , subtraction , multiplication and division ( five of each ) within 2 min . this was tested by steadiness tester , which consists of holes of different size sand subjects had to insert stylus into the hole without touching its sides . this was tested by steadiness tester , which consists of holes of different size sand subjects had to insert stylus into the hole without touching its sides . the volunteers were asked to indicate the state of their current feeling by marking on a 100 mm horizontal line . the opposite mood - related adjectives at each end were as follows : wide awake - extreme sleepyalert - dullactive - tired wide awake - extreme sleepy volunteers marked their subjectively felt side effects on a sheet . the tests used were anova followed by post - hoc newman - keuls multiple comparison test . the volunteers were asked to indicate the state of their current feeling by marking on a 100 mm horizontal line . the opposite mood - related adjectives at each end were as follows : wide awake - extreme sleepyalert - dullactive - tired wide awake - extreme sleepy the tests used were anova followed by post - hoc newman - keuls multiple comparison test . in the study , nortriptyline 50 mg dose decreased the substitution of symbols score on dsst and the cancellation of digits score on 6dct [ table 1 ] . it reduced the cfft threshold and aa score suggestive of impairment of central integrative capacity and central processing ability respectively [ table 1 ] it increased errors in the hand steadiness test , suggestive of motor impairment [ table 2 ] . these findings of nortriptyline on objective tests are also reflected in the subjective assessment of vas-1 , vas-2 and vas-3 with a significant shift of the scale toward drowsiness , tiredness and dullness [ table 2 ] . nortriptyline when compared with fluvoxamine and placebo had shown significant impairment on objective [ table 3 ] and subjective tests at 4 h [ table 4 ] . thus , in the present study nortriptyline at the dose of 50 mg significantly affected the psychomotor functions . tricyclics like nortriptyline cause adverse effects of drowsiness and psychomotor impairment due to their antihistaminic , antimuscarinic and 1-antagonist action . . effects of fluvoxamine and nortriptyline at 0 , 2 and 4 h effects of fluvoxamine and nortriptyline at 0 , 2 and 4 h interdrug comparison of mean difference at 2 and 4 h interdrug comparison of mean difference at 2 and 4 h it is seen from the studies of curran and lader fairweather , et al . fleishaker and hulst that fluvoxamine 50 mg had no significant effect on objective tests except the study of van harten in which performance was impaired . in our study , fluvoxamine in the dose of 50 mg did not show any significant effect on objective tests such as 6dct , dsst , cfft , aa test [ table 1 ] and hand steadiness test [ table 2 ] . however , on subjective parameters such as vas-1 , vas-2 and vas-3 , there was a significant effect indicating a shift of the scale toward drowsiness , tiredness and dullness [ table 2 ] . also , nortriptyline in comparison with fluvoxamine impaired psychometric tests significantly [ tables 3 and 4 ] . in a recent study of the receptor binding of a wide range of antidepressants in human post - mortem brain , fluvoxamine was among the least - potent compounds at 1 , 2 , h1 and muscarinic receptor sites . this may account for its lack of sedation and consequently lack of impairment of psychomotor function . thus , the findings of effect of fluvoxamine on various psychometric tests in our study substantiate those of the other workers . further , there is limitation of analogue system as words may fail to describe the exactness of the subjective experience . the volunteers complained dryness of mouth with nortriptyline due to anticholinergic action and nausea headache with fluvoxamine [ table 5 ] . the cause for nausea , vomiting with fluvoxamine is increased synaptic availability of serotonin which stimulates 5ht3 receptors . nortriptyline significantly depresses the objective and subjective psychometric performance in comparison with placebo and fluvoxamine . dryness of mouth is the reported adverse effect of nortriptyline , whereas nausea and headache are the adverse effects of fluvoxamine . hence , fluvoxamine can be a better alternative to nortriptyline as it causes minimal psychomotor impairment .

background : today , many antidepressants are available , but they often cause adverse effects , particularly psychomotor and cognitive . it leads to patient maladjustment and may impair psychomotor performance . fluvoxamine is a newer antidepressant and hence the present study was planned to investigate its effect on psychomotor functions and compare with nortriptyline and record their adverse reactions.materials and methods : a total of 26 healthy volunteers were included in this double - blind , placebocontrolled , crossover study . single oral doses of fluvoxamine 50 mg , nortriptyline 50 mg and placebo were administered following a latin square design . the objective parameters - six digit cancellation test , digit symbol substitution test , critical flicker fusion test , arithmetic ability test , hand steadiness test and subjective parameters such as visual analogue scale 1 , 2 , 3 were tested at 0 , 2 and 4 h. the side - effects were also investigated.results:nortriptyline impaired all subjective and objective psychomotor functions while fluvoxamine did not show any significant effect on objective tests . however , on subjective parameters , there was a significant effect . the side - effects observed were dryness of mouthwith the nortriptyline and nausea and headache with fluvoxamine.conclusion:fluvoxamine is a better antidepressant drug in comparison with nortriptyline as it causes a less impairment of psychomotor functions .

glycans ( carbohydrate chains ) are one of the major classes of biological molecules , like nucleic acids and proteins . there is a substantial amount of structural information about glycan 3d structures in the protein data bank ( pdb ) ( 1 ) , and this is the major resource in the structural biology of glycans . there are two major classes of modified glycans , namely n - glycans ( asparagine - linked glycans ) and o - glycans ( serine or threonine - linked glycans ) . the accuracy of the glycan structures in the pdb has been in question for years . it was reported that there are some hundreds of asparagine - linked n - acetylglucosamines with inaccurate anomeric forms ( 2,3 ) . furthermore , 30% of saccharide units in the pdb contain errors , mainly in monosaccharide nomenclature ( 4 ) . so far , there is only one web service for checking the correspondence between the structure and nomenclature of a saccharide unit in a pdb file ( 5 ) . recently , crispin et al . ( 6 ) pointed out that glycan structures with unreported primary structure motifs were observed in the pdb . models of glycan 3d structures built by x - ray crystallography should be supported by the glycan primary structure data derived by other methods ( nmr , hplc , mass spectrometry and so on ) . our recent comprehensive survey revealed that 13.6% of glycans in the pdb contains substructure(s ) which are not found in the glycan primary structure database ( 7 ) , which suggested that the pdb contains a substantial number of glycans of which primary structures can not be synthesized by known biological pathways . a tool to verify the glycan primary structures of 3d models is in urgent demand . the glycoconjugate data bank : structures ( gdb : structures ) is a database of annotated glycan structures . getcarbo. furthermore , n - glycans were compared with entries in the glycan primary structure database , kegg glycan ( 8) . the kegg glycan entry with the most similar structure to the pdb glycan is selected by using a glycan structure search function implemented in getcarbo , and unmatched substructure(s ) between the glycan found in the pdb and the most similar kegg glycan entry were noted graphically . gdb : structures also provides a web service for checking glycan structures in a user - uploaded structure file by getcarbo . as far as we know , there have been no verification services for glycan primary structures . the widely used site , pdb - care ( 5 ) , a verification service for nomenclature of a saccharide unit , does not have a functionality to verify a glycan primary structure . gdb : structures provides functionality not only of verifying monosaccharide structures , but also that of glycan primary structures , and will compensate for the lack of tools for modeling biologically meaningful glycan 3d structures . gdb : structures is running on ruby on rails framework with lighttpd web server and mysql database management system . all the glycans in gdb : structures are classified into three types : ligands , n - glycans and o - glycans . users can retrieve lists of glycans by specifying the type and length of the glycans . users can draw query glycan primary structures on the flash web interface and obtain a list of similar glycans in gdb : structures . the contents of gdb : structures will be updated regularly , and the statistics of the current content is also presented . in each glycan information page , the primary structure of the glycan and annotations for the glycan and monosaccharide units are presented . in the case of n - glycan , the most similar kegg glycan entry is also presented . for each monosaccharide unit , the identifier in the pdb , iupac nomenclature ( 9 ) , common name , anomeric form and chair conformation are presented . the kegg glycan entries are linked to the original data in kegg ( 10 ) . the three - letter - identifiers of each monosaccharide unit are linked to het - pdb navi ( 11 ) . each of the pdb entries in gdb : structures is mutually linked with that in the pdbj ( 1 ) . users can interactively browse the 3d structural model of the pdb entry by using a jmol applet ( www.jmol.org ) . users can upload their structure file ( pdb format ) to gdb : structures to annotate glycan structure(s ) in the file by getcarbo . the results of the annotation will be sent back to the users by email , normally within a few minutes after uploading . the html file presents the results in the same format as the glycan information page of gdb : structures . in the case of n - glycan , the most similar kegg glycan entry is presented , and unmatched substructures are noted by red question marks . o - glycans are not checked in gdb : structures , because studies on the structures of ( especially , non - mammalian ) o - glycans have not reached the critical mass to perform database searches compared to those on n - glycans , of which primary structures and biosynthetic pathways are well known . an html file containing results of glycan annotation is sent back to the user who submitted a structure file ( pdb format ) . the glycan structure detected in the user - uploaded file is shown in the structure record and the most similar kegg glycan entry is shown in the kegg analogue record . unmatched substructures ( glycoside bonds between mannose residues ) are indicated by red question marks . an html file containing results of glycan annotation is sent back to the user who submitted a structure file ( pdb format ) . the glycan structure detected in the user - uploaded file is shown in the structure record and the most similar kegg glycan entry is shown in the kegg analogue record . unmatched substructures ( glycoside bonds between mannose residues ) are indicated by red question marks . gdb : structures is not only an annotated glycan structure database , but also a web service for verifying the primary structures of glycan 3d structures , which is in high demand by structural biologists ( 12 ) . this database will help users to determine the characteristics of the glycan structures of their interests and also allow structural biologists to verify their determined glycan structures . our n - glycan checking process is not always valid and is limited due to the nature of the reference glycan primary structure database . if the glycan primary structure is not found in the reference database , the annotation by getcarbo will point out unmatched substructures on a query glycan structure , even though the 3d structure is built on x - ray diffraction data fine enough to assign unreported motifs . : structures will be publicly available following the establishment of an international consensus on the glycan description format ( 1315 ) .

glycobiology has been brought to public attention as a frontier in the post - genomic era . structural information about glycans has been accumulating in the protein data bank ( pdb ) for years . it has been recognized , however , that there are many questionable glycan models in the pdb . a tool for verifying the primary structures of glycan 3d structures is evidently required , yet there have been no such publicly available tools . the glycoconjugate data bank : structures ( gdb : structures , http://www.glycostructures.jp ) is an annotated glycan structure database , which also provides an n - glycan primary structure ( or glycoform ) verification service . all the glycan 3d structures are detected and annotated by an in - house program named getcarbo. when an n - glycan is detected in a query coordinate by getcarbo , the primary structure of the glycan is compared with the most similar entry in the glycan primary structure database ( kegg glycan ) , and unmatched substructure(s ) are indicated if observed . the results of getcarbo are stored and presented in gdb : structures .

intestinal pseudo - obstruction is a clinical syndrome that involves bowel obstruction without any mechanical cause.1 it can be either acute or chronic and may occur in the small bowel or the colon . chronic intestinal pseudo - obstruction ( cip ) usually exhibits a relapsing clinical course and may either be idiopathic or occur due to other systemic disorders . pregnancy can be a precipitating factor of colonic pseudo - obstruction.2 recently , we experienced a case of a woman with intractable colonic pseudo - obstruction that was aggravated after pregnancy . endoscopic decompression could delay surgical treatment until a gestational age of 21 weeks and finally a full - term delivery could be achieved . a 31-year - old woman presented with abdominal pain , distension , and constipation at a fetal gestational age of 17 weeks . the patient 's symptoms aggravated at fetal gestational age of 10 weeks and her last pregnancy was aborted 2 years earlier at another hospital due to severe intestinal obstruction . she had suffered from unexplainable obstructive symptoms 5 years earlier and was diagnosed with cip because of repetitive obstructive symptoms without any visible obstructive lesion observed on abdominopelvic computed tomography ( ct ) , barium enema , or colonoscopy ( fig . she was most recently admitted to our hospital 5 months ago because of recurrent obstructive symptoms . because the intravenous administration of neostigmine was not effective , colonoscopic decompression was performed at that time . laboratory examination revealed a white blood cell count of 8,120/mm , a hemoglobin level of 9.9 g / dl , a platelet count of 281,000/mm , a blood sugar level of 99 mg / dl , a blood urea nitrogen level of 12.2 mg / dl , a creatinine level of 1.1 mg / dl , a sodium level of 139 meq / l , a potassium level of 3.8 meq / l , a chloride level of 104 meq / l , a calcium level of 8.7 mg / dl , a phosphorous level of 3.6 mg / dl , and a magnesium level of 1.8 mg / dl . neither radiologic study nor neostigmine administration could be performed because of the risk to the fetus . colonoscopy was performed to provide decompression because the patient 's pain and distension worsened after 5 days of conservative care . the colonoscope was passed just beyond the splenic flexure , at which point the lumen was found to be obstructed by a large fecal bezoar ( fig . 2 ) . attempts to break the fecal bezoar with an endoscopic snare ( olympus disposable electrosurgical snare sd-210u-10 ; olympus medical systems corp . , tokyo , japan ) met with limited success . after suctioning the retained gas and contents of the proximal colon , a drainage catheter ( enbd-7-liguory , 7 fr , 250 cm ; cook medical inc . , winston - salem , nc , usa ) was placed through the working channel of the endoscope . the catheter was irrigated periodically with normal saline to prevent obstruction and ensure that the intestinal contents and gas were drained effectively . the patient 's symptoms improved for a few days after decompression but recurred soon thereafter . additional two attempts at endoscopic decompression were made and a new drainage catheter was inserted in each of the attempts until surgery could be performed . subtotal colectomy with endileostomy was performed electively at a fetal gestational age of 21 weeks . ileorectal anastomosis could not be performed due to the enlarged uterus and was postponed until after delivery . the proximal portion from the cecum to the descending colon was dilated up to 16 cm in diameter and a focally narrowed transitional zone was observed around the sigmoid colon ( fig . full colonic sections were obtained for histopathological analysis , which revealed no apparent histopathological alteration in the muscularis propria or neural plexuses ( fig . however , immunohistochemistry for c - kit ( cd 117 ) revealed fewer interstitial cells of cajal ( iccs ) in dilated portions of the colon compared to the undilated part ( fig . stool passage was normalized after surgery and pregnancy was maintained and resulted in a full - term delivery . pregnancy was one of the most important precipitating factors contributing to cip in this case . elevated progesterone , prostaglandin , and glucagon levels as well as the pressure of the gravid uterus are suggested as factors that exacerbate the pseudo - obstruction experienced by the patient during pregnancy.2 constipation , progressive abdominal pain , and abdominal distension are common symptoms in pregnancy and may delay the diagnosis of pseudo - obstruction . moreover , abdominal radiographs and ct scans , which may be required for evaluation and are typically diagnostic , may be limited in the case of a pregnant woman due to the desire to limit radiation exposure to the fetus.3 fortunately , our patient had already been diagnosed with cip . intravenous administration of neostigmine is recommended in patients who do not show improvement after conservative management . neostigmine may lead to resolution of acute colonic pseudo - obstruction and may also be effective in acute exacerbations of cip.4,5 in this case , the patient 's unresponsiveness to neostigmine 5 months earlier and the possible risks to the fetus deterred the authors from using it again . endoscopic decompression can be another option for treating colonic pseudo - obstruction when neostigmine is not effective or contraindicated.6 efficacy of endoscopic decompression is increased when a cecal tube is inserted at the time of colonoscopy . although the cecum could not be intubated due to a large fecal bezoar in our case , placements of a decompression tube beyond the obstruction site was available . tubes for colorectal decompression include commercial tubes specifically aimed for decompression , tubes for enteroclysis , and nasogastric tubes . however , commercial tubes for colorectal decompression are not currently available in korea . moreover , all the tubes above should be inserted by seldinger technique under fluoroscopic guidance . in contrast , nasobiliary tubes can be easily inserted through the working channel of endoscopy without fluoroscopy . radiation exposure should be avoided since our patient was pregnant.7 although the small diameter of nasobiliary tubes limits effective decompression , periodic irrigation can prevent plugging of the tube and ensure effective drainage . colonoscopy may be relatively safe without large fetal risks during the second trimester with limited data during the other trimesters.8 repetitive colonoscopic decompression was able to relieve the patient 's symptoms until the second trimester of pregnancy when surgery was available . cip can be classified into three major categories based on the underlying pathological abnormality : enteric visceral myopathy , neuropathy , and mesenchymopathy.9 this classification is based on the involvement of smooth muscle cells , the enteric nervous system , and iccs , respectively . choe et al.10 examined the surgical specimens of patients who received surgery for intractable constipation and found that a substantial number of patients presented with a distinct transitional zone with segmental hypoganglionosis . another study by do et al.11 suggested a novel classification of hypoganglionosis patients into two groups : type i with a focally narrowed transition zone and type ii without a transition zone . our patient showed dilation of the proximal to mid colon with distinct narrowing around the sigmoid colon . however , pathologic studies of the narrowed segment did not reveal any abnormality in the ganglion cells or the neural plexuses . the only pathologic abnormality were marked reduction of iccs in multifocal areas of the dilated colon . it has been speculated that alterations in the icc network may result in impaired control of peristalsis resulting in cip . however , the diagnostic criteria of mesenchymopathic type of cip is poorly defined with reference to the mean number of iccs and distribution of the iccs . it is also not clear whether the multifocal decrease of iccs in our patient is the primary cause of cip or secondary to continuous colon dilation . in summary , we have reported a case of cip which was aggravated severely by pregnancy . however , in such cases , radiologic studies and administration of neostigmine may be limited due to the associated fetal risks . endoscopic decompression can be performed repetitively with minimal fetal risks until elective surgery can be performed .

chronic intestinal pseudo - obstruction is a rare clinical syndrome which is characterized by intestinal obstruction without occluding lesions in the intestinal lumen and pregnancy is one of the important aggravating factors . here , we report a case of a woman with intractable intestinal pseudo - obstruction that was precipitated by pregnancy . she could not make any stool passage for more than 4 weeks until a fetal gestational age of 17 weeks was reached . however , the patient could be maintained by repetitive colonoscopic decompressions and finally total colectomy could be performed successfully at a fetal gestational age of 21 weeks .

our study was part of a systematic prospective study to assess the epidemiology of respiratory virus infections in children admitted to the severo ochoa hospital ( legans , madrid province , spain).we conducted a specific study to determine the incidence of respiratory virus infections in all infants admitted after altes during november 2004december 2008 . an alte in a child < 1 year of age was defined as an episode that is frightening to the observer and characterized by some combination of apnea , color change , marked change in muscle tone , choking , or gagging so the observer fears the infant has died ( 6 ) . nasopharyngeal aspirate ( npa ) specimens were acquired from each eligible patient at the time of hospital admission ( on monday friday ) . samples were sent for virologic study to the influenza and respiratory virus laboratory ( national centre for microbiology , institute of health carlos iii , spain ) . total nucleic acids were extracted from 200-l aliquots by using a qiaamp minelute virus spin kit in a qiacube automated extractor ( qiagen , valencia , ca , usa ) . simple or multiplex reverse transcription nested pcr assays ( rt - pcr ) previously described ( 79 ) were used to assess the virus diagnosis , including 16 respiratory viruses or groups of viruses . degenerated primers for hrv and enteroviruses were designed between the 3 end of the 5 noncoding region ( ncr ) and the viral protein ( vp ) 4/vp2 polyprotein gene ( tciggiaryttccasyaccaicc-3 and ctgtgttgawacytgagciccca-3 ) . hrvs from positive samples were identified by sequencing and phylogenetic analysis of these sequences . amplified products ( about 500 bp , depending on hrv serotype ) were purified and sequenced in both directions by using an automated abi prism 377 model sequencer . positive results were confirmed by testing a second aliquot of the sample stored at 70c . all patients were < 5 months of age ( range 7 days5 months , mean age 7.6 weeks , median 4 weeks ) . a total of 11 ( 69% ) npa specimens were positive for at least 1 viral agent . for 9 of these patients , positive results for hrv were confirmed , and for the other 2 patients , respiratory syncytial virus was detected . * altes , acute life - threatening events ; urti , upper respiratory tract infection ; rsv , respiratory syncytial virus ; hrv , human rhinovirus ; ev , enterovirus ; gerd , gastroesophageal reflux disease . phylogenetic analyses of 9 sequences obtained from patients showed distribution of hrv in 3 clusters . three sequences were included in previously characterized clades , defined by hrv group a ( hrv - a , so4923eu697826 ) and b ( hrv - b , so3970fj841954 and so4998eu697832 ) . sequence from patient so4923 had a low sequence similarity with the other serotypes of hrv - a . in contrast , sequences from patients so3970 and so4998 were closely related to hrv-35 and hrv-79 , respectively . six sequences were included in the third group corresponding to the new hrv - c : so5854 , so6666 , so5797 , so6819 , so5986 , so6813- fj841955 - 57 and fj841959 - 61 ) ( 3,10 ) ( figure ) . different genotypes ( collectively called hrv - cs ) were identified in 6 npa specimens from children with altes ( 67% of total hrv ) . two received cardiopulmonary resuscitation at home ; for these 2 patients , a respiratory syncytial virus and an hrv - c were identified . phylogenetic analysis of 5 noncoding region and viral protein ( vp ) 4/2 coding region of 9 human rhinoviruses ( hrvs ) identified in infants with apparently life - threatening events in spain , november 2004december 2008 . phylogeny of nucleotide sequences ( 492 bp ) was reconstructed with neighbor - joining analysis by applying a jukes - cantor model ; scale bar indicates nucleotide substitutions per site . included for reference are sequences belonging to the novel genotype reported previously ( qpm and 024 , 025 , 026 ) and all hrv - a and -b serotypes available in genbank . the most common discharge diagnoses reported for altes are gastroesophageal reflux disease ( gerd ) , unknown causes , seizures , and lower respiratory tract infections ( 11 ) . our series suggests that altes of previously unknown etiology could be related to hrv infections . rhinovirus infections are known to be a major cause of illness and hospital admission for young children , particularly infants < 2 years of age ( 12 ) . detection of viral genomes by nested rt - pcr in npa specimens led us to analyze the effect of hrv infections in different clinical situations . respiratory infections associated with hrv might play a major role in young infants , probably with few clinical signs , and might contribute to apnea as a first manifestation . gerd is the most frequent hospital discharge diagnosis in published series ( 5,11 ) . for our patients , gerd also was the most frequent clinical diagnosis ( 9 patients ) , but for 7 of them , a respiratory virus was identified . we can not conclude whether gerd is a risk factor for apnea or whether signs are so nonspecific that diagnoses could be confused . alternatively , the new hrv - c group could account for as many as a quarter or even half of hrv infections ( 4,13 ) . in children , it has been associated with bronchiolitis , wheezing , and asthma exacerbations severe enough to require hospitalization ; the percentage of these children with hypoxia was substantial ( 13 ) . in a case ( 4 ) found hrv - c only in case - patients , supporting the pathogenic role of this genogroup . they considered that hrv - c infections could be associated with more severe clinical manifestations than infections with other hrv genogroups a and b. these data could also support the role of hrv - c in infants with altes found in this work . although we had no control group for our patients , we recently published a study of a cohort of 316 newborns up to 6 months of age tested weekly for respiratory diseases ( mainly upper respiratory tract infections ) , coincident in age and time with our patients ( 14 ) . two viruses were genetically identified as hrv - c , demonstrating they form distinct genetic clusters , and no genetic similarity was obtained with the alte related hrv - c viruses . in addition , a second group of asymptomatic children of different ages but in coincident epidemic seasons was studied . the group of children with hrv was substantially smaller than the group of children with respiratory disease ( 15 ) . rhinoviruses , especially hrv - c , could cause a respiratory infection with few symptoms in young infants and could trigger altes in this age group . therefore , hrvs and posterior genotyping should be included in studies of the etiology of altes to help identify the true relevance of hrv - c infection to these episodes .

to assess whether infants hospitalized after an apparently life - threatening event had an associated respiratory virus infection , we analyzed nasopharyngeal aspirates from 16 patients . nine of 11 infants with positive virus results were infected by rhinoviruses . we detected the new genogroup of rhinovirus c in 6 aspirates .

staphylococcus epidermidis is the most common bacteria isolated from the human skin and is the most persistent bacteria in some body parts . staphylococcus epidermidis , which is part of the human flora , is also recognized as an opportunistic pathogen and causes nosocomial infections associated with medical devices ( 1 ) . more information about bacterial physiology not only under infectious conditions but also when s. epidermidis is in a symbiosis condition could help evaluate the therapeutic strategies in the case of infection . it has been proposed that s. epidermidis acts as a probiotic and prevents the colonization of pathogens such as s. aureus ( 2 , 3 ) . staphylococcus epidermidis causes chronic infections associated with medical devices , such as intravascular catheter or prosthetic joint infections , vascular graft infection , surgical site infection , central nervous system shunt infection , and cardiac device infection ( 4 ) . the expression of fbe is poor in vitro and increased in the presence of serum . in the presence of anti - fbe antibody , adherence of s. epidermidis to fibrinogen was blocked and infection was attenuated in animal models ( 5 , 6 ) . the ica operon , includes icaa , icab , icac and icad genes and encodes polysaccharide intercellular adhesin ( pia ) , a microbial surface component - recognizing adhesive matrix molecule ( mscramm ) of s. epidermidis that affects biofilm formation and is crucial for bacterial adhesion ( 7 ) . the is256 is a mobile genetic element present in the genome of s. epidermidis at several copy numbers . it is believed that is256 is associated with virulence determinant genes , contributes to genetic adaptation , and is active in invasive strains during infection . is256 increases the production of pia , which plays an important role in biofilm formation and immune system invasion ( 4 , 8) . accumulation - associated protein ( aap ) is a 140-kd protein essential for s. epidermidis accumulation on the surfaces by formation of aap - based fibril - like structures , which can potentially underlie the formation of biofilm ( 9 , 10 ) . biofilm - associated protein ( bap ) , a 239-kd surface protein , is found only in some s. aureus strains . bap homologue protein plays an important role in bacterial adhesion and colonization and catalyzes biofilm formation ( 11 ) . the aim of this study was to determine the prevalence of icaa , is256 , aap , fbe and bhp in clinical isolates of s. epidermidis . overall , 59 s. epidermidis strains , isolated from blood ( n = 50 ) , urine ( n = 4 ) , tracheal ( n = 4 ) and wound ( n = 1 ) samples , were obtained from patients at intensive care units of various hospitals of tehran , iran . for s. epidermidis identification , the sample was cultured on sheep blood agar ( merck , germany ) , overnight under aerobic conditions at 37c ; staphylococci should produce white , smooth , medium colonies on sheep blood agar . catalase test was performed and catalase positive colonies were cultured on mannitol salt agar ( merck , germany ) , overnight under aerobic conditions at 37c . staphylococci can growth on mannitol salt agar while s. epidermidis and some other staphylococci are not able to ferment mannitol , thus the medium remained red . staphylococcus epidermidis and some other staphylococci are coagulase negative and could not produce clot in the tube . final identification of s. epidermidis was performed by the ability of urease production and carbohydrate fermentation . it is also unable to ferment d - trehalose , thus the medium turned red , while it is able to ferment d - manose and d - maltose , thus the medium turned yellow ( 12 , 13 ) . dna of each s. epidermidis isolate was extracted from 1 ml of overnight bacterial culture . extraction was performed by adding te [ 10 mm tris , 1 mm edta ( ph = 8) ] buffer and lysostaphin , boiling at 95c for five minutes , then cooling at 0c for five minutes , followed by centrifugation at 10000 rpm for five minutes . dna was measured using a biophotometer ( eppendorf , germany ) to determine the concentration and purity . ( 14 ) with the specific primers ( pishgam biotech , iran ) shown in table 1 . amplification was performed in a mj mini gradient thermal cycler ptc-1148 , usa . the amplified products were visualized by uv light after electrophoresis on 1% agarose gel ( figures 1 - 5 ) . a positive control and negative control ( reaction mixture without dna ) were included in each pcr run . 1 - 3 , positive clinical strains ; 4 , positive control ( 215 bp ) ; 5 , marker ( 100 bp ) . 1 , marker ( 100 bp ) ; 2 , positive control ( 251 bp ) ; 3 - 6 , positive clinical strains . 1 , marker ( 100 bp ) ; 2 , positive control ( 465 bp ) ; 3 , negative control ; 4 - 9 , positive clinical strains . 1 , marker ( 100 bp ) ; 2 , s. epidermidis strain k28 ( positive control , 273 bp ) ; 3 - 5 , positive clinical strains . 1 , marker ( 100 bp ) ; 2 , positive control ( 1548 bp ) ; 3 and 4 , positive clinical strains . confidence interval test was used to assess the statistical significance with confidence level of 95% ( = 0.05 ) . overall , 59 s. epidermidis strains , isolated from blood ( n = 50 ) , urine ( n = 4 ) , tracheal ( n = 4 ) and wound ( n = 1 ) samples , were obtained from patients at intensive care units of various hospitals of tehran , iran . for s. epidermidis identification , the sample was cultured on sheep blood agar ( merck , germany ) , overnight under aerobic conditions at 37c ; staphylococci should produce white , smooth , medium colonies on sheep blood agar . catalase test was performed and catalase positive colonies were cultured on mannitol salt agar ( merck , germany ) , overnight under aerobic conditions at 37c . staphylococci can growth on mannitol salt agar while s. epidermidis and some other staphylococci are not able to ferment mannitol , thus the medium remained red . staphylococcus epidermidis and some other staphylococci are coagulase negative and could not produce clot in the tube . final identification of s. epidermidis was performed by the ability of urease production and carbohydrate fermentation . it is also unable to ferment d - trehalose , thus the medium turned red , while it is able to ferment d - manose and d - maltose , thus the medium turned yellow ( 12 , 13 ) . dna of each s. epidermidis isolate was extracted from 1 ml of overnight bacterial culture . extraction was performed by adding te [ 10 mm tris , 1 mm edta ( ph = 8) ] buffer and lysostaphin , boiling at 95c for five minutes , then cooling at 0c for five minutes , followed by centrifugation at 10000 rpm for five minutes . dna was measured using a biophotometer ( eppendorf , germany ) to determine the concentration and purity . polymerase chain reaction was performed as described by rohde et al . ( 14 ) with the specific primers ( pishgam biotech , iran ) shown in table 1 . amplification was performed in a mj mini gradient thermal cycler ptc-1148 , usa . the amplified products were visualized by uv light after electrophoresis on 1% agarose gel ( figures 1 - 5 ) . a positive control and negative control ( reaction mixture without dna ) were included in each pcr run . 1 - 3 , positive clinical strains ; 4 , positive control ( 215 bp ) ; 5 , marker ( 100 bp ) . 1 , marker ( 100 bp ) ; 2 , positive control ( 251 bp ) ; 3 - 6 , positive clinical strains . 1 , marker ( 100 bp ) ; 2 , positive control ( 465 bp ) ; 3 , negative control ; 4 - 9 , positive clinical strains . 1 , marker ( 100 bp ) ; 2 , s. epidermidis strain k28 ( positive control , 273 bp ) ; 3 - 5 , positive clinical strains . 1 , marker ( 100 bp ) ; 2 , positive control ( 1548 bp ) ; 3 and 4 , positive clinical strains confidence interval test was used to assess the statistical significance with confidence level of 95% ( = 0.05 ) . the most frequent virulence determinant in this study was fbe [ 89.8% ( 95% ci : 97.5 - 82.1 ) ] and the least frequent virulence determinant was bhp [ 15.3% ( 95% ci : 24.5 6.1 ) ] . the frequency of is256 , icaa and aap were 72.9% ( 95% ci : 84.2 61.6 ) , 55.9% ( 95% ci : 68.6 43.3 ) and 64.4% ( 95% ci : 73.4 55.4 ) , respectively . coexistence of icaa and is256 was observed in 44.1% ( 95%ci : 56.8 31.4 ) of the isolates . coexistence of aap and icaa was seen in 39% ( 95% ci : 51.4 26.6 ) of the isolates . in six isolates [ 10.1% ( 95% ci : 17.8 2.4 ) only one of the investigated virulence determinants was observed , while in three isolates [ 5% ( 95% ci : 10.5 0 ) ] all of the investigated virulence determinant was observed . staphylococcus epidermidis , which was previously regarded only as part of the human flora , is now considered as an infectious agent that causes infections associated with medical devices . these infections may be transmitted from the patient s skin to the hospital staff during device insertion . the adhesion ability of s. epidermidis is one of the most important mechanisms through which it causes infections ( 4 , 15 ) . polysaccharide intercellular adhesin , which is produced by ica operon , catalyzes cell cell adhesion and biofilm formation ( 16 ) . thus , ica operon , producing pia and adhesion to host protein , coated medical devices are the two main determinants of s. epidermidis invasiveness ( 8 , 17 ) . fbe , an adhesion protein present in s. epidermidis and s. aureus , facilitates binding to fibrinogen - coated device surfaces , which is an essential mechanism for bacterial persistence in or on the human body that leads to infections ( 18 ) . thus , ica operon and is256 are the two determinants of s. epidermidis invasiveness , which play an important role in biofilm formation and immune system invasion ( 4 , 8) . it is believed that aap is one of the most important factors for pia - independent biofilm formation in s. epidermidis ( 9 ) . the increased expression of aap may lead to biofilm formation ( 19 , 20 ) . furthermore , bhp plays an important role in bacterial accumulation and adhesion and catalyzes biofilm formation ( 11 , 21 ) . in our study , diemond - hernandez et al . ( 22 ) reported that the frequency of icaa was 51.1% while koskela et al . the frequency observed in our study was significantly lower than that reported in these studies . in our study , frequency of is256 was found to be 72.9% , which is not significantly different from 81% reported by koskela et al . ( 8) ; however , it is significantly lower than 93.8% reported by rohde et al . fbe was found in 89.8% of the isolates , which is significantly less than 100% reported by rohde et al . ( 14 ) , and does not show significant difference with 50.8% reported by mekni et al . overall , 15.3% of investigated isolates in this study harbored bhp which is not significantly different from 10% reported by rohde et al . , the frequency of aap was found to be 64.4% , which is significantly higher than 17% reported by okee et al . coexistence of aap and icaa was detected in 39% of the isolates in our study , which is not significantly different from 37.1% reported by liduma et al . coexistence of is256 and icaa was detected in 44.1% of the isolates in our study , which is significantly lower than 58% reported by koskela et al . prevalence of fbe and aap observed in our study was significantly different from that reported by other similar studies ; however , the frequency of bhp was in accordance with that reported by other studies . prevalence of icaa and is256 was not significantly different from that reported by some studies yet was significantly different from other studies .

backgroundstaphylococcus epidermidis , a member of the human flora , is recognized as an opportunistic pathogen and cause of nosocomial infections . staphylococcus epidermidis surface components are able to establish bacteria on the host surface , and cause infection.objectivesthe frequency of icaa , is256 , aap , fbe and bhp in clinical isolates of s. epidermidis were investigated in this study.materials and methodsfifty - nine s. epidermidis isolates were collected from blood ( 50 ) , wound ( 1 ) , urine ( 4 ) and tracheal ( 4 ) samples ( tehran , iran ) . staphylococcus epidermidis isolates were identified with conventional bacteriological tests . virulence - associated genes were detected by specific polymerase chain reactions ( pcrs).resultsof the 59 s. epidermidis , fbe was found in 89.8% , while aap and bhp were observed in 64.4% and 15.3% of the samples , respectively . coexistence of aap and fbe was found in 32 isolates , while coexistence of bhp and fbe was observed in five isolates . two isolates were negative for the investigated genes.conclusionsprevalence of fbe and aap was significantly different from similar studies , yet frequency of bhp was in accordance with other studies . prevalence of icaa and is256 was not significantly different from some studies while a significant difference was observed when results were compared with some other studies .

verrucous hemangioma is a rare variety of angiomatous nevi usually involving the , lower extremities . it has been reported under a diversity of names such as angiokeratoma circum - scriptum neviforme , unilateral verrucous heman - gioma , keratotic hemangioma etc . they are best treated by excision while still small , as they enlarge with body growth and do not regress spontaneously . in contrast to angiokeratomas , which respond to various means of therapy ( e.g. , cryotherapy , electrocautery , and argon laser ) , verrucous hemangiomas require a large , deep excision as a superficial therapeutic approach would be unsuccessful because of the deep angiomatous proliferation . a 14-year - old girl presented with an exuberant warty brownish growth on her right great toe . history revealed that when she was 4 years old , she had a small similar lesion , a part of which was biopsied by a general surgeon and was reported as angiokeratoma . , the lesion recurred and continued to grow in a slow but progressive manner to the present size without any treatment . examination revealed a solitary hyperpigmented , hyperkeratotic plaque consisting of closely set warty papules measuring 20 25 mm involving the pulp space of the right great toe . surface of the lesion was firm and verrucous with no ulceration , bleeding , or atrophy . we considered a clinical differential diagnosis of tuberculosis verrucosa cutis and angiokeratoma [ figure 1 ] . the entire growth was excised by a wide excision resulting in a defect that involved one - third of the pulp space of the great toe extending till the bone . a plantar digital artery flap was designed in a v - y fashion adjacent and just proximal to the excision wound . skeletonizing this pedicle permitted the elevated flap to advance and cover the excision defect completely with sensate , glabrous plantar skin without any contour defect . hyperpigmented verrucous plaque over the pulp space of the great toe the excised material was subjected to histological examination . h and e stained sections of the specimen showed marked hyperkeratosis , parakeratosis , papillomatosis , and elongation of the rete ridges . extending from the dermo - epidermal junction into the deeper dermis , there were numerous small to large vascular channels lined by flattened endothelial cells and filled with blood . lesions are mostly seen at birth or appear during childhood . initially , they are soft , bluish - red vascular lesions , but with time they enlarge and develop keratotic and verrucous features . secondary bleeding and infection are frequent complications , which often result in reactive papillomatosis and hyperkeratosis and thus the older lesions acquire a warty surface . unlike other angiomatous nevi , they do not involute spontaneously . clinically , verrucous hemangioma mimicks angiokeratoma , but histopathologically they can be clearly differentiated as the former involves the dermis and subcutaneous fat and the latter involves only the papillary dermis . hence , deep excisional surgery is the proper treatment for verrucous hemangioma as a superficial therapeutic approach would be unsuccessful because of the deep angiomatous proliferation . superficial ablative procedures such as electrocautery , cryosurgery , and laser ablation almost invariably lead to recurrence of the lesion . a combined approach using surgery and erbium laser have been reported with good results . in our case , as the large defect size would not permit a direct primary closure , either a skin graft or a flap was needed . a skin graft would have had disadvantages such as ; ( a ) uncertain acceptance on the bare bone with risk of delayed healing , ( b ) a sunken appearance resulting in poor aesthesis causing social anxiety , and ( c ) poor tolerance to wear and tear . although conventional local flaps would heal the wound reliably , loss of the toe contour and the skin graft needed on the flap donor area would leave obvious cosmetic deformity on the young girl 's toes . therefore , we performed a wide local excision of the growth and closed the defect with a plantar digital artery flap designed in a v - y fashion just proximal to the excision wound . excellent color , contour match as well as preservation of sensation in 2 weeks ensured a good aesthetic reconstruction . the digit shape was also preserved to the satisfaction of the patient [ figures 2a d ] ( a ) verrucous growth excised by a wide local excision . ( b ) a plantar digital artery flap was designed in a v - y fashion adjacent and just proximal to the excision wound . ( c ) the pedicle was skeletonized permitting the flap to advance by about 1 cm to cover the entire excision defect . skin lesions needing excisions very often can not be closed primarily or tension of primary closure results in unacceptable distortion of adjacent anatomic landmarks . while the former problem may present in any area of the body , the latter usually presents on vital areas such as face , hand , foot , or genitals . when wound healing alone is the concern , simple skin grafts - either partial / split ( stsg ) or full thickness ( ftsg ) may suffice . however , these are usually associated with problems of function ( unable to tolerate wear and tear , inadequate sensation or contraction of graft ) or aesthesis ( color or texture mismatch , contour defect ) . in this case , there was the additional uncertainty of poor acceptance of the graft on bare bone with the risk of delayed healing . although conventional local flaps would heal the wound reliably , loss of the toe contour and the skin graft needed on the flap donor area would leave obvious stigmas on the young girl 's toes . this final problem can also be avoided by careful design and dissection of the flap to permit direct closure of flap donor areas , as demonstrated in our case [ figures 3a and b ] . ( b ) postoperative picture with acceptable contour and good aesthetic reconstruction of the great toe yang and ohara reported 14 patients presenting with small , localized lesions that were cured by one session of surgery without recurrence , while the 9 patients with wider and more extensive lesions required combination therapy in several stages for optimal results . reported a case of verrucous hemangioma over the lateral aspect of left leg of a 19-year - old girl , treated with multiple sessions of electrocautery , which healed with scarring and hyperpigmentation . used percutaneous injection of n - butyl cyanoacrylate ( nbca ) prior to excision of the lesion which on contact with tissue fluid , causes inter compartmental tissue adhesion , thereby causing cessation of blood flow into the vascular malformation tissue . after few injections , the whole mass forms a solid polymer , which is then excised . during excision , there is remarkably minimum bleeding . when dimensions permit , local flaps are far better than distant flaps in vital areas , on grounds of better function and aesthesis . the limit for local flap dimensions in critical areas is reached when the donor area can not be closed primarily and is likely to need a skin graft . in areas with axial pattern blood supply , flaps can be islanded and creatively designed to permit larger donor areas to be closed primarily . this ensures the best of wound healing , function , and aesthesis with minimal scars , which is called aesthetic reconstruction . ability to restore the toe virtually back to normal permits a fearless and wide excision needed for definitive cure of the disease .

a 14-year - girl presented with solitary exuberant warty plaque over her right great toe since the age of 4 years . ten years ago , an excisional biopsy was performed by a surgeon , and a histopathological diagnosis of angiokeratoma was made . a wide local excision of the lesion followed by a plantar digital artery flap in a v - y fashion adjacent and just proximal to the excision wound was performed . this procedure has not only led to complete growth removal , but also a well - preserved digit with an excellent color and contour match .

since antibodies were first described late in the 19th century , antibodies have become the single most highly recognized mediators of immunity . during the past century , the general public has also become familiar with the practice of passive immunization for the treatment of a variety of infections that include tetanus and rabies . the downside of antibody therapy , a form of hypersensitivity known as serum sickness that develops after exposure to heterologous immunoglobulins ( i.e. , from other species ) , is also well - known . antibodies have been used in a diagnostic capacity for many diseases and for identifying serotypes within single species of pathogens ( including distinguishing between the multiple capsular polysaccharide serotypes of streptococcus pneumoniae ) , a job which they still discharge remarkably well . for many years , the functions of antibodies in infection were thought to be limited to opsonization of microorganisms followed by fc receptor - mediated phagocytosis and to the fixing of complement . today , it is rare to find an issue of a medical journal that does not include a report that uses chimeric monoclonal antibodies as therapy for any one of a broad spectrum of diseases ( 1 ) . consequently , therapeutic monoclonal antibodies are undergoing an unprecedented and fast expansion in the drug market . this antibody renaissance is due to the extraordinary success of molecular biology that permitted ( i ) the grafting of the fab fragments from animal sources onto the fc - bearing domains of class - specific human immunoglobulins , and ( ii ) the creation of transgenic mice that can produce human immunoglobulins for the creation of hybridomas to many diverse immunogens ( 2 ) . other approaches using antibodies have been tested with various degrees of success and hold much hope of further development for specific infectious and noninfectious diseases . antibodies have been linked to drugs and radioisotopes to target specific organisms and cells without having the effects of broad toxicity . the specificity of the antibody combined with the targeted toxicity of a drug or isotope clearly limits undesirable side effects to nontarget tissues . is not new , but it has received a new jump start with increasing knowledge of the production and properties of antibodies . in addition , it is now possible to create single - chain fragments of variable regions ( scfv ) and single domains or nanoantibodies that retain therapeutic activity and other desirable properties such as specificity . the innovative technologies that are applied to monoclonal antibody therapy are now indispensable for treatment of diseases that had no known cure and for improved modalities against certain types of infection where rapid intervention is required . not unexpectedly , in the last few years , new mechanisms of action for antibodies have been discovered . the versatile collection of antibody functions that clear microorganisms includes new findings such as complement independent - bacteriolytic immunoglobulins , which kill several species of borrelia ( 3 , 4 ) , and direct antimicrobial effects on gene expression in fungi ( 5 ) , among others . as mentioned above , antibodies are used to identify the serotypes of s. pneumoniae that are critical for the formulation of the current pneumococcal vaccines . the most effective type of host response to s. pneumoniae is centered on antibody binding to the pneumococcal capsular polysaccharide followed by fc receptor - mediated phagocytosis . moreover , this traditional mechanism of opsonization - phagocytosis is also thought to be essential for the response to active immunization with both the 7- and 23-valent pneumococcal capsular polysaccharide vaccines ( 6 ) . in contrast to the traditional understanding that opsonization - phagocytosis is necessary for pneumococcal clearance , we now know that there are a number of nonopsonic antibodies to the capsular polysaccharides that have the capacity to protect both experimentally and clinically . a number of these nonopsonic antibodies have been identified and are both polyclonal and monoclonal , can be derived from humans and mice , and protect against pneumonia and sepsis in experimental models . the study by yano and coworkers in the laboratory of liise - anne pirofski published in mbio ( 7 ) identifies one mechanism that was heretofore unappreciated : the nonopsonic antibodies enhance the transformation competence of two s. pneumoniae serotypes , which leads to an overall increase in genetic exchange and bacterial variability and sharply lowers the number of organisms . while the bactericidal end result has obvious therapeutic relevance , the road taken to elucidate this mechanism is also of much biological interest and one that crisscrosses microbiology and immunology at many points . a protective nonopsonic monoclonal antibody ( 1e2 , 1gg1 specific for s. pneumoniae serotype 3 ) induced a higher transformation frequency in the appropriate strains when added to competence - stimulating peptide ( csp ) than csp alone or the other opsonic subclass - matched monoclonal antibodies that were used as controls . moreover , a human monoclonal nonopsonic igm had the same effect as 1e2 , indicating that this mechanism is not specific to the immunoglobulin class . similar effects obtained with antibodies to s. pneumoniae serotype 8 also showed that the induction of transformation efficiency could be obtained with more than one pathogenic strain of pneumococcus and with antibodies derived from both human and mouse hybridomas . agglutination of the pneumococcus appeared to be a factor in the induction of higher transformation frequency . interestingly , agglutination , at least in s. pneumoniae , appears to be a necessary precondition for achieving the competent phenotype . competence - stimulating peptides ( csp ) are pheromones secreted by s. pneumoniae for interbacterial communication through the activation of the com pathway that regulates genetic transformation and therefore induces competence in these bacteria , the physiological state that allows incorporation of exogenous dna . in general , csp released into the medium activates a two - component system ( comde ) that results in the expression of comx , leading to the upregulation of genes associated with competence ( 8) . along these lines , the 1e2 monoclonal antibody induced late competence and altered gene expression . incubation of csp and antibody with the appropriate specific type 3 pneumococcus resulted in an induction of comx expression after 8 minutes of incubation , representing a new second wave of expression that followed the peak expression induced by csp alone after 2 min . the entire process of competence development in s. pneumoniae occurs rapidly , within 15 minutes , a period of time that can easily encompass the 2- and 8-min observation of upregulation of comx in organisms exposed to csp and the nonopsonic antibody in the yano et al . likewise , the com - induced regulon has genes that function at different times ( 9 ) , and these genes are also induced by exposure to the nonopsonic antibodies . yano et al . ( 7 ) also reveal some interesting findings regarding the competent state of s. pneumoniae and the production of lytic factors that are capable of eliminating the cells that do not become competent following exposure to csp ( 7 ) . eliminating noncompetent cells supports the idea that permissiveness to accept exogenous dna is the preferred condition following an episode of stress . this killing phenomenon was characterized as fratricide ( 10 ) and results in the release of dna and a number of virulence factors . yano and colleagues show that induction of comx expression by exposure of s. pneumoniae to csp and nonopsonic antibodies was followed by marked upregulation in the expression of genes associated with fratricide ( 7 ) . it could be argued that enhancing fratricide , particularly if directed to cells that can not accept new genetic information , may also work in favor of preserving the competent cells by the acquisition of resistance factors to the effects of the nonopsonic antibodies . likewise , 1e2 increased by 2-fold the mortality of pneumococcus over and above the mortality achieved by csp alone . if conditions are such that the majority of cells in an s. pneumoniae culture can accept dna more readily than before , those cells could well acquire new resistance factors . in this scenario , the random acquisition of new genes could result in the expression of new antigens not recognized by the antibodies , new exogenous proteases that can cleave immunoglobulins , or a number of other possible factors that would enhance the establishment and continuation of an infection . there may be an advantage to s. pneumoniae to respond to the stress and danger of specific antibodies with the ability to acquire new dna . this is a prime area for expansion for the pirofski laboratory following their observations published in mbio ( 7 ) . the fact that an antibody can induce fratricide begs the question of who enjoys the advantages of this interaction , the host or the pathogen ? can s. pneumoniae benefit from eliminating noncompetent cells in the hope that the surviving competent organisms can have a chance to acquire a factor that would make them resistant to the antibodies ? this is another question to be answered as a follow - up to these intriguing observations . moreover , what does this mean for pneumococcus ? is this bacterium helped or harmed by the action of these antibodies ? it would appear that the altered gene expression consistent with fratricide could result in fewer organisms , which in turn could act synergistically in the clearing capacity of the opsonizing antibodies , benefiting the host . on the other hand , an antibody effect that bestows increased fitness on the capacity for genetic exchange could result in acquired resistance in much the same manner as it occurs with antibiotics , benefiting the pathogen . the data presented by yano and coworkers on the mechanism of action of the nonopsonic antibodies is reminiscent in general scope to the mechanism of action of bacteriostatic antibiotics ( 7 ) . bacteriostatic antibiotics work indirectly by weakening the bacteria so that the host response is more effective . in fact , the functional similarity between certain types of antibodies and antibiotics is already more than theory . the term antibiobodies has been used to characterize anti - idiotypic recombinant antibodies that have toxin - like activity against fungal pathogens ( 1113 ) . nonopsonic antibodies to s. pneumoniae also work indirectly to trigger fratricide of at least part of the population and thus allow the host to clear the infection faster . further studies of these new and revealing antibody functions will likely add another chapter to the burgeoning story of the diversity and versatility of the immune response to bacteria .

abstract antibodies have been used in a diagnostic capacity for many diseases and for identifying serotypes within single species of pathogens , notably between the multiple capsular polysaccharide serotypes of streptococcus pneumoniae . for many years , the functions of antibodies in infection were thought to be limited to the opsonization of microorganisms followed by phagocytosis and to the fixing of complement . the thought that antibodies could have other functions has emerged only recently . the study by yano and coworkers from the laboratory of liise - anne pirofski published in mbio [ m. yano , s. gohil , j. r. coleman , c. manix , and l .- a . pirofski , mbio 2(5):e00176 - 11 , 2011 ] identifies one mechanism whereby nonopsonic antibodies enhance the transformation competence of two s. pneumoniae serotypes , which leads to an increase in genetic exchange and bacterial variability with a resulting population reduction through fratricide . these new and revealing antibody functions will add another chapter to the burgeoning story of the diversity and versatility of the immune response to bacteria .

hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion ( siadh ) during amiodarone therapy is a rare but potentially lethal adverse effect . we report a case of severe hyponatremia associated with amiodarone , and discuss its clinical implications . an 84-year - old caucasian man with a past medical history of hypertension and diabetes was admitted to the hospital with a non - st elevation myocardial infarction . mmol / l at discharge and subsequently decreased to 105 mmol / l 11 days later , at which time the patient represented with altered mental status . the diagnosis of siadh was made based on euvolemic hypoosmotic hyponatremia , lack of any other medication known to cause siadh and urine that was less than maximally dilute . the serum sodium increased gradually to 123 mmol / l after 36 h of treatment with hypertonic saline , demeclocycline and fluid restriction . is associated with significant neurological damage and mortality , clinicians should carefully monitor serum sodium during amiodarone therapy . amiodarone is an effective antiarrhythmic agent with well - known noncardiac toxicities including pulmonary fibrosis , hypo- or hyperthyroidism , liver function abnormalities , corneal deposits and photosensitivity . hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion ( siadh ) during amiodarone therapy is a rare but potentially lethal adverse effect of this drug . we also review the previously reported cases of siadh - induced hyponatremia secondary to amiodarone and discuss salient clinical implications . an 84-year - old caucasian man with a past medical history of hypertension and diabetes was admitted to the hospital with a non - st elevation myocardial infarction . urgent left heart catheterization showed multivessel disease , and the patient subsequently underwent coronary artery bypass graft . on postoperative day 2 , the patient developed atrial fibrillation with rapid ventricular response . he was started on intravenous amiodarone with a loading dose of 150 mg , followed by a continuous infusion of 1 mg / min . after 24 h , intravenous amiodarone was discontinued and switched to 400 mg orally every 8 h. the oral dose of amiodarone was tapered over 7 days to 400 mg daily . the patient 's atrial fibrillation converted to normal sinus rhythm after the loading dose of amiodarone . he was discharged on postoperative day 7 on amiodarone 400 mg daily . at the time of discharge , the patient then presented to the emergency room 11 days later due to altered mental status , weakness and loss of appetite . thyroid stimulating hormone and cortisol levels were 0.7 iu / ml ( normal range : 0.3505.000 iu / ml ) and 16 g / dl ( normal range : 3.0922.40 g / dl ) , respectively . serum osmolality was 228 mosm / kg and urine osmolality was 251 mosm / kg . it was noted that the patient was on furosemide 20 mg daily prior to his admission . repeat testing after discontinuation of furosemide revealed a serum osmolality of 256 mosm / kg and a urine osmolality of 506 mosm / kg . the diagnosis of siadh was made based on euvolemic hypoosmotic hyponatremia , with a urine osmolality greater than the serum osmolality , urine sodium level greater than 40 mmol / l , normal thyroid and adrenal function and the absence of other medications known to cause siadh . his serum sodium increased gradually to 117 and 123 mmol / l after 36 and 48 h of treatment , respectively . hypertonic saline was discontinued after 3 days , and demeclocycline was added , together with fluid restriction . the patient 's mental status improved and his serum sodium normalized after 10 days of treatment ( fig . siadh was first reported by schwartz et al . in 1957 in patients with bronchogenic carcinoma and meningitis . in 1971 , since then , a variety of drugs have been added to the list of drugs that cause siadh . amiodarone , a benzofuran derivative , was developed by a belgian company ( labaz ) in 1961 by the chemists tondeur and binon as an antianginal drug . a few years later , amiodarone was widely used as an antiarrhythmic drug in europe and other countries . it was not until the mid-1980s that amiodarone was approved by the fda as a class iii antiarrhythmic agent in the united states . in 1996 , the first case of amiodarone - induced hyponatremia was reported . since then , a total of 10 cases of amiodarone - induced siadh have been published in the literature ( table 1 ; [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ] ) . it could possibly be due to the independent secretion of arginine vasopressin relative to plasma osmolality , full suppression of secretion of this hormone or mutations of the aquaretic ( i.e. water channel regulating ) vasopressin receptor . most medications cause siadh either by sensitizing the kidneys to antidiuretic hormone , by stimulating the release of antidiuretic hormone or by both . of note , shavit and sherer speculated that amiodarone might induce siadh by its channel - modulating properties on either renal or neural tissues . among the 10 reported cases , the majority of patients were elderly men ( 8 out of 10 ) with a median age of 69 years . age and sex may be contributing factors to amiodarone - induced siadh . the elderly appear to be particularly at risk for drug - induced siadh . in a study on 736 cases of selective serotonin re - uptake inhibitor - induced siadh , the duration of time from the initiation of amiodarone to the development of siadh varied from 3 days to 6 months in the reported cases . the onset of hyponatremia ranged from day 3 to day 11 in patients who received loading doses of amiodarone . in contrast , hyponatremia occurred at 14 days to 6 months in patients receiving maintenance doses . in 7 cases , the serum sodium level normalized within 714 days after discontinuation of amiodarone and fluid restriction . it appears that amiodarone - induced siadh is more prevalent after a loading dose of the drug . however , because of the long half - life of amiodarone , the cumulative effect on the development of siadh remains undefined . mmol / l ) has been associated with serious sequelae , including confusion , hallucinations , seizures , coma and respiratory failure leading to death . the degree of hyponatremia in the majority of reported cases of amiodarone - induced siadh was 110120 mmol / l . in 2 cases , . 's and our case , serum sodium levels were less than 110 mmol / l ( 107 and 105 mmol / l , respectively ) . it is important to note that in hospitalized patients , the mortality was 28% in patients with serum sodium < 125 mmol / l and 50% in patients with serum sodium level < 115 mmol / l . therefore , amiodarone - induced siadh is a rare but lethal adverse effect , which occurs predominantly in elderly patients , who typically have multiple comorbidities , especially cardiovascular diseases , for which the drug is used . the only definitive treatment of siadh is the elimination of its underlying cause [ 3 , 14 ] . in all but 3 cases , amiodarone was discontinued and fluid restriction was instituted . in the remaining cases , the dose was decreased . one patient required hemodialysis due to decreasing serum sodium coupled with the development of altered mental status . to our knowledge , a total of 10 cases of amiodarone - induced siadh this adverse effect can occur as early as 3 days after receiving a loading dose or as late as 6 months in patients on maintenance doses . therefore , clinicians should be aware of this important complication when treating patients with amiodarone .

introductionhyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion ( siadh ) during amiodarone therapy is a rare but potentially lethal adverse effect . we report a case of severe hyponatremia associated with amiodarone , and discuss its clinical implications.case reportan 84-year - old caucasian man with a past medical history of hypertension and diabetes was admitted to the hospital with a non - st elevation myocardial infarction . he underwent coronary artery bypass graft and developed atrial fibrillation on postoperative day 2 . a loading dose of amiodarone followed by a maintenance dose was started . the serum sodium level was 136 mmol / l at discharge and subsequently decreased to 105 mmol / l 11 days later , at which time the patient represented with altered mental status . the diagnosis of siadh was made based on euvolemic hypoosmotic hyponatremia , lack of any other medication known to cause siadh and urine that was less than maximally dilute . the serum sodium increased gradually to 123 mmol / l after 36 h of treatment with hypertonic saline , demeclocycline and fluid restriction.conclusionsiadh-induced hyponatremia associated with amiodarone occurs rarely . since severe hyponatremia is associated with significant neurological damage and mortality , clinicians should carefully monitor serum sodium during amiodarone therapy .

rectal and perianal pain is common.1 it is usually perceived as mild discomfort , but sometimes it is incapacitating . it may be due to hemorrhoids , anal fissure , proctalgia fugax , or chronic perianal pain syndrome , and less commonly to cancers , proctitis , rectal prolapse , and inflammatory bowel diseases.2 the diagnosis is based on history , physical examination , and ancillary work - up . the pain of proctalgia fugax is sudden and intense , usually lasting less than a minute . the pain is described as sharp , stabbing , or cramp - like occurring at the anal opening . the attacks occur in clusters , appearing daily for a while and then disappearing for weeks or months.3 pain related to the levator ani syndrome is a constant or frequently occurring dull pain that is felt higher up inside the rectal passage . ancillary tests are performed according to the history and examination , and they may consist of a rectal examination , proctoscopy or full colonoscopy , and in some instances a barium enema . a 59-year - old woman was admitted to rasool - akram hospital ( affiliated with the tehran university of medical sciences , tehran , iran ) with a 2-year history of paroxysmal perianal pain . her physical examination including both rectal and pelvic examinations were normal . she underwent a full work - up including proctoscopy , sigmoidoscopy , full colonoscopy , and barium enema , all of which were unremarkable . then she was prescribed some anxiolytics and gabapentin with the diagnosis of neuralgic pain and referred to the neurology clinic . lumbosacral magnetic resonance imaging ( mri ) was performed for an evaluation of the referred pain ( fig . 1 ) . the lumbosacral mri showed an extramedullary - intradural lesion at the level of l5 with fairly uniform enhancement . her paroxysmal pain was gone , and she no longer needed medication for the pain ( fig . myelogram , sagittal , and axial t2 of lumbosacral magnetic resonance imaging show an extramedullary lesion . postoperative lumbosacral magnetic resonance imaging shows removal of the lesion with meningocele formation . although one should consider the usual causes of colorectal pain such as hemorrhoids , anal fissure , anal herpes , ulcerative proctitis , perianal hematoma , perianal or ischiorectal abscess , pilonidal sinus , perianal warts , anal carcinoma , proctalgia fugax , and chronic perianal pain syndrome,4 we should keep in mind that some referred pain may mimic local pathologies and should be evaluated properly . neurofibromas are fibroblastic neoplasms of peripheral nerves that are benign tumors.5 they account for 16 to 30% of all spinal tumors and 13.7% of spinal tumors of nerve sheath origin.6 neurofibromas and schwannomas are the most common spinal tumors that are evenly distributed along the spinal canal . about 1 to 55% of spinal neurofibromas are located in the sacral region.7 8 multiple and plexiform neurofibromas are associated with von recklinghausen disease ( neurofibromatosis type 1 [ nf1 ] ) . cutaneous solitary neurofibroma may be a typical and exclusive lesion of nf1 , although 90% of central and peripheral neurofibromas may be solitary and unrelated to systemic nf.5 9 10 the imaging characteristics of neurofibromas depend on their fibrous and myxoid tissues . of nerve sheath origin , they occur as a fusiform enlargement of the nerve , and neural fibers are dispersed within the lesion . neurofibromas are slow growing and noninvasive , and their elastic consistency permits them to be shaped by adjacent bone structures ; the bone reacts by remodeling around the lesions . they rarely calcify and frequently have a bibbed dumbbell appearance . on mri , neurofibromas are isointense with muscle on t1-weighted images and show a hypersignal on t2-weighted images . they may be heterogeneous.11 the most common signs and symptoms are due to compression of the affected nerve root . the neurologic outcome is related to the tumor bulk and whether or not the adjacent nerve root can be spared.12 malignant degeneration to neurofibrosarcoma occurs in 4 to 11% of patients with neurofibromatosis.13 teichmann et al reported a case of solitary neurofibroma of the lumbosacral plexus causing pain and leg paresis.14 daniel and his colleagues reported a young woman with low back pain and a left s1 nerve root mass enlarging the neural foramen and extending extradurally into the presacral soft tissues with a final diagnosis of neurofibroma.15

rectal and perianal pain is a common problem . most people have experienced it at least once in their lifetime . it usually manifests as mild discomfort , but sometimes the pain can be so severe that it is incapacitating . a 59-year - old woman admitted with a 2-year history of paroxysmal perianal pain underwent a full work - up including proctoscopy , sigmoidoscopy , full colonoscopy , and barium enema that were unremarkable . lumbosacral magnetic resonance imaging with and without gadolinium showed an intradural - extramedullary lesion at the level of l5 . the pathologic diagnosis was a neurofibroma . she underwent surgery , and after a few weeks she felt well and medication was no longer needed for her paroxysmal pain . although one should consider the usual causes of colorectal pain such as hemorrhoids , anal fissure , proctalgia fugax , and chronic perianal pain syndrome , we should keep in mind that some referral pain may mimic local pathologies and should be evaluated properly .

a clinical nephrology readership needs no convincing of the importance of proteinuria : it has prognostic significance in patients with a wide variety of forms of renal disease and is a potent independent cardiovascular risk factor . in health , this has a tripartite structure comprising podocytes ( visceral glomerular epithelial cells ) on the outer ( urinary ) aspect , fenestrated glomerular endothelial cells on the inner ( luminal ) aspect and the highly negatively charged glomerular basement membrane lying between the two cell types . it should be stated at the outset that each of these three components exerts an important influence on the selective permeability of the glomerular capillary wall and it is a mistake to think of any of the components in isolation . nevertheless , much of the focus in recent years has been on the podocyte and its actin cytoskeleton : these will be the focus of this article and i will attempt to highlight the clinical and therapeutic relevance of recent advances in the understanding of their cellular and molecular biology . podocyte injury and repair are relevant to the diverse forms of renal disease , including major clinical problems such as diabetic nephropathy , but many of the key principles are illustrated by focal segmental glomerulosclerosis ( fsgs ) , a common and important cause of nephrotic syndrome . it is now generally accepted that the predominant glomerular lesion in fsgs is an injury to podocytes . fsgs is one of the most difficult renal diseases to manage , with a real possibility that the cumulative toxicity of the various agents used in treatment has the potential to make the therapy as bad as or worse than the disease . although our drugs are often effective in controlling the nephrotic state , we have all seen patients whose physical appearance , bones , skin , glucose tolerance , etc . have been wrecked by long - term treatment with corticosteroids or whose kidney function has been damaged by calcineurin inhibitor toxicity . we urgently need more specific agents : there is accumulating evidence that the podocyte is the appropriate cellular target , and in particular , agents that stabilize the actin cytoskeleton are likely to be beneficial . podocytes imaged by scanning electron microscopy are , in the opinion of this author , aesthetically very pleasing ( figure 1 ) . they have a cell body , long primary processes and a complex network of interdigitating secondary processes . this complex cellular architecture is maintained by a precise organization of microtubules and actin filaments in the cellular cytoplasm . 1.scanning electron micrograph of podocytes on urinary aspect of normal glomerular capillary showing : ( a ) cell bodies , ( b ) primary processes and ( c ) interdigitating secondary processes that form filtration slits resembling the teeth of a zipper . scanning electron micrograph of podocytes on urinary aspect of normal glomerular capillary showing : ( a ) cell bodies , ( b ) primary processes and ( c ) interdigitating secondary processes that form filtration slits resembling the teeth of a zipper . transmission electron microscopic imaging will be more familiar to nephrologists from looking at real biopsies and shows that the normal glomerular capillary wall , on the urinary side , has a series of filtration slits between the foot processes of the podocytes ( figure 2a ) . it has been known for decades that a cardinal feature of the glomerular capillary wall in proteinuric states is flattening or effacement of the foot processes due to disruption of this precise organization . the key to understanding the importance of the actin cytoskeleton is the demonstration ( figure 2b ) that this effacement of foot processes is associated with flattening of the actin filaments . ( a ) shows the normal appearance : arrows indicate endothelial fenestrations , arrowheads indicate filtration slits between podocyte foot processes and asterisks indicate actin filaments in podocyte cytoplasm . ( b ) shows podocyte foot process effacement as seen in proteinuric states : note flattening of the actin filaments ( asterisked ) longitudinally associated with the loss of normal foot process architecture . ( a ) shows the normal appearance : arrows indicate endothelial fenestrations , arrowheads indicate filtration slits between podocyte foot processes and asterisks indicate actin filaments in podocyte cytoplasm . ( b ) shows podocyte foot process effacement as seen in proteinuric states : note flattening of the actin filaments ( asterisked ) longitudinally associated with the loss of normal foot process architecture . in recent years , it has become ever clearer that the precise organization and regulation of the actin cytoskeleton in the podocyte are essential for the maintenance of its normal structure and function , that disruption thereof is a feature of podocyte diseases and is associated with proteinuria , and perhaps most importantly of all that therapeutic agents which have beneficial effects in nephrotic syndrome are capable of restoring the podocyte actin cytoskeleton . many of the recent advances in the understanding of podocyte biology have come from studies of rare inherited forms of nephrotic syndrome which have been found to be due to mutations in podocyte genes ( reviewed in ) . one example with particular relevance to the importance of the actin cytoskeleton concerns the gene encoding alpha - actinin iv , which plays an important role in actin polymerization . elegant work from martin pollak 's group showed that mutations in alpha - actinin iv were associated with autosomal dominant late - onset familial fsgs and that the mutant form of the protein binds more avidly to actin and affects the mechanical properties of actin gels , providing an explanation for its effect on the podocyte structure . another group then showed that podocyte - specific transgenic expression of the mutant alpha - actinin iv gene in mice leads to fsgs , demonstrating that it is the effects of the gene in the podocyte rather than any other cell that is responsible for the disease . the final proof of the causative role of the mutation came in experiments in which pollak 's group showed that , when the mutant gene was knocked - in in mice , the animals developed fsgs , showing that this gene defect alone is capable of causing the disease . the mechanisms underlying the effects of the mutant protein have now been demonstrated in detail . pollak 's group have provided further evidence that the physicochemical characteristics of actin fibres formed with the mutant alpha - actinin iv show altered flexibility that can explain the effects on the podocyte . most recently , the alpha - actinin iv protein mutants have been shown to mislocalize to the cell cytoplasm and lose their ability to associate with nuclear receptors and activate gene transcription . other groups have reported different gene mutations which affect the actin cytoskeleton and also cause fsgs : for instance , in the gene encoding cd2-associated protein which encodes a protein that is important in linking to actin fibres . clinical nephrologists will inevitably ask whether these rare genetic forms of fsgs are analogous to the much more common sporadic forms of the disease . shared mechanisms are likely to exist : for example , in relation to the glomerular disease associated with human immunodeficiency virus ( hiv ) in which podocytes are specifically targeted by the virus , a key hiv protein called nef interacts with actin and alters the shape of podocytes . we do not yet know for sure , but recent observations on the mechanisms of action of drugs which are effective in fsgs have caused real excitement and shown the way to more specific forms of treatment . calcineurin inhibitors , especially cyclosporin , are widely used in the treatment of proteinuric diseases including fsgs ; their use originally being based on the assumption that the diseases are immune - mediated and that , therefore , the immunosuppressive effects of such drugs are likely to be helpful . made the novel observation that the anti - proteinuric effects of cyclosporin can be explained by direct effects on the podocyte actin cytoskeleton ( and therefore the cell 's shape ) and are independent of its effects on t lymphocytes . thus , cyclosporin prevents the degradation of synaptopodin , stabilizes the actin cytoskeleton and protects against proteinuria . this suggestion is further supported by analysis of the effects of corticosteroids , widely used in nephrotic syndrome , without us having much idea how they work . dexamethasone is the corticosteroid usually studied in vitro because it is not a pro - drug : it has potent effects on human podocytes including on their size and shape and has recently been shown to interact with alpha - actinin iv in stabilizing the podocyte actin cytoskeleton and protecting it from the injurious effects of adriamycin . many of the effects of dexamethasone on podocytes can be mimicked by another currently available form of therapy , thiazolidinediones ( glitazones ) and this may help us explain the anti - proteinuric effects of this group of drugs . the fact that many of the treatments that we currently use have potent effects on podocytes is of great interest , but clearly these agents are non - specific and have many unwanted effects . if we are to bring benefits to our patients from the recent scientific advances , we need to develop more specific therapeutic approaches . one pathway that can be selectively targeted by drugs is the system of small gtpase proteins of the rho family . there is still some controversy about which protein forms the most logical target , with another recent paper suggesting that rhoa is not the key member of the family in podocytes , instead providing evidence that another rho family gtpase , cdc42 , is the key one for maintenance of the podocyte actin cytoskeleton . a protein which is activated by rhoa , arhgap24 , has also been suggested as a downstream target since this molecule is important in the maintenance of normal podocyte shape and a gene mutation in the arhgap24 gene was found in a family with fsgs . rho kinase inhibitors are already available for therapeutic use and should be tested in humans for their effectiveness in proteinuric disease . other promising targets with protective effects on the podocyte actin cytoskeleton , and for which therapeutic agents are already available , include blockade of the tumour necrosis factor alpha pathway , and stimulation of the calcium - sensing receptor . finally , just to reiterate that podocytes are not the whole story : glomerular endothelial cells also depend for their integrity on an actin cytoskeleton , and this too is regulated by rho - kinases . disease situations such as diabetes mellitus are likely to affect both glomerular cell types , and in thinking about novel therapeutic approaches , as we strive for greater specificity we need to remember that we may need to target more than one cell type . the shape and structural complexity of podocytes underlie their function , and when disrupted lead to proteinuria . the actin cytoskeleton is a dynamic , highly regulated intracellular scaffold that maintains this shape and is disrupted in genetic ( and probably also in acquired ) forms of the nephrotic syndrome . currently used therapies undoubtedly have effects on podocytes and this may explain some or all of their usefulness in some forms of glomerular disease . other currently available therapies , as yet untested in proteinuric diseases , may have great potential . new pathways are being identified in glomerular cells that may provide even better therapeutic targets in future . podocytes are structurally and functionally complex cells which play a key role in the normal prevention of proteinuriain many renal diseases , including fsgs and diabetic nephropathy , podocyte injury / loss is a major pathogenetic and prognostic factorthe actin cytoskeleton in podocytes is responsible for the maintenance of their shape and their functionpodocyte foot process effacement is associated with major alterations in the actin cytoskeletoncurrently used therapies including steroids and cyclosporin have direct effects on the podocyte actin cytoskeletonour ever - improving knowledge of glomerular cell biology in health and disease will allow new more specific forms of therapy to be developed podocytes are structurally and functionally complex cells which play a key role in the normal prevention of proteinuria in many renal diseases , including fsgs and diabetic nephropathy , podocyte injury / loss is a major pathogenetic and prognostic factor the actin cytoskeleton in podocytes is responsible for the maintenance of their shape and their function podocyte foot process effacement is associated with major alterations in the actin cytoskeleton currently used therapies including steroids and cyclosporin have direct effects on the podocyte actin cytoskeleton our ever - improving knowledge of glomerular cell biology in health and disease will allow new more specific forms of therapy to be developed conflict of interest statement . none declared .

the podocyte is a key cell in the selective filtering action of the glomerular capillary wall . podocyte injury is of pathogenetic and prognostic significance in human glomerular disease ; podocyte repair and regeneration are important therapeutic targets . in particular , podocyte function is dependent on the cells ' actin cytoskeleton : this maintains their complex structure . alterations in the actin cytoskeleton arise from a variety of genetic and acquired causes . therapeutic agents that are beneficial in proteinuric disease may act at least partly by restoring the cell shape via effects on the actin cytoskeleton . recent studies of podocytes in vivo and in vitro are described , highlighting clinically relevant observations and those that help us understand the ways in which we may harness nature 's own mechanisms to repair and/or renew these specialized glomerular cells , with a particular focus on their actin cytoskeleton . drugs that have beneficial effects on podocytes can improve our ability to treat important renal diseases including diabetic nephropathy . currently available agents can be applied in this way and the rapid progress in the study of podocytes is highlighting new therapeutic targets that can bring even more specificity .

there has never been a prospective , randomized , controlled trial of cerclage versus no cerclage . emergency or rescue cerclage as it is coined is a desperate measure to prevent fetal loss before viability of very preterm babies with poor survival . the outcome of pregnancy with emergency cervical cerclage is based on limited information and success factors are not well known . previous studies suggest that advanced cervical dilatation , significant cervical effacement , presence of prolapsed membranes , and presence of vaginal infection cause cerclage failure . between 2007 and 2009 in a period of three years , 20 pregnant patients with dilated cervix and protruding membranes were treated with emergency cervical cerclage at al wasl hospital , dubai . at the time of cerclage , gestational age ranged from 17 to 26 weeks ( median = 21 ) and the cervix was dilated > 4 cm dilated at the time of the procedure . special note was made that there was no rupture of membranes or leaking of amniotic fluid vaginally . infection was excluded clinically by absence of pyrexia and uterine tenderness , white blood cell count . out of 20 patients 14 patients were mildly contracting , and one of them had a large intramural fibroid in the lower segment which caused premature effacement and dilatation of the cervix . 5 patients had positive cultures of gardnerella vaginalis which was treated with metronidazole ; subsequent cultures were negative . most of these patients were treated initially with broad spectrum antibiotics intravenously , to treat infection as cultures may not be available for another 48 hours . cervical swabs and high vaginal swabs were examined for chlamydia trachomatis ( elisa ) and cultured for bacteria and mycoplasma ( bacterial vaginosis ) in all patients . most of the patients were observed for 1224 hours before insertion of the suture to ensure that all uterine contractions had settled and if infection was present subclinically . if present , it was taken care by intravenous antibiotics started at the initial assessment . women with persisting contractions , overt infection , and those who had a recent history of antepartum hemorrhage suggestive of placental abruption , or ruptured membranes after or before admission were excluded . we waited for a period of 1224 hours as there were two patients who ruptured their membranes and were excluded . the patients whose uterus stopped contracting by tocolysis by infusion of tractocile ( 7.5 mg in 500 ml of 0.9% saline ) were given nsaid ( voltaren , diclofenac acid , 100 mg ) rectally in all patients at the time of admission after assessment . under general anesthesia they were placed in lithotomic position with steep trendelenberg tilt , and the situation was assessed cautiously by examination with a sims speculum . if the cervix was visible all round the bulging membrane , attempt was made to grasp the cervical lip with sponge holder gently . then the vagina is washed with aqueous betadine solution , and the sponge holders are brought close to each other . an attempt is made to push the membranes into the uterus with an inflated foleys catheter with 30 ml of water , as described by holman and sher . this allows insertion of the sutures without risk of putting a needle through the amniotic sac causing rupture of membranes and failure of continuation of the pregnancy . amniocentesis was not attempted in any patients as we could insert the suture in all patients . we also wanted to avoid any introduction of infection and also add the risk of loss of pregnancy with amniocentesis . 18 patients in our series had mersilene tape ( ethicon ltd ) suture inserted using the mcdonald technique . four of the patients had additional sutures using interrupted nylon or prolene sutures ( 0 metric gauges ) above the first suture or between the anterior and posterior surface of the cervix . the sutures were tied to bring the anterior and posterior surface of the cervix together , without occluding the circulation . tocolysis was continued for 24 hours postoperatively , and patients were observed for any pain , contractions , or other complications . prophylactic broad spectrum antibiotics were given intravenously , before or during the procedure , and continued orally for the next 5 days . most patients received zinocef ( cefuroxime 1.5 gms 8 hourly ) and metronidazole ( 1 gm 12 hourly ) and were kept in hospital for 1014 days . they were commenced on clexane 40 mg ( enoxaparine ) to prevent deep vein thrombosis . additionally , all these patients received primolut 250 mg ( progesterone ) once weekly , till 32 weeks of pregnancy , which acts as a uterine relaxant . on discharge , instructions were given to lead a quiet life , avoid intercourse , and attend the antenatal clinic for assessment at 2 weeks intervals . most patients delivered within 4 hrs of admitting to the labor ward and all were satisfied with the outcome ( figure 1 ; tables 1 and 2 ) . cervical cerclage is an intervention that is widely used to prevent miscarriage or delivery in the second trimester of pregnancy . in cases with advanced cervical dilatation and bulging membranes , it has been referred to as ( heroic cerclage ) or rescue cerclage due to its poor success rate . we have managed a case of successful cerclage in a woman 8 cm dilated with membranes bulging up to introitus . mechanical support of a weak cervix was thought to be the main factor required to prolong the pregnancy . the classic description of pregnancy loss due to cervical incompetence is unexpected sudden painless delivery . most commonly , miscarriage in the second trimester or early preterm delivery occurs following premature ripening and shortening of the cervix and the onset of painful contractions . the probable mechanism is that a degree of cervical incompetence , not sufficient to cause sudden pregnancy loss , exposes the fetal membranes to vaginal bacteria , and this leads to stimulation of the inflammatory process responsible for the onset of labor . cervical cerclage in advanced cervical dilatation with bulging membranes in the second trimester is controversial . the outcome of these pregnancies is usually poor , but without a cerclage the loss of pregnancy is inevitable . the outcome can be improved if initially a uterine contraction suppressant is used and vaginal infection can be treated . these patients need a lot of counseling and be made aware of the risk of losing the pregnancy . prolonging pregnancy to reach just viable gestations may also increase overall morbidity . it has been suggested that infection is likely to play a part in many cases of miscarriage in the second trimester and therefore screening for infection before insertion of the suture may predict prognosis . however , in women with bulging membranes , delay in the insertion of the suture is likely to increase the risk of infection , due to the increased exposure of the fetal membranes to vaginal bacteria [ 6 , 7 ] . reported survival rates following emergency cerclage vary from 12.5% to 63% in women with cervical dilatation of > 3 cm . use of tocolytics helps to suppress the uterine contractions and also reduce the intrauterine pressure thus reducing the bulging membranes . use of nsaid drugs usually acts as anti - inflammatory and reduces the inflammatory response and reduce the liquor production . assessment of the cervical length by transvaginal ultrasound after cervical cerclage may help predict the outcome of pregnancy [ 9 , 10 ] . they showed that the length of the endocervical canal and the length of the closed cervix above the suture predicted delivery before 36 weeks of gestation . although some authors have seen improvements in the state of the cervix , this has not been reported after cerclage with advanced cervical dilatation . owen et al . described 29 cases of cervical cerclage following shortening or funneling of the cervix seen on transvaginal scan . our one case with advanced cervical dilatation was probably due to the presence of fibroid causing cervical dilatation , rather than infection . however , we suggest that despite an advanced degree of cervical dilatation , the insertion of a cervical suture may lead to remodeling of the cervix . by replacing the membranes and closing the cervix , the risk of exposure to vaginal infection is reduced and therefore the inflammatory - like process which is responsible for the cervical ripening and onset of contraction is also reduced . this causes the cervix to close and lengthen and prolong the pregnancy ( figure 2 ) . all women with advanced cervical effacement or dilatation or both should be counseled about the paucity of data to support the efficacy of the emergency or rescue cerclage , as well as the potential associated maternal and neonatal morbidity . despite its overall poor prognosis , proper selection of cases results in successful outcome . follow - up by transvaginal scan for cervical length , screen for bacterial vaginosis , and treatment with antibiotics covering aerobic and anaerobic organism , and pre- and postoperative tocolysis is likely to be helpful in prolonging the pregnancy and thus improving outcome . it is also important to exclude placental abruption and labor in women with cervical dilatation in the second trimester but we did not find this to be difficult clinically . to add , a period of observation is helpful before considering emergency cerclage . by adopting this approach there appears to be little hazard to the women and an over 60% chance of survival for the infant .

the aim of our study is to verify whether some maternal features are related to pregnancy outcomes of emergency cerclage when membranes are protruding through the dilated cervix . we present a retrospective review of 20 cases of emergency cervical cerclage performed over a 3-year period at al wasl hospital , a tertiary level centre in dubai . analysis shows presence of membrane prolapse with infection causing rupture of membranes , to be the strongest predictor of poor outcome . analysis also reveals a significant association between initial white blood cell count and perinatal outcome . this information is helpful in decision making and counseling patients regarding the likely outcome .

the survival of children with osteosarcoma has improved substantially over the last 30 yr . however , as the number of long - term survivors has increased , there have been increasing concerns about the potential of late sequelae , especially in the development of second malignant neoplasms ( smn 's ) . in previous reports with long follow - up durations , 2 - 5% of osteosarcoma patients developed an smn at a median interval of 5 - 8 yr after osteosarcoma treatment ( 1 - 4 ) . the pathogenic mechanisms for smn 's mainly consist of genetic predisposition and therapy - related factors including chemotherapy and especially radiation therapy . thyroid carcinomas have been described as an smn in survivors of leukemia and hodgkin lymphoma , occurring after craniospinal irradiation that includes the thyroid gland ( 5 , 6 ) . , we report the occurrence of thyroid papillary carcinoma after the treatment of osteosarcoma in two patients who had neither a family history of cancer nor history of radiation therapy . a 13-yr - old girl visited a local clinic for painful swelling of right arm after a minor trauma in 1988 ( fig . a pathologic fracture was suspected upon initial radiographs , and as a result , an incisional biopsy was performed , which revealed a fibroblastic osteosarcoma . she was transferred to our institution after the biopsy and was diagnosed as having in clinical stage iib according to the enneking 's classification . she had received preoperative chemotherapy consisting of cisplatin ( 100 mg / m , every 3 - 4 weeks , total 780 mg / m ) and doxorubicin ( 60 mg / m , every 4 weeks for a total of 293 mg / m ) . despite the treatment , the patient 's poor clinical response and her parents ' refusal to definite surgery led us to change the chemotherapy regimen . after seven courses of bleomycin , cyclophosphosphamide and actinomycin d , the tumor was resected with a wide margin , and reconstructed with a tumor prosthesis - bone cement composite . the changed chemotherapy regimen was considered to be effective based on the clinical and histologic response , and the patient had received 4 more courses of chemotherapy with the same agents . the patient complained of dyspnea during the last course of postoperative chemotherapy and was brought in for a cardiac consultation . the echocardiogram and endomyocardial biopsy revealed the patient to be afflicted with dilated cardiomyopathy , which was consideraed to have been caused by doxorubicin . her cardiac symptoms were mild and well - controlled with diuretics , and she had been doing well for 12 yr until a mass in her neck was discovered . she underwent total thyroidectomy without neck dissection and a pathologic evaluation of the tissue revealed the papillary carcinoma of conventional type ( fig . 1b ) . the mass had a 1.2 cm diameter , and the tumor did not invade the thyroid capsule . she has not undergone radioactive iodine therapy and has been treated on thyroid replacement therapy . she showed no evidence of either malignancy at 18 yr after the diagnosis of her osteosarcoma and at 4 yr after the diagnosis of her thyroid carcinoma . an 18-yr - old boy was diagnosed with a chondroblastic type osteosarcoma of the right proximal tibia in 2001 . according to the enneking 's criteria , after completing two cycles of chemotherapy that included a high - dose methotrexate , adriamycin , and cisplatin , he was treated with a limb salvage operation ( fig . ( 5 yr after the diagnosis of osteosarcoma ) , a thyroid nodule was incidentally found on a follow - up chest ct image ( fig . the cytologic findings of a fine - needle aspiration were consistent with papillary thyroid carcinoma , and he underwent a total thyroidectomy with modified radical neck dissection shortly thereafter . the pathologic evaluation revealed a conventional type papillary carcinoma in the left thyroid lobe ( fig . 2c ) . a total of 15 lymph nodes were dissected , 10 of which were found to be positive for tumor cells . after the surgery , he was treated with radioactive i and maintained on thyroid hormone replacement therapy . six years after the diagnosis of osteosarcoma and 1 yr after the diagnosis of thyroid carcinoma , he has been and remains free of malignancies . a 13-yr - old girl visited a local clinic for painful swelling of right arm after a minor trauma in 1988 ( fig . a pathologic fracture was suspected upon initial radiographs , and as a result , an incisional biopsy was performed , which revealed a fibroblastic osteosarcoma . she was transferred to our institution after the biopsy and was diagnosed as having in clinical stage iib according to the enneking 's classification . she had received preoperative chemotherapy consisting of cisplatin ( 100 mg / m , every 3 - 4 weeks , total 780 mg / m ) and doxorubicin ( 60 mg / m , every 4 weeks for a total of 293 mg / m ) . despite the treatment , the patient 's poor clinical response and her parents ' refusal to definite surgery led us to change the chemotherapy regimen . after seven courses of bleomycin , cyclophosphosphamide and actinomycin d , the tumor was resected with a wide margin , and reconstructed with a tumor prosthesis - bone cement composite . the changed chemotherapy regimen was considered to be effective based on the clinical and histologic response , and the patient had received 4 more courses of chemotherapy with the same agents . the patient complained of dyspnea during the last course of postoperative chemotherapy and was brought in for a cardiac consultation . the echocardiogram and endomyocardial biopsy revealed the patient to be afflicted with dilated cardiomyopathy , which was consideraed to have been caused by doxorubicin . her cardiac symptoms were mild and well - controlled with diuretics , and she had been doing well for 12 yr until a mass in her neck was discovered . she underwent total thyroidectomy without neck dissection and a pathologic evaluation of the tissue revealed the papillary carcinoma of conventional type ( fig . 1b ) . the mass had a 1.2 cm diameter , and the tumor did not invade the thyroid capsule . she has not undergone radioactive iodine therapy and has been treated on thyroid replacement therapy . she showed no evidence of either malignancy at 18 yr after the diagnosis of her osteosarcoma and at 4 yr after the diagnosis of her thyroid carcinoma . an 18-yr - old boy was diagnosed with a chondroblastic type osteosarcoma of the right proximal tibia in 2001 . according to the enneking 's criteria , after completing two cycles of chemotherapy that included a high - dose methotrexate , adriamycin , and cisplatin , he was treated with a limb salvage operation ( fig . ( 5 yr after the diagnosis of osteosarcoma ) , a thyroid nodule was incidentally found on a follow - up chest ct image ( fig . the cytologic findings of a fine - needle aspiration were consistent with papillary thyroid carcinoma , and he underwent a total thyroidectomy with modified radical neck dissection shortly thereafter . the pathologic evaluation revealed a conventional type papillary carcinoma in the left thyroid lobe ( fig . 2c ) . a total of 15 lymph nodes were dissected , 10 of which were found to be positive for tumor cells . after the surgery , he was treated with radioactive i and maintained on thyroid hormone replacement therapy . six years after the diagnosis of osteosarcoma and 1 yr after the diagnosis of thyroid carcinoma , he has been and remains free of malignancies . thyroid cancer accounted for 7.5% of the smn 's reported in a series of childhood survivors of malignancy ( 7 ) . most second thyroid cancers have been reported to develop after radiation therapy in survivors of leukemia and hodgkin lymphoma . a genetic predisposition to thyroid malignancy has been observed in familial syndromes such as pendred , hamartoma , and gardner 's syndromes ( 8) , while familial retinoblastoma , li - fraumeni , rothmund - thomson , and bloom syndromes were associated with osteosarcoma . in our series , moreover , there was no family history of genetic disease or malignancy on either of the maternal and paternal sides . however , there still remains a possibility that our patients may have a genetic syndrome such as rothmund - thomson syndrome , especially since the clinical features of this syndrome could be subtle . genotype analysis of the recql genes including recql4 ( for rothmund - thomson syndrome ) , recql2 ( for bloom syndrome ) , and recql3 ( for werner syndrome ) are mandatory to rule out these syndromes . although most second thyroid malignancies develop after exposure to radiotherapy , none of our patients underwent radiation therapy . some of the thyroid malignancies may have been unrelated to the primary tumors , and ocurred as it would in the general population rather than being related to either the primary cancer or the therapy . several etiologic factors for the second thyroid cancer aside for radiation therapy have been proposed , such as the sequelae of immune suppression , the oncogenic potential of systemic chemotherapy , or some combinations of these factors . chemotherapy can have numerous long - term effects including , most importantly , the leukemogenic effect . there are several reports on secondary leukemias and myelodysplastic syndromes in patients treated with multi - agent chemotherapies for osteosarcoma . recent reports have emphasized the concern of treatment - related myelodysplasia / myeloid leukemia for regimens that use high cumulative doses of alkylating agents in addition to combination therapy with topoisomerase ii inhibitors . reported 3 cases of thyroid cancer arising in patients treated with alkylating agents without radiation ( 9 ) . this binding resulted in damage to the normal and neoplastic cells . in the current series , the first case was administered with several alkylating agents and topoisomerase ii inhibitor ( including cisplatin , cyclophosphamide , ifosfamide , and adriamycin ) , which might have heralded the development of thyroid cancer ( 10 ) . eight cases of thyroid carcinoma occurring in association with osteosarcoma have been reported to date ( 11 - 15 ) . of the eight , four patients had genetic abnormalities ( most commonly the werner syndrome ) . the clinical characteristics of the syndrome include small stature , scleroderma - like skin alterations , juvenile cataracts , premature facial aging , ectopic calcification , refractory ulcers , and joint contracture . thyroid cancer , osteosarcoma , and malignant melanoma are frequently associated with this syndrome ( 16 ) . in our series , no patients showed the clinical features of werner 's syndrome . among the remaining four patients , two underwent radiation therapy , which might have exerted deleterious effects of radiation scatter on the thyroid area , and the other two patients did not have genetic abnormalities or risk factors for smn 's . the two patients documented in previous reports and the second patient of the present report would be good candidates for the screening of unknown genetic predisposition , including single nucleotide pleomorphism . in conclusion , vigilant surveillance and long - term follow - up should be emphasized in all survivors of osteosarcoma .

we report two cases of papillary thyroid carcinoma occurring after the successful treatment of osteosarcoma . one of the patients was administered with several alkylating agents and topoisomerase ii inhibitor as part of the primary treatment of osteosarcoma . the onset of thyroid carcinoma occurred after 5 and 12 yr after cessation of the osteosarcoma therapy . all the patients involved in this study are alive and free of their malignancies . there have been eight case reports of these two malignancies occurring in the same patient . thyroid carcinoma rarely occurs in patients with osteosarcoma ; however , vigilant surveillance and long - term follow - up should be emphasized for all survivors .

the prethromboticstates include various primary as well as secondary clinical disorders characterized by an increased tendency for thromboembolism . primary hypercoagulable states include relatively rare inherited disorders of coagulation , such as protein c and protein s deficiency and abnormalities of the fibrinolytic system . secondary hypercoagulable states are generally acquired , and include different conditions , such as pregnancy , malignancy , myeloproliferative syndromes , and systemic diseases . still , in 25 to 50% of patient with first - time venous thrombosis , no readily identifiable risk factor can be found . several previous studies suggest that hyperthyroidism represent a potential hypercoagulable and hypofibrinolytic state , which may contribute to the increased risk of thromboembolism . most reports have focused on only the venous thromboembolism risk , and few of them have studied specifically the association between hyperthyroidism and pulmonary embolism ( pe ) . in this report , we describe two patients with graves disease complicated by pe . a 32 year - old man , with a family history of graves disease in a maternal aunt , was admitted to the hospital with a history of weight loss , excessive sweating , palpitation , tremors of the hands and irritability of sixmonths duration . on clinical examination pulse was 132 per minute and irregular . blood pressure ( bp ) was 110/70 mmhg . he also had clinical signs of right heart failure , including edema of lower limbs , hepatomegaly and hepatojugular reflux . laboratory tests revealed normocytic normochromic anemia with a hemoglobin level of 11.8 g / dl . thyroid function tests confirmed a state of thyrotoxicosis with free t4 ( ft4 ) of 51 pmol / l ( reference range 10 - 24 ) , and tsh of 0.07 u / ml ( reference range 0.4 - 4.5 ) . electrocardiogram ( ecg ) showed complete arrhythmia due to atrial fibrillation ( ca / fa ) . echocardiography revealed dilated right cavities , mild tricuspid insufficiency , and elevated pulmonary pressure reaching 64 mmhg . the diagnosis of pe was suspected by the presence of significant pulmonary hypertension , and was confirmed by a lung perfusion - ventilation scan test that showedhypoperfusion of the left lung [ figure 1 ] . ventilation - perfusion scintigraphy of the patient n1 hypoperfusion on his left lung no conventional venous thromboembolism risk factors were identified . thrombophilia screen , including protein c and s , antithrombin , activated protein c resistance , lupus anticoagulant , and anti - cardiolipin antibody were negative . benzylthiouracil ( basdne ) treatment was also initiated at a dose of 225 mg daily , associated with beta - blocker propranolol . two months later , radioactive iodine treatment ( 8 mci ) was administered , resulting in incomplete recovery from thyrotoxicosis . the patient died of acute heart failure secondary to a chest infection 2.5 months after radioactive iodine treatment . a 23-year - old female patient , whose sister was affected by graves disease , had been treated since 2007 for graves disease . this diagnosis was made on the basis of hyperthyroid symptoms , moderate homogenous and elastic goiter , elevated ft4 level ( 94.9 pmol / l , normal range 10 - 24 ) with suppressed tsh ( 0.05 u / ml , normal range 0.4 - 4.5 ) , and elevated titer of antithyroid - stimulating antibodies ( 43.3 ui / l , normal range < 2 ) . the patient was put under antithyroid drugs : benzylthiouracil ( basdne ) at a dose of 225 mg daily in combination with a beta - blocker ( propranolol , 60 mg daily ) . the patient showed poor compliance and frequent discontinuation of her treatment . facing the reappearance of hyperthyroidism , she had a body mass index of 21.38 kg / m , bp of 140/80 mmhg . in addition to the signs of thyrotoxicosis , the patient had a moderate bilateral exophthalmos associated with a moderate homogenous and vascular goiter . her ecg showed sinus tachycardia with right axis deviation , and sokolow - lyon criteria for left ventricular hypertrophy . on hormonal investigations , ft4 was higher than 100 pmol / l ( normal range 10 - 24 ) and tsh was 0.005 u / ml ( normal range 0.4 - 4.5 ) . during hospitalization , serum level of d - dimer was higher than 500 ng / ml . pe was suspected and was confirmed by a lung perfusion - ventilation scan test confirmed which showed several bilateral segmental perfusion defects [ figure 2 ] . the patient was put under heparin relayed by anticoagulants . in addition , radioactive iodine treatment was administered ( 7 mci ) , and then the patient was again put under benzylthiouracile . etiological investigation of pe has revealed a 200% elevation of plasma concentration of coagulation factor viii . she was clinically euthyroid , and since then she was lost to follow - up . a 32 year - old man , with a family history of graves disease in a maternal aunt , was admitted to the hospital with a history of weight loss , excessive sweating , palpitation , tremors of the hands and irritability of sixmonths duration . on clinical examination pulse was 132 per minute and irregular . blood pressure ( bp ) was 110/70 mmhg . he also had clinical signs of right heart failure , including edema of lower limbs , hepatomegaly and hepatojugular reflux . laboratory tests revealed normocytic normochromic anemia with a hemoglobin level of 11.8 g / dl . thyroid function tests confirmed a state of thyrotoxicosis with free t4 ( ft4 ) of 51 pmol / l ( reference range 10 - 24 ) , and tsh of 0.07 u / ml ( reference range 0.4 - 4.5 ) . electrocardiogram ( ecg ) showed complete arrhythmia due to atrial fibrillation ( ca / fa ) . echocardiography revealed dilated right cavities , mild tricuspid insufficiency , and elevated pulmonary pressure reaching 64 mmhg . the diagnosis of pe was suspected by the presence of significant pulmonary hypertension , and was confirmed by a lung perfusion - ventilation scan test that showedhypoperfusion of the left lung [ figure 1 ] . ventilation - perfusion scintigraphy of the patient n1 hypoperfusion on his left lung no conventional venous thromboembolism risk factors were identified . thrombophilia screen , including protein c and s , antithrombin , activated protein c resistance , lupus anticoagulant , and anti - cardiolipin antibody were negative . benzylthiouracil ( basdne ) treatment was also initiated at a dose of 225 mg daily , associated with beta - blocker propranolol . two months later , radioactive iodine treatment ( 8 mci ) was administered , resulting in incomplete recovery from thyrotoxicosis . the patient died of acute heart failure secondary to a chest infection 2.5 months after radioactive iodine treatment . a 23-year - old female patient , whose sister was affected by graves disease , had been treated since 2007 for graves disease . this diagnosis was made on the basis of hyperthyroid symptoms , moderate homogenous and elastic goiter , elevated ft4 level ( 94.9 pmol / l , normal range 10 - 24 ) with suppressed tsh ( 0.05 u / ml , normal range 0.4 - 4.5 ) , and elevated titer of antithyroid - stimulating antibodies ( 43.3 ui / l , normal range < 2 ) . the patient was put under antithyroid drugs : benzylthiouracil ( basdne ) at a dose of 225 mg daily in combination with a beta - blocker ( propranolol , 60 mg daily ) . the patient showed poor compliance and frequent discontinuation of her treatment . facing the reappearance of hyperthyroidism , she had a body mass index of 21.38 kg / m , bp of 140/80 mmhg . in addition to the signs of thyrotoxicosis , the patient had a moderate bilateral exophthalmos associated with a moderate homogenous and vascular goiter . her ecg showed sinus tachycardia with right axis deviation , and sokolow - lyon criteria for left ventricular hypertrophy . on hormonal investigations , ft4 was higher than 100 pmol / l ( normal range 10 - 24 ) and tsh was 0.005 u / ml ( normal range 0.4 - 4.5 ) . during hospitalization , serum level of d - dimer was higher than 500 ng / ml . pe was suspected and was confirmed by a lung perfusion - ventilation scan test confirmed which showed several bilateral segmental perfusion defects [ figure 2 ] . , radioactive iodine treatment was administered ( 7 mci ) , and then the patient was again put under benzylthiouracile . etiological investigation of pe has revealed a 200% elevation of plasma concentration of coagulation factor viii . she was clinically euthyroid , and since then she was lost to follow - up . our two reported cases are in agreement with previous observations of pe and venous thrombosis in patients with hyperthyroidism . in a recent systematic analysis , the authors concluded that there was an increased risk of venous thrombotic complications in overt hyperthyroid patients . there are few reports of pe associated with hyperthyroidism . a recent study , using a nationwide population - based dataset , aimed to estimate the risk of pe among hyperthyroidism patients during a five year period . the study included 8903 patients with hyperthyroidism as a study cohort and 44515 randomly selected patients without hyperthyroidism as a comparison cohort . after adjustment for potential confounders , the risk of having pe during the five year follow - up period was 2.31 times greater ( 95% confidence interval 1.20 - 4.45 , p = 0.012 ) for patients with hyperthyroidism than for patients in the comparison cohort . pe is , in the overwhelming majority , a consequence of deep venous thrombosis ; the two together constitute venous thromboembolism ( vte ) . three primary influences predispose a patient to thrombus formation ; these form the so - called virchow triad , which consists of decreased flow rate of the blood , damage to the blood vessel wall and hypercoagulability . possible predisposing factors for the development of venous thrombosis and pe in patients with thyrotoxicosis are also in line with this triad . indeed , patients with hyperthyroidism may often have accompanying endothelial dysfunction , decreased fibrinolytic activity , and hypercoagulablestates , which contribute to the development of venous thrombosis and increased risk of pe . patients with hyperthyroidism had elevated levels of von willibrand factor , tissue plasminogen activator inhibitor-1 and antithrombin iii , decreased levels of tissue plasminogen activator , shortened activated partial thromboplastin time , increased turnover of coagulation factors ii , vii , ix and x , and increased plasma homocysteine and fibrinogen levels . it is well established that plasma coagulation factor viii activity positively correlates with tissue metabolic rate and plasma catecholamine levels . an excessive adrenergic activity , occurring in hyperthyroid patients , may directly contribute to an increased production of fviii , as illustrated by the fact that propanolol may inhibit the increase of fviii in patients with hyperthyroidism . elevated factor viii levels seem to be a significant , prevalent , independent , and dose - related risk factor for venous thrombosis . this entity may also account for a significant proportion of idiopathic hypercoagulable states . the factor viii level typically falls as the thyroid function becomes normalized . in our first case , the factor viii could not be determined in the acute phase , while in the second observation ; factor viii was high reaching 200% , thus corroborating the literature data . previous intervention studies , performed in healthy volunteers , showed a dose dependent increase in factor viii and ix levels , von willebrand factor , and endothelium - associated proteins concentrations during administration of oral thyroid hormones . in line with these findings , notably , the thrombotic risk was substantially increased for ft4 levels well within the physiologic range . moreover , ft4 levels were particularly associated with the risk of unprovoked deep veinous thrombosis , indicating ft4 as a potential novel risk factor . in addition to overt hyperthyroidism , subclinical hyperthyroidism seems also to be associated with increased risk of venous thrombosis . in this context , patane et al . , describe a case of recurrent pe associated with subclinical hyperthyroidism , in an 81-year - old italian woman . in addition , alterations in fibrinogen and d - dimer levels , and increased factor x activity were reported in patients with subclinical hyperthyroidism . all these findings represent a potential hypercoagulable state , which could contribute to increased thromboembolic risk in subclinical hyperthyroidism . in summary our study emphasizes the need for thyroid evaluation in patients with unprovoked venous thromboembolic events . conversely , the diagnosis of venous thromboembolism and pe should be considered in patients with hyperthyroidism , particularly if additional prothrombotic risk factors are present .

several disorders of coagulation and fibrinolysis have been widely reported in patients with hyperthyroidism . most reports have focused on only the venous thromboembolism risk , and few of them have studied specifically the association between hyperthyroidism and pulmonary embolism ( pe ) . we report two cases of graves disease complicated by pe . the first patient is a 32 year - old man , and the second patient is a 23-year - old female . pe was suspected on the basis of pulmonary hypertension in patient one , and clinical presentation in the other patient . the first patient had also right heart failure . pe was confirmed in both patients by a lung perfusion - ventilation scan test . thrombophilia screen revealed normal findings in the first patient and an elevation in coagulation factor viii in the second one . both patients received heparin , followed by oral anticoagulant therapy . in addition , they were treated with radioactive iodine resulting in partial recovery from hyperthyroidismforpatient oneand clinical euthyroidism for patient two . the former died of acute heart failure secondary to a chest infection , while the later was lost to follow - up . in conclusion , hyperthyroidism is associated with increased risk of venous thromboembolism , including pe . potential mechanisms involved in this association include endothelial dysfunction , decreased fibrinolytic activity , and increased coagulation factors levels . thyroid evaluation is recommended in patients with unprovoked venous thromboembolic events . conversely , the diagnosis of venous thromboembolism should be considered in patients with hyperthyroidism , particularly if additional prothrombotic risk factors are present .

it is a major health problem , brings much morbidity , early mortality and great deal of misery for a family both financially and emotionally . patients with thalassemia major should receive blood transfusion regularly to maintain optimal hemoglobin ( hb ) level . such transfusion will increase exposure to hepatitis b virus ( hbv ) , hepatitis c virus ( hcv ) and human immunodeficiency virus ( hiv)[1 , 2 ] . transmission of hepatitis b virus ( hbv ) infection through donated blood is more common than hepatitis c virus ( hcv ) infection ( 1:60000 vs. 1:103000 ) . there are more than 2 billion people with hepatitis b infection worldwide with 350 million people as hepatitis b virus carriers . at least 35% of iranians have been exposed to hbv and 3% are chronic carriers . hence , prevention in this high risk group is of great importance . on the other hand , thalassemic patients may have iron overloading due to chronic blood transfusion which could lead to impaired immune response toward vaccination . active immunization through the hepatitis b vaccination before exposure to virus is the most effective way to prevent infection . based on the serum levels of anti - hbs , subjects are categorized as good responder ( anti - hbs > 100iu / ml ) , low responder ( anti - hbs 10 - 100 iu / ml ) and non - responder ( anti - hbs < anti - body will appear in serum and remains for a long period of time . in 50% of cases , level of the anti - body is not detectable after vaccination and they need to be revaccinated . in a study from 217 thalassemic patients who were vaccinated against hbv , the aim of this study was to evaluate the efficacy of hbv vaccine and the prevalence of hbv infection in children with thalassemia major disease in tehran . patients : in a cross - sectional study , sera of 99 beta - thalassemic children who had received hree doses ( 10/20 g ) of recombinant hbv vaccine in months 0 , 1 and 6 were selected . these children were studied at virology lab of iranian blood transfusion organization ( ibto ) during 2007 - 2008 . the study population included 55 males ( 55.1% ) and 44 females ( 44.9% ) , aged 3 to 12 years ( mean 7.2sd 2.56 ) . on the basis of their age , the patients were classified into 3 groups of 1 - 5 , 6 - 10 , 11 - 15 years old . about half ( 59.6% ) of our study population was in the second group ( 6 - 10 year - olds ) . in the first group , there were 15 males ( 55.5% ) and 12 females ( 44.4% ) , in the second group there were 31 males ( 52.5% ) and 28 females ( 47.4% ) and in the third group there were 8 males ( 66.6% ) and 4 females ( 33.3% ) . this study was approved by the medical ethics committee of ibto . elisa test : serological markers of hbv infection such as hbsag , and antibodies to hepatitis b core antigen ( anti - hbc ) and to hbsag ( anti - hbs ) were tested using commercial enzyme linked immunosorbent assay ( elisa ) kit ( enzygnost , dade - behring , germany ) according to the instructions of the manufacturer . hbv dna extraction : hbv dna was extracted from all serum samples with the high pure viral nucleic acid kit ( roche , germany ) according to the instructions of the manufacturer . for suspension of hbv dna , 30 l elusion buffer was used . nested - pcr : nested - pcr was performed on all of thalassemics extracted dna using amplification of a segment of the hbv surface antigen . the s gene sequence was amplified by nested - pcr on the most conserved regions . in brief , 5l of the resuspended dna was added to an amplification mixture containing 2l of 10x pcr buffer for each sample , 0.5l dntp , 0.2l for each of outer primers , 0.3 l ( 1.5u ) of taq polymerase ( roche , usa ) and 11.8 l water ( total volume of 20 l ) . the pcr profile was an initial 3 min denaturation at 94c , followed by 35 cycles of amplification including denaturation for 45 s at 94c , annealing for 60 s at 53c , and extension for 90 s at 72c . a 1l of the first round pcr products was then used for the second round pcr under the same condition but with the inner primers and water was 15.8l . pcr products were analyzed by horizontal gel electrophoresis on 2% agarose gel in tae 1x buffer at 85 v/1h . a single 585 bp band was preserved in all cases after the second pcr . a total of 99 thalassemic children with mean age 7.22.56 ( range 3 to 12 ) years consisting of 55 males and 44 females were investigated in this study . depending on patients ' status , the average blood transfusions in these children was 3 - 4 times per year . 89 ( 89.9 % ) children were anti - hbs positive ( responders ) and 10 ( 10.1% ) anti - hbs negative ( non - responders ) ; 6 of them were in age group 1 - 5 , and 4 in age group 6 - 10 year - olds . 1 ( 1.01% ) was hbsag positive and 3 ( 3.03% ) were anti - hbc positive ; all of them were in age group 6 - 10 year - olds . hbv dna was not shown in any of cases and none of them was ( hbv- dna ) pcr positive ( table 1 ) . markers of hbv infection in thalassemic patients on the basis of the immune status , the thalassemic patients were classified into 4 categories : 87 ( 87.87% ) were immune to hbv via vaccination , 2 ( 2.02% ) were immune to hbv via natural disease ( past infection ) , 1 ( 1.01% ) was carrier of hbv and 10 ( 10.1 ) were not immune to hbv ( table 2 ) . immune status of thalassemic patients with hbv infection there was no meaningful association between sex and age with anti - hbs response , hbs ag and anti - hbc in our study . thalassemic patients are considered to be one of the high risk groups suffering from post - transfusion viral infection such as hbv . several studies with controversial results regarding immunity level and duration of acquired immunity from hepatitis b vaccination have been performed in different countries . in a study on children in china , serum anti - hbs was 75% within 2 years of vaccination and decreased to 48.2% , 7 years post vaccination . in taiwan , 15 years after the vaccination of neonates , 75% were anti - hbs positive , but the level was not determined . the rate of seropositivity of anti - hbc was 2.9% . in a study on 150 vaccinated children between 1 - 4.5 years of age in our country , 136 children were anti - hbs positive and 14 cases were anti - hbs negative . in a study in iran , there was no difference between the immune response of the two sexes , but in others , the immune response in females was more than that in males . the reason could be related to differences in average weight of girls and boys . in kerman , iran , from 215 children with major thalassemia , 34.8% were no responders and the remaining were either low or good responders . in a study in south khorasan province , of 38 children with major beta - thalassemia , 16 patients ( 42.1% ) were anti - hbs positive and 22 patients ( 57.9% ) anti - hbs negative . in our study , 89.9% of these children were hbs anti - body positive ( responders ) and 10.1% negative ( non - responders ) . this study is in close agreement with the study which has reported on 150 vaccinated children between 1 - 4.5 years of age . in the same group , when the anti - hbs titer falls to less than 10miu / l hbv infection may occur but this is always subclinical and usually without detectable serum hbsag . the suspected poor response to hepatitis b vaccine in these children , is due to their immunological abnormalities and frequent transfusion therapy ( such as iron overloading ) . anti - hbc alone may be present in relatively high titers after the disappearance of anti - hbs and indicating recent infection . anti - hbc is the only anti - body detected after self limited infections in 10% of patients , who never acquire detectable anti - hbs . in addition , anti - hbc is produced in person exposed to hbv and may be a good marker of past hbv infection . in one study in india , from 70 children with thalassemia , 75.7% had titers exceeding 10iu / l ( responders ) and 24.3% were non - responders . the seroprevalence of hbv marker ( hbsag and anti - hbc ) was 5.7 % and 20% . hbv dna was detected in 22 of 70 ( 31.4% ) of these thalassemic children . in a study in south khorasan province , none of these patients were positive for hbsag and anti - hbc anti - body . in our study , 3.03% of our samples were anti - hbc positive and 1 ( 1.01% ) was hbsag positive ( carrier of hbv ) but none of them was hbv dna positive . these results showed that in iran the prevalence of hbv infection in beta thalassemic patients is lower than in general population . in our study in a region with intermediate hbv prevalence , we have shown frequency of anti - body response to hbv vaccine in a cohort of thalassemic children . 89.9% of these children were hbs anti - body positive and 10.1% negative . a recent study on 416 vaccinated thalassemic patients ( mean age 25.6 yr ) who had low titer of hbsab and received a booster dose showed that the numbers of positive vicinal patients have been increased from 46.9 % to 69.4% . also , in close agreement with our study , this report revealed that response rate to vaccination was more than 95% after complete course ( 3 doses ) in healthy individuals but failure to fulfill vaccination seems a problem in chronic transfused patients . therefore , additional studies such as screening of thalassemic pediatric patients should be strictly followed to determine the efficacy of vaccination to protect these patients from hbv infection . to challenge with hbv , it is necessary to measure anti - hbs antibody level and according to their need , booster dose vaccination should be given especially in a high - risk group like thalassemic children . in our study , there are a few limitations . the sample size was limited to patients who were referred to our lab and all sickle thalassemia and alpha - thalassemia patients were excluded from this study . there was little information about ferritin level and liver enzymes which indicated an iron load in thalassemic patients . in addition , many factors such as genetic features , hla structure and t cell subgroups may influence response to the hepatitis b vaccination . our results have revealed that hepatitis b vaccine is highly immunogenic for children with thalassemia and particularly well tolerated . according to our findings most thalassemic patients ( 87.87% ) were immune to hbv ( responders ) and 10.1 % of them were not immune to hbv ( non - responders ) . however , in non - immune to hbv ( non - responder ) revaccination is recommended .

objectivein thalassemic children , hbv infection is common , thus immunization against hbv will reduce and prevent the rate of infection . the aim of this study was to evaluate the efficacy of hbv immunization and the prevalence of hbv infection in beta - thalassemic children in tehran.methodsto assess the efficacy of immunization and determine the immune response of children with beta - thalassemia , sera of 99 children who had received three doses ( 10/20 g ) of recombinant hbv vaccine in months 0 , 1 , 6 , were selected and tested for hbsag , hbsab and anti - hbc by elisa method . also , these sera were tested for hbv dna using nested - pcr method.findingsin 99 beta - thalassemic children , 89 ( 89.9 % ) were anti - hbs positive ( responders ) and 10 ( 10.1% ) anti - hbs negative ( non - responders ) . 3 ( 3.03% ) were anti - hbc positive and 1(1.01% ) was hbsag positive . hbv dna was not detected in any of them.conclusionour results have revealed that hepatitis b vaccine is highly immunogenic for thalassemic children and particularly well tolerated .

sweet disease , which is also known as acute febrile neutrophilic dermatosis , is a multisystemic inflammatory disease that was first described in 1964 ( 1 ) . it is characterized by fever , peripheral neutrophil leukocytosis and tender erythematous skin lesions that heal without scarring . the skin lesions of sweet disease are commonly asymmetrical and are predominantly located on the face , neck and upper extremities ( 1 ) . cutaneous manifestations of the disease may be preceded by a fever lasting from several days to weeks ( 2 ) . skin biopsies of cutaneous edematous erythematous plaques reveal deep dermal infiltration of mature neutrophils and the absence of vasculitis ( 3 ) . several cases of sweet disease with cns involvement have been reported ( 47 ) and neuro - sweet disease ( nsd ) has been proposed as a novel concept ( 8) . although the aetiology of nsd remains elusive , it has previously been suggested that nsd is a distinct clinical entity that may account for various cases of idiopathic encephalitis or meningitis ( 8,9 ) . systemic corticosteroid therapy is highly effective for the treatment of the majority of the neurologic symptoms detected in patients with nsd ( 7,10,11 ) . it may be useful to classify nsd as benign , however , there is a high frequency of symptom relapse ( 8,9 ) . in the present case report , a rare case of nsd with normal brain magnetic resonance imaging ( mri ) and positive modified acid - fast staining of the cerebrospinal fluid ( csf ) . the patient 's meningitis and skin lesions were successfully treated with systemic corticosteroids , and antiviral and anti - tuberculotic combination therapy . in july 2013 , a previously healthy 30-year - old chinese man presented with headache , neck stiffness and fever at the first affiliated hospital of xi'an jiaotong university ( xi'an , china ) . although these symptoms were alleviated following treatment with antibiotics , including 1 g compound polymyxin b ointment ( zhejiang reachall pharmaceutical co. , ltd . , zhejiang , china ) administered thrice daily and 3.75 g intravenous mezlocillin sodium and sulbactam sodium ( shanxi c&y pharmaceutical group co. , ltd . , datong , china ) two days later , the patient 's headache and neck stiffness symptoms had worsened and intermittent fever ( 3839c ) persisted . nodules subsequently developed on the patient 's face , neck and chest ; therefore , antiviral drugs , including 0.3 g ribavirin granules ( sichuan baili pharmaceutical co. , ltd . , jinjiang , china ) every 4 h , . were administered for a presumed herpes zoster infection ; however , the symptoms did not improve . the patient was then admitted to xijing hospital ( xi'an , china ) on 22 july , 2013 . upon physical examination , raised tender erythematous plaques were detected on the face , neck and upper trunk of the patient . 1 ) . routine laboratory tests revealed the patient 's white blood cell ( wbc ) count was 10.3610/l ( normal range , 3.59.510/l ) with 82.4% neutrophils , the erythrocyte sedimentation rate ( esr ) was 99 mm / h ( normal range , 020 mm / h ) , and the serum c - reactive protein ( crp ) level was 132 mg / l ( normal range , 05 mg / l ) . serological tests demonstrated that the patient was positive for antibodies to epstein - barr virus ; whereas tests for antibodies to hepatitis b and c viruses , human immunodeficiency virus and treponema pallidum were negative . the lipopolysaccharide ( lps ) level was 289 pg / ml ( normal range , 010 pg / ml ) and the 1,3--d - glucan level was within the normal range . extensive autoimmune screening revealed that the patient was positive for antinuclear antibodies , however he did not present with any of the typical symptoms of either systemic lupus erythematosus , mixed connective tissue disease , rheumatoid arthritis or dry syndrome ; therefore this result was considered insignificant . a subsequent lumbar puncture demonstrated a pressure of > 300 mmh2o , and cytological analysis indicated that the csf contained 80 leukocytes / mm ( 83% lymphocytes ; 8.5% mononuclear cells ; 6% neutrophilic cells ; and 2.5% plasma cells ) . these results were outside of the normal range and were outside of the normal range , suggesting inflammation in the patient 's central nervous system . immunoglobulin ( ig)m levels were raised at 2.69 mg / l ( normal range , 01.0 mg / l ) , which indicated possible acute viral meningitis . a modified acid - fast stain test was performed on the csf sample according to the staining methods described by feng et al ( 12 ) , which gave a positive result ( fig . tests for antibodies against common viruses were negative , and subsequent brain mri , electroencephalogram and x - ray examination of the chest did not detect any abnormalities . since these results initially suggested the patient was suffering from viral meningitis , intravenous ganciclovir ( 750 mg / day for 15 days ) and dexamethasone ( 20 mg / day for 5 days , then 10 mg / day for 5 days ) was administered , followed by oral prednisone acetate tablet ( 40 mg / day , gradually tapered by 10 mg weekly ) . on 25 july 2013 , a biopsy was taken from one of the erythematous plaques on the left side of the patient 's neck . the tissue sample was paraffin - embedded and serial 3 m - thick sections were cut and subsequently stained with hematoxylin and eosin . furthermore , the positive csf modified acid - fast stain result indicated infection with mycobacterium tuberculosis ; therefore the patient received anti - tuberculotic therapy whilst the results of the skin biopsy were awaited . anti - tuberculotic therapy included 0.45 g rifampicin capsules ( q.d . ) , 0.5 g pyrazinamide tablets ( both chengdu jinhua pharmaceutical co. , ltd . , tianjin , china ) via an intravenous drip , ganciclovir ( hidragon pharmaceutical co. , ltd . , following 3 days of treatment , the fever was alleviated , and a second lumbar puncture indicated a pressure of 225 mmh2o , and csf analysis detected 27 leukocytes / mm ( 96.5% lymphocytes ; 3.5% mononuclear cells ; and 0% neutrophilic cells and plasma cells ) . the igm level was low at 1.22 mg / l , and the csf modified acid - fast stain was negative . the wbc count was 8.9010/l ( 70.2% neutrophils ; 26.5% lymphocytes ; 3.1% monocytes ; and 0.2% eosinophils ) , lps was < 5.00 pg / ml , and the esr and crp levels had decreased to 40 mm / h and 0.92 mg / l , respectively . these clinical findings indicated that treatment was effective and the patient was recovering well . subsequently , the skin biopsy demonstrated massive infiltration of neutrophils into the dermis and dermal edema without vasculitis ( fig . furthermore , human leukocyte antigen ( hla ) typing indicated the patient was positive for cw1 and negative for b51 . cw1 and b51 hla typing is often used for differential diagnosis of nsd ( positive cw1 and negative b51 ) from neuro - behet disease ( nbd ) ( positive b51 ) ( 9 ) . the differences between nsd and nbd are as follows : 1 ) both sexes are evenly affected by nsd , whereas men are affected ~3.4 times as frequently as women with nbd ; 2 ) individuals aged 3070 are most commonly affected by nsd , whereas nbd preferentially affects those aged 2040 ; 3 ) in nsd , any region of the cns may be involved without site predilection , resulting in various neurological symptoms , whereas the basal ganglia and brainstem are preferentially affected in nbd ; 4 ) some patients with nsd demonstrate ocular signs , including episcleritis and conjunctivitis , whereas uveitis is common in nbd ; and 5 ) there is a strong hla - cw1 and b54 association in nsd , whereas there is a high frequency of hla - b51 in patients with nbd ( 9 ) . as a result of the clinical features , csf analysis and hla typing , the patient was discharged following 17 days of hospitalization , at which point his headache and neck stiffness were alleviated and the erythematous plaques had receded without scarring . the patient was subsequently followed - up as an outpatient , and he remains well on a tapering dose of prednisone acetate tablets , oral aciclovir ( 300 mg / dose , 3 times / day for 6 days ) and anti - tuberculotic drugs ( for 3 months ) . at 15-month follow - up , the patient demonstrated no recurrence of symptoms or erythematous plaques . the patient presented with clinical features of viral meningitis and the cutaneous manifestations of classical sweet disease . although the brain mri was normal , which has rarely been demonstrated in previous patients with nsd ( 4,9,1316 ) , the present patient fulfilled all the essential points of the diagnostic criteria for nsd , including : i ) high fever of 3840c ; ii ) painful and dull red erythematous plaques on the face , neck and upper part of the trunk ; iii ) neutrophilic infiltration of the dermis without uveitis ; iv ) positive hla - cw1 and negative hla - b51 ; and v ) good response to corticosteroid therapy ( 8) . combination therapy with corticosteroids and antiviral agents was initiated due to suspected viral meningitis , prior to the final diagnosis of nsd . in addition to corticosteroids and antiviral therapy , anti - tuberculotic agents were also administered as the csf modified acid - fast stain was positive , which suggested that the patient was concurrently suffering from an endogenous infection of m. tuberculosis and , therefore , corticosteroid administration would have lead to the spread of m. tuberculosis . the patient responded well to these drugs . given the rarity of nsd , it is understandable that the correct diagnosis was not immediately achieved . the present case reinforces the value of an early skin biopsy in order to confirm the diagnosis , avoid unnecessary therapy , allow the prompt initiation of the appropriate treatment and achieve successful therapeutic management .

neuro - sweet disease ( nsd ) is sweet disease with central nervous system ( cns ) involvement . to the best of our knowledge , the present case report is the first to describe nsd complicated by endogenous infection with mycobacterium tuberculosis . the present case report describes a male patient who developed nsd - induced meningitis , which initially manifested as a fever , headache and neck stiffness . painful erythematous plaques subsequently developed on his face , neck and upper trunk . brain magnetic resonance imaging was performed and the results were normal , whereas modified acid - fast stain analysis of the cerebrospinal fluid ( csf ) provided a positive result . the patient was thus diagnosed with viral meningitis and tuberculosis . however , subsequent skin biopsy results demonstrated neutrophilic infiltration into the dermis without vasculitis , and subsequent human leukocyte antigen typing was positive for cw1 and negative for b51 and the patient was diagnosed with nsd . following treatment with corticosteroids , and antiviral and anti - tuberculotic agents , the clinical symptoms were reduced and the previously abnormal findings in the csf examinations and associated laboratory data were improved . the present case indicates that the diagnosis of nsd is not easily achieved , and early skin biopsy is vital to ensure a fast and effective diagnosis . in addition to systemic corticosteroids , comprehensive treatment is also recommended for patients with nsd complicated by additional complex medical problems .

one of the major challenges of teaching is finding an approach to increase students level of understanding and learning ( 2 ) . various teaching techniques have resulted in different outcomes . from more than half a century , teaching behavior reflects the beliefs and values of the teacher in teaching and learning activities ( 3 ) . it is documented that students preserve about 20% of items taught during a 45-minute lecture , but active participation of students in the learning process would increase the level of students understanding . as an example , using a cooperative - learning technique is found to be significantly effective in increasing the students level of understanding and learning ( 4 ) . the effects of frequent examinations and quizzes on science teaching and learning have been surveyed at different educational levels from elementary schools to universities . this method can have favorable effects in the earlier detection of the students ' errors and in raising and maintaining high standards of learning attainment ( 5 ) . quizzes and assignments , as teaching aid equipment , can provide appropriate feedback and error correction for students during educational courses ( 6 ) . the quiz is a tool for encouraging and monitoring the progress of students , especially when they are taken frequently . it may also have desirable effects such as improving academic achievement , reducing anxiety , augmenting the student - professor communication , and decreasing the study time for the final exam ( 7 ) . conversely , in some cases it can increase the students ' anxiety , and in other cases may have poor or negative effects on the learner 's performance ( 6,8,9 ) . similar to the other areas of higher education , the learners in the field of medical sciences are considered as the core . through active participation in the educational processes , they would acquire the desired education , and by attaining knowledge , attitudes and necessary expertise , they achieve certain professional skills to serve the community ( 10 ) . owing to the importance of the aforementioned points in taking frequent examinations and quizzes for improving the students performance , and on the other hand considering the controversial effects of this technique on the final grades of students , as well as the difficulty of taking and correcting frequent quizzes for the instructors , we aimed to assess its effectiveness in a representative sample of iranian medical students . this experimental study was conducted in 2009 to perform research in the field of education in the kurdistan university of medical sciences , iran . the study comprised all the 42 fifth - semester medical students taking the parasitology module ; 5 of them were excluded because of their recurrent absences or their previous failure in this course . the course consisted of two topics of helminthology and protozoology , in which the basic information were provided about different types of protozoa and worms . in accordance with the course syllabus , it was presented in numerous sessions during the fifth semester of the basic medical science education . initially , in the teaching of helminthology , ten routine sessions were handled with lectures and interactive questions and answers . then at the beginning of the protozoology topic in the beginning of all of the next 9 sessions , the students were informed that they will have a quiz at the end of each session . the quiz consisted of one or two essay questions about the subjects taught in the session , and the score was applied to the students ' final grades . according to the sequence of discussions and number of the sessions , five quizzes were taken from the protozoology topics . quiz sheets were corrected and the scores were kept until the end of the academic semester . in the final exam , two series of questions about the topics of helminthology and protozoology were designed and implemented . questions consisted of multiple - choice questions , short essays , and false - true questions . the final results obtained from the two topics of helminthology and protozoology , and also the results and scores from the quizzes were compared using paired t and repeated measure tests . data analysis was conducted by spss software , version 14.0 ( spss inc . , chicago , illinois , usa ) . the final results obtained from the two topics of helminthology and protozoology , and also the results and scores from the quizzes were compared using paired t and repeated measure tests . as presented in table 1 , the mean final scores in the topics of protozoology , taken with the frequent quizzes during the semester , was not significantly different from that of the helminthology topics ( 10.45 2.75 vs.11.25 2.56 on the scale of 20 , respectively , p=0.13 ) . likewise , there was no significant difference in the mean score of the five quizzes ( 9.163.55 ) compared with the mean final examination score of protozoology ( 10.452.75)(p=0.1 ) ( table 2 ) . table 3 shows that the overall mean scores in the topics of helminthology ( 11.252.56 ) , protozoology ( 10.452.75 ) , and the quizzes ( 9.163.55 ) had significant differences ( p<0.001 ) . in this study , taking frequent quizzes was not associated with higher final scores than the regular training technique . this finding is not consistent with some previous studies ( 3 - 7,11),which showed positive effects on the students learning . a study on iranian dentistry students with four methods of the problem - based learning , film screening , lectures , and frequent quizzes showed that the final score was higher in the group with frequent quizzes compared with the group taught by the lecture method ( 5 ) . in another study conducted among nursing students in iran , repeated oral quizzes were more effective than the lecture method in increasing the scores , and in enhancing the students satisfaction from the learning contents ; though it increased the students anxiety ( 3 ) . a study in the us showed that the performance of medical students increased significantly by taking oral quizzes after group discussion at the end of the class ( 4 ) . the effect of group discussion on the favorable results of this study should be taken into account ; we did not use this method in the current study . in a study among medical students in croatia , obtaining daily quizzes , consisting of 10 questions , increased the final scores and the success rate of passing the course ( 11 ) . compared with our findings , the higher number of quizzes and questions might have been the reason for the effectiveness of this method in that study . our findings are consistent with some previous studies showing limited or no effect of taking frequent quizzes . in the study conducted among 227 introductory psychology students in the us the feedback provided through the pre - test did not show any effect on increasing the general knowledge of the students ( 4 ) . in this study , the quizzes were conducted as pre - tests , but in our study they were taken immediately at the end of the teaching sessions . in a project , for getting a professional doctoral degree in education , three methods of conventional education , quiz with prior notification ( announced quizzes ) , and quiz without prior notification were implemented for high school students of economy . it showed that obtaining the quizzes had no effects on improving the students ' economy scores ( 9 ) . the participants in the survey were high school students , with different levels of mental maturity and motivation compared with the university students in our study . in a study among undergraduates in the us , conducting announced quizzes did not improve the final exam scores of the students in the psychology course , although it increased the presence of the students in the classroom and their better preparation for the exam ( 8) . in our study , the students viewpoints were not investigated . a study on 287 college men , which used different measures of baseball performance for predicting the overall performance of professional baseball players , showed that confidence in judgment increased with practice and efforts ( 12 ) . the problem of judgment bias should be also taken into account ; it is documented that poor performance of students on a test can be because they may be more overconfident regarding their answers to hard questions , particularly those they answer wrongly , than are students who achieve better ( 7 ) . the lack of effectiveness of frequent quizzes in our study may be because the students believed that by taking the quizzes , they were more ready for the topic of protozoology , so they spent most of their time to study the helminthology lessons , and therefore got better scores in the final exam . it can also be suggested that students had less attraction and attention to the protozoology topics than to the helminthology topics . another possible reason may be the easier learning of the subjects of helminthology than the protozoology discussions . although from our points of view , we had considered the resemblance in course contents , in complexity of the lessons and teaching methods for the students attraction toward the lesson , as well as in the design and scoring of the questions in the final exam ; and taking all these similarities into account is our study strength . however , the non - effectiveness of our teaching method could be due to limitations such as the contents of the discussions , the small number of quizzes , the small sample size , as well as the different types of questions in the quizzes and the final exam , i.e. essay versus a variety of multiple choice questions . the lack of effectiveness of frequent quizzes in our study may be because the students believed that by taking the quizzes , they were more ready for the topic of protozoology , so they spent most of their time to study the helminthology lessons , and therefore got better scores in the final exam . it can also be suggested that students had less attraction and attention to the protozoology topics than to the helminthology topics . another possible reason may be the easier learning of the subjects of helminthology than the protozoology discussions . although from our points of view , we had considered the resemblance in course contents , in complexity of the lessons and teaching methods for the students attraction toward the lesson , as well as in the design and scoring of the questions in the final exam ; and taking all these similarities into account is our study strength . however , the non - effectiveness of our teaching method could be due to limitations such as the contents of the discussions , the small number of quizzes , the small sample size , as well as the different types of questions in the quizzes and the final exam , i.e. essay versus a variety of multiple choice questions . frequent announced quizzes had no significant effects on increasing the medical students ' motivation and learning . it is possible that this method did not increase the attractiveness of students , their learning , and improvement of their final scores just in this course . given the dissimilarities of our findings with some other studies , we recommend to conduct further investigations in this field by studying the effects of the quizzes on the same and exactly equal topic but in the different groups of students .

backgroundthe effect of frequent examinations on the students learning has had inconsistent results . this study aimed to assess the effectiveness of frequent announced quizzes on the learning of a representative sample of iranian medical students.methodsthis experimental study was conducted among 37 fifth semester medical students who had taken the course in protozoology and helminthology , in which the same basic information were provided about different types of protozoa and worms . initially , in the teaching of helminthology , ten routine sessions were handled with lectures and interactive questions and answers . then at the beginning of the protozoology topic in the beginning of all of the next 9 sessions , the students were informed that they will have a quiz at the end of each session . at the end of the semester , the total scores of quizzes were compared with the mean final scores of protozoology and helminthology using paired t and repeated measure tests.resultsthe mean final scores of the protozoology lesson were not significantly different from that of the helminthology ( 10.45 2.75 vs.11.25 2.56 on the scale of 20 , respectively , p=0.13 ) . there was no significant difference in the mean score of the five quizzes compared with the mean final term score of protozoology . the overall mean scores in the helminthology lesson ( 11.252.56 ) , protozoology lesson ( 10.452.75 ) , and the quizzes ( 9.16 3.55 ) were significantly different ( p < 0.0001).conclusionfrequent announced quizzes were not effective on increasing the medical students motivation and learning .

it presents with a wide spectrum of clinical manifestations ranging from inapparent infection to fulminant and fatal disease . the clinical spectrum of the disease may be an influenza - like fever to a serious presentation like weil 's syndrome , which is characterized by hepatic , renal , neurological , and hematological abnormalities . it is uncommon for leptospirosis to present as a primary neurological disease ( neuroleptospirosis ) . leptospirosis is a worldwide disease with predominance in tropical , rural areas and its presentation in combination with paraparesis and weil 's syndrome is uncommon . a thorough knowledge of clinical manifestations is especially valuable in communities that lack diagnostic facilities and hence the need for clinical judgment and suspicion is paramount . a 28-year - old male patient presented to the emergency department with a history of fever , diarrhea of five days duration , icterus , oliguria , breathlessness , edema of the legs , and bilateral lower limb motor weakness of one day duration with no sensory or bladder involvement . clinical evaluation revealed pitting edema legs , icterus , sinus tachycardia ( pulse:120/min . ) , tachypnoec ( respiratory rate:32/min ) normotension ( blood pressure 120/80 mm hg ) , bilateral basal rales on auscultation , paraparesis ( grade 1/5 motor power ) , and no sensory or bladder abnormalities . examination of the higher functions , cranial nerves , and cerebellar systems did not reveal any remarkable findings ; there were no meningeal signs . deep tendon reflexes , sensory system plantar response were normal . for further management and evaluation patient was transferred to an intensive care unit ( icu ) . urine analysis showed proteinuria ( 2 + ) , a few red blood cells and occasional pus cells . the hemoglobin level was 12.5 g / dl , total leukocyte count was 6800 cells / cubic mm , and the platelet count was 75000/cubic mm . renal function tests revealed severe renal failure ( blood urea : 198 mg / dl , serum creatinine : 4.8 mg / dl , sodium : 152 meq / l , potassium : 6.9 meq / l ) . liver function tests showed a total bilirubin : 8.8 mg / dl ; direct bilirubin : 4.7 mg / dl , aspartate aminotransferase : 201 u / l , alanine aminotransferase : 167 u / l , alkaline phosphatase : 57 u / l , serum total protein : 5.6 g / dl , and albumin : 2.6 g / dl . also observed were corrected serum calcium : 8.8 mg / dl , phosphorus : 4.5 mg / dl , serum creatinekinase : 670 u / l and serum lactate dehydrogenase : 142 u / l . urine and blood cultures were sterile . serum immunoglobulin m ( igm ) antibodies for leptospira were done , detected by enzyme linked immunoassay . titer of igm antibodies for leptospira was 60 u / ml , which was significantly high and positive ( < 15 u / ml : 15 - 20-intermediate : > 20 positive ) . the kidneys were echogenic and bulky on ultrasonography while computed tomography of the brain was normal . arterial blood gas analysis ( abga ) was favoring metabolic acidosis with ph of 6.9 spo2 : 96% pao2 : 82 mmhg , paco2 : 35 mm hg , hco3:8 t wave suggestive of hyperkalemia chest radiograph pa view : bilateral mid and lower zone diffuse infiltrates considering his oligouric acute renal failure , metabolic acidosis and ecg changes of hyperkalemia , the patient was admitted in an icu . in the icu the patient underwent hemodialysis for acute renal failure and to control hyperkalemia at the earliest to avoid life - threatening cardiac arrhythmias . nerve conduction velocity ( ncv ) studies were suggestive of bilateral lumbosacral polyradiculopathy with no evidence of myopathy on electromyography ( emg ) . cerebrospinal fluid ( csf ) study was done which showed no cell with normal sugar and proteins level and no organism on staining . considering the ncv findings and persistence of paraparesis even after correcting hyperkalemia , the high possibility of leptospirosis manifesting with weil 's syndrome and paraparesis was strongly favored . patient 's hyperkalemia was corrected with glucose insulin drip and hemodialysis in the initial 24 h. hypernatremia with water deficit was corrected slowly over 48 h with 5% dextrose . care was taken to prevent patient from landing up with hepatic encephalopathy by providing carbohydrate diet , lactulose bowel wash , avoidance of protein diet etc . patient 's renal functions started improving after nine days as evidenced by increase in renal output and maintenance of creatinine without dialysis . patient received parenteral fluid depending on central venous pressure ( cvp ) monitoring and daily output chart . he was transferred to the general ward from the icu after the ninth day of admission . he was discharged in an ambulatory state with improved renal function and liver function with grade 5 motor power in both lower limbs after a period of 21 days . infection may be asymptomatic but can be fatal in 515% of all cases associated with hepatic , renal , neurological and hematological abnormalities . the other presentations are myeloradiculopathy , myelopathy , guillain - barr syndrome - like presentation , meningoencephalitis , intracerebral bleed , cerebellar dysfunction , iridocyclitis , and tremor / rigidity . paraparesis due to myelitis or radiculopathy is very rare.[24 ] in the study by panicker et al . myelopathy was seen in seven patients , myeloradiculopathy in seven , and guillain - barr syndrome - like presentation in three . panicker et al . , in their study mentioned only the prevalence of neuroleptospirosis and not its association with severe hepato - renal dysfunction ( weil 's syndrome ) . the patient in present case report can not be compared to the prevalence of paraparesis mentioned by panicker et al . the present case had paraparesis as a part of neuroleptospirosis along with weil 's syndrome . in contrast to the prevalence of paraparesis mentioned by panicker et al . , mathew et al . , in their study of 31 patients , reported no presentation with myelitis or myeloradiculopathy . sethi et al . , reported 11.6 % prevalence of neuroleptospirosis , but there was no case weil 's syndrome with paraparesis . it is characterized by fever , headache , myalgia , conjunctival congestion and a host of non - specific features that may include mild cough , lymphadenopathy , rash , anorexia , nausea , and vomiting . this phase is followed by a brief afebrile period of variable duration that , in turn , is followed by the immune phase of illness . the severe form of leptospirosis , also known as weil 's disease , is characterized by a fulminant course with rapid onset of hepatic and renal failure and high mortality . in an endemic area , leptospirosis is often confused with dengue fever and malaria due to the similarities of clinical features . therapy should be initiated on the basis of clinical judgment , as laboratory confirmation can be delayed by days and weeks or is unavailable in several regions and early institution of appropriate therapy is known to reduce mortality . poor prognostic markers in leptospirosis include hypotension , oliguria , hyperkalemia , and presence of pulmonary rales . other studies have reported dyspnea , white blood cell count greater than 12,900/mm , repolarization abnormalities on electrocardiograms , alveolar infiltrates , hemoptysis , metabolic acidosis , and thrombocytopenia as markers of increased mortality . this patient presented with sudden onset paraparesis rather than the common presentation of neuroleptospirosis that is aseptic meningitis . along with the paraparesis component of neuroleptospirosis the patient had acute renal failure with hyperkalemia and jaundice . serological igm antibodies were also used in other studies with good sensitivity and specificity.[911 ] the patient improved with antibiotics and dialysis support , and was discharged in an ambulatory state with improved hepatic and renal function . in reviewing the cause of the paraparesis ( leptospirosis vs. hyperkalemia ) , it may be logical to conclude that the paraparesis was secondary to the leptospirosis because of the slow improvement in motor function of both lower limbs despite the early correction of hyperkalemia by hemodialysis . neuroleptospirosis should be considered in the differential diagnosis of all neuroinfections with hepato - renal dysfunction , especially in endemic areas . clinicians need to be aware of the possibility of leptospirosis , even if the illness presents with unusual features like paraparesis . there should be a high degree of suspicion for proper diagnosis and early institution of treatment .

leptospirosis is an important emerging zoonosis with a worldwide distribution that is characterized by a broad spectrum of clinical manifestations ranging from inapparent infection to fulminant disease . leptospirosis has protean clinical manifestations . the classical presentation of the disease is an acute biphasic febrile illness with or without jaundice . unusual clinical manifestations may result from involvement of pulmonary , cardiovascular , neural , gastrointestinal , ocular and other systems . immunological phenomena secondary to antigenic mimicry may also be an important component of many clinical features and may be responsible for reactive arthritis . the presentation of paraparesis in combination with weil 's syndrome is rare . few cases were reported with leptospirosis and paraparesis in india and abroad . it is important to bear in mind that leptospiral illness may be a significant component in cases of dual infections or in simultaneous infections with more than two pathogens . here we are reporting a case of weil 's syndrome with paraparesis in 28-year - old male patient who was critically ill due to severe hepatorenal dysfunction and hyperkalemia .

although ultrasound guidance has rendered regional anesthesia safe and predictable , often its cost is considered a big bane by the hospital administration . hence , we conceptualized this study with the aim to compare the cost of ultrasound - guided brachial plexus blocks for upper extremity surgeries with the cost of general anesthesia ( ga ) for the same procedure . we hypothesized that the ultrasound - guided blocks would be more cost - effective than ga . we included patients who underwent upper extremity surgeries in our institute solely under ultrasound - guided brachial plexus blocks during the period from august 2012-august 2013 . the demographics of these ninety patients and their american society of anaesthesiologists grading were recorded . the type of surgeries and the approach to brachial plexus blocks were noted . the brachial plexus blocks were performed using ultrasound machine ( sonosite micromax ; sonosite inc . , bothell , wa , usa ) in awake patients . the procedure was explained to them in details and the block was conducted under strict aseptic precautions . eighty - nine patients were sedated with dexmedetomidine 0.5 g / kg / h and one patient received midazolam 0.05 mg / kg and fentanyl 1 g / kg . we noted the duration of each surgery . we estimated the cost of ga per hour in our institute [ table 1 ] . the cost of sevoflurane nitrous oxide , and ventilator ( anesthesia machine ) were added upon hourly basis . cost of general anesthesia for an hour ( in our institute ) we also calculated the cost required for usg - guided regional block and sedation . we excluded the cost of ultrasound machine but included the cost of local anesthetic drugs used , syringes , needles , and drugs used for sedation , such as bupivacine 0.5% ( rs 37 ) , lignocaine adrenaline 2% ( rs 34 ) , injection dexamethasone ( rs 9 ) , injection dexmedetomidine ( rs 150 ) , oxygen ( 30 rs / h ) , and syringes ( rs 100 ) . this cost was subtracted from the cost that would have been incurred if the surgery was done under ga . this benefit , when put up as the charge for the ultrasound machine per case gave us the duration in years , required to recover the cost of ultrasound machine . the cost of usg guided block was also evaluated as per type of surgery , type of block , and duration of surgery . analysis of variance ( anova ) was applied to compare mean benefits as per surgery , block , and duration . analysis of variance ( anova ) was applied to compare mean benefits as per surgery , block , and duration . of the 90 patients , 31 were american society of anaesthesiologists ( asa ) i , 48 were asa ii , 10 were asa iii , and 1 patient was asa iv . type of surgeries undertaken , their respective numbers , and benefit ( mean standard deviation ) per type of surgery are shown the benefit ( amount saved due to regional block or the cost difference between amount for ga regional anesthesia ) was statistically significant as the p = 0.004 . table 3 shows numbers and types of ultrasound - guided brachial plexus blocks and benefit as per block . table 4 shows the duration of surgeries and the respective benefits . numbers and types of ultrasound - guided brachial plexus blocks and benefits as per block duration of surgery and benefits as per duration total benefit of ultrasound - guided blocks as compared to ga per years = 323270.rough cost of usg machine = 10 lakhs ( approximately).recover cost of usg machine in about 3 years . total benefit of ultrasound - guided blocks as compared to ga per years = 323270 . benefits differed significantly as per the type of surgery , type of block , and duration of the surgery . with the cost benefit that we have obtained , for any concept to be viable in everyday practice , its economical aspect has to be considered . as per our study the economic benefit obtained from the ultrasound - guided block is in the range of rs 323,270/year . the cost benefits would increase if the number of surgery done with ultrasound - guided blocks increases and vice versa . the mean benefit shown for each type of surgery can be put up as the charge of ultrasound machine to recover the cost of ultrasound machine . with our results , it can be assumed that we can recover the cost of ultrasound machine in about 3 years if 90 upper extremity surgeries are performed successfully solely with ultrasound - guided blocks . here , we have assumed that the cost of ga in other institutes could be somewhat similar to that of ours . we analyzed benefits in terms of types and duration of surgeries and types of blocks separately . in our study , they all seem to be interrelated . the interscalene blocks ( n = 52 ) were given mainly for shoulder arthroscopic repairs ( n = 23 ) and shoulder replacements ( n = 7 ) , which also coincided with the longest duration of procedures . humerus fracture had a combination of interscalene ( main block ) and subclavian perivascular ( around 5 ml local anesthetic given ) . these surgeries took almost 33.5 h. fracture clavicle surgeries ( n = 2 ) also received interscalene but were of a relatively shorter duration . the combination of subclavian perivascular and infraclavicular blocks was mostly given for elbow surgeries that were of a relatively longer duration ; hence , table 2 depicts the cost of these blocks accordingly . the radius fracture and the wrist fractures were done under axillary or a combination of subclavian perivascular and axillary block . in general , it is not the type of the brachial plexus block that mattered but the duration of surgery undertaken with the block determined the cost benefit . in this study , we did not consider the cost of operation theater and the staff at all . this study compared the cost - effectiveness of interscalene ultrasound - guided blocks given for shoulder arthroscopies with ga . they either received block or ga . in our study , we had derived the cost of ga depending on the duration of the surgery . this was done after calculating the cost of ga for each hour in our institute . they investigated the following anesthesia - related times : ready for surgical preparation ( from arrival in the or until end of anesthesia induction ) , or emergence time ( from end of dressing until leaving the or ) , anesthesia control time ( from patient 's arrival in the or until readiness for positioning plus time from the end of surgery to patient 's discharge from the or ) , and postanesthesia care unit ( pacu ) time ( from patient 's arrival in the pacu to the eligibility for discharge to normal ward ) . . we did take into consideration the analgesia time rendered by the block in the postoperative period . in this study , they too had excluded the personnel costs from statistical analysis which is similar to us . the main difference is we estimated the period of amortization of the ultrasound machine which turns out to be approximately 3 years with our assumptions . of course , the period can be shorter if the number of surgeries increases and would be longer if the machine is more expensive than the cost we have considered . the retrospective nature of our study is one of the main limitations of this study . . it may not be always possible to keep track of them as they comparatively inexpensive and most casually used . in case , we have missed on them surely the difference is innocuous . it is important to know that the cost of ga almost repeats itself every hour , unlike regional anesthesia . from this study , we believe that ultrasound - guided regional anesthesia is cost - effective . this is besides the fact that ultrasound equipment can be used for several purposes such as venous cannulation and shared with other users too . the safety and predictability it renders to regional blocks can not be compared in cost . there were significant cost benefits using ultrasound guidance as compared to gabenefits differed significantly as per type of surgery , blocks , and durationthe cost of usg machine can be recovered in about 3 years . there were significant cost benefits using ultrasound guidance as compared to ga benefits differed significantly as per type of surgery , blocks , and duration the cost of usg machine can be recovered in about 3 years . investment in an ultrasound machine solely for regional anesthesia need not be considered as a big bane .

background and aims : the cost effectiveness of ultrasound - guided regional anesthesia is an issue which requires discussion . based on our experience , we hypothesized that this is an economically viable option.material and methods : in this retrospective study , we included 90 patients who underwent upper extremity surgeries in our institute solely under ultrasound ( usg)-guided brachial plexus blocks in a year . the cost of the block was derived by adding the cost of the material and drugs used for the block . this cost was subtracted from the cost that otherwise would have been incurred for general anesthesia ( ga ) of similar duration . this cost difference or benefit per case was then used to calculate the duration in years required to recover the cost of the ultrasound machine.statistics:data were analyzed using spss 15.0 . analysis of variance was applied to compare mean benefits as per surgery , block , and duration . ninety - five percent confidence interval for mean were calculated . level of significance was taken as p = 0.05.results:there were significant economic benefits using ultrasound guidance as compared to ga . benefits differed significantly as per the type of surgery , type of block , and duration of the surgery . with the cost benefit that we have obtained , the cost of usg machine can be recovered in about 3 years.conclusion:usg regional anesthesia is an economically viable concept . the cost benefit increases with the duration of a given surgery and increases with the number of blocks .

in addition to obtaining physical maturation with enhanced strength , speed , and fitness , puberty is also accompanied with emotional and cognitive changes . timing of puberty may be important in expecting longitudinal health risks like obesity and cancers in adulthood . longer exposure to steroidal hormones might increase the risk of steroidseries dependent cancers such as breast and ovarian cancers in women , and possibly prostate cancer in men . furthermore , increased rates of obesity in early developers might amplify oxidative stresses that in turn would exacerbate the risks for a range of cancers . true precocious puberty in girls is typically defined as the appearance of secondary sexual characteristics before the age of 6 years . during the past decades , secular trends of earlier age at onset of puberty different research studies have reported the reduction in the age of puberty around the world . precocious puberty in boys is generally defined as the appearance of secondary sexual characteristics before the age of 9 years . however , the rapid worldwide decrease in pubertal timing over the past decades clearly indicates that it should have an environmental etiology . significant diversities in the age of pubertal stages of girls living in various regions with different ethnicity and geographic characteristics are documented . moreover , obesity as an epidemic event has received special attention and is related both to early puberty and environmental factors . furthermore , changes in nutrition and dietary habits , physical activity , and exposure to endocrine disrupting chemicals ( edcs ) are possible factors influencing the maturation time of the reproductive system . edcs are natural and synthetic chemicals that would disturb the normal function of the endocrine system . these compounds interfere with normal hormonal function through influence on the activity of estrogen receptors . edcs are exogenous chemicals that usually imitate hormones , block hormonal action sites or trigger inappropriate hormone activity . different studies determined the role of some pollutants as polychlorinated biphenyls ( pcbs ) , polybrominated biphenyl ( pbb ) , dioxins , phthalates , etc . , on pubertal growth and its signs . these compounds are usually highly lipophilic and hydrophobic ; they accumulate sometimes to a high concentration in lipid - rich tissues . this study aims to systematically review the literature that assessed the associations of organohalogens and phthalates with the timing of puberty . we attempted to explore papers in which the associations of organohalogens exposure on pubertal signs have been reported . a literature search was done in following databases : embase , pubmed , scopus , isi web of science , and cochrane library from 1995 to january 2014 , with the major concentration on latest papers . the following keywords or their combinations were used : early puberty , precocious puberty , menarche , organohalogens , pcbs , dichlorodiphenyltrichloroethane , dichloro diphenyldichloro ethylene , organochlorine , dioxin , phthalates , girl , boy , children , adolescents . further studies were observed by a manual search through references of relevant manuscripts , relevant reviews , and consultation with experts in this field . search evaluation was done randomly by two independent researchers , and it was confirmed that all relevant studies were considered . two independent reviewers ( pp and ea ) determined the appropriateness of the study according to the prearranged criteria and subsequently extracted characteristics : related data of participants ( number , age , type of disorder ) , study features ( type , duration , applied intervention ) , measured parameters ( first menarche , breast development , testicular development , tanner stage signs , body size ) and outcomes . exposure to one or more than one organohalogens during childhood or adolescence.measurement of related criteria as first menarche , breast development , testicular development , tanner stage signs , body size.no history of using drugs or other determined compounds with the effects on endocrine systems . measurement of related criteria as first menarche , breast development , testicular development , tanner stage signs , body size . no history of using drugs or other determined compounds with the effects on endocrine systems . we attempted to explore papers in which the associations of organohalogens exposure on pubertal signs have been reported . a literature search was done in following databases : embase , pubmed , scopus , isi web of science , and cochrane library from 1995 to january 2014 , with the major concentration on latest papers . the following keywords or their combinations were used : early puberty , precocious puberty , menarche , organohalogens , pcbs , dichlorodiphenyltrichloroethane , dichloro diphenyldichloro ethylene , organochlorine , dioxin , phthalates , girl , boy , children , adolescents . further studies were observed by a manual search through references of relevant manuscripts , relevant reviews , and consultation with experts in this field . search evaluation was done randomly by two independent researchers , and it was confirmed that all relevant studies were considered . two independent reviewers ( pp and ea ) determined the appropriateness of the study according to the prearranged criteria and subsequently extracted characteristics : related data of participants ( number , age , type of disorder ) , study features ( type , duration , applied intervention ) , measured parameters ( first menarche , breast development , testicular development , tanner stage signs , body size ) and outcomes . exposure to one or more than one organohalogens during childhood or adolescence.measurement of related criteria as first menarche , breast development , testicular development , tanner stage signs , body size.no history of using drugs or other determined compounds with the effects on endocrine systems . measurement of related criteria as first menarche , breast development , testicular development , tanner stage signs , body size . no history of using drugs or other determined compounds with the effects on endocrine systems . exposure to one or more than one organohalogens during childhood or adolescence.measurement of related criteria as first menarche , breast development , testicular development , tanner stage signs , body size.no history of using drugs or other determined compounds with the effects on endocrine systems . measurement of related criteria as first menarche , breast development , testicular development , tanner stage signs , body size . no history of using drugs or other determined compounds with the effects on endocrine systems . the flowchart of the search is depicted in figure 1 . at first , 215 likely relevant articles were found . of those , 202 articles were removed by evaluating abstracts , and it was cleared that those papers could not meet the inclusion criteria of the current study . finally , 13 articles were selected to read their full texts and to determine the eligible articles to be included in this systematic review . flowchart and characteristics of studies included / excluded for review as aforementioned , 13 articles were selected according to the inclusion criteria . this review included 6572 participants in nine countries from three continents ( europe , north america , and asia ) . of these , seven studies had a cohort design , two were cross - sectional , one was retrospective , and three were case - control . the flowchart of the search is depicted in figure 1 . at first , 215 likely relevant articles were found . of those , 202 articles were removed by evaluating abstracts , and it was cleared that those papers could not meet the inclusion criteria of the current study . finally , 13 articles were selected to read their full texts and to determine the eligible articles to be included in this systematic review . as aforementioned , 13 articles were selected according to the inclusion criteria . this review included 6572 participants in nine countries from three continents ( europe , north america , and asia ) . of these , seven studies had a cohort design , two were cross - sectional , one was retrospective , and three were case - control . this review confirmed the effects of pollutants on maturation signs and pubertal stages and confirmed the association of organohalogens and phthalates with early puberty , notably in girls . such an effect may have short - term and long - term health effects , and warrants interventions to reduce these pollutants . it is an important stage of life with elevated increased risk of health and psychosocial problems . it is documented that an independent relationship might exist between early puberty and adult metabolic syndrome - related derangements both in males and females . this finding underlined that the mechanisms accelerating puberty may also contribute to adult metabolic disorders . we reviewed several articles from different areas of the world , and it is unanimous that variation in puberty timing trends is a global issue , both in developed and developing countries . though the age of puberty is related to different parameters including genetic factors , disorders and malformations of central nervous system , and some metabolic diseases , the important role of environmental pollutants and edcs should be taken into account . environmental pollutants including pbc , pbb , dioxin , and phthalates are widespread in different societies and have several adverse health effects . one of the important consequences of edcs is disturbing the normal process of puberty timing , especially their influence on early maturation in both sexes , particularly in girls . in boys , pollutants exposure is associated with reaching to genital stages earlier than normal time . in girls , a higher concentration of edcs in the body is associated with early menarche and breast development with or without growth of pubic hair . a recent review studied the trends of puberty and its relationship with environmental pollutants and concluded that the age at pubertal onset has been declining in the last two decades in usa and europe . thus , age at breast development is now going on 1 - 2 years earlier in comparison with previous studies . prominently , the age at menarche has changed by 0.3 - 0.6 years in the same period , signifying a prolonged duration of the pubertal transition and found that development of glandular breast tissue at much younger ages at short period of time are highly suggested to have environmental origins . weight status is associated with the pubertal age , given that environmental pollutants may increase the risk of overweight , therefore the decline in the age of puberty may be explained , at least in part , by excess weight due to exposure to some environmental pollutants . it should be acknowledged that in original studies included in the current review , the exact time and the duration of exposure were not considered ; moreover recall bias may exist in reporting the age of puberty . chronic diseases origin in early life , and it is well documented that exposure of children and adolescents to environmental pollutants is related with risk factors of noncommunicable diseases . furthermore , the age of puberty , which in turn might be related to exposure to environmental factors , is associated with chronic diseases . the findings of this review propose that organohalogens and phthalates are disturbing the normal process of puberty timing with special influence on early maturation in girls . the current decline in the age of puberty might be related , at least in part , to exposure to some environmental chemicals , and in turn it might increase the risk of noncommunicable diseases in the future . these findings underscore the necessity of implementing wide - ranging interventions to reduce the pollution burden for health promotion and disease prevention at the global level . all authors contributed in the study concept and design , in conducting the literature search , in drafting the paper and its revision . all authors approved the final version for submission , and accept the responsibility for the paper content .

background : early puberty is a common worldwide problem . different parameters as genetics , metabolic diseases , obesity , as well as environmental factors may affect the age of puberty . this systematic review aims to survey the related literature on the effects of environmental pollutants and especially organohalogens and phthalates on early puberty.materials and methods : a systematic review of papers published in the english language was completed in january 2014 . studies on the associations of organohalogens and phthalates with the puberty time were included . a literature search was conducted in embase , pubmed , scopus , isi web of science , and cochrane library from 1995 to january 2014 ; moreover manual search through references of relevant manuscripts was considered . the literature search identified 212 papers , of which 13 papers fulfilled the inclusion criteria of the current study . two reviewers independently identified relevant papers for potential inclusion and assessed the methodological quality.results:this review included 6572 participants in nine countries from three continents ( europe , north america , and asia ) . different studies determined the effects of pollutants on maturation signs and pubertal stages and confirmed the association of organohalogens and phthalates with early puberty.conclusion:based on the studied literature , environmental pollutants surround and accumulate in human societies and their adverse health effects are well documented . it can be concluded that organohalogens and phthalates are disturbing the normal process of puberty timing ; especially their influence on early maturation in girls should be underscored .

the irritable bowel syndrome ( ibs ) is a condition that afflicts 10 - 20% of the population with a variable combination of abdominal pain , bloating , constipation , and diarrhoea . to patients , scientists and doctors unfamiliar with recent research , it is a condition with no known cause , no animal models , no biomarkers , and no effective treatment . perhaps because of this , ibs , as well as other functional gastrointestinal disorders , are often perceived to be psychological disorders . however , recent studies on a subset of patients who develop ibs following an episode of gastrointestinal infection , has allowed us to articulate an inflammation - immunological model that has now been applied as well to other groups of ibs and also to functional dyspepsia . in this review , i will first present the research in post - infectious ibs that supports this model , and then draw attention to recent research that has implicated similar pathogenic factors in non - post - infectious ibs and functional dyspepsia . studies of pi - ibs have provided us with one of the best working model for understanding the aetiopathogenesis of ibs . in the early studies from sheffield , patients with acute gastroenteritis were followed prospectively to document the development of ibs and to identify predisposing factors . stress , as represented by the presence of recent traumatic life events , and a neurotic personality trait , were found to be the best predictors of who might develop ibs post - infection ( table 1).1 at 3 months post - infection , both , patients who had developed ibs and patients who were asymptomatic , demonstrated accelerated colonic transit and increased rectal sensitivity compared with uninfected controls , with the ibs patients having more severe disturbances.2 rectal biopsies were obtained from a number of patients to study inflammatory markers . comparing pi - ibs patients with post - infection controls and healthy non - infection controls , we found that ibs patients had relatively greater mucosal cellularity which we interpreted as an indication of a subcolitic inflammatory process . to further support a pathogenic role for inflammation , we demonstrated increased expression of pro - inflammatory cytokine interleukin 1m rna in rectal biopsies taken at 3 months post - infection in pi - ibs patients which was not observed in post - infection patients without ibs.3 putting all these data together we proposed a bio - psychophysiological model for pi - ibs . an episode of infectious diarrhoea may produce changes in the gastrointestinal physiology that predispose to the development of ibs symptoms like diarrhoea and pain . however , the manifestation of ibs develops when psychological factors exist in association with more severe inflammatory and physiological disturbances . conversely , this could also be used to explain why the majority of patients with psychiatric disturbances do not complain of ibs symptoms . spiller 's group from nottingham studied a group of patients with campylobacter jejuni gastroenteritis.4 serial rectal mucosal biopsies taken post - infection demonstrated increased counts of intra - epithelial lymphocytes and enteroendocrine cells at 2 weeks , that gradually normalised over 12 weeks , but appeared to persist in patients with pi - ibs . furthermore , pi - ibs patients had significantly elevated cd3 and cd8 lymphocytes . in these post - campylobacter patients , intestinal permeability was also observed to be increased at 6 weeks and 12 weeks post - infection , even in some patients who were asymptomatic . in a subsequent study from nottingham , it was reported that the intestinal permeability of pi - ibs subjects was increased in the proximal small intestine compared with controls , but this was not as severe as diarrhoea predominant ibs without a history of infection.5 in another series of pi - ibs , marshall and colleagues from ontario , canada , studied a cohort of patients involved in a large waterborne outbreak of gastroenteritis , and found increased intestinal permeability in those who developed ibs compared with non - ibs controls.6 in animal models , stress has been demonstrated to increase intestinal permeability with enhanced trans - epithelial passage of luminal antigens.7 in a recent study women exposed to moderate background stress ( in the form of recent life events ) , demonstrated a defective jejunal epithelial response ( increased albumin permeability ) to stimuli ( cold pain stress ) that could predispose them to gut mucosal inflammation ( increased luminal tryptase and -defensins release).8 a study from china followed a large cohort of patients who had presented with shigella dysentery between april and october 1998 , and their family members who had not suffered dysentery.9 biopsy specimens were taken from the terminal ileum and rectosigmoid regions . in post - shigella interestingly , they also found increased numbers of mast cells in biopsies taken from the terminal ileum of both pi - ibs as well as non - post infectious ibs ( non - pi - ibs ) patients , compared with controls . furthermore , in the samples from these ibs patients , both pi - ibs and non - pi - ibs , they observed an increased density of nerve fibres in the vicinity of mast cell collections . at the same time , in bologna , barbara et al . had demonstrated a correlation between abdominal pain and the proximity of mast cells to neurons in the distal colonic mucosa in a non - specific group of ibs patients.10 recently , in a study from korea involving a small number of pi - ibs patients , increased numbers of enterochromaffin cells , mast cells , and lamina propria t lymphocytes were also reported in biopsies taken from the rectum.11 the idea that ibs could be an inflammatory disorder has now been extended to other forms of ibs , and in particular diarrhoea predominant ibs ( d - ibs ) . chadwick et al , reported that almost 90% of a group of ibs patients ( 55% had d - ibs , 36% had pi - ibs ) showed evidence of immune activation regardless of the type of onset.12 the authors found higher numbers of cd25 cells in ibs patients compared with asymptomatic controls . cd25 cells are regulatory t cells that are considered important in the prevention of autoimmunity , as well in controlling inflammatory responses in the gut ; their absence in mice leads to spontaneous colitis . the increased presence of cd25 cells in ibs raises the possibility that there is auto- or exogenous antigen challenge in these patients , and that the cd25 cells are preventing the progression to a more florid inflammatory response . in another study involving d - ibs patients ( 30% with pi - ibs ) intra - epithelial cd3 lymphocytes were also found to be increased in jejunal biopsies.13 in addition , this group of d - ibs patients also presented evidence of mast cell involvement as evidenced by markedly increased mast cell numbers in the jejunal biopsies as well as higher jejunal fluid tryptase concentrations , when compared with healthy controls . in a study involving a highly selected group of ten severe ibs patients , full thickness biopsy was obtained from the jejunum laparoscopically and examined for and shown to have low grade infiltration of lymphocytes in the myenteric plexus.14 there is dynamic evidence of intestinal immune activation in ibs . ohman et al . from sweden provided evidence of an augmented cell - mediated intestinal immune response.15 peripheral blood lymphocyte were examined for t - cell expression of integrin 7 , while colonic biopsies were examined for endothelial expression of mucosal addressin cell adhesion molecule-1 ( madcam-1 ) , in samples taken from ibs patients ( 60% d - ibs ) , ulcerative colitis patients and asymptomatic patients with a negative colonoscopy for other indications . t lymphocytes that have been activated in gut - associated lymph nodes express integrin 7 which mediates homing to intestinal mucosa by binding to its endothelial expressed ligand madcam-1 . in this study ibs patients had an increased frequency of integrin 7 and madcam-1 resembling that seen in patients with ulcerative colitis . another study provides evidence of activation of the mucosal innate defence system by studying human defensins which are human antimicrobial protein induced by probiotic microorganisms and pro - inflammatory cytokines . in particular , human beta - defensin-2 ( hbd-2 ) has been reported to be expressed in active intestinal inflammation in ulcerative colitis ( uc ) . in the study by langhorst , faecal hbd-2 levels were measured by enzyme - linked immunosorbent assay ( elisa ) , while colonic biopsies were tested for hbd-2 peptides by immunohistochemistry.16 compared with healthy controls , patients with uc and ibs ( all of whom had diarrhoea ) were found to have elevated hbd-2 faecal levels , and in these patients beta - defensin 2 peptides were demonstrated in colonic epithelial enterocytes . these results support a pro - inflammatory response in ibs patients . in another recent study , liebregts et al . , examined peripheral blood mononuclear cell ( pbmc ) production of pro - inflammatory cytokines tnf- , il-1 and il-6 in ibs patients as a group compared with healthy controls.17 of particular interest was that patients with diarrhoea type ibs , of which pi - ibs formed a substantial number , demonstrated increased basal and escherichia coli ( e. coli ) lipopolysaccharide - induced production of tnf-. furthermore , there was a positive correlation of tnf- production with anxiety scores . as the production of cytokines is under genetic control , it is possible to study the role of genetics by evaluating the genotypes for various pro- and counter - inflammatory cytokines . two studies have reported lower frequency in ibs patients of genotypes promoting production of il-10 which is a counter - inflammatory cytokine.18,19 in one study , increased frequency of genotypes that promoted the production of tnf- , a pro - inflammatory cytokine , was reported in ibs patients.19 in this study , pi - ibs patients comprised 21% of the study group ; comparing pi - ibs with non - pi - ibs patients the frequency of genotypes for il-10 and tnf- appeared similar between the two groups . however , when comparing predominant bowel habits , d - ibs patients had significantly higher prevalence of tnf- producer genotypes . a recent study employing microarray expression profiling has identified differential expression of genes associated with the host mucosal immune response to microbial pathogens , between ibs patients and healthy controls.20 in 2002 , an outbreak of salmonella gastroenteritis occurred in a spanish village as a result of contamination of cream cakes from a bakery.21 when these subjects were followed up prospectively , it was found that salmonella gastroenteritis was a significant risk factor not only for ibs , but also for functional dyspepsia ( fd ) . furthermore , a substantial number of subjects had an overlap syndrome of ibs and fd . it was observed that while over time the number of subjects who had dyspepsia alone declined progressively , the number of fd - ibs subjects appeared to remain fairly stable . a paper from norway reported the outcome of an outbreak of waterborne giardiasis in bergen that occurred in 2004.22 out of a total of 1,300 symptomatic cases with giardia lamblia identified in stool samples , 139 had persistent symptoms despite several treatment courses . twenty - two post - giardia infection patients with ibs by rome ii criteria and 19 patients who had recovered from giardia infection after treatment with metronidazole , were enrolled into a meat soup gastric emptying study . the post - giardia ibs patients had lower drinking capacity and slower gastric emptying . in some patients sequential duodenal biopsies demonstrated microscopic inflammation that subsided with time despite the persistence of symptoms.23 in a long term follow - up study of 82 patients from this post - giardia ibs cohort , the authors reported that close to 60% reported exacerbation of their symptoms by specific foods.24 beyond these two well defined cohorts , studies of what is termed post - infectious functional dyspepsia ( pi - fd ) , are more limited , but nevertheless provides support for an inflammatory and immunological mechanism in the pathogenesis . in a recent study from belgium , duodenal biopsies were obtained from patients with presumed pi - fd and patients with unspecified fd ( u - fd).25 focal aggregates of t cells and focal cd8 aggregates were found in pi - fd but not in u - fd patients . furthermore , gastric emptying was studied , and found to be delayed in patients with these focal aggregates . in a study from shanghai , 550 patients with acute gastrointestinal infection were followed - up for half a year , and the prevalence of pi - fd was estimated to be 6.7% and epigastric pain , epigastric burning sensation , and early satiety were the major symptoms in these patients.26 in gastric biopsies from pi - fd patients , the number of activated mast cells , as evidenced by the total amount of tryptase and histamine released in the gastric mucosa , was reported to be higher than non - pi - fd patients and healthy controls . furthermore , the number of mast cells located within 5 microns of nerve fibers was significantly higher in pi - fd patients than in the other two groups . in a large study from sweden , duodenal biopsies were obtained from asymptomatic and symptomatic subjects drawn from a large community cohort offered screening gastroscopy.27,28 insufficient information was provided to determine the proportion of subjects with pi - fd . however , unusually , helicobacter pylori infection was significantly less common in their fd subjects than subjects with ibs criteria . in their cohort , fd subjects had duodenal eosinophilia compared to asymptomatic controls , and an association with early satiety was reported . these recent studies enable us to better conceptualise how immunological events may lead to the development of ibs and fd , and how environmental , genetic and psychological factors modulate the outcome . the hope is that with this more sophisticated approach we can overcome the prejudices associated with the psychosomatic model , and become better at identifying biomarkers , and at developing animal models and more effective treatments , in what were traditionally functional gastrointestinal disorders .

this review presents studies that support an inflammation - immunological model for the pathogenesis of post - infectious irritable bowel syndrome ( ibs ) , and highlights recent studies that support a similar disease model in non - post - infectious ibs , in particular , diarrhoea - predominant ibs , as well as in post - infectious functional dyspepsia . these recent studies are highlighted to demonstrate that one line of research in functional gastrointestinal disorders has moved away from the old psychosomatic concepts . it is hoped that this will encourage future students of this field to explore the role of immunological events .

stickler syndrome alternately known as hereditary arthro - ophthalmopathy is an inherited disorder of collagen formation manifesting itself through a spectrum of ocular , orofacial , auditory , and musculoskeletal abnormalities.1,2 the disease is relatively uncommon , with a reported incidence of one in 7,5009,000 births , and presents with highly variable signs and symptoms in affected individuals.3 this diversity of phenotypes reflects the heterogeneous mutations affecting the formation of types ii , ix , and xi collagen , which are integral to the structure and function of the vitreous , cartilage , and other connective tissues.4,5 specific ocular manifestations include high myopia , optically empty vitreous , open - angle glaucoma ( from dysgenesis of the anterior chamber drainage angle ) , cortical cataract , and perivascular retinal lattice degeneration with strong vitreous adhesions along the borders of these lesions.6 these vitreoretinal changes predispose patients to the development of giant retinal tears ( grts ) and associated rhegmatogenous retinal detachments ( rrd ) relatively early in life , often in the second and third decades of life.4,6,7 stickler syndrome is the most common inherited cause of rrd , in spite of its low incidence overall.8 given the low incidence of stickler syndrome , long - term data on surgical outcomes in patients with stickler syndrome are few : only two published studies have previously detailed the surgical treatment and outcomes of retinal detachment ( rd ) repair in patients with stickler syndrome.9,10 we reviewed the long - term anatomical and visual outcomes of rd in our cohort of patients with stickler syndrome who underwent surgical repair . this study is a retrospective , single - center , interventional , case series of patients with stickler syndrome undergoing surgery for rd . patients were screened via billing codes , surgical logs , and genetic testing and were seen during the period from january 1 , 2009 , through december 31 , 2014 . patient records were reviewed to confirm a diagnosis of stickler syndrome , and data collection was completed , as outlined later . patients were excluded if they did not have a confirmed diagnosis of stickler syndrome , if there were confounding causes for rrd ( eg , ocular trauma ) or confounding reasons for severe vision loss ( eg , end - stage glaucoma ) , or if they did not undergo surgery primarily for rd . the study was approved by the western institutional review board , and it complied with the health insurance portability and accountability act of 1996 and adhered to the tenets of the declaration of helsinki . the requirement to obtain informed consent from patients was waived due to the nature of the study . data collection included demographic information , details of surgical interventions , and multimodal retinal imaging including color fundus photography , fluorescein angiography , and optical coherence tomography . best corrected visual acuity ( bcva ) and anatomical outcomes were recorded pre - and postoperatively . snellen visual acuities were converted to the logarithm of the minimum angle of resolution units for statistical analyses . nonparametric paired significance testing was performed using the wilcoxon signed - rank test ; statistical tests were two - tailed , and significance was defined as p<0.05 . stata version 9.0 ( statacorp lp , college station , tx , usa ) was used for statistical analyses . sixteen eyes from 13 patients with stickler syndrome met the inclusion criteria , with three patients ( 23% ) undergoing bilateral surgeries for rd repair . the average age at the time of initial diagnosis with rrd was 10.4 years ( range : 1 month22 years ) , and the mean follow - up duration was 94 months ( range : 5313 months ) . mean visual acuity ( va ) at the time of presentation was 1.66 ( sd 0.86 ; snellen equivalent : 20/914 ) , which slightly improved at final evaluation to 1.60 ( sd 1.01 ; snellen equivalent : 20/796 ; p=0.81 ) . improvement in va was seen in five eyes ( 31% ) , while five ( 31% ) remained stable and six ( 37.5% ) experienced a decline . three eyes ( 18.8% ) had single retinal breaks , five eyes ( 31.3% ) had multiple breaks , and the remaining eight ( 50% ) had grts with at least 3 clock - hours of peripheral retinal involvement . the mean number of vitreoretinal surgeries required for retinal reattachment was 3.1 ( range : 113 ) . in eyes requiring multiple surgical interventions ( 13 of 16 eyes , 81.3% ) , the mean interval prior to redetachment ( after the primary intervention ) was 4.8 months ( range : 4 days36 months ) . six retinas ( 37% ) were attached without silicone oil tamponade , while the remaining ten retinas ( 63% ) were attached utilizing silicone oil tamponade . stickler syndrome , though rare , presents certain diagnostic and therapeutic challenges to the vitreoretinal surgeon . several factors may contribute to the complexity of rrd repair in these patients , including the presence of multiple retinal tears , grts , the young age of presentation , and the abnormal vitreous syneresis seen in patients with stickler syndrome . this difficulty is evident in the average number of surgeries until complete rrd repair in these patients , which was shown to be 3.1 in our study . given these confounding factors , however , all 16 eyes in our study achieved successful retinal reattachment , with a mean postoperative follow - up to almost 8 years . in our series , patients with poorer presenting va were more likely to require silicone oil tamponade for successful reattachment . anatomical success in the presence of silicone oil tamponade is consistent with previous studies , which also showed anatomical success when silicone oil tamponade was utilized.9,10 in spite of successful anatomical outcomes , visual outcomes remain modest , improving only slightly from va at presentation : in our cohort , patients with rrd presented with an average best corrected visual acuity of 20/914 ( snellen equivalent ) . after an average of 3.1 surgeries , mean best corrected visual acuity only improved to 20/796 though this improvement did not achieve statistical significance ( p=0.81 ) and the va outcomes were widely variable , ranging from 20/20 to hand motions . of note , presenting va bore prognostic significance , as it showed strong correlation with the postoperative va at final follow - up ( p<0.001 ) . the variability of va outcomes after surgical intervention for rd in our cohort is similar to those va results reported by abeysiri et al,9 where 33% of patients had improved va , 40% maintained va , and 27% experienced a decrease in va , and alshahrani et al,10 where 64.29% of patients had improved va while 28.57% maintained va . most eyes ( 81.3% ) in our study required multiple surgeries to successfully achieve retinal reattachment . the five eyes demonstrating the greatest improvements in va postoperatively required , on average , approximately five surgeries before retinal reattachment . when surgical treatments are performed to repair these difficult and complex rds , our series demonstrated that initial surgery with scleral buckle , vitrectomy , and combined vitrectomy and scleral buckle procedures all yielded equally successful anatomical outcomes with 100% retinal reattachment . these results contrast to those of previous studies , one of which showed superior anatomical outcomes with vitrectomy , while the other suggested combined vitrectomy and scleral buckle procedure with silicone oil injection to be the treatment of choice for treating rd in patients with stickler syndrome.9,10 our data overall underscore a few critical points for stickler syndrome patients with rd : first , the 75% rate of proliferative vitreoretinopathy seen in our study , as well as the average of 3.1 surgeries required to repair these rds , highlights the complicated nature of surgical therapy for these patients . second , in our cohort , patients presented with rrd at a mean age of 10.5-years old , which is a younger age compared to previous series.9,10 finally , given this younger age of presentation , as well as the challenges of surgery and the modest visual gains , these data further reinforce the importance of early diagnosis and prophylactic therapy in patients with stickler syndrome . previous studies have demonstrated that prophylactic cryotherapy markedly reduces the risk of rds in stickler syndrome patients.11,12 recognition of patients with a stickler ocular phenotype by primary care doctors , ophthalmologists , and other health care providers is essential for preventing the severe retinal complications in these patients . limitations of our study include its retrospective design and the small sample size studied a frequent limitation of reviews of stickler syndrome . this small sample size inevitably magnifies any diagnostic or therapeutic biases in our cohort , and significant caution is warranted in drawing conclusions from subgroup analyses . however , as our data tended to corroborate those of previous publications , the conclusions drawn from the overall cohort are likely to be sound . our study affirms the feasibility of successful retinal reattachment in cases of rrd in stickler syndrome , usually after multiple vitreoretinal surgeries . however , va outcomes are highly variable and show only a small improvement from presenting va in long - term follow - up overall . complicated peripheral retinal pathology , high rates of grt , high rates of proliferative vitreoretinopathy , and frequent redetachment requiring additional surgeries are the norm in this cohort , and early diagnosis ( within the first decade of life ) should be the goal for these patients .

purposethe aim of the study was to present the long - term anatomical and visual outcomes of retinal detachment repair in patients with stickler syndrome.patients and methodsthis study is a retrospective , interventional , consecutive case series of patients with stickler syndrome undergoing retinal reattachment surgery from 2009 to 2014 at the associated retinal consultants , william beaumont hospital.resultssixteen eyes from 13 patients were identified . patients underwent a mean of 3.1 surgical interventions ( range : 113 ) with a mean postoperative follow - up of 94 months ( range : 5313 months ) . twelve eyes ( 75% ) developed proliferative vitreoretinopathy . retinal reattachment was achieved in 100% of eyes , with ten eyes ( 63% ) requiring silicone oil tamponade at final follow - up . mean preoperative visual acuity ( va ) was 20/914 , which improved to 20/796 at final follow - up ( p=0.81 ) . there was a significant correlation between presenting and final va ( p<0.001 ) , and patients with poorer presenting va were more likely to require silicone oil tamponade at final follow - up ( p=0.04).conclusionrepair of retinal detachment in patients with stickler syndrome often requires multiple surgeries , and visual outcomes are variable . presenting va is significantly predictive of long - term va outcomes .

we screened stool specimens for sav by using rt - pcr and described the genetic diversity of virus - positive specimens . a total of 95 stool specimens were collected from children < 18 years of age treated for gastrointestinal illness at the sydney children 's hospital . these specimens were negative for common foodborne bacterial pathogens ( salmonella , shigella , and campylobacter ) and enteric viruses ( rotavirus , adenovirus , astrovirus , and norovirus ) ( ideia enzyme - linked immunosorbent assay , dako cytomation , ely , uk ) . the specimens included 67 of 110 specimens obtained from children hospitalized between august 2001 and august 2002 and 28 of 60 specimens from outpatients between february 2004 and august 2004 . specimens were not tested for the presence of sav if an etiologic agent was already identified ( n = 75 ) . ten microliters of rna was reverse transcribed by using superscript iii rnaseh ( ) reverse transcriptase according to the manufacture 's instructions ( invitrogen , carlsbad , ca , usa ) . pcr was conducted by using a nested approach with primers directed against the n - terminal capsid region ( 4 ) . the pcr products were analyzed by 2% agarose gel electrophoresis and visualized by staining with ethidium bromide . pcr - generated amplicons were excised from the gel and purified by using the qiaquick gel extraction kit ( qiagen , hilden , germany ) . nucleotide sequences were determined by using the terminator cycle sequence kit ( version 3.1 ) and the abi 3100 avant sequencer ( perkin - elmer abi , boston , ma , usa ) . nucleotide sequences were aligned by using clustalx , and distances were calculated by using the 2-parameter method of kimura ( 8) . phylogenetic trees with bootstrap analysis from 1,000 replicas were generated by using the neighbor - joining method as described previously ( 8) . sav was detected in 7 of 95 stool specimens from children 9 months to 7 years of age with previously unknown causes of acute gastroenteritis . two sequences ( strains sydney31 and sydney40 ) , which shared 99% nucleotide ( nt ) identity and belonged to genogroup gi , closely matched ( > 99% nt identity ) the manchester sequence . three sequences ( strains sydney53 , sydney77 , and sydney4106 ) that belonged to genogroup gii had 69%77% nt identity . sydney4106 had 98% nt identity with the mc10 sequence , sydney53 had 90% nt identity with the c12 sequence , and sydney77 had 99% nt identity with the bristol sequence . phylogenic tree of sapovirus ( sav ) sequences isolated in this study ( represented in boldface ) . sav nucleotide sequences were constructed with the partial n - terminal capsid region , using sav pec strain ( a porcine sav ) as an outgroup . genbank accession numbers for the reference strains are as follows : arg39 , ay289803 ; bristol/98 , aj249939 ; c12 , ay603425 ; cruise ship/2000 , ay289804 ; ehime1107 , dq058829 ; houston/27/90 , u95644 ; london/29845/90 , u95645 ; manchester , x86560 ; mc2 , ay237419 ; mc10 , ay237420 ; mex340/1990 , af435812 ; nk24 , ay646856 ; parkville , u73124 ; pec , af182760 ; sapporo/82 , u65427 ; stockholm/318/97 , af194182 ; sakaeo15 , ay646855 ; and sw278 , dq125333 . phylogenetic analysis of the nonstructural region ( i.e. , genome start to capsid start ) grouped mc10 and c12 in 1 gii cluster ( 7 ) , and the structural region ( i.e. , capsid start to genome end ) grouped mc10 and c12 into distinct gii genotypes ( 7 ) . evidence suggested that the recombination site occurred at the polymerase and capsid junction in open reading frame 1 , as we recently described with recombinant norovirus strains ( 9 ) . further sequence analysis of the nonstructural region ( i.e. , 800 nt of the polymerase gene ) showed that sydney4106 had 99% nt identity with mc10 , and sydney53 had 92% nt identity with c12 . these findings suggest that sydney4106 and sydney53 were also recombinant strains and indicate the widespread distribution and genetic stability of recombinant sav strains . one sequence ( strain sydney3 ) belonged to genogroup giv and had 99% nt identity with the sw278 sequence , which recently caused an outbreak of gastroenteritis in adults in sweden in march 2004 ( 1 ) . another sequence ( strain sydney4402 ) belonged to genogroup gv and had 100% nt identity with the nk24 sequence , which was isolated from an infant with gastroenteritis in thailand in december 2002 ( 10 ) . white blood cells were detected in the stool specimens of 3 children infected with sav genogroups gii , giv , and gv ( strains sydney4106 , sydney3 , and sydney4402 , respectively ) . in our previous study ( 10 ) , an infant infected with nk24 ( sav genogroup gv ) had a fever for 11 days and vomiting for 3 days , which was notably longer than the duration of symptoms in other infants infected with sav gi and gii strains ( unpub . these results suggest that some sav genogroups could be more virulent than others , although additional studies are needed . data from these reports indicate that sav is an uncommon cause of acute gastroenteritis in australia . when the proportion of sav present in the total calicivirus isolations was used , sav was estimated to be the etiologic agent of gastroenteritis in 0.56% ( 11 ) , 0.32% ( 12 ) , and 0.46% ( 14 ) of cases . our results have shown that sav is an important cause of acute gastroenteritis in children in sydney , with a minimum prevalence of 4.1% , which is higher than previously reported . this is the first report of sav giv genogroup - associated infection in australia and widespread distribution of sav . however , a more comprehensive study is needed to determine whether predominant sav strains are circulating , as observed with noroviruses ( 7,11,15 ) .

sapovirus was detected in 7 of 95 stool specimens from children with gastroenteritis of unknown etiology in sydney , australia , from august 2001 to august 2002 and from february 2004 to august 2004 , by using reverse transcription polymerase chain reaction . sequence analysis of the n - terminal capsid region showed all human sapovirus genogroups .

late - onset urea cycle deficiencies are defined as those that have clinical onset after an age of 28 days . this disorder occurs due to the deficiency of any of the following enzymes - ornithine transcarbamylase ( otc ) , carbamoyl - phosphate synthetase ( cpsi ) , argininosuccinate synthetase ( ass ) , argininosuccinate lyase ( asl ) , and ( nags ) , which acts as a co - factor [ figure 1 ] . a 33-year - old primigravida , four days post - cesarean section , was referred to us with 2 days history of altered sensorium progressing to coma . she had past history of self - limiting episodes ( 3 in the last 5 years ) of altered behavior and confusional state . in the intensive care unit ( icu ) , she was found to be in grade iv encephalopathy ( glagow coma scale ( e1v1m2 ) , pupils were bilateral mid dilated and reactive to light . her blood investigations showed a serum ammonia 286 mmol / l and serum urea of 13 mg / dl . anti - ammonia measures were instituted in the form of lactulose ( 30 ml q4h ) and tablet rifaximine ( 300 mg twice - daily ) through nasogastric tube . the next day , ammonia levels rose to 300 mmol / l , despite passage of good amount of loose stools . , we received the report of amino acid levels with citrulline levels of 933 ( normal < 70 ) micromol / l , glycine 970 ( normal < 505 ) micromol / l and phenyalanine 181 ( normal < 120 ) micromol / l . ammonia levels after a second cycle of hemodialysis was 160 mmol / l.serum ammonia level showed a progressive decline [ figure 2 ] over the next 3 days through 3 cycles of hemodialysis . she could be transferred out of icu on day 7 and discharged on day 9 of hospitalization in a stable condition . in april 2000 , research experts at the urea cycle consensus conference estimated the incidence of the disorders at 1 in 30,000 births . symptoms may be triggered by illness or stress i.e. , viral illnesses , childbirth , fasting , and use of valproic acid at almost any time of life , resulting in elevations of plasma ammonia concentration . in patients with partial enzyme deficiencies , many of the adult onset ucds leading to coma are precipitated in the peripartum period . the signs and symptoms during such episodes are vague and non - specific and usually include confusion , migraine headaches , loss of appetite , cyclical vomiting , lethargy , sleep disorders , delusions , hallucinations , psychosis , seizures , bizarre behavior , or psychomotor delay . deficiency of the fifth enzyme , arginase ( arg ) , results in a chronic debilitating disease affecting primarily the nervous system . this patient had history of self - limiting episodic confusion and abnormal behavior lasting only for few hours . hyperammonemia in the absence of hepatic dysfunction and a normal lft should raise the suspicion for an ucd . an elevated serum ammonia levels with a low serum urea and a normal blood sugar , anion gap , and liver function test results raised strong suspicion for ucd in our case . the first mri brain of the patient done within 6 hours of coma was normal . follow up mri ( 48 hrs post - symptoms ) exhibited diffusion restriction in bilateral perisylvian cortex [ figure 3 ] , thalamus and cerebral cortices , sparing the occipital areas [ figure 4 ] , suggestive of systemic metabolic or hypoxic insult . her repeat mri on 4 day showed restricted diffusion in the splenium [ figure 5 ] . extensive literature search yielded a few case reports revealing similar findings in hyperammonemia due to citrullinemia . diffusion restriction in peri - sylvian area and thalamic region bilaterally bilateral temporal lobe flair hyperintensity with occipital sparing diffusion weighted images showing bright areas in splenium plasma citrulline is formed upstream to ass enzyme action site ; a decrease in plasma citrulline level distinguishes otc and cps1 from other enzyme defects ( i.e. , ass , asl , arg ) . laboratory values in our case showed a high plasma citrulline with a low plasma arginine . this ruled out the possibility of arg enzyme defect , which presents as an increased plasma arginine [ figure 2 ] . this plasma quantitative amino acid analysis enabled us to narrow our possible diagnosis to ass or asl enzyme deficiency . urinary orotic acid is high in deficiency of otc , ass , and asl deficiency . deficiency of ornithine synthesis in intestinal cells of the newborn or of either argininosuccinate synthetase or argininosuccinate lyase in liver and kidney in the face of hyperammonemia can result in mild orotic aciduria together with a low rate of arginine synthesis . our patient presented with a high urinary orotic acid level , which is consistent with ass or asl deficiency . treatment modalities found to be successful pertains to management of the acute phase and prevention of repeat episodes . in the acute phase , the mainstay of treatment involves rapid reduction in plasma ammonia level , dietary nitrogen restriction , and management of cerebral edema . the treatment for hyperammonemia involves administering intravenous fluids , lactulose , and rifaximine to reduce the concentration of ammonia . restricting nitrogen in the diet is essential . in older patients , alternative - pathway therapy i.e. sodium phenylacetate , sodium benzoate , and arginine therapy are the initial treatment options . hemodialysis can be successfully used for hyperammonemia not responsive to drug therapy or when obtundation or coma persisted . in a study , it was documented that dialysis was a more often used modality in neonates as compared to adults . conventional hemodialysis has the highest ammonium clearance rate , as compared with other methods such as peritoneal dialysis , exchange transfusion , and hemofiltration . in our case , ucds are uncommonly encountered in adults . a comprehensive family history , clinical presentation , plasma ammonia concentration , ph , co2 , anion gap , quantitative plasma amino acids analysis , and analysis of urine organic acids and urine orotic acid , and molecular genetic testing lead to near - confirmed diagnosis . though alternative methods to hemodialysis are effective in correcting hyperammonemia , use of early hemodialysis is warranted in the setting of worsening coma . hemodialysis for reducing serum ammonia level should be considered especially in patients with a poor neurological status .

urea cycle disorders ( ucd ) are common during neonatal period , and it is rarely reported in adults . we are reporting a patient presenting with post - partum neuropsychiatric symptoms rapidly progressing to coma . markedly raised serum ammonia level on presentation with an initial normal magnetic resonance imaging ( mri ) of brain and normal liver function tests led to the suspicion of ucd , which was confirmed on the basis of urine orotic acid and elevated serum amino acid levels . we had to resort to hemodialysis to correct the hyperammonemic coma , which was unresponsive to conventional anti - ammonia measures . she exhibited remarkable improvement with a progressive decline in serum ammonia with repeated hemodialysis and made a full recovery . timely diagnosis and early institution of hemodialysis in the setting of a poor neurological status maybe considered a suitable treatment option .

night blindness occurs in response to a decrease in rhodopsin in retinal light - sensitive rod cells . night blindness is usually due to retinitis pigmentosa , which is an inherited disorder ( 1 ) . rhodopsin also decreases in response to vitamin a deficiency ( vad ) ( 2 ) . according to a world health organization ( who ) report , the prevalence of night blindness in iran is moderate ( more than 1% and less than 5% in pre - school age children ) . but this prevalence is highly variable in different areas of iran because of different nutritional situations ( 3 ) . it is well known that vad is associated with a higher prevalence of night blindness and eye disorders ( 4 ) . xerophthalmia is advanced form of vitamin a deficiency that is associated with dry and unclear conjunctiva ( 5 , 6 ) . photosensitivity , decreased tearing , ulcers , and infection are also more prevalent in these patients . studies in iran have shown a high prevalence of vad among pregnant women in hormozgan , which is an important health issue in this province ( 7 ) . the prevalence of night blindness is classically an indicator of nutritional and vitamin a deficiency situations . the aim of the current study is to assess the prevalence of night blindness in bashagard in 2011 . this descriptive cross - sectional study was done in the winter of 2011 in the bashagard district , located in hormozgan province . considering the prevalence of night blindness in different studies ( 2% ) and a confidence interval of 95% , a sample size of 819 was selected . considering the geographical diversity of the bashagard district , cluster sampling therefore , the calculated sample size was divided between the covered populations of five health centers ( goharan , tisoor , tidar , sar dasht , and jakdan ) . a checklist ( including demographic data such as name , family name , place of residence , covering health center , sex , age , and educational level ) was used to collect the data . in the second section the data about the duration of the disease and treatments received for the disease were also recorded . the third section concerned the patient s history of eye trauma , surgery , and ophthalmic infection . in the final section , some questions about nutrition and meat , fruit , and vegetable consumption were asked . table 1 shows the frequency and percentage of the studied people in each of the five health centers . among the 814 people studied , 32 had disturbances in their vision at night . the youngest individual with night blindness was 5 years old and the oldest one was 70 years old . twelve people in tidar , ten in sar dasht , eight in jakdan , one in goharan , and one in tisoor had night blindness . therefore , the prevalence of night blindness in males and females was 3.4% and 4.4% , respectively . the mean duration of the disease was 2.5 years . among all patients , two ( 6.25% ) had physician visits and were using drugs for their disease . another four ( 12.5% ) had physician visits and were using glasses for their disease . one ( 3.1% ) had a history of eye trauma , another one ( 3.1% ) had a history of eye infection , and one ( 3.1% ) also had a history of eye surgery . twenty - one patients ( 65.6% ) had nt met the daily recommended consumption of fruits and vegetables , one ( 3.1% ) had nt even met the once - a - week recommended meat consumption , and three ( 9.4% ) had nt met the twice - a - week milk and dairy recommended consumption . among the 814 people studied , seventy - four were 2 to 6 years old ; among them , one ( 1.4% ) had night blindness . of 341 women between 15 to 49 years old , six among them ( 1.8% ) had night blindness . one of the most important known etiologies is vitamin a deficiency ( 8) . according to who statistics , the prevalence of night - blindness is less than one percent , meaning a mild to moderate prevalence ( 9 ) . in the current study , we found that the prevalence of night - blindness is 3.93% in bashagard , which is three times greater than the average national prevalence . the prevalence of visual disorders and ophthalmic diseases are higher in this province , which may be due to vitamin a deficiency . the prevalence of night blindness in beshno and cistomacity ( 9.43% and 9.45% , respectively ) indicates a higher prevalence in some areas of bashagard , which calls for immediate action . vitamin a plays a vital role in prevention of the disease and development , in addition to its role in the visual system . it is especially important in children 2 to 6 years old and pregnant women ( 10 ) . another important point in this study was that about 60% of the participants are non - educated . therefore , they have a low socioeconomic level and need support and attention . according to who indexes , vitamin a deficiency is a important health issue in areas with a prevalence of 1 to 5 percent of night blindness ( 9 ) . therefore , our findings show that vitamin a deficiency is an important health issue in bashagard . vitamin a deficiency in rural areas and towns in hormozgan is shown in previous studies and needs the attention of health system policy makers . it is shown that vitamin a supplementation and nutrients and also diet changes in the areas with significant levels of vitamin a deficiency can significantly decrease ophthalmic and visual problems . in this study , the initial assessment of a health issue problem in bashagard was done . we recommend other studies on the measurement of vitamin a serum level , ophthalmic assessment , and specific tests and interventions in the study population .

background : night blindness is a visual disorder associated with unusual vision during the night or in darkness . vitamin a deficiency ( vad ) , which is easily preventable , is the main known etiology of night blindness . malnutrition is a common health issue in bashagard and some other areas in the hormozgan province of iran . the aim of the current study was to determine the prevalence of night blindness in bashagard.methods:this descriptive cross - sectional study was done on 814 bashagard residences . data was analyzed using spss software and descriptive studies.results:about 60% of the study participants were uneducated people or people with low education . thirty - two out of 814 people that were studied had problems with night vision . therefore , the prevalence of night blindness in bashagard was 3.93%.conclusion : prevalence of night blindness in bashagard is three times higher than its prevalence in all of iran . therefore , preventive interventions such as dietary regimes with vitamin a enrichments or supplementations are recommended .

the prevalence of chronic tinnitus increases with age , peaking at 14.3% in people 6069 years of age . the increase in prevalence of tinnitus with age is at least partly explained by the fact that hearing loss ( hl ) is an important risk factor for tinnitus ; 12% of people experiencing tinnitus develop anxiety , sleep disorders , or depression . it is not known why a few patients are truly disturbed and disabled by tinnitus . the amount of tinnitus distress appears to be associated with comorbid anxiety , comorbid depression , personality type , psychosocial situation , the amount of related hl , and the loudness of the tinnitus . the subjective nature of tinnitus , lack of objective quantification , diversity of causes , and heterogeneity of affected patients contribute to the poor understanding of stress related to tinnitus . two hundred and thirty - six women and 234 men with objective tinnitus visited the tinnitus clinic at the department of otorhinolaryngology , seoul st . mary 's hospital , catholic university of korea , seoul , korea , between january 2009 and june 2010 . patients were divided into three age groups for evaluation : under 40 years , 4160 years , and over 60 years . all patients were evaluated using the same systematic protocol for evaluation of tinnitus and sound intolerance . this protocol was the basis for selecting the clinical data , features of tinnitus , and symptoms for review . patients were evaluated using the korean version of the tinnitus handicap inventory ( thi ) . the thi score was graded as negligible ( 016 ) , mild ( 1836 ) , moderate ( 3856 ) , severe ( 5876 ) , or catastrophic ( 78100 ) . the perceived stress was evaluated using the brief encounter psychosocial instrument - korean version ( bepsi - k ) . the total score of the bepsi - k was interpreted using three severity levels : low ( < 1.3 ) , moderate ( 1.42.3 ) , and severe ( > 2.4 ) . the beck 's depression index ( bdi ) questionnaire was used for measuring depression and was scored as normal ( 110 ) , mild ( 1116 ) , borderline ( 1720 ) , moderate ( 2130 ) , or severe ( 3140 ) . a complete clinical otorhinolaryngolic and head and neck examination patients were evaluated using pure tone audiometry in an acoustically treated booth to test frequencies at 250 , 500 , 1000 , 2000 , 3000 , 4000 , 6000 , and 8000 hz ( sa 203 audiometer ; entomed , malm , sweden ) . tinnitus features and characteristics of all age groups were compared using the t test or analysis of variance ( anova ) test , depending on the data type . statistical analysis was performed using spss 20.0 software ( ibm , armonk , ny , usa ) . the influence of patient age on perceived tinnitus was evaluated . tinnitus features and characteristics of all age groups were compared using the t test or analysis of variance ( anova ) test , depending on the data type . statistical analysis was performed using spss 20.0 software ( ibm , armonk , ny , usa ) . four hundred and seventy patients , 234 men ( 49.8% ) and 236 women ( 50.2% ) , were evaluated . the age of the patients ranged from 12 to 86 years [ mean : 53 7.9 ( standard deviation ) years ] . the mean age among women was 54 years and among men was 51.5 years . there was no difference in patient age by sex ; 18.1% of patients were less than 40 years of age , 46.2% were 4060 , and 35.7% were above 60 . patients of 4060 years of age were seen most frequently ( p=0.02 , anova ) ; 45.9% of patients less than 40 year , 44.7% between 40 and 60 , and 59.5% above 60 were women . patients above 60 years of age were more frequently women ( p=0.005 , t test ) and younger patients were more commonly men ( p=0.02 , anova ) [ table 1 and figure 1 ] . patients above 40 years of age had tinnitus for longer duration than younger patients ( p=0.02 , anova ) [ table 1 and figure 2 ] . the duration of symptoms was longest in patients above 60 years of age ( p=0.02 , anova ) . patients were asked to localize their tinnitus . of those with unilateral tinnitus , 26.4 and 25.7% reported left and right - sided tinnitus , respectively ; 8.9% of patients could not localize their tinnitus , describing it only as in the head . of patients below 40 years of age , 54.12% had unilateral tinnitus , 38.82% bilateral tinnitus , and 7.06% poorly localized tinnitus [ table 1 and figure 3 ] . of patients aged 4060 years , 52.63% had unilateral tinnitus , 40.67% bilateral tinnitus , and 6.70% poorly localized tinnitus . of patients older than 60 years of age , 50.30% had unilateral tinnitus , 36.97% bilateral tinnitus , and 12.73% poorly localized tinnitus . unilateral tinnitus was more common than bilateral tinnitus in all the age groups ( p=0.001 , anova ) . patient characteristics by age subgroup * = men affected more frequently than women , anova = above 12 months more common , anova anova : analysis of variance gender percentage by age group duration of tinnitus by age group location of tinnitus by age group patients described the type of sound they perceived as tonal or noise [ table 1 ] . more than one type of sound was reported in 56.9% of all patients , and was most common in patients less than 60 years of age . there was no difference in the type of sound reported by the age groups [ table 1 ] . patients below 40 years of age most commonly reported that their tinnitus began at a mild level and increased over a period of years ; 10% ( n=47 ) had onset of their tinnitus associated with a specific event , such as trauma , an explosion , or some other loud noise ; 32.14% of patients below 40 years of age had gradual onset of tinnitus and 67.86% had acute onset [ table 1 and figure 4 ] ; 61.67% of patients above 60 years of age had acute onset of tinnitus and 38.33% had gradual onset ; and 63.08% of patients between 40 and 60 years experienced acute onset of tinnitus . the perception of loudness greatly varied ; 53.2% of the patients thought the tinnitus was loud , with most of these patients in the above 40-year age group . these patients tended to have a high annoyance visual analogue scales ( vas ) score , greater than 5 in 59.6% of these patients . type of onset by age group patients rated the severity of their tinnitus using the thi scoring system [ table 2 and figure 5 ] . half ( 196/392 ) of all patients evaluated in our clinic had slight or mild tinnitus . only 24.23% of all patients evaluated had a moderate level and 15.31% a severe level . the greatest number of patients with a mild , moderate , or severe score was found in the 40 to 60-year age group . the greatest number of patients with a catastrophic score was found in the above 60-year age group . the subjective severity of tinnitus was weakly correlated with bepsi - k ( pearson correlation coefficient r=0.25 , p<0.001 ) [ table 2 and figure 6 ] and bdi score ( pearson correlation coefficient r=0.48 , p=0.001 ) [ table 2 and figure 7 ] . psychological characteristics by age subgroup = greater hearing loss in patients greater than 40 years of age , anova . anova : analysis of variance , bdi : beck s depression index , bepsi : brief encounter psychosocial instrument - korean version tinnitus handicap inventory tinnitus severity score by age group brief encounter psychosocial instrument - korean version stress score by age group becks depression score by age group hearing threshold in the high frequency range was evaluated [ table 2 and figure 8 ] ; 40.5% of all patients had normal hearing . the one exception to this was the high prevalence of patients 4060 years of age in the worst category , that is , severe . subjective tinnitus is experienced in different forms , with a wide range of severity and character . about half of patients had unilateral tinnitus . previous reports have shown a wide range in the frequency of unilateral versus bilateral tinnitus . this variation has been explained by differences in population characteristics and definitions of tinnitus and its severity . the presence of tinnitus has been reported to progressively increase with age , affecting 5% of individuals 2030 years of age and 12% of individuals above 60 years of age . the prevalence of tinnitus increases to 7085% in the hearing - impaired population ; 40 to 60-year - old individuals were most commonly affected , followed by individuals above 60 years of age , followed by individuals below 40 years of age . the prevalence of findings in patients 4060 years of age may be because of this age range comprising 67.7% of patients with severe sensorineural hl . the finding of women being affected more frequently than men in the above 60 age group may be because of their greater longevity . the location and type of onset of tinnitus in patients was similar to that in the previous reports . affected patients commonly had a gradual worsening of their tinnitus over years , starting out at a mild level and worsening over time . this referral pattern could have led to patients being referred after their symptoms were observed for longer than 12 months and patients with transient tinnitus were less likely to be referred to our clinic . also , some patients may not have been motivated to seek medical help until their symptoms worsened . this pattern was especially valid in the oldest patients , wherein some non - life - threatening symptoms were more likely to be tolerated and not evaluated . this finding was different from the previous reports , wherein the most common tinnitus was reported to be tonal in nature . this is in contrast to the previous reports that used a predetermined category to describe the tinnitus ; 16.3% of patients below 40 years of age , 36.9% between 40 and 60 , and 18.3% above 60 years of age described a moderately high - pitch tinnitus on a vas ( 60/100 points ) , similar to the previous reports ; 47.2% of patients above 40 years of age described moderately high loudness on a vas ( 50/100 points ) , greater than the previous reports . this loudness may be attributed to delayed referral or referral of patients with greater symptoms . only 12.9% of patients below 40 years of age described their tinnitus loudness as low on a vas ( less than 50 of 100 points ) . these patients most frequently had low psychological impact scores . a significant correlation has been reported between the loudness of tinnitus and annoyance to tinnitus , similar to our patients . this finding supports the theory that a patient 's reaction to tinnitus is a complex interaction between acoustic phantom symptoms , somatic attention , and depressive symptoms ; 50.8% of patients who were above 40 years of age judged their annoyance from tinnitus to be moderately high on a vas ( 5 of 10 points ) . this higher score of annoyance has been associated with increased risk for depression and anxiety , similar to our patients . the severity of tinnitus can be influenced by different factors , such as sociodemographic or tinnitus characteristics or additional health complaints ; 12.8% of the patients above 40 years of age and 2.6% of patients below 40 years of age had severe tinnitus , according to thi testing , and 9.7 and 0.8% , respectively , had catastrophic tinnitus . studies in australia , the united kingdom , and brazil have not shown an association between advanced patient age and an increased incidence of catastrophic tinnitus . marciano et al . reported that 77% of consecutively screened tinnitus patients fulfilled the criteria for at least one diagnostic and statistical manual of mental disorders , 4th edition ( dsm - iv ) mental disorder and had elevated scores on the minnesota multiphasic personality inventory depression , hysteria , and hypochondria scales . patients who were above 40 years of age most frequently reported moderate stress scores ( 41.9% ) . few patients had a high beck depression score , with patients above 40 years of age being at greatest risk . tinnitus severity has been reported to be positively correlated with patient depression , insomnia , and anxiety . this lack of association in such patients may be because of the relatively large number of patients with slight or mild tinnitus ( 50% ) . the role of cognitive functioning in the development and maintenance of severe tinnitus and associated psychological distress has been well described . early intervention would appear to be required to break the cycle of tinnitus severity , psychological distress , and maladaptive coping . our results demonstrate that patients above 40 years of age were most commonly affected with severe tinnitus . it is important to evaluate affected patients for potentially modifiable risk factors for severe tinnitus and treat them . future research should prospectively examine the relationship between patient age , risk factors for tinnitus ( smoking , hypertension , and noise exposure ) , personality traits , and mental health for their role in the development of tinnitus .

objectives : the aim of this study was to characterize tinnitus in affected patients.methods:a retrospective review of medical records from 470 consecutive patients who visited a tertiary care hospital for evaluation of chronic subjective tinnitus between january 2009 and june 2010 was performed . patients were divided into three subgroups based on age . clinical , audiological , and psychological characteristics of each subgroup were analyzed.results:of the 470 patients evaluated , 85 were less than 40 , 217 between 40 and 60 , and 168 above 60 years of age . most patients were men and complained of unilateral , acute high - pitched tinnitus . most patients above the age of 40 years complained of loud and annoying tinnitus and had worse stress and severity scores.conclusions:chronic tinnitus in older adults is subjectively louder , more annoying , and more distressing than that found in younger patients . we recommend considering age in the patient management plan .

mixed gonadal dysgenesis is a condition of unusual and asymmetrical gonadal development leading to an unassigned sex differentiation . a number of differences have been reported in the karyotype , most commonly a mosaicism 45,x/ 46 , xy . a 16-year - old person , reared as female , born out of nonconsanguineous marriage , presented to our clinic with complaints of genital ambiguity and primary amenorrhoea along with lack of secondary sexual characters . there was no h / s / o crisis or cyclical abdominal pain in the past . however , the patient was taking 5 mg of prednisolone after being labeled as a case of congenital adrenal hyperplasia ( cah ) . other past history , family history , antenatal history , perinatal history , and developmental history were noncontributory . on earlier evaluations , a small uterus was found on ultrasonogrphy ( usg ) studies but no gonads were visualized . on examination , genital examination revealed a single perineal opening , phallic length of 5 cm , with a well - formed glans and a well - formed scrotal sac . there was no evidence of hypocortisolemia ( cortisol 9.08 g / dl , adrenocorticotropic hormone [ acth ] 82.5 pg / ml ) or elevated level of 17-oh- progesterone ( 0.16 ng / ml ) . basal testosterone level was 588 ng / dl with basal androstenedione level of 1.83 ng / ml ( male : 0.7 - 3.6 , female : 0.3 - 3.5 ) . pooled luteinizing hormone ( lh ) was 11.79 miu / ml and follicle - stimulating hormone ( fsh ) was 66.37 miu / ml . basal and 72 h post beta - human chorionic gonadotropin ( hcg ) levels of androstenedione and testosterone levels were done ( basal testosterone of 652 ng / dl and basal androstenedione of 1.17 ng / ml ; 72 h post hcg testosterone of 896 ng / dl and androstenedione of 1.34 ng / ml ) . mri pelvis [ figure 1 ] revealed uterus didelphys with obstructed right moiety and bilateral ovarian - like structures . magnetic resonance imaging ( mri ) showing rudimentary uterus and bilateral ovarian - like structures the patient was managed in collaboration with department of gynecology and obstetrics and discussions with patient party and a decision was taken to remove the gonads and mullerian structures laparoscopically . however at the time of surgery , only right sided gonads and adjacent tubal structures were visualized and removed . however , left sided mullerian remnants could not be removed due to adhesion to sigmoid colon . histopathological examination [ figure 2 ] revealed presence of testicular tissue showing atrophic seminiferous tubules with hyperplasia of leydig cells . epididymal tissue and an epididymal cyst are also present . however , no ovarian tissue was seen . histopathological examination ( hpe ) of resected gonads showing atrophic seminiferous tubules ( 20 ) the patient is still admitted with us as on the day of writing this manuscript and is being managed with oral estrogens . there was no evidence of hypocortisolemia ( cortisol 9.08 g / dl , adrenocorticotropic hormone [ acth ] 82.5 pg / ml ) or elevated level of 17-oh- progesterone ( 0.16 ng / ml ) . basal testosterone level was 588 ng / dl with basal androstenedione level of 1.83 ng / ml ( male : 0.7 - 3.6 , female : 0.3 - 3.5 ) . pooled luteinizing hormone ( lh ) was 11.79 miu / ml and follicle - stimulating hormone ( fsh ) was 66.37 miu / ml . basal and 72 h post beta - human chorionic gonadotropin ( hcg ) levels of androstenedione and testosterone levels were done ( basal testosterone of 652 ng / dl and basal androstenedione of 1.17 ng / ml ; 72 h post hcg testosterone of 896 ng / dl and androstenedione of 1.34 ng / ml ) . mri pelvis [ figure 1 ] revealed uterus didelphys with obstructed right moiety and bilateral ovarian - like structures . magnetic resonance imaging ( mri ) showing rudimentary uterus and bilateral ovarian - like structures the patient was managed in collaboration with department of gynecology and obstetrics and discussions with patient party and a decision was taken to remove the gonads and mullerian structures laparoscopically . however at the time of surgery , only right sided gonads and adjacent tubal structures were visualized and removed . however , left sided mullerian remnants could not be removed due to adhesion to sigmoid colon . histopathological examination [ figure 2 ] revealed presence of testicular tissue showing atrophic seminiferous tubules with hyperplasia of leydig cells . epididymal tissue and an epididymal cyst are also present . however , no ovarian tissue was seen . histopathological examination ( hpe ) of resected gonads showing atrophic seminiferous tubules ( 20 ) the patient is still admitted with us as on the day of writing this manuscript and is being managed with oral estrogens . this 16-year - old normotensive person reared as a girl came with a labeled diagnosis of 46xx disorder of sexual differentiation ( dsd ) ( diagnosed to be 46xx on the basis of buccal smear examination done outside ) , thought to be due to cah and started on prednisolone 5 mg once a day , even without a history suggestive of salt losing crisis . before the karyotype report was available , since the patient could not produce documents or investigation reports favoring the diagnosis of cah and thus justifying the use of prednisolone , we thought of reevaluating the patient completely . we stopped the corticosteroid for 3 days and then reevaluated the adrenal axis , which was normal . since the basal testosterone level was high , aromatase deficiency and partial androgen insensitivity syndrome ( pais ) were next in the line of diagnostic possibilities . pais was ruled out due to presence of mullerian structures visualized on mri pelvis , as mullerian - inhibiting substance ( mis ) secretion is not hampered in pais . the patient had no clinical or hormonal features suggestive of aromatase deficiency in the form of absence of virilization of mother during pregnancy , presence of significant values of serum estradiol levels , low normal levels of serum androstenedione and an absence of a significant rise of serum androstenedione levels even after beta - hcg stimulation . lastly , we were left with diagnostic considerations of ovotesticular dsd ( ot - dsd ) and mgd . the syndromic diagnoses associated with abnormal gonadal development were not suspected as patient did not reveal any of the known features of such defects ( e.g. , wild type [ wt]-1 , steroidogenic factor [ sf]-4 , dax-1 , etc . ) . since patient was reared as female with history of clitoroplasty and vaginoplasty in the past and functionality of the external genital organs was not expected , a combined decision involving the patient party , gynecologist , and our department was taken to remove the gonads and assign a female sex to the patient . on histopathological examination ( hpe ) of the gonadal tissue , only testicular tissue was seen , which favored the diagnosis of mgd over ot - dsd . also a 46xx karyotype is more likely to be found in patients with ot - dsd . although 46xo/46xy is the most common karyotype in patients with mgd , 46xy karyotype has also found in such patients . the only method of differentiating 46xy mgd from 46xy ot - dsd is by histopathological demonstration of testicular tissue . another point favoring mgd over ot - dsd is the presence of mullerian structures and testicular tissue on the same side , which is not seen in ot - dsd , as the testicular tissue is functional and secretes adequate amounts of mis . however , in mgd , since the testicular tissue is dysgenetic , mullerian structures may be preserved on the side of testicular tissue . the points that do not favor a diagnosis of mgd in our patient include an absence of short stature and turner 's stigmata . the most common genotype in these patients is 46xo / xx , however 46xy genotype has also been described , which can be difficult to distinguish from 46xy ot - dsd . the management of these patients can be difficult as phenotypically females may need multiple staged procedures for clitoroplasty , vaginoplasty , and gonadal biopsies / gonadectomies . phenotypically male patients may need multiple procedures for hypospadias repair with limited gain in corporal tissue . these patients are at increased risk of cancer , so it is prudent to remove the nonfunctional gonadal tissues . these patients usually need a multidisciplinary approach for management , but still long - term data on fertility and functional improvement of each approach of treatment is lacking .

a 16-year - old person , reared as female presented with complaints of genital ambiguity and primary amenorrhoea along with lack of secondary sexual characters , but without short stature and turner 's stigmata . she was taking steroids after being misdiagnosed as congenital adrenal hyperplasia ( cah ) . karyotype analysis revealed 46xy karyotype . there was no evidence of hypocortisolemia ( cortisol 9.08 g / dl , adrenocorticotropic hormone [ acth ] 82.5 pg / ml ) or elevated level of 17-oh - progesterone ( 0.16 ng / ml ) . pooled luteinizing hormone ( lh ) was 11.79 miu / ml and follicle - stimulating hormone ( fsh ) was 66.37 miu / ml . serum estradiol level was 25 pg / ml ( 21 - 251 ) . basal and 72 h post beta - human chorionic gonadotropin ( hcg ) levels of androstenedione and testosterone levels were done ( basal testosterone of 652 ng / dl and basal androstenedione of 1.17 ng / ml ; 72 h post hcg testosterone of 896 ng / dl and androstenedione of 1.34 ng / ml ) . magnetic resonance imaging ( mri ) pelvis ( with ultrasonogrphy [ usg ] correlation ) revealed uterus didelphys with obstructed right moiety and bilateral ovarian - like structures . right sided gonads and adjacent tubal structures were visualized laparoscopically and removed . left sided gonads were not visualized and mullerian remnants were adhered to sigmoid colon . histopathological examination revealed presence of testicular tissue showing atrophic seminiferous tubules with hyperplasia of leydig cells . no ovarian tissue was seen . based on these results a diagnosis of 46xy mixed gonadal dysgenesis ( mgd ) was made , which is rare and is difficult to distinguish from 46xy ovotesticular disorder of sexual differentiation ( ot - dsd ) . the patient was managed with a multidisciplinary approach and fertility issues discussed with the patient 's caregivers .

reports of spontaneous cholecystocutaneous fistulae have been found in medical literature dating back to the 17 century . fortunately , spontaneous cholecystocutaneous fistulae are a rare complication of cholelithiasis nowadays as prompt medical and surgical treatments address the underlying pathology when symptomatic . diagnosis of this rare entity often proves challenging as a significant proportion of patients with this complication present with non - specific symptoms . an 85-year - old lady with diagnosed gallstones ( 1996 ) , venous leg ulcers , congestive heart failure , hypertension , atrial fibrillation , anaemia and hypothyroidism presented to her gp with a 10 day history of a swelling in her right flank . three days later the mass spontaneously ruptured and she arrived at the emergency department with a 3 cm 2 cm erythematous , soft and non - tender mass which appeared to be discharging a serous - like material . when questioned she denied any previous history of pain , sudden weight loss , anorexia , jaundice or upper or lower gastrointestinal disturbances . physical examination was essentially unremarkable aside from a heart rate of 128 beats per minute . laboratory investigations revealed that she was anaemic ( haemoglobin ; 10.3g / dl ) , hyperkalaemic ( 5.3 mmol / l ) and her wbc count was within the lower limits of normal ( 4.8 x 10/ l ) . at this point a working diagnosis of an eroding / fungating caecal tumor was made . a computed tomography scan showed a low density mass measuring 8.1 2.6 5.1 cm in the right lateral wall of the abdomen ( figure1a ) . there was no evidence of a bowel related mass ; however there was a track of abnormal density that appeared to extend either from the biliary tree or the second part of the duodenum to the abdominal wall ( figure1b ) . the gallbladder was unidentifiable and the common bile duct measured 1 cm in diameter ; the upper limit of normal . a wedge biopsy reported purulent granulomatous tissue formation consistent with abscess formation and stated that there was no evidence of atypia or malignancy . the patient was discharged back under the care of her gp with the view of managing what was thought to be an abscess . a computed tomography scan showing the mass in the right lateral wall of the abdomen ( red circle ) and the fistulous track ( red arrows ) . over a three month period it was only when the district nurse reported 11 small , brown , hard calculi present in the dressings it became clear that the abscess was in fact a tract that directly communicated with the gallbladder / biliary tree ; a spontaneous cholecystocutaneous fistula . the diagnosis was later confirmed by magnetic resonance imaging cholangiopancreatography ( mrcp ) which reported a track of fluid that ran from the superior aspect of the common bile duct and passed to the lateral abdominal wall ( figure 2a ) . additionally , there is a track of fluid which runs from the superior aspect of the common bile duct and extends to the lateral abdominal wall it was thought that removal of any remaining calculi may aid spontaneous closure of the fistula . given the patient 's age and co - morbid state it was decided that a conservative approach was appropriate and removal of the calculi was performed by endoscopic retrograde cholangiopancreatography ( ercp ) balloon trawl and sphincterotomy.figures 3 and 4 show the fistula 6 months after initial presentation and following endoscopic retrograde cholangiopancreatography and balloon trawl . the opening of the fistula 6 months after initial presentation . note : the erythematous lesions surrounding the fistula are resultant of continuous dressing of the area . spontaneous cholecystocutaneous fistulae generally form as a result of neglected cholelithiasis , although a handful of cases have reported acalculous cholecystitis and carcinoma of the gallbladder as causative factors ( 1,2 ) . biliary outflow obstruction increases intramural pressure , restricts gallbladder perfusion and precipitates necrosis and perforation of the gallbladder . once perforated , it may drain into the peritoneal cavity , adjacent viscera or less commonly adhere to the abdominal wall to form an external fistula . most frequently , external biliary fistulae drain via a sinus in the right upper quadrant , however alternative locations such as the umbilicus , right groin , anterior chest wall and the gluteal region have also been reported ( 3,4 ) . treatment should include broad - spectrum antibiotics , drainage of the abscess and elective cholecystectomy with excision of the fistula . malik et al describe an approach that involves the laparoscopic removal of the gallbladder and dissection but not excision of the fistula from the abdominal wall ( 3 ) . this approach may provide an alternative option to open excision of the fistula for co - morbid elderly patients . this case elucidates the importance of maintaining a high level of suspicion and a low threshold for referral if a similar picture presents in primary care , particularly if the patient is elderly . a significant proportion of elderly patients do not have the classic symptoms normally associated with cholecystitis ( 5 ) . their symptoms tend to be more non - specific and often complicated by co - existent disease . delays in presentation due to psychosocial obstacles consequently mean that their disease may be more advanced or associated with more complications at initial presentation .

spontaneous cholecystocutaneous fistula , one of the rarest complications of acute cholecystitis , has been reported in fewer than 25 cases over the past 50 years . not only is this case rare but interestingly the patient experienced no pain or symptoms consistent with gallbladder pathology leading up to her hospitalisation . furthermore , laboratory studies , microbiology and computed tomography scanning did not establish a diagnosis until the fistula passed calculi.an 85-year - old lady with multiple co - morbidities presented to the emergency department with an erythematous soft and non - tender mass in her right flank . the mass had spontaneously ruptured and was discharging a serous - like material . prior to further investigation a working diagnosis of an eroding / fungating caecal tumour was made . the lesion continued to discharge over a 3 month period which heralded the passage of 11 small , brown calculi thought to be gallstones . at this point spontaneous cholecystocutaneous fistula was diagnosed and was later confirmed by magnetic resonance imaging cholangiopancreatography .

patients with overt diabetes and hypertension are exposed to an exceptionally high risk of cardiovascular death , and are generally thought to need a more intensive risk factor control . epidemiologic studies have shown that left ventricular hypertrophy ( lvh ) is the most powerful independent risk factor for cardiovascular morbidity and mortality in these patients . the prevalence of lvh in patients with essential hypertension is in average 40% ( range 12% to 70% ) , depending to a large extent on the measurement technique used [ 2 - 6 ] . the relationships between glucose metabolism abnormalities and lvh have been described in several reports [ 7 - 10 ] . however , the findings were controversial and inconclusive . the goal of this work was to elucidate whether gender differences in left heart structure and mass are present in hypertensive patients with type 2 diabetes . the international nifedipine gits study of intervention as a goal in hypertension treatment ( insight ) trial has studied hypertensive patients with at least one additional cardiovascular risk factor and thus with a clear - cut elevation in overall risk . the insight trial has also conducted a number of side arms in different countries to address several important issues for which information is still limited . over the course of 18 months 585 high risk patients with hypertension plus at least one additional risk factor who were recruited to the insight study in our region underwent echo - doppler examination . a total of 25 patients dropped out during the recruitment because of the technical reasons ( suboptimal echocardiographic images . therefore , 560 patients ( 314 men and 246 women , age 52 to 81 , mean 66 6 years ) , were enrolled in the present analysis . in 200 ( 36% ) of them 108 men and 92 women type 2 diabetes mellitus found upon enrollment ( prevalent diabetes group ) . the diagnosis of diabetes was made on the basis of the reported history and medical records . coronary artery disease ( cad ) was diagnosed in accordance with the insight clinical trial protocol : documented previous myocardial infarction , obstruction equal or more than 70% in at least one of the major epicardial arteries on coronary angiography , percutaneous transcoronary angioplasty or coronary artery bypass grafting , and based on accepted reliable medical records ( hospitalization summary and/or coronary angiography protocol . examinations were performed at baseline with a hewlett - packard ultrasound imaging system model sonos 1000 , 1500 or 2500 with a 2.5 and 3.5 mhz transducer . standard images were obtained from the left parasternal ( long and short axis view ) , apical ( long , two chamber and four chamber ) and subcostal views . two - dimensionally guided m - mode echocardiograms of the left ventricle ( lv ) were taken at cordal level , with the patient in partial left decubitus position , and three to five measurements were averaged . end - diastolic measurements of interventricular septal thickness ( ivs ) , lv internal diameter , and posterior wall thickness ( pwt ) were carried out in accordance with the american society of echocardiography recommendations . the left ventricular mass ( lvm ) was calculated by the formula introduced by devereux and reicheck and was indexed for body surface area to obtain the lvm index ( lvmi ) . left ventricular hypertrophy was diagnosed when lvmi was > 134 g / min men and > 110 g / min women . only frames with optimal visualization of interfaces and showing the septum , lv internal diameter and posterior wall simultaneously were used for reading all studies were recorded on a super - vhs tape and evaluated by 2 cardiologists with expertise in echocardiography , who were blinded to the presence or absence of diabetes . in case of disagreement statistical analysis for inter- and intra - gender comparisons was performed using the student 's t test . examinations were performed at baseline with a hewlett - packard ultrasound imaging system model sonos 1000 , 1500 or 2500 with a 2.5 and 3.5 mhz transducer . standard images were obtained from the left parasternal ( long and short axis view ) , apical ( long , two chamber and four chamber ) and subcostal views . two - dimensionally guided m - mode echocardiograms of the left ventricle ( lv ) were taken at cordal level , with the patient in partial left decubitus position , and three to five measurements were averaged . end - diastolic measurements of interventricular septal thickness ( ivs ) , lv internal diameter , and posterior wall thickness ( pwt ) were carried out in accordance with the american society of echocardiography recommendations . the left ventricular mass ( lvm ) was calculated by the formula introduced by devereux and reicheck and was indexed for body surface area to obtain the lvm index ( lvmi ) . left ventricular hypertrophy was diagnosed when lvmi was > 134 g / min men and > 110 g / min women . only frames with optimal visualization of interfaces and showing the septum , lv internal diameter and posterior wall simultaneously were used for reading all studies were recorded on a super - vhs tape and evaluated by 2 cardiologists with expertise in echocardiography , who were blinded to the presence or absence of diabetes . in case of disagreement , comparisons of proportions were made using the chi - square test . statistical analysis for inter- and intra - gender comparisons in inter - gender comparisons , men were older ; the prevalence of smoking and proven cad was significantly higher among them . no inter - gender differences were found regarding systolic and diastolic blood pressures on inclusion . in patients of both genders ( intra - gender comparisons ) no differences were found regarding age , systolic and diastolic blood pressures on inclusion , duration of hypertension and prevalence of cad . however , mean lvmi was significantly higher among diabetic women ( 112.5 29 vs 105.6 24 , p = 0.03 ) . only among diabetic women a significantly higher prevalence of increased ivs thickness , lvmi and left atrial diameter was found on intra - gender comparisons ( table 2 , figures 1 , 2 , 3 ) . the age adjusted relative risk for increased lvmi in diabetics vs nondiabetics was 1.47 ( 95% ci : 1.02.2 ) in females and only 0.8 ( 0.51.3 ) in males . baseline characteristics of the study population : number ( % ) or mean standard deviation sbp , dbp systolic and diastolic blood pressures on inclusion ; cad coronary artery disease ; htn duration - duration of hypertension ( years ) ; t2 dm type 2 diabetes mellitus ; * p < 0.05 . echocardiographic data in study patients * p < 0.05 , * * p < 0.001 ; ivs = interventricular septum , pw = posterior wall , lvmi = lv mass index > i 10 ( female ) and > 134 gr / m2(male ) ; la = left atrial diameter ; t2 dm type 2 diabetes mellitus . data are number ( % ) of patients . gender differences in increased left ventricular mass index ( lvmi ) prevalence ( percent ) . diabetic women present a larger lvmi than nondiabetic women , while opposite results are seen in men . both diabetic women and diabetic men present a larger ivs than their nondiabetic counterparts , but differences are significant only for women . both diabetic women and diabetic men present a larger la than their nondiabetic counterparts , but differences are significant only for women . in the present study diabetes mellitus was associated with increased prevalence of lvh ( in terms of increased lvmi and ivs ) in hypertensive women . it is predictor a poor prognosis , independently of blood pressure levels . in the framingham , the relative risk of cardiovascular mortality for every 50 g increment in echo lv mass was 1.73 in men and 2.12 in women , even after correction for risk factors such as blood pressure . in patients with established cad , the extra risk for cardiac death due to lvh is 2.8 , when adjusted for age , gender and hypertension . in these patients , this extra risk due to echo lvh appears to be greater than that for multivessel coronary disease or to lv dysfunction . recently , the close relationship between glucose metabolism abnormalities and other cardiovascular risk factors and diseases was emphasized [ 18 - 20 ] . in a previous study , lvh was present in 31% of diabetics , and systolic blood pressure was of no value in identifying those diabetics who had lvh , possibly because insulin resistance itself stimulates lvm growth . supposed that in addition to circulating insulin , insulin growth factor-1 is also an independent determinant of lvm and geometry in essential hypertension . however , galvin et al . concluded that insulin resistance and hyperinsulinemia are not independent predictors of left ventricular mass in humans . in a relatively healthy , population - based sample of hypertensive adults , type 2 diabetes was associated with higher lvm , more concentric lv geometry , and lower myocardial function , independently of age , sex , body size , and arterial blood pressure . in the present study , similarly to framingham cohort in addition , the prevalence of patients with increased left atrium diameter was significantly higher among diabetic women . we assumed that the latter phenomenon may be associated with increasing left atrial filling pressure following more pronounced lvh - related diastolic dysfunction . it is well established that diabetic women present a greater risk for cardiovascular morbidity and mortality compared to their male counterparts [ 24 - 26 ] . in this context , our findings could represent an important component of the underlying mechanism . whether diabetes is associated with changes in left heart structure independently of blood pressure and metabolic abnormalities type 2 diabetes mellitus was associated with a significantly higher prevalence of lvh and left atrial enlargement in hypertensive women . cad : coronary artery disease ; insight : intervention as a goal in hypertension treatment ; ivs : interventricular septal thickness ; lv : left ventricle ; lvmi : left ventricular mass index ; lvh : left ventricular hypertrophy . at and js envisioned the concept and prepared the initial draft of the article . at , ezf and ezf , es , ya and mm critically revised the manuscript for important intellectual content . this work was supported in part by the cardiovascular diabetology research foundation ( ra 58 - 040 - 684 - 1 ) , holon , israel , and the research authority of tel - aviv university ( grant 01250234 ) .

backgroundleft ventricular hypertrophy ( lvh ) is a powerful independent risk factor for cardiovascular morbidity and mortality among hypertensive patients . data regarding relationships between diabetes and lvh are controversial and inconclusive , whereas possible gender differences were not specifically investigated . the goal of this work was to investigate whether gender differences in left heart structure and mass are present in hypertensive patients with type 2 diabetes.methodsfive hundred fifty hypertensive patients with at least one additional cardiovascular risk factor ( 314 men and 246 women , age 52 to 81 , mean 66 6 years ) , were enrolled in the present analysis . in 200 ( 36% ) of them 108 men and 92 women type 2 diabetes mellitus was found upon enrollment . end - diastolic measurements of interventricular septal thickness ( ivs ) , lv internal diameter , and posterior wall thickness were performed employing two - dimensionally guided m - mode echocardiograms . lvh was diagnosed when lv mass index ( lvmi ) was > 134 g / m2 in men and > 110 g / m2 in women.resultsmean lvmi was significantly higher among diabetic vs. nondiabetic women ( 112.5 29 vs. 105.6 24 , p = 0.03 ) . in addition , diabetic women presented a significantly higher prevalence of increased ivs thickness , lvmi and left atrial diameter on intra - gender comparisons . the age adjusted relative risk for increased lvmi in diabetics vs. nondiabetics was 1.47 ( 95% ci : 1.02.2 ) in females and only 0.8 ( 0.51.3 ) in males.conclusiontype 2 diabetes mellitus was associated with a significantly higher prevalence of lvh and left atrial enlargement in hypertensive women .

bladder perforation should be included in the differential diagnosis , especially if patients are known to have an indwelling catheter . the laparoscopic approach is the best short recovery and less traumatic treatment for simple and accessible bladder injuries . a 73-year - old woman with a medical history of parkinson 's disease and chronic restrictive respiratory failure due to kyphoscoliosis was hospitalized for acute coronary syndrome . during hospitalisation , a bladder foley catheter of size 16 french was placed for drainage and haemodynamic monitoring . forty - eight hours later , she presented with acute respiratory distress and septic shock requiring ventilatory assistance . laboratory tests showed serum urea 10 mm / l and serum creatinine 232 m / l . plain radiographs of the abdomen did not reveal any signs of perforation or intestinal obstruction . together with vasoactive medication , intravenous antibiotics ( tazocilline and linezolid ) for nosocomial - acquired pneumonia were administrated . the pelvic sagittal scan showed the foley catheter perforated the urinary bladder and liquid effusion likely to be urine ( figure 1 ) . sagittal ct image showing urethral catheter in the abdominal cavity . due to systemic infection with no sign of improvement the patient underwent laparoscopic surgery with three trocars , a 10 mm umbilical trocar and two 5 mm trocars , one in each iliac fossa . abdominal exploration found bowel loops of the ileum clustered at the bladder and liquid in the peritoneal cavity . despite adhesiolysis methylene blue dye was injected through the foley catheter and it highlighted a 1 cm perforation in the bladder dome ( figure 2 ) with no other macroscopic lesions . methylene blue dye highlighting the bladder perforation the patient 's condition improved 24 hours after surgery allowing cessation of catecholamine and extubation . laparoscopic repair of intraperitoneal bladder perforation was first described in 1994 and since then , a few cases of such approach have been reported to treat traumatic , spontaneous and iatrogenic bladder rupture , avoiding laparotomy ( 1 ) . the laparoscopic approach is the best short recovery and less traumatic treatment allowing visualization of the entire peritoneal cavity to exclude others lesions . it can avoid laparotomy in 63% of the cases , decreasing its associated morbidity ( 2 ) . in the presence of simple and accessible injuries abdomino - pelvic ct scan is frequently performed in hospitalised patients and the bladder is included in the examination . in many cases familiarity with the different bladder pathologies and a routine meticulous search for them are indicated in every case . ( 3 ) early diagnosis and laparoscopic treatment might decrease the high mortality rate associated with this uncommon but treatable condition ( 4 ) . aged patients with an acute abdomen might not complain of abdominal pain , and abdominal tenderness might be relatively mild ( 5 ) . however , bladder perforation should be included in the differential diagnosis , especially if patients are known to have an indwelling catheter .

intraperitoneal perforation can occur as a rare but life threatening complication of indwelling urethral catheters . computed tomography ( ct ) revealed the bladder perforation by the foley catheter . the injury could not be managed conservatively due to the presence of systemic infection . we present the case of a successful laparoscopic repair of the bladder due to indwelling urethral catheter .

fournier 's gangrene ( fg ) is a life - threatening , rapidly progressive necrotizing infection of the perineal , perianal , and genital regions . the mortality of fg ranges between 7.5% and 88% , depending on patient risks , comorbidities , and severity of presentation , with most reports citing 2040% mortality . prompt diagnosis is essential in order to facilitate immediate operative debridement because the sequential progression of tissue necrosis can reach 23 cm per hour . consequently , diagnostic and therapeutic delays have been shown to increase morbidity , extent and number of surgical intervention(s ) , as well as mortality . although clinical examination in conjunction with confirmatory imaging ( usually computed tomography ) constitute the traditional diagnostic approach to fg , increasing number of clinical reports advocate the use of focused bedside sonography as an adjunctive imaging method in the setting of suspected fg.[579 ] a middle - aged man with a history of metastatic adenocarcinoma of the colon presented to the emergency department complaining of vomiting , severe testicular pain , and scrotal edema . his vital signs on arrival showed a blood pressure of 78/45 mmhg , a heart rate of 124 beats / min , and a temperature of 97.6 f. initial laboratory evaluation featured an elevated serum lactate of 3.5 mg / dl , leukocytosis ( white blood cell count 14,900 ) , and acute renal failure ( creatinine 3.14 mg / dl ) . his physical exam revealed acute edema and erythema of the scrotum , with crepitus and exquisite tenderness to palpation extending from the left scrotum to the left lower abdominal wall . bedsides , ultrasonography was performed to evaluate gas in the subcutaneous tissue of the scrotum and lower abdominal wall . the ultrasound showed small foci of gas within the tissues of the scrotum , with posterior acoustic shadowing [ figure 1 ] . concurrently , the patient underwent computed tomography of the pelvis and scrotum , which showed foci of subcutaneous air [ figure 2 ] . given these findings , the patient was immediately taken to the operating room with general and urological surgery services where he underwent extensive debridement of necrotic tissue of his scrotum and abdominal wall . scrotal ultrasound with subcutaneous gas bubbles and associated hyperechoic shadowing ct scan transverse showing subcutaneous air tracking from the left scrotum into the abdominal wall the patient recovered well postoperatively . his initial hospital care took place in the surgical intensive care unit , mainly due to the need for conscious sedation during serial wound - dressing changes and initial hemodynamic resuscitation related to underlying infection / sepsis . following the acute phase of his wound care , he underwent subsequent split - thickness skin grafting of the scrotum at approximately 2 weeks postadmission . . however , these findings can be present with other processes such as epididymitis or cellulitis . the hallmark of necrotizing infections is gas production by the bacterial organisms , which can sometimes ( but not always ) be appreciated on physical exam . in fact , estimates are that crepitus may not be detectable in as many as one - third of patients with the diagnosis of necrotizing infection . this may be especially relevant at the early infection stage when surgical intervention is least extensive . in addition to the physical exam , there are several diagnostic studies that can be used to evaluate necrotizing infections . plain radiography of the pelvis may reveal subcutaneous emphysema in the involved tissue planes . computed tomography ( ct ) may demonstrate adipose stranding , fascial thickening , as well as trace amounts of subcutneous gas . ct scan may also help in delineating the etiology of any associated and/or underlying infection , such as a perirectal abscess or other abdominal / pelvic processes . imaging evaluation in patients with fg may be limited by the frequent presence of concurrent acute renal failure ( thus precluding the use of intravenous contrast material ) or patient hemodynamic instability making transport to the imaging department unsafe [ figure 3 ] . ultrasound constitutes an excellent minimally invasive alternative in such situations because it allows for bedside evaluation for any associated scrotal pathology or soft tissue collection / abscess , and has been shown to identify subcutneous gas , even prior to the overt development of crepitus on physical exam . the characteristic ultrasonographic features of necrotizing infections include the presence of gas in the tissue , which will be bright ( hyperechoic ) with hyperechoic shadowing distally . this report highlights a case in which focused bedside ultrasonography was used in a critically ill patient to help delineate the etiology of his illness and expedite appropriate treatment . the diagnosis of fg is certainly a lot easier to make in the setting of advanced disease , when the patient has crepitus on exam , but these findings may only be seen in 1964% of cases on early presentation . it is in these cases where one needs to maintain a high index of suspicion for necrotizing infection and consider further diagnostic evaluation to determine the etiology . multiple imaging modalities may be used and it is up to the provider to balance time constraints , comfort with bedside diagnostics , and the role of imaging in their management of the emergent conditions at hand . ultrasound can easily be used at the bedside to evaluate for subcutaneous gas as well as other possible etiologies associated with similar clinical presentation , including testicular , scrotal , and soft tissue pathology .

fournier 's gangrene ( fg ) is a life - threatening , rapidly progressive necrotizing infection . if not recognized and treated early , it is associated with high morbidity and mortality . the classic physical exam findings of crepitus are seen in approximately two - thirds of patients during the early stages of fg . focused bedside sonography performed in cases of suspected gangrene represents an excellent adjunct in confirming the presence of subcutaneous gas and other signs of necrotizing infection . we present an illustrative case of a patient with fg who was evaluated with focused bedside ultrasonography .

this report describes a case of an unusual developmental venous anomaly ( dva ) which presented as intracerebral hemorrhage ( ich ) and intraventricular hemorrhage ( ivh ) associated with a single arteriovenous fistula ( avf ) demonstrated by superselective angiography and treated by endovascular glue embolization and to review relevant literatures . an 18-year - old male presented with sudden - onset drowsy mentality and vomiting during physical exercise , 30 minutes before admission in addition to left upper and lower extremity weakness ( grade iii / v ) . his initial glasgow coma scale score was 13 ( e3v4m6 ) and initial brain ct performed with a 64-slice multidetector scanner ( brilliance 64 , philips medical systems , cleveland , oh ) immediately after admission . the ct revealed severe ich with surrounding brain edema in the right parietal lobe and ivh in the bilateral lateral , 3rd and 4th ventricles ( fig . three - dimensional computerized tomographic angiography performed on the admission day showed no vascular abnormality suggesting ich . a post - operative neuroangiography was performed ( integris allura ; philips medical systems , best , the netherlands ) to highlight a prominent distal parietal branch of the pericallosal artery of the right anterior cerebral artery ; in the late arterial phase , dilated medullary veins and caput medusae appearance of a dva were seen . the superselective angiography clearly showed a single arterial feeder from the dilated distal parietal branch of the right pericallosal artery , and a single avf ; this fistula shared the dva - like venous channel ( fig . n - butyl cyanoacrylate - lipiodol mixture was injected at several millimeters proximal to the avs ( fig . after glue embolization of the avf , early venous drainage disappeared and dva was visualized only in the venous phase during control angiography ( fig . the early postembolization recovery was satisfactory and the patient was discharged one week after embolization with symptomatic sequelae as a result of ich . at five months after embolization , vascular malformations in the central nervous system have traditionally been classified into four categories : arteriovenous malformations , capillary telangiectasia , venous malformations and cavernous malformations ( 1 ) . dvas have been known by a variety of terms , including venous malformation , medullary venous malformation and venous angioma ( 1 ) . according to hussain et al . ( 2 ) and mullan et al . ( 3 ) , dvas represent an arrest during the development of the venous system , which results in the retention of primitive embryological medullary veins draining into a single large vein . dvas are not always detected on computerized tomography ( ct ) or magnetic resonance image ( mri ) , but they are never angiographically occult . characteristically , dvas have numerous dilated deep medullary veins presenting in " spoke wheel " or caput medusae configurations , which drain into a few dilated deep and/or superficial veins . angiographically , the arterial phase of a dva is normal and the venous phase shows one or more enlarged draining veins ( 2 , 4 ) . the most common vascular anomaly associated with a dva is a cavernous angioma , which occurs in 8% to 33% of patients ( 2 , 4 ) . the association of dva and arteriovenous malformation ( avm ) seems to be the least common ( 5 ) . there have been several reports describing hybrid malformations consisting of an avm and dva as a rare subset of mixed cerebrovascular malformations ( 3 , 6 - 12 ) . the majority of the reported hybrid cases were in fact a combination of typical dvas and additional avfs ( 3 , 6 - 12 ) . these lesions have been variously described as follows : mixed malformations of atypical avms and venous angiomas , arterialized venous anomalies , atypical avms , transitional forms between venous malformations and avms , avms draining into a large dva , or small avms with venous predominance ( 5 , 13 ) . mullan and colleagues ( 3 ) presented a particularly detailed analysis of the angiographic characteristics of dvas associated with avfs . all of them featured the classic star cluster of a dva , but additionally exhibited arterial fistulizations . ( 13 ) reported a series of 15 patients with intracranial vascular malformations that were angiographically classified as atypical dvas with arteriovenous shunts . this type of vascular malformation showed a fine arterial blush without a distinct nidus and early filling of the dilated medullary vein that drained these arterial components during the arterial phase on angiography . an angiographically defined arterial feeding vessel was noted in only one case and a preoperative embolization was performed . it was tabulated as one of their cases with no representative figures showing the vascular lesion . similarly , two cases have been reported by fok et al . ( 11 ) who showed unusual dva combined with an avf by superselective angiography . in contrast , we clearly demonstrated the angioarchitecture of atypical dvas associated with single avss . the potential risk of a dva appears to be due to its frequent association with other vascular lesions , which are under - recognized ( 5 ) . it has been suggested that the majority of hemorrhagic changes found in dva territories are usually due to their associated cavernous malformations ( 1 , 2 ) . also , many authors suggested that arterialized dvas or dvas with avm are at greater risk to developing complications than simple dvas , and that their natural history resembles that of classic avms ( 8 , 10 , 13 , 14 ) . in addition , we confirmed that an associated avf was the cause of spontaneous ich in dva by angiography . increased systemic venous pressure or increased local venous pressure secondary to stenosis of the draining transparenchymal vein or other venous obstruction could lead to hemorrhagic or ischemic complications ( 2 ) . recent knowledge of the benign nature of a dva without avf encourages a more conservative approach ( 1 , 14 ) . the risk of cerebral venous infarction occurring after excision or obliteration of a dva is significant and well known ( 15 ) . consequently , when an avm and a dva coexist , it is advisable to treat the avm while preserving the dva , which should serve as an important channel of the venous drainage from the regional brain ( 15 ) . ( 14 ) postulated that the prognosis of dva with an avf seems to be essentially as benign as that of a dva without an avf ; hence , conservative treatment is recommended , except for cases with a large hematoma or with a coexisting avm or a symptomatic , accessible cavernous angioma , which may be treated by surgical intervention . to treat a case of dva associated with an avm could be a challenge because resection will necessarily lead to an unfavorable alteration in the hemodynamic situation , with the removal of the venous drainage of nearby normal parenchyma ( 5 ) . in conclusions , the case presented here clearly demonstrated the detailed angiographic findings of atypical dva associated with an avf , including the arterial feeder , shunt site , and draining vein by superselective angiography . furthermore , the angioarchitecture described in this case would help understand a rare subtype of cerebral vascular malformation .

we present a case of developmental venous anomaly associated with arteriovenous fistula supplied by a single arterial feeder adjacent to a large acute intracerebral hemorrhage . the arteriovenous fistula was successfully obliterated by superselective embolization while completely preserving the developmental venous anomaly . two similar cases , including superselective angiographic findings , have been reported in the literature ; however , we describe herein superselective angiographic findings in more detail and demonstrate the arteriovenous shunt more clearly than the previous reports . in addition , a literature review was performed to discuss the association of a developmental venous anomaly with vascular lesions .

mucolipidosis ii ( ml ii disease , inclusion cell disease or i - cell disease ) and iii ( ml iii , pseudo - hurler polydystrophy ) are autosomal recessive disorders caused by defects in the glcnac-1-phosphotransferase ( ec 2.7.8.17 ) complex , which is composed by three subunits : , , and . mutations in the gene encoding the - and -subunits ( gnptab ) lead to ml ii alpha / beta ( omim # 252500 ) , or to the less clinically severe condition , ml iii alpha / beta ( omim # 252600 ) . ml iii gamma ( omim # 252605 ) is caused by mutations in the gene encoding the -subunit of glcnac-1-phosphotransferase , , and is thought to be the mildest form of the disease . very few cases of ml iii gamma are reported in the literature , maybe because the disease is underdiagnosed due to its relatively mild and unspecific clinical findings , which is suggested by a recent report of ml iii gamma patients diagnosed through next generation sequencing . to date , approximately 28 mutations have been reported in the gnptg gene . a large number of these mutations are unique or rare . de novo mutations are not rare events and the perception they are potentially important in genetic diseases , even in autosomal recessive conditions , have major implications for genetic counseling , . the present study consists of a report of a brazilian compound heterozygote patient with ml iii gamma resulting from the inheritance of one mutant paternal allele and one maternal allele that had most likely undergone a de novo or germline mutation . the proband , a female born at term to young ( maternal and paternal age at conception was 27 years old ) and non - consanguineous parents , has been described previously . she was referred for clinical genetic evaluation due to large joint contractures . on physical examination , the patient presented contractures and restrictions of movement , especially in the hands , feet and shoulders , and heart systolic murmur , audible mainly at the left sternal border . the two - dimensional color doppler echocardiography revealed the presence of mild thickening of aortic valve leaflets with mild regurgitation . the exam was performed through the subcostal window , as thoracic deformity prevented the use of standard echocardiographic measures of pulmonary artery systolic pressure . electroneuromyography of the upper limb was normal , and showed no electrophysiological evidence of peripheral neuropathy . the patient was diagnosed as having ml iii when she was 8 years old ( table 1 ) , and is currently stable . at the time of the study , she was 16 years old and attended regular school . genomic dna was extracted from leukocytes ( patient and both parents ) , buccal cells ( patient and mother ) and fibroblasts ( patient ) after informed consent was given . gnptg was amplified in five fragments containing exons 1 to 2 , 3 , 4 to 7 , 8 to 9 and 10 to 11 as described by persichetti et al . with modifications . the fragment which comprises exons 4 to 7 , where the mutation c.244_247dupgagt is located , was also amplified using a second pair of primers . samples were submitted to dna sequencing , performed on an abi prism 3500 genetic analyzer ( applied biosystems , foster city , ca ) . the sequence of the gnptg gene used as a template was genbank accession no . ng_016985.1 . total rna extraction was performed on a whole blood sample of the patient and her relatives , as well as three controls using the paxgene blood rna kit ( qiagen , germany ) , and conversion to cdna was made using the high capacity cdna reverse transcription kit ( applied biosystems ) , according to the manufacturer 's instructions . the gnptg mrna levels were determined by qrt - pcr using 2 sybr green pcr master mix ( applied biosystem ) with the mx3000p ( stratagene , amsterdam , nl ) . primers and conditions were performed as described by ho et al . with modifications . the relative quantification of the rna was normalized to the level of gapdh mrna in the same cdna using the comparative ct method ( 2 ) . for maternity testing , dna from each sample was analyzed by pcr multiplex reaction using the ampflstr identifiler pcr amplification kit ( applied biosystems ) , which enables the analysis of the 15 str markers ( strs ) using fluorescent primers , according to the manufacturer 's instructions . pcr products were then resolved by capillary electrophoresis in an abi3130xl genetic analyzer ( applied biosystems ) using genescan 500 liz as an internal marker and alleles were identified through genemapper software v1.2 ( applied biosystems ) . values obtained for the relative quantification of gnptg mrna in patient , parents and control samples were compared using student 's test ( ibm spss statistics version 20 ) . the proband , a female born at term to young ( maternal and paternal age at conception was 27 years old ) and non - consanguineous parents , has been described previously . she was referred for clinical genetic evaluation due to large joint contractures . on physical examination , the patient presented contractures and restrictions of movement , especially in the hands , feet and shoulders , and heart systolic murmur , audible mainly at the left sternal border . the two - dimensional color doppler echocardiography revealed the presence of mild thickening of aortic valve leaflets with mild regurgitation . the exam was performed through the subcostal window , as thoracic deformity prevented the use of standard echocardiographic measures of pulmonary artery systolic pressure . electroneuromyography of the upper limb was normal , and showed no electrophysiological evidence of peripheral neuropathy . the patient was diagnosed as having ml iii when she was 8 years old ( table 1 ) , and is currently stable . at the time of the study , she was 16 years old and attended regular school . genomic dna was extracted from leukocytes ( patient and both parents ) , buccal cells ( patient and mother ) and fibroblasts ( patient ) after informed consent was given . gnptg was amplified in five fragments containing exons 1 to 2 , 3 , 4 to 7 , 8 to 9 and 10 to 11 as described by persichetti et al . with modifications . the fragment which comprises exons 4 to 7 , where the mutation c.244_247dupgagt is located , was also amplified using a second pair of primers . samples were submitted to dna sequencing , performed on an abi prism 3500 genetic analyzer ( applied biosystems , foster city , ca ) . the sequence of the gnptg gene used as a template was genbank accession no . ng_016985.1 . total rna extraction was performed on a whole blood sample of the patient and her relatives , as well as three controls using the paxgene blood rna kit ( qiagen , germany ) , and conversion to cdna was made using the high capacity cdna reverse transcription kit ( applied biosystems ) , according to the manufacturer 's instructions . the gnptg mrna levels were determined by qrt - pcr using 2 sybr green pcr master mix ( applied biosystem ) with the mx3000p ( stratagene , amsterdam , nl ) . primers and conditions were performed as described by ho et al . with modifications . the relative quantification of the rna was normalized to the level of gapdh mrna in the same cdna using the comparative ct method ( 2 ) . for maternity testing , dna from each sample was analyzed by pcr multiplex reaction using the ampflstr identifiler pcr amplification kit ( applied biosystems ) , which enables the analysis of the 15 str markers ( strs ) using fluorescent primers , according to the manufacturer 's instructions . pcr products were then resolved by capillary electrophoresis in an abi3130xl genetic analyzer ( applied biosystems ) using genescan 500 liz as an internal marker and alleles were identified through genemapper software v1.2 ( applied biosystems ) . values obtained for the relative quantification of gnptg mrna in patient , parents and control samples were compared using student 's test ( ibm spss statistics version 20 ) . the genotype of the proband was c.[244_247dupgagt];[ 112c > g ; 328 g > t ] ( or p.[f83x];[e110x ] ) , as determined by leukocyte dna sequencing . to confirm this result paternal allele sequencing identified a heterozygous p.e110x mutation , which had been previously found by our group in two other unrelated brazilian ml iii patients always in cis with the 112c > g mutation ; sequencing of 100 control alleles did not show the presence of both mutations ( data not shown ) . based on these findings , buccal cells were collected from both individuals , and fibroblasts were obtained from the patient in order to investigate the possibility of mosaicism for the c.244_247dupgagt mutation in the patient and her mother . quantitative rt - pcr revealed that the amount of gnptg mrna found in blood samples of the patient , her father and her mother was approximately 1.6% , 54% and 88.5% of the levels found in controls ( fig . 2 ) . the probability of maternity was determined as 99.9999% by assessment of 15 different dna markers in the patient and her parents . on the basis of the present results , we propose that the new mutation c.244_247dupgagt is attributable to a de novo event which occurred in only one ovum , or to germline mosaicism in the mothers ' ova . although there is the possibility of mosaicism in the patient , this is an unlikely alternative , since more than one tissue was analyzed in the present study . unfortunately , the possibility of germline mutation or germline mosaicism could only be confirmed in this case through ovarian biopsy . we also consider very unlikely the possibility of preferential amplification of the normal allele ( e.g. , allele dropout of the mutant allele ) in the mother due to the presence , in cis , of any genetic variation in the annealing region of one of the primers used to amplify exons 4 to 7 of gnptab , since we use two different pairs of primers to amplify this fragment , both showing the same results . besides that , rna studies showed a decreased gnptg mrna in patient and her father , but not in her mother , supporting the hypothesis of a de novo or germline mutation . on average , 74 de novo single - nucleotide variants ( snvs ) and three novel indels are believed to occur in an individual 's genome per generation . the rates at which these phenomena occur are strongly influenced by factors such as parental sex and age , and dna sequences located next to the mutation , , . in the present case , maternal and paternal age at conception was not advanced , but just upstream to c.244_247dupgagt mutation , an indel ( tmp_esp_16_1411876 deletion ) has already been described , a finding which suggests this region of the gnptg is prone to mutations ( e.g. , a hot spot site ) . as expected , de novo germline mutations have been described more frequently in dominant disorders such as achondroplasia , apert syndrome and multiple endocrine neoplasia than in recessive disorders . studies of autosomal recessive disorders have also detected de novo germline mutations in one patient with ataxia - telangiectasia and in two patients with gaucher disease . from a genetic counseling perspective , the recurrence risk for an autosomal recessive disorder changes from 25% if both parents are carriers of a pathogenic mutation to a negligible value if only one parent is a carrier and there is no germline mosaicism in the other parent . there are few studies estimating the rates of germline mosaicism in recessive disorders , but for x - linked recessive disorders such as duchenne muscular dystrophy and hemophilia a , maternal germline mosaicism is believed to occur in up to 5% and 11% of mothers , respectively . this is the first report of a de novo mutation in ml iii gamma , and suggests that this kind of event probably occurs more often than currently recognized in recessive disorders . the present findings have major implications for genetic counseling , and strongly recommend that the carrier status of non - consanguineous parents of a child with - recessive disorders should always be confirmed through dna analysis .

mucolipidosis iii ( ml iii ) gamma is a very rare autosomal - recessive disorder characterized by the abnormal trafficking and subcellular localization of lysosomal enzymes due to mutations in the gnptg gene . the present study consists of a report of a brazilian compound heterozygote patient with ml iii gamma resulting from one mutant paternal allele and one allele that had most likely undergone a de novo or maternal germline mutation . this is the first report of a de novo mutation in ml iii gamma . this finding has significant implications for genetic counseling .

according to the updated recommendations of the international committee of medical journal editors ( icmje ) , " duplicate publication is publication of a paper that overlaps substantially with one already published , without clear , visible reference to the previous publication " ( 1 ) . for example , editors of influential cardiothoracic journals defined duplication as a result of : employing similar hypotheses and methodologies , reporting the same sample sizes and results , listing common authors , and presenting no or little new information ( 2 ) . generally , the practice of duplicate publications is unethical because it skews citation analyses , flaws evidence in meta - analyses , wastes reviewers ' and editors ' precious time and publishers ' resources , and shatters the integrity of research reporting ( 2 , 3 ) . the rate of duplicate publications has been examined in a few studies from different subject categories . the estimated rate ranged from 1.39% to 28.2% across clinical journals ( 4 - 10 ) . moreover , initial systematic evaluation of evidence processing revealed that 17% of randomized controlled trials and 40% of systematic reviews were published repetitively ( 11 , 12 ) . in 2012 , an analysis of 2,047 retractions of articles indexed in pubmed found that duplicate publication became one of the leading causes of retractions in recent years ( 13 ) . on a national scale , our initial evaluation of 455 korean original research papers indexed in the koreamed database in 2004 yielded the incidence of duplicate publication of around 6% ( 14 ) . to calculate the exact rate of duplication in national journals , it is essential to search through the most comprehensive country - based database of biomedical literature . the database is maintained by the korean association of medical journal editors ( kamje ) with support from the korean academy of medical science ( 15 ) . the committee for health technology planning and evaluation of the kamje has been running koreamed since december 1997 to ease access to local medical journals . in addition , there is the koreamed synapse database which is a digital archive and reference - linking platform for korean medical journals launched by kamje in november 2007 ( 15 ) . several recent cases of breach of publication ethics in korea highlighted the importance of adhering to the standards of publishing ethics and preventing scientific misconduct . one of the major steps towards implementing national ethical standards was the organization of the committee for publication ethics within kamje in 2006 . the committee has already positioned itself as a regulatory structure for maintaining publication ethics standards in korea . the kamje claimed that duplicate publication was the most common form of scientific misconduct and took the lead in a campaign against it in 2006 . as part of this campaign , the association examined the incidence rate and pattern of duplication in korean medical articles indexed in koreamed in 2004 . the aim of the current study is to analyze trends in duplicate publishing of local medical articles indexed in the koreamed database between 2004 and 2009 . we also aimed to evaluate the effectiveness of the kamje 's campaign against scientific misconduct . briefly , we reviewed 5% of the original research articles which were indexed in koreamed from january 2004 to december 2009 . the search was performed on 1st november each year from 2007 to 2012 by one librarian . after that , we searched through pubmed and google scholar using keywords from the title and names of the first , second and last authors of each indexed article . to retrieve korean medical articles which were not covered by pubmed , we performed additional searches through kmbase and koreamed employing the same search terms . three authors reviewed full texts of the screened articles regardless of whether the index and the returned article were or were not duplicates according to the criteria of duplication ( 2 ) and acceptable secondary publication ( 1 ) ( table 1 ) . if all the three authors ( reviewers ) agreed that the suspicious articles were duplicates , no further action was taken . when there was a disagreement , the decision was taken based on opinions of the two authors in agreement ( fig . we considered different patterns of duplicate publication which were earlier described by von elm et al . ( 12 ) as copying , salami slicing ( fragmentation ) and aggregation ( imalas ) . the number of duplicate publications and the direction of publication of the index articles and duplicates were also recorded . out of 455 , 467 , 460 , 462 , 466 , and 505 articles indexed in 2004 , 2005 , 2006 , 2007 , 2008 , and 2009 , respectively , 49 , 46 , 43 , 38 , 19 , and 23 original research articles were selected for screening . after a thorough check of full texts of the screened articles , 27 , 28 , 33 , 21 , 13 , and 6 items were confirmed as duplicates ( table 2 ) . prior to and at the start of the campaign against duplicate publications ( 2004 - 2006 ) , the duplication rate was relatively high in the range from 5.9% to7.2% . after the campaign ( 2007 - 2009 ) , the duplication rate steadily declined to 1.2% in 2009 ( fig . 2 ) . of the 133 duplicate articles , 71 ( 53.4% ) were copied , 37 ( 27.8% ) were salami sliced , and 25 ( 18.8% ) were aggregated ( imalas ) . the percentage of copied duplicates decreased from 65.5% in 2004 to 42.9% in 2008 , but the rate of salami - sliced items increased from 13.8% in 2004 to 42.9% in 2008 ( table 3 ) . of the 128 index articles , one was duplicated four and three times ( table 4 ) . of the 133 duplicate articles , 72 ( 54.1% ) were initially published in local journals and duplicated in international journals ; 42 ( 31.6% ) were published in local journals and duplicated in the same or other local journals ; and the remaining 19 articles ( 14.3% ) were published in international journals and duplicated in local ones . the shift from local to international sources was apparent during the study period ( table 5 ) . out of 455 , 467 , 460 , 462 , 466 , and 505 articles indexed in 2004 , 2005 , 2006 , 2007 , 2008 , and 2009 , respectively , 49 , 46 , 43 , 38 , 19 , and 23 original research articles were selected for screening . after a thorough check of full texts of the screened articles , 27 , 28 , 33 , 21 , 13 , and 6 items were confirmed as duplicates ( table 2 ) . prior to and at the start of the campaign against duplicate publications ( 2004 - 2006 ) , the duplication rate was relatively high in the range from 5.9% to7.2% . after the campaign ( 2007 - 2009 ) , the duplication rate steadily declined to 1.2% in 2009 ( fig . of the 133 duplicate articles , 71 ( 53.4% ) were copied , 37 ( 27.8% ) were salami sliced , and 25 ( 18.8% ) were aggregated ( imalas ) . the percentage of copied duplicates decreased from 65.5% in 2004 to 42.9% in 2008 , but the rate of salami - sliced items increased from 13.8% in 2004 to 42.9% in 2008 ( table 3 ) . of the 128 index articles , one was duplicated four and three times ( table 4 ) . of the 133 duplicate articles , 72 ( 54.1% ) were initially published in local journals and duplicated in international journals ; 42 ( 31.6% ) were published in local journals and duplicated in the same or other local journals ; and the remaining 19 articles ( 14.3% ) were published in international journals and duplicated in local ones . the shift from local to international sources was apparent during the study period ( table 5 ) . we found that the national duplicate publication rate in korean medical journals was relatively high throughout the pre - campaign period ( 2004 - 2006 ) : 5.9% in 2004 , 6.0% in 2005 , and 7.2% in 2006 . the rates dropped to 4.5% in 2007 , 2.8% in 2008 , and 1.2% in 2009 during the active campaigning by our medical editors ( fig . the current study suggests that positions of publishing ethics in the medical sciences have strengthened in korea . and we can now proudly claim that the ethics campaign involving experts from the kamje , the national research foundation and many korean societies achieved its goals . the kamje assigns the digital object identifier ( doi ) prefixes provisionally and the synapse links articles using the crossref system . the operation of these two national databases forms a basis for improved visibility of korean medical articles . importantly , koreamed and synapse were instrumental for tracking duplicate publications in local journals and curbing , at least partly , the problem of unethical publications . the widely known case of hwang woo suk , which surfaced as an appalling scientific misconduct in 2006 , affected the whole korean scientific community . as a consequence , experts and public at large became more concerned over the issues of duplicate publications and other forms of unethical conduct such as self - plagiarism . as part of the campaign , the committee on publication ethics of the kamje issued a position statement on duplicate publication and authorship . several guidelines were developed and a series of educational meetings arranged . in 2008 , google scholar started to cover data from the koreamed database . and that also allowed to properly organize actions against duplicate publications . the korean committee for publication ethics , established in 2006 , now successfully regulates medical ethics in korea . the committee accepted that duplicate publication is a serious threat to the medical community , and published a guide book of publication ethics in 2008 , which was revised in 2013 ( 16 ) . additionally , all known local cases of duplicate publication were categorized and published in a separate book in 2011 ( 17 ) . both publications are essential references on publication ethics for korean biomedical specialists . educational activities included five large meetings on publication ethics organized by kamje and dozens of individual trainings and public relation events . the korean committee for publication ethics has processed more than 120 cases referred from various institutions since 2006 . the kamje 's website now provides updates on publication ethics through the links to the relevant pages of the icmje and the committee on publication ethics ( cope ) . over the past years , the korean research foundation with the government 's support was also actively engaged in educational activities on research and publication ethics and contributed greatly to the national achievements in publication ethics . our data on a decline in duplicate publication rates are a clear evidence of the success of joint national efforts . first of all , we searched korean medical journals indexed in koreamed only , and it is possible that journals indexed in other databases have different rates and patterns of duplication . as of august 2013 , the rate of duplicate publications might have been low because of this relatively short time interval . third , the present study did not analyze duplication in different academic fields , subject categories , and authors ' posts . the declined from 5.9% to 1.2% rate of duplicate publications in korean medical journals reflects the impact of the publication ethics awareness campaign . the results of this study , monitored by koreamed and koreamed synapse , point to the positive changes in national ethics .

the purpose of this study was to examine trends in duplicate publication in korean medical articles indexed in the koreamed database from 2004 to 2009 , before and after a campaign against scientific misconduct launched by the korean association of medical journal editors in 2006 . the study covered period from 2007 to 2012 ; and 5% of the articles indexed in koreamed were retrieved by random sampling . three authors reviewed full texts of the retrieved articles . the pattern of duplicate publication , such as copy , salami slicing ( fragmentation ) , and aggregation ( imalas ) , was also determined . before the launching ethics campaign , the national duplication rate in medical journals was relatively high : 5.9% in 2004 , 6.0% in 2005 , and 7.2% in 2006 . however , duplication rate steadily declined to 4.5% in 2007 , 2.8% in 2008 , and 1.2 % in 2009 . of all duplicated articles , 53.4% were classified as copies , 27.8% as salami slicing , and 18.8% as aggregation ( imalas ) . the decline in duplicate publication rate took place as a result of nationwide campaigns and monitoring by koreamed and koreamed synapse , starting from 2006.graphical abstract

known human influenza dates back to the 12th century , but most lessons about its epidemiology have been learned from the three welldocumented pandemics of the 20th century that occurred during 19181919 , 19571958 , and 19681969 . influenza pandemics occur when a novel influenza virus emerges because of an antigenic shift , against which the vast majority of the world s population has no immunity . the 2009 pandemic is known to have been due to h1n1 virus related to swine influenza in 19181919 , a process referred to as antigenic recycling . natural influenza transmission in humans occurs over short distances , primarily via droplets and by contact . artificially aerosolized swine flu virus in air samples on chick embryos survived for 16 h. during influenza infection , the virus is shed in nasal and pharyngeal secretions and dispersed through sneezing and coughing . a recent review of experimental influenza studies in volunteers found that viral shedding peaked on the 2nd day of inoculation and stopped completely by the 6th or 7th day . however , viral shedding level and duration can be reduced by treatment . on the other hand , patients with seasonal influenza may be able to infect others 1 day before symptoms appear and up to 5 days after they appear . the united states centers for disease control and prevention ( us cdc ) have estimated that the incubation period of influenza a could be between 1 and 7 days but is more likely to be between 1 and 4 days . a study in japan indicates that most secondary cases are probably infected around the time of symptom onset of the index case ( ic ) . the world health organization ( who ) reported that the current estimates of the secondary attack rate ( sar ) of influenza a ( h1n1 ) was 2233% , while that of seasonal influenza was 515% . factors affecting sar are different both between and within countries . followup studies to measure the communicability of influenza a ( h1n1 ) is a priority for its prevention and control . the objective of this study is to quantify influenza transmission in household contacts of cases attending king khalid university hospital in riyadh , saudi arabia . this is a prospective study conducted between august and october 2009 and involved all reverse transcriptasepolymerase chain reactionconfirmed cases of influenza diagnosed at king khalid university clinics and confirmed as influenza a / h1n1 or seasonal influenza . only cases wherein the patient was the first person in his or her household to be affected by the disease were identified as the ic . a list of all household contacts was requested from the patient or his or her companions . on assumption that the attack rate is 25% ( 2030% ) among household contacts , the required number of household contacts to satisfy the study objectives was 288 . considering the average family size to be five persons and a response rate of 80% , 73 households were required . a complete history of the clinical picture and the history of exposure to suspected sources of infection were obtained for each case . the households of the ic were contacted by telephone every other day for 12 days . for all , personal data ( age and sex ) , relationship to the ic , and underlying diseases were collected in the first contact . an individual with acute respiratory illness , fever ( reported or documented ) and cough , sore throat , shortness of breath , difficulty in breathing , or chest pain was suspected to have h1n1 influenza . on the other hand , a suspected case of seasonal influenza is defined by the presence of fever > 38c ; feverishness when the temperature was not taken ; or at least two of the following symptoms : cough , sore throat , nasal congestion , rhinorrhea , sneezing , fatigue , headache , stiffness , or myalgia . sar was calculated as the number of h1n1 cases among the household contacts divided by the total number of household contacts . reproduction number was calculated as the number of secondary cases generated by the ic during its period of infectiousness . the chisquare test was used to test the association between categorical variables and the occurrence of suspect cases among contacts . relative risk ( rr ) and its 95% confidence interval ( ci ) were used to assess the association between manifestations of ic and infection among contacts . data were analyzed using spss version 17 ( spss inc . , chicago , il , usa ) . sar was calculated as the number of h1n1 cases among the household contacts divided by the total number of household contacts . reproduction number was calculated as the number of secondary cases generated by the ic during its period of infectiousness . the chisquare test was used to test the association between categorical variables and the occurrence of suspect cases among contacts . relative risk ( rr ) and its 95% confidence interval ( ci ) were used to assess the association between manifestations of ic and infection among contacts . patients with h1n1 influenza were significantly ( p = 0000004 ) younger ( 228 94 years ) than those with the seasonal flue ( 319 135 years ) . men constituted 578% of the total sample . while onethird of seasonal influenza patients were nonsaudi nationals , only 58% of h1n1 cases were nonsaudi nationals ( p = 0000 ) . cough was the most common symptom ( 899% ) followed by sore throat ( 783% ) and fever ( 739% ) in the case of h1n1 . cough and runny nose occupied the same rank ( 802% ) , followed by sore throat ( 78% ) in seasonal influenza ( table 1 ) . characteristics of cases of influenza in riyadh in 2009 included in the study as shown in table 2 , there were a total of 849 household contacts , 432 h1n1 cases , and 417 seasonal cases . a total of 157% household contacts , 169% h1n1 contacts , and 144% seasonal influenza contacts satisfied the suspected influenza criteria . suspected cases of influenza among contacts of h1n1 and seasonal influenza cases in large families in riyadh in 2009 the household reproduction number of h1n1 influenza among household contacts was 106 ( 084128 ) ( 73/69 ) , but it was only 066 ( 051081 ) ( 60/91 ) among household contacts of patients with seasonal influenza . table 3 reveals that among h1n1 influenza contacts , the incidence of infection was the highest among children 15 years of age ( 31% ) , followed by children 615 years of age ( 258% ) and adults > 15 years of age ( 119% ) . preschool children also had the highest incidence among seasonal influenza contacts ( 222% ) . men and women contacts had more or less the same incidence in both h1n1 ( 174% and 164% , respectively ) and seasonal influenza ( 143% and 145% , respectively ) . nonsaudi nationals had a higher incidence of both h1n1 and seasonal influenza than that of saudi nationals ( 375% versus 165% and 247% versus 114% , respectively ) . characteristics of h1n1 and seasonal influenza contacts and the occurrence of suspected influenza among them in large families in riyadh in 2009 table 4 shows that the risk of infection was nearly twice as high in contacts of h1n1 cases with runny noses compared with cases without runny noses ( rr = 186 , 95% ci = 119292 ) . this risk increased to 3fold in cases with coughing ( rr = 328 , 95% ci = 124869 ) . the risk of the infection of seasonal influenza contacts did not differ significantly in the presence of runny nose or cough ( rr = 113 , 95% ci = 063204 and rr = 063 , 95% ci = 037106 , respectively ) . knowledge of influenza pandemic transmissibility estimates is crucial in the development of effective mitigation strategies . households have historically comprised the bestdefined setting and lend themselves to natural laboratories for the study of transmission rates . , the reproduction number is a quantitative measure of pathogenic transmissibility . in this work , it was 106 ( 084128 ) for h1n1 and 066 ( 051081 ) for seasonal influenza , indicating that h1n1 is more infectious than seasonal influenza , but may also reflect the effect of media , which was more concerned about h1n1 and insisted the strict application of control measures in all the community including households . applied the epidemic model to weekly indicators of influenza mortality data from the usa , france , and australia and reported that an epidemic may occur if the reproduction number is > 1 , whereas transmission can not be sustained if it is < 1 . the same authors calculated the reproduction number of seasonal influenza in the usa , france , and australia and found it to be 13 for each with substantial interannual variability . this may indicate that the influenza virus is more transmissible in cold weather in the northern hemisphere than in the hot weather in the kingdom of saudi arabia . reviewed the literature and reported that the best estimate of the sar in usa was 273% among h1n1 influenza contacts . however , recent studies investigating the transmissibility of h1n1 influenza in japan , the uk , and the usa reported that the overall percentage of infected nonic ranged from < 5% to > 25% with infection rates of 811% and 13% in the largest studies . , , one of the findings of this study was that the sar is higher among young children contacts than adult contacts . one biological explanation for this finding is that younger children are less likely to be protected by prior immunity . monto , concluded that children are more susceptible than older age groups and that they contribute more extensively to spreading the virus across populations . they compared sequence data for the hemagglutinin of novel h1n1 with sequences of h1n1 viruses from 1918 to the present . in their composite , over 75% of confirmed cases of novel h1n1 occurred in persons 30 years old , with peak incidence in the age range , 1019 years . less than 3% of cases occurred in persons over 65 , with a gradation in incidence between ages 20 and 60 years . the sequence data indicate that novel h1n1 is most similar to h1n1 viruses that circulated before 1943 . we used the clinical who definition of influenza without laboratory testing to define influenza in contacts . however , studies have reported that 7580% of household transmission occurs directly from the influenzapositive index patient or from the same source of infection as the ic . , another limitation of the current study was that we could not identify asymptomatic cases ; as a result , the role of asymptomatic transmission was not investigated . also the calculated reproduction numbers are actually sars within families , which do not represent the reproduction numbers for the population as a whole ; the possible role of community in estimates of the reproduction number at the household level could not be excluded . studies conducted on the genetic sequences of influenza viruses recovered in families in the usa and canada suggested that transmission from community sources was rare in families in which an index patient had tested positive for influenza a. we calculated a sar of 169% among household h1n1 contacts and 144% among seasonal influenza contacts . preventive measures should be applied in households , particularly for children and contacts of cases presenting with cough or a runny nose . further research is needed to explain the propagation of seasonal influenza with an apparent reproduction number < 1 .

please cite this paper as : mohamed et al . ( 2011 ) communicability of h1n1 and seasonal influenza among household contacts of cases in large families . influenza and other respiratory viruses 6(3 ) , e25e29 . background quantitative knowledge of the transmissibility of influenza is crucial to its prevention and control . objectives to quantify the transmission of influenza a ( h1n1 ) and seasonal influenza in household contacts of patients with influenza diagnosed in a large university hospital . patients / methods a prospective study was conducted between september and october 2009 in which all confirmed cases of influenza diagnosed at king khalid university hospital were included . all household contacts were followed by telephone calls every other day for 12 days . they were asked about the development of influenza symptoms in addition to their age and nationality . results overall , 432 household contacts of 69 influenza a ( h1n1 ) cases and 417 contacts of 91 seasonal influenza cases were included . suspected influenza was diagnosed in 169% and 144% of household contacts of h1n1 and seasonal influenza patients , respectively . household reproduction numbers were 106 ( 084128 ) for h1n1 and 066 ( 051081 ) for seasonal influenza . children in households were more susceptible than were adults ( 222% versus 137% , respectively ) . evidence of coughing in the index case tripled the risk of infection in households afflicted with the h1n1 influenza [ relative risk ( rr ) = 328 , ci = 124869 ] , while evidence of a runny nose doubled it ( rr = 189 , ci = 119292 ) . conclusions communicability of influenza in households in riyadh is comparable to that in other countries . children are more susceptible to influenza infection . the presence of a cough or runny nose in the index cases increases the risk of infection .

intracranial pial arteriovenous fistula ( avf ) is a rare cerebrovascular malformation , accounting for only 1.6% of all vascular malformation of the brain.9)10 ) pial avf was once regarded as a type of arteriovenous malformation ( avm ) . however , current evidence suggests that the pathological characteristics and clinical presentations of pial avf , as well as its therapeutic options , are different from those of avm.23 ) pial avf has a single or multiple arterial connections to single venous channel without any intervening nidus . pial avf differs from dural avf in that the arterial supply is derived from pial or cortical arterial vessel and the location is not within the dural leaflets.10 ) because of high flow dynamics , pial avf is often associated with a venous varix.16 ) the majority of pial avf is considered congenital , and it is well known to be associated with congenital hereditary vasculopathies.7 ) disconnection of the arteriovenous shunt is sufficient to obliterate the lesion , so lesion resection is unnecessary . a 50-year - old man with a decreased mental state and a tonic seizure event was brought to our hospital . he had no past medical history and no history of head trauma . on initial neurological examination , he was in a drowsy state ( glasgow coma scale score of e3 v3 m6 ) with grade 2 left hemiparesis . computed tomography ( ct ) of the brain showed a subcortical hematoma measuring approximately 7 ml in the right temporoparietal lobe ( fig . 1 ) . on three - dimensional cerebral artery ct performed to evaluate the cause of the hemorrhage , there was no evidence of a definite vascular abnormality . cerebral angiography ( philips allura clarity fd 20/20 , best , netherlands ) was performed for further evaluation of vascular malformation and other causes of the hemorrhage . we performed super - selective angiography via utilization of a micro - catheter , and identified a pial avf supplied by the distal branch of the inferior division of the right middle cerebral artery , with early drainage into the right superior cerebral vein ( fig . 2 ) . under general anesthesia , the embolization procedure was performed using marathontm micro - catheter ( covidien , irvine , ca , usa ) . the working micro - catheter was primed with normal saline and dimethyl sulfoxide ( dmso ) in the standard fashion . a total of approximately 0.1cc of onyx 34 ( 8% ethylene vinyl alcohol copolymer , covidien , irvine , ca , usa ) was infused slowly under continuous fluoroscopic visualization . angiography obtained through a guide - catheter injection showed that the fistula had been obliterated and the onyx cast was seen stable . the patient 's mental state recovered to alertness , and his left - sided motor strength was improved . he was transferred to the department of rehabilitation medicine two weeks later for active rehabilitation . intracranial pial avf is a rare cerebrovascular lesion that for decades was considered a variant of avm . however , subsequent studies have revealed that pial avf is a distinct entity from cerebral avm , dural avf , or other cerebral vascular lesions due to the different angiographic findings , clinical course , and therapeutic options for pial avf.13 ) the abnormality from a pial avf arises from its high - flow nature . communication between an arterial feeder directly into a solitary draining vein without an intervening tangle of vessels creates conditions for rapid high flow . associated venous varices are produced by the high and turbulent flow from arteriovenous shunting.1)3)4)5)8 ) due to lack of intervening of vessels , there is higher pressure gradient , which can make such lesions more vulnerable to rupture , leading to a poor prognosis.2 ) pial avf can result from trauma17 ) or may be congenital . these lesions are more common in children and are frequently associated with hereditary hemorrhagic telangiectasia.12)22 ) it is possible that a misstep in embryological development of the cerebrovasculature produces these lesions . alternatively , abnormal angiogenesis and associated vascular growth factors and cytokines may play important roles.10 ) due to their rarity , little is known about the natural history of intracranial pial avfs . one study reported an association between conservative management of pial avf and high mortality : five ( 63% ) of eight patients who received conservative management died due to acute or subsequent fatal bleeding . therefore , due to its unfavorable natural course , pial avf requires surgical or endovascular treatment.15 ) patients with pial avf lesions can present with hemorrhage , seizure , headache , high - output cardiac failure in neonates and infants , macrocephaly , neurological deficits , intracranial bruit , and symptoms of increased intracranial pressure.6)14)18)19 ) the manifestations of pial avf vary according to patient 's age and the presence of a varix . in one report , younger patients ( < 15 years old ) were more likely to have a varix and symptoms related to shunting effect , while hemorrhage was the main presentation in older patients.23 ) treatment of pial avf differs from that of avm . because there is no nidus , disconnection of the arteriovenous communication could eliminate the abnormality without the necessity of lesion resection . in avm , resection of the entire lesion occlusion of only the feeding arteries of an avm leaves behind the nidus , which can recruit new arterial feeders that are often even more difficult to access by transarterial embolization . in addition , in avm , the draining veins must be obliterated because they may persist after resection and may recruit recommunication with collaterals . the pathological features of a congenital pial avf arise principally from its high - flow nature . treatment of pial avf by simply cutting off the shunt connection through surgery or endovascular intervention is sufficient , with removal of the entire vascular malformation was unnecessary.10)24)25 ) disconnection of the high - flow system leads to elimination of the abnormality and its accompanying elements , such as venous varices . disconnection of the arteriovenous shunting has traditionally been accomplished surgically by either clip application or cauterization of the vessel . . however , some lesions may be in deep or surgically inaccessible locations and are thus associated with high surgical risk . recent endovascular applications have been reported as successful means of disconnecting avf with a variety of different agents such as balloons , coils , glue , silk sutures , or polyvinyl alcohol.19)20)21 ) accessing the lesion via an endovascular route avoids the risks associated with craniotomy and surgical - dissection approach to the abnormality . however , endovascular attempts are not always successful or safe . high - flow lesions can make it difficult to deliver the desired embolic agent precisely to the fistulous point . delivery of embolic material into the draining vein can compromise venous outflow of the fistula or cause pulmonary embolus . restricted venous outflow in the setting of an incompletely obliterated fistula can have disastrous consequences.8)11)15)18)19 ) newman et al.16 ) reported that balloons have been used successfully to modulate and arrest the flow of feeding artery . it is therefore important to choose the safer and more effective therapeutic method in a case - by - case manner . as endovascular technologies continue to rapidly advance , we expect higher pial avf detection rates , as well as higher success rates with endovascular flow disconnection of arteriovenous shunting . pial avfs are rare intracranial vascular malformations , and due to their poor natural course and significant morbidity / mortality , prompt diagnosis followed by appropriate treatment is very important . with recent advancement in micro - catheters , embolic agents ( such as onyx ) , and other modalities ( such as recent interventional x - ray system ) , the endovascular approach can be a delicate and safe procedure for the treatment of pial avf .

intracranial pial arteriovenous fistulas ( avfs ) are rare cerebrovascular lesions consisting of one or more arterial connections to a single venous channel without an intervening nidus . because of the location and high flow dynamics of these lesions , neurosurgeons may have a difficulty deciding between endovascular treatment and open surgical treatment . we report on a patient who underwent endovascular treatment with liquid embolic agent . a 50-year - old man with a decreased mental state and a tonic seizure event was brought to our hospital . computed tomography ( ct ) of the brain showed a subcortical hematoma in the right temporoparietal lobe . on three - dimensional cerebral artery ct , there was no evidence of definite cerebrovascular abnormality . cerebral angiography showed a pial avf supplied by the right middle cerebral artery with early drainage into the right superior cerebral vein . the patient was treated with onyx embolization for definitive closure of the fistula . the patient was transferred to the department of rehabilitation medicine two weeks later with grade 4 left hemiparesis . the application of advanced equipment , such as the latest angiography and endovascular tools , will facilitate the correct diagnosis and delicate treatment of pial avf .

juvenile polyposis syndrome ( jps ) is an uncommon hamartomatous disorder with significant gastrointestinal malignant potential . approximately one - third of all jps cases have familial juvenile polyposis ( fjp ) , with a history of similar lesions in at least one first - degree relative.1 fjp is a rare ( < 1 out of 100,000 people ) autosomal dominant disorder with variable penetrance , which is characterized by isolated or multiple juvenile polyps.2 these polyps usually occur in the colon , but they can also be found in the stomach and the small bowel.1 - 3 jps is associated with germline mutations in several genes , including smad4 , bmpr1a , pten , and possibly eng.3 - 7 about 20% of jps patients have a germline mutation in smad4.6,7 the mechanism by which any of the known jps mutations cause hamartomas is not yet understood ; however , genetic testing is now commonly available for these syndromes . we report a novel germline mutation in exon 10 of the smad4 gene in fjp patients . a 21-year - old man presenting rectal bleeding visited our hospital . based on initial laboratory results , his hemoglobin was mildly decreased of 12.7 g / dl , but no additional abnormalities were found . histological examination revealed hamartomatous polyps with cystically dilated glands , which were surrounded by stroma and showed prominent inflammatory cell infiltration ( fig . upper endoscopy identified the presence of other lesions and revealed numerous reddish polypoid lesions in the whole stomach ( fig . capsule endoscopy was conducted and it showed numerous polypoid lesions in the jejunum and the ileum ( fig . we planned the surveillance with upper endoscopy and colonoscopy every 1 to 2 years , and also planned the evaluation of small bowel every 2 to 3 years . the patient 's 47-year - old mother had a history of subtotal gastrectomy due to gastric polyposis with anemia 15 years earlier . she had also undergone a right hemicolectomy because of ascending colon cancer 2 years previously . a colonoscopy performed during that time indicated a pedunculated polyp , which is similar to the type of polyp found in her son ( fig . the histological analysis of the polyps showed hamartomatous features that were consistent with juvenile polyposis ( fig . 2c ) upper endoscopy revealed multiple erythematous polyps in the stomach including cardia which are similar to her son ( fig . 2d ) . given the clinicopathological findings and the family history , the diagnosis was fjp . subsequently , written informed consent was obtained from both patients to perform genetic testing , and screening was performed to determine the presence of a germline mutation in the smad4 , pten , and eng genes in both patients . all coding exons and the flanking intronic regions of the smad4 , pten , and eng genes were amplified by polymerase chain reaction on a thermal cycler ( applied biosystems , foster city , ca , usa ) using primer pairs designed by the authors . direct sequencing was performed using the same primers on the abi prism 3130 genetic analyzer using the bigdye terminator cycle sequencing reaction kit ( applied biosystems ) . the sequences were analyzed using the sequencher program ( gene codes corp . , ann arbor , mi , usa ) and compared with the reference sequence . the direct sequencing analysis revealed a novel nonsense mutation in the smad4 gene in both the mother and the son . the mutation , a c to g transition at position 1239 in exon 10 , resulted in premature stop codon at tyrosine 413 ( p.tyr413 ) ( fig . jps is a rare form of the hereditary polyposis syndrome and is generally diagnosed using one or more of the following accepted clinical criteria:8 more than five juvenile polyps in the colorectum , juvenile polyps throughout the gastrointestinal tract , and any number of juvenile polyps in conjunction with a family history of juvenile polyposis . the disease usually presents with rectal bleeding and/or anemia in about two - thirds of cases . less common presentations include rectal prolapse of polyps , abdominal pain , or intestinal obstruction.2,3 juvenile polyposis is associated with an increased risk of gastrointestinal cancer . a recent cancer risk analysis calculated a cumulative lifetime risk for colorectal cancer in jps of 38.7%.9 in addition , several cases of stomach , duodenal , and pancreatic cancer in patients with jps have been described in the literature.2 cancer is thought to arise from a dysplastic change within the hamartomas.3 the risk of developing dysplasia or adenocarcinoma was greatest in patients who had at least three juvenile polyps or a family history of juvenile polyps.10 macroscopically , juvenile polyps vary in size from 5 to 50 mm , and they typically have a spherical , lobulated , and pedunculated appearance , with surface erosion.1,11 microscopically , a juvenile polyp is characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands , which are lined by cuboidal to columnar epithelium with reactive changes.1,11 mutations in genes related to the transforming growth factor- ( tgf-)/smad pathway have been linked to the development of jps . the smad4 gene is located on chromosome 18q21.1 and encodes a cytoplasmic mediator of the tgf- signaling pathway , which regulates a variety of biological processes , such as cell proliferation and immune modulation.12 most smad4 germline mutations published to date are small insertions / deletions and single base substitutions leading to nonsense , splice - site , or missense mutations.1,11 the most common mutation in smad4 is a 4 base deletion in exon 9 , which is therefore a mutational hotspot.13,14 loss of the wild - type smad4 which known as a tumor suppressor gene initiates tumorigenesis , the epithelium of jps polyps is intimately involved in the formation of the hamartoma and its subsequent progression to carcinoma.15 in addition , smad4 mutations are associated with a more aggressive gastrointestinal phenotype . they are involved in a higher incidence of colonic adenomas and carcinomas and more frequent upper gastrointestinal polyps and gastric cancer than patients with other mutations , such as the bmpr1a mutation.3,6,16 in the current report , both the patient and his mother affect upper gastrointestinal polyp and developed the colon cancer in his mother . evaluation and management of jps is mainly based on expert opinion . at risk patients or those with a high suspicion of jps should undergo endoscopic screening of the colon and upper gastrointestinal tract at age 15 or at the time of first symptoms.2,17 if a diagnosis of jps is made , the entire gastrointestinal tract should be examined for the presence of polyps . upper endoscopy / enteroscopy , upper gastrointestinal series , or small bowel follow - through have been recommended for use in upper gastrointestinal evaluation.1,17 capsule endoscopy can be used to detect intestinal polyps . it can identify small - sized polyps in the small intestine beyond the range of standard endoscopy.18 as capsule endoscopy is a safe and well - tolerated procedure , it may appropriately be employed as a baseline investigation in order to identify patients with small - bowel polyps . in our case , capsule endoscopy was conducted and it helps to identify the small bowel involvement of jps , as well as clarify the characteristics , including the size and shape of polyps . genetic testing can be useful for at - risk members of families where germline mutations have been identified . howe et al.19 suggested that with genetic testing noncarriers may no longer require frequent screening endoscopy , whereas gene carriers can be targeted for close endoscopic surveillance and early intervention to prevent the development of gastrointestinal cancers . endoscopic examinations of the colon and the upper gastrointestinal tract are recommended every 2 to 3 years in patients with jps.17 in patients with polyps , endoscopic screening should be performed yearly until the patient is deemed to be polyp free . patients with mild polyposis can be managed with frequent endoscopic examinations and polypectomy.20 endoscopic treatment of gastric polyps can be difficult , and patients with symptomatic gastric polyposis ( e.g. , severe anemia ) may need subtotal or total gastrectomy.1,3 in summary , this report describes a new smad4 mutation in a fjp family . careful family history , genetic screening , and endoscopic screening in jps patients are needed to identify fjp and the risk of malignancy in the gastrointestinal tract , and regular surveillance is recommended .

familial juvenile polyposis ( fjp ) is a rare autosomal dominant hereditary disorder that is characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of cancer . recently , germline mutations , including mutations in the smad4 , bmpr1a , pten and , possibly , eng genes , have been found in patients with juvenile polyps . we herein report a family with juvenile polyposis syndrome ( jps ) with a novel germline mutation in the smad4 gene . a 21-year - old man presented with rectal bleeding and was found to have multiple polyps in his stomach , small bowel , and colon . his mother had a history of gastrectomy for multiple gastric polyps with anemia and a history of colectomy for colon cancer . a review of the histology of the polyps revealed juvenile polyps in both patients . subsequently , mutation screening in dna samples from the patients revealed a germline mutation in the smad4 gene . the pair had a novel mutation in exon 10 ( stop codon at tyrosine 413 ) . to our knowledge , this mutation has not been previously described . careful family history collection and genetic screening in jps patients are needed to identify fjp , and regular surveillance is recommended .

according to the eau guidelines nephron - sparing surgery ( nss ) has a similar oncological outcome to that of radical surgery . however , nss is not suitable in some patients with localized renal cell carcinoma ( rcc ) because : 1 ) of locally advanced tumor growth , 2 ) partial resection is not technically feasible because the tumor is in an unfavorable location , 3 ) and/or significant deterioration of the patient 's general health . in these situations the gold standard curative therapy remains radical nephrectomy , which includes radical removal of the tumor - bearing kidney . acute pancreatitis has not yet been described in the published literature as a complication of radical nephrectomy . a 56-year - old patient was referred to the department of urology at the medical university of graz for right renal tumor ( ct scan verified a 12 cm renal mass ) to perform a radical nephrectomy . the preoperative anesthetic screening of our patient showed asa ii according to the american association of anesthesiology and well - controlled hypertension with normal laboratory blood tests . there were no co - existing infections the histological examination of the right kidney revealed a renal cell carcinoma ( rcc ) . the operation was uneventful . however , one day later the patient complained of gradually increasing , serious abdominal and back pain , including jaundice and fever . on physical examination , the patient had neither a history of biliary lithiasis nor chronic alcohol consumption or infections . laboratory data ( blood ) demonstrated urea 61 mg / dl ( n : 10 - 45 ) , uric acid 8.5 mg / dl ( n : 3.4 - 7 ) , potassium 4.3 mmol/ ( n : 3.5 - 5 ) , calcium 1.99 mmol / l ( n : 2.202.65 ) , aspartate aminotransferase 216 iu / l ( n : 0 - 35 ) , alanine aminotransferase 134 iu / l ( n:0 - 45 ) , lactate dehydrogenase 404 iu / l ( n:120 - 240 ) and amylase 989 iu / l ( n : 13 - 53 ) , lipase 2154 ( 0 - 60 ) , and procalcitonin 3.45 ( n:0 - 0.5 ) . white blood cell count was also raised ( 13000 ) , as well as crp 268 mg / l ( n:0 - 8 ) , bilirubin 1.43 ( n:0.1 - 1.2 mg / dl ) , and creatinine 2.78 mg / dl ( 0.6 - 1.3 ) . an abdominal ct scan was performed and demonstrated parenchymal edema of the pancreas ( figs . 1 and 2 ) . the patient was referred to the intensive care unit and treated conservatively for 15 days his medical condition improved and he was referred to the department of gastroenterology , where mr cholangiopancreatography showed no biliary stones , and a normal liver . the international symposium on acute pancreatitis in 1992 defined pancreatic necrosis as the presence of one or more diffuse or focal areas of non - viable pancreatic parenchyma . so , based on the patient 's clinical presentation and ct scan findings , the diagnosis of acute pancreatitis as a complication of radical nephrectomy was considered . the patient was referred to the intensive care unit ( icu ) and oral intake was prohibited . a nasogastric tube was inserted for decompression and parenteral nutrition was started from a central vein . ten days later , serum pancreatic enzyme levels and white blood cell count returned to normal ranges bowel movements became normal , and the patient passed stool . on the same day , the nasogastric tube was removed and restricted oral intake was permitted . on day 16 transperitoneal radical open nephrectomy is a generally accepted treatment for a renal mass greater than 10 cm in size . in the published literature according to burkey retroperitoneal dissection and ischemia could be risk factors for postoperative pancreatitis . however , this was not the case in our patient and trauma to the head of pancreas was avoided . according to milian et al the mortality rate of pancreatitis was 8.3% for conservative medical treatment versus 26.5% for surgical treatment . physicians should consider pancreatitis as a potentially life - threatening adverse event associated with propofol [ 6 , 7 ] , which may be due to failure of free fatty acid metabolism secondary to inhibition of free fatty acid entry into the mitochondria . we hypothesize that propofol could have played a role in the pathophysiology in this condition , because no biliary stone was demonstrated on preoperative or postoperative radiologic studies in the presented case . additionally , no other predisposing factors ( e.g. alcohol , infection , addiction or hypercalcemia as well as history of chronic pancreatitis ) for pancreatitis were present in our patient .

radical open nephrectomy is considered the standard treatment for kidney tumors or masses greater than 10 cm . we present a rare case of acute pancreatitis that occurred after right radical transperitoneal nephrectomy , which was treated by nonsurgical conservative interventions.the incidence of acute pancreatitis after renal surgery is not known in the literature.a 56-year - old man developed acute pancreatitis postoperatively after radical transperitoneal nephrectomy . an initial ct scan showed an enlarged pancreas with hypodense , heterogeneous consistency and with peripancreatic , perihepatic , mesenteric , and pelvic fluid collections . this complication was managed conservatively .

serotonin syndrome is a potentially life - threatening condition caused by excessive serotonergic activity in the central nervous system . it is characterized by mental status changes ( eg , confusion , agitation , lethargy , coma ) , autonomic instability ( eg , hyperthermia , tachycardia , diaphoresis , nausea , vomiting , diarrhea , dilated pupils ) , and neuromuscular hyperactivity ( eg , myoclonus , hyperreflexia , rigidity , trismus ) . serotonin syndrome classically occurs in patients receiving two or more serotonergic drugs , but it can occur with monotherapy . we report a case of a 20-year - old man who developed serotonin syndrome resulting from overdose of escitolapram with concomitant use of cocaine . it is a very important area in medicine as serotonin syndrome should be suspected especially in drug abusers who are being treated with psychotropic agents for mental illnesses . a 20-year - old male patient was admitted for altered mental status and agitation of unknown etiology . his past medical history was notable for depression and anxiety for which he had recently begun treatment with escitolapram ( selective serotonin re - uptake inhibitor ) , qetiapine ( atypical antipsychotic ) , and clonazepam ( benzodiazepine ) . approximately four hours prior to admission , he had snorted multiple crushed tablets consisting of percocet , escitolapram 20 mg , quetiapine 100 mg and clonazepam because of abdominal pain and worsening feelings of sadness . it was also reported that he had been using cocaine for one year for recreational purposes . the exact time of his last recreational cocaine use could nt be determined as patient was non - cooperative . on admission , the patient was confused , lethargic , non - communicative , disoriented and agitated with glasgow coma scale score of 10 . his physical examination was significant for tachycardia ( 133 beats / minute ) , elevated body temperature ( 101.4 f ) , slow and shallow breathing ( 11 breaths / minute ) , diaphoresis and generalized anxiousness . neurologic exam was positive for hyperreflexia , clonus on dorsiflexion of the feet , and muscular rigidity . the patient s respiratory rate gradually decreased with acompanying desaturations to 80% necessitating intubation with mechanical ventilation . serotonin syndrome was considered after ruling out infection and cerebrovascular accidents as potential etiologies for the patient s condition . he received one dose of lorazepam ( 2 mg iv push ) for agitation . within 24 hours , the patient s mental status had improved and he was able to be extubated . by the second hospital day , the patient was declared medically stable and transferred to the psychiatric ward . percocet ( oxycodone / acetaminophen ) , clonazepam and qetiapine ( serotonin , dopamine and adrenergic antagonist with negligible anticholinergic properties ) are known to depress cns function and may have contributed to patient s mental status but the clinical history and physical exam with autonomic instability ( hyperthermia , tachycardia , diaphoresis ) and neuromuscular hyperactivity ( hyperreflexia , rigidity , and myoclonus ) pointed more towards serotonin syndrome with the main culprits being escitolapram and cocaine as they both increase serotonin activity in the brain . this case represents a rare incidence of serotonin syndrome occurring after an intentional overdose of escitolapram . as such , it highlights the importance for physicians to maintain a high suspicion for serotonin syndrome as a potential diagnosis when encountering an agitated and confused patient known be on serotonin - modifying drugs . escitalopram is a selective serotonin reuptake inhibitor ( ssri ) , used to treat depression and generalized anxiety disorder . common side effects seen with escitolapram use are nausea , constipation , diarrhea , dizziness and impotence . an adverse effect of escitolapram , as with other ssris , is the serotonin syndrome.1 the symptoms are variable and can easily be missed.1 no single receptor appears to be responsible for the development of the serotonin syndrome , although several studies suggest that agonism of serotonin-1a ( 5-ht1a ) and serotonin-5a ( 5-ht2a ) receptors contribute substantially to the condition.2 cocaine prevents serotonin uptake and its combination with esciolapram may lead to serotonin syndrome.9 the diagnosis of serotonin syndrome is made clinically . it is characterized by mental status changes ( eg , confusion , agitation , lethargy , coma ) , autonomic instability ( eg , hyperthermia , tachycardia , diaphoresis , nausea , vomiting , diarrhea , dilated pupils ) , and neuromuscular hyperactivity ( eg , myoclonus , hyperreflexia , rigidity , trismus).1 the combination of ssris with other serotonergic drugs ( eg , tryptophan , illicit drugs like cocaine and mdma , ecstasy ) or drugs with serotonin properties ( eg , lithium , meperidine , triptans ) can lead to serotonin syndrome.3 serotonin syndrome classically occurs in patients receiving two or more serotonergic drugs , but it can occur with monotherapy . selective serotonin reuptake inhibitor ( ssri ) monotherapy has an incidence of 0.5 to 0.9 cases of ss per 1000 patient - months . 3 concomitant use of an ssri with a monoamine oxidase inhibitor ( maoi ) poses the greatest risk of developing serotonin syndrome . the hunter serotonin toxicity criteria are used to diagnose serotonin syndrome and require the presence of one of the following classical features or groups of features : spontaneous clonus , inducible clonus with agitation or diaphoresis , ocular clonus with agitation or diaphoresis , tremor and hyperreflexia , hypertonia , temperature above 100.4 f ( 38 c ) , and ocular or inducible clonus.3 there are no specific laboratory tests to diagnose serotonin syndrome . blood 5-ht levels are not useful because it is the local concentration at nerve terminals that is responsible for the physiologic effects.4,5 a strong clinical suspicion , known exposure to serotonergic agents , demonstration of specific signs and symptoms , and exclusion of other medical and psychiatric conditions are required for the diagnosis . key differential diagnoses to the serotonin syndrome are the other potentially life - threatening hyperthermic syndromes : neuroleptic malignant syndrome ( nms ) , malignant hyperthermia and anticholinergic poisoning.3 however , important points in history and physical examination facilitate the distinction between the three . nms is a reaction to several antipsychotic drugs , eg , such as chlorpromazine and haloperidol.5 nms is due to dopamine receptor blockade and it usually starts with muscular rigidity followed by hyperthermia and altered consciousness . unlike the serotonin syndrome , nms is exclusively caused by dopaminergic drugs . symptoms develop over days and resolve over days to weeks.5 in the serotonin syndrome , the onset and resolution of symptoms occur within hours . most patients present within 6 hours of increasing dosage , starting a new drug , or taking an overdose . a history of neuroleptic usage combined with the presence of bradykinesia or rigidity on examination distinguishes the nms from that caused by serotonin excess.5 it is important to note that serotonergic agents include nonprescription drugs , illicit drugs , and diet supplements . malignant hyperthermia ( mh ) is a rare life - threatening condition that is usually triggered by exposure to certain drugs used for general anesthesia ; specifically , the volatile anesthetic agents and the neuromuscular blocking agent , succinylchloine . it is due to an abnormally increased release of calcium from the sarcoplasmic reticulum.6,7 susceptibility to mh is often inherited as an autosomal dominant disorder , for which there are at least 6 genetic loci of interest , most prominently the ryanodine receptor gene ( ryr1).6 the syndrome occurs within minutes of exposure to the anesthetic agents , unlike serotonin syndrome , and presents with muscular rigidity , a hypermetabolic state reflecting increased oxygen consumption and increased carbon dioxide production , metabolic acidosis , and hyperthermia.7 the onset of symptoms , history of exposure to anesthetic agents , family history , and physical examination positive for skin mottling and hyporeflexia may distinguish malignant hyperthermia from serotonin syndrome.8 on the other hand , anticholinergic syndrome ( acs ) is produced by the inhibition of cholinergic neurotransmission at muscarinic receptor sites . the distinguishing feature of anticholinergic syndrome is dryness of the skin compared with diaphoresis in serotonin syndrome . successful management of serotonin syndrome relies upon prevention , early recognition , and supportive care . combinations of serotonergic medications should be avoided and at least 2 to 4 weeks should pass between discontinuation of an maoi and initiation of another serotonergic agent.6 acute management is based on 2 simple principles : discontinuation of all serotonergic medications and provision of necessary supportive care . severe forms of the syndrome may require aggressive measures , including neuromuscular - blocking agents , mechanical ventilation , benzodiazepines ( for sedation ) , and external cooling.6 mild cases generally resolve within 24 to 72 hours with conservative therapy and removal of the causative drugs . patients who are severely hyperthermic with temperatures > 41 c ( 106 f ) should be given iv sedation , paralyzed , and intubated . in addition , pharmacologic therapy in the acute management of serotonin syndrome includes benzodiazepines ( lorazepam or diazepam ) and nonspecific serotonin receptor blockers such as cyproheptadine , chlorpromazine , methysergide , and propranolol.6 benzodiazepines are used for control of agitation and preferred over physical restraints . the efficacy of cyproheptadine in the treatment of serotonin syndrome has been documented.4 atypical antipsychotic agents with serotonin antagonist properties ( eg , olanzapine 10 mg sl ) have been tried with some success . this case shows a rare incidence of serotonin syndrome with escitolapram use and concomitant abuse of cocaine.9 it is very important that physicians are familiar with the signs and symptoms of serotonin syndrome and should suspect it in anyone with altered mental status who is taking serotonin - modifying drugs . because of its protean manifestations , the illness can easily be missed while the patient is subjected to a variety of unnecessary tests . in addition , the offending agent may be continued , causing an exacerbation of the syndrome with devastating consequences . this case emphasizes the fact that drug abusers with mental illness on psychotropic pharmacological agents have a very high incidence of developing serotonin syndrome .

introductionserotonin syndrome is a potentially life - threatening condition caused by excessive serotonergic activity in the central nervous system . it is characterized by mental status changes ( eg , confusion , agitation , lethargy , coma ) , autonomic instability ( eg , hyperthermia , tachycardia , diaphoresis , nausea , vomiting , diarrhea , dilated pupils ) , and neuromuscular hyperactivity ( eg , myoclonus , hyperreflexia , rigidity , trismus ) . serotonin syndrome classically occurs in patients receiving two or more serotonergic drugs , but it can occur with monotherapy . we report a case of a 20-year - old man who developed serotonin syndrome resulting from overdose of escitolapram with concomitant use of cocaine . it is a very important area in medicine as serotonin syndrome should be suspected especially in drug abusers who are being treated with psychotropic agents for mental illnesses .

the quantitative study of brain development in vivo during childhood and adolescence began in the late 1980s . subsequent cross - sectional and mixed longitudinal/ cross - sectional studies have confirmed that although total brain volume changes negligibly between ages 5 and 18 , this masks robust and complex changes in white and gray matter compartments . white matter volume and signal intensity increase linearly during this age range , presumably reflecting increasing myelination , and gray matter volume increases until early to mid - adolescence before decreasing during late adolescence , apparently representing synaptic pruning and reduction in neuropil , which has been documented during these developmental periods . though most existing studies begin after age 4 , these show that cortical gray matter volumes reach their peak at about age 12 in frontal and parietal lobes , and that the maximum for temporal lobe gray matter occurs about 4 years later . in healthy normal volunteers , the white matter intensity of the left ( but not the right ) arcuate fasciculus increases monotonically with increasing age throughout adolescence , suggesting that continuing development , of language - related functions may be reflected in these anatomical changes . the cross - sectional area , of anterior regions of the corpus callosum also reaches adult , size long before posterior regions . since changes in white matter volumes may reflect more than just myelination , it is not clear if these findings contradict the tentative conclusions formulated by yakovlev and lecours , but novel techniques such as diffusion tensor imaging should help clarify this question . anatomic hypotheses of the substrates of adhd have focused on the role of the prefrontal brain . normally , the right , anterior brain is slightly , but . significant , decreases in this asymmetry in adhd have been observed using computed tomography and magnetic resonance imaging ( mri ) . volumetric measures have also detected smaller rightsided prefrontal brain regions in boys with adhd , which were correlated with neuropsychological performance on tasks that required response inhibition . in the only study to date to use voxel - based unbiased analyses , gray matter deficits in adhd were found in right superior frontal gyrus ( brodmann areas 8 and 9 ) and right posterior cingulate gyrus ( brodmann area 30 ) . such voxelbased methods have not yet . been applied to the national institute of mental health ( nimh ) dataset of mri images . algorithmically obtained measures recently applied to these images have shown that total cerebral volume is decreased in subjects with adhd by 3% to 4% by comparison to age- and sex - matched controls . these differences were roughly equivalent , across all four major lobes ; laterality measures were not obtained because of limitations of the algorithm used . along with the prefrontal cortex , the caudate nucleus and its associated circuits have long been suspected to play a pivotal role in adhd . abnormalities of caudate nucleus volume or asymmetry have been reported , although the studies differ in whether the normal caudate is asymmetric , and whether this asymmetry normally favors the right or the left caudate . these inconsistencies may reflect differences in methodology and comorbidity . in girls with adhd , we found no differences in asymmetry relative to controls , but the adhd girls had smaller left and total caudate volumes , which remained significant after covariance for total cerebral volume and wechsler intelligence scale for children - revised ( wisc - r ) vocabulary subscale score . combining boys and girls , we were unable to measure right and left caudate nucleus volumes separately when caudate volumes were compared with those of controls , diagnostic differences were only present for subjects between ages 6 and 15 years . neither of the anatomic mri studies that reported putamen volumes detected significant diagnostic group differences . however , studies of secondary adhd suggest that the putamen lesions can contribute to adhd symptomatology . in a study of 76 children with severe closed head injury , those who developed secondary adhd were significantly more likely to demonstrate lesions in the right putamen . likewise , children with focal strokes and adhd symptoms were significantly more likely to have involvement of right ventral putamen . . this impressive convergence of information is then processed and emerges from the output , nuclei of the basal ganglia , which , in primates , are the internal segment , of the globus pallidus and the substantia nigra pars reticulata . however , the volume of the latter can not be reliably measured with current mri parameters , and the size of the globus pallidus can only be measured as a unit ( internal and external segments together ) , and then only with difficulty . still , this region was found to be significantly reduced in size in boys with adhd , although these two studies differed in side of the larger difference ( left or right ) . globus pallidus volume differences in girls with adhd did not survive covariance for total cerebral volume and iq . a report of two cases of severe iatrogenic adhd presumed to have been caused by traumatic amniocentesis at 17 weeks ' gestation found complete ablation of right caudate , putamen , and globus pallidus in both . an early computed tomography study found a trend toward greater cerebellar atrophy in adults with a prior history of hyperkinetic minimal brain dysfunction . in a quantitative mri study of 112 subjects , the volumes of the cerebellar hemispheres were found to be significantly smaller in adhd boys . in a follow - up study within the same sample , the cerebellar vermis as a whole , and particularly the posterior - inferior lobules ( lobules viii to x ) were found to be significantly smaller in adhd . smaller lobules viii - x were independently replicated in boys with adhd , and in girls with adhd where the posteriorinferior cerebellar vermis was the only structure that was rigorously replicated , with a comparable standardized effect size ( d=0.66 in boys , d=0.63 in girls ) . recently completed automated analyses of brain anatomy in 152 children and adolescents with adhd and 139 age- and sexmatched controls revealed highly significant global decreases in overall cerebral volume in patients , which were statistically comparable in all four lobes , and which were statistically more prominent only in cerebellum . although most , studies have used small samples and quantitative methodology is still evolving , anatomic mri studies support , the notion that a distributed circuit underlies some of the manifestations of adhd . at least in boys , this circuit appears to include right prefrontal brain regions , the caudate nucleus , globus pallidus , cerebellar hemispheres , and a subregion of the cerebellar vermis . with one exception , all groups have reported reduced volumes ( or areas ) , which is consistent with the broad notion that the relevant brain regions are hypofunctioning . is generally accepted , to a first , approximation , that cortico - striatal - thalamocortical ( cstc ) circuits select , initiate , and execute complex motor and cognitive responses , and that cerebellar circuits provide on - line guidance of these functions . the remarkable selectivity of the result within the cerebellar vermis , ie , that , the region involved is limited to the posterior - inferior lobules , together with the finding that this is the only region in the cerebellum that receives a dense dopaminergic innervation , support , the speculation that the vermis exerts important regulatory influences on prefrontal - striatal , circuitry via the ventral tegmental area and locus cerulcus . such effects may go beyond known cerebellar vermal influencing of cardiovascular physiology and heart rate conditioning , which have been implicated in the state dysregulation hypothesis of adhd . more specifically , it is possible that findings such as smaller anticipatory cardiac deceleration and greater low frequency heart rate variability , which are associated with poor motor activation state and greater difficulty in allocating effort , respectively , may be anatomically linked to dysfunction in the vermis outputs to midbrain monoaminergic nuclei . also worth considering is the hypothesis that the remarkable trial - to - trial variability in responding on speeded reaction time tasks by patients with adhd may reflect , deficiencies in temporal computations performed within cerebellum . while there remain many questions yet to be addressed using anatomic neuroimaging , testing these specific hypotheses will require interdisciplinary efforts that are just now beginning .

neuroimaging techniques are increasingly being applied to the study of attention - deficit / hyperactivity disorder ( adhd ) . this review focuses on magnetic resonance imaging studies of the brain anatomy of adhd . such studies were first conducted over a decade ago , and most focus on frontal - striatal regions and tend to find smaller volumes in adhd children than in controls . recently published analyses with the largest sample so far of patients and controls found that adhd is associated with a statistically significant 3% to 4% global reduction in brain volume in both boys and girls , with abnormally small caudate nuclei only being found in younger patients . after adjusting for global brain differences , only cerebellar hemispheric volumes remained significantly smaller in adhd , and these differences continued throughout childhood and adolescence . pathophysiological models of adhd need take into account cerebellar dysfunction , as well as prefrontal - striatal dysregulation .

kidney injuries following blunt abdominal trauma in humans are described in 310% of cases [ 1 , 2 ] . the most common cause of blunt renal trauma is the mechanism of rapid kidney deceleration , which occurs in motor vehicle accidents , falls from height , or on a direct impact in the lumbar area . these may result in damage to the kidney , which is classified on the basis of diagnostic imaging and exploratory surgery as grade i to v , according to a scale developed by the american association for the surgery of trauma ( aast ) . after this scale , the most severe type of kidney injury is its fragmentation or vascular pedicle avulsion from the main renal vessels with the interruption of renal blood flow ( grade v injury ) . among the atypical kidney injuries reported are : a complete avulsion of the renal pelvis from the kidney with its main blood supply maintained , avulsion of the renal pelvis with the renal calyxes from the renal hilum , pedicle avulsion accompanied by spleen rupture , post traumatic spleen rupture with concurrent pedicle avulsion , as well as cases of renal vascular pedicle avulsion in animals as a result of blunt abdominal trauma in a traffic accident . grade v renal injury is regarded as life threatening , requiring urgent surgical intervention . if renal injury is accompanied by another abdominal organ injury , a wide transperitoneal approach for surgical procedure the authors present a case of blunt abdominal trauma with subsequent rupture of the spleen and avulsion of the left renal artery from the aorta . a male patient aged 29 years was admitted to the hospital emergency department ( sor ) of the hospital trauma centre wss5 in sosnowiec in serious condition following a massive multiorgan injury after being crushed by a large block of coal in a mine . basic blood tests showed erythrocytes 2.19 1012/liter , hemoglobin 5.2 grams / liter , hematocrit 21.3% , plt 125 thousand , na 143 , k 6.7 , creatinine 27.36 mmol / liter , urinalysis revealed ph 5 , sg 1.010 , leukocytes 0 , and erythrocytes single / lpf . the arterial blood pressure ranged from 70/50 to 110/80 mmhg and the pulse rate from 90 to 115/min . after controlling the shock and stabilizing the vital functions by transfusion of sufficient amount of colloid solutions , crystalloids , and erythrocyte mass , a left pleural cavity drain was made because of emphysema . then a full body contrast enhanced ct scan was performed , which revealed fluid of the density of 40 hu extravasated blood in the abdominal subphrenic area and around the lower edge of the liver ; no injuries to the right kidney ; a lack of contrast of the injured left kidney in the arterial phase , no cortex enhancement ; the left renal artery visible only in the proximal section , not contrasted in the farther section ( figure 1 ) . a small amount of extravasated blood around the left kidney , and much grater amount around the spleen was visible . within the central part of the spleen a visible part of uncontrasted parenchyma suggested a rupture gap . a lack of contrast of the injured left kidney in the arterial phase . the opening of the peritoneal cavity by a median incision revealed the presence of 1,000 ml of blood and a longitudinal rupture of the spleen , which was removed . on palpation of the retroperitoneal space a small hematoma was found on the left side . after a posterior lamina incision and kidney dissection , its significant pallor was noted with no signs of renal parenchyma damage . a pedicle dissection revealed the pararenal stump of the renal artery and the intact renal vein . vascular clamps were put on the left renal vein , the ureter was ligated and the kidney was removed . the para aortic stump of the renal artery was rotated back from the aorta , shrunken and bleeding , and it was therefore ligated . the patient was transferred to the intensive care unit ( icu ) . in the following days , due to increasing signs of renal failure and metabolic acidosis , the patient underwent several hemodialyses . the patient was discharged home in a good condition fifty five days after the trauma . injuries to the main trunk of the renal artery or its large branches constitute 2.54% of the blunt renal trauma incidence . described herein , the complete interruption of the left renal artery was accompanied by the splenic rupture . most authors are of the opinion that the conservative treatment of isolated injuries of large renal vascular trunks should be applied in specific cases and is related to a very high risk of massive bleeding . as described by elliot et al . of 81 cases of major and segmental renal arterial injuries , concomitant damage to any abdominal organ is an indication for urgent open surgery . in such cases the kidney removal is performed , however , some authors describe corrective surgeries of the damaged renal vessels , underlining that the postoperative recovery of these patients is worse . the effect of revascularization after blunt trauma , leading to the interruption of the renal artery is worse than in the case of revascularization after a sharp vessel cut . the authors suggest that after blunt trauma , damage to the endothelium leads to thrombosis . such thrombosis was observed by the authors who have described renal blunt trauma and renal artery avulsion in a dog . in the case presented herein , on the retroperitoneal revision , the para aortic section of the stump of the renal artery did not bleed , probably due to resulting thrombosis . this mechanism explains why such a serious injury , that is , a complete interruption of the main trunk of the renal artery did not lead to the death of the patient . czyak et al report two cases of renal pedicle injury , which were treated conservatively . the second patient was operated on the fourth day after the injury , which revealed the presence of a perirenal hematoma . the para aortic stump of the renal artery was not found , and the kidney was removed following ligation of the renal vein . an assessment of the appropriate type of renal injury is crucial in deciding the treatment . the widely used i v aast classification refers to a diagnosis based on imaging studies and intraoperative assessment of the kidney . federle 's classification distinguishes four grades of renal injury , wherein grade iv corresponds to grades iv and v of the aast scale . in our case we have relied on the aast scale , categorizing this type of injury as the interruption of the continuity of at least one of the structures of the renal hilum with its total ischemia ( grade v ) . it was decided , therefore , to explore the retroperitoneal space and thoroughly search for the confirmation of the diagnosis made on the basis of ct . during the exploration of the kidney its pallor accompanied by a small hematoma in the retroperitoneal space and the absence of any damage to the renal parenchyma were observed . however , there is justifiable fear that without the initial diagnosis made on the basis of ct , such a serious injury as a complete interruption of the continuity of the artery could be overlooked during the routine inspection of the retroperitoneal space , as has been pointed out by czyak et al . . it allows for indicating the exact location and type of the injury to all the abdominal organs , including the kidneys . the lack of contrast enhancement of the kidney is a pathognomonic indication of vascular pedicle injuries . when one kidney is damaged , the assessment of the functional status of the other kidney helps decide about the choice of suture of the injured kidney . in blunt trauma , especially in falls from height , this results in a reflex contraction of the renal artery , which in the radiographic imaging ( ct , urography ) is displayed as an inactive kidney , suggesting extensive renal injury , including damage to the kidney pedicle . in this type of isolated injury , a patient 's clinical condition is good , and the kidney imaging repeated after a few hours shows a normal kidney . in polytrauma , patients are usually unstable . doppler ultrasound should be used as a valuable tool in the diagnosis of renal vascular trauma . in life threatening hemodynamic cases requiring urgent surgical intervention , an intravenous contrast dose of 2 ml / kg and x ray after 10 minutes allows for making a decision as to the type of intervention . unstable patients who require emergency surgical exploration should undergo one shot of ivp with bolus intravenous injection of 2 ml / kg contrast . during renal exploration at laparotomy , special attention should be paid to the color of the renal parenchyma , not merely to the damaged parenchyma , or the condition of the upper urinary tract .

this study presents a case of avulsion of the left renal artery from the aorta and splenic rupture after blunt abdominal trauma accompanied by an extensive crush syndrome . based on contrast enhanced abdominal ultrasound and computed tomography ct , the patient was qualified for urgent surgical intervention with removal of the injured kidney and spleen .

rocket af was a multicentre , randomised , double - blind , double - dummy , trial comparing fixed - dose rivaroxaban with adjusted - dose warfarin ( target international normalized ratio 2.03.0 ) for prevention of all stroke ( ischaemic or haemorrhagic ) or systemic embolism . the study randomized 14171 patients from 1178 clinical sites and hospitals at 45 countries with electrocardiographically documented paroxysmal , persistent , or permanent af . increased stroke risk was indicated by a history of stroke , transient ischaemic attack , or systemic embolism , or at least two of the following risk factors : heart failure or left ventricular ejection fraction 35% or lower ; hypertension ; age 75 years or older ; or diabetes ( chads2 score 2 ) . patients were randomly assigned with to receive rivaroxaban ( 20 mg or 15 mg daily in patients with a creatinine clearance of 3049 ml / min ) or dose - adjusted warfarin ( target international normalized ratio of 2.03.0 ) . the main results of rocket af concluded that rivaroxaban was non inferior to warfarin for the prevention of stroke or systemic embolism . . however , less intracranial hemorrhage rates were observed in the rivaroxaban arm . in rocket af , 5239 ( 37% ) of 14 171 patients patients with af given digoxin were significantly more likely to be female , have a history of heart failure , have diabetes , and have persistent af than those who were not . these patients also tended to have a higher baseline heart rate than those not given digoxin . the overall rate of stroke or systemic embolism , the primary endpoint of rocket af , was similar in patients given digoxin at baseline compared with those that were not ( 2.11 vs 2.37 events per 100 patient - years ; adjusted hazard ratio [ hr ] 0.92 ; 95% ci 0.771.10 ; adjusted p = 0.34 ) . adjusted rates of the primary safety endpoint ( major and non - major clinically relevant bleeding ) were similar between patients on baseline digoxin and those that were not . baseline digoxin use was associated with increased all - cause mortality ( 5.41 vs 4.30 events per 100 patient - years ; adjusted hr 1.17 [ 95% ci 1.041.32 ] ; adjusted p = 0.0093 ) , vascular death ( 3.55 vs 2.69 ; 1.19 [ 1.031.39 ] ; p = 0.0201 ) , and sudden death ( 1.68 vs 1.12 ; 1.36 [ 1.081.70 ] ; p = 0.0076 ) . on the other hand , baseline use of digoxin was not associated with increased all - cause admission to hospital ( 14.83 vs 15.40 events per 100 patients - years ; adjusted hr 1.02 [ 95% ci 0.951.10 ] ; p = 0.64 ) . however , given the retrospective nature of most of these observations , and the large amount of potential confounders , the question whether digoxin is harmful would be hard to answer without a large randomized trial of the drug in patients with af . furthermore , non of the recent studies showing worse outcomes with digoxin use , including the current rocket af subanalyses , have had detailed information about how digoxin was used . knowing more about digoxin dosages , how often digoxin levels were checked , and how often were the digoxin levels outside the therapeutic ranges would add an important clinical insight to the consistent observed adverse outcomes . some clinicians claim they never encounter these adverse outcomes in their daily practice if they have enough knowledge and experience on how to adminster digoxin properly to their patients . yet , bearing in mind the current data , it is unlikely that digoxin would yield a clinical improvement for patients . for the time being , in patient with af , digoxin should be a last - line agent and should be used with prudence when there are no other available options .

in a recent article in the journal , we have reviewed the adverse cardiovascular outcomes observed with digoxin use in the pallas study.1 the pallas study was designed to determine if dronedarone would reduce major vascular events in patients with permanent atrial fibrillation ( af).2 however the study was stopped early because of safety reasons , as a significant number of patients on the dronedarone arm reached the co - primary end point composite of stroke , myocardial infarction , systemic embolism , or cardiovascular death . data sub - analyses suggested that digoxin - dronedarone interaction was responsible for the higher arrhythmic death rate observed in the trial . these observations are consistent with several other studies that demonstrate the potential hazard of the use of digoxin in heart failure and/or atrial fibrillation.a more recent article published in the lancet studied the use and outcomes of digoxin in the rivaroxaban once daily oral direct factor xa inhibition compared with vitamin k antagonism for prevention of stroke and embolism in atrial fibrillation ( rocket af ) trial.3 the investigators concluded that digoxin treatment was associated with a significant increase in all - cause mortality , vascular death , and sudden death in patients with af .

wound exudate is composed of fluid and cells including neutrophils and macrophages . in the inflammatory phase , wound exudate is part of the normal healing process1 ; however , excessive postoperative exudate can increase pain , swelling , seroma , and risk of infection2 . furthermore intraoral vertical ramus osteotomy ( ivro ) and sagittal split ramus osteotomy ( ssro ) are representative methods of mandibular ramus osteotomy . the prominent difference between ssro and ivro is the presence of inter - segmental fixation5 . inter - segmental fixation is required after ssro , whereas bone segments are free from each other after ivro . also , the extent of subperiosteal dissection and the design of osteotomy are different . given the above differences , the purpose of this study was to measure the amount of postoperative drainage after ivro and ssro by inserting a closed suction drainage system into the bilateral mandibular osteotomy sites . this study followed the declaration of helsinki on medical protocol and ethics , and the regional ethical review board of yonsei dental hospital institutional review board approved the study ( irb no . this retrospective cohort study includes subjects who underwent ivro or ssro orthognathic surgery for correction of dentofacial deformities by two expert surgeons at the department of oral and maxillofacial surgery , yonsei dental hospital between 2007 and 2013 . the exclusion criteria were existing medical , physical , and mental conditions that would increase bleeding tendency ; correction of mandibular deformity by another technique ; abnormal preoperative prothrombin time , partial thromboplastin time , bleeding time , or platelet count ; and other hematologic abnormalities that could affect the result . the 20 patients treated with ivro were placed in group i , and the 20 patients treated with ssro were placed in group ii . one patient in group i and three patients in group ii underwent only mandibular operations . mean age and standard deviation ( sd ) of the 40 patients were 23.95 years and 4.78 years . mean age ( sd ) was 22.1 ( 2.94 ) years in group i and 25.8 ( 5.57 ) years in group ii . two expert surgeons performed all operations , and there was no difference in osteotomy design of ivro and splitting technique and osteosynthesis in ssro . a closed suction drainage system was inserted at the operation site of the mandibular ramus following mandibular osteotomy and repositioning . data was collected and analyzed with independent t - test using the pasw statistics 18.0 software ( ibm co. , armonk , ny , usa ) . results were described as the amount of postoperative drainage from a drain bulb per person every 8 hours postoperatively.(table 2 , fig . 1 ) immediately after the operation , the mean ( sd ) amount of drainage was 31.20 ( 12.31 ) ml and 30.25 ( 20.72 ) ml in group i and group ii , respectively ; however , the difference was not statistically significant ( p=0.861 ) . at 8 hours postoperatively , the mean ( sd ) amount of drainage was 19.90 ( 10.94 ) ml and 25.75 ( 18.08 ) ml in group i and group ii , respectively ; however , the difference was not statistically significant ( p=0.225 ) . at 16 hours postoperatively , the mean ( sd ) amount of drainage was 13.90 ( 6.37 ) ml and 19.70 ( 9.38 ) ml in group i and group ii , respectively , and the difference was statistically significant ( p=0.029 ) . at 24 hours postoperatively , the mean ( sd ) amount of drainage was 9.47 ( 5.2 ) ml and 8.50 ( 8.29 ) ml in group i and group ii , respectively ; however , the difference was not statistically significant ( p=0.658 ) . at 32 hours postoperatively , the mean ( sd ) amount of drainage was 4.95 ( 4.57 ) ml and 5.91 ( 6.67 ) ml in group i and group ii , respectively ; however , the difference was not statistically significant ( p=0.601 ) . the total amount ( sd ) of drainage from the closed suction drainage system was 79.42 ( 23.86 ) ml and 90.11 ( 42.85 ) ml in group i and group ii , respectively . there was no statistically significant difference between the two groups ( p=0.338).(table 3 ) postoperatively , volume usually decreased every 8 hours in both groups . at 32 hours the first phase is the inflammatory phase , which includes formation of hematoma , extravasation , release of cytokines , and aggregation of immune cells the second phase of fractured bone healing is formation of a soft callus characterized by cartilage around a fractured bone to connect a bony gap . then the soft callus becomes a hard callus in the third phase , and the final phase of bone healing is the remodeling phase . in the remodeling phase these same four phases of bone healing begin with exudate and swelling in the inflammatory phase . we inserted a closed suction drainage system into bilateral mandibular osteotomy sites to decrease postoperative swelling , seroma , and incidence of infection . clifton et al.7 reported a systematic review with a closed suction drainage system after operation for hip fracture and demonstrated that there was no significant difference in the occurrence of complications between a drained wound and an undrained wound . though there is some debate about its necessity , closed suction drainage is considered a useful device for decreasing postoperative complications in various fields . he et al.8 performed a systematic review of randomized controlled trials studying insertion of a drain after axillary lymph node dissection for breast cancer . in comparison with undrained wounds , therefore , we inserted closed suction drainage systems into osteotomy sites , expecting a decrease in postoperative complications . ueki et al.9 showed that the amount of intraoperative bleeding was lower after ivro than after ssro . the study demonstrated that blood loss was 216.6 ml after ssro and 125.5 ml after ivro . yet , there is no comparative study examining the amount of postoperative drainage from osteotomy areas after ivro and ssro . therefore , we measured the amount of postoperative drainage after each type of operation by inserting a closed suction drainage system into mandibular osteotomy sites after orthognathic surgery . some clinicians assume that the amount of intraoperative bleeding and postoperative exudate from osteotomy areas is larger after ivro than after ssro because bone segments after ivro are not fixed by screws . we hypothesized that the amount of postoperative drainage might be larger after ssro than ivro because sagittal split osteotomy on ramus causes more extensive medullary exposure than vertical osteotomy on ramus . these data allowed comparison of drainage output from the bulb of a closed suction drainage system between group i and group ii . our findings may help determine which method can reduce postoperative swelling , seroma formation , and risk of infection . although patients in group i showed less postoperative drainage than group ii , these data did not show any statistically significant difference between the groups ( p=0.338 ) . thus , surgeons do not need to consider postoperative drainage when determining which method is preferred for mandibular surgery . these data further suggest that the closed suction drains may be removed 32 hours after orthognathic surgery , because the amount of postoperative drainage during the last 8 hours was below 10 ml in both groups . at that time , the risk of swelling , hematoma formation , and probability of infection would decrease . first , the two surgeons usually performed ssro only for mandibular advancement , whereas they did ivro for mandibular setback . mandibular segments had less exposed bone marrow after mandibular setback . consequently , the differing surgical plan for each method may have affected our results . the above variables may influence the amount of postoperative drainage from a closed suction drainage system . there may also be some difference in the ability of our two surgeons , though they performed the same osteotomy technique for ivro and ssro . ivro and ssro have different osteotomy design and different exposure of medullary bone ; therefore , one might think that the amount of postoperative drainage from a closed suction drainage system is different from each method . our results revealed that there was no statistically significant difference in postoperative drainage of blood and exudate from bilateral mandibular osteotomy areas after ivro and ssro .

objectivesthe purpose of this retrospective study was to compare the amount of postoperative drainage via closed suction drainage system after intraoral vertical ramus osteotomy ( ivro ) and sagittal split ramus osteotomy ( ssro).materials and methodswe planned a retrospective cohort study of 40 patients selected from a larger group who underwent orthognathic surgery from 2007 to 2013 . mean age ( range ) was 23.95 ( 16 to 35 ) years . patients who underwent bilateral ivro or ssro were categorized into group i or group ii , respectively , and each group consisted of 20 patients . closed suction drainage system was inserted in mandibular osteotomy sites to decrease swelling and dead space , and records of drainage amount were collected . the data were compared and analyzed with independent t-test.resultsthe closed suction drainage system was removed at 32 hours postoperatively , and the amount of drainage was recorded every 8 hours . in group i , the mean amount of drainage was 79.42 ml in total , with 31.20 ml , 19.90 ml , 13.90 ml , 9.47 ml , and 4.95 ml measured at 0 , 8 , 16 , 24 , and 32 hours postoperatively , respectively . in group ii , the mean total amount of drainage was 90.11 ml , with 30.25 ml , 25.75 ml , 19.70 ml , 8.50 ml , and 5.91 ml measured at 0 , 8 , 16 , 24 , and 32 hours postoperatively , respectively . total amount of drainage from group i was less than group ii , but there was no statistically significant difference between the two groups ( p=0.338 ) . there was a significant difference in drainage between group i and group ii only at 16 hours postoperatively ( p=0.029).conclusionivro and ssro have different osteotomy design and different extent of medullary exposure ; however , our results reveal that there is no remarkable difference in postoperative drainage of blood and exudate .

radiation retinopathy is a chronic and progressive retinal microangiopathy that can occur even years after radiation treatment for cancer . radiation retinopathy has been reported secondary to treatment of intraocular tumors , such as uveal melanoma , retinoblastoma , as well as cephalic , nasopharyngeal , orbital , and paranasal tumors [ 1 , 2 , 3 ] . pathological vascular changes include a pattern of capillary occlusion , dilatation , and leakage , often within the macula which may progress to microaneurysms , telangiectatic - like vessels exudation and subsequent cystoid macular edema ( cme ) . capillary nonperfusion may also result in vasoproliferative sequelae , including retinal neovascularization , secondary vitreous hemorrhage , and neovascular glaucoma . current treatment of radiation retinopathy includes thermal laser photocoagulation , intravitreal antivascular endothelial growth factor ( anti - vegf ) injections , intravitreal steroid injections , and hyperbaric oxygen . however , despite treatment patients often may have progressive visual loss due to the significant amount of ischemic damage . conventional thermal laser photocoagulation for cme may result in macular scarring and eventually vision loss due to progressive atrophy from direct laser scars . subthreshold micropulse laser has been increasingly recognized as an effective and safe treatment for cme secondary to other retinal vascular diseases , including diabetic macular edema , retinal vein occlusion , and central serous retinopathy . unlike conventional thermal laser , micropulse laser delivers short bursts of laser energy in microsecond pulses micropulses rather than a continuous wave , resulting in less thermal damage and minimal or no scarring . also , yellow ( 577 nm ) wavelength laser light may be theoretically safer than conventional green ( 532 nm ) wavelength laser light when treating the macular area due to less thermal absorption by the xanthophyll pigments . here , we report a case of cme secondary to radiation retinopathy which was treated successfully with yellow pattern 577-nm micropulse laser . a 60-year - old asian man presented with a 2-month history of reduced vision and metamorphopsia in the left eye . he had mild controlled hypertension and hypercholesterolemia . he also had a history of nasopharyngeal carcinoma which was treated with local radiation and chemotherapy 23 years and 9 years previously . best - corrected visual acuity ( bcva ) was 20/16 in the right eye and 20/40 in the left eye . fundoscopy showed some intraretinal hemorrhages in the left temporal macula with telangiectatic vessels and scattered microaneurysms ( fig . 1 ) . fluorescein angiography revealed patchy capillaries , nonperfusion , and left late macular leak consistent with cme ( fig . optical coherence tomography ( oct ; heidelberg engineering , heidelberg , germany ) showed left cme ( fig . following informed consent , a solid - state subthreshold yellow 577-nm wavelength pattern micropulse laser ( supra scan 577 ; quantel medical , cournon d'auvergne , france ) with an adapter attached to a haag - streit type slit - lamp microscope was used to treat the left eye . using fluorescein angiography guidance to treat the leaking areas , single - spot and 9-spot square patterns of 100-m diameter were used with a duration of 0.02 s and a duty cycle of 15% ( the laser stayed on for 15% of the time ) . two months following treatment , subjectively the patient noted improved symptoms , bcva had improved to 20/20 in the left eye and the oct examination demonstrated reduced intraretinal edema ( fig . ten months after the micropulse laser , bcva had stabilized to 20/20 in the left eye and the oct examination revealed absence of the previously found intraretinal edema ( fig . subthreshold micropulse laser is an innovative therapy for retinal disorders which has been shown to be safe and effective in the treatment of macular edema [ 6 , 7 ] . the yellow pattern 577-nm micropulse laser in this case converts each laser shot into a pulse envelope consisting of a sequence of extremely short pulses of laser ( 1020 ms ) with intervening periods of zero laser energy to the treatment site . when the multi - spot pattern mode is used , the pulses are not produced simultaneously ; however , they formed in rapid succession with low - energy pulses during each laser shot . previous studies have shown that subthreshold laser performed in this way was sufficient to show a consistent retinal pigment epithelium - confined photothermal effect , and also to allow the inner retinal temperature to remain below the threshold of coagulative damage , sparing the transparency of the retina and lowering the risk of hemorrhage . because the micropulse laser treatment has no or minimal damage to the retina or choroid , and is less likely to produce chorioretinal scars , retreatment of the same area is feasible . as a result , it is possible to safely treat macular edema in a transfoveal location using subthreshold micropulse laser . however , the possibility of undertreatment is always a concern due to the difficulty in titrating treatment without a visible end point . in our case , we utilized fluorescein angiography guidance to treat the leaking areas ( overlay of the treatment map provided in fig . 2 ) . a previous study demonstrated that indocyanine green dye - guided micropulse diode laser was effective in the treatment of central serous chorioretinopathy . the pathogenesis of radiation retinopathy still remains elusive . in 1994 , in a review , archer et al . proposed that initial radiation caused the immediate death of retinal endovascular cells which created microscopic foci of epithelial damage . a vicious cycle of retinal vascular endothelial cell death , migration , division , and further death thus ensues , outstretching the ability of endothelial cells to maintain an unbroken endothelial lining and triggering inflammation and clotting cascades [ 4 , 5 ] . as a result , occlusion of discrete retinal capillary beds creates hemodynamic stress on neighboring capillaries which dilate to accommodate . however , many such capillary collaterals are compromised by radiation damage , leading to vascular leakage or further occlusion . occurring within the macular area , such vascular leakage results in cme . our patient presented with retinopathy and macular edema 23 years after initial radiotherapy . the onset of pathological changes may possibly be delayed due to the slow turnover of retinal vascular endothelial cells . our patient with macular edema secondary to radiation retinopathy was successfully treated with 1 session of subthreshold yellow pattern 577-nm micropulse laser with no detectable complications or retinal scarring . postulated processes include modification of inflammatory cytokines or induction of heat shock proteins in retinal pigment epithelium cells . in this case report , we presented a 60-year - old asian man with radiation retinopathy who was treated successfully with 1 session of yellow pattern 577-nm micropulse laser photocoagulation , resulting in improving symptoms and fluid resolution . further studies are needed to elucidate possible mechanisms of subthreshold laser and to develop better therapeutic as well as preventive treatment strategies for radiation retinopathy . the patient was informed that imaging related to his case would not be able to identify him personally and may be published and he consented for the publication . the authors declare that no conflicts of interest are involved in the present case report .

we report a case of a 60-year - old asian male who developed radiation retinopathy 23 years after initial radiotherapy for nasopharyngeal carcinoma and was successfully treated with yellow pattern 577-nm micropulse laser . secondary macular edema and visual acuity improved following a single treatment session with minimal scarring . yellow pattern micropulse laser is a safe and effective treatment for macular edema secondary to radiation retinopathy .

optic nerve atrophy ( oa ) is a wide spectrum of hereditary or acquired optic neuropathies arising from various etiologies . the clinical characteristics of the disease include color vision deficits , loss of contrast sensitivity , scotomas of variable density with partial or total loss of visual acuity , and development of unilateral or bilateral atrophy of the optic nerve [ 1 , 2 ] . high - resolution retinal imaging technologies , such as scanning laser ophthalmoscope infrared ( slo - ir ) imaging and spectral domain optical coherence tomography ( sd - oct ) , and both b - scans and en face , were shown to help define the location and extent of structural damage occurring in several chorioretinal diseases . in a previous study , the authors had noticed the presence of macular microcysts in the retinal inner nuclear layer ( rinl ) in patients suffering from advanced oa . these microcysts are never observed in normal eyes . in this study , using high - resolution retinal imaging technologies , the authors analyzed prospectively the incidence , in different ocular pathologies , of these rinl microcystic changes that are associated with atrophy of the optic nerve ( on ) . this clinical study was conducted at the department of ophthalmology at rothschild foundation in paris , france . the clinical charts of patients , who were known to have a significant defect of the retinal nerve fiber layer ( rnfl ) in at least one quadrant , as measured with sd - oct , were included in this study . exclusion criteria were the presence of any associated retinopathy such as diabetic retinopathy ( dr ) , retinal vein occlusions ( rvo ) , age - related macular degeneration ( amd ) , epiretinal membrane ( erm ) , viral retinitis , retinitis pigmentosa ( rp ) , and radiation retinopathy . all patients who had previously had an intraocular surgery or taken any drug known to be toxic to the retina and/or the on ( e.g. , fingolimod or sildenafil ) were excluded as well . after an explanation of the purpose of the study and procedures to be used after the inclusion and during the followup , informed consent was obtained from all patients . the procedures used conformed to the tenets of the declaration of helsinki . all patients with significant rnfl defect had had a detailed ocular and medical history , as well as a thorough bilateral ocular evaluation . the ocular examination included careful testing of standardized early treatment of diabetic retinopathy study ( etdrs ) visual acuity ( va ) , a thorough anterior segment examination , intraocular pressure ( iop ) recording with a goldmann applanation tonometer , and detailed fundus evaluation by indirect and direct ophthalmoscopy . in addition , all patients had 30-degree color fundus photographs centered on the macula and optic nerve , slo - ir imaging , fluorescein fundus angiography ( ffa ) , b - scans , and en face sd - oct , to detect small round hyporeflective microcysts confined to the rinl . automated central macular thickness ( cmt ) was generated by an sd - oct instrument . using automated eye tracking and image alignment based on slo images , the software allowed the averaging of a variable number of single images in real time ( art [ automated real time ] module ; heidelberg engineering ) . macular mapping consisted of 197 transverse sections in a 5.79 mm 5.79 mm central retinal area . tridimensional reconstruction generated by the pooling of these sections provided a virtual macular brick , through which 496 shifting sections in the coronal plane resulted in c - scan , or en face oct , while b - scan , or conventional oct , was derived from sagittal and transverse sections . the results were then compared with data from classical imaging , namely , fundus photography , ffa , and slo - ir imaging . retinal vessel crossing points were automatically used as constant landmarks to allow alignment of the en face sd - oct images with that of the fundus slo - ir imaging . each layer was switched on and off to evaluate precisely the correspondence between the extent of lesions on en face sd - oct and the adjacent layers . average rnfl measurement and rnfl thickness in the temporal , inferior , nasal , and superior quadrants were obtained as well , using the same sd - oct instrument . statistical analysis was performed using commercially available software ( spss version 20.0 , inc . , unpaired student 's t - tests were used for statistical comparison between cmt of involved eyes and that of control eyes . the statistical significance was set at p < 0.05 . two hundred and one eyes of 138 patients [ 55 females ( 39.8% ) and 83 males ( 60.2% ) , p = 0.231 ] demonstrating a significant rnfl defect in at least one quadrant ( temporal , superior , inferior , or nasal ) met the inclusion criteria and were included in the analysis . mean best - corrected visual acuity ( bcva ) in the affected eye at the time of presentation was 20/30 . table 1 summarizes the different etiologies responsible for the rnfl defect as shown in our patients . of the 201 eyes presenting those rnfl defects , there were 40 eyes ( 19.9% ) presenting with hereditary optic atrophy [ mitochondrial or autosomal dominant optic atrophy ( adoa ) ] , 6 eyes ( 3% ) with ischemic optic neuritis ( ion ) , 4 eyes ( 2% ) with drusen of the on , 9 eyes ( 4.5% ) with compressive oa as diagnosed with brain and orbital magnetic resonance imaging ( mri ) , 27 eyes ( 13.4% ) with inflammatory optic neuropathy from multiple sclerosis ( ms ) , 27 patients ( 13.4% ) with oa from undetermined origin , 85 eyes ( 42.3% ) with primary open - angle glaucoma ( poag ) , 2 eyes ( 1% ) with idiopathic intracranial hypertension ( iih ) , and 1 eye ( 0.5% ) presenting with juxtapapillary toxoplasmic retinochoroiditis . further analysis of those eyes with rnfl defects with slo - ir , b - scans , and en face sd - oct showed in 71 eyes ( 35.3% ) a hyporeflective perifoveal crescent - shaped lesion composed of small round hyporeflective microcysts confined to the rinl without any extension to the adjacent layers . these microcysts measured between 2030 microns to 7090 microns within an x - y axis conjugate plane and were located between 500 and 2200 microns from the center of the fovea as measured with sd - oct . they could be found either superiorly , temporally , inferiorly , or nasally to the fovea ( figure 1 ) . associated hyperreflective pinpoint lesions were also observed within the rinl adjacent to the microcysts network in all cases ( figure 2 ) . as shown in figure 3 , this hyporeflective network lesion shown on the en face sd - oct correlated with the same hyporeflective crescent - shaped perimacular lesion as shown with slo - ir imaging . mean age of patients presenting those microcysts was 44.13 years , whereas mean age was 58.40 in patients who did not . as shown in table 1 , this round microcysts network was found in 30 cases ( 75% ) of eyes presenting mitochondrial oa or adoa , 3 cases ( 50% ) of eyes presenting ischemic optic neuritis , 2 cases ( 50% ) of eyes having drusen of the on , 4 cases ( 44.4% ) of eyes presenting a compressive oa , 12 cases ( 32% ) of eyes presenting ms , 5 cases ( 18.5% ) of eyes presenting oa from undetermined origin , and 15 cases ( 17.6% ) of eyes having poag . no similar lesion was found in eyes presenting iih or toxoplasmic retinochoroiditis . in all cases , the rnfl thickness of the involved eyes was significantly lower than that of the normal eyes when the etiology involved only one eye ( table 2 ) . by stratifying our results to the different quadrants or clock hours around the optic disc , mean rnfl thickness in eyes presenting intraretinal cysts in the superior , temporal , inferior , and nasal quadrants were , respectively , 74.28 m , 35.28 m , 71.95 m , and 52.90 m . they were significantly lower than that of the fellow normal eyes , respectively , in the superior ( 113 m , p < 0.001 ) , temporal ( 56.27 m , p < 0.001 ) , inferior ( 115.90 m , p < 0.001 ) , and nasal ( 65.54 m , p < 0.05 ) quadrants . mean central rnfl thickness of patients presenting oa was 58.50 m od and 56.73 m os when microcysts were present , and 62.90 m od and 60.88 m os when these were absent . this prospective study of a large population of patients with oa shows that microcystic changes in the rinl observed in oa are not specific of an etiology as previously thought in multiple sclerosis [ 58 ] but are found in many diseases of various etiologies , mostly genetic . effectively , microcysts were found in 75% of eyes presenting mitochondrial oa or adoa , 50% of eyes presenting ischemic optic neuritis , 50% of eyes having drusen of the on , 44.4% of eyes presenting a compressive oa , 32% of eyes presenting ms , 18.5% of eyes presenting oa from undetermined origin , and 17.6% of eyes having poag . the highest incidence found in patients with genetic oa could indicate that these microcysts may be directly linked to the dysfunction of the mitochondrial system rather than an inflammatory process . it is known that the gene mutated in cases of hereditary oa such as optic atrophy type 1 ( opa 1 ) is a gene that encodes a dynamin - related gtpase . dynamin is a large gtpase regulating vesicular traffic and endocytosis at the plasma membrane that has been shown to maintain the mitochondrial genome . on the other hand , it is known that mller glial cells that are located within the rinl ensure the homeostasis of the retina by regulating neurotransmitters such as glutamate and gamma - amino - butyric acid ( gaba ) , thus protecting the adjacent retinal ganglion cells ( rgcs ) [ 1013 ] . therefore , we suggest that most of this mitochondrial dysfunction as well as accumulation of neurotransmitters could have led to pseudocysts in the rinl that could represent a microglial or mller cells metabolism problem as seen with sd - oct . as the incidence of the rinl microcysts was different according to the pathology inducing oa , they may reflect a phase in the evolution of the disease . this sign must be taken into account for the presence of an oa due to an ocular or cerebral disease . moreover recognizing these pseudocysts is crucial as they may be confused with cystoid macular edema . during followup of already known oa , this sign must be looked for in order to appreciate the severity or evolution of the affection . in conclusion , microcystic changes in rinl of patient with oa is a nonspecific finding and is easy to detect with new retinal imaging technologies , that should always be looked for . this clinical sign is frequently found in various diseases with oa and not only in ms . ultimately , as this study was based on a limited number of etiologies that had led to oa , further prospective studies with larger series as well as deeper molecular investigation remain mandatory in order to fully confirm our results and uncover the mysteries of the pathophysiology underlying these rinl microcysts .

purpose . this study aimed at assessing the prevalence of pathologies presenting retinal inner nuclear layer ( rinl ) microcystic perimacular changes associated with optic nerve atrophy ( oa ) . the charts of patients presenting a significant defect of the retinal nerve fiber layer ( rnfl ) were included prospectively in this study . patients were classified according to the etiology of the rnfl defect . two hundred and one eyes of 138 patients were enrolled in this analysis . retinal images obtained showed the typical hyporeflective perifoveal crescent - shaped lesion composed of small round hyporeflective microcysts confined to the rinl in 35.3% of the eyes . those findings were found in 75% of eyes presenting hereditary oa , 50% of eyes presenting ischemic optic neuritis , 50% of eyes with drusen of the optic nerve ( on ) , 44.4% of eyes presenting a compressive oa , 32% of eyes presenting inflammatory optic neuropathy from multiple sclerosis , 18.5% of eyes presenting oa from undetermined origin , and 17.6% of eyes having primary open - angle glaucoma . this study demonstrates that microcystic changes in rinl are not specific to a disease but are found in oa of various etiologies . moreover , their incidence was found to be dependent upon the cause of oa , with the highest incidence occurring in genetic oa .

it consists of fusion between two adjacent vertebrae across the lamina and transverse processes.1 fusion depends on host and surgical factors including the selection of an appropriate graft . iliac crest autograft has long been considered the gold standard for bone graft procedures . however , its use is associated with significant disadvantages including insufficient availability , donor site pain , increased operative time , increased estimated blood loss , and longer hospital stay.2 many autologous or heterologous bone substitutes are used to reach fusion . currently , there are over 200 different commercial types of bone graft extenders , enhancers , and substitutes available from which to choose.3 the objective is to find an osteoinductive and osteoconductive substrate that is also safe and easy to apply . the efficacy of platelet - rich plasma ( prp ) as an osteoinductive material has been studied by several authors.4 5 6 preliminary results about using prp in posterolateral fusion have been encouraging.7 in this article , we analyze the effectiveness and practicality of using an heterologous cancellous bone substitute with autologous prp obtained directly in the operating theater . we evaluated 20 consecutive patients who underwent posterior decompression , vertebral fixation with pedicle screws , and posterolateral fusion from january 2012 to january 2013 at the department of neurological and neurosurgical sciences of sapienza university of rome . the inclusion criteria were degenerative or traumatic lumbosacral spine disease and normal platelet count ( 150 to 450 10/ml ) . the exclusion criteria were previous lumbosacral surgery , fixation involving dorsal vertebrae , neoplastic disease , blood dyscrasias , and abnormal platelet count . the following method was used : cancellous bone substitute ( 25 50 30 mm ) soaked with autologous prp was implanted on the right hemifield and cancellous bone substitute ( 25 50 30 mm ) soaked with saline solution on the left hemifield . tecnoss ( torino , italy ) sp - block soft bs7e ( 25 50 30 mm ) was used as a bone substitute . if hydrated with saline solution for 5 to 10 minutes , it becomes flexible and malleable . autologous prp was obtained in the operating theater by taking peripheral venous blood from the patient . the regen system ( regenlab , lausanne , switzerland ) was used , consisting of an 8-ml patented test tube regen tht - sp and a regen centrifuge ( h19-f regen centrigel ) placed directly in the operating theater . the test tube containing 3 0.1 g of polyester gel and 1 0.05 ml of sodium citrate solution was centrifuged for 8 minutes at 3,100 rpm ( 1,500 g ) . this removes 95 to 100% of total red blood cells , with 80% of white blood cells and a platelet concentration between 2.5 and 4.5 10/l remaining . after centrifugation , the content was divided into red blood cells below the filter at the base of the tube and prp with buffy - coat superiorly . each tube contained 4.5 ml of prp , immediately available for application and enough to cover about two levels of arthrodesis unilaterally . the contact of the prp with the porosity of the cancellous bone substitute and the addition of 2 ml of calcium gluconate favored the activation of the coagulation cascade and platelet activation ( fig . investigations into bone density were obtained by comparative analysis of region of interest ( roi ) on computed tomography ( ct ) scan images . a square area 0.4 cm in size ( roi ) is traced over the axial ct scan across the lamina and transverse processes . the electronic calculation of the mean pixel content ( bidimensional unit of measurement ) can be done in hounsfield units ( hus ) . the numerical value obtained is the average of the densitometric values of the pixels contained in the area ; hu = 0 corresponds to water , 1,000 to air , and + 1,000 to cortical bone . ( b ) after centrifugation , red blood cells trapped below the filter of gel content at the base of the tube . the upper portion is divided in the platelet - rich plasma and in the upper buffy - coat ; ( c ) bone block ; ( d ) intraoperative picture . the 20 patients included 8 males and 12 females with mean age = 70 ( standard deviation [ sd ] = 10.9 ) . the platelet count in the whole blood varied between 173 and 390 10/ml . a ct scan 6 and 12 months after surgery was performed in all patients ( figs . 2 and 3 ) . investigations into bone density were obtained by comparative analysis of roi ( table 1 ) . the data were analyzed with two repeated - measures variance analyses with value of density after 6 months and value of density after 12 months as factors ( density on the right hemifield versus density on the left hemifield ) using age , levels of arthrodesis , and platelet count ( in the whole blood ) as covariates . region of interest ( roi ) analysis on computed tomography scan 6 months after surgery . the main effect of value of density after 6 months was significant ( f(1,19 ) = 5.522 , p < 0.05 ) : the value of density on the right hemifield after 6 months was significantly different from the value of the density on the left hemifield ( mean = 830.353 [ sd 61.8 ] for the right hemifield versus mean = 632.890 [ sd 59.5 ] for the left hemifield ) . the post hoc mean comparison showed that the value of density on the right hemifield was significantly greater than the value of density on the left hemifield after 6 months ( = 197.463 ; f(1,19 ) = 43 , p < 0.001 ) . the interaction with age was marginally significant ( f(1,19 ) = 3.700 , p = 0.72 ) ; the interaction between the levels ( f(1,19 ) = 2.070 , p = 0.169 ) and the platelet count ( f(1,19)= 0.64 , p = 0.804 ) was not significant , which suggests no effects of these variables on results . these data demonstrate increased bone density using prp and heterologous cancellous block in the first 6 months after surgery ( fig . the analysis of variance on the value of the density after 12 months showed that at this time no significant difference was observed in the two hemifields ( f(1,19)= 1.100 , p = 0.310 ) . in fact , the mean of the value of the density on the right hemifield was 871.810 versus 837.011 of the left hemifield after 12 months ( = 34.79 ; f(1,19 ) = 0.665 , p = 0.426 ) . also in this case , no interaction between the covariates of age ( f(1,19 ) = 0.573 , p = 0.460 . ) , levels ( f(1,19 ) = 1.407 , p = 0.253 ) , and platelet count ( f(1,19 ) = 0.117 , p posterolateral arthrodesis is a fusion between two adjacent vertebrae across the lamina and transverse processes.1 many autologous or heterologous bone substitutes are generally used as an implantation to reach fusion.3 the objective is to find an osteoconductive and osteoinductive substrate that is also safe and easy to apply . collagen binding to fibronectin promotes the anchorage of mesenchymal stem progenitors , on which it exerts its chemotactic action and induces differentiation into osteoblasts . it has a rigid and malleable consistency and maintains the original graft volume from 6 to 18 months from application . this is particularly important to allow the rapid development of the bony bridge between the transverse processes . this also reduce the risk of pseudarthrosis and nonunion present in arthrodesis performed with other substitutes.8 moreover , cancellous bone substitute can be used also in association with autologous bone graft ( laminectomy bone chips ) ; future investigations to analyze this option are necessary . in this study because posterior elements are intact in vertebral body fractures , the cohort of patients is homogeneous . fusion was assessed with computerized analysis of roi , a square area 0.4 cm in size traced over the axial ct scan across the lamina and transverse processes . it is important to emphasize that the numerical value obtained from this measurement is the average of the densitometric values of the pixels contained in the area studied . prp has an osteoinductive effect increasing the bone regeneration and production.9 10 this is due to the action of growth factors released by platelets upon activation . platelets are a potential source of multiple autologous growth factors , and proteins are involved in the physiologic processes of healing and tissue regeneration . the products rich in platelets have the goal to replace the blood clot with a preparation enriched in platelets that , once activated , secrete large amounts of proteins and growth factors ( platelet - derived growth factor , epidermal growth factor , transforming growth factor- , vascular endothelial growth factor , insulin - like growth factor 1 ) . they exert mitogenic action on osteoblasts and induce the differentiation of mesenchymal stem progenitors into osteoblasts.11 autologous prp can be obtained directly in the operating theater . prp has to be prepared to effectively separate the platelets from red blood cells , taking care not to damage the platelets . this method is important because the growth factors contained within the platelet -granules are activated at the same time that the granules themselves merge with membrane platelet.12 13 14 the properties of the prp in tissue repair have already been documented in numerous studies . therefore , the molecular mechanisms through which the growth factors stimulate repair are complex and depend on the different types of tissues and types of cells that receive the messages.15 prp is obtained by platelet sequestration and concentration . the exact relationship between the platelet count and the concentration of growth factors remains unclear . no correlation between bone density and whole blood platelet count was found in our series . several in vitro studies seem to point out that the content of platelet growth factors is quite variable among individuals and is not necessarily proportional to the platelet count.16 prp is an autologous product and is completely safe for the patient . moreover , it promotes leukocyte chemotaxis and has antibacterial effect and also increases tissue repair and remodeling.16 several studies demonstrated that iliac crest autograph is the gold standard for bone graft procedures including posterolateral fusion.2 3 as its use is associated with significant disadvantages ( including insufficient availability , donor site pain , increased operative time , increased estimated blood loss , longer hospital stay ) , many surgeons prefer to use heterologous bone substitutes even if it is proved that their validity is lower . in this study the validity of our method has not been compared with autograph , but the technique can be improved in the future . prp used with cancellous bone substitute increases the speed of bone production in posterolateral arthrodesis joining osteoinductive and osteoconductive effect .

study design prospective cohort study . objectives to analyze the effectiveness and practicality of using cancellous bone substitute with platelet - rich plasma ( prp ) in posterolateral arthrodesis . methods twenty consecutive patients underwent posterolateral arthrodesis with implantation of cancellous bone substitute soaked with prp obtained directly in the operating theater on the right hemifield and cancellous bone substitute soaked with saline solution on the right . results computed tomography scans at 6 and 12 months after surgery were performed in all patients . bone density was investigated by comparative analysis of region of interest . the data were analyzed with repeated - measures variance analyses with value of density after 6 months and value of density after 12 months , using age , levels of arthrodesis , and platelet count as covariates . the data demonstrated increased bone density using prp and heterologous cancellous block resulting in an enhanced fusion rate during the first 6 months after surgery . conclusions prp used with cancellous bone substitute increases the rate of fusion and bone density joining osteoinductive and osteoconductive effect .

tuberculosis ( tb ) remains a major cause of morbidity and mortality in developing countries affecting millions of people worldwide ( 1,2 ) . skeletal tb , constituting 1020% of all the extrapulmonary tb ( etb ) , is a well - recognized clinical condition that is easily diagnosed and managed with an excellent outcome ( 2 ) . however , the occurrence of multifocal skeletal involvement , which is defined as osteoarticular lesions that occur simultaneously at two or more locations in the skeletal system , is exceptional and constitutes < 5% of all skeletal tb cases , even in countries where tb is endemic ( 36 ) . radiological examinations , including conventional roentgenography , magnetic resonance imaging ( mri ) and computed tomography ( ct ) scans , can be used to assist the diagnosis of multifocal skeletal tb ( 4,5,7 ) . however , the diagnosis and treatment of multifocal skeletal tb are frequently delayed due to the rarity and vague symptoms of the disease , thus allowing progression to severe deformities and functional deficits ( 3,5,6 ) . in the present study , a case of atypical disseminated multifocal skeletal tb unusual radiological images were observed , which were more compatible with a hematological malignancy or metastatic disease rather than an infectious disease . despite widespread osteoarticular involvement , a 19-year - old male patient was admitted to subei people 's hospital of jiangsu ( yangzhou , china ) on 5th september 2011 with a 2 month history of recurrent fever and intermittent thoracic back pain . the recurrent fever did not occur at specific times and the temperature did not exceed 38.0c . the patient also reported limited mobility , decreased appetite and weight loss , but did not experience chills or night sweats . the patient presented a normal general physical condition , with a body temperature of 37.3c . a physical examination revealed slight tenderness over the mid - thoracic spine , lumbar spine and left sacroiliac joint . no paraspinal swelling or spasms were observed , while the sensation , muscle strength and muscle tone of the lower extremities were normal . laboratory examinations showed a normal white blood cell count [ 6.610/l ; normal range ( nr ) , 3.59.510/l ] and normal levels of hemoglobin ( 120 g / l ) , human leukocyte antigen - b27 ( 78 ; nr , 0145 ) and rheumatoid factor ( 5.0 iu / ml ; nr , 014 iu / ml ) . in addition , tests for autoantibodies , immunoglobulin , tb antibodies and tumor - associated antigens were negative . the erythrocyte sedimentation rate ( esr ) was 75 mm / h , which was higher than the normal range ( 015 mm / h ) , and the c - reactive protein level was normal ( 10 mg / l ; nr , 010 mg / l ) . human immunodeficiency virus ( hiv ) and purified protein derivative ( ppd ) tests were negative . further imaging analysis showed normal abdominal ultrasound findings and x - rays of the chest , thorax , lumbosacral region and pelvis . ct reconstruction of the sacroiliac joint indicated multiple round hypodense lesions with a hyperdense center , as well as some cortical destruction and soft tissue swelling in the lumbar and sacral vertebrae , and the left ilium regions ( fig . 1 ) . a contrast - enhanced ct scan of the chest , with omnipaque ( 1.5 ml / kg ; ge healthcare life sciences , shanghai , china ) as the contrast enhancement agent , demonstrated an irregular patchy hypodense signal in the left lung lobe with a patchy translucent shadow inside , which was enhanced heterogeneously ( fig . 2 ) . a chest ct scan showed multiple round hypodense lesions with higher central density in the thoracic vertebrae , ribs and sternum ( fig . 3 ) . furthermore , a ct reconstruction of the thoracic spine indicated bone destruction with partial cortical perforation ( fig . mri scans revealed multiple round ring signal shadows with a continuous finishing border from th12 to s4 in the anterior , central and posterior elements , but not in the end plate . in addition , sagittal t1-weighted and t2-weighted images revealed a hypodense signal in the internal of the lesions and a slightly hypodense signal in the peripheral region , which was accompanied by soft tissue swelling , with visible ring enhancement and soft tissue enhancement following intravenous administration of gadolinium ( ge healthcare life sciences ) ( fig . 5 ) . based on the symptoms and all the aforementioned examinations , lymphoma , metastatic disease or bone tb since the ct and mri findings did not allow for a final diagnosis , a ct - guided biopsy from the lesions in the th7 vertebral , left iliac and adjacent left lung using an 8-gauge needle ( yangzhou city jiangzhou medical instrument co. , ltd . , yangzhou , china ) was performed to confirm the diagnosis . however , no evidence of granulomata , necrosis , lymphoma or other malignancies was observed . subsequently , an open biopsy was performed in order to establish a pathological diagnosis , during which fish - shaped soft tissue adhesion with surrounding tissues under the lamina of th7 and local sequestrum formation were observed . part of the surrounding soft tissues and bone lesions were removed for pathological examination and culturing . upon hematoxylin and eosin staining of the tissue and visualization under the olympus bx43 microscope ( olympus corporation , tokyo , japan ) , a large amount of necrosis , epithelioid cells , langerhans giant cells and dead bone 6 ) , which are characteristics of tb ( 2,5 ) . the results of acid - fast bacilli culturing ( sinobest biotech co. , ltd . , shanghai , china ) were negative ; however , a polymerase chain reaction performed by shanghai genechem co. , ltd . postoperatively , the patient was administered a common quartet anti - tb chemotherapy regimen ( 2,5 ) , including isoniazid ( 300 mg / day ) , rifampicin ( 600 mg / day ) , pyrazinamide ( 750 mg / day ) and ethambutol ( 750 mg / day ; all shanghai sine pharmaceutical co. , ltd . , the patient 's symptoms greatly improved after 1 month of anti - tb treatment and the esr decreased to 65 mm / h . at the final follow - up on 11th march 2013 , the patient was free of symptoms and the esr had decreased to the normal value . mri scans obtained following 20 months of anti - tb therapy showed that the range of the extensive abnormal signal intensity had become smaller , as compared with that before anti - tb treatment was initiated ( fig . informed consent was obtained from the patient 's family prior to the publication of the present case . tb remains a major cause of morbidity and mortality worldwide , and is responsible for ~1.6 million deaths per year ( 1,4 ) . according to the world health organization , ~8.8 million new cases of tb occur every year worldwide ( 5,8 ) . multifocal skeletal tb has rarely been reported in non - immunocompromised patients and in patients with normal pulmonary findings , particularly in china ( 5,9 ) . the spine is the most commonly affected site , of which the upper lumbar and lower thoracic regions are the most frequently involved , comprising 50% of all multifocal skeletal tb cases ( 36 ) . the average number of vertebrae that are affected by multifocal tb , as seen radiologically , is 3.0 in children and 2.53.8 in adults ( 10 ) . in the present case , there were multiple round hypodense lesions in the ribs , sternum , multi - segment thoracic , multi - segment lumbar and sacral vertebrae , and ilium regions , accompanied by some adjacent soft tissue swelling . a positive ppd test is a fundamental finding in tb patients ; however , a negative test is not sufficient to exclude the disease . although radiological findings do not firmly establish the diagnosis in the case of a negative ppd result , imaging remains the most useful diagnostic tool in such cases ( 5,6,10 ) . the characteristic findings of spinal tb include destruction of two adjacent vertebral bodies , destruction of the intervening disc , and the occurrence of paravertebral and epidural abscesses ( 7,11 ) . skeletal tb does not present any specific features on radiological images in the early stages of the disease , thus mimicking metastatic tumors or certain primary osseous lesions , such as eosinophilic granuloma , particularly if multiple destructive lesions are present ( 5,7,12 ) . plain radiography is of little help unless the collapse of the disc margin or vertebra body appears ( 47 ) . in addition , ct scans are unable to show the early alterations in the vertebral marrow and to differentiate an infectious disease from neoplastic involvement ( 47 ) . by contrast , mri has been shown to be a more sensitive and specific imaging modality that may guide the diagnosis at early stages of skeletal tb . the typical mri patterns are abnormal signal intensities appearing hypointense or isointense on a t1-weighted image of the affected vertebral bodies and discs and hyperintense on a t2-weighted image of the osseous , and soft - tissue changes with heterogeneous enhancement of the vertebral body ( 47,11 ) . overall , the sensitivity and specificity of mri for tb may be 100 and 88.2% , respectively ( 5,7 ) . in the present case , the mri features included multiple round hypodense lesions with finishing borders in the thoracic , lumbar and sacral vertebrae , which was not sufficient evidence for the diagnosis of tb ; on the contrary , these observations were suggestive of hematological malignancies , such as lymphoma or multiple myeloma , or metastatic diseases . the common characteristics of end - plate disruption and high signal intensity of the intervertebral disc were not demonstrated . therefore , the presentation of the tb case reported in the current study is considered unusual . to the best of our knowledge , the present study is the first to report an extremely rare case of multifocal osteoarticular tb with multiple round hypodense lesions and a surprisingly negative ppd test result . the etb and disseminated forms of the disease are usually more frequent in certain patients , such as those with a much older age , malnutrition and hemodialysis , as well as immunocompromised and in particular hiv - infected individuals ( 5,6 ) . however , the current patient was a healthy 19-year - old male with no signs of systemic involvement and a negative hiv status . this demonstrated the diagnostic difficulties of the atypical forms of tb . in patients with skeletal tb , the onset of symptoms is generally insidious , without general alarming signs , such as fever , night sweats , toxicity or extreme weakness . although ct and mri are reliable techniques that help establish a diagnosis , biopsy or ct - guided needle aspiration remain essential for accurate diagnosis and adequate treatment . the advantage of needle aspiration is that it is a less invasive technique ; however , only a small number of specimens can be obtained , particularly when the lesions are sclerotic , and thus the diagnosis rate is only 81.0% in children ( 13 ) and 91.3% in adults ( 14 ) . hao et al ( 15 ) concluded that the diagnostic accuracy of ct - guided thoracic spinal biopsy using a 16-gauge needle was 90.5% overall , as the diagnostic accuracy was significantly lower for the middle thoracic spine ( 90.0% ) compared with that for the lower spine ( 97.6% ) , as well as lower for sclerotic lesions ( 81.3% ) compared with that for lytic lesions ( 96.4% ) . similarly , in the present study , the ct - guided aspiration using an 8-gauge needle was not able to confirm the diagnosis , possibly due to the limited amount of tissue acquired and the histological nature of the lesion itself , resulting in the use of open biopsy to establish the diagnosis . multidrug anti - tb therapy including isoniazid , rifampin , ethambutol and pyrazinamide advocated for an approximate duration of 1218 months usually leads to complete resolution of tb ( 2,5 ) . medical treatment is highly effective when administered appropriately , as performed in the present study . the mean time to diagnosis is reported to be 1619 months after the presentation of symptoms ( 11 ) . ringshausen et al ( 12 ) described the fatal case of a patient with spinal tb , who was mistakenly irradiated for suspected metastatic lung cancer of the spine . the authors claimed that the most common cause in delayed diagnosis is failure to consider this disease ( 12 ) . thus , tb should be considered in all patients with multiple round hypodense lytic lesions of the skeletal system , especially in countries endemic for tb , in order to avoid delays that may result in irreversible damage and in a high mortality rate . in conclusion , the diagnosis of multifocal skeletal tb is difficult for various reasons , requiring careful consideration and numerous examinations . a high index of suspicion for the possibility of tb appearance has to be maintained in any patient with multiple round hypodense lytic lesions of the skeletal system in countries endemic for tb . in addition , mri is particularly valuable in the diagnostic and follow - up procedures .

tuberculosis ( tb ) of the musculoskeletal system is a rare clinical condition . multifocal bone involvement is extremely rare and difficult to recognize . thus , due to the diverse and atypical clinical manifestations of multifocal skeletal tb , the disease is easy to misdiagnose . in the present study , a rare case of atypical disseminated multifocal skeletal tb was reported , which exhibited uncommon findings in radiological images that were more suggestive of a hematological malignancy or metastatic disease . in conclusion , the diagnosis of this condition by conventional diagnostic methods is challenging . the importance of ct - guided needle biopsy and open biopsy in the diagnosis of skeletal tb was emphasized .

obesity in children is becoming one of a huge world s health and socioeconomic problems . body mass index in children is counted on the same way as in adults but must be compared to the child population of the same sex and age . children with bmi over 85 percentile belong to a group of overweight and those over 95 percentile are obese ( 1 ) . it is estimated that 10% of world children populations have obesity problems and the numbers are continuously increasing especially during last three decades ( 2 ) . genetic factors of child obesity lost it s importance comparing to factors as nutrition , exercise practicing and so on . child obesity is seen more often in poor families than in those with good socioeconomic situation . only 5% of child obesity is affected by some another decease ( 3 ) . adenotonsillectomy and adenoidecomy are the most often surgical intervention in children ( 4 ) . generally considered these operations belong to group of relatively safe procedures where patients death is registered on every 16000- 35000 patients . the most often anesthesiology complications during adenotonsillectomy and adenoidectomy are multiple laryngoscopy attempts , affected mask ventilations , upper respiratory system obstruction ( 5 ) . laryngospasm is the most often and most dangerous anesthesiology complication which appears after patient extubation , while during shallow anesthesia bronchospasm is possible . postoperative nausea and vomiting are noticed often after adenotonsillectomy with incidence over 70% ( 6 ) . approximately 1 - 2% of patients which are operated in general anesthesia are obese and 13 - 20% of them develop cardiorespiratory complications with high risk of acute pulmonary embolism ( 7 ) . overweight in children increase incidence of difficult mask ventilation , respiratory obstruction , bronchospasm and another respiratory incidents . most important predictors for postsurgical respiratory morbidity in children are younger children population , obesity and obstructive sleep apnea ( 9 ) . study is retrospective - prospective analysis of 162 children , both genders and 3 - 11 years old , who are hospitalized and operated ( adenotonsillectomies and adenoidectomies ) on otorhinolaryngology clinic of university clinical centre tuzla in the period of 4 years . children are divided in two groups according to the type of surgery and there was 100 children with adenotonsillectomy and 62 with adenoidectomy . all children according to anesthesiology criteria belonged to asa i and asa ii groups . there was counted body mass index for every child preoperatively on the base of measured weight and height and after they have been divided in two groups of normal and overweight . anesthesiology complications which have been noticed during intubation , operative period , and extubation were difficult intubation , upper respiratory obstruction ( laryngospasm and bronchospasm ) . adenotonsillectomies and adenoidectomies are done with standard operative technique and anesthesia was led by experienced anesthesiologist . every patient had its own protocol with all necessary data who have been processed with standard methods of descriptive statistics ( central tendency measures , dispersion measures ) and statistical significance testing ( x2-test , student s t - test , mann whitney test ) . adenotonsillectomy have been done in 100 patients ( 61,7% ) while adenoidectomy in 62 patients ( 38,3% ) . average patients age was 6,95 years ( 3 - 11.9 years ) . according to its gender there was 100 males and 62 females operated on and comparison have been made between two groups for both operations ( figure 1 ) . gender structure of operated patients measuring body mass index ( bmi ) for every patients there have been created bmi categories ( figure 2 ) . patients bmi categories table 1 shows distinction between bmi groups according to gender and figure 3 according to the type of operation . there was not statistically significant distinction in incidence between two categories ( x=6,14 ; df=3 ; p=0.11 ) . bmi groups of operated patients bmi categories for adenoidectomies and adenotonsillectomies anesthesiology complications have been noticed in 12 patients ( 7,4% ) and it s incidence for both types of operations has been measured ( figure 4 ) . there was not statically significant distinction between two types of operations ( x=0,003 ; df=1 ; p=0,95 ) the most often anesthesiology complication was bronchospasm while laryngospasm during extubation and difficult intubation were noticed once ( table 2 ) types of anesthesiologic complications comparing bmi categories of patients with incidence of anesthesiology complications for both types of operations there was noticed positive and significant correlation during adenotonsillectomy while it was not case during adenoidectomy ( table 3 ) . obese patients who are planned for adenotonsillectomy have 12,14 times bigger chance for anesthesiology complications incidence of anesthesiologic complications for all bmi cathegories using spearman s nonparametric correlation it is evident , there is smooth , positive and significant correlation between bmi and presence of complications . adenoidectomies et adenotonsillectomies as the most frequent operations in childhood have been researched for so many times and from different angles ( 10 ) . nafiu in it s similar study in 2007 have shown that average patients age was 7,2 ( + /-3,8 ) ( 11 ) . children who were adenoidectomisied and adenotonsillectomisied have prevalence of overweight and obesity in the study realized in 2009 , by costa and mitchel while children with normal bmi were dominant in this study ( 12 ) . too , conlon in his study in 1997 indicates that children who are planned for adenoidectomy et adenotonsillectomy from year to year show increase in its bmi ( 13 ) . from the other side 2170 children in united states of america who have had these two types of operations shown 10% lower bmi comparing with healthy populations of children with same age ( 14 ) . this study indicates direct and significant connection between obesity in children and incidence of anesthesiology complications during adenotonsillectomy , and with similar results drake - lee and stokes in 1998 propose that adenoidectomy as surgery with a rare anesthesiology complications could be done as daily surgery while it was not case with adenotonsillectomy which is mentioned as potentially very dangerous ( 15 ) . analyzing 413 children with the same operations as in this study kendrick and gibbin brought the number of 5,6% patients with anesthesiology complications which is little lower comparing with this studies ( 7,6% patients ) two or more anesthesiology complications were noticed in one patient . in the other studies risk factor for anesthesiology complications was from 4 - 13 while in this study it was 12,14 . it was shown that obesity in children does nt influence longer postoperative hospitalization for both types of operations . complication incidence during adenoidectomy and adenotonsillectomy was 7,6% and is lightly bigger than in same other similar studies . bronchospasm was the most often complication ( 3,7% ) and is followed by extubation laryngospasm ( 2,5% ) and difficult intubation ( 0,6% ) . obese children show much more anesthesiology complications comparing to children with normal body weight and risk factors indicates 12 times higher chance for complications in obese children comparing to normal bmi categories . all these data form general conclusion that every anesthesiologist should be very careful and well prepared for all operations done on obese children .

introduction : obesity in children is becoming from year to year enormous medical and socio - epidemilogical problem according to increasing number of overweight and obese children . overweight and obesity in children mostly affects on cardiovascular , respiratory and endocrine system disturbances . adenoidectomy and adenotonsillectomy belong to group of most often done operation in children population . anesthesiology complications during adenodecotomy and adenotonsillectomy in children are known as very disturbing and dramatic.methods:retrospective-prospective study includes 162 children , both genders , 3 to 12 years old , who are hospitalized and operated ( adenoidectomies and adenotonsillectomies ) on otorihinolaryngolic clinic of university clinical centre tuzla in the four year period . purpose of the study is to show the influence of overweight in children on appearance of anesthesiology complications such as difficult intubation , bronchospasm and laryngospasm . body mass index ( bmi ) , which is used as universal measure , is adapted with gender specific scales of national statistic centre of united states of america . all children with bmi over 25 are referred as overweight and those over 30 as obese . these children categories were compared to those with normal bmi according to anesthesiology complications incidence.results:overweight in operated children is noticed in 21% , and 11% of children was obese and there was nt distinction between boys and girls . anesthesiology complications are evaluated in 12 of them ( 7.4% ) . total analyzed sample show significant connection and influence of overweight with appearance of anesthesiology complications . separate comparison for two types of operations is indicating that during adenoidectomies there hasnt been noticed connection between overweight and anestehesiological complications , while in case of adenotonsillectomies direct and significant correlation is proven.conclusions:according to increased risk of anesthesiology complications in overweight and obese children during adenodectomies and adenotonsillectomies it is important for anesthesiologists to do much serious preoperative evaluation of obese children , and to be more prepared for every of possible unwished supersize during perioperative period .

ameloblastomas are locally invasive , highly destructive benign tumors of odontogenic origin . their recurrence rate is high even for patients who undergo surgical excision of the tumor with a safety tissue margin around . the mechanism of such local aggressiveness is still not known . for a better understanding of the aggressive behavior of ameloblastomas , investigations were carried out using biochemical and immunohistochemical methods to study the expression of metalloproteinases , growth factor receptors and their proliferative activity . among the various methods used for evaluation of proliferative activity , argyrophilic nucleolar organizer region ( agnor ) uses silver to stain the proteins associated with the active nucleolar organizer regions ( nors ) . nucleolar organizer regions ( nors ) are loops of dna that transcribe to ribosomal rna and direct ribosome formation and protein synthesis . nor sites are located on the short arm of five acrocentric chromosomes , 13 , 14 , 15 , 21 and 22 . nor - associated acidic proteins related to sites of r - rna transcription can be demonstrated in interphase nuclei in histologic sections by silver staining , which is due to reactivity of sulphydryl groups and can be visualized as black dots , referred to as agnors . recent studies show that the number and/or the size of the agnor dots in a nucleus are correlated positively with the ribosomal gene activity and therefore with cellular proliferation . a rapidly dividing tumor population shows a greater percentage of cells in the early g1 stages , with a consequently high number of agnors . on the contrary , nuclei of tumors with a reduced number of cells actively proliferating are more likely to show a single nor . it has been consistently shown that agnors quantification represents a valuable parameter of cell kinetics and , therefore cell proliferation . automated image analysis helps to reduce inter and intra - examiner variability and allows both enumeration and quantification of agnor size and type . the aim of this study was to compare the area and number of agnors between the follicular and plexiform variants of ameloblastoma in order to analyze their cell proliferation rates . morphometric data obtained from images of silver - stained histological sections were used in this study to compare the nor pattern between the two variants of ameloblastoma to observe if any consistent change existed between these lesions . the retrospective study was carried out on tissue sections obtained from histopathologically diagnosed cases of follicular and plexiform ameloblastomas . the study group comprised of 30 cases of follicular and 30 cases of plexiform ameloblastoma . equipment and armamentarium used for the study were silver staining solution , carl zeiss trinocular microscope , digital camera ( nikon ) with photomicrography adaptor and image analysis software : image pro - express media cybernetics , usa . the agnor staining solution was obtained by mixing solution a and solution b in the ratio of 2:1 . solution a was prepared by dissolving 25 grams of silver nitrate in 50 ml of de - ionized water . after dissolving silver nitrate crystals solution b was prepared by dissolving 500 mg of gelatin in 25 ml of de - ionized water . . 0.25 ml of 90% formic acid was then added to the solution and mixed well . from each paraffin embedded block 4m thick section was cut using rotary microtome ( leica r.m.2245 , germany ) . the sections were deparaffinized , rehydrated and then washed in running de - ionized water for 10 minutes . slides were then stained with silver colloidal solution freshly prepared by mixing solution a and solution b in the ratio of 2:1 and incubated in the dark at 30c for 45 minutes . the sections were then washed in running de - ionized water , dehydrated , cleared and mounted in synthetic resin medium . the staining procedure was standardized after a pilot study was carried out in the department , using internal controls such as the development of silver dots on lymphocytes . for each case , 50 nuclei of tumor cells from five microscopic fields were examined under 100x oil immersion lens ( ten cells were selected randomly from each microscopic field ) . images were captured using a 3 chip digital camera attached to a carl zeiss trinocular microscope with a 100x oil immersion objective lens . the images were classified , transferred and stored in the computer [ figures 1 and 2 ] . only well - defined and sharply stained intra - and extra - nucleolar agnor dots were included in the counting regime and morphometry . agnors which were located within the nuclei at the border of the microscopic field or superimposed nuclei were not included in the study . , where all silver stained structures were counted but when lying in clusters , each cluster was counted as one unit . agnor stained follicular ameloblastoma ( 100 ) agnor stained plexiform ameloblastoma ( 100 ) the analysis of agnor dots was done using two parameters , namely area measurement of agnors [ figure 3 ] and manual tag for the number of agnors [ figure 4 ] using the image analyzer software image - pro - express ( media cybernetics , usa ) . the data collected was analyzed statistically by student 's t - test and results were expressed as mean standard error of mean . morphometric analysis of area measurement of agnors using the image analyzer software image - proexpress counting of agnors using manual tag for the number of agnors using the image analyzer software image - proexpress the analysis of agnor dots was done using two parameters , namely area measurement of agnors [ figure 3 ] and manual tag for the number of agnors [ figure 4 ] using the image analyzer software image - pro - express ( media cybernetics , usa ) . the data collected was analyzed statistically by student 's t - test and results were expressed as mean standard error of mean . morphometric analysis of area measurement of agnors using the image analyzer software image - proexpress counting of agnors using manual tag for the number of agnors using the image analyzer software image - proexpress agnors were located within the cell nucleus and were distinctly stained in black as dots and blebs ; the rest of the nucleus stained yellow - brown . by careful control of the silver technique during preliminary experiments , it was possible to reduce the background staining which does not interfere with the identification and/or counting of agnors . lymphocytes in the tumor stroma serve as internal controls , as these most often demonstrate single or double agnor dots per cell . anova test showed significant difference between the group with respect to the mean number and area of agnors ( p<0.05 ) . anova test showed a significant difference in agnor area and number between follicular and plexiform ameloblastoma ( p < 0.05 ) . the results of the morphometric analysis of agnor dots from both the variants of ameloblastoma are shown in table 1 . plexiform ameloblastoma showed a higher mean agnor area of 0.831 m than the follicular variant with the mean area of 0.528 m , whereas follicular ameloblastoma showed a higher mean agnor number of 1.71 than plexiform variant with the mean number of 1.43 . the average number of agnor dots per nucleus in plexiform variant was significantly lower than in the follicular variant [ graph 1 ] , whereas mean value for area of agnor was significantly higher for plexiform ameloblastoma than follicular variant [ graph 2 ] . morphometric analysis of agnors in follicular and plexiform ameloblastoma bar graph showing the comparison of mean number of agnors in follicular and plexiform ameloblastoma bar graph showing the comparison of mean area of agnors in follicular and plexiform ameloblastoma clinically they have very similar growth patterns , with local invasiveness and rare metastasis , but have different recurrence rates , for this reason we performed qualitative and quantitative analysis of agnors in these two variants of ameloblastoma to compare their cell proliferation rates . the variation in nor distribution within the nucleus , however a nucleolar fragmentation occurs resulting in the dispersion of nors throughout the nucleus . nor counting has been used as a method to assess the rate of cellular proliferation . thus , nors are more likely to be observed in greater numbers in proliferative conditions . this assumption is confirmed by studies showing a correlation between the number of nors and other cellular proliferation parameters , such as ki-67 antigen and dna flow cytometry . cytokinetics of the lesions assessed by bromodeoxyuridine labeling index showed a linear correlation with agnor counts . agnor number is related to degree of tumor histologic differentiation and pathologic stage . for this reason , several authors have applied this technique and suggested that agnor enumeration can be useful in estimating the proliferation potential of neoplasms in the practice of surgical pathology . eusebi et al . , studied agnors and other parameters of breast carcinoma and found that only agnor counts showed an important relationship with clinical behavior . ohno et al . , analyzed the agnor counts in osteosarcomas , and found that osteosarcomas with a better prognosis have lower agnor numbers than those with a poorer prognosis . the mean number of agnor dots per nucleus in both the variants of ameloblastoma evaluated in this study was compatible with the values found for benign lesions , that is a mean value below 3 agnor dots per nucleus , in agreement with findings reported by rosa et al . and eslamini et al . the mean value found is compatible with the slow growth of ameloblastomas and suggests that the increase in proliferative activity of tumor cells may not be the only factor responsible for the infiltrative behavior of the lesion , as suggested by do carmo and silva . plexiform ameloblastoma showed a significantly smaller average number of agnor dots per nucleus than follicular variant . in our study , we observed that the mean area of agnors ( mean sd ) in plexiform ameloblastoma was 0.8310.148m , and in follicular ameloblastoma was 0.5280.179m . the mean number of agnor dots per nucleus in follicular ameloblastoma was 1.71 0.35 and in plexiform variant was 1.43 0.43 . our results were similar to the study by do carmo and silva ( 1998 ) where the mean agnor number in plexiform ameloblastoma was 1.49 0.15 and in follicular ameloblastoma was 1.87 0.39 . previous studies by ueno et al . , and reichart et al . , demonstrated a greater recurrence rate and a greater proliferative activity for follicular ameloblastoma than plexiform ameloblastoma . a significantly higher number of agnor dots per nucleus were found in follicular ameloblastoma than in plexiform ameloblastoma cells . most of the plexiform variant contained one or two agnor dots per nucleus , while most of the follicular variant contained two or three agnor dots per nucleus . in addition , plexiform ameloblastoma cells contained no more than three agnor dot per nucleus , while follicular ameloblastoma cells contained upto five agnor dots per nucleus . morphometric area of agnor dots yielded significantly higher mean values for the plexiform ameloblastoma than those for the follicular variant . agnors in follicular ameloblastoma were smaller , more numerous and more widespread than in plexiform ameloblastoma , which possibly demonstrates a higher degree of cellular proliferation in follicular variant of ameloblastoma . therefore , we may infer that almost half of the ameloblastoma cells would be synthesizing protein and this protein might participate in a mechanism that would contribute in part to the growth pattern of this neoplasm . this secretory activity could involve proteolytic enzymes linked to an invasive phenotype such as the metalloproteinase collagenase iv . this hypothesis is supported by the detection of collagenase iv in different stages of developing tooth . further studies demonstrating an increased production of metalloprotenases in ameloblastoma are necessary to confirm this hypothesis . furthermore , the combination of counting and area measurement defined a significant overall difference between agnor profiles in these two variants of ameloblastoma . in conclusion , we have determined that although follicular and plexiform ameloblastoma are epithelial tumors exhibiting similar clinical behavior they are composed of tumor cell populations with statistically significant differences in agnor patterns that reflect differences in cellular and nuclear activities .

aims : to compare the area and number of agnors ( silver stained nucleolar organizer regions ) by morphometry between follicular and plexiform variants of ameloblastoma in order to analyze their cell proliferation rates.materials and methods : this retrospective study was carried out on 30 cases each of follicular and plexiform ameloblastoma . the sections were obtained and stained with silver staining technique to identify the nucleolar organizer regions . agnors were quantified using two parameters ; manual tag for the number of agnors and area measurement using the image analyzer software , image-pro-express.results:morphometric area measurements of agnor were significantly higher for plexiform ameloblastoma ( 0.831m2 ) than follicular ameloblastoma ( 0.528m2 ) . enumeration of the number of agnors showed a significantly higher number of agnor for follicular ameloblastoma ( 1.71 ) than plexiform ameloblastoma ( 1.43 ) . among the groups studied , follicular ameloblastoma was more aggressive than plexiform ameloblastoma , as it showed smaller agnor area and higher agnor number.conclusion:the combination of counting the number and measuring the area of agnor dots showed a significant overall difference between agnor profiles of follicular and plexiform variants of ameloblastoma .

general practitioners ( gps ) can be paid by a variety of methods : capitation fees , fee for service , and salary being the most common . fee for service tends to result in overtreatment of patients , whereas capitation tends to encourage undertreatment and preventive measures . in addition to the method of payment , financial incentives have been used in various countries to attract gps to locate in disadvantaged areas . the incentives are typically in the form of payments calculated based on the socioeconomic characteristics of practice catchments . however , targeting on the basis of areas may result in a failure to reach many deprived individuals as not all deprived people live in deprived areas and not all people in a deprived area are necessarily deprived . in ireland , and unlike the united kingdom , gps are paid through a combination of fee for service for private patients and capitation fees for eligible patients funded by the state . the capitation rates are linked to the age and sex of the patient and the distance they live from the gp practice . approximately thirty percent of the irish population is covered for gp care under the general medical services ( gms ) scheme , while the remaining 70% of the population pay full fees to access gps . although covering only a third of the population nationally , the gms scheme accounts for 57% of gp income and is highly valued by gps as it is superannuated and attracts staffing subsidies . patient eligibility for the gms scheme is determined on a means - tested basis , and gps are reimbursed on a capitation basis for treating gms patients . prior to the 2002 general election , the government decided that gms eligibility should be extended to all over-70-year olds . having announced their intentions prior to entering contract talks , the government found itself in a weak negotiating position . only the fees for the newly eligible over-70-year olds were under negotiation , and the existing coverage and capitation fees were maintained . universal eligibility for over-70-year olds was removed at the end of 2008 although it was estimated that 95% of over-70-year olds would continue to be eligible for free care . the cessation of universal cover for over-70-year olds was accompanied by a new unified capitation fee for all over-70-year olds to end the differential fee . while in situ , the differential capitation rate for the over-70-year olds may have worked to attract gms gps to affluent areas with a large elderly population , but a previous study by the authors established that variation in access to gp services by deprivation in urban parts of ireland is relatively small . it appeared that the gms scheme had not unfairly distorted the distribution of gps in relation to deprivation . however , the provision of free care to over-70-year olds largely irrespective of income may be directing resources away from those most in need . the aim of this paper is to analyse the relationship between gp income derived from the gms scheme and deprivation amongst dublin - based gps , taking into account the population distribution of over-70-year olds . county dublin is a predominantly urban area with a population of 1.2 million as of the 2006 census , equivalent to 28% of the national population . seven percent of the dublin population is over 70 years of age , slightly below the national figure of 7.7% . there are 322 electoral divisions ( eds ) in county dublin with a mean population of 1244 ( range 7632288 ) . thirty percent of the dublin eds are in the most deprived decile nationally and 22% in the least deprived decile nationally . half of the over-70-year olds in dublin are split equally between least deprived decile and the most deprived decile of eds . since 1989 , under the general medical services ( gms ) scheme , the state has contracted gps to provide care free at the point of use for the poorest 30% of the population on a capitation basis . coverage of the gms scheme has varied between 28.1% and 32.5% of the population from 1999 to 2008 . since 2005 approximately 96% of gp practices nationally provide care under the gms scheme although within dublin the figure is closer to 85% . from 2001 to 2008 , the capitation fee for a patient over-70-year old without prior eligibility for the gms was 672 compared to 147 and 162 for previously eligible ( i.e. , based on means testing ) males and females over-70-year olds , respectively . since january 2009 , there has been an average capitation fee of 290 for all over-70-year olds eligible for the gms scheme . the gross weekly income limits for gms eligibility are 184 , 201.50 , and 700 for a single person aged under 66 , 66 to 69 and over 70 years , respectively . the primary care reimbursement service ( pcrs ) publishes the list of gps in receipt of gms payments . the most recent year available was 2009 with data distinguishing between practice support and gms fees . multiple gps in the same practice may be in receipt of practice support which is used to subsidise the cost of a practice manager and nursing and secretarial staff . the addresses of gps were obtained from a variety of sources including the irish college general practitioners ( icgp ) , cervicalcheck , and the irish medical directory [ 1113 ] . the deprivation index is similar in structure to that of the townsend deprivation index used extensively in the uk . the index combines four indicators of material deprivation into a score : unemployment , low social class , car ownership , and local authority housing . the deprivation score can also be expressed in deciles to label the most deprived 10% of eds . for this study , the deprivation score is used in preference to the deciles to capture the variability that can occur within a single deprivation decile . as the deprivation score is positively skewed , the most deprived decile spans a wide range of scores the deprivation and population contribution of each ed to a catchment profile reduced with increasing distance from the practice ed . the distance weighting was estimated using a distance decay function developed in a previous study . a practice - specific deprivation score was computed using the nearest 20 eds to the practice ed . the deprivation scores were weighted using a combination of the weights generated by the distance decay function multiplied by the ed populations . catchment area population is not a measure of practice list size but acts as a proxy for demand in a practice catchment area . restrictions apply as there is a cap on how many gms patients a gp can have in his list at any one time , but there is a scope for choice of practice on the part of the patient . a large number of gms gps in a locality can represent oversupply and reduce incomes . as a proxy for competition , we determined the number of gms gps and the average gms income of gps within 2 km of each practice . to acknowledge the clustered data structure and the large number of clusters ( n = 202 ) involved , total practice income was analysed using a bayesian hierarchical model with practice ( level 1 ) nested within electoral division ( level 2 ) . total practice income was transformed to the loge scale to address both skewness and heteroscedasticity in the distribution of income and then back transformed for purposes of reporting results . the bayesian modelling was carried out via jags using the r statistical program with the rjags package ( v 2.2.0 - 3 ) employing 3 chains . all model coefficients had successfully converged based on a gelman & rubin statistic of 1.04 and the heidelberger & welch test offered by coda . predictions of total practice income were simulated using the distribution of the dependent variable conditional on the estimated parameters from the model . as is customary in bayesian model reporting , to assess the significance of the model coefficients , a 95% bayesian credible interval is reported in lieu of a p value . the mgcv package ( v 1.7 - 2 ) within r was used with the default choice of smoothing spline to visualise the dependency between predicted total practice income and deprivation . five hundred and eighty - four dublin - based gps are listed as having some gms income in 2009 . address records could not be found for three gps leaving 581 included in this analysis . after address coding , a total of 383 distinct practices were identified which were distributed across 202 eds . the average number of gms patients per gms gp in dublin is 528 compared to a figure of approximately 540 nationally . the overall mean practice income was 271,572 which comprised practice support ( mean = 49,738 ) and gms fees ( mean = 221,847 ) . the mean estimated percentage of patients over 70 years old per practice was 7.6% ( range 1.5%14.5% ) . sixty eight percent of practices had only one gp in receipt of gms fees with only 6 practices having 5 or more gms gps . the median and interquartile ranges ( iqr ) for the main practice level and ed level characteristics are given in table 1 . using a regression model , deprivation and proportion population over-70-year olds were found not to be significant predictors of the number of gms gps in a practice . thus , there was no tendency for larger practices in more or less deprived areas or in areas with high proportions of over-70-year olds . there is a modest trend for a decreasing proportion of over-70-year olds in the catchment population with increasing practice deprivation ( see figure 1 ) . the size of the circles in figure 1 is proportional to the total practice income . few of the practices at the least deprived end of the spectrum have large gms - derived incomes . it is likely that almost all gms income for these practices comes from treating eligible patients of over-70-year olds . conversely , for practices in the most deprived areas , the income comes almost entirely from gms patients under 70 years of age . the contribution of different predictors to total practice gms income was estimated using a hierarchical bayesian model ( see table 2 ) . deprivation is a significant predictor of practice income ; however , as the relationship is quadratic , total income tends to fall again at high levels of deprivation ( see figure 2 ) . the percentage of over 70s has , on average , no impact on total income . the number of gms gps within 2 km negatively impacts on total income ; as anticipated , competition acts to reduce practice income . gms incomes in practices in the least deprived areas are lower with the largest incomes in areas with moderate levels of deprivation ( figure 2 ) . however , low incomes are also observed in the practices with the most deprived catchments . these practices are characterised by mostly being single handed with low proportion of patients of over-70-year olds . gps in ireland are funded through a mixture of fee for service for private patients and capitation fee for publicly funded patients . practices in more deprived areas have higher gms incomes than those in affluent areas suggesting that state - funded care is both profitable and generally reaching those who can least afford to pay for care . the profitability in deprived areas stems primarily from the high volume of patients under 70 years of age . the biggest impact on total practice gms income is predictably the number of gps in the practice . the percentage of over-70-year olds has a modest positive impact on income , and we have shown that less deprived areas have higher percentages of over-70-year olds . the level of competition from neighbouring practices has a significant negative impact on practice gms income highlighting the contribution of supply and demand to practice income . practice deprivation score plays a relatively minor role differentiating ireland from uk , where population level deprivation has traditionally made an important contribution due to the explicit use of deprivation scores in primary care resource allocation . this study has only investigated income from the gms which represents 57% of total gp income . for practices in more deprived areas , the gms income may well represent most if not all of practice income . in more affluent areas , on the other hand , where a significant proportion of patients pay for services , the gms income will only represent a small portion of the total practice income . a patient over 70 is , in monetary terms , equivalent to 3 to 4 patients aged 16 to 44 years and 2 patients aged 45 to 69 years . clearly , a small number of patients of over-70-year olds can provide a useful source of income in affluent catchment areas . incomes in practices serving the most deprived communities are relatively low compared to other deprived areas . it is probable that gps working in the most deprived areas work fewer sessions in an effort to control workload and stress . we were not able to adjust the results for the number of sessions or list size . data are not available on non - gms practice income which would provide useful counterbalance and enable an estimate of the value of gms patients of over-70-year olds in affluent areas . although gp utilisation increases with age , the disparity in both capitation fee and eligibility criteria between those under and over 70 years of age is introducing inequity into the health care system . in a fixed - budget health system with limited resources , if care can not be provided for all , then it must surely be directed to those most in need . but , by providing free gp care to those of over-70-year olds largely irrespective of the level of personal wealth , the state directs resources away from those most in need and provides a valuable income to gps located in the least deprived areas . a small nondeprived but elderly catchment can be as valuable as a larger deprived catchment with a younger population . the combination of higher workloads and stress associated with practice in a deprived catchment and the differential capitation payments may act to encourage gps to locate in less deprived areas . we have shown that despite the near universal cover for over-70-year olds , gms incomes are highest in deprived areas although they are lower in the most deprived areas . it is encouraging to observe that gps continue to locate in deprived areas . however , in the absence of universal free gp care , resources should not be channelled away from those who can not afford to pay towards those who can .

the general medical services ( gms ) scheme provides care free at the point of use for the 30% most economically deprived section of the population and the elderly . almost all people of over-70-year olds are eligible for the gms scheme potentially directing resources away from those most in need . the aim of this study is to analyse the relationship between practice gms income and deprivation amongst dublin - based general practitioners ( gps ) . the practice gms income in dublin was analysed in relation to practice characteristics including the number of gps , catchment area population , proportion of over-70-year olds in the catchment area , catchment deprivation , number of gms gps within 2 km , and average gms practice income within 2 km . practice gms income was highest in deprived areas but is also a valuable source of income in the least deprived areas . the capitation rate for over-70-year olds provides an incentive for gps to locate in affluent areas and potentially directs resources away from those in greater need .

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

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

congenital hypothyroidism in neonates and very young infants is usually caused by thyroid dysgenesis associated with an absent , ectopic , or hypoplastic thyroid gland , and can be detected by neonatal screening in the general population . although this illness itself is considered to be unchanged throughout the patient s life , it can be transient in certain cases , for example , infants of mothers with chronic autoimmune thyroiditis ( 1 ) . hypothyroidism in young children is mostly caused by chronic autoimmune thyroiditis , but it is quite rare before the age of 3 ( 2 ) . thomas et al . described four children , nine months to two years of age at the time of diagnosis , who had hypothyroidism that was most likely to have been caused by chronic autoimmune thyroiditis ( 3 ) . trab , such as tsh - binding inhibitor immunoglobulin ( tbii ) and thyroid stimulating antibody ( tsab ) , have been detected in most patients with hyperthyroidism due to graves disease . this patient trab changed from a blocking type to a stimulating type in association with the development of hyperthyroidism ( 4 ) . in this report , we describe a first case with hyperthyroidism , who was diagnosed with ch at neonatal screening and since then had been treated for 13 yr with thyroid hormone . his mother was healthy , and his father had a clinical history of hyperthyroidism , which was treated with antithyroid drugs for one year when he was 42 . the patient s birth weight was 2770 g , and his gestational age was 40 wk . at the age of 16 d , he was referred to our hospital because of positive results at neonatal screening for ch . the dried blood tsh at the ages of 5 and 12 d were 76.76 u / ml and 38.08 u / ml , respectively . at the age of 16 d , the serum levels of tsh , t4 and t3 were 91.0 u / ml ( adult normal range : 0.45.0 ) , 6.9 g / dl ( adult normal range : 3.712.1 ) and 1.36 ng / ml ( adult normal range : 0.71.8 ) , respectively . the size of the right distal femoral epiphysis was 6 3 mm and that of the left was 6.5 4 mm on x - ray examination . he was diagnosed with subclinical congenital hypothyroidism and received hormone replacement therapy from the age of 34 d. the initial dose was 15 mg of desiccated thyroid a day . at the age of 55 d , the patient s serum level of tsh was 38.5 u / ml and serum level of free t4 was 0.94 ng / ml ( adult normal range : 0.782.12 ) . at the age of 18 mo , the scan demonstrated a thyroid gland normally located with homogeneous uptake of radioactive iodine ; the uptake rate was 15% ( normal range , 1040% ) at 24 h. the potassium thiocyanate discharge test showed 25% , and a defect in iodine organification was suspected . his growth spurt started at about the age of 13 and his adolescence was of the slightly delayed type . ) . at the age of 3 , both the serum level of anti - microsome antibody and anti - thyroglobulin antibody were negative . at the age of 6 , the medication was changed to l - thyroxine from desiccated thyroid . at the age of 8 , the patient s iq score on wisc - r intelligence test was 133 ( normal 105.4 20.7 ) , and his evaluated bone age was delayed one year compared with his chronological age . the dosage of l - thyroxine was gradually increased as he grew and the maximum dose was 110 g / day at the age of 11 ( fig . the dosage of thyroid hormone was gradually increased as he grew and the maximum dose was 110 g / day . at the age of 13 yr and 4 mo , the serum level of tsh dropped to an undetectable level . ) . until the age of 13 , however , at the age of 13 yr and 4 mo , his serum level of tsh dropped to an undetectable level . the dosage of l - thyroxine was tapered off and eventually eliminated at the age of 14 . the patient s height and weight were almost the mean until the age of 11 . his growth spurt started at about the age of 13 and his adolescence was of the slightly delayed type . the dosage of thyroid hormone was gradually increased as he grew and the maximum dose was 110 g / day . at the age of 13 yr and 4 mo , the serum level of tsh dropped to an undetectable level . physical findings at the age of 14 were as follows : height , 165.1 cm ; weight , 50.2 kg ; blood pressure , 124/63 mmhg ; pulse rate , 109 beats / min . blood examination revealed the following data : free t4 , 4.22 ng / dl ( 0.821.63 ) ; free t3 , 12.0 pg / ml ( 2.04.9 ) ; tsh , less than 0.03 u / ml ( 0.414.01 ) ; trab , 62.5% ; anti - microsome antibody , 25600 ; anti - thyroglobulin antibody , negative . a thyroid scan demonstrated a diffuse goiter with homogeneous uptake of radioactive iodine ; the uptake rate was 60% at 24 h. having confirmed hyperthyroidism , therapy was started with antithyroid drugs ( fig . one month after the start of therapy , the serum level of free t4 was normalized . after two months of therapy , the serum level of tsh had risen to a detectable level . ) . one month after that , the patient s serum level of free t4 was normalized , and the dosage of mmi was tapered . two months after the therapy , the patient s serum level of tsh had risen to a detectable level ; however trab was still high , and the dosage of mmi was tapered again and l - thyroxine therapy was added . one month after the start of therapy , the serum level of free t4 was normalized . after two months of therapy , the serum level of tsh had risen to a detectable level . the patient s height and weight were almost the mean until the age of 11 . at annual x - ray examinations , bone ages were delayed only one year as compared with his chronological age , and the patient s growth spurt started at about the age of 13 . his adolescence was of the slightly delayed type . at the age of 15 , his height was 167 cm , and his weight was 57 kg ( fig . the mental development of children with ch has been improved as a result of early detection by neonatal screening and an appropriate therapy ( 5 , 6 ) . newborns classified false positive at ch screening have a very high risk of subclinical hypothyroidism in infancy and early childhood ( 7 ) . nevertheless , it is difficult to decide whether a case should be treated or not in cases such as transient hypothyroidism , transient hyperthyrotropinemia , mild congenital hypothyroidism , and persistent hyperthyrotropinemia at the early phase of consultation ( 8) . the present case was considered subclinical ch with high tsh and normal t4 levels . thus thyroid hormone replacement therapy was started at the age of 34 d. the patient s serum levels of tsh were sometimes high , and as he grew , the dosage of thyroid hormone was escalated to a maximum dose of 110 g / day until the age of 11 . his clinical course was consistent with that of permanent ch till the age of 13 , and it is speculated that he suffered from an iodine organification defect at that time . van der gaag et al . found transplacental passage of maternal immunoglobulins may play a part in the pathogenesis of ch ( 9 ) . kato et al . described two cases of ch detected by screening whose sera contained high levels of antibodies in early childhood , and concluded that the antibodies were not derived from maternal immunoglobulins but produced on their own ( 10 ) . therefore we hypothesize that in the present case hypothyroidism was transient due to immaturity of iodine organification in the thyroid gland as nose et al . described previously ( 11 ) , and that afterwards hyperthyroidism developed due to an autoimmune disease , and was diagnosed with the results of serum trab and the thyroid scan . it is also possible that the patient had several clones of antibodies against thyroid from his early infancy . although the patient s mother had no thyroid disease and his antibodies were negative in early childhood , a clonal change in his antibodies might have happened and their binding properties could have been altered from the blocking type to the stimulating type ( 4 , 12 ) . further analysis of thyroid function is apparently necessary to assign the immunological basis of this case and additional follow - up data should be accumulated during the treatment course of this patient .

we encountered a case with hyperthyroidism at the age of 14 who had been diagnosed with congenital hypothyroidism ( ch ) and had received thyroid hormone replacement therapy . at the age of 16 d , the patient was referred to our hospital because of positive results at neonatal screening for ch . serum level of tsh was 91.0 u / ml and serum level of t4 was 6.9 g / dl . the patient was diagnosed as having hypothyroidism , and hormone replacement therapy was started . thereafter the dosage of thyroid hormone was adjusted and increased gradually as he grew to a maximum dose of 110 g / day at the age of 11 . until the age of 13 , the patient s serum levels of tsh were within the normal range ; then , at the age of 13 yr and 4 mo , his serum level of tsh dropped to a level below the detectable range . the dosage of administered thyroid hormone was tapered off and eventually eliminated at the age of 14 . a thyroid scan and a radioactive iodine uptake test demonstrated a diffuse goiter with homogeneous uptake of radioactive iodine ; the uptake rate was 60% at 24 h , and the serum level of tsh receptor antibody ( trab ) was 62.5% at that time . administration of an antithyroid drug was started after confirmation that our patient had developed hyperthyroidism . there have been no case reports similar to our case .

a reappraisal of the priorities of cardiopulmonary resuscitation by pepe and colleagues calls attention to the evidence that defibrillation may not be the optimal initial intervention . initial precordial compression after more than perhaps 3 minutes of untreated cardiac arrest greatly improves the likelihood of successful conversion of ventricular fibrillation with restoration of spontaneous circulation . since it is often very difficult to gauge this time interval , and whether it exceeds 3 min , a number of both preclinical investigators [ 4 - 6 ] and clinical investigators have sought an electrocardiographic predictor of the likelihood that an electrical shock will restore circulation . it is to this extent that we applaud the authors ' call for caution lest the availability and promotion of automated external defibrillators diminishes the preparedness of the rescuer to proceed with more conventional basic life support . pepe and colleagues then extend their discussion to advanced cardiac life support , and especially pharmacological interventions . in the context of the time dependency of interventions , they are not prepared to discard the possibility that high - dose epinephrine will improve outcome . indeed , they favor the use of cocktails , entertaining the possibility that epinephrine may be administered conjointly with antioxidants and anti - arrhythmic drugs . although we agree with pepe and colleagues in implicating the myocardial energy / supply relationship as an important issue , we wish to point out that beta - adrenergic agonists , and to a lesser extent the alpha1 actions , greatly increase myocardial energy consumption and thereby intensify the severity of myocardial injury . although the alpha - adrenergic effects increase coronary perfusion pressure and transiently increase myocardial blood flow , the downside is major . the inotropic and chronotropic effects produce greater global myocardial ischemia , greater post - resuscitation ventricular ectopy and recurrent ventricular tachycardia , and recurrent ventricular fibrillation . even more importantly , the adrenergic inotropic and chronotropic actions result in greater severity of post - resuscitation myocardial dysfunction . although epinephrine has been used as a resuscitative drug for more than a century , and although there is evidence that epinephrine may facilitate initial resuscitation , there is no proof of ultimate clinical benefit in terms of survival . to the contrary , we suspect that vasopressor agents with no inotropic and chronotropic actions are likely to come to the fore . this has prompted interest in more selective vasopressor agents , including -methylnorepinephrine and nonadrenergic vasopressin . moreover , as yet unpublished preclinical studies from our group now suggest a place for beta - adrenergic blocking agents . looking to the future , we also see an opportunity for much improvement in sequencing interventions . in support of the conclusions reached by pepe and colleagues , additional precision in sequencing cardiopulmonary resuscitation interventions has a high likelihood of improving outcomes . perhaps one measurement , not cited by the authors , is end - tidal carbon dioxide . both experimentally and clinically , end - tidal carbon dioxide has been a noninvasive monitor of blood flow generated by precordial compression . it serves as quality control of precordial compression and allows chest compression to remain uninterrupted . no longer will advanced cardiac life support rescuers need electrocardiographic confirmation of the return of spontaneous circulation because it is overtly signaled by an overshoot in the end - tidal carbon dioxide .

the contribution by pepe and colleagues provides additional evidence that initial defibrillation is not necessarily the optimal intervention for victims of cardiac arrest and especially when cardiac arrest has been untreated for more than 3 min . precordial compression therefore remains the mainstay of basic life support cardiopulmonary resuscitation after sudden death . it is increasingly apparent that neither epinephrine whether in conventional or high doses nor vasopressin improve ultimate survival . to the contrary , there is evidence favoring 1-adrenergic blockade .

non - alcoholic fatty liver disease ( nafld ) is one of the most common liver diseases in the western hemisphere , affecting 20% to 30% of the adult population . approximately 10% to 25% patients with nafld can progress to non - alcoholic steatohepatitis ( nash ) and 10% to 15% patients with nash develop hepatocellular carcinoma . in addition , nafld is closely associated with metabolic syndrome , type 2 diabetes mellitus ( t2 dm ) and cardiovascular morbidity and mortality . despite these associated pathologies , glucagon - like peptide-1 ( glp-1 ) is an incretin secreted by l - cells in the small intestine in response to food intake . the main roles of glp-1 are stimulation of glucose - dependent insulin secretion , inhibition of postprandial glucagon release , delay of gastric emptying , and induction of pancreatic -cell proliferation . once in circulation , glp-1 has a short half - life ( 1 to 2 minutes ) due to rapid degradation by the ubiquitous endogenous enzyme dipeptidyl peptidase-4 ( dpp-4 ) . to overcome this obstacle , glp-1 receptor agonists that have increased resistance to dpp-4 ( such as exenatide and liraglutide ) or dpp-4 inhibitors ( such as sitagliptin , vildagliptin , saxagliptin , alogliptin , and linagliptin ) have been used in animal and human studies . recent studies have shown that exendin-4 could improve hepatic steatosis by modulation of lipid metabolism and hepatic insulin signaling in ob / ob mice and in human hepatocyte . additional studies have demonstrated that treatment with exendin-4 and liraglutide could reduce steatosis by enhancing autophagy . treatment with exendin-4 and liraglutide leads to reduced endoplasmic reticulum ( er ) stress - related apoptosis in human hepatocytes treated with fatty acids as well as in mice fed a high fat diet , respectively . in this review the liver , as a key organ for lipid homeostasis , has roles in various aspect of energy metabolism . hepatic lipid homeostasis is usually maintained through balance between the influx or production of fatty acids and their use for oxidation or secretion as very low density lipoprotein ( vldl ) triglycerides [ 11 - 13 ] . hepatic steatosis is associated with the alteration of nuclear receptors , membrane transport proteins and cellular enzymes . sterol regulatory element binding protein1c ( srebp-1c ) transcription factor and peroxisome proliferator - activated receptor ( ppar ) are essential regulators for steatosis in obese patients . enhancement in the srebp-1c / ppar ratio , an indication that lipogenesis is higher than fatty acid oxidation , was found in obese patients with hepatic steatosis . mice had impaired induction of hepatic genes coding for fatty acid biosynthesis ( e.g. , acetyl - coa carboxylase , fatty acid synthase , and stearoyl - coa desaturase ) compared to wild type mice . these results suggest that nafld is caused by both increased lipid storage ( from circulating fatty acid uptake and de novo lipogenesis ) and decreased lipid removal ( via fatty acid oxidation or vldl - triglycerides secretion ) . pleiotropic effects of glp-1 on glucose metabolism , appetite , weight , blood pressure , cardiovascular risk factors , cardiovascular function , and the central nervous system have been reported . glp-1 achieves its roles by binding to its specific receptor ( glp-1r ) on human hepatocytes . in addition , we recently reported that exendin-4 increases expression of glp-1r in a dose - dependent manner in human hepatoma cell lines . several human and animal studies have demonstrated the therapeutic effects of glp-1 receptor agonist in slowing the progression of nafld . exenatide therapy decreased hepatic fat accumulation , insulin resistance , and the risk of cardiovascular disease in patient with t2 dm and also improved fatty acid -oxidation and insulin sensitivity in the livers of rats on a high fat diet . hepatic gluconeogenesis and insulin sensitivity were improved in ob / ob mice treated with recombinant adenovirus expressing glp-1 ( rad - glp-1 ) . protective effects of glp-1 against hepatic steatosis were found in only diet - induced obese mice . sitagliptin , a dpp-4 inhibitor , showed a decrease in liver triglyceride content , expression of lipogenesis genes and gluconeogenesis in wild type mice . ultimately , exendin-4 may play role as a novel treatment of nafld via direct effect on hepatic lipid and glucose metabolism . in mammalian liver , fatty acids oxidation serves as a source for energy generation and occurs in both the mitochondria and the peroxisomes . short and medium - chain fatty acids ( scfas : < 6 carbons long and mcfas : 6 to 12 carbons long ) are oxidized in the mitochondria , long - chain fatty acids ( lcfas : c12 to c20 ) are oxidized in both the mitochondria and peroxisomes , and very long - chain fatty acids ( vlcfas : > , excess fatty acids can impair fatty acid oxidation by inhibiting the activities of enzymes involved in fatty acid oxidation . ppar is a transcriptional factor regulating the expression of a number of genes involved in mitochondrial and peroxisomal fatty acid -oxidation . exendin-4 significantly increases the expression of ppar and acyl - coenzyme a oxidase ( acox ) mrna in ob / ob mice . hepatocytes isolated from rats with nash demonstrated reduced expression of hepatic ppar and its downstream target genes : acox and carnitine palmitoyltransferase 1a ( cpt1a ) . acox is a rate - limiting enzyme involved in peroxisomal fatty acid -oxidation and cpt1a is a key enzyme allowing the initial transport of fatty acids into mitochondria for -oxidation . expression of ppar , and subsequently acox and cpt1a , was improved by exendin-4 treatment . amp - activated protein kinase ( ampk ) and silent mating type information regulation 2 homolog ( sirtuin , sirt ) 1 are metabolic sensors regulating energy homeostasis and various intracellular systems . these include fatty acid oxidation , lipogenesis , glucose uptake , gluconeogenesis , mitochondria biosynthesis , and insulin sensitivity . they are also involved in mediating the effect of adiponectin in inhibiting the accumulation of liver fat . ampk and sirt1 are activated by an amp and nad dependent mechanism and acts through regulation of phosphorylation and deacetylation of their targets , respectively . pgc-1 is a common target of the two metabolic sensors , and has been shown to have protective effects in patients with metabolic diseases . nampt / visfatin is a mammalian nad+ biosynthetic enzyme that controls sirt1 activity by mediating the conversion of nicotinamide ( nam ) to nad . however , the precise mechanism of interaction between ampk and sirt1 is still controversial and varies with tissue and condition . reported that ampk regulates sirt1 activity by increasing cellular nad levels in mouse skeletal muscle ( fig . recent studies reported that glp-1 increases the phosphorylation of ampk in hepatocytes and reverses hepatic steatosis by stimulating fatty acid oxidation . moreover , we recently demonstrated that activating glp-1 receptor by exendin-4 treatment enhances the expression of nampt , sirt1 , and ampk in mouse liver . sirt1 inhibitor ( nam ) leads to a decrease in phosphorylation of ampk in human hepatocytes , indicating that sirt1 stimulates ampk ( fig . thus , glp-1 could improve hepatic lipid metabolism by regulation of nampt / sirt1/ampk signaling . the liver has a vast range functions in the body , including immunity against infection , synthesis of proteins and cholesterol , detoxification , glycogen storage , excretion of bile for fat digestion , and regulation of metabolism . however , insults such as alcohol , autoimmune malfunction , hereditary diseases , and metabolic diseases could result in liver dysfunction . in a study investigating human hepatocytes treated with fatty acids , exenatide was shown to reduce fatty acid storage and improve hepatocyte viability and markers of autophagy . a clinical trial evaluating the effects of exenatide in patients with t2 dm over a period of 3 years revealed that treatment lead to significant improvements in hepatic markers , such as elevated liver enzymes , and other cardiovascular risk factors were significantly improved . a case study exploring the efficacy of exenatide therapy in a 59-year - old nafld patient , reported a 73% reduction in hepatic fat content and significant improvements in liver enzymes 44 weeks post - treatment . a modified glucose clamp study demonstrated that exenatide reduces postprandial glucose by increasing the hepatic uptake of exogenous glucose . furthermore , glp-1 in obese mice reduces hepatic gluconeogenesis by inhibiting phosphoenolpyruvate carboxykinase ( pepck ) and glucose-6-phosphatase ( g6pase ) . park et al . reported that exendin-4 treatment decreases hepatic glucose output at hyperinsulinemic states and promotes hepatic insulin signaling by potentiating tyrosine phosphorylation of the insulin receptor substrate-2 in 90% pancreatectomized diabetic rats fed high fat ( 40% energy from fat ) diets . disruption of lipid metabolic homeostasis has been recognized as a major cause of nafld , which is associated with insulin resistance , t2 dm , obesity , and cardiovascular disease . although the incretin glp-1 has been widely studied for its effects on stimulation of glucose - dependent insulin secretion in pancreatic -cell , glp-1 receptor agonists have other important effects in peripheral tissues . treatment with glp-1 mimetics improves hepatic insulin signaling in nafld animal models , and these effects could be invoked by direct stimulation of hepatic glp-1 receptor . glp-1 is expected to have pleiotropic effects on the liver , and more research is needed to explore its mechanism .

non - alcoholic fatty liver disease ( nafld ) , one of the most common liver diseases , is caused by the disruption of hepatic lipid homeostasis . it is associated with insulin resistance as seen in type 2 diabetes mellitus . glucagon - like peptide-1 ( glp-1 ) is an incretin that increases insulin sensitivity and aids glucose metabolism . in recent in vivo and in vitro studies , glp-1 presents a novel therapeutic approach against nafld by increasing fatty acid oxidation , decreasing lipogenesis , and improving hepatic glucose metabolism . in this report , we provide an overview of the role and mechanism of glp-1 in relieving nafld .

a 69-year - old gentleman presented with a history of episodic blurred vision in his right eye . on examination , visual acuity was 6/12 , the intraocular pressure was 48 mmhg , but aside a mild anterior chamber cellular reaction and fine stellate kps , ocular examination was unremarkable . the patient 's medical history included type 2 diabetes and terminal ileal crohn 's disease , for which he was prescribed rosiglitazone and azathioprine 150 mg od . a diagnosis of posner - schlossman syndrome was made , and topical corticosteroids and timolol were prescribed . following treatment , the ocular condition rapidly resolved with complete resolution of anterior chamber inflammation and normalization of iop , but over the ensuing 3 months , the patient presented with 2 further episodes of presumed pss . on each occasion , the condition was controlled with topical corticosteroids and timolol . on a further attendance 6 weeks later , the visual acuity was noticeably more reduced than previously ( 6/36 ) , and in addition to a mild anterior chamber reaction and high intraocular pressure ( 42 mmhg ) , there was also a moderate vitritis . an examination of the posterior pole at this attendance revealed a small discrete area ( 2 disc diameters ) of granular retinal pallor in the temporal periphery . the patient was treated with topical and systemic prednisolone with resolution of the ocular inflammation and improved visual acuity . over the ensuing 12 weeks , the systemic and topical steroids were tapered , but the ocular inflammation recurred as the dose was reduced . it was also noted that the previously noted white patch had enlarged [ fig . 1 ] and a chorioretinal and vitreous biopsy organized . vitreous pcr [ lightcycler fret technology ( roche ) ] was positive for cytomegalovirus ( cmv ) and negative for hzv , hsv 1 and 2 . transmission electron microscopy revealed herpes family virus particles , and immunohistochemistry demonstrated cmv protein [ fig . 2 ] . in particular , 3 generation hiv test ( elisa ) was negative , his cd4 counts were consistently above 350 , and his full blood count was normal . despite treatment with intravenous ganciclovir and long - term oral valcyclovir ( as per local guidelines ) , there is an area of granular retinal pallor in the temporal periphery , which had enlarged over 4 months . there is a possible satellite lesion at the fovea , an associated vitritis and new vessels at the disc chorioretinal biopsy ( a ) hematoxylin and eosin stained chorioretinal biopsy . the black arrows point to cytomegalic - like inclusions within the eosionophilic , necrotic neural retina ( magnification , 400 ) , ( b ) immunohistochemistry : chorioretinal tissue stained with monoclonal antibodies to cytomegalovirus protein shows positive brown signal within the necrotic neural retina ( magnification , 400 ) , ( c ) transmission electron microscopy shows herpes family viruses particles within the necrotic neural retina ( magnification , 20000 ) ocular cmv infection is most commonly known for the typical retinitis that is seen in those patients who are severely immunocompromised or receiving combination immunosuppressive therapy . it is however recognized that cmv infection may also be implicated in pss/ hypertensive iridocyclitis. currently , the pathophysiology of cmv associated hypertensive iridocyclitis remains obscure . anterior chamber involvement in patients with cmv retinitis secondary to aids is occasionally seen , but when present , is not typically a posner - schlossman like syndrome . the anterior chamber inflammation , observed in patients with aids , could be due to either primary anterior segment infection or it may also simply be an inflammatory response , secondary to posterior segment pathology . the discovery of positive pcr for cmv in anterior chamber isolates from immunocompetent patients presenting with isolated pss suggests that , at least in some patients , hypertensive iridocyclitis may actually be caused by primary herpetic infection of the anterior chamber and thus mimics pss . with the benefit of hindsight , it is likely that in the case we describe the cmv infection was unrecognized for some months . the fact that the patient had a moderate vitritis also caused confusion as cmv retinitis is typically associated with a quiet vitreous . only one can assume that the vitritis represented an inadequate immunological response to the virus , a response that is often not generated in patients with low cd4 counts associated with hiv cmv retinitis . therefore , although the presentation of pss in our patient predated the definitive diagnosis of cmv retinitis by 6 months , it is tempting to speculate that the initial presentation of pss in our case also coincided with the primary presentation of cmv in the eye . whilst not conclusive , we suggest that our case provides further evidence that cmv infection of the eye can present with a clinical syndrome of hypertensive iridocyclitis , which without further diagnostic testing , is indistinguishable from pss . the evolving clinical scenario presented a number of diagnostic difficulties . with hindsight , the cumulative effect of diabetes and azathioprine on the immune surveillance system proved sufficient to render the patient susceptible to cmv retinitis . in patients without hiv , it is regrettably not unusual for the diagnosis of cmv retinitis to be delayed . this case therefore also emphasizes the need to maintain a high index of suspicion for unusual infections when managing patients with compromised immune systems , from whatever cause .

we describe a case of primary hypertensive iridocyclitis with biopsy - proven cytomegaloviral retinitis . it is an observational case report of a 69-year - old diabetic gentleman on azathioprine for crohn 's disease who presented with recurrent episodes of hypertensive iridocyclitis . on the 4th attendance in 5 months , a granular white lesion was noted in the temporal periphery of the mid - peripheral fundus and a chorioretinal and vitreous biopsy performed . vitreous pcr was positive for cytomegalovirus ( cmv ) . hematoxylin and eosin staining revealed cytomegalic - like inclusions within necrotic neural retina . transmission electron microscopy revealed herpes family virus particles and immunohistochemistry demonstrated cmv protein . this case provides further evidence implicating cmv infection in the etiology of hypertensive iridocyclitis . with hindsight , the cumulative effect of diabetes and azathioprine on the immune surveillance system proved sufficient to render the patient susceptible to cmv retinitis .

a 74-year - old woman was hospitalized with a diagnosis of antineutrophil cytoplasmic antibody ( anca)-positive vasculitis . her treatment included daily plasma exchanges via a right internal jugular vascular catheter that was placed on the 5th hospital day . on day 21 of admission , she had a low - grade fever that resolved after removal of the catheter , the tip of which produced a culture of diphtheroids . the patient was discharged after 1 month but was readmitted 4 weeks later for control of vasculitis . on admission she was anemic ( hemoglobin 7.0 g / dl ) and had persistent microscopic hematuria and elevated c - reactive protein . she had no new vasculitic manifestations and , as previously , a grade ii systolic murmur was noted at the left sternal edge . transesophageal echocardiogram ( toe ) showed a large mobile vegetation on the mitral valve , with prolapse and mild to moderate mitral regurgitation . a combination of intravenous vancomycin and oral rifampicin was begun , and the fever resolved within 48 hours . a follow - up toe at 15 months showed improvement in mitral valve features and no vegetations . the antibiotics were stopped after 16 months , and 5 months later the patient had no clinical evidence of disease recurrence . iid = indwelling intravascular device ; anca = anti - neutrophil cytoplasmic antibody ; hd = hemodialysis ; av = arteriovenous ; cvc = central venous catheter . a 69-year - old woman with hemodialysis - dependent chronic renal failure secondary to anca - positive vasculitis was admitted after acute thrombosis of a goretex dialysis fistula in her left arm . she had required temporary vascular access for hemodialysis for the preceding 12 days . on examination she was unwell and feverish . she had a grade i systolic murmur over the cardiac apex ; no previous echocardiogram was available . two sets of blood cultures grew c. striatum ( table 1 ) , as did the tip of her vascular catheter on removal . a toe revealed a large vegetation on her mitral valve . because of penicillin allergy , intravenous vancomycin and oral rifampicin were begun . the prosthetic arteriovenous fistula could not be removed completely , although it was considered a potential reservoir of infection . the patient had a mitral valve replacement 22 days into medical therapy , on the 29th hospital day . antibiotics were continued for another 15 days ; however , the patient had postoperative complications and died 4 weeks later . a 53-year - old man underwent mitral valve replacement with a starr edwards metal valve . his postoperative course was complicated by acute renal failure , for which he required temporary hemodialysis by vascular catheter for 36 days . cultures of four vascular catheter tips after their removal grew both diphtheroids and coagulase - negative staphylococci , which were considered to be normal skin flora . during this time , a low - grade fever developed that resolved after a change of lines . serial echocardiograms over the following 2 weeks , however , showed a worsening paraprosthetic leak . the patient completed 6 weeks of intravenous vancomycin and oral rifampicin for prosthetic valve endocarditis and was well on discharge . at follow - up , toe studies showed no further increase in the paraprosthetic leak , and the patient had no clinical evidence of relapse of infection . a 74-year - old woman was hospitalized with a diagnosis of antineutrophil cytoplasmic antibody ( anca)-positive vasculitis . her treatment included daily plasma exchanges via a right internal jugular vascular catheter that was placed on the 5th hospital day . on day 21 of admission , she had a low - grade fever that resolved after removal of the catheter , the tip of which produced a culture of diphtheroids . the patient was discharged after 1 month but was readmitted 4 weeks later for control of vasculitis . on admission she was anemic ( hemoglobin 7.0 g / dl ) and had persistent microscopic hematuria and elevated c - reactive protein . she had no new vasculitic manifestations and , as previously , a grade ii systolic murmur was noted at the left sternal edge . transesophageal echocardiogram ( toe ) showed a large mobile vegetation on the mitral valve , with prolapse and mild to moderate mitral regurgitation . a combination of intravenous vancomycin and oral rifampicin was begun , and the fever resolved within 48 hours . a follow - up toe at 15 months showed improvement in mitral valve features and no vegetations . the antibiotics were stopped after 16 months , and 5 months later the patient had no clinical evidence of disease recurrence . iid = indwelling intravascular device ; anca = anti - neutrophil cytoplasmic antibody ; hd = hemodialysis ; av = arteriovenous ; cvc = central venous catheter . a 69-year - old woman with hemodialysis - dependent chronic renal failure secondary to anca - positive vasculitis was admitted after acute thrombosis of a goretex dialysis fistula in her left arm . she had required temporary vascular access for hemodialysis for the preceding 12 days . on examination she was unwell and feverish . she had a grade i systolic murmur over the cardiac apex ; no previous echocardiogram was available . two sets of blood cultures grew c. striatum ( table 1 ) , as did the tip of her vascular catheter on removal . a toe revealed a large vegetation on her mitral valve . because of penicillin allergy , intravenous vancomycin and oral rifampicin were begun . the prosthetic arteriovenous fistula could not be removed completely , although it was considered a potential reservoir of infection . the patient had a mitral valve replacement 22 days into medical therapy , on the 29th hospital day . antibiotics were continued for another 15 days ; however , the patient had postoperative complications and died 4 weeks later . a 53-year - old man underwent mitral valve replacement with a starr edwards metal valve . his postoperative course was complicated by acute renal failure , for which he required temporary hemodialysis by vascular catheter for 36 days . cultures of four vascular catheter tips after their removal grew both diphtheroids and coagulase - negative staphylococci , which were considered to be normal skin flora . during this time , a low - grade fever developed that resolved after a change of lines . serial echocardiograms over the following 2 weeks , however , showed a worsening paraprosthetic leak . the patient completed 6 weeks of intravenous vancomycin and oral rifampicin for prosthetic valve endocarditis and was well on discharge . at follow - up , toe studies showed no further increase in the paraprosthetic leak , and the patient had no clinical evidence of relapse of infection . interest in the taxonomy of the nondiphtheriae corynebacteria has increased , with a resultant reclassification of earlier defined taxa and discovery of new pathogens in the group ( 1,8 ) . since 1966 , several case reports and reviews have described 191 cases of nondiphtheriae corynebacterial endocarditis on both prosthetic and native valves . in only six ( 3.1% ) of these cases was association with an indwelling intravascular device specifically documented : two patients in association with chronic hemodialysis ( 6 ) , one case attributed to an infected permanent pacemaker wire ( 9 ) , two in connection with ventriculo - peritoneal shunts ( 6 ) , and one in association with a ventriculo - atrial shunt ( 10 ) . of reports pertaining to hospital - acquired endocarditis in particular , in four case series totaling 80 cases , corynebacterium species were not identified as causative agents ( 7,1113 ) . in another series , corynebacterium species accounted for 1 ( 3.3% ) of 30 cases ( 14 ) , this case occurring postcardiac catheterization . a further series of 14 cases of hospital - acquired endocarditis describes 3 ( 21.4% ) cases due to coryneform species but gives no species identification or source of infection ( 15 ) . we have described three cases of nondiphtheriae corynebacterial nosocomial endocarditis associated with iid , all occurring in a single hospital , accounting for one third of 10 cases occurring in an 18-month period . these cases include the first reported case of endocarditis caused by c. amycolatum . of the remaining seven cases , two were due to methicillin - resistant s. aureus and five to methicillin - sensitive s. aureus . since lehmann and neumann proposed in 1896 that bacteria morphologically resembling the diphtheria bacillus be incorporated with it into the genus corynebacterium , the classification of the coryneform bacteria has been drastically altered ( 8) . this change has , in turn , increased the difficulty of identifying these organisms , as methods that reliably differentiate related species , such as mycolic acid chromatography , gas liquid chromatography , and molecular amplification techniques , can not easily be used in the routine laboratory setting . during 1987 to 1995 , commercial identification systems need to be updated to include those species relevant in human disease . c. amycolatum has only recently been included in the updated api coryne database 2.0 ( 4 ) , which , as illustrated by our case , may still lead to misidentification if used alone . that there have been no previous reports of c. amycolatum causing endocarditis may be due to its misidentification as other nonlipophilic fermentative corynebacteria species such as c. xerosis and c. minutissimum ( 3,16 ) , both of which are associated with human disease . published material provides useful schema for differentiating c. amycolatum , c. minutissimum , and c. striatum by using colonial morphology , carbohydrate assimilation tests , and sensitivity to amoxycillin and the vibriostatic compound o/129 , in conjunction with the api coryne and api 20ne systems ( 17 ) . antibiotic sensitivity patterns may support identification , with c. amycolatum and c. jeikeium generally resistant to multiple antibiotics ( 18 ) . in contrast , c. striatum , c. minutissimum , and c. xerosis generally are sensitive to a wide range of antibiotics . ( 1 ) have published guidelines for identifying the coryneform bacteria , including simple phenotypic characteristics but also recommending more complex chemotaxonomic investigations and molecular genetic analysis if phenotypic characteristics do not differentiate between species . these guidelines are intended to facilitate the establishment of true disease associations of these organisms . in our experience , morphologic features combined with antibiogram profiles and the coryne api allowed identification of two out of three corynebacteria ( table 2 ) . as the colonial morphology and the coryne api profile did not match in the isolate from case 1 , the organism was sent to our reference laboratory , where identification as c. amycolatum was confirmed by gas liquid chromatography ( microbial identification system , microbial i d , newark , de ) . api = analytical profile index ; glc = gas liquid chromatography ; cip = ciprofloxacin ; ery = erythromycin ; f = fucidin ; gent = gentamicin ; pen = penicillin ; rif = rifampicin ; teic = teicoplanin ; trim = trimethoprim ; vanc = vancomycin . treatment regimens described include penicillin alone , beta - lactam antibiotics or erythromycin plus gentamicin , and vancomycin . this combination has not previously been described but was effective in two of the three patients ( including the case of prosthetic valve endocarditis ) , who were both free from infection at least 5 months after cessation of therapy . in a review of 19 patients with prosthetic valve endocarditis due to diphtheroids ( 19 ) , 4 ( 57.1% ) of 7 patients treated with antibiotics alone of 12 patients treated both medically and surgically , 7 ( 58.3% ) were reported as having a microbiologic cure ( 19 ) . specifically , clinicians and microbiologists must be aware of the potential risk factors for nondiphtheriae corynebacterial endocarditis in the hospital setting and the danger of overlooking positive long - line tip cultures as normal skin flora or contaminants . stringent identification of clinical isolates will be required to define the role of the nondiphtheriae corynebacteria in human disease .

the nondiphtheriae corynebacteria are uncommon but increasingly recognized as important agents of community - acquired endocarditis in patients with underlying structural heart disease , as well as of prosthetic - valve endocarditis . we describe three cases of nondiphtheriae corynebacterial endocarditis , including the first reported case of endocarditis caused by corynebacterium amycolatum , occurring over an 18-month period , all in association with indwelling intravascular devices .

in the previous issue of critical care , the review by xie and colleagues aims to answer the following questions . is noise the most disruptive factor to sleep for intensive care unit ( icu ) patients ? indeed , the medical literature appears to give conflicting results : of 11 original articles reviewed , five studies assert that noise is the most significant cause of sleep disturbance whereas six other papers suggest that noise is responsible for only a small proportion of sleep disruptions . similarly , studies examining the effectiveness of noise reduction strategies suggest variable outcomes , with relative improvements in sleep ranging from 10 to 68% . first , the impact of noise must be weighed relative to other factors that may be more or less disruptive to patients ' sleep . but how can we determine the relative significance of noise when we do not fully understand or can not accurately measure all of the factors that may share responsibility for the sleep disturbance ? in a seminal work in this field , gabor and coworkers found that noise and patient - care activities accounted for less than 30% of arousals and awakenings , while the cause of the remaining 70% of sleep disruptions remained unidentified . second , these studies measured similar outcomes from differing perspectives : those of the patient , of the bedside observer , and of the sleep specialist . although it is clearly valuable to obtain information regarding patients ' perceptions and experiences , it may be difficult for healthy individuals , let alone critically ill patients , to identify all factors that disrupted their sleep . furthermore , patients may be more apt to recall experiences that fall within a previously established frame of reference . most people have experienced sleep disruption due to a noisy environment at some point in their lives ; therefore , patients may be more likely to attribute poor - quality sleep to noise in the icu rather than other factors they might be unaware of , such as patient - ventilator asynchrony or the severity of their illness . an alternate approach to surveying patients is to have an independent observer at the bedside to assess and quantify noises and occurrences that arouse the patient from sleep . direct observation of sleep , however , has been shown to be unreliable when compared with polysomnography . a recent paper by beecroft and colleagues demonstrated that nursing assessment underestimated the number of awakenings from sleep , and actigraphy ( monitoring of gross motor activity ) overestimated total sleep time and sleep efficiency compared with polysomnography . researcher observation without polysomnography may therefore underestimate the amount of sleep disruption due to noise , or may incorrectly attribute awakenings to noise without identifying other important contributing factors . even polysomnography , the gold standard of sleep quantification , may be difficult to interpret for icu patients using standard rechtschaffen and kales methodology . ambrogio and coworkers demonstrated good intraobserver reliability for identifying individual sleep stages and periods of wakefulness in critically ill patients , but poor interobserver reliability . this finding suggests that even though individual studies utilizing a single sleep expert to score all polysomnograms may have good internal validity , the variability in results across studies may be due in part to disagreement between polysomnographers . this inhomogeneity in outcome assessment compounds the difficulty of arriving at a single conclusion with respect to the impact of noise on sleep disruption in the icu . a third factor that may account for the discrepancy in reported results is the breadth and depth of the study question . investigators typically attribute arousals from sleep to noise when the arousal occurs within 3 seconds of a measurable ( > 10 decibels ) increase in sound level . since both noise peaks and arousals are common in the icu , some of the arousals may coincidentally occur after a noise peak but not be causally related . if other factors potentially contributing to sleep fragmentation are not systematically examined , investigators may overestimate the effect of noise on patients ' sleep . additionally , the authors of this review point out that most research in this area has focused purely on noise level , but other acoustic parameters such as spectrum and reverberation time may impact sleep quality . sound masking appears to be the most effective strategy for improving sleep , but acoustic absorption has not been evaluated in this regard . comprehensive sound reduction strategies developed by acousticians in collaboration with physicians may yield more impressive results . in conclusion , the impact of noise and noise reduction on patients ' sleep in the icu is a very complex topic to dissect , due to variability between patients in their perception , recall , and arousal response to noise , due to poor reliability in quantification of sleep by direct observation , and due to suboptimal interobserver agreement in reading polysomnograms of critically ill patients . furthermore , the significance placed on noise will depend in part on the number of other factors examined as potential contributors to sleep disruption . nonetheless , this paper lays the groundwork for further research in this area by providing a comprehensive review of the literature published to date and highlighting a broader view of acoustic parameters that have yet to be thoroughly examined in the icu setting . if noise reduction strategies can improve sleep to any degree , such strategies are worth exploring for our most vulnerable patients .

the review article by xie and colleagues examines the impact of noise and noise reduction strategies on sleep quality for critically ill patients . evaluating the impact of noise on sleep quality is challenging , as it must be measured relative to other factors that may be more or less disruptive to patients ' sleep . such factors may be difficult for patients , observers , and polysomnogram interpreters to identify , due to our limited understanding of the causes of sleep disruption in the critically ill , as well as the challenges in recording and quantifying sleep stages and sleep fragmentation in the intensive care unit . furthermore , most research in this field has focused on noise level , whereas acousticians typically evaluate additional parameters such as noise spectrum and reverberation time . the authors highlight the disparate results and limitations of existing studies , including the lack of attention to other acoustic parameters besides sound level , and the combined effects of different sleep disturbing factors .

increasingly , cardiac biomarkers have provided important information in predicting short - term and long - term risk profiles in patients with acute coronary syndromes ( acs ) , particularly when they are used in combination . among the numerous biomarkers , high - sensitivity c - reactive protein ( hscrp ) has received widespread interest and a large database has been accumulated on their potential role as predictor of cardiovascular events [ 2 , 3 ] . growth - differentiation factor-15 ( gdf-15 ) is one of more than 40 members of the transforming growth factor- superfamily and it was originally identified in activated macrophages . accumulating evidence indicates that circulating levels of gdf-15 are associated with the risk of death and myocardial infarction , independent of clinical variables and other biomarkers , including hscrp and cardiac troponins [ 5 , 6 ] . the inflammatory response triggered in the acs setting is the cumulative result of preexisting , low - grade inflammation in vulnerable atherosclerotic plaques and the ongoing myocardial ischemic damage during the progression of an acute coronary event . consistently , the magnitude of the inflammatory response as reflected by the peripheral levels of inflammatory markers is largely determined by the temporal interval between symptom onset and the time point of biochemical measurement . optimal interpretation of the elevated circulating levels of biomarkers would , therefore , require knowledge of their release curves and consideration of the time point of blood sampling [ 8 , 9 ] . however , the long - term temporal changes of hscrp levels and the relation between the changes of gdf-15 levels have not been examined , after an episode of non - st - segment elevation acs ( nste - acs ) . consequently , the aims of our study were todescribe changes of hscrp and gdf-15 levels over time after an episode of nste - acs , examine whether changes of hscrp and gdf-15 levels are associated with long - term major cardiovascular adverse events ( mace ) . describe changes of hscrp and gdf-15 levels over time after an episode of nste - acs , examine whether changes of hscrp and gdf-15 levels are associated with long - term major cardiovascular adverse events ( mace ) . three hundred and eighty consecutive acs patients were admitted to the coronary care unit of a university hospital . one hundred and twenty - five patients were excluded from analysis for the following reasons : patients with a history of systemic inflammatory diseases , such as infections or autoimmune disorders , neoplastic or haematological disease , administration of anti - inflammatory or immune - suppressive drugs , and surgical procedures or trauma in the preceding 3 months , patients with an equivocal or uninterpretable electrocardiogram , including left bundle branch block or persistent st - segment elevation due to a myocardial infarction and patients with significant changes in medical therapy during followup . patients were followed up for three years regarding the occurrence of mace ( death , myocardial infarction , and unstable angina ( class iiib ) ) . therapeutic management during hospitalisation and in the outpatient clinic was left to the discretion of the attending cardiologist , according to the patients ' clinical course , standard institutional protocols , and current guidelines . the ethics committee of our institution approved the research protocol , and all patients gave written , informed consent for inclusion in the study . serial venous blood samples were obtained on admission from 8 am to 3 pm , to avoid the diurnal variation of inflammatory biomarkers reported by our group . blood samples were also obtained on a follow - up evaluation 36 months after admission . serum samples were obtained by centrifugation , after the formation of the clot of blood , and stored at 70c for subsequent analyses . concentrations of the serum hscrp were measured , by an ultrasensitive , enzyme - linked , immunosorbent assay kit ( drg instruments gmbh , germany ) . in this enzyme - linked immunosorbent assay , serum gdf-15 concentrations were measured using a commercially , enzyme - linked immunosorbent assay ( biovendor gmb , heidelberg , germany ) . in this assay , troponin i was determined immune enzymatically , using a technique based on sandwich elisa ( boehringer mannheim , germany ) . all other biochemical measurements were performed in the biochemistry laboratory of our hospital from the samples obtained at baseline , using standard methods . personnel , blinded to patient 's baseline characteristics and clinical outcomes , carried out all measurements . results for normally distributed continuous variables are expressed as mean sd ; nonnormally distributed continuous variables are presented as median and interquartile range . analysis of normality of the continuous variables was performed with the kolmogorov - smirnov test . unpaired 2-tailed t - tests and the mann - whitney u - test assessed differences between the groups for continuous variables , as appropriate . categorical data and proportions were analysed by use of or fisher 's exact test when required . gdf-15 and hscrp levels had a nonnormal distribution and were , therefore , logarithmically transformed before regression analysis to fulfill the conditions required for this type of analysis . the information regarding the appearance of the endpoint , combined at a 36-month followup , was available for all patients included in the study . in patients who died during the 36-month followup period , the blood sample was not available , so we evaluated independent predictors of unstable angina ( class iiib ) and myocardial infarction ( combined primary endpoint ) . we defined the value delta , as a value that represents the difference between the concentrations of inflammatory markers at admission and at 36-month followup . independent predictors of changes were identified by multiple linear regression analysis and multivariable regression analysis , as appropriate . tested covariates included sex , age , current smoking , diabetes mellitus , hypertension , dyslipidemia , coronary revascularisation , left ventricular ejection fraction , and troponin i. delta gdf-15 concentrations were introduced into the multivariate model as a binary variable , considering the median as the cut - off value . backward stepwise selection was used in multivariate analysis to derive the final model for which significance levels of 0.1 and 0.05 were chosen to exclude and include terms , respectively . differences were considered to be statistically significant if the null hypothesis could be rejected with > 95% confidence . the spss 15.0 statistical software package ( spss inc . demographic and clinical data of patients with and without mace are presented in table 1 . after 36 months of followup , the combined endpoint ( ( cardiac death ( 7 patients ) , myocardial infarction ( 3 patients ) , and unstable angina class iiib ( 35 patients ) ) appeared in 45 patients ( 17.6% ) . there were no significant differences in age , sex , cardiovascular risk factors , timi risk score , severity of coronary artery disease , treatment , and standard biochemical results between the two groups . regarding inflammatory biomarkers , we found no differences between both groups in levels of hscrp at admission and after a three - year followup ( table 2 ) . however , delta hscrp concentrations were higher in patients who developed mace compared to patients who did not ( p = 0.01 ) ( table 2 ) . we found significant differences in the gdf15 levels after the three - year followup between both groups ( p < 0.001 ) ( table 2 ) . moreover , delta gdf-15 concentrations were higher in patients who developed mace ( p < 0.001 ) ( table 2 ) . multivariate analysis showed that delta gdf-15 ( or = 52.3 , ci 95% 7 - 388.5 , p < 0.001 ) was the unique independent predictor of the combined endpoint ( class iiib unstable angina and myocardial infarction ) at 36-month followup . variables such as age ( p = 0.15 ) , sex ( p = 0.23 ) , smoking ( p = 0.33 ) , diabetes mellitus ( p = 0.24 ) , hypertension ( p = 0.55 ) , dyslipidemia ( p = 0.57 ) , revascularization ( p = 0.70 ) , left ventricular ejection fraction ( p = 0.50 ) , and troponin i ( p = 0.15 ) were not independent predictors of mace . the results from our study demonstrate different patterns of release of the hscrp and gdf-15 with , over time , between patients with nste - acs . moreover , this is the first study to show that the changes in gdf-15 , over time , are of prognostic relevance in nste - acs patients . the predictive value of gdf-15 measured on admission has been investigated in the two large nste - acs populations : the global utilisation of strategies to open occluded arteries iv ( gusto - iv ) and fast revascularisation during instability in coronary artery disease ii ( frisc ii ) cohorts [ 5 , 12 ] . in another study , damman et al . have evaluated the long - term prognostic value of gdf-15 , regarding death or myocardial infarction in nste - acs patients . they have shown that the kaplan - meier curves diverged early and continued to diverge up to five years . in a recent study , the circulating concentration of gdf-15 was measured at baseline ( n = 1734 ) and at 12 months ( n = 1517 ) in patients randomised in the valsartan heart failure trial ( val - heft ) . they demonstrated increases in gdf-15 over 12 months , which were independently associated with the risks of future mortality and first morbid event also , after adjustment for clinical prognostic variables , b - type natriuretic peptide , hscrp , and high - sensitivity troponin t and their changes . in another study recent , eggers and colleagues analysed gdf-15 concentrations in participants from the prospective investigation of the vasculature in uppsala seniors ( pivus ) study . they demonstrated that the gdf-15 concentrations and their changes over time are powerful predictors of mortality in elderly community - dwelling individuals . in the results of our study , we found that nste - acs patients , who developed mace , displayed higher levels of gdf-15 at the 36-month followup than at admission . furthermore , we were able to show that delta gdf-15 is associated with adverse outcomes , independently of established clinical and biochemical risk markers . our results support the notion that gdf-15 integrates information on several relevant aspects and pathways in cardiovascular disease . the prominent antiapoptotic , antihypertrophic , and anti - inflammatory actions of gdf-15 in cardiovascular disease models indicate that this cytokine exerts protective effects in the context of acute cardiovascular injury . whether chronic increases in gdf-15 concentrations in nste - acs patients play an adaptive or maladaptive role remains to be investigated . in relation with hscrp in our study the delta value or rate of change of the hscrp was useful to differentiate the group of patients with worse clinical outcome during 36 months of followup . however , after adjusting by different confounders , we have not demonstrated that delta hscrp can predict mace in nste - acs patients . recently , in a study by karakas et al . , they serially measured hscrp concentrations in up to 6 blood samples , taken at monthly intervals from 200 postmyocardial infarction patients , who participated in the airgene study . the implementation of hscrp measurement into clinical practice requires sound data on the reliability of such measurement . data is still scarce for the long - term analytical variation of hscrp measurement in patients with cardiovascular disease . the present study shows that the rate of change of hscrp measured at the 36-month followup was not predicting long - term mace in nste - acs patients . however , the delta gdf-15 at the 36-month followup seems to be a stronger predictor of mace than during an acute unstable phase .

among the numerous emerging biomarkers , high - sensitivity c - reactive protein ( hscrp ) and growth - differentiation factor-15 ( gdf-15 ) have received widespread interest , with their potential role as predictors of cardiovascular risk . the concentrations of inflammatory biomarkers , however , are influenced , among others , by physiological variations , which are the natural , within - individual variation occurring over time . the aims of our study are : ( a ) to describe the changes in hscrp and gdf-15 levels over a period of time and after an episode of non - st - segment elevation acute coronary syndrome ( nste - acs ) and ( b ) to examine whether the rate of change in hscrp and gdf-15 after the acute event is associated with long - term major cardiovascular adverse events ( mace ) . two hundred and fifty five nste - acs patients were included in the study . we measured hscrp and gdf-15 concentrations , at admission and again 36 months after admission ( end of the follow - up period ) . the present study shows that the change of hscrp levels , measured after 36 months , does not predict mace in nsteacs - patients . however , the level of gdf-15 measured , after 36 months , was a stronger predictor of mace , in comparison to the acute unstable phase .

this case illustrates the use of femoral nerve and sciatic nerve peripheral catheters with an elastomeric infusion pump for major intramedullary nailing surgery . a 36-year - old male with fractures to the left leg bones presented for placement of an intramedullary nail under spinal anesthesia . at the end of the procedure , access to the lateral femoral and sciatic continuous nerve block was achieved by using a stimulator connected to a 110 mm 18 g tuohy needle . postoperative analgesia was provided with a 40-hour infusion of 0.1% bupivacaine ( 400 ml ) at a rate of 10 ml hour with an elastomeric pump . the analog scale remained with scores below 3 during the 40 hours after surgery , and boluses were not necessary . the use of a femoral and sciatic nerve peripheral catheter offered an alternative to conventional pain control . sciatic peripheral blockade via a skin puncture with an infusion of 0.1% bupivacaine with elastomeric pumps is a safe and effective procedure in adults . a 36-year - old man ( 66 kg , 170 cm , physical status american society of anesthesiology [ asa ] i ) with fractures to the left leg bones was scheduled for an intramedullary nail under spinal anesthesia . the patient was evaluated and signed the informed consent to undergo a single needle entry combined approach of continuous peripheral blocks ( figure 1 ) . after routine monitoring , spinal anesthesia was performed with a 27 g quincke needle ( bbraun , melsungen , germany ) in the l3l4 space through a median approach with the patient in a lateral position . the patient was injected with 15 mg of isobaric 0.5% bupivacaine . during the procedure , a transpatellar approach was used for the proximal tibia , which was opened with a solid awl under image intensification . the proximal fracture site was opened and a reaming rod was inserted ; the distal fracture site was reduced and closed . the canal was reamed , and one poller screw was inserted in the distal fragment . we introduced a 9 mm diameter cannulated nail and achieved distal locking with two screws ( freehand locking technique ) . 1000 ml of crystalloids and 500 ml of voluven ( 6% hydroxyethyl starch 130/0.4 in 0.9% saline ) were administered . no urinary catheter was utilized during the procedure . at the end of the procedure , access to lateral femoral and sciatic continuous nerve block was achieved using a stimulator ( hns12 ; bbraun ) connected to a 110 mm 18 g tuohy needle ( bbraun ) . the needle was advanced and the quadriceps were stimulated with a 0.5 ma current until a response was observed . after negative aspiration of blood , 20 ml of 0.2% bupivacaine was injected through an extension connector of the needle . while maintaining the needle in the same position , a 20 g catheter was inserted 7 cm into the inguinal compartment and was fixed in place with adhesive material and an occlusive dressing . another needle was then advanced posteriorly and caudally to reach the sciatic nerve , which was identified by stimulation of the common fibular nerve or tibial nerve , confirmed by movements of the foot . approximately 5 ml of contrast ( iohexol with 300 mg ml ominipaque ) was injected in each catheter to study the dispersion of the local anesthetic , and an anteroposterior x - ray was taken within 1 minute ( figure 2 ) . before his discharge , a disposable elastomeric pump ( easypump , bbraun ) containing 400 ml of 0.1% bupivacaine was connected to the catheters of both nerves . the pump was programmed for infusion at a rate of 10 ml hour . upon completion an analog scale was used to divide patients pain into categories of mild or no pain ( 03 ) , moderate pain ( 47 ) , and severe pain ( 810 ) . he received instructions to trigger the bolus device , which is part of the pump , in case of severe pain . toxicity symptoms of the local anesthetic were recorded . during the 40 postoperative hours , boluses were not necessary . both catheters were removed without intercurrences and were sent for bacteriological examination after removal ; pain was then controlled with oral ketoprofen and dypirone . sciatic nerve approach via a single skin puncture for postoperative analgesia for tibial intramedullary nailing has not been reported . since this method administers a local anesthetic close to the continuous combined femoral sciatic nerve , analgesia can be prolonged , especially in patients with a tibial shaft fracture . the results of this case demonstrate that an elastomeric pump for a continuous peripheral nerve block with infusion of a local anesthesia in adult patients is an effective and safe analgesic method after extensive orthopedic procedures . although many closed fractures of the tibial shaft can be treated nonoperatively,6 there are numerous indications for operative treatment . the choice of surgical approach , specifically using the transpatellar or parapatellar tendon , has been reported as a contributory factor in chronic anterior knee pain following tibial nail insertion . in a retrospective study in which a nail was inserted via a paratendinous incision in 65 fractures and via a tendon - splitting incision in 36 fractures , insertion of an intramedullary nail through the paratendinous incision resulted in a 50% incidence of knee pain , whereas this incidence in the transtendinous incision group was 77%.7 this is in contrast to other reports of no significant difference.8 in this case study the incision was transpatellar . a lateral entrance in the inguinal lumbar plexus allows the needle to find the femoral nerve before reaching the femoral artery . an entry perpendicular and below the greater trochanter reaches the sciatic nerve after touching the femur bone . the lateral entrance reduced the risk of lateral displacement , facilitating the movement of the patient and allowing personal hygiene , such as changing the dressing to reduce the risk of infection . the use of bupivacaine ( 0.1% to 0.25% ) as used in our case study did not result in toxic blood levels in postoperative analgesia for 2472 hours.9 the venous level of bupivacaine during continuous lumbar plexus analgesia was 0.51.8 g ml,10 while levels above 2 g ml are considered toxic . continuous peripheral nerve block analgesia , regardless of catheter location , provided superior postoperative analgesia and fewer opioid - related side effects when compared with an opioid analgesia.11 in surgery , the continuous plexus block is used primarily to improve the quality of postoperative analgesia and allow early rehabilitation . there was no difference in pain between rest and movement , showing that continuous analgesia decreased the incidence of postoperative pain to 3 on the visual analog scale during the 48 hours following the operation . a lateral , continuous , combined , femoral sciatic block was performed with a peripheral nerve stimulator , and we observed the distribution of contrast around both nerves . the distribution of contrast showed a higher level in the inguinal region through the femoral nerve and below the subtrochanteric femur in the region through the sciatic nerve . if the elastomeric pump lies below the catheter tip , the delivery of the agent can be impaired to a variable extent . the rate of flow of the anesthetics is dictated by the elastomeric reservoir and the gauge of the tube , which prevents the infusion of a large bolus and overdose . although the pump has its own bacterial filter , we used a second filter to increase patient safety . the elastomeric pump has several advantages over the electronic pump , including portability , ease of use , and few technical problems , such as undesirable alarms.12 severe infectious complications have been reported after continuous blockade , with about 29% of peripheral nerve catheters being colonized with up to 3% bacteria , resulting in localized inflammation.13 continuous peripheral nerve block ( cpnb ) duration ( > 48 hours ) was a strong risk factor for local infectious problems.13 we prospectively reported an incidence of 57% colonized femoral catheters ( 1.5% with bacteremia ) after 48 hours of continuous infusion of bupivacaine or ropivacaine.14 given the results of infection after 48 hours , the pump was scheduled to stop 48 hours after surgery . with lateral access to the axilar brachial plexus and inguinal lumbar plexus , we did not observe any bacterial growth in 20 catheters , similar to our finding that in 48 hours there was no sign of inflammation at the puncture site.15 likewise , bacteriological examination of both catheters found no bacterial growth . the use of extended local anaesthesia for postoperative pain has previously been reported and has several advantages over other methods , including ease of placement , safety , reliability , lower cost , and effectiveness . sciatic peripheral nerve block via a single skin puncture with infusion of 0.1% bupivacaine via an elastomeric pump is a safe and effective procedure in adults for surgical treatment of tibia fractures by intramedullary nailing .

backgroundthe prevalence of anterior knee pain following intramedullary tibial nail insertion is high . continuous peripheral nerve blockade is an alternative method of pain control to opiods . this case illustrates the use of femoral nerve and sciatic nerve peripheral catheters with an elastomeric infusion pump for major intramedullary nailing surgery.case reporta 36-year - old male with fractures to the left leg bones presented for placement of an intramedullary nail under spinal anesthesia . at the end of the procedure , access to the lateral femoral and sciatic continuous nerve block was achieved by using a stimulator connected to a 110 mm 18 g tuohy needle . postoperative analgesia was provided with a 40-hour infusion of 0.1% bupivacaine ( 400 ml ) at a rate of 10 ml hour1 with an elastomeric pump . anesthetic dispersion and contrast were investigated . the analog scale remained with scores below 3 during the 40 hours after surgery , and boluses were not necessary.conclusionthe use of a femoral and sciatic nerve peripheral catheter offered an alternative to conventional pain control . continuous femoral sciatic peripheral blockade via a skin puncture with an infusion of 0.1% bupivacaine with elastomeric pumps is a safe and effective procedure in adults .

however , both treatment modalities may be impossible in certain situations , such as giant or fusiform thrombosed aneurysm , in which efferent or adjacent arterial branches may be involved . under these situations , an alternative surgical strategy using revascularization may be required6,7 ) . although revascularization using harvested graft vessels has been used for high - flow replacement in proximal vessels , local techniques of revascularization without a graft ( in situ ) may be sometimes more useful for distally located aneurysm . we report our surgical experience using in situ bypass technique for the treatment of giant serpentine distal anterior cerebral artery ( daca ) aneurysm . a 49-year - old woman presented with loss of consciousness ( loc ) and history of headache . on initial neurologic examination , she had no specific symptoms or previous seizure history . a non - contrast computed tomography scan showed a 31.8 cm sized , rim calcified , and round shaped mass lesion in the interhemispheric area , along the anterior falx above the head of the corpus callosum ( fig . brain t2-weighted structural magnetic resonance image ( mri ) scan revealed partially thrombosed , signal voided aneurysm , without parenchymal edema ( fig . cerebral angiography demonstrated an irregular serpentine aneurysm , involving the entire a2 segment of daca , measuring 4.5 cm in the anteroposterior dimension and 1.8 cm in the transverse dimension ( the proximal portion of aneurysm , fig . the patient was placed in the supine position , with the head slightly tilted at 20 degrees in the 3 pin fixation . the right calf lesion was prepped for possible bypass , using a venous interposition graft from the superficial temporal artery to the distal end of the anterior cerebral artery . to secure the wider surgical field , we performed cerebrospinal fluid ( csf ) drainage via lumbar puncture and midline bifrontal interhemispheric craniotomy with the neuronavigation system ( medtronics ) . 44 cm sized bone flap was made , then dura mater was opened with small straight incision . the superior sagittal sinus was ligated , cut , and reflected up and downward bidirectionally ( fig . 2a ) . under the operating microscope , we advanced with dissection of the interhemispheric fissure and indentified the distal end of the fusiform aneurysm ( fig . after further dissection , the left pericallosal artery was indentified just adjacent to the aneurysm . thus , at this point , we considered that it might be possible to perform the in situ bypass between right a3 just distal aneurysm sac and left a3 . to see the proxymal portion of aneurysm and parent artery , we further dissected the interhemspheric fissure toward anterior direction and were very cautious not to injury the both olfactory nerves ( fig . 2c ) . this complication can be avoided by making wide , precautious dissection to minimize posterior and lateral brain retraction . therefore , we did not fully dissect the aneurysm from the brain , in order to avoid postoperative parenchymal contusion . blood flow was measured at approximately 20 cm / s , in both distal artery to the fusiform aneurysm and opposite left pericallosal artery . when we placed the temporary clip on the proximal parent artery of aneurysm , blood flow was not visible on the micro - doppler recording . thus , we finally decided to perform aneurysm trapping with a right end - to - left side in situ bypass , to preserve the flow to the right daca . before anastomosis , the patient was placed into burst suppression with propofol , and the mean arterial pressure was raised 25% above the patient 's baseline , in order to improve the collateral circulation . intraoperatively , both somatosensory and motor evoked potentials were also used for monitoring . at the time of the anastomosis , 2000 iu of heparin both arteries were dissected as movable as possible , and a rubber dam was passed under both vessels . after placing two temporary clips on the right side , the atherosclerotic distal artery of the aneurysm was clearly trimmed with jeweler forceps , and marked with marking pen . two temporary clips were then placed on the left side , and following heparin irrigation , a small arteriotomy was made equal to the opposite arterial opening , using a diamond knife ( fd 115d aesculap , pa , usa ) . a marking pen is usually used to color the borders of the arteriotomy for idenfication of the margin of the transparent thin vessels . after both toe and heel stitches were placed at the proximal and distal ends of the anastomosis with 10 - 0 nylon suture ( ethicon co. , nj , usa ) , the posterior wall was sutured in a continuous fashion and the anterior wall was sutured in an interrupted pattern . on completion of the end - to - side bypass , robust blood flow in the right daca was observed in the distal segment to the bypass site ( fig . permanent clips were applied proximal and distal to the aneurysm , without removal of the thrombosed aneurismal mass , because the aneurysm itself was severely stuck to the brain surface . instead of leaving the thrombosed aneurysm , we aspirated the blood clot from the aneurysm using 14-gauzed needle , to identify total obliteration of the aneurysm and to reduce the mass effect postoperatively ( fig . postoperative cerebral angiography on day 7 demonstrated no residual filling of the aneurysm and excellent flow through a patent bypass into both the daca vascular territories ( fig . follow up t2-weighted brain mri at 3 months after surgery showed remarkably reduced mass size in the interhemispheric area , along the genu portion of corpus callosum ( fig . the patient was placed in the supine position , with the head slightly tilted at 20 degrees in the 3 pin fixation . the right calf lesion was prepped for possible bypass , using a venous interposition graft from the superficial temporal artery to the distal end of the anterior cerebral artery . to secure the wider surgical field , we performed cerebrospinal fluid ( csf ) drainage via lumbar puncture and midline bifrontal interhemispheric craniotomy with the neuronavigation system ( medtronics ) . 44 cm sized bone flap was made , then dura mater was opened with small straight incision . the superior sagittal sinus was ligated , cut , and reflected up and downward bidirectionally ( fig . 2a ) . under the operating microscope , we advanced with dissection of the interhemispheric fissure and indentified the distal end of the fusiform aneurysm ( fig . after further dissection , the left pericallosal artery was indentified just adjacent to the aneurysm . thus , at this point , we considered that it might be possible to perform the in situ bypass between right a3 just distal aneurysm sac and left a3 . to see the proxymal portion of aneurysm and parent artery , we further dissected the interhemspheric fissure toward anterior direction and were very cautious not to injury the both olfactory nerves ( fig . 2c ) . this complication can be avoided by making wide , precautious dissection to minimize posterior and lateral brain retraction . therefore , we did not fully dissect the aneurysm from the brain , in order to avoid postoperative parenchymal contusion . blood flow was measured at approximately 20 cm / s , in both distal artery to the fusiform aneurysm and opposite left pericallosal artery . when we placed the temporary clip on the proximal parent artery of aneurysm , blood flow was not visible on the micro - doppler recording . thus , we finally decided to perform aneurysm trapping with a right end - to - left side in situ bypass , to preserve the flow to the right daca . before anastomosis , the patient was placed into burst suppression with propofol , and the mean arterial pressure was raised 25% above the patient 's baseline , in order to improve the collateral circulation . intraoperatively , both somatosensory and motor evoked potentials were also used for monitoring . at the time of the anastomosis , 2000 iu of heparin both arteries were dissected as movable as possible , and a rubber dam was passed under both vessels . after placing two temporary clips on the right side , the atherosclerotic distal artery of the aneurysm was clearly trimmed with jeweler forceps , and marked with marking pen . two temporary clips were then placed on the left side , and following heparin irrigation , a small arteriotomy was made equal to the opposite arterial opening , using a diamond knife ( fd 115d aesculap , pa , usa ) . a marking pen is usually used to color the borders of the arteriotomy for idenfication of the margin of the transparent thin vessels . after both toe and heel stitches were placed at the proximal and distal ends of the anastomosis with 10 - 0 nylon suture ( ethicon co. , nj , usa ) , the posterior wall was sutured in a continuous fashion and the anterior wall was sutured in an interrupted pattern . on completion of the end - to - side bypass , robust blood flow in the right daca was observed in the distal segment to the bypass site ( fig . permanent clips were applied proximal and distal to the aneurysm , without removal of the thrombosed aneurismal mass , because the aneurysm itself was severely stuck to the brain surface . instead of leaving the thrombosed aneurysm , we aspirated the blood clot from the aneurysm using 14-gauzed needle , to identify total obliteration of the aneurysm and to reduce the mass effect postoperatively ( fig . postoperative cerebral angiography on day 7 demonstrated no residual filling of the aneurysm and excellent flow through a patent bypass into both the daca vascular territories ( fig . follow up t2-weighted brain mri at 3 months after surgery showed remarkably reduced mass size in the interhemispheric area , along the genu portion of corpus callosum ( fig . since the first bypass reported in 1986 by ikeda , including the microvascular side - to - side anastomosis technique3 ) , the concepts and techniques for bypass have evolved over time and diverse surgical methods have been tried and evaluated for cerebral revascularization , in order to get the best surgical outcomes . the ideal surgical technique is to make an artificial conduit for blood flow between two adjacent vessels of similar caliber . this type of in situ bypass has been often applied for the treatment of complex brain aneurysms6,7 ) . the overall incidence of daca aneurysms has been known to be from 2% to 9% of all intracranial aneurysms4,5 ) ; however , only 0.6% were fusiform , and is still unclear whether these were giant aneurysms . dunn et al.1 ) were the first to demonstrate the technique as well as challenges of performing the a3 : a3 bypass to treat a large fusiform aneurysm located in the daca . thus , this presented case is only the second reported end - to - side in situ a3 : a3 bypass with aneurysm trapping . furthermore , to the best of our knowledge , giant serpentine aneurysm has not been reported previously in the literature in this daca location . herein , we described a successful surgical experience for the treatment of giant serpentine daca aneurysm . considering surgery in the interhemisheric lesion , the operation field is quite deep and narrow that we often have difficulty with performing surgery in this location . furthermore , daca aneurysm is sometimes adhesive to the cingulated gyrus and often has wide or atherosclerotic neck , with difficulty to confirm the parent artery and surrounding structures5 ) . therefore , it is important to secure wider surgical field and brain relaxation , using csf drainage and infusion of hyperosmolar fluid . although this type of bypass surgery may be technically challenging because of aforementioned obstacles , meticulous dissection and enough surgical space can lead to successful completion of the anastomosis . dunn et al.1 ) reported one bypass for large ( 17 mm ) fusiform a3 aneurysm , with resection of the aneurysm after end - to - side bypass . aneurysmal resection was impossible in our case , because the aneurysm was 4.5 cm in length and too large to resect . the goal of surgery was total obliteration of the aneurysm , with preservation of blood flow to the parent vessel territory and bypass revascularization in the end . therefore , we did not remove the trapped aneurysm , to avoid injury of the adhesive tissue between the brain and the aneurysm wall . 3b ) , the mass size was decreased and the patient was symptom free postoperatively . in a recent study , gelfenbeyn et al.2 ) suggested that venous graft should be prepared , if necessary , to be used as interposition graft between the superficial temporal artery and the distal artery of the resected aneurysm . if there is a large , broad neck a2-a3 aneurysm , it might be difficult to perform the end - to - end anastomosis after aneurysm resection . as previously suggested , we also prepared the venous interposition graft in the patient 's calf , but we did not use it , because this procedure should be tailored to the operative findings and availability of donor and recipient vessels . giant serpentine aneurysm in a2-a3 are very rare and can be difficult to treat with standard surgical methods , because of their atherosclerotic pathology and characteristically narrow surgical field . we describe an end - to - side in situ bypass technique combined with aneurysm trapping .

objectiveto report our surgical experience using in situ end - to - side bypass for giant serpentine distal anterior cerebral artery aneurysm , unsuitable for microsurgical clipping.methodsa 49-year - old woman presented with headache and intermittent loss of consciousness . the brain computed tomography scan revealed a partially calcified mass in the interhemispheric fissure . on cerebral angiography , that was giant ( 3018 mm sized ) , serpentine aneurysm originating from the a2 to a3 segment of the distal anterior cerebral artery ( daca ) . the aneurysm was trapped with clips , and the right a3 segment to left a3 segment of daca , end - to - side in situ bypass was performed . surgical result was favorable , with no newly developed ischemic event in the acute recovery period . postoperative angiography showed total occlusion of the aneurysm and good patency , with preserved distal flow.conclusiongiant fusiform aneurysms of the daca are extremely rare and can be particularly challenging to treat . end - to - side a3 : a3 bypass with aneurysm trapping could be a treatment modality for these locations .

stem - end rot disease - infected potato tubers were collected from commercial potato growing areas of gangwon - do ( korea ) in september 2013 . the disease - infected tubers with corky rot had slightly sunken circular lesions with sharply defined margins and had white fungal mycelium growth on the surface of the stem - end portions of the potatoes ( fig . infected tubers were collected in sterilized plastic polythene bags and transported to the laboratory for pathogen isolation . the potato pieces were surface - sterilized with 0.1% sodium hypochlorite ( naocl ) for one minute , washed three times with sterile distilled water , and then dried with sterilized filter paper . next , the potato pieces were placed in petri plates containing potato dextrose agar ( pda ) medium ( difco , detroit , mi , usa ) and incubated at 25 2 for 5 days . for pure culture isolation , the mycelia growth obtained on the pda plates was used to inoculate fresh pda plates . to characterize the pathogenicity of the fungus , 40-day - old potato plants cv . superior were transplanted into plastic pots containing commercial soil ( baroker ; seoul bio co. , ltd . , two weeks after planting the potato plants , 25 ml f. oxysporum conidial suspension ( adjusted to 1 10 conidia per ml by using a hemocytometer and prepared by suspending conidia from pda cultures in sterile water ) was applied by soil drenching . the greenhouse temperature was maintained at 25 2 and the plants were watered twice weekly . seven weeks after inoculation , small , purple - brown or light yellow corky rot developed on the potato tubers at the stem - end portions ( fig . the fungal pathogen was re - isolated from the disease lesions of the inoculated plants and the re - isolated pathogen exhibited the same morphological characteristics as those of the original isolates . thus , the fungal pathogen fulfilled the four criteria stipulated by the koch 's postulates and was identified as the causative agent of the potato stem - end rot . the pathogen was isolated from the disease lesion of the potatoes by using the surface sterilization method . mycelia were obtained from a 7-day - old culture on pda . for dna extraction , mycelia were grown in 250-ml flasks containing 100 ml potato dextrose broth , which were incubated for 6 days at 25 on a rotary shaker at 150 rpm . mycelia were harvested by vacuum filtration through whatman grade 1 filter paper and then lyophilized for 24 hr before grinding them to a fine powder . next , 100 mg of the ground powder was transferred to a 1.5-ml eppendorf tube and dna was extracted by using the ctab extraction method . the extracted dna was used for pcr sequencing of rdna genes by using universal primers for internal transcribed spacer ( its ) 1 ( 5'-tccgtaggtgaacctgcgg-3 ' ) and its 4 ( 5'-tcctccgcttattgatatgc-3 ' ) . the amplification was performed in a 25 l reaction mixture containing 0.5 l of each primer , 0.5 l of taq dna polymerase ( bioneer , daejeon , korea ) , 0.5 l of each dntp , 2.5 l of 10 pcr reaction buffer , 18.5 l of distilled water , and 2.0 l of template dna . the reaction was performed in eppendorf mastercycler gradient ( eppendorf , hamburg , germany ) under the following conditions : pre - denaturation at 94 for 5 min , followed by 35 cycles of denaturation at 94 for 35 sec , annealing at 52 for 55 sec , and elongation at 72 for 1 min and then final extension at 72 for 10 min . the obtained nucleotide sequences were searched through blastn at the genbank database ( http://www.ncbi.nlm.nih.gov/blast/ ) . phylogenetic analysis of f. oxysporum was performed by using the mega5 program with the neighbor - joining method . total 5 fungal strains were obtained from the stem - end root of potato , and strain f2 among 5 strains was examined for identification . strain f2 was identified as f. oxysporum by analyzing the morphological characteristics of the isolated fungus and by performing rdna sequencing analysis . the fungal colonies were isolated on pda and consisted of white aerial mycelia that later produced dark violet pigments that are characteristic of f. oxysporum ( fig . f. oxysporum has three types of conidia : macroconidia , microconidia , and chlamydospores . on the other hand , other fusarium spp . the its sequence was compared to the genbank database sequences by using the ncbi blast search tool . the sequences identified based on rrna - its alignment were 100% similar to those of several f. oxysporum species ( accession nos . thus , f. oxysporum was identified as the causative agent of potato stem - end rot in korea ( fig . this is the first report of stem - end rot of potato tubers in korea .

in this study , we identified the causative agent of stem - end rot in potatoes that were grown in gangwon alpine areas of korea in 2013 . the disease symptoms included appearance of slightly sunken circular lesion with corky rot on the potato surface at the stem - end portion . the fungal species isolated from the infected potatoes were grown on potato dextrose agar and produced white aerial mycelia with dark violet pigments . the conidiophores were branched and monophialidic . the microconidia had ellipsoidal to cylindrical shapes and ranged from 2.6~11.4 1.9~3.5 m in size . the macroconidia ranged from 12.7~24.7 2.7~3.6 m in size and had slightly curved or fusiform shape with 2 to 5 septate . chlamydospores ranged from 6.1~8.1 5.7~8.3 m in size and were present singly or in pairs . the causal agent of potato stem - end rot was identified as fusarium oxysporum by morphological characterization and by sequencing the internal transcribed spacer ( its1 and its4 ) regions of rrna . artificial inoculation of the pathogen resulted in development of disease symptoms and the re - isolated pathogen showed characteristics of f. oxysporum . to the best of our knowledge , this is the first study to report that potato stem - end rot is caused by f. oxysporum in korea .

most of the dual infections cause a diagnostic dilemma and require a high degree of suspicion in susceptible individuals . however , dual infections with mucormycosis may follow a fulminant course and may be associated with higher mortality and morbidity . we hereby report coinfection of pulmonary tuberculosis ( tb ) with mucormycosis in a diabetic male that worsened rapidly in spite of the antimicrobial therapy targeted toward the same . a 72-year - old nonsmoker male , known case of diabetes mellitus type ii since 10 years , on oral hypoglycemic agents , presented with the complaints of altered sensorium with low - grade fever associated with pain abdomen and vomiting and was diagnosed to have severe urinary tract infection . he was being managed in the ward for diabetic ketoacidosis for the same and was doing well until the 9 day of admission when he developed cough , expectoration , and difficulty in breathing . subsequently , the patient was intubated and transferred to intensive care unit ( icu ) for mechanical ventilation with synchronized intermittent mandatory ventilation mode and further managed according to the institutional protocol . all routine biochemical and hematological investigations including the chest x - ray ( cxr ) were sent . blood sugar levels were found to be 460 mg% and total lymphocyte count was 1200 mm , and urine ketones were found to be positive . arterial blood gas on the day of admission at fio2 of 0.6 had a pao2/fio2(pf ) ratio of 261 . empirical antibiotic therapy and vasopressor support with noradrenaline ( 0.5 g / kg / min ) was started as per protocol . sputum examination undertaken in the ward itself was negative for acid fast - bacilli ( afb ) . the cxr showed bilateral cavitary lesions in all the zones on the very 1 day of icu admission . with a high index of suspicion for fungal pneumonia based on the clinical and radiological findings and negative sputum for afb , antifungal ( caspofungin 70 mg intravenous [ iv ] loading dose followed by 50 mg iv once daily ) however , no clinical improvement was noticed over 5 days , and radiological deterioration was evident by the appearance of new cavitary lesions developing over every 24 h [ figure 1 ] . the pf ratio also started deteriorating consistently with the values of 161 on the 3 day falling to 114.5 on the 9 day with fio2 going up to 0.9 . with patient condition deteriorating as evidenced by higher ionotropic support and decreasing pf ratio , bronchoalveolar lavage ( bal ) was performed , and wastings were sent for afb staining , pyogenic culture , and fungal culture . subsequently , antitubercular treatment was also initiated as per the revised national tuberculosis control program guidelines for the same . although the potassium hydroxide wet mount revealed no fungal elements , fungal culture showed growth of rhizopus species on the 2 day of inoculation [ figure 2 ] , following which amphotericin b ( in the dose of 0.5 mg / kg iv loading dose followed by 1 mg / kg once daily ) was introduced as per culture sensitivity . on the 11 day , the pf ratio had further fallen to 71 on fio2 of 1.0 . however , the patient failed to improve and succumbed on the 12 day of admission to icu . multiple cavitatory lesions on day 5 lactophenol cotton blue mount showing rhizopus microsporus species ( lcb 200 ) opportunistic fungal organisms such as candida species , aspergillus species , mucor species , and cryptococcus neoformans may be encountered in diabetic patients who are usually immunocompromised by virtue of the disease itself . diabetes mellitus may predispose to mucormycosis in 3688% of patients which is a serious , potentially fatal fungal infection that needs a high degree of suspicion for the diagnosis . patients with uncontrolled hyperglycemia , particularly those with ketoacidosis , are the most susceptible and it may be the first manifestation in patients with undiagnosed diabetes mellitus . the most common presentation is rhino - orbital - cerebral involvement followed by pulmonary infection . patients with diabetes are prone to develop tb and have high chances of treatment failure . a large proportion of people with diabetes further developing tb are not diagnosed , or diagnosed too late , may be due to lack of awareness on the part of the patient to report early for any development of chest symptoms . coinfection with pulmonary tb and mucormycosis in immunocompromised patients may present a diagnostic dilemma owing to similar clinical presentation and need a high degree of clinical suspicion and early aggressive treatment . both clinical entities in addition , the radiological features of consolidation , cavitation , infiltrates , and effusion are common to both the diseases and , therefore , histopathological examination or culture sensitivity should be undertaken at the earliest to make definitive diagnosis . it is possible that the high relapse cases , treatment failures , resistance , and high mortality associated with tb infection are partly attributed to coinfection with opportunistic fungal pathogens and drug - resistant non - tb bacteria . in the present case , an immunocompromised state prevailing as a result of diabetes and tb made the patient prone to acquire coinfection with mucormycosis . although cavitation was evidenced on the very 1 day of admission to icu , negative sputum examination in the ward made tb an unlikely diagnosis . however , conclusive diagnosis was made only after bal which demonstrated the presence of afb on smear and ubiquitous filamentous fungus rhizopus species , of mucorale order , colonization on culture . there are isolated reports of coinfection of mucormycosis and tb in immunocompromised patient where the patients were successfully treated . in the present case , the unfavorable outcome may be the result of delayed diagnosis which was probably missed for the first 8 days in a ward where primarily the focus was on treating diabetic ketoacidosis . meanwhile , the hyperglycemic environment that favors immune dysfunction ( e.g. , damage to the neutrophil function , depression of the antioxidant system , and humoral immunity ) flared up coinfection of mucormycosis with latent tb progressing to active tb and followed a fulminant course . latent tb and drug - resistant tb in patient with diabetes make them susceptible to opportunistic infections with potentially fatal fungal infections . simultaneous infection with mycobacterium tuberculosis and mucormycosis is a rare finding and requires high clinical vigilance . now - a days , it is imperative to consider fungal infections as an important differential diagnosis . early and aggressive treatment targeting the isolated organisms may help reduce the mortality and morbidity . meanwhile , screening the patients with diabetes for coinfections , especially in nonresolving pneumonias are imperative and should be practiced in a protocolized form in early stages of diabetes .

herein , we present the case report of an adult male diabetic patient who had coinfection with mycobacterium tuberculosis and mucormycosis , which otherwise is a rare clinical entity . diabetes mellitus may predispose a patient to tuberculosis ( tb ) infection which further weakens immune system thus making him susceptible to other fungal or bacterial infections which may pose various treatment difficulties . therefore , there is a need for mycological and bacteriological investigations in patients with pulmonary tb to rule out secondary coinfections thus contributing to better management .

due to its simplicity and convenience , acupuncture has become popular as a complementary therapy . in this chinese medicine , doctors have to find the traditional meridian acupuncture points before the needle is punctured into those points . because of the significant remedial effects , acupuncture has drawn a lot of attention from the western world over the past 30 years . around 2002 , there were 42 states in the united states that had established statutory licensure governing more than 14,000 acupuncture practitioners . in the past decade , acupuncture had been widely practiced to treat various diseases . besides , moxibustion , which is an important auxiliary part of acupuncture , may enhance the effect of curing disease by conducting heat to certain points or areas on the surface of the body through regulation of the function of meridians and visceral organs . when performing direct moxibustion , moxa sticks are burnt at acupuncture points on the skin . on the contrary , in indirect moxibustion , the moxa cone ( i zh ) does not touch the skin and is burnt insulated , by some substance , against the skin . in traditional chinese medicine , moxibustion is usually used for the patients with cold pattern such as rheumatic arthritis , joint pain , diarrhea , or cold numbness limbs . warm - needling acupuncture ( wna ; wn zhn ji ) is classified under the category of indirect moxibustion . when practicing wna , the moxa cone is firstly put on the tail of the needle , and is then lighted up in such a way that the heat of moxa will be transmitted through the punctured needle to the correspondent acupuncture point . however , in some unexpected situations , practitioners might get burns while removing the needles after treatment . in order to prevent the practitioners from getting burns , it is necessary to study the temperature changes in some designated parts of the needles . we conducted an experiment to record the temperatures in the designated portion of the needles at some predetermined time intervals . the extreme temperatures are outlined , and 95% confidence interval of the average temperatures in different portions at different time intervals is determined . according to the outcome of the statistical analysis , we may propose a warning suggestion for the practitioners conducting wna . in section 2 , the method of this study is described . in the experiment , two groups with 10 stainless steel needles ( an chi handy acupuncture needle , iso 13485 ) and 10 pieces of cylinder - shaped moxa [ figure 1 ] were used . in the first group , each moxa used in wna had a weight of 0.6 g , and in the second group each moxa was enlarged with a weight of 1.0 g. the main ingredient of the moxa is dried mugwort ( artemisia argyi ) . the size , shape , and weight of the moxa ( ) were designed according to the traditional literature ; for example , the base of 0.6 g moxa had a diameter of 10 mm and the height of the moxa was 10 mm . the 1.0 g moxa had a diameter of 13 mm and the height of the moxa was 15 mm . the length of the needles was 1.5 inch 32 gauge , and the needles were divided into two parts the handle and the needle body . a standard moxa for warm acupuncture the needles were punctured into polystyrene plastics in good upright positions . the handles of the needles were surrounded by the moxa cylinders in the middle part [ figure 2 ] . there were 40 moxa cones used for each group . in order to estimate the mean and extreme temperatures in different parts of the needles , we measured for each needle the temperatures of the upper end of the handle , the lower end of the handle , the needle body above the polystyrene plastics , and the tip of the needle body , respectively . the distance between upper end of the handle and the moxa cone was 1.5 cm , between lower end of the handle and the moxa cone was also 1.5 cm , at the needle body above the polystyrene plastics was 2.0 cm , and between the tip of the needle body and the polystyrene plastics was also 2.0 cm . the temperature and moisture of the laboratory were controlled to be stable . after lighting up the figures and tables given in appendix illustrate the changes in temperature recorded every 30 seconds in each of the four designated parts of a needle . the experimental results show the hazardous time and positions when conducting a warm acupuncture ( wn zhn ) . the extreme ( maximal ) temperature at each recording time is especially important as it might cause danger . eight groups of warming needles from tables a1 and a2 , it seems that the highest temperature occurs around 430 or 530 from ignition . the two tables summarize the mean temperatures of the warm needles using 0.6 g moxa . in particular , table a2 shows the highest temperatures at the designated parts of the needles . in group 1a ( temperatures taken at the upper end of the handle ) , the highest temperature may reach 344c and it still remains 45c at 9 min 30 seconds . in group 2a ( temperatures taken at the lower end of the handle ) , note that in group 2a , the highest temperature may reach 320c at 5 min 30 seconds . in group 3a ( temperatures taken at the needle body above the polystyrene plastic ) , the temperatures are lower than those in groups 1a and 2a . tables a3 and a4 show the temperatures of the warming needles using 1 g moxa . the highest temperature ( 375c ) in group 1b is 31c higher than that ( 344c ) in group 1a . because the moxa used in group b is more than in group a , the required cooling time also gets prolonged . it takes almost 15 min for the needles to cool down to the temperature before ignition . the time series plots of the temperatures recorded in group a are shown in figures a1a to a4a , while those in group b are illustrated in figures a1b to a4b . if the effects of energy transmission were via the needles , the bodies of the needles should not have lower temperatures as suggested by the present study . a possible explanation for the remedial effect of wna may be due to radiation or convection . while some researchers suggested that the therapeutic effect of moxibustion is correlated with the temperature , some others have shown that infrared irradiation might have the same effect . there are also some studies suggesting that indirect heating may be a possible effect of moxa . lin suggested that the effect of moxibustion is highly associated with thermal as well as the pharmacological reaction of the materials used . the treatment effects of moxibustion are not only induced by heat but also by its chemical function . also , a study shows the safety of ph level , heavy metals , and uv absorbance spectrum on the cytotoxicity and hemolysis of the needle . the radical scavenging effect of moxa or moxa - tar is measured by a chemical reaction with 1,1-diphenyl-2-picrylhydrazyl . the inhibitor effects of moxa or moxa - tar on superoxide production are caused by the radical scavenging mechanism . as the above references suggest , the chemical ingredients of moxa play an important role in the therapeutic effect . in the present study , the main difficulties arose when we measured the temperatures of four designated parts of a warming needle . there are some studies observing the temperature changes in the human body during the burning of moxa ball . but they did not check needle tip temperature . since it is impossible to measure the temperatures of the needles punctured into patients , we designed an experiment to mimic the real situations . in tcm , wna is an efficient way for the patients with cold pattern . traditional chinese physicians believed that wna can transmit heat to the meridian acupuncture points of the patients . however , when the physicians remove the needles from the patients , they might suffer burns . so far , there is no related study on the possible hazardous time when conducting wna . for the sake of medical safety , it is necessary to investigate the proper time at which the needles can be removed from the patients . when conducting acupuncture , the handle of the needles is frequently touched . in the present study , no matter which moxa we used , the most hazardous part of a warming needle is around the handle . fortunately , when conducting wna , the other parts of a needle do not cause burns . when the weight of a moxa increases from 0.6 to 1 g , the temperature of the warming needle also increases and the required cooling time also gets prolonged . we suggest that a safer timing for a tcm physician to remove the needles should not be earlier than 930 ( resp . 1330 ) for a 0.6 g moxa ( resp . 1 g moxa ) as the heat source . since mugwort in this study has been made of the moxa cone , the study investigates the routine use of moxa cone and the burning time , in order to avoid the practitioner suffering from burns . future studies could focus on the influence of the production process of a. argyi leaves .

due to its simplicity and convenience , acupuncture has become popular as a complementary therapy . in this chinese medicine , doctors have to find the traditional meridian acupuncture points before puncturing the needles into them . moxibustion ( i ji ) is also an important part of the acupuncture remedy . treatment by acupuncture can be classified roughly into two types direct moxibustion and indirect moxibustion . warm - needling acupuncture ( wn zhn ji ) is classified under the method of indirect moxibustion . in the present study , 10 standard stainless steel acupuncture needles with 10 pieces of cylinder - shaped moxa cone ( i zh ) as the heat source of warm needles were used . in order to prevent the practitioners from getting burns , it is necessary to study the temperature changes in some designated parts of the needles . two sizes , 0.6 g and 1.0 g , of moxa cones were used for comparison of the measured temperatures . the needles are typically divided into two parts the handle part and the needle body . in our experiment , the temperatures of wna at different parts of the needles were measured . the larger the size of moxa cone is , the longer is the burning time . based on the observations we suggest that when 0.6 g moxa is used , the physicians should better pick out the needles around 9 min after ignition ; however , while using the 1 g moxa , it might be safer to pick out the needles around 13 min after ignition .

we report an unusual case of a dj stent that was misplaced into the supra - renal portion of the inferior vena cava ( ivc ) during a boari flap procedure . six months later , she presented with right flank pain and was diagnosed to have a mid - ureteric stricture . a boari flap repair was performed with insertion of a dj stent . in view of persistent flank pain and urinary infection 6 weeks after the repair , computed tomography ( ct ) urography was performed . to the surprise of the treating urologist , the ct showed that the stent had traversed through the boari flap and entered the ivc , with the upper coil of the stent in the supra - renal ivc [ figure 1 ] . further , the normal upper ureter was not connected to the boari flap but was in continuation with the lower ureter [ figure 2 ] . the boari flap , unconnected to the upper ureter , appeared like an out - pouching from the bladder . stent has the upper coil in the inferior vena cava ( single arrow ) and lower coil in the bladder through the boari flap ( double arrow ) the right lower ureter is in contuinity with the normal upper ureter while the boari flap is not connected to the upper ureter . stent exits through the boari flap and has upper coil in the inferior vena cava at this stage , the patient was referred to our center for further management . after discussion with the patient , it was planned to remove the stent cystoscopically with a vascular team on standby . the stricture was subsequently managed by endoureterotomy and a stent was placed in the normal ureter . it has been reported both during open and endourological procedures . during retrograde placement of the stent , there can be a simultaneous perforation of the ureteral wall and an adjacent inter - communicating vein through which the stent gets direct access to the vascular system . through the vein , such perforations can happen if the rigid reverse end of the guide wire is mistakenly pushed in the ureter or during a difficult ureteroscopy complexed by poor vision and lack of fluoroscopic guidance . during open surgery not only does the vein get anastomosed to the urinary system but also the stent gets placed in the vascular system through the vein . after such an occurrence , the patient can have significant hematuria that continues till the vein gets thrombosed . kim et al . have reported cardiac migration of the stent during a difficult hysterectomy . in the presence of significant bleeding and bladder injury , the present case is novel because endovascular positioning of the stent occurred during an elective boari flap repair . we postulate that the surgeon mistook the gonadal vein as the upper ureter and anastomosed it to the boari flap . this is further suggested by the fact that the proximal ureter was not connected to the boari flap and it remained joined to the normal lower ureter . it is difficult to explain why the patient did not have bleeding from the gonadal vein or from the stent once the stent was placed in the ivc . it is possible that some degree of hematuria was ignored as a normal post - surgery consequence . absence of prolonged post - operative bleeding could be due to intra - catheter blood clotting and gonadal vein thrombosis . this problem could have been avoided by proper intra - operative identification of the ureter . in the retroperitoneal space , both the ureter and the gonadal vein run parallel to each other , with the ureter lateral to the vein . it is important to trace the tubular structures on both the sides and to look for peristalsis to confirm it to be the ureter . intra - operative hydration and diuretics would help document efflux of urine from the cut end . if in doubt , ureteral stents can be placed safely with fluoroscopic assistance , and any positioning problems can be identified and corrected at the time of insertion . the management of a ureteral stent that has migrated into the vascular system includes open surgical techniques , interventional radiological techniques and transurethral removal . in the present case , cystoscopy was selected for removing the migrated dj stent as it had one accessible coil in the bladder and was placed for over 6 weeks without any urinary bleeding .

a 30-year - old lady underwent a boari flap repair for post - hysterectomy mid - ureteric stricture . the upper end of the double j stent inserted during the procedure was misplaced in the supra - renal inferior venal cava . cystoscopic stent removal could be performed uneventfully , while the stricture was managed by endoureterotomy .

continuous blood supply to active muscles is necessary to maintain exercise . in patients with cardiovascular diseases , it has been suggested that synchronization between the heart beat and locomotor rhythm [ cardiac - locomotor synchronization ( cls ) ] can optimise blood flow to muscles and minimise cardiac load1 , 2 . the mechanism of this phenomenon is speculated to be peak intra - arterial pressure due to cardiac contraction occurring at the lowest phase of the intramuscular pressure cycle . niizeki reported evidence for physiological cls using computer - assisted bilateral thigh - cuff occlusion and suggested that cls may be associated with the improved perfusion of exercising muscles2 . if cls has the physiological significances described above , cls has the potential to improve the exercise capacity of patients with cardiovascular diseases and thus may be useful in rehabilitation programs . however , the physiological significance of cls for muscle blood perfusion during walking , running and cycling , which are usually performed in physical therapy , has not yet been clarified in healthy subjects . therefore , we examined whether cls has physiological significance for lower leg muscle blood perfusion during walking to obtain evidence of physiological cls in healthy subjects . eleven healthy men ( mean sd , height : 167.8 4.5 cm , weight : 56.1 5.0 kg , age : 21.3 2.2 years ) were included in this study after obtaining their informed consent . this study was approved by the ethics committee of seirei christopher university ( approval number : 09008 ) . physical activity and alcohol and caffeinated beverage consumption were prohibited for 24 h before testing . drinking and eating , except water , were also prohibited for 3 h before testing . we determined each subject s treadmill load ( treadmill speed and grade ) at which their heart rate ( hr ) was maintained at approximately 120 beats / min ( bpm ) . the target heart rate was derived from the 5070% of estimated maximal heart rate , which is the formula of optimal heart rate during exercise for heart failure patients in japan . subjects walked on a treadmill ( autorunner ar-200 , minato medical science co. , ltd . , osaka , japan ) , with gradually increasing treadmill speed within the range in which subjects can walk ( limited at 6.0 km / h ) . when the load was insufficient , the treadmill grade was increased until the target hr was achieved . subjects walked at the determined treadmill speed and grade for at least 5 min to confirm appropriate load . subjects then rested for at least 15 min during which they were instrumented for data collection . electrodes for electrocardiography ( ecg ) , a foot switch sensor and a near - infrared spectroscopy ( nirs ) probe were placed on the chest , right heel and posterior surface of the lower left leg , respectively . thereafter , subjects were instructed to perform two treadmill protocols in a random order . in one , subjects walked at the frequency of their hr to induce cardiac - locomotor synchronization ( cls protocol ) . in the other , subjects walked at their preferred pace ( free protocol ) . both protocols were performed at the individual s predetermined treadmill load for 20 min . the first 10 min was the warm - up period , and it was followed by 10 min of measurement . as the treadmill load was fixed for each subject , the effort was identical in both protocols . subjects rested in a sitting position for at least 15 min between protocols . to achieve cls in the cls protocol , subjects walked at their predetermined load for 5 min and then for 5 min with a buzzer signal generated by an ecg monitor ( bedside monitor bsm-2400 series life scope 1 , nihon kohden corp . , after their hr reached a steady state , they walked in synchrony with the buzzer signal for 10 min , and data was collected during this period . in the free protocol , subjects walked at their predetermined load for 10 min and then at their preferred pace for 10 min and data were collected during the latter 10-min walking period . thus , identical treadmill loads and exercise times were established for both protocols . the r - r interval ( rri ) the ecg signal was amplified and band - pass filtered between 10300 hz to distinguish r waves of the qrs complex and to suppress movement artifacts . the ecg signal was digitised at s sampling frequency of 1 khz using a personal computer - based system ( chart 5 for windows , ad instruments , shanghai , china ) equipped with an analogue - to - digital converter ( ml880 powerlab 16/30 , ad instruments ) . the heel contact interval ( hci ) was measured by a foot switch sensor ( inline foot contact sensor , noraxon ) on the right heel . the foot switch signal was collected at a sampling frequency of 1.5 khz using a personal computer - based system ( myoresearch xp , noraxon ) . as ecg and foot switch signals were recorded using separate computers , ecg and hci recordings began at same time . in addition , a near infrared spectrophotometer ( omega monitor ; bom - l1 trw , omega wave , tokyo , japan ) was used to monitor tissue oxygen saturation . using these three wavelengths , it is possible to differentiate between oxygenated and deoxygenated haemoglobin . the sum of oxygenated and deoxygenated haemoglobin reflects the total amount of haemoglobin ( total hb ) , which can be interpreted as blood volume in the underlying tissue3 . the nirs signal is generally used with artery or venous occlusion to examine tissue blood flow and tissue metabolism4 , 5 . it was not possible to compress the subjects lower extremities , because the focus of this study was muscle blood perfusion when cls occurred during walking . therefore , the index of muscle blood perfusion during walking was defined as total hb only . a probe with a dedicated light - occluding holder was attached to the posterior surface of the lower left leg section with the greatest diameter with surgical tape and an elastic bandage . rri and hci data were translated into text files and opened in microsoft office excel 2007 ( redmond , wa , usa ) . each successive hci signal was halved to estimate the foot switch rate for both legs . the time at which each r wave occurred and the onset of each step cycle were calculated by adding the first onset time and interval times . to obtain the relative phase relationship between the cardiac and locomotor rhythms ( r , h ) , the time ( tr ) at which r r wave occurred in a one - step cycle was calculated from the onset of the step cycle , where tr is the time of the r marked event . the onset of the step cycle was defined as th . the relative phase ( r , h ) of the r heartbeat in a one - step cycle was calculated as follows : where r and h are integers . the synchronization index , , was calculated to quantify the strength of phase locking between the heartbeat and step cycle as follows : where n indicates the number of consecutive data samples . was calculated from 60-point windows ( approximately 30 s epochs ) with a sliding window of 10 points . mean was calculated as the average of the entire measurement period of each protocol . the fractional points were rounded down when points of relative phases were insufficient at the end of calculations . was restricted to 0 1 , and a higher value indicates stronger phase locking between the two rhythms . a surrogate data technique was also used to determine the probability of entrainment between the cardiac and locomotor rhythms6 . the surrogate data were generated by randomly shuffling the original order of raw hci data , while successive rris remained the same to create a new phase relationship between the two rhythms . the phase relationships between the heartbeat and locomotor activity rhythm were destroyed because of the random order of hci . if two rhythms had an exact phase relationship , a relative phase similar to the original relative phase would occur in the surrogate data . the average value of original data was compared with that of surrogate data calculated from an identical observation window . mean hr , mean step rate ( sr ) and total hb in the lower left leg muscles were calculated over the final 10 min of each protocol to investigate the cls physiological response . cls occurrence was defined as exceeding 0.3 , where is the difference in between the cls and free protocols ( cls free ) , because values show substantial individual variability even during cls induction7 . in subjects whose exceeded 0.3 , values were compared between the two protocols using the paired t - test to determine whether phase synchronization occurred during the cls protocol . in addition , the values of the original and surrogate data of both protocols were compared using the paired t - test to determine whether phase synchronization occurred by entrainment . for subjects whose exceeded 0.3 , mean hr , mean sr and total hb were compared between the two protocols using the paired t - test to examine the effect of cls on muscle blood perfusion during walking . furthermore , for all subjects , the relationship between and total hb ( % ) , calculated as the ratio between total hb in the cls and free protocol , using pearson s product - moment correlation coefficients was investigated . all statistical analyses were performed using spss version 19 for windows software ( spss japan , inc . , tokyo , japan ) . in 9 of 11 subjects , the difference in the synchronization index , , between the cls and free protocol ( ) exceeded 0.3 , indicating the occurrence of cls during the cls protocol in the majority of subjects . in subjects whose exceeded 0.3 , the mean value was also significantly greater in the cls protocol than in the free protocol ( 0.54 0.16 vs. 0.06 0.06 , n = 9 , p < 0.05 ) and that of the surrogate data ( 0.54 0.16 vs. 0.24 0.08 , n = 9 , p < 0.05 ) , indicating that phase synchronization was the result of heartbeat entrainment by locomotor activity . in contrast , the mean value of the free protocol did not differ from that of the surrogate data ( 0.06 0.06 vs. 0.05 0.05 , n = 9 , not significant ) , indicating that phase synchronization did not occur in the free protocol . in subjects whose exceeded 0.3 , mean hr and mean sr did not differ significantly between the two protocols ( mean hr : 122 6.5 vs. 120 7.1 beat / min , mean sr : 122 6.3 vs. 124 7.9 step / min , n = 9 , not significant ) . however , despite the identical treadmill load of the two protocols , total hb during the cls protocol was significantly higher than that during the free protocol ( 17.8 2.6 vs. 17.5 2.7 10 pieces / mm , n = 9 , p < 0.05 ) . for all subjects , correlation analysis revealed a significant relationship between ( range , 0.160.65 ) and total hb ( range , 98104% ) ( r = 0.64 , n = 11 , p < 0.05 ) . the main finding of the present study was that total hb in the lower leg muscles increased with the value during walking . furthermore , the value of the cls protocol was significantly greater than that of both the surrogate data and the free protocol , indicating that the difference in the physiological data between the two protocols possibly shows a physiological response when cls occurs . the increased lower leg muscle blood perfusion during walking suggests that this entrainment can enhance exercise efficiency . total hb increased significantly during the cls protocol compared with that during the free protocol , despite the identical treadmill load . in addition , a positive correlation was observed between total hb and , strongly suggesting a causal relationship between the increase in total hb and cls occurrence . a possible explanation for this is the occurrence of an optimal phase relationship between arterial and intramuscular pressures , leading to improved muscle blood perfusion . during locomotion , muscle contraction induces an elevation in intramuscular pressure and compresses the vascular bed , leading to cessation of perfusion8 . niizeki reported evidence of a physiological cls using computer - assisted bilateral thigh - cuff occlusion to simulate intramuscular pressure changes during bipedal locomotion2 . alternating cuff occlusion at hr resulted in phase synchronization , and individual heart beats were unlikely to overlap with elevated cuff pressure . in addition , kimura et al . suggested that cls with an appropriate phase difference attenuates peripheral vascular resistance and systolic blood pressure while increasing stroke volume9 . it is possible that there is a specific phase difference between cardiac systole and muscle contraction that confers peak leg arterial pressure during the lowest muscle capillary resistance . first , the effect of respiratory rhythm on the relationship between cardiac and locomotor rhythms was not assessed . respiration could indirectly influence the occurrence of cls as respiratory sinus arrhythmia modulates the heartbeat through neural effects10 , and ventilation modulates venous return through movement of the diaphragm11 . second , changes in total hb on the time scale of individual cls events could not be assessed . as a result , the beat - by - beat cls physiological response during exercise was unclear . additional studies are required to assess this relationship in other populations , such as patients with cardiovascular diseases who may benefit from cls to improve the capacity for therapeutic exercise .

[ purpose ] the purpose of this study was to investigate whether the occurrence of cardiac - locomotor synchronization ( cls ) improves lower leg muscle blood perfusion during walking . [ subjects and methods ] eleven healthy men were studied while performing two treadmill protocols . the cls protocol involved subjects walking at the frequency of their heart rate ( hr ) to induce cls . the free protocol ( reference ) involved subjects walking at a self - selected cadence . the treadmill load was identical in the two protocols . electrocardiographic signals for hr , foot switch signals for step rate and near - infrared spectroscopy ( nirs ) signals for total haemoglobin ( total hb ) in the lower leg muscles were measured continuously for 10 min after hr reached a steady state . [ results ] the mean hr and mean step rate did not differ between the cls and free protocols . however , total hb was significantly higher in the cls protocol than in the free protocol . the rate of increase in total hb positively correlated with the strength of cls . [ conclusion ] these results suggest that the occurrence of cls enhances lower leg muscle blood perfusion by increasing the strength of cls during walking .

the origin of the fluorescence is not fully clear , though it seems unlikely that apatite is responsible for the basal values associated with healthy enamel . the explanation may be the result of the combination of the inorganic matrix with the absorption of organic molecules . carious lesions fluoresce more strongly than healthy tissues at an excitation wavelength in the red and infrared part of the spectrum . this increase in observed fluorescence is related to two processes : demineralization of the tooth and bacteria with their metabolic products ( porphyrins ) . most of the fluorescence is induced by the organic components , rather than by crystal disintegration and transmission through scantly homogeneous enamel . this hypothesis is based on the fact that laser fluorescence ( lf ) does not detect lesions caused in the laboratory with acids instead of bacterial activity . bacteria responsible for caries would produce certain endogenous porphyrins ( fluorophores ) that fluoresce when excited by red laser light . the lf - based device for caries diagnosis is equipped with a laser diode providing the excitation light source , wavelength 655 nm , necessary for detection of these fluorophores . most studies evaluating lf have been carried out in vitro , though there are also a number of in vivo studies . the results of in vitro studies can not be extrapolated to in vivo conditions and the limitations of these studies are well - known . in order to get the maximal sensitivities and specificities from the lf device and to obtain an appropriate guideline for the practitioner to interpret the results , several cut - off values were presented , thus making the diagnostic decision even more difficult . in many cases , the cut - off values determined in vitro proved to be lesser than the cut - off values obtained from clinical studies . this may be due to the way in which the teeth are preserved , or changes in their organic content after extraction , inducing alterations in dental tissue fluorescence . these could promote variations in the optical properties of the teeth and consequently in their lf response . teeth being the most essential part of the dental research methodologies invariably need to be stored under proper conditions in order for various in vitro studies to be carried out authentically . there is a need to clarify the effect of different storage media on the fluorescence readings during a specified span of time . hence , the prime objective of this investigation was to evaluate the change in lf for teeth stored in different storage solutions as a function of time and to give cut - off values for different storage media at different time intervals to get them at par with the clinical / in vitro conditions and to see which medium gives best results with the least change in lf values and while enhancing the validity of diagnodent in research . extracted teeth were collected and subjected to an autoclave cycle for 40 min as per the guidelines of centers for disease control , usa based on the study by pantera and schuster . initially , all the teeth were frozen and stored at 20c immediately after extraction and had no contact with any storage solution for 7 days . following this , the teeth were then defrosted to room temperature over a period of 14 h placing them in plastic containers . nearly 100% humidity was insured by placing a wet blotting paper at the bottom of each container making sure that no contact was made between the teeth and the blotting paper . all teeth were then cleaned with a toothbrush under tap water for 15 s. only the teeth with an lf 30 , indicative of requiring definitive restorative procedures , were used . 90 extracted teeth were selected from this pool and a specific site was selected and recorded for measurement . each specimen had a mean fluorescence value of 92 varying from 85 to 96 . measurements were made for each tooth after which the samples were stored as follows : group 1 in 1% chloramine , group 2 in 10% formalin , group 3 in 10% buffered formalin , group 4 in 0.02% thymol , group 5 in 0.12% chlorhexidine , group 6 in 3% sodium hypochlorite , group 7 in a commercially available saliva substitute - wet mouth ( icpa pharmaceuticals ) and group 8 in normal saline . lf measurements were performed with the same lf - based device - diagnodent ( kavo , biberach , germany ) throughout the study . prior to each measurement , measurements were repeated at 30 , 45 , 60 , 160 and 365 days . in order to repeat the readings at the same site each time , an indentation was marked near the site on the teeth with a round bur [ table 1 , figure 1 ] . laser fluorescence values of groups at different time intervals laser fluorescence values for groups 1 - 9 over t30 , t45 , t60 , t160 and t365 before each measurement , all teeth were defrosted to room temperature for 14 h. group 9 ( frozen teeth ) were kept at 100% humidity while the other groups were kept in their respective storage solutions following which they were rinsed under tap water for 3 min to remove residual solution before carrying out measurements . after measurement , groups 1 - 8 was placed in fresh solutions while group 9 was frozen at 20c again . all specimens were placed in darkness . in order to allow comparisons between individual lf measurements with time , the baseline was set at 0.00 and curves were plotted [ figure 2 ] . change in laser fluorescence values plotted as a function of time the mean change in lf values for the eight storage media and frozen condition was calculated . average change at different time intervals were used as cut - off values as compared to the in vitro condition . statistical package for social sciences for windows , version 20 . statistical significance was set at p = 0.05 . the mean change in lf values in different storage mediums at different time intervals were compared using two - way anova . extracted teeth were collected and subjected to an autoclave cycle for 40 min as per the guidelines of centers for disease control , usa based on the study by pantera and schuster . initially , all the teeth were frozen and stored at 20c immediately after extraction and had no contact with any storage solution for 7 days . following this , the teeth were then defrosted to room temperature over a period of 14 h placing them in plastic containers . nearly 100% humidity was insured by placing a wet blotting paper at the bottom of each container making sure that no contact was made between the teeth and the blotting paper . all teeth were then cleaned with a toothbrush under tap water for 15 s. only the teeth with an lf 30 , indicative of requiring definitive restorative procedures , were used . 90 extracted teeth were selected from this pool and a specific site was selected and recorded for measurement . each specimen had a mean fluorescence value of 92 varying from 85 to 96 . measurements were made for each tooth after which the samples were stored as follows : group 1 in 1% chloramine , group 2 in 10% formalin , group 3 in 10% buffered formalin , group 4 in 0.02% thymol , group 5 in 0.12% chlorhexidine , group 6 in 3% sodium hypochlorite , group 7 in a commercially available saliva substitute - wet mouth ( icpa pharmaceuticals ) and group 8 in normal saline . lf measurements were performed with the same lf - based device - diagnodent ( kavo , biberach , germany ) throughout the study . prior to each measurement measurements were repeated at 30 , 45 , 60 , 160 and 365 days . in order to repeat the readings at the same site each time , an indentation was marked near the site on the teeth with a round bur [ table 1 , figure 1 ] . laser fluorescence values of groups at different time intervals laser fluorescence values for groups 1 - 9 over t30 , t45 , t60 , t160 and t365 before each measurement , all teeth were defrosted to room temperature for 14 h. group 9 ( frozen teeth ) were kept at 100% humidity while the other groups were kept in their respective storage solutions following which they were rinsed under tap water for 3 min to remove residual solution before carrying out measurements . after measurement , groups 1 - 8 was placed in fresh solutions while group 9 was frozen at 20c again . in order to allow comparisons between individual lf measurements with time , the baseline was set at 0.00 and curves were plotted [ figure 2 ] . change in laser fluorescence values plotted as a function of time the mean change in lf values for the eight storage media and frozen condition was calculated . average change at different time intervals were used as cut - off values as compared to the in vitro condition . statistical package for social sciences for windows , version 20 . statistical significance was set at p = 0.05 . the mean change in lf values in different storage mediums at different time intervals in all specimens the difference was statistically significant for all groups except for the frozen specimens . all curves dropped dramatically immediately after a storage in solutions in groups 1 - 8 . maximum drop occurred between days 1 and 30 after which the drop was gradual . the change in lf values at 30 days as a percentage of total change was evaluated and presented in the form of a bar diagram [ figure 3 ] . change in laser fluorescence values at 30 days as a percentage of total change it was discerned that specimens stored in wet mouth , sodium hypochlorite , chloramine and normal saline exhibited a slower initial decline in lf values ( up to day 30 ) as compared to formalin , buffered formalin , thymol and chlorhexidine . therefore , it can be clearly discerned from figures 2 and 3 that for short - term storage purposes - wet mouth , sodium hypochlorite , chloramines or normal saline should be preferred while for studies requiring long - term storage of teeth as specimens - formalin , buffered formalin , thymol or chlorhexidine should be preferred . however , the best storage condition would undoubtedly be the frozen condition which showed a statistically insignificant change ( p > 0.05 ) in lf values over the entire period of the study . most of the research studies carried out in dentistry are first evaluated under laboratory or in vitro conditions and only after a hypothesis is tested under these conditions , is the methodology extrapolated onto the clinical or in vivo condition . various factors such as room temperature , humidity and storage media need to be considered when working under laboratory conditions . in the in vitro condition , the variable hypothesized to affect differences in cut - off values in different studies has been the storage solutions . most of the storage solutions , used in dental research for preservation of extracted teeth , are antiseptics or disinfectants which are basically a protoplasmic poison for the bacteria . this probably leads to decrease in the concentration of fluorophores in the specimen by dilution ultimately leading to a reduction in the lf signal . moreover , the chemicals used might even cause a modification of the fluorophores or affect the optical properties of dental hard tissues like dispersion and scattering over time . on the other hand , freezing is known to exert a bacteriostatic effect , as this is commonly used for preservation of bacterial cultures . furthermore , it is highly unlikely that bacteria or their endogenous products ( fluorophores ) will undergo a change if no solution is in contact with them , such as in the frozen condition . very few studies have dealt with the issue of effect of storage on lf response . in a study spectroscopic changes in human dentine exposed to various storage solutions were measured in the ultraviolet , visible and near - infra - red spectral ranges with an integrating sphere spectrophotometer over a 28 day period . it was concluded that changes in surface chemistry and optical properties of dentine did occur as a function of storage solution and time , which must be considered when studying dentine . another study had a conflicting finding of increase in fluorescence after formalin fixation . however , in that experiment , the specimens had been stored in thymol saturated saline followed by subsequent storage in neutral - buffered formalin unlike our study where no prior contact was made with any other solution . few other studies have been conducted in the recent past which concluded that a decrease in lf values takes place when teeth are stored in different storage solutions as functions of time which is in concurrence with our findings . our study evaluated a change in lf values for eight different storage solutions in comparison with the frozen condition which has not been previously conducted . in our study , a temporal relationship has been established in the drop in lf values wherein the maximum drop was seen during the first 30 days of storage following which the drop in the readings was found to be gradual . the observed drop in the lf values was significant for each of the eight solutions while it remained insignificant for the frozen condition , which is in agreement with the previous studies of lussi et al . since there was little or no change in the lf values for the frozen teeth , hence it may not be wrong to assume that the frozen condition may be comparable to the in vivo condition thus enabling the practitioner to interpret results and extrapolate them with more accuracy to the clinical condition . the study validates use of diagnodent as a reliable evaluating measure in various researches being conducted globally in the field of dentistry . recently , many researches have been conducted , utilizing diagnodent as a primary tool for studying mineralization of dental specimens . it is our study that goes a step ahead in providing cut - off values for each case at different time intervals in an attempt to obtain appropriate guidelines for undertaking such studies in the future . only a few studies can be found in the literature dealing with the issue of the influence of storage on lf response . the inevitable inherent change in lf due to various storage media commonly used , at different time intervals is put forth by the study . the values thus obtained can help remove the bias caused by the storage medium and the values of lf thus obtained can hence be conveniently extrapolated to the in vivo condition . the study enables better use of diagnodent as an evaluating measure in various in vitro studies .

aims : the aim of the following study is to evaluate the change in laser fluorescence ( lf ) values for extracted teeth stored in different solutions over 1 year period , to give cut - off values for different storage media at different time intervals to get them at par with the in vivo conditions and to see which medium gives best results with the least change in lf values and while enhancing the validity of diagnodent in research.materials and methods : ninety extracted teeth selected , from a pool of frozen teeth , were divided into nine groups of 10 each . specimens in groups 1 - 8 were stored in 1% chloramine , 10% formalin , 10% buffered formalin , 0.02% thymol , 0.12% chlorhexidine , 3% sodium hypochlorite , a commercially available saliva substitute - wet mouth ( icpa pharmaceuticals ) and normal saline respectively at 4c . the last group was stored under frozen condition at 20c without contact with any storage solution . diagnodent was used to measure the change the lf values at day 30 , 45 , 60 , 160 and 365.statistical analysis used : the mean change in lf values in different storage mediums at different time intervals were compared using two - way anova.results:at the end of 1 year , significant decrease in fluorescence ( p < 0.05 ) was observed in groups 1 - 8 . maximum drop in lf values occurred between day 1 and 30 . group 9 ( frozen specimens ) did not significantly change their fluorescence response.conclusions:an inevitable change in lf takes place due to various storage media commonly used in dental research at different time intervals . the values obtained from our study can remove the bias caused by the storage media and the values of lf thus obtained can hence be conveniently extrapolated to the in vivo condition .

lung cancer has become a disease of great global impact and remains the leading cause of death from cancer in the world.1 as smoking and environmental pollution can not be controlled in the short term , the incidence of lung cancer continues to increase , especially in females.2,3 in brazil , the estimate for 2010 is approximately 18 new cases per 100 000 men and 10 per 100 000 women , corresponding to 17 800 and 9 930 new cases of lung cancer among men and women respectively.4 advances in lung cancer therapy have been improving survival rates , although the prognosis remains poor . the 5year survival rate is around 15% in developed countries1 and 10% in brazil.4 therefore , the impact of both disease and treatment on the health and psychosocial functioning of these patients should be considered.5 in this context , quality of life assessment and the analysis of the main symptoms that lead to functional capacity limitation have become issues of utmost importance in the evaluation of lung cancer patients . however , in brazil , there are few studies that evaluate this aspect of the disease , mainly because of the lack of specific tools adapted to and reproducible for the brazilian portuguese language . several instruments are currently used to evaluate the quality of life in patients with lung cancer . the functional assessment of cancer therapylung ( factl ) was generated by the functional assessment of chronic illness therapy ( facit ) group . it is a specific , multidimensional questionnaire widely used in clinical studies.6 - 9 moreover , the factlung symptom index ( flsi ) , which is a brief measure involving five common symptoms in lung cancer patients , can be applied in combination with the factl or alone . although the factl is currently used in brazil , mainly in international multicenter trails , there is no study assessing the reliability of this questionnaire in the brazilian portuguese language . therefore , the purpose of this study was to evaluate the reproducibility of the factl and the flsi for brazilian lung cancer patients . a convenience sample comprising 30 patients with lung cancer was recruited from the outpatient lung cancer clinic of the so paulo hospital federal university of so paulo . this study was approved by the institutional review board of our center , and a term of informed consent was signed by all patients . the following inclusion criteria were used : histologically proven lung cancer ; 18 years of age or older ; a minimum score of 21 on the mini mental state examination ( mmse);10,11 out of chemotherapy / radiotherapy treatment ; and clinical stability during the study and at least 10 days before the beginning of the evaluations . clinical stability was defined as the absence of change in cough , sputum , and dyspnea , assessed by a structured form filled out during outpatient followup , and no hospitalizations or modifications in the therapeutic regimen . the sample size was based on previous reliability studies of other quality of life questionnaires related to respiratory diseases in brazil.1215 clinical evaluation and physical examination were performed by a team of physicians , based on a structured form . the drug regimen used by the patients remained unchanged during the 15day interval between questionnaire applications . in the first visit , the following independent variables were collected : gender ( male and female proportion ) , age ( in years ) , history of tobacco use ( yes or no ) and consumption ( pack years ) , histologic subtypes ( adenocarcinoma , squamous cell , small cell lung cancer and others),16 staging according to the 1997 tnm classification for nonsmall cell lung cancer ( nsclc ) patients ( stratified from ia to iiia and from iiib to iv),17 karnofsky performance status ( kps),18 spirometry ( forced expiratory volume in the first second ( fev1 ) and forced vital capacity ( fvc ) percentage of predicted and fev1/fvc percentage),19 mmse , and factl and flsi scores.9 the portuguese version of the factl and flsi was released for use by the facit group ( the developer of the questionnaire ) . the translation into brazilian portuguese , back translation and review by an expert committee to access the semantic , conceptual , idiomatic , cultural and metabolic equivalences were previously done by that group.20,21 the factl , version 4 , is a combination of the 27item factgeneral ( factg ) and the 9item lung cancer subscale ( lcs ) . a total factg score is calculated by summing the physical wellbeing ( pwb ) , social / family wellbeing ( swb ) , emotional wellbeing ( ewb ) , and functional wellbeing ( fwb ) subscale scores , with a score ranging from 0 to 108 . a total factl score is obtained by summing the factg score with the lcs ( two of the nine items are not scored ) . the factl score ranges from 0 to 136.6 the factl trial outcome index ( factl toi ) is , a priori , an index that sums the pwb , fwb , and lcs into a 21item scale . its score ranges from 0 to 84.6 the flsi is a symptom index with six questions regarding the five most frequent symptoms reported by lung cancer patients , especially in the advanced stages : dyspnea , fatigue , pain , weight loss , and coughing . the score on each aspect of the factl and flsi is obtained according to the option chosen by the patient . , a little bit , somewhat , quite a bit , or very much . the higher the score obtained by each patient in question , the greater the final score of the subscale and the better the quality of life . however , these scores have a nonlinear behavior . patients answered the questionnaire after being read each question , all by the same interviewer . the questionnaires were reviewed at the end of the interview to avoid any missed questions . the response time was timed in the two visits . all doubts expressed by patients during the questionnaire patients were also asked not only about what they felt in terms of question content , but also about the length of the questionnaire . the test the scores obtained on different scales and subscales of factg were compared with reference values established by the facit group.22 for this comparison , we used the minimal clinically significant difference , determined by the same group.6 variables were expressed as mean and standard deviation . the intraclass correlation coefficient ( icc ) and kappa reliability coefficient were calculated to assess the reliability of the questionnaire and questions respectively . to compare the two groups , we used the chisquare test for categorical variables , t test for parametric continuous variables , and mann whitney test for nonparametric continuous variables . for the correlations between spirometry and questionnaire scores , the spearman 's correlation coefficient was used . the intraclass correlation coefficient ( icc ) and kappa reliability coefficient were calculated to assess the reliability of the questionnaire and questions respectively . to compare the two groups , we used the chisquare test for categorical variables , t test for parametric continuous variables , and mann whitney test for nonparametric continuous variables . for the correlations between spirometry and questionnaire scores , the spearman 's correlation coefficient was used . the main characteristics of the 30 patients who completed the study are shown in table 1 . there was no statistically significant difference between genders regarding age , kps , spirometry , staging , and histological type . among patients who never smoked , there was a prevalence of smoking habits in males ( p = 0.04 ) , with a higher tobacco smoke load for men than for women , consuming a mean of 53.2 pack years ( sd = 31.6 ) and 29.6 pack years ( sd = 25.5 ) respectively ( p = 0.02 ) . eight patients ( 26.7% ) were diagnosed with chronic obstructive pulmonary disease ( copd ) , according to the gold guideline.23 the mean values for each scale of the factl and flsi are illustrated in table 2 . the intraclass correlation coefficient values for the different scales of the factl and flsi showed excellent correlations ( table 2 ) . the kappa coefficient was used to test question reliability , which was less than 0.4 on questions gp1 , gp5 ( pwb ) , gs3 , gs4 , gs5 ( swb ) , gf1 , gf2 , gf3 , gf5 , gf6 ( fwb ) , and lcl4 ( lcs ) . as for the flsi , the kappa coefficient was moderate on question b1 . in the other questions , the kappa coefficient was less than 0.4 . the mean score of the factg scales was similar to the reference values for all scales that have these values established.22 table 3 shows the mean values for the scales of factg and factl described in several studies of reliability and cultural adaptation into other languages . the time spent by patients in answering the questionnaire the response time on the second application was significantly lower ( p = 0.001 ) . the focus of this study was to analyze the reliability of the factl and the flsi , a specific instrument for assessing the quality of life of lung cancer patients in the brazilian population . the factl is an instrument that has been widely used in phase i , ii , and iii clinical trials . it has been translated and adapted into several languages and cultures.2,3,7,22,2427 a feature of this instrument is the nonlinearity of the scores of its scales , a factor that complicates the interpretation of isolated study data . to facilitate the explanation of the results , the authors of the general questionnaire ( factg ) have developed normative values from two reference groups , one from normal adults and another from adults with cancer in general.22 however , these normative values are only for the general questionnaire ( factg ) and its scales . when comparing the results obtained in our study with the reference values , we observe that the score was similar in all scales and for the total value . a possible explanation for the fact that our patients have quality of life similar to patients with other cancer types is that , in the study for the establishment of benchmarks , besides including patients with various types of cancer , such as breast cancer , colon and rectum cancer , and cancer of the head and neck , they also included patients with lung cancer . furthermore , 76.7% of the sample comprised patients treated and in remission from the underlying disease and , therefore , with better quality of life . when our factl results are compared with those from other studies using the same questionnaire , we find that there is great variability between countries and different cultures,2,3,7,22,2427 which may be due to differing perceptions of the questions according to each culture and also differences in patient characteristics , such as staging , age , socioeconomic status , among others . the flsi is an index designed to identify the presence of the major symptoms related to lung cancer , including dyspnea , pain , fatigue , cough , and weight loss.28 these symptoms can negatively influence quality of life . in this study , in addition to the medical evaluation , flsi was also used to assess the patient 's clinical stability . the reliability for all scores of the factl showed icc values greater than 0.75 , ranging from 0.78 ( swb ) to 0.96 ( factl toi ) . these values show excellent reliability and are similar to those found in other studies . in the validation study of the korean version of the factl,25 the icc ranged from 0.52 to 0.84 . the chinese version3 varied from 0.76 to 0.82 . in the reliability study of the original version , the icc ranged from 0.56 ( swb ) to 0.89 ( factl toi).7 the flsi also showed high reliability , which confirms the stability of the sample . most of the factl questions showed adequate reliability , analyzed by the kappa coefficient . in this study , the reliability analyses were conducted with a convenience sample similar to other studies evaluating the reliability and cultural adaptation of other questionnaires to the portuguese language.1215 in our sample , males predominated , in agreement with the worldwide prevalence of lung cancer.1 the mean age was 61.3 years , which is consistent with most studies that include patients with lung cancer.1,5 regarding histological type , adenocarcinoma was the most prevalent , consistent with several epidemiological studies in developed countries.1 unfortunately , regarding staging , there was a predominance of stage iii and iv , stages with less chance of survival after treatment.29 the mean fev1 ( % predicted ) and fev1/fvc ratio in our study were similar to the results reported by young et al . , who observed a fev1 ( % predicted ) mean of 73% and fev1/fvc mean of 64% in smokers with lung cancer.30 in our study , there was no correlation between the questionnaire and the analyzed lung function parameters , consistent with other studies that found no significant correlation when investigating the effects of altered pulmonary function on the quality of life of cancer patients.31,32 the process of translating the factl questionnaire and flsi into the portuguese language ( brazil ) was performed by the facit group . only a few doubts were reported by the patients , which warrants its use in the current form . few patients had difficulty in interpreting the word muitssimo ; however , many of the patients interviewed understood the meaning of the term not because it is a familiar word , but because they realized that it was a scale with a progressive score in which the numerical value assigned to the word muitssimo alterations to this tool were proposed only for question q1 independentemente do seu nvel a(c)tual de a(c)tividade sexual , favor de responder pergunta a seguir . se preferir no responder , assinale o quadrculo e passe para a prxima seo . despite not raising doubts , the words atual and atividade do not require the letter ( c ) , and there is no need to use the preposition we conclude that the brazilian version of the factl questionnaire and flsi is reproducible , fast , and of simple application , and that they are capable of measuring the quality of life in lung cancer patients in brazil .

objectives : the purpose of this study was to assess the reliability of the brazilian version of the functional assessment of cancer therapylung ( factl ) with the factlung symptom index ( flsi ) questionnaire.introduction:the assessment of quality of life in patients with lung cancer has become an important evaluative endpoint in current clinical trials . for lung cancer patients , one of the most common quality of life tools available is the factl . despite the amount of data available regarding this questionnaire , there are no data on its performance in brazilian lung cancer patients.methods:the factl with the flsi questionnaire was prospectively administered to 30 consecutive , stable , lung cancer outpatients at baseline and at 2 weeks.results:the intraclass correlation coefficient between test and retest for the factl ranged from 0.79 to 0.96 and for the flsi was 0.87 . there was no correlation between these questionnaire dimensions and clinical or functional parameters.conclusions:the brazilian version of the factl with flsi questionnaire is reliable and is quick and simple to apply . this instrument can now be used to properly evaluate the quality of life of brazilian lung cancer patients .