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to determine the prevalence of infection in adults and children , cultures were performed by standard techniques on fecal samples from several groups of adults and children , all residents of lusaka , the capital of zambia . group a was 124 adults and 105 children , all hiv - seropositive patients with persistent diarrhea , studied from 1995 to 1999 during three clinical trials of antiprotozoal or nutritional therapies . the average number of samples tested was 2.1 for each adult and 2.8 for each child . group b was 216 adults enrolled in a longitudinal study of intestinal infection in a cohort of adults in a representative urban community in lusaka ; this group was studied to provide an estimate of asymptomatic carriage rates . to define the profile of antimicrobial sensitivity , isolates from group a were analyzed together with additional isolates of nontyphoidal salmonellae , shigella dysenteriae , and s. flexneri from a third source ( group c ) : routine stool or blood cultures from aids patients in the university teaching hospital from 1995 to 1999 . all isolates were cultured and tested for antimicrobial susceptibility by using standard antimicrobial discs ( oxoid ltd , basingstoke , uk ) on mueller - hinton agar . zones of growth inhibition were compared with standard tables ( 4 ) , and control organisms of known sensitivity were tested beside clinical isolates for verification . of 124 adults with persistent diarrhea in group a , 6 ( 5% ) were infected with nontyphoidal salmonella spp . and 9 ( 7% ) with s. flexneri or s. dysenteriae . of 105 children with persistent diarrhea , also in group a , 21 ( 20% ) were infected with nontyphoidal salmonella spp . and 3 ( 3% ) with s. flexneri or s. dysenteriae . in group b , 7 ( 4% ) of 174 adults had one or more fecal samples positive for nontyphoidal salmonella spp . in one year ( 1999 ) , and 10 ( 6% ) had one or more positive for s. flexneri or s. dysenteriae . as each adult submitted samples approximately monthly ( for a total of 1,440 samples ) , the point prevalence in these asymptomatic adults was < 1% for either infection . studies of patients with hiv - related persistent diarrhea in other countries in africa have found the prevalence of enterobacterial infection to be higher . in rwanda and kenya , prevalences of nontyphoidal salmonellae were 11% and 16% , respectively , and of shigellae were 22% and 4% , respectively ( 5,6 ) . in recent years , hiv seroprevalence in lusaka has been estimated to be 22% to 30% ( 7 ) , and the overall rate of hiv - related diarrhea is high ( 8) . antimicrobial sensitivity patterns indicate that resistance is a substantial problem among enterobacteria in lusaka ( table ) . the isolates we tested came from a tertiary hospital , which may have resulted in some selection bias , as treatment failures may be overrepresented in such patients . however , only a few bacteria tested were sensitive to sxt , in marked contrast to data from west africa and more closely resembling the situation in malawi ( 3 ) . this level of resistance may compromise the usefulness of sxt in preventing bacterial infection in hiv - infected persons , although any effect in preventing pneumocystis carinii pneumonia or isosporiasis would be valuable . emergence of resistance to sxt was noted in san francisco after its widespread use as prophylaxis against pneumocystosis ( 9 ) . for treatment of infection with these enterobacteria in zambia , affordable parenteral antimicrobial agents for the efficient treatment of septicemic infection in hospitals and health centers is likely to be difficult . as clinical response sometimes occurs even when susceptibility testing in vitro suggests that the antimicrobial agent used is ineffective , controlled clinical trials are needed for these infections in different geographic regions of africa . 158 isolates of nontyphoidal salmonellae , 31 isolates of s. flexneri , and 19 isolates of s. dysenteriae were tested against all these antimicrobial agents except for azithromycin , against which 69 , 9 , and 19 isolates were tested respectively . antimicrobial sensitivity appeared to decrease from 1995 to 1999 , when these isolates were being collected . for example , over this period gentamicin resistance increased from 0% to 32% in s. flexneri and from 0% to 34% in nontyphoidal salmonellae ( p<0.001 ) . in s. flexneri , cefuroxime resistance increased from 22% to 88% and cephalexin resistance from 18% to 42% over the same period ( p = 0.001 ) . the scale of use of cephalosporins in the community did not suggest that selection pressure for resistance was likely to be high . mechanisms of resistance to cephalosporins include reduced permeability and modification of penicillin - binding protein , and emergence appears to be rapid . the most reliable results are likely to be obtained with fluoroquinolones or azithromycin , but these are expensive and their availability is limited . gentamicin or chloramphenicol are less expensive and would be acceptable alternatives , although the probability of adverse effects is greater . unfortunately , few antimicrobial compounds that are likely to be effective and affordable could also be given easily and safely to aids patients in primary and secondary care settings in zambia . as the epidemic in zambia enters its third decade , the situation is likely to worsen if no action is taken . we have been able to reduce antimicrobial resistance in vibrio cholerae by instituting a policy of rotating the recommended antimicrobial agents during epidemics , thereby prolonging the useful life of affordable antimicrobial agents ( j. mwansa , unpub . we are also considering clinical trials with combinations of antimicrobial drugs to treat these clinical syndromes in aids patients . as antimicrobial sensitivity patterns seem to vary across africa , it may be difficult to generalize the results of clinical trials from one part of the continent to another .

enterobacteria contribute to two serious clinical syndromes seen in african aids patients : diarrhea and septicemia . in west africa , prophylaxis with sulfamethoxazole - trimethoprim ( sxt ) reduced illnesses . we report reduced sensitivity of enterobacteria to available antimicrobial agents in zambia , with only 22% of nontyphoidal salmonellae and 6% of shigellae sensitive to sxt .

to obtain the representative whole - genome transcriptome sequencing data , sample preparation is one of the critical steps in this study . firstly , as to the dosage of mo injected in the zebrafish embryos , we compared different dosages of rpl11 mo , together with control mo , which has a few nucleotide mutations , to reduce the non - specific effects of rpl11 mo . 0.5 ng mo / each embryo was found to be sufficient to completely inhibit gfp - rpl11 fusion gene expression . secondly , as to the generated rpl11-knockdown zebrafish embryos , we observed the obvious hematopoietic defects of rpl11-deficient zebrafish embryos as early as the start of hematopoietic 48 hpf by comparing with that of mo ctrl . at this stage , thirdly , to increase the reproducibility of the experimental results , we selected about 4050 zebrafish embryos from at least three experiments and mixed them together to obtain the representative biological repeat . this strategy was also used in previous high - throughput sequencing studies , . to obtain the representative data , the manipulations for two samples of rpl11 mo and control mo , including rna extraction , mrna - library construction ( illumina mrna - seq library preparation kit ) and sequencing on the high - seq 2000 platform , paired - end sequencing mode ( 2 100 bp ) was employed to match more accurately the reference genome sequence and improve sequencing efficiency . moreover , pair - end sequencing data has more biologically analytical options including alternative splicing analysis . in this study , 46 g of sequencing data the present sequencing data was completely saturated and sufficient for subsequent analysis ( fig . 1 ) . the collected transcriptome sequencing data was mapped to the latest version of the zebrafish genome ( zv9 ) . more than 10,000 gene transcripts were mapped to known zebrafish genes , which is similar to previous studies , . to reduce the background from sequencing , genes with fpkm less than 1 were removed from analyses . differentially expressed genes ( degs ) were identified as per the criterion of fold change > 2.0 and p - value < 0.05 ( fig . 2 ) . the identified up - regulated ( 89 ) and down - regulated ( 483 ) degs were used for subsequent bioinformatic analysis , including characterization of the affected hematopoietic genes , perturbed molecular networks and signaling pathways . 75% of zebrafish genes have the homologue in the human genes , and the majority of human genes in zebrafish have the corresponding functions . however , ipa software has not been available for zebrafish gene analysis , therefore , in this study we converted the zebrafish gene to the human gene and analyzed by ipa in order to assess the impacts of rpl11 deficiency on human dba pathogenesis using zebrafish model . to assess the quality of rna - seq sequencing data , we selected some critical genes associated with hematopoiesis and evaluated their gene expression by qpcr analysis . the samples used for qpcr evaluation were from a batch of freshly prepared zebrafish embryo samples with rpl11 mo and control mo . each qpcr experiment was repeated 3 times to represent the true gene expression level . as shown in fig . 3 , the correlation between rna - seq and qpcr results has a good correlation coefficient of 93.7% , indicating that we obtained a representative dataset of transcripts expressed in zebrafish rpl11 mo and control embryos . to obtain the representative whole - genome transcriptome sequencing data , sample preparation is one of the critical steps in this study . firstly , as to the dosage of mo injected in the zebrafish embryos , we compared different dosages of rpl11 mo , together with control mo , which has a few nucleotide mutations , to reduce the non - specific effects of rpl11 mo . 0.5 ng mo / each embryo was found to be sufficient to completely inhibit gfp - rpl11 fusion gene expression . secondly , as to the generated rpl11-knockdown zebrafish embryos , we observed the obvious hematopoietic defects of rpl11-deficient zebrafish embryos as early as the start of hematopoietic 48 hpf by comparing with that of mo ctrl . at this stage , thirdly , to increase the reproducibility of the experimental results , we selected about 4050 zebrafish embryos from at least three experiments and mixed them together to obtain the representative biological repeat . to obtain the representative data , the manipulations for two samples of rpl11 mo and control mo , including rna extraction , mrna - library construction ( illumina mrna - seq library preparation kit ) and sequencing on the high - seq 2000 platform , were carried out in parallel completely . paired - end sequencing mode ( 2 100 bp ) was employed to match more accurately the reference genome sequence and improve sequencing efficiency . moreover , pair - end sequencing data has more biologically analytical options including alternative splicing analysis . in this study , 46 g of sequencing data the present sequencing data was completely saturated and sufficient for subsequent analysis ( fig . 1 ) . the collected transcriptome sequencing data was mapped to the latest version of the zebrafish genome ( zv9 ) . more than 10,000 gene transcripts were mapped to known zebrafish genes , which is similar to previous studies , . to reduce the background from sequencing , genes with fpkm less than 1 were removed from analyses . differentially expressed genes ( degs ) were identified as per the criterion of fold change > 2.0 and p - value < 0.05 ( fig . 2 ) . the identified up - regulated ( 89 ) and down - regulated ( 483 ) degs were used for subsequent bioinformatic analysis , including characterization of the affected hematopoietic genes , perturbed molecular networks and signaling pathways . 75% of zebrafish genes have the homologue in the human genes , and the majority of human genes in zebrafish have the corresponding functions . however , ipa software has not been available for zebrafish gene analysis , therefore , in this study we converted the zebrafish gene to the human gene and analyzed by ipa in order to assess the impacts of rpl11 deficiency on human dba pathogenesis using zebrafish model . to assess the quality of rna - seq sequencing data , we selected some critical genes associated with hematopoiesis and evaluated their gene expression by qpcr analysis . the samples used for qpcr evaluation were from a batch of freshly prepared zebrafish embryo samples with rpl11 mo and control mo . each qpcr experiment was repeated 3 times to represent the true gene expression level . as shown in fig . 3 , the correlation between rna - seq and qpcr results has a good correlation coefficient of 93.7% , indicating that we obtained a representative dataset of transcripts expressed in zebrafish rpl11 mo and control embryos .

to comprehensively reflect the roles of rpl11 on the transcriptome of zebrafish model of diamond - blackfan anemia ( dba ) , we performed whole - genome transcriptome sequencing on the illumina hi - seq 2000 sequencing platform . two different transcriptomes of zebrafish rpl11-deficient and control morpholino ( mo ) embryos were collected and analyzed . the experimental design and methods , including sample preparation , rna - seq data evaluation and treatment , were described in details so that representative high - throughput sequencing data were acquired for assessing the actual impacts of rpl11 on zebrafish embryos . we provided the accession number gse51326 for easy access to the database .

cryoglobulins are special serum immunoglobulin 's that usually precipitate at a temperature between 0c and 4c and dissolve when re - warmed to 37c . this in vitro phenomenon can be observed in a wide spectrum of infectious diseases , autoimmune disorders and with hematological malignancies . both type i and type ii are associated with lymphoproliferative disorders . during the winters in the north india temperature such cold weather is likely to produce cold - induced symptoms in patients with cryoglobulinemia . as very low temperature is unusual in indian subcontinent , cases of cryoglobulinemia are usually remains symptomless and hence undetected . we encountered an interesting case of cryoglobulinemia in a 68-year - old - male who presented with cryoglobulinemic manifestations for the last 18 months . a 68-year - old male patient who was chronic alcoholic presented with complain of headache on and off for the last 18 months before presenting to us in september 2011 . , there was hepatomegaly ( 3 cm below costal margin ) and splenomegaly ( 2 cm below costal margin ) however no palpable lymph nodes are noted . in the past history however , he was not able to get any report since his sample clotted soon after sampling . although , phlebotomist had taken the venous blood sample but it clots itself even in the presence of anticoagulants . following this , patient was called on the next day and sampling was done by maintaining the whole set up temperature at 37c and above . serological investigations for hepatitis b virus , hepatitis c virus , and human immunodeficiency virus infection were performed to exclude any viral infection and no associated infective etiology was found . serum sample for detection of antibodies ( rheumatoid factor , antinuclear antibodies , smooth muscle antibody , anti - mitochondrial antibody ) for any underlying autoimmune disorder was sent for however all the tests came negative . the hemogram showed bicytopenia with hemoglobin of 3.9/dl and total leucocyte count of 2.9 10/l . the marrow was cellular and clotted ; however showed the presence of homogenous pale pink background due to the presence of cryoglobulins [ figure 1b ] . differential nucleated cell count showed extensive increase in lymphocytes ( 73% ) along with plasma cells ( 8% ) [ figure 1c ] . the sinusoids were dilated and are filled with pale eosinophillic material ( cryoglobulins ) [ figure 1d ] . immunophenotying was performed on bone marrow sample and that showed expression of cd19 , cd79b along with heterogeneous expression of cd23 [ figure 2 ] . serum protein electrophoresis showed the presence of sharp m band in the gamma region , hence proving monoclonality of disease . on the basis of peripheral blood , bone marrow and flowcytometry findings a diagnosis of lymphoplasmacytic lymphoma was made . the patient was started on prednisolone 1 mg / kg / day and was asked to report weekly . the patient is now in follow - up and show improvement in their symptoms and easy sampling of blood . peripheral blood shows rouleaux formation ( mgg - giemsa , 400 ) ( a ) . bone marrow aspirate shows presence of pink homogenous material due to cryoglobulins ( mgg - giemsa , 200 ) ( b ) . high power view demonstrates increase in numbers of lymphocytes and plasma cells ( mgg - giemsa , 1000 ) ( c ) . dilated sinusoids filled with pale eosinophillic material are seen on trephine biopsy section ( h and e , 100 ) ( d ) panel of scatter plots showing the multicolor immunophenotyping of bone marrow aspirate sample by flow cytometry . the gating of cells in each tube has been done on side scatter - a ( ssc - a ) versus forward scatter - a ( fsc - a ) ( a ) . the cell is lymphoid region p1 were subsequently gated in ssc - a versus cd19 plot with the gated p2 population showing surface cd19 expression ( b ) . the gated cells show heterogeneous expression of cd23 along with homogeneous expression of cd79b ( c and d ) cryoglobulins are proteins that can precipitate at low temperatures ( < 4c ) and dissolve when re - warmed to 37c . the cryoglobulin can be defined on the basis of its composition : polyclonal or monoclonal immunoglobulins ; or the presence of rheumatoid activity ( ra ) . three types of cryoglobulinemia have been identified namely : type i includes monoclonal cryoglobulins ( igm , igg and iga ) without any ra ; type ii includes a monoclonal component ( usually igm with ra ) and a polyclonal component ( usually igm / igg ) ; type iii have several polyclonal components and a component with ra ( usually igg / igm ) . type ii and type iii are classically referred to as mixed cryoglobulinemia . in general , cryoglobulinemia regardless of their type are associated with skin manifestations , but may also cause rheumatologic symptoms that involve the kidneys , the peripheral nerves or central nervous system , the lungs , the myocardium and the gastrointestinal tract . interesting type i cryoglobulinemia is associated with low grade lymphoproliferative disorders such as multiple myeloma , waldenstrom macroglobulinemia , chronic lymphatic leukemia and account for 10 - 15% of all cases of cryoglobulinemia . type ii cryoglobulinemia is associated not only with lymphoproliferative diseases but also with autoimmune disorders and infective etiologies especially hepatitis . this case is also having lymphoplasmacytic lymphoma and hence can be categorized in to type i cryoglobulinemia . in tropical and subtropical countries like india where the winter is either nonexistent or very brief , most of the patient with cryoglobulinemia did not show any symptoms and remain undetected . in this case , difficulty in processing of sample raises the suspicion of disease which was confirmed by bone marrow examination and by exclusion of other autoimmune etiology along with infective pathology . the diagnosis of lymphoplasmacytic lymphoma on bone marrow aspiration solves the underlying pathogenesis of the cryoglobulinemia . we presented a case of cryoglobulinemia which is very rare in indian subcontinent and was suspected due to the problem in sampling and processing of the blood .

cryoglobulinemias rarely been reported from india even though associated conditions such as hepatitis c infection , rheumatoid arthritis and plasma cell dyscrasias , etc . , are common occurrences . in many regions of the country , temperatures in winter can be conducive to the precipitation of cryoglobulins , yet epidemiology of the disease suggests that it is a common condition in the west . we encountered a 68-year - old - male patient who presented with a history of headache off and on along with hepatosplenomegaly . the rare occurrence of cryoglobulinemia in our setting can delay the diagnosis , as happened in our case , since the index of suspicion of clinicians and laboratory personnel is low . we are reporting this case because of the rarity and protean clinical manifestations of cryoglobulinemia .

commercial products are often available in dark grey powder or pellets . it is generally misused intentionally for suicidal purpose and accounts for about 2.6% of the mortality due to poisonings in an iranian report . it is proposed that after ingestion of metal phosphides , phosphine ( ph3 ) , the active ingredient , will release on contact with moisture or hydrochloric acid in the stomach . however , some doubts made recently because of the unique presentations after zn2p3 poisoning , and a novel idea of liberation and absorption of ph3 via luminal tract was formed . an 18-year - old male presented to emergency department approximately 5 h after consumption of about 20 g of zn2p3 . on arrival , he was conscious but irritable , with pulse rate of 85/min , blood pressure ( bp ) of 120/75 mmhg , respiratory rate of 14/min , and temperature of 37.2c . the first venous blood gas ( vbg ) analysis was normal . per abdominal examination revealed normal . an intravenous access was established and monitoring with electrocardiogram ( ecg ) , bp , and pulse oximetry . the first episode of defecation occurred after an hour . despite three - time of defecation , control abdominal x - ray 6 h later showed a considerable amount of the radiopaque material at the end of the transverse colon at the splenic flexure . hence , 60 cc of castor oil was prescribed for the patient twice within the next 6 h. afterward , a repeat abdominal x - ray was clear . during this period , although the first and second vbgs were normal , the third vbg components revealed a slight metabolic acidosis ( ph = 7.34 , pco2 = 30.1 mm hg , hco3 = 16.2 meq / l ) , which was recovered to normal levels after the decontamination of luminal tract , without administration of alkalization agents . afterward , the ph and bicarbonate levels remained stable , indicating that the patient did not develop severe systemic toxicity . in the 2 day of admission , the patient developed mild coagulopathy ( prothrombin time : 18 s , partial thromboplastin time : 32 s , and international normalized ratio of 2.15 ) , as well as marked aminotransferase elevations ( aspartate aminotransferase ( ast ) : 68 iu / l , alanine aminotransferase ( alt ) : 37 after 2 days his coagulation tests were normal , however , his liver function tests ( lfts ) components changed to ast : 69 iu / l and alt : 92 iu / l . hence , he discharged with silymarin 70 mg three times a day for 2 weeks and psychology outpatient follow - up . however , authors generally believe that liberation of ph3 gas in the stomach is responsible for causing symptoms , the clinical manifestation of aluminum and zn2p3 poisonings are not usually similar . the most important dissimilarities are the relatively long time interval between ingestion of zn2p3 and presentation of its systemic toxicity as well as the progression of acute liver failure during the 1 week , exclusively in the case of zn2p3 poisoning . hence , an innovative report disproved the current belief of ph3 liberation after contact of zn2p3 and gastric contents . it intended that phosphonium ( ph4 ) , as an intermediate product will create and pass through the stomach , which then will reduce to produce ph3 in the luminal tract . however , the ph4 is not radiopaque , zinc , the potentially radiopaque ingredient is visible on abdominal radiography . recently , hassanian - moghaddam et al . suggested performing abdominal x - ray in the case of suspected zn2p3 poisoning , even if the patient is asymptomatic . we start castor oil to induce bowel movement . despite several episodes of defecation , a control abdominal x - ray 6 h later revealed residual radiopaque material in colon . however , the patient remained asymptomatic during the first 12 h of admission ; the third vbg components revealed a slight metabolic acidosis ; which was recovered to normal levels after the decontamination of luminal tract . as the determination of metabolic acidosis may reflect the severity of ph3 toxicity , we can argue forceful intestinal decontamination in this case could prevent more toxin absorption . however , hassanian - moghaddam et al . in their report administered polyethylene glycol to help the patient move toxin through his bowel , since it is a water - soluble product ; we use castor oil to prevent reduction of ph4 in the luminal tract . this approach was first proposed to prevent more ph3 liberation after ingestion of metal phosphides in shiraz , iran . reported that zn2p3 poisoning is the most common cause of drug / toxin - induced acute liver failure in india . however , we still do not know what the exact mechanism is , but in our case , development of coagulopathy and elevation of aminotransferase levels in the 2 day could be explained by direct toxic damage of ph3 to the liver , after being transported by the portal vein . in fact , based on the theory of ph4 reduction and ph3 absorption from the luminal tract , it just directly reaches to hepatic cells . hence , compared to other metal phosphides , acute liver dysfunction might be an exclusive presentation of zn2p3 poisoning . moreover , saraf et al . reported that higher doses may result in earlier onset of hepatotoxicity and acute liver failure . by the way , in our case , despite ingestion of large amounts of toxin , after forceful intestinal decontamination , this complication was provisional , and could not take the patient to a fatal outcome . however , there are many reports of fatal outcome due to cardiovascular collapse or hepatic failure ; it seems that we have more time to use decontamination techniques in the case of zn2p3 poisoning compared to other metal phosphides . in our case , we used castor oil to induce bowel movement with an aim of removing unabsorbed intermediate toxic product , the ph4 . however , the theory of production of ph4 is not unanimously accepted ; it could explain every fact in the case of zn2p3 poisoning . according to an article published in 2014 , more aggressive gastrointestinal decontamination is necessary in patients with positive radiography . we also strongly suggest following removal of the radiopaque material by repeated abdominal radiography to ensure complete decontamination .

zinc phosphide ( zn2p3 ) rodenticide , is generally misused intentionally for suicidal purpose in iran . for many years , scientists believe that liberation of phosphine ( ph3 ) on contact with acidic content of the stomach is responsible for clinical presentations . however , relatively long time interval between ingestion of zn2p3 and presentation of its systemic toxicity , and progression of acute liver failure could not be explained by the current opinion . hence , an innovative theory intended that phosphonium , as an intermediate product will create and pass through the stomach , which then will reduce to produce ph3 in the luminal tract . here , we present a case of massive zn2p3 poisoning . in our case , we used repeated doses of castor oil to induce bowel movement with an aim of removing unabsorbed toxin , which was proved by radiography . interestingly , the patient presents only mild symptoms of toxicity such as transient metabolic acidosis and hepatic dysfunction .

horner 's syndrome , along with weakness and atrophy of upper limb , as well as anaesthesia to pain and temperature , is well recognized finding in patients with syringomyelia . few cases have been reported regarding isolated horner 's syndrome as a presenting manifestation of a chiari i malformation with syringomyelia . we report a 41 year old man with left side hemi hidrosis probably a part of horner 's syndrome who was found to have a chiari i malformation with holocord syrinx . a 41-year - old man presented in medicine ward with a complaint of neck and back pain and loss of sweating in right side of the body that had begun eight months before . there was no history of hypertension , diabetes , and immunocompromised status . on examination whole left side of body including face was dry , there was no evidence of sweating [ figures 1 and 2 ] . this test is described as drawing a metal spoon across the surface of the skin after adequate physical exercise . neurological examination was unremarkable with no limb weakness , wasting or numbness and temperature impairment on the side of anhidrosis . this was done to rule out any mass in the upper lobe of the lung which may present as horner syndrome . mri spine was performed which showed hyperintense signal ( red arrow head ) in t2-weighted sections extending whole spinal cord up to eighth thoracic cord level with herniation of cerebellar tonsil ( blue arrow head ) compatible with syringomyelia along with chiari i malformation [ figure 3 ] . dry left nipple with anhyrosis holocord syrinx up to 8 spinal cord level ( red arrow head ) , herniation of cerebellar tonsil ( blue arrow head ) syringomyelia is the development of a fluid - filled cavity or syrinx within the spinal cord . more than half of all cases are associated with chiari type 1 malformations in which the cerebellar tonsils protrude through the foramen magnum and into the cervical spinal canal . it may occur after a trauma , secondary to a tumor , craniocervical or intracerebral pathology or idiopathic . fibers originating in the cerebral cortex traverse the hypothalamus , and then cross in the medulla to the lateral horn of the spinal cord . these fibers leave the spinal cord to synapse in the sympathetic ganglia with neurons that innervate the sweat glands . thus , a cortical lesion will cause contralateral anhidrosis , a lesion in the medulla could result in contralateral or ipsilateral anhidrosis , and any lesion distal to the medulla will cause ipsilateral anhidrosis . slowly progressive tissue damage around the syrinx reaches the lateral horn , it will segmentally affect the sympathetic preganglionic neurons or adjacent structures . search for publications dealing with anhidrosis in syringomyelia there was lack of information regarding this . in our case probable hypothesis may be hypo activity due to autonomic disturbances because of progressive and irreversible damage to the sympathetic preganglionic neurons due to expanding syrinx . physicians should be aware of the different ways in which syringomyelia can present to ensure its early diagnosis . anhidrosis of the face and upper part of the body , segmental anhidrosis is reported in horner syndrome and syringomyelia but hemi hidrosis of the whole boy was unique in this case .

we present a 41-year - old man with chiari type 1 malformation and syrinx up to tenth thoracic level who presented with left side hemi anhidrosis . neurological findings of syrinx were absent in this case . though horner 's syndrome is reported , this report is probably first .

when present in an untreated pregnant woman , it may lead to series of miscarriage , preterm delivery , still birth , low birth weight and normal child , ( known as kassowitz law ) . it is divided into three categories : ( 1 ) early , ( 2 ) late , and ( 3 ) stigmata . here , we report a case of late congenital syphilis presenting as palatal perforation and saddle nose deformity , also fulfilling the kassowitz law . a 9 year - old girl , born as the fourth child to non - consanguineous parents , was reported to our department with perforation of palate for routine venereal disease research laboratory ( vdrl ) screening from the ent department . the patient had history of regurgitation of food and change of voice for the past 6 months . there was no history of trauma , loss of weight , skin lesions or fever . physical examination revealed saddle nose deformity [ figure 1 ] and perforation of hard palate [ figure 2 ] . vdrl was reactive in 1:8 dilutions and was later confirmed with treponema pallidum hemagglutination ( tpha ) . patient with saddle nose deformity intra - oral photograph of the patient showing perforation of palate her parents and siblings ( one elder and two younger ) were screened for syphilis . parents were vdrl reactive in 1:4 dilutions , elder sibling ( female , 11 years old ) was vdrl reactive in 1:8 dilutions and all were confirmed with tpha . patient 's father gave a history of unprotected , premarital sexual contact , with an unknown female , 14 years back . three weeks later he developed a genital ulcer for which he was treated and the ulcer healed without any scar . her first male baby was delivered 12 years back which died on the same day because of seizures . the second female baby was delivered 2 years later which also died on the 10 th day due to low birth weight . her third female child ( 11 years old ) is the elder sibling of the patient , who had non - development of upper central incisors [ figure 3 ] . elder sibling of the patient showing absent upper central incisors pedigree chart showing the deceased children at day 1 and day 10 respectively , elder sibling , patient and normal children routine blood investigations , cerebrospinal fluid ( csf ) analysis , mantoux test , chest x - ray , x - ray skull and long bones were normal for the patient . computed tomography ( ct ) scan of paranasal sinus ( pns ) showed perforation of palate [ figure 5 ] with bilateral maxillary and nasal polyps [ figure 6 ] . her parents refused for biopsy of polyps . from the above history , clinical examination and investigations , diagnosis of late congenital syphilis with stigmata was made . the patient was treated with injection benzathaine penicillin 50,000 international units / kg body weight , deep intramuscular , once weekly , for 3 weeks , after test dose . the elder sibling and parents were also treated with injection benzathaine penicillin 24 lakh international units , once weekly , for 3 weeks . ct pns showing the perforation of right side of hard palate ct pns showing the bilateral maxillary and nasal polyps in india , the incidence of congenital syphilis is reported to vary from 0.18 to 1.4% . early congenital syphilis refers to individuals with syphilis from the first 2 years of life . the lesions of early congenital syphilis are infectious and it could be compared to the secondary stage of acquired syphilis . late congenital syphilis refers to the individuals with syphilis from the age of 2 to 30 years . in most of the cases , clinical features may present as interstitial keratitis , eighth nerve deafness or clutton 's joints . stigmata resulting from early congenital syphilis are saddle nose deformity , hutchinson 's teeth , rhagades , choroid scarring and onychia . stigmata due to late congenital syphilis are perforation of palate , corneal opacities , optic atrophy and periosteal changes of tibia . the transmission of infection to the fetus can occur at any time , but in most of the cases it occurs in utero . once the infection enters the fetal circulation , dissemination occurs to all the tissues and elicits an inflammatory response of lymphocytes and plasma cells . if the infection is not severe , it may interfere with normal development at various stages of intra- uterine and extra- uterine life . certain manifestations like interstitial keratitis and clutton 's joints are due to hypersensitivity and not because of the direct effects of the organism . in our patient the perforation of palate was due to chronic necrosis by the localized gumma . also , the edges of palatal perforation were regular which rules out the traumatic cause . the saddle nose deformity was due to the failure of development of nasal bones . in the elder sibling the infection had affected the development of middle and lateral denticles , resulting in absence of upper central incisors . out of series of six deliveries , the patient 's mother had perinatal death , neonatal death , two affected children , followed by two normal children . congenital syphilis could be treated either by penicillin or erythromycin , but the drug of choice is penicillin for which resistance has not been confirmed .

late congenital syphilis refers to the people with syphilis from the age of 2 to 30 years . we report a case of late congenital syphilis in a 9 year old girl with perforation of palate and saddle nose deformity . kassowitz law was also observed ( if a woman with untreated syphilis has series of pregnancies , the likelihood of infection of the fetus in later pregnancies becomes less ) . venereal disease research laboratory ( vdrl ) and treponema pallidum hemagglutination ( tpha ) were reactive . computed tomography ( ct ) scan of paranasal sinus showed maxillary and nasal polyps . the case reported here is a rare presentation of late congenital syphilis with perforation of palate and saddle nose deformity .

although drug - eluting stents ( des ) have significantly reduced the rate of restenosis by effectively suppressing neointimal growth compared with that of bare metal stents , complications such as in - stent restenosis and stent thrombosis still occur . the incidence of stent fracture is 1 - 8%.1 ) most stent fractures are found in patients who were treated with a sirolimus - eluting stent.2)3 ) we experienced an unusual case of stent fracture after implantation of a zotarolimus - eluting stent ( zes ) , which occurred during repeat revascularization for in - stent restenosis lesions of a saphenous vein graft . one year ago , he suffered from exertional chest pain and underwent a follow - up coronary angiogram . coronary angiography showed two newly developed significant stenotic lesions with 80% luminal narrowing at the ostium and 90% luminal narrowing at the mid - portion of the saphenous vein graft from the ascending aorta to the left anterior descending artery ( fig . the lesions were successfully treated with zess ( 3.515 and 3.030 mm , respectively ) ( endeavor resolute , medtronic , santa rosa , ca , usa ) ( fig . four months after stent implantation , he was admitted again due to exertional dyspnea . coronary angiography revealed 90% in - stent restenosis at the ostium and a patent stent at the mid - portion of the saphenous vein graft ( fig . fluoroscopic images showed angulation of the proximal portions of the zes at the ostium ( fig . 2a ) , the inflated balloon catheter was suddenly pulled back outside of the saphenous vein graft during adjunct balloon dilatation with a noncompliance balloon catheter ( 3.515 mm ) ( fig . at the same time , a stent fracture occurred and the fractured stent segment and migrated into the ascending aorta along the inflated balloon catheter ( fig . the migrated fractured struts were successfully pushed into the ostium of the saphenous vein graft without deflating the balloon catheter ( fig . 2c ) and were inflated at higher inflation pressure with the same noncompliance balloon catheter . although a distal part of the fractured stent segment was attached to the ostium of the saphenous vein graft , a gap was evident between the fractured stent segment and the residual stent , and a proximal part of the fractured stent segment was located outside of the saphenous vein graft ( fig . therefore , a sirolimus - eluting stent ( 3.518 mm ) ( cypher , cordis , miami , fl , usa ) was deployed to connect the distal part of the fractured stent and the proximal part of the residual stent to prevent systemic stent embolization ( fig . fluoroscopic images after implantation of the sirolimuseluting stent showed that the separated zes segments were well connected without a gap after using an additional stent ( fig . the final angiogram with a noncompliance balloon catheter after adjunct angioplasty showed no residual stenosis ( fig . stent fracture is sometimes observed after des implantation . the most notable mechanisms of stent fracture are metal fatigue due to mechanical forces and shearing stress.1 ) the right coronary artery , tortuous vessels , and long stents are predictors of stent fracture.1)3)4 ) additionally , stents implanted in saphenous venous grafts seem to be more susceptible to fracture.5 ) the type of implanted dess is also strongly related to stent fracture . of those , the sirolimus - eluting stent , which has a more rigid closed - cell stent design , has a tendency for more frequent fracture , compared with zes , which has an open - cell stent design.2)3 ) in this case , we experienced a rare case of zes fracture in an ostial in - stent restenostic lesion of the saphenous vein graft . stent angulation could be one of the contributing factors for stent fracture . furthermore , balloon dilatation for repeat revascularization of in - stent restenosis could be an additional aggravating mechanical force for stent fracture and separation of a des implanted in angulated segments . because the fractured stent segment migrated with the dilated balloon catheter along the guidewire system , we easily moved this fractured segment into the remnant distal segments for re - union . this case shows how to manage the migration of a fractured zes using balloon dilatation in a restenotic ostial lesion of a saphenous vein graft followed by additional des implantation .

stent fracture is a complication following implantation of drug eluting stents and is recognized as one of the risk factors for in - stent restenosis . we present the first case of successfully managing a stent fracture and subsequent migration of the fractured stent into the ascending aorta that occurred during repeat revascularization for in - stent restenosis of an ostium of saphenous vein graft after implantation of a zotarolimus - eluting stent . although the fractured stent segment had migrated into the ascending aorta with a pulled balloon catheter , it was successfully repositioned in the saphenous vein graft using an inflated balloon catheter . then , the fractured stent segment was successfully connected to the residual segment of the zotarolimus - eluting stent by covering it with an additional sirolimuseluting stent .

although tuberculosis ( tb ) is a common infection in india , tuberculids of the penis are rarely reported . here we are reporting a case of papulonecrotic tuberculid on glans penis in a patient without any primary tuberculous focus . a 65-year - old man presented with recurrent crops of multiple asymptomatic papulopustules over the glans penis since last 1 year . there was no history of trauma , drug intake , fever , cough , and constitutional symptoms . examination revealed multiple , nonindurated , well - defined ulcers of size 0.5 cm 0.5 cm over the ventral aspect of glans . the ulcers were nontender on touch and there was no bleeding on palpation of the ulcers . multiple , nonindurated , well - defined ulcers of size 0.5 cm 0.5 cm over the ventral aspect of glans . note irregular depressed scars surrounding the ulcers all hematological and biochemical investigations were normal except for highly raised erythrocyte sedimentation rate ( 50 mm in the 1 h ) . tuberculin ( mantoux ) test was strongly positive ( 30 mm 20 mm ) . ziehl - neelsen stain of the pus did not demonstrate any acid fast bacilli ( afb ) . radiological and ultrasound evaluation of the genitourinary system was normal . human immunodeficiency virus ( hiv ) antibodies test and venereal disease research laboratory test ( vdrl ) test were nonreactive . biopsy from the edge of the ulcer ( glans penis ) showed dermoepidermal necrosis surrounded by a poorly formed granulomatous infiltrate composed of lymphocytes and macrophages [ figure 2 ] . we were unable to perform tissue polymerase chain reaction ( pcr ) due to financial constraints . histopathology shows dermoepidermal necrosis surrounded by granulomatous infiltrate composed of lymphocytes , macrophages , and a langhans giant cell ( a ) ( h and e , 40 ) , histopathology showing necrosis ( b ) ( h and e , 4 ) he was treated with antituberculous treatment ( att ) for a period of 6 months . four weeks after the initiation of therapy , the existing lesions over the glans had healed [ figure 3 ] . papulonecrotic tuberculids ( pnt ) are characterized by recurrent eruptions of asymptomatic , dusky red papules , which ulcerate and crust , and heal after a few weeks with varioliform scarring . tuberculids are hypersensitivity reactions to mycobacterium tuberculosis or its products in individuals with good immunity . the formation of tuberculids is explained by the haematogenous dissemination to the skin of mycobacterial antigens from an internal tuberculous focus in a hypersensitive patient . the tuberculids may present in different morphological forms but , m. tuberculosis is not usually identified by afb stains , culture , or pcr . however , some recent authors have found mycobacterial deoxyribonucleic acid ( dna ) in erythema induratum and pnt lesions using pcr . penile tuberculids is an extremely rare condition with majority of cases reported from japan and south africa . a series of 121 japanese patients with papulonecrotic tuberculid principally involving the glans was reported by nishigori et al . the clinical features of tuberculids of the penis have been reported as ulceration or scars . as described in other reports , the characteristic irregular depressed scars are seen only in pnt on the glans penis . in indian literature , padmavathy et al . , and vijaikumar et al . differential diagnosis of the pnt on glans includes syphilis , recurrent herpes simplex , erythroplasia , drug eruption , balanitis , behet 's disease , and squamous cell carcinoma . the histological findings may vary from acute leukocytoclastic vasculitis in early lesions to mature granuloma formation in older ones . a response to att can confirm the diagnosis of cutaneous tb , as in our case . a correct diagnosis of pnt on glans can be done on basis of characteristic irregular depressed scars , histopathological finding of tuberculous granuloma , and a good response to att ; however it may remain undiagnosed for years together due to lack of knowledge about this entity in practitioners . though most cases of pnt on glans were not associated with systemic tb , there are reports of their associations ; and hence , the patient should be thoroughly investigated for underlying active systemic tb .

a 65-year - old man presented with multiple asymptomatic papulo - pustules and ulcers over glans penis since last 1 year . the lesions used to resolve spontaneously in a few days with scarring . the clinical features and histopathology were suggestive of papulonecrotic tuberculids of the glans penis .

neurofibromatosis type 1 ( nf1 ) is an autosomal dominant , multisystemic disorder caused by mutations of the gene nf1 that encodes the tumor suppressor protein neurofibromin . head and neck lesions may present as asymptomatic masses , pendulous and grotesque tumors , or space - occupying lesions producing pressure effects on the craniofacial bones and underlying structures . these tumors can show significant vascularization with abnormal vessel structure ; however , spontaneous massive hemorrhage , a life - threatening complication , is rarely reported . moreover , to date there are no reports in the literature about the 3d ultrasound features of hemorrhagic complications of nf in the scalp . only a few reports on computed tomography ( ct ) of scalp findings in nf are available in the literature . as far as we know , none of the computed tomography reports have shown the tomographic features of the fully active phase of the bleeding in scalp nf which differs from the old hemorrhage . a 48-year - old male with a history of nf1 showing multiple caf - au - lait spots and peripheral neurofibromas presented a sudden and tender swelling in the right parieto - temporal region of the scalp . the patient was referred to the department of radiology for a 2d-3d color doppler ultrasound ( cdus ) examination that demonstrated a hypodermal structure with lobulated margins and heterogeneous echogenicity , 8.3 cm long 8.9 cm transverse 1.6 cm depth axes . a 3.1 mm ( thickness ) serpiginous tubular mixed echogenicity ( hypoechoic - anechoic ) solid tract was also detected in the vicinity of the lesion . neither intralesional blood flow nor involvement of the bony margin of the skull was detected on cdus . a ct scan performed after the ultrasound examination demonstrated a fully hyperdense soft tissue mass in the same location of the scalp . a surgical excision of the mass was performed and was consistent with the diagnosis . the histological analysis ( hematoxylin and eosin stain ) demonstrated a proliferation of spindle monomorphic cells embedded in the adipose tissue , some mastocytes , inflammatory cells , prominent capillary vessels and the presence of multiple hemorrhagic areas . the patient presented a sudden and tender swelling in the right parieto - temporal region 2d and 3d ultrasound ( a ) 2d panoramic grey scale transverse view ; ( b ) 3d reconstruction longitudinal view ; 5 - 8 seconds sweep ) demonstrated a hypodermal structure with lobulated margins and heterogeneous echogenicity ( 8.9 cm transverse 1.6 cm depth axes ) . notice the anechoic areas ( o ) within the mass that corresponded to the most liquefied parts of the bleeding . there is a mixed echogenicity ( anechoichypoechoic ) serpiginous tract ( arrow ) in the vicinity of the structure . d : dermis , h : hypodermis , b : bony margin of the skull computed tomography showing a hyperdense hemorrhagic soft tissue mass ( * ) in the right parieto - temporal region histology ( hematoxylin and eosin stain 100 magnification ) demonstrates a proliferation of spindle monomorphic cells ( arrows ) surrounding the adipose cells and the presence of a prominent hemorrhagic area ( * ) our local ethics committee has waived the request of an informed consent for reporting this case , and the clinical , ultrasound and ct examinations were performed following the helsinki principles of medical ethics . the clinical presentation of neurofibromas is variable and according to their morphology these entities can be classified into localized , diffuse and plexiform and they may show cutaneous , subcutaneous ( hypodermal ) or intraneural locations . the characteristics and the degree of severity of nf1 are highly variable and its main clinical features include multiple caf - au - lait spots , axillary freckling , hamartomas of the iris ( lisch nodules ) , optic pathway gliomas , peripheral nerve - sheath tumors and osseous involvement . the ultrasound imaging appearance of uncomplicated plexiform nf in the scalp has been previously described as a hypoechoic solid mass . this appearance differs greatly in its imaging presentation from the complicated ultrasound features of the same tumor under hemorrhage , which shows a mixed echogenicity ( heterogeneous ) hypoechoic and anechoic solid - cystic structure . even though the diagnosis can be performed with 2d ultrasound images , 3d images that require only a 5 to 8 seconds sweep show a more understandable representation of the pathology to the clinician . the serpiginous anechoic / hypoechoic tract that was observed in the periphery of the hematic fluid collection on ultrasound corresponds to a thick neural bundle , typically seen in plexiform nf . only a few cases have been described of the use of ct in giant plexiform neurofibromas affecting the scalp and cranio - maxillofacial regions . these reports show old ( non - active ) areas of hemorrhage with heterogeneous density . this imaging presentation also differs from the fully active hemorrhage which is hyperdense in ct as in our case . the presence of bleeding usually adds a more severe feature to the clinical condition that requires urgent treatment . furthermore , hemorrhage in nf1 , although rare , may be severe and recurrent and fatalities have been reported . the differential diagnosis of this case may include other soft tissue lesions of the scalp such as lipomas , trichilemmal cysts or pilomatrixomas where highly available imaging modalities such as ultrasound have been proven useful for assessing the diagnosis . in conclusion , we report this sudden hemorrhagic complication of a plexiform neurofibroma of the scalp that required urgent and coordinated work from the clinical , imaging and pathology staffs . this management was critical for the quick resolution of the case and shows the importance of prompt imaging support and the imaging characteristics of the bleeding in this entity both on multidimensional ultrasound and ct . multidimensional imaging including 3d and 2d ultrasound as well as computed tomography can play a vital role in the assessment of the activity of the hemorrhagic complication of neurofibromatosis type 1 . this is the first report of the simultaneous usage of 3d ultrasound and computed tomography in an actively bleeding neurofibroma of the scalp .

active bleeding in plexiform neurofibromatosis can be a life - threatening complication in neurofibromatosis type 1 ( nf1 ) . the prompt imaging support of 2d-3d ultrasound ( us ) and computed tomography ( ct ) during the active hemorrhage phase of cutaneous neurofibromas has not been previously reported . we report a case with nf1 who experienced a sudden swelling in the parieto - temporal region that corresponded to a massive and active hemorrhage within a plexiform neurofibroma . the us and ct imaging characteristics of this bleeding tumor are shown . active hemorrhage in a plexiform neurofibroma of the scalp appeared in us as a heterogeneous hypodermal mass . ct demonstrated a fully hyperdense soft tissue mass . these characteristics differ from the non - complicated or old hemorrhagic imaging appearances of scalp plexiform neurofibromas and encourage prompt surgical treatment . this case report demonstrates the usefulness of imaging support in the early diagnosis of this hemorrhagic complication of nf1 in the scalp and also stimulates multispecialty management .

gummy smile is a frequent cause of patient dissatisfaction , which can occur because of various intraoral or extraoral etiologies . the extraoral causes of a gummy smile are vertical maxillary excess ( vme ) , hypermobile upper lip ( hul ) , or a short upper lip ( sul measured from the subnasale to the inferior border of the upper lip ) . the average length of the maxillary lip is 20 - 22 mm in young adult females and 22 - 24 mm in young adult males . various treatment modalities have been tried till date for the treatment of egd which include orthognathic surgery 's for correcting jaw deformity . performing myectomies to detach the smile muscle attachment , use an alloplastic or autogenous separator which are placed with a nasal approach between the elevator muscles of the lip and the anterior nasal spine and lip repositioning has also been performed in conjunction with rhinoplasty . thus it is vital that the clinician evaluate the essentials of the patient 's smile and studies the dynamic association between the patient 's dentition , gingivae and lips while smiling . we report on the use of a minimally invasive surgical procedure for the management of a egd associated with sul . a healthy 18-year - old girl presented with a chief complaint of a gummy smile [ figure 1 ] and incompetent lips [ figure 2 ] . a periodontal examination performed revealed moderate gingival biotype with probing depths in the range of 1 - 3 mm . the gingival line in the maxillary anterior sextant was found to be symmetrical and she had adequate width of attached gingiva . the posterior extent of the dynamic smile extended to the distal aspect of the first molars , with 4 - 5 mm of excessive gingival tissue display and the maxillary anterior teeth had normal anatomic proportions . two treatment options were presented to the patient : maxillary orthognathic surgery or lip repositioning surgery ( lrs ) . after careful discussion , the patient opted for the lrs as it was minimally invasive , less aggressive and had the potential for fewer postoperative complications . pre - operative view smiling pre - operative view showing incompetent lips a written informed consent was taken and the patient was educated about post - surgical complications such as possible scar formation , mucocele formation , post - operative bruising and extraoral swelling . local anesthetic ( xylocaine with 1:200,000 adrenalines ) a marking pen was used to outline the apical , coronal and lateral boundaries of the elliptical incision [ figure 3 ] . the coronal boundary was at the mucogingival junction and was used as a reference point to mark the apical boundary at a distance of 2 times gd . the coronal and apical incisions were parallel to each other and a partial - thickness incision was made at the mucogingival junction from the mesial line angle of the right first molar to the mesial line angle of the left first molar . the epithelium was removed within the outline of the incisions exposing the underlying connective tissue [ figure 4 ] . care was taken to avoid damage to any minor salivary glands in the submucosa and tissue tags were removed . the mucosal flap was advanced and sutured with interrupted stabilization sutures at the midline and other locations along the borders of the incision mucogingival junction using 5 - 0 vicryl sutures [ figure 5 ] . post - operative instructions included soft diet , limited facial movements , no brushing around the surgical site for 14 days and placing ice packs over the upper lip . the patient was instructed to rinse gently with 0.2% chlorhexidine gluconate twice daily for 2 weeks . post - operative amoxicillin 500 mg t.d.s and ibuprofen 400 mg b.d for 5 days were prescribed . post - operative healing occurred and the patient reported minimal post - operative bruising , or extraoral swelling and slight pain when smiling for 1 week after surgery . sutures were removed 2 weeks later . the suture line healed in the form of a scar that was concealed in the upper lip mucosa and not visible when the patient smiled . reduction in the amount of gd at the 1-year follow - up visit was stable along [ figure 6 ] with competent lips [ figure 7 ] . exposed connective tissue suturing done with interrupted sutures post - operative view smiling post - operative view with improved lip competency this report documents the use of lrs for the management of egd seen with a sul . the original technique for the procedure was described as cosmetic surgery by rubinstein and kostianovsky for correction of a gummy smile caused by hypermobile lip . this surgical procedure was designed to have fewer postoperative complications when compared to orthognathic surgery besides being shorter and less aggressive . this procedure was re - advocated by litton and fournier for the correction of egd in a case of sul by separating the muscles from the basal bony structures to coronally place the upper lip . miskinyar however did not report when or how much relapse had occurred in his patient group . these patients were reoperated using a more aggressive approach which included myectomy and a partial resection of the muscle- levator labii superioris along with nerve repositioning before muscle resection . the only post - operative complication reported by the author was a postoperative paraesthesia that lasted 2.5 months for one patient . case reports by rosenblatt and simon and simon et al . used an elliptical - shaped incision at the mucogingival junction and the alveolar mucosa , to reflect a partial - thickness flap , and an arbitrary excision of 10 to 12 mm of epithelium . similar surgical procedure has been reported by humayun et al . with one year follow - up providing good results . accurate diagnosis and a pertinent case selection are critical for the success of any lr procedure . contraindications to lr surgery include the presence of a minimal zone of attached gingiva , which can create difficulties in flap design , stabilization , and suturing , and severe vme ( > 8 mm of gingival display ) . this case report demonstrates that lrs may be used effectively for treatment of excessive gd caused by sul by positioning the upper lip in a more coronal location . proper diagnosis evaluation of the severity of vme , hul , or a short lip and an appropriate case selection are critical for the success of any surgical procedure . it is a less invasive , viable substitute for patients , has fewer post - operative complications and provides a faster recovery compared to orthognathic surgery . long - term follow - up studies are needed to evaluate the stability and effectiveness of this treatment modality , but it holds promise as an alternative treatment modality in perio - esthetics .

in our esthetic conscious society people are now demanding all types of treatments possible to have a pleasing and attractive personality . a dazzling and beautiful smile can work wonders for anyone 's personality . our smile mirrors our persona , our unique being . however , a beautiful smile comprises of a perfect balance of the white and pink . this imbalance of excessive gingival display ( egd ) can be managed by a variety of treatment modalities , depending on accurate diagnosis . this case report demonstrates the successful management of egd with a lip - repositioning procedure in a patient with incompetent short upper lip . this was accomplished by removing a partial thickness strip of mucosa from the maxillary buccal vestibule and suturing the lip mucosa to the mucogingival line . this resulted in a narrower vestibule and restricted muscle pull , thereby resulting in competent lips and reduced gingival display during smiling .

immunoglobulin g4-related disease ( igg4-rd ) has been recognized as a wide spectrum immune - mediated inflammatory disease in past few years . it can involve multiple organs and tissues such as the pancreas ( autoimmune pancreatitis ) , biliary tract , lacrimal gland , salivary gland ( sclerosing sialadenitis - mikulicz disease ) , thyroid gland ( riedel 's thyroiditis ) , lung , kidney , mediastinum ( mediastinal fibrosis ) , and the retroperitoneum ( retroperitoneal fibrosis / lymphoplasmacytic aortitis ) , all characterized by a typical histopathological finding of infiltration by igg4 rich plasma cells and storiform fibrosis . igg4-related retroperitoneal fibrosis can occur as part of multisystem disease or can present in isolation . metabolic imaging with f - fluorodeoxyglucose ( f - fdg ) positron emission tomography / computed tomography ( pet / ct ) can play an important role in diagnosis of igg4-related retroperitoneal fibrosis . we here present a case of igg4-related retroperitoneal fibrosis and discuss the potential implications of f - fdg pet / ct in such patients . a 63-year - old male presented with progressive pain abdomen , weight loss , and loss of appetite of 4 months duration . ultrasound of the abdomen revealed dilated left pelvicalyceal system and left upper ureter . left kidney was otherwise normal . also noted were multiple matted preaortic lymph nodes with mass formation , compressing the middle part of the left ureter , causing obstructive left hydronephrosis . he underwent cystoscopy with bilateral retrograde pyelography and left dj stenting . suspecting a malignant etiology , the patient underwent contrast - enhanced f - fdg pet / ct . pet / ct findings revealed a heterogeneously enhancing retroperitoneal soft tissue mass encasing the left ureter , aorta , left renal vessels , and left common iliac vessels , with heterogeneous f - fdg uptake [ maximum standardized uptake value ( suvmax)-3.7 ] [ figures 1a c and 2a i ] . no other hypermetabolic lesion was seen in the rest of the body . based on pet / ct findings , diagnosis of active retroperitoneal fibrosis was given . to get a definitive tissue sample , the patient underwent exploratory laparotomy and incisional biopsy . operative findings revealed diffuse plaque like retroperitoneal mass engulfing the left ureter and adherent to aorta and iliac vessels . biopsy was taken from the most metabolically active part of the mass near aortic bifurcation . histopathology revealed intense storiform fibrosis with dense lymphoplasmacytic infiltrate in collagenized connective tissue stroma and many reactive lymphoid follicles . maximum intensity projection positron emission tomography ( pet ) image ( a ) showing the patchy retroperitoneal lesion with moderate to intense f - fluorodeoxyglucose ( f - fdg ) uptake ( arrows , maximum standardized uptake value-3.7 ) . coronal ( b ) and sagittal ( c ) pet / computed tomography images demonstrating f - fdg avid retroperitoneal soft tissue mass encasing the abdominal aorta ( arrows ) transaxial contrast - enhanced computed tomography ( ct ) images of the abdomen ( a - c ) showing heterogeneously enhancing retroperitoneal soft tissue mass extending from the level of superior mesenteric artery to left iliac region and encasing abdominal aorta , left renal vessels , left iliac vessels , and left ureter ( arrows ) . on transaxial positron emission tomography ( pet ) ( d - f ) and pet / ct ( g - i ) images , heterogeneous f - fluorodeoxyglucose uptake is seen in the retroperitoneal mass ( arrows ) immunoglobulin g4-related disease can mimic malignancy , clinically as well as on imaging , but can be treated easily with corticosteroids . making a diagnosis of igg4-rd is a challenge due to the wide spectrum of clinical presentations . recently , two diagnostic criteria have been proposed for igg4-rd : ( 1 ) serum igg4 concentration > 135 mg / dl and ( 2 ) > 40% of igg positive plasma cells being igg4 positive and > 10 cells / high powered field of biopsy sample . in the present case , the serum igg4 levels were elevated ( 167 mg / dl ) and there was a preponderance of igg4 positive plasma cells in the tissue biopsy . in addition , it is not ethical or feasible to biopsy all sites of suspected disease involvement or biopsy may not be adequate for diagnosis . these difficulties can be obviated with the use of f - fdg pet / ct . f - fluorodeoxyglucose pet / ct is commonly employed in oncological imaging . in patients with igg4-rd , pet / ct is generally employed to differentiate it from malignancy . in the present case too , pet / ct was performed to exclude lymphoma . while the pattern of disease on f - fdg pet / ct was strongly suspicious for igg4-related retroperitoneal fibrosis in this patient as per the criteria ( patchy retroperitoneal lesion with moderate to intense f - fdg uptake ) described by zhang et al . , histopathology is required to confirm the diagnosis . due to the metabolic nature of the study , f - fdg pet / ct can also be employed for selecting the appropriate site of biopsy . in the present case , biopsy was performed from the most metabolically active portion of the mass , near the aortic bifurcation . another major contribution of f - fdg pet / ct is whole body mapping of disease extent in igg4-rd . in the present case apart from retroperitoneal mass , no other hypermetabolic lesion was seen in the rest of the body . another potential application of f - fdg pet / ct can be for the assessment of therapeutic response in igg4-rd . unfortunately , in this present , patient post therapy pet / ct was not available . f - fluorodeoxyglucose pet / ct can play an important role in the management of igg4-related retroperitoneal fibrosis by supporting the diagnosis , demonstrating the disease extent , helping the selection of appropriate biopsy site and possibly for monitoring therapeutic response .

immunoglobulin g4 ( igg4)-related disease encompasses a wide variety of immune disorders previously thought be distinct . igg4-related retroperitoneal fibrosis is one such entity . metabolic imaging with 18f - fluorodeoxyglucose ( 18f - fdg ) positron emission tomography / computed tomography ( pet / ct ) can be useful in the management of igg4-related retroperitoneal fibrosis . we here discuss the case of 63-year - old male with igg4-related retroperitoneal fibrosis and the role , 18f - fdg pet / ct played in his management .

inflammatory myofibroblastic tumors ( imts ) are rare neoplasms that occur preferentially in children and young adults.1 imts most commonly occur in the lungs , mesenteries , omentum , and retroperitoneum.1,2 imts involving the stomach are extremely rare . these distinctive tumors are composed of myofibroblastic cells accompanied by an inflammatory infiltrate of plasma cells , lymphocytes , and eosinophils.3 imts present with nonspecific clinical symptoms , and their preoperative diagnosis can be difficult . imts in the gastrointestinal tract can present with bleeding , obstruction , anemia , or intussusception , depending on the site.4 herein , we present a case of an imt that involved nearly the entire proximal stomach . his symptoms were not associated with abdominal pain , dyspepsia , fever , or weight loss . the patient had no notable medical or operational history except an admission for bronchial asthma during childhood . emergency gastric fibroscopy detected a protruding mass 44 cm in size , with central ulceration at the posterior wall of the fundus and two slightly protruding submucosal lesions with central erosion on the lesser curvature side of the upper stomach body ( fig . a biopsy of the fundic protruding lesion revealed no diagnostic information except that it was a spindle cell - type lesion ( tests for cd34 , cd117 , actin , and s-100 were all negative ) . computed tomography showed a 3.6-cm enhancing ulcerofungating mass with a 4-cm eccentric wall thickening and an enhancing mucosal layer on the lesser curvature side of the upper stomach body ( fig . although the diagnosis was uncertain , an operation was planned due to the risk of rebleeding . because the fundic mass and the thickened portion of the lesser curvature formed one continuous , massive lesion , laparoscopic proximal gastrectomy was performed to resect the entire area involved . the cut surface of the resected specimen revealed two lesions and involvement of the muscle layer ( fig . the tumor was mainly composed of spindle - shaped cells in a hyalinized stroma with lymphoplasmacytic infiltration compatible with a diagnosis of imt . although rearrangement of the anaplastic lymphoma kinase ( alk ) gene was not found , the tumor was focally positive for actin , and other immunohistochemical results ( cd34 , cd117 , and s-100 tests were all negative ) excluded gastrointestinal stromal tumor , leiomyoma , and neurogenic tumor . in addition , immunoglobulin g4 ( igg4)-related sclerosing disease could be ruled out because igg4/igg ratio was less than 0.4 ( fig . the patient showed an uneventful postoperative course , and no local recurrence or distant metastasis was found during the 18-month follow - up . imt was first described in 1937 as a primary lung tumor and has since been reported in various sites , including the mesenteries , the retroperitoneum , and the gastrointestinal tract.4 it mainly occurs in young adults and children , and the lung is the most frequent location . various terms have been used to describe this entity , such as ' inflammatory pseudotumor , ' ' pseudosarcomatous myofibroblastic proliferation , ' and ' plasma cell granuloma . ' primary gastric imts have been reported in only 17 adult patients.5 the pathogenesis of imt is unclear . allergic , immunologic , and infectious reactions have been postulated.6 approximately half of imts harbor a clonal cytogenetic aberration that activates the alk tyrosine kinase receptor gene on the 2p locus of chromosome 23.7 rearrangement of the alk gene is another postulated pathogenesis . manifestations of gastric imt may include abdominal pain , hematemesis , melena , a palpable mass , anemia , and high fever.6,8 hemoperitoneum has rarely been reported as an initial finding in patients with gastric imt.9 because gastric imts localize in the submucosal layer , endoscopy can not distinguish them from other submucosal tumors . thus , surgical resection with an adequate margin is the most reliable diagnostic and treatment method . abdominal computed tomography is helpful for determining the necessary extent of resection.6 in the present case , a proximal gastrectomy was performed because the gastric imt involved nearly the entire proximal stomach . the histological appearance of gastric imts is characterized by proliferation of spindle - shaped myofibroblastic cells and lymphocytic infiltration among tumor cells . differential diagnoses for imt include inflammatory fibrinoid polyp , gastrointestinal stromal tumor , leiomyoma , and follicular dendritic cell sarcoma.3 alk expression distinguishes imt from its differential diagnoses . however , not all gastric imts are positive for alk rearrangement ; only about 50% of imts in children and young adults show such rearrangement.1 in addition , imts test positive for actin with most immunohistochemical tests.3 immunohistochemical tests for cd117 , cd34 , and s-100 can help distinguish imt from differential diagnoses . the typical characteristics of an imt were observed in the present case ( myofibroblastic proliferation , lymphoplasmacytic infiltration distributed among the tumor cells ) . although our case failed to show the alk mutation , the diagnosis was made based on morphological characteristics , the focally positive actin test , and negative results for cd34 , cd117 , and s-100 staining . imt has intermediate biological potential , frequently recurring but rarely metastasizing.10,11 among 17 reported gastric imt cases in adults , only one case recurred , as a peritoneal dissemination following total gastrectomy , distal pancreatectomy , splenectomy , transverse colectomy , and lymph node dissection , which were necessitated by the large size of the tumor . resection with an adequate margin is the only treatment option , and regular follow - up is mandatory .

inflammatory myofibroblastic tumors ( imts ) of the stomach are extremely rare in adults , and their oncologic prognosis is not well understood . we present a 28-year - old man with a proximal gastric imt . the patient visited the emergency department of yeouido st . mary 's hospital with syncope and hematemesis . hemoglobin levels were < 5.5 g / dl . gastric fibroscopy showed a protruding mass 44 cm in size , with central ulceration on the posterior wall of the fundus and diffuse wall thickening throughout the cardia and anterior wall of the upper body . endoscopic biopsy revealed indeterminate spindle cells , along with inflammation . given the risk of rebleeding , an operation was performed despite the uncertain diagnosis . because the mass was circumferential , laparoscopic proximal gastrectomy and double - tract anastomosis were performed to ensure a safe resection margin . the pathological diagnosis was consistent with an imt originating from the stomach , although the tumor was negative for anaplastic lymphoma kinase gene mutation .

most cases have been reported in association with previous spine surgery or in highly active athletic individuals . pedicles have great intrinsic strength and short moment arms , and therefore , can resist substantial cyclic shear forces . spondylolysis and fracture of the pars interarticularis are the most common injuries of the neural arch . several reports have investigated fractures of the contralateral pedicle in patients with unilateral spondylolysis , especially during advanced stages of the pars defect , and in these reports , it was proposed that instability of this segment created by a unilateral pars defect leads to fracture of the contralateral pedicle38 ) . we report a rare case of unilateral pedicle fracture accompanying bilateral spondylolytic defects in a patient with spondylolisthesis in the absence of any major trauma , previous spine surgery , or stress - related activity . a 55-year - old man experienced progressively worsening low back and bilateral leg pain over 7 months . he had a history of mild back pain of several years duration but the leg pain had progressively increased without any traumatic episode or spinal surgery . a neurological examination revealed no motor weakness or sensory change , but marked tenderness was in the low back area with reduced back motion , especially in backward extension . plain radiographs showed spondylolytic spondylolisthesis at the l5 level and irregularity of the l5 pedicle suggesting a pedicle fracture ( fig . 1 ) . computed tomography ( ct ) and magnetic resonance imaging ( mri ) revealed an unilateral right pedicle fracture at l5 level accompanying spondylolytic spondylolisthesis ( fig . 2 , 3 ) . he was treated by posterior lumbar interbody fusion of l5-s1 with percutaneous screw fixation . at his 12 month follow up assessment , no residual low back pain or radiating pain was evident and he had returned to normal activities ( fig . unilateral spondylolysis with sclerosis and hypertrophy of the contralateral side of the neural arch has been described in the literature38 ) . sclerosis of contralateral side is believed to occur as a compensatory mechanism secondary to the redistribution of forces in an unstable neural arch resulting from a contralateral defect in the pars interarticularis1 ) . pedicle stress fractures have been reported in association with contralateral spondylolysis , and up to 40% of such pedicles exhibit reactive changes on mr images10 ) . sherman et al.9 ) reported 11 patients with reactive sclerosis and hypertrophy of the pedicle and lamina contralateral to unilateral spondylolysis . they proposed that if the buttressing effect is insufficient to resist continued stress on the lumbar spine , a bilateral or unilateral defect of the pars interarticularis might also develop . pedicle fractures have also been reported in association with bilateral spondylolysis in otherwise normal adults , but the pathophysiological mechanism still remains unknown2 ) . however , unilateral pedicle fracture accompanying bilateral spondylolytic defects with spondylolisthesis is extremely rare and to the best of our knowledge , no case of spondylolisthesis accompanying a unilateral pedicle stress fracture has been previously reported . in our patient , fractures were not fresh , because some sclerotic change was evident at fracture margins . jeong et al.6 ) reported a contralateral pedicular fracture associated with unilateral spondylolysis at the l5 level that was successfully treated by rehabilitation and activity modification . however , our patient , who showed bilateral spondylolytic defects with spondylolisthesis and foraminal stenosis , was treated by screw fixation and interbody fusion for stabilization . we fused the l5-s1 segment to stabilize the pedicle fracture and spondylolytic spondylolisthesis , and the stabilization resulted in pain relief and allowed our patient to return to normal activities . repetitive mechanical stress fractures in posterior elements are usually located in the pars interarticularis or to a substantially lesser extent , in the pedicle . the pedicle has great intrinsic strength and a short moment arm from the vertebral body , and can therefore resist substantial cyclic shear force4 ) . sometimes diagnosis of pedicle fracture in a patient with unilateral spondylolysis is possible by plain radiography . combined pars defect is easily detected and linear cleft or sclerosis of the pedicle may be demonstrated in some of these patients . however , the sensitivity of plain radiography is limited . on the other hand , ct , which is widely regarded as the method of choice for the diagnosis of such lesions , clearly demonstrated the stress fracture as a linear defect at the base of the sclerotic pedicle . we report a rare case of unilateral pedicle fracture accompanying spondylolytic spondylolisthesis without predisposing risk factors .

unilateral pedicle stress fracture accompanying spondylolytic spondylolisthesis is rare even in the elderly . most are associated with major trauma , previous spine surgery , or stress - related activity . here , the authors describe an unique case of unilateral pedicle fracture associated with spondylolytic spondylolisthesis at the l5 level , which was successfully treated by posterior lumbar interbody fusion with screw fixation at the l5-s1 level . as far as the authors ' knowledge , no such case has been previously reported in the literature . the pathophysiological mechanism of this uncommon entity is discussed and a review of relevant literature is included .

an mri of the lumbar spine was then performed , which clearly demonstrated a lesion of the fifth lumbar vertebra , within the confines of the vertebral cortex , having low t1- and high t2-weighted signal intensities , and showing no enhancement ( fig . there was no evidence of soft tissue extension . in the presence of only mild trabecular sclerosis and no bone destruction as seen on computed tomography ( ct ) , the provisional diagnosis of a gvnr was deemed most likely and the patient was subject to close follow - up with bimonthly intervals . repeat mri , dwi and ct , performed one year after the patient first presented with symptoms failed to demonstrate any lesion growth ( fig . 1c - h ) . based on the nonaggressive radiological pattern and the lack of morphological features associated with a chordoma , the patient was considered as having a gvnr and has been recommended to continue follow - up . fourteen months after her first presentation , the patient is alive and well , and her back pain has benefited greatly from medical and physical therapy . a chordoma is a rare tumor ( 0.2 cases per 100,000 ) of the axial skeleton found most commonly at the sacrococcygeal and spheno - occipital regions ( 6 ) . the presence of soft tissue invasion and its location makes complete surgical excision difficult to perform and can lead to a poor prognosis . they have a predilection for the spheno - occipital and sacral regions , where branching of the notochord occurs and chordomas are also usually found ( 5 ) . intravertebral notochordal rests are rare autopsy findings ( about 1% of autopsy series ) and when found are microscopic in size ( 6 , 7 ) . the actual rate of transformation for these intravertebral vestiges into a chordoma is not known . however , when their incidence are compared the transformation seems to be a rare event ( 7 ) . the diagnosis of giant vertebral notochordal rest in the above presented case is certainly debatable . until recently , a similar patient would have invariably undergone a vertebrectomy with a leading diagnosis of a chordoma . currently , the concept that a benign notochordal rest , termed a gvnr could present similarly in a patient has been accepted following strong debate , with a total of seven cases published in the literature ( 5 - 8 ) . the distinction between these two entities relies mostly on imaging findings and is of obvious clinical importance since the management and prognosis of a gvnr and a chordoma is completely different . the lack of progression , bone destruction or soft tissue extension are important imaging criteria agreed by most investigators that suggest a radiological diagnosis of a gvnr ( 7 ) . it is also well known that at the time of diagnosis , a chordoma invariably shows bone destruction and , in almost all cases , has obvious soft tissue extension ( 6 ) . in the above presented case , the lesion met all of the defined radiological criteria and showed no progression between follow - up , establishing the diagnosis of a gvnr . other possible benign vertebral lesions that can be considered in the differential diagnosis include an atypical hemangioma , a simple bone cyst , an osteoid osteoma and an osteoblastoma . although both an atypical hemangioma and bone cyst might show similar mri findings , they can readily be distinguished by their ct appearances . apart from clinical presentation , both an osteoid osteoma and osteoblastoma can easily be differentiated by their intense contrast enhancement . an important reproach can be made for not performing a percutaneous needle biopsy to confirm the diagnosis in the above presented case . however , due to the histological heterogeneity of a chordoma , its distinction from a notochordal rest may be impossible to determine when presented with material from a needle biopsy tissue alone , which shows only physaliphorous and univacuolated cells ( 6 ) . in these circumstances an excisional biopsy in the form of a vertebrectomy is needed for final diagnosis . considering the benign nature of a gvnr , this procedure is not always preferred , making its diagnosis very much dependent upon the radiological findings . considering its ability to detect altered water - proton mobility , there have been recent efforts to implement dwi in the evaluation of spinal disorders . dwi has been particularly useful for distinguishing acute benign osteoporotic from malignant vertebral compression fractures ( 9 , 10 ) . increased diffusion of interstitial water is a common phenomenon and may be observed in acute posttraumatic edema of the bone resulting in low signal intensity on dwi ( 10 ) . in contrast , densely packed tumor cells restrict the diffusion , resulting in a lower phase shift with high signal intensity on dwi with low signal intensity on apparent diffusion coefficient ( adc ) maps ( 9 ) . to the best of our knowledge there are no previous reports concerning dwi findings of a gvnr . in the above presented case , dwi performed with a b value of 600 sec / mm showed high signal intensity on both trace images and the corresponding adc maps . based on these findings , we hypothesized that increased signal intensities on dwi and corresponding adc maps are not related to diffusion alteration , but are greatly influenced by the t2 shine - through effect and reflect the non - infiltrative character of the lesion . in conclusion , a gvnr is a new , benign entity , which can easily be confused with a vertebral chordoma . differentiation between these two entities can readily be made radiologically , with dwi being a useful new supplementary imaging tool . management of a gvnr found incidentally during radiological imaging should be conservative , with periodic follow - up imaging in order to detect possible transformation of the lesion into a chordoma .

a giant vertebral notochordal rest is a newly described , benign entity that is easily confused with a vertebral chordoma . as microscopic notochordal rests are rarely found in adult autopsies , the finding of a macroscopic vertebral lesion is a new entity with only seven previously presented cases . we report here radiological findings , including diffusion weighted images , of a patient with a giant notochordal remnant confined to the l5 vertebra , with an emphasis on its distinction from a chordoma .

the incidence of inguinal hernia in females is 1.9% , the ratio of boys to girls being 6:1 . the site of presentation being 68.1% on the right side , 23.4% on the left and 8.5% bilateral . the sac is formed by the unobliterated portion of the prenatal peritoneal invagination of the canal of nuck that runs along and partly covers the round ligament . around 15% of the childhood hernias are incarcerated , especially those in young infants . a case of bilateral inguinal hernia in a female of 10 years old is reported below . a 10-year - old female child presented to our outpatient department ( opd ) at st . george hospital along with her mother with bulge on both groin of 8 months duration . the swelling appeared on straining , on coughing and laughing and was reduced on lying down . the child was born full term normal delivery and there were no significant findings in the history . on examination there was expansible impulse on coughing and internal ring occlusion test was positive ( figure 2 ) . ultrasound confirmed bilateral inguinal hernia with ovaries as contents on both sides ( figure 3 ) . on exploration , patient was found to be having a sliding hernia containing incarcerated ovary as contents on both sides . the contents were reduced back into the peritoneal cavity after division of the external ring , as there were no signs of strangulation . the patient was followed up in surgical opd and there was no recurrence after six months . once the diagnosis of inguinal hernia in a female is made , repair should be carried out promptly because incarceration occurs in the first year of life . sliding hernias of the tube , ovaries and the uterus occurs occasionally in newborn female infants and some authors suggest ultra sonography for the diagnosis of inguinal hernia in premature female infants . in our case the mesenteric attachment of tube and the ovary frequently form part of the hernia sac in girls . in our case the contents were only ovary , which could be due to a long ovarian ligament and broad ovarian mesentery . the ligament which runs along an inguinal hernia sac in females is believed to be round ligament of uterus , is actually the suspensory ligament of the ovary and terminates in the hernia sac . as seen in our case it is supposed to be female gubernaculums that has altered anatomy and localization because of absence of androgen responsiveness . its modified presentation in a processus vaginalis raises the suspicion that ovary in the hernia sac may not be simply prolapsed , but is a descended gonad mimicking the descent of the testis . the sac wall may seem too thick in the medial or lateral quadrants in these cases and there may be difficulty in reducing the contents back within the peritoneal cavity . the sac should be opened in the normal appearing portion , and the walls inspected for a sliding component . the mesenteric attachment of the inner sac wall is divided in the bloodless plane within the sac . the freed up tube and the ovary is then reduced easily with no compromise in the blood supply and the neck of the sac is closed in the usual way . since the tubes were not present in the sac , we were able to reduce the ovaries easily intra peritoneally and excise the sac after ligation at neck . immediate operation should be done in all patients who are ill with obstructed or locally inflamed hernia , without attempting reduction . approximately 1.6% of these children presenting with inguinal hernia and having apparent female genitalia prove to be of male nuclear sex with intra - abdominal testes but female anatomy and endocrine function - complete androgen insensitivity syndrome previously called the testicular feminization syndrome . the possibility sliding hernias containing genital structures such as ovaries , fallopian tubes or even the uterus should be kept in the mind in all female hernia . the inguinal hernia in females should raise the surgeon s suspicion about the child s nuclear sex , particularly if the condition is bilateral . all female inguinal hernias should undergo ultra sonography to prove the presence of ovaries in the sac . if ovaries form the contents of the sac then a immediate surgery is required to avoid complications .

inguinal hernias are rare in females . the authors report a case of bilateral inguinal hernias in a 10-year - old female . on exploration , the patient was found to be having a sliding hernia containing incarcerated ovary as contents on both sides . peroperatively the contents were reduced , the sac was transfixed at its base and the redundant sac was excised . the repair of this form of hernias is more difficult because of adhesions between the contents and the wall of the sac and risk of damage during dissection . a description of this clinical presentation in the pre operative assessment and operative management are discussed in this report .

september 2011 , mosquito larvae were collected in irrigated rice fields surrounding tiassal , southern cte divoire ( 55247n ; 44948w ) and reared to adults in insectaries on a diet of mikromin ( tetra , melle , germany ) fish food . mosquitoes , 35 days of age , were exposed to 1 of 5 insecticides ( 0.1% bendiocarb , 1.0% fenitrothion , 0.75% permethrin , 0.05% deltamethrin , 4% ddt ) or a control papers for 1 hour , according to standard who procedures ( 7 ) . dna was extracted from individual mosquitoes according to the livak method ( 8) , and a subsample of 500 mosquitoes were all found to be the m molecular form of an . the target site mutation g119s in the ace-1 gene ( ace-1 ) and l1014f and l1014s kdr mutations were screened by using restriction fragment length polymorphism ( 10 ) or taqman assays ( 11 ) , respectively . according to who criteria , an . gambiae mosquitoes from tiassal are resistant to all insecticide classes , and resistance is extremely prevalent ; more than two thirds of mosquitoes survived the diagnostic dose for 4 of the 5 insecticides tested ( table 1 ) . to assess the level of resistance , we exposed the tiassal population and a susceptible laboratory population of an . gambiae ( kisumu ) mosquitoes to the pyrethroid deltamethrin or the carbamate bendiocarb for a range of exposure times and assessed deaths 24 hours later ( technical appendix ) . we found an unexpectedly strong resistance phenotype to the 2 insecticides ( figure 1 , figure 2 ) . for deltamethrin , 4 hours of exposure were required to kill 50% ( median lethal time , [ lt50 ] ) ; in comparison , the lt50 for the susceptible kisumu strain was < 2 minutes ( resistance ratio = 138 ) ( technical appendix ) . similarly , the lt50 for bendiocarb was nearly 5 hours for the tiassal strain yet < 12 minutes for the susceptible strain ( resistance ratio = 24 ) ( technical appendix ) . all mosquitoes were resistant according to world health organization classification ( < 80% dead ) ( 7 ) . time - mortality curve for wild - caught anopheles gambiae mosquitoes from tiassal , southern cte divoire , exposed to deltamethrin ( median time to death = 248 minutes ) . logistic regression line was fitted to time - response data by using sigmaplot version 11.0 ( www.sigmaplot.com ) . time - mortality curve for wild - caught anopheles gambiae mosquitoes from tiassal , southern cte divoire , exposed to bendiocarb ( median time to death = 286 minutes ) . logistic regression line was fitted to time - response data by using sigmaplot version 11.0 ( www.sigmaplot.com ) . to investigate the causes of this resistance , we screened a subset of mosquitoes for the target site mutations , kdr 1014f and 1014s . only the 1014f kdr mutation was detected , and this resistance allele was found at high frequency ( 83% ) . there was a significant association between presence of the 1014f kdr allele and ability to survive exposure to ddt but not to either pyrethroid ( table 2 ) . in contrast , the ace-1 allele was strongly associated with survival after exposure to bendiocarb and fenitrothion ( table 2 ) . * f and l represent mutant resistant alleles ( phenylalanine ) and wild - type alleles ( leucine ) , respectively ; s and g represent mutant resistant alleles ( serine ) and wild - type alleles ( glycine ) , respectively . no resistant homozygotes gg were found among the 186 mosquitoes genotyped for ace-1 by restriction fragment length polymorphism ( a subset of 48 was further screened by using the taqman assay ; congruence between the 2 methods was 100% ) . the frequencies were calculated for each insecticide and mosquito status ( alive / dead ) after exposure . genotypic odds ratios ( ors ) are shown because these exceed allelic ors for ddt ( recessive model ) , bendiocarb , and fenitrothion ( both overdominant models ) , and are similar for permethrin and deltamethrin . for bendiocarb and fenitrothion absence of gg genotypes in the alive group means that ors are infinity , therefore ors are shown if one gg was present . f and l represent mutant resistant alleles ( phenylalanine ) and wild - type alleles ( leucine ) , respectively ; s and g represent mutant resistant alleles ( serine ) and wild - type alleles . gambiae mosquitoes was first reported from cte divoire in 1993 ( 12 ) ; carbamate resistance was detected in the 1990s ( 13 ) . nevertheless , 2 decades later , it is surprising and worrying to find complete resistance to all insecticides tested , particularly for deltamethrin and bendiocarb at such high levels . ace-1 is strongly associated with organophosphate and carbamate resistance , and the absence of 119s homozygotes might be attributable to the high fitness cost of the ace-1 allele in the absence of insecticide ( 14 ) . presence of the 1014f kdr allele alone does not confer the ability to survive diagnostic doses of pyrethroids ; thus , alternative mechanisms must be responsible for the high - level pyrethroid resistance in this population . the selective pressures responsible for this intense multiple - insecticide resistance in tiassal mosquitoes are unclear . there is a high coverage of insecticide - treated bed nets , but this coverage does not differ from that in other parts of the continent , and indoor residual spraying has not been conducted in this region . this use is perhaps the most likely explanation in this district of intense commercial production of rice , cocoa , and coffee . whatever the cause , the implications of this resistance scenario for malaria control are severe . with no new classes of insecticides for malaria control anticipated until 2020 at the earliest ( 15 ) , assessing the effect of pyrethroid resistance on the efficacy of insecticide - treated bed nets is complex because of the poorly understood associations between net integrity , insecticide content , net usage , and net efficacy . nevertheless , resistance levels , such as those reported here , combined with continual selection pressure will inevitably lead to suboptimal mosquito control by use of insecticide - treated bed nets and indoor residual spraying . if unchecked , this resistance could spread rapidly and threaten the fragile gains that have been made in reducing malaria across africa . time - mortality curve for anopheles gambiae mosquitoes , kisumu strain , exposed to deltamethrin and bendiocarb , and time - death data for adult female a. gambiae s.s . mosquitoes , tiassal strain , and standard susceptible colony kisumu 24 hours after exposure to bendiocarb or deltamethrin .

preventing malaria used to seem as simple as killing the vector , the mosquito ; however , a recent study shows that this concept is now anything but simple . the highly effective use of insecticide - treated bed nets and indoor insecticide spraying is being challenged by mosquito resistance to insecticides . in west africa , populations of this mosquito vector are now resistant to all 4 classes of insecticide approved for this use . and no new classes of insecticide are anticipated until 2020 , at the earliest . development of newer classes of insecticide is crucial because if resistance continues unchecked , the hard - earned progress in malaria control in africa could be quickly reversed .

a 29-month - old boy presented with acute onset of esodeviation and limitation of ocular movement in his right eye . six weeks earlier , he had right otitis media , but no improvement was achieved . five days before onset of esodeviation , he had a high fever ( over 39 ) , otorrhea , and cough . laboratory evaluation revealed a white blood cell ( wbc ) of 30,127/ul and c - reactive protein ( crp ) of 51.60 mg / l . a blood culture was positive for streptococcus pneumoniae , suggesting a septic condition . on his second day in the hospital , the patient had a recurrent high fever due to mastoiditis complicated by otitis media . on his fourth day in the hospital , his fever was controlled but he complained of mastoid tenderness , otalgia , rhinorrhea , nasal stuffness , and postnasal drip , and his right eardrum was yellowish brown . laboratory evaluation revealed a wbc of 15,000/ul , crp of 19.68 mg / l , erythrocyte sedimentation rate of 115 mm / hr , and d - dimer of 739 ng / ml , suggesting a septic condition . on his fifth day in the hospital , he underwent myringotomy and insertion of a ventilation tube into the right ear . a serous discharge was drained from the myringotomy site . on the first day after surgery , an esotropia of 30 prism diopters ( pd ) and an abduction limitation ( -4 ) occurred in his right eye , and facial turn to the right appeared ( fig . six days after surgery , he underwent magnetic resonance imaging ( mri ) to assess other defects in intracranial or optic nerve pathways . the mri showed right mastoiditis , and stasis of the transverse sinus and internal jugular vein . temporal bone computed tomography showed erosive changes in the right mastoid adjacent to the sigmoid sinus , but petrous apicitis was not observed ( fig . one week after mastoidectomy , he had mostly recovered from the septic condition caused by the mastoiditis , but the esotropia of 30 pd , the abduction limitation ( -4 ) in the right eye , and the facial turn to the right were sustained . three weeks after mastoidectomy , we observed improvements in the esotropia ( 25 pd ) , abduction limitation ( -2 ) and alternate fixation . four months after surgery , he had fully recovered from the esotropia , limitation of ocular movement , and anomalous head posture ( fig . acute mastoiditis and intracranial complications resulting from otitis media were very common prior to the introduction of antibiotics . although the incidence of these complications dropped dramatically after antibiotics were developed , intracranial complications caused by mastoiditis remain serious complications , especially in infants , with an incidence of about 10% to 15% . abducens nerve palsy is a rare complication resulting from direct damage to abducens nerve pathways caused by gradenigo 's syndrome , petrous apicitis , cavernous sinus thrombosis or lateral sinus thrombosis . the abducens nerve is the cranial nerve most frequently involved in acquired cranial ocular motor palsy . the causes of this condition can be microangiopathy , cerebral trauma , tumor , and inflammation , or it may be idiopathic . the causes of abducens nerve palsy are similar in children and adults , although vascular diseases and viral infections are less common in children , whereas trauma and neoplasia occur more frequently . spontaneous recovery within 6 months is common , although the rate of recovery varies according to the cause [ 5 - 7 ] . abducens nerve palsy complicated by otitis media without petrous apicitis is very rare . in our patient , the most likely cause of abducens nerve palsy was inflammatory invasion of the periosteum of the petrous apex from the middle ear caused by pachymeningitis , extradural abscess or thrombophlebitis from the lateral or inferior petrosal sinus . the inferior petrosal sinus runs postero - inferiorly from the cavernous sinus in a groove between the petrous and basilar occipital bone . shortly after leaving the cavernous sinus , the inferior petrosal sinus runs parallel to the sixth nerve as the nerve pierces the dura . in our patient , abducens nerve palsy was accompanied by mastoiditis and sepsis complicated by otitis media , but there was no evidence of petrosal apicitis , cavernous thrombosis or thrombophlebitis from the lateral sinus responsible for ipsilateral abducens nerve palsy . venous stasis of the lateral sinus and a case report of thrombosis caused by perisinus fibrin deposition and phlebitis of the lateral sinus reinforce the hypothesis that abducens nerve palsy is secondary to inferior petrosal sinus thrombosis . this hypothesis is further reinforced by the absence of trigeminal nerve involvement . due to its small size , however , the inferior petrosal sinus is very difficult to visualize in radiologic diagnostic images . any disorder that causes an abduction deficit should be included in the differential diagnosis of patients with abducens nerve palsy . a syndrome involving constant otorrhea , headache , and diplopia , thought to be due to inflammation of the petrous apex , is called gradenigo 's syndrome . in the present patient , however , this syndrome was excluded on the basis of the absence of apicitis , retrobulbar pain , and trigeminal nerve palsy . we describe here a 29-month - old infant with a very rare case of abducens nerve palsy complicated by septic thrombosis of the inferior petrosal sinus due to mastoiditis without petrous apicitis .

we present a very rare case of a 29-month - old boy with acute onset right abducens nerve palsy complicated by inferior petrosal sinus septic thrombosis due to mastoiditis without petrous apicitis . four months after mastoidectomy , the patient fully recovered from an esotropia of 30 prism diopters and an abduction limitation ( -4 ) in his right eye .

our patient , a 64 year old gentleman presented via the emergency department with wet gangrene of the right fourth toe , associated with a severe cellulitis affecting the distal third of the right lower limb . the patient had been treated in the community for ulcers of mixed aetiology over the right lateral malleolus and heel . co - morbidities included mrsa colonisation , niddm , hypertension and peripheral vascular disease , the latter of which had resulted in left below knee amputation three years prior . conservative management was instituted , including intravenous rehydration , antibiotics ( vancomycin and metronidazole ) , with mri angiogram assessment demonstrating mild disease of the right external iliac artery and severely diseased right - sided arterial runoff below the trifurcation . following initial improvement secondary to intravenous antibiotics , no further progress was noted and resolution of cellulitis suggested involvement of the third and fifth digits . the patient also consented to below knee amputation if this was deemed necessary intra - operatively . the procedure was performed under regional anaesthesia , with a racket incision centred over the fourth metatarsophalangeal joint necessary to excise the fourth digit . the incision began 1 cm proximal to the metatarsophalangeal joint and passed distally to the base of the proximal phalanx which was divided to pass around the toe and across the plantar surface at the level of the flexor crease . the amputated segment was removed and sent to the laboratory for microbiological microscopy , culture and sensitivity analyses . the skin of the third and fifth toes adjacent to the fourth toe was debrided as necessary , although no further amputation was required . we opted to close this wound by constructing a tissue flap rather than leaving the wound to granulate by secondary intention . in this instance we utilised the fifth digit as a novel osteo - myocuteanous flap , rather than using conventional techniques . as can be seen from the x - ray studies performed postoperatively , we modified standard myocutaneous flap construction techniques by incising the medial border of the fifth digit to the periosteum , which was then mobilised to the superior / inferior surface of the fifth phalanxes , with the bone remaining in - situ ( figure 1 ) . the xray also demonstrates the phalanxes of the fifth toe being used to construct the flap used to close the defect . the patient made an uneventful recovery and following resolution of the cellulitis and after social services input he was discharged nine days postoperatively . amputation is frequently required to treat wet gangrene secondary to peripheral vascular disease , with numerous procedures reported including : limited digital , ray , transmetatarsal , and hindfoot amputations . ultimately , the level at which amputation must occur will be determined by the distribution of lower limb disease . nevertheless , good preoperative assessment is mandatory for each individual patient presenting with a gangrenous foot , to balance limb preservation following limited distal amputation against the superior wound healing associated with above / below knee amputation . while the psychological and physical benefits associated with limb preservation are well established , conventional procedures are not without complication . the wound generated by amputation of a single toe is usually either closed primarily or left to heal by secondary intention , although both strategies are frequently impaired by diabetic vascular disease . this complication may be more troublesome following ray amputation since the skin defect and tissue loss is more extensive . in contrast , this report suggests that the use of an osteo - myocuteanous flap may result in effective wound healing following limited digital amputation in the setting of diabetic microvascular disease , presumably due to increased vascularity at the wound site . while the use of an osteo - myocutaneous flap will result in loss of two digits , this is often necessary to adequately remove gangrenous tissue and does not cause any disturbance in function . the results in this patient have been good and no complications were observed within the first 30-day period postoperatively . consequently , we believe this technique may be of great benefit to those patients for whom single toe amputation may not have been considered as healing might have been problematic . however , we do acknowledge that toes amputated using this technique may still be susceptible to the complications that may occur in toe amputations using the conventional technique . these include deviation of the remaining toes to fill the gap left by the amputation thereby altering the biomechanics.(1 ) this risk is increased in amputations involving the second toe and may result in a hallux valgus deformity . further prospective randomised studies are thus required to compare this procedure with conventional techniques , to confirm the efficacy of osteo - myocuteanous flap construction and other potential postoperative complications .

amputation is frequently required to treat wet gangrene secondary to peripheral vascular disease . although different types of amputations have been reported , limited digital and ray amputation are the commonest amputations performed . the level of amputation will be determined by the distribution of lower limb disease but for every patient a balance between limb and functional preservation at lower levels versus better wound healing at higher levels should be sought.in this article we describe the novel osteo - myocutaneous flap , which we have used in our patient . we believe that this flap results in improved wound healing and although it results in loss of two digits , it does not impair function .

serum tumor markers including -human chorionic gonadotrophin , -fetoprotein , and lactate dehydrogenase were within normal limits . 1b ) imaging showed a 2.5-cm - sized poorly enhancing cystic mass at the right testis . pathological examination demonstrated that the cystic mass was confined within the testicular parenchyma , with a size of 2.52.41.7 cm . on macroscopic examination microscopically , the cyst was surrounded by a thick fibrous wall and was filled with mucinous material ( fig . the cyst had a single layer of columnar mucinous epithelial cells without nuclear atypia ( fig . the inflammatory cells were composed of lymphocytes , plasma cells , and histiocytes ( fig . teratomatous elements , such as cartilage , bone , or other mesenchymal teratomatous components , were not found . microscopically , the tumor was limited to the testicular parenchyma without involvement of the tunica albuginea . immunohistochemically , the lining epithelial cells were positive for cytokeratin 20 ( ck20 ) ( fig . 3c ) , as well as focally positive for cytokeratin 7 ( ck7 ) ( fig . 3d ) , d2 - 40 , wt-1 , and cytokeratin 5/6 ( ck5/6 ) . this study was approved by the institutional review board ( irb ) of seoul national university hospital . mucinous neoplasms of the testis or paratestis are rare and not well described in the medical literature . the first reported case of mucinous neoplasm was mucinous cystadenoma in the paratestis of an 11-year - old boy by kellert in 1959 . to date , most reported testicular / paratesticular ovarian - type surface epithelial neoplasms have been of the serous subtype , and previous papers reported approximately 24 cases of mucinous neoplasms of the testis or paratestis ; among these , only four reports described three cases of serous borderline tumors of the testis / paratestis and two cases of paratesticular mucinous cystadenomas were found , but there has been no report of any mucinous cystadenoma of the testicular parenchyma to date [ 3 - 7 ] . the histologic features of mucinous cystadenomas of the testis resemble those of common ovarian mucinous cystadenomas . that is , the cyst is typically composed of mucinous epithelium with tall , columnar endocervical - like cells lacking nuclear atypia . however , there are several histologic differences between testicular mucinous cystadenomas and ovarian mucinous cystadenomas . testicular mucinous cystadenomas are generally not as large as ovarian tumors , purportedly because the testicular tumors are found by patients earlier than their ovarian counterparts due to the sites at which the tumors arise . testicular tumors are more often unilocular and more frequently exhibit mucus extravasation associated with fibrosis or calcification than ovarian tumors , possibly because of trauma due to their superficial location . the origin of testicular mucinous neoplasms has not yet been clarified ; thus , several hypotheses have been suggested . ulbright and young supported the theory that the tumors arise from metaplasia of the mesothelium of the visceral tunica vaginalis . the theory that the tumors arise from the remnants of the mllerian ducts persisting in the male appendix , testis , or extratesticular scrotal contents is considered the most reasonable by some researchers . differential diagnoses include testicular mucinous borderline neoplasms / carcinomas , germ cell tumors , mesotheliomas , and metastatic mucinous tumors . in comparison with mucinous borderline tumors or mucinous carcinomas , mucinous cystadenomas testicular mucinous carcinomas or borderline neoplasms have been reported more frequently than testicular mucinous cystadenomas . to date , seven mucinous borderline neoplasms and four mucinous carcinomas have been reported . it is also important to rule out germ cell tumors , for example , teratomas with prominent mucinous components . teratomas almost always have components other than mucinous epithelial lined cysts , and 90% of those tumors occurring in adults are accompanied by intratubular germ cell neoplasia of unclassified type . unlike testicular mucinous cystadenomas , mesotheliomas exhibit positivity for calretinin , which is known to be expressed in mesothelial cells . the appropriate immunohistochemical staining , cytologic atypia , and history of mucinous carcinoma are critical for determining the origin of the tumor . the immunohistochemical profile of the tumor has not been specified until now . however , in several reports , testicular mucinous neoplasms have shown immunostaining that is positive for both ck7 and ck20 or positive for ck20 and negative for ck7 . the present case showed positive staining for ck20 and focal positive staining for ck7 , a result similar to previous studies . additionally , the present case also showed positive staining for cdx2 and negative staining for pax8 , d2 - 40 , and ck5/6 . cdx2 is known to be useful in distinguishing primary ovarian mucinous tumors from metastases of lower gastrointestinal tract origin . there has been only one case report of cdx2 expression in testicular or paratesticular mucinous neoplasms , revealing cdx2-positive and pax8-negative staining . together with the results of this report , testicular or paratesticular mucinous tumors may express cdx2 . immunohistochemical results for calretinin , ck5/6 , d2 - 40 , and pax8 suggest that testicular mucinous cystadenoma does not originate from mesothelium or mllerian duct remnants , while the results support the possibility of monodermal teratoma differentiation . although only a small number of testicular mucinous cystadenomas have been reported , these reported cases have shown good prognosis , similar to the prognosis of ovarian mucinous cystadenomas . in conclusion , mucinous cystadenoma of the testis is an extremely rare benign tumor and likely expresses cdx2 .

mucinous cystadenoma of the testis is a very rare tumor . herein , we report a case of mucinous cystadenoma arising in the testis of a 61-year - old man , along with a literature review . computed tomography showed a 2.5-cm - sized poorly enhancing cystic mass . grossly , the tumor was a unilocular cystic mass filled with mucinous material and confined to the testicular parenchyma . histologically , the cyst had a fibrotic wall lined by mucinous columnar epithelium without atypia . immunohistochemical staining was positive for cytokeratin 20 and cdx2 , as well as focally positive for cytokeratin 7 . the pathologic diagnosis was mucinous cystadenoma .

the following section describes the treatment procedure for patients with deep infection following tka using modified static spacers . the original prosthesis was removed , followed by intensive irrigation and wide debridement of the infected soft tissue . a 36 fr - diameter straight thoracic catheter ( mallinckrodt medical , athlone , ireland ) and a steinmann pin measuring 3.0 mm in diameter and 22 cm in length vancomycin ( 2 g ) was then added to the gentamicin bone cement ( depuy , warsaw , in , usa ) . at the late liquid stage of the cement , the steinmann pin was inserted into the tube , and the prepared cement was delivered through the tube . during this procedure , the tube was removed from the cement rod using a surgical knife . finally , a cement rod measuring 9 mm in diameter and 22 cm in length was formed ( fig . an entry hole was created at the center of the distal femur and proximal tibia for the insertion of the cement rod . the rod was then inserted into the femur and tibia through this hole . during insertion , it was important to place the center of the cement rod on an imaginary joint line . the proximal medullary canal of the tibia was filled with antibiotic - impregnated cement up to the surface of the proximal tibia , while the surgical assistant maintained proper anatomic alignment and joint space . the space between the cement of the distal femur and the proximal tibia was filled with more antibiotic - impregnated cement . finally , the suprapatellar pouch and medial and lateral gutter space were filled with antibiotic - impregnated cement to reduce soft tissue adhesion ( fig . cylinder splint immobilization was required for three days after the operation , after which a fixed - angle knee brace was used and toe - touching ambulation was allowed until the reimplantation surgery . from april to november 2007 , the authors performed the static technique in four patients using the novel antibiotic - impregnated cement rod for the treatment of infected tka ( culture : staphylococcus in three cases and no bacteria in one case ) . follow - up laboratory studies , including erythrocyte sedimentation rate and c - reactive protein , culture study via knee aspiration and a frozen biopsy from the second - stage operation ( < 5 polymorpho - leukocytes / high power field ) were performed to confirm successful eradication of the infection . the second - stage reimplantation was performed when all the criteria for the validation of infection control were met ( fig . the second - stage reimplantation was performed using the rectus snipping approach , and more than 90 of flexion was obtained intra - operatively . in all four patients , no re - infection was evident after two and a half years of follow - up . the range of motion of the knee joints were respectively improved from 50 to 80 , 95 , and 100 , and the knee society scores were 70 , 86 , 65 , and 84 , respectively , in the last follow - up evaluation . fehring et al.8 ) emphasized the importance of resting the joint in septic joint conditions . others also reported that the static spacer technique provides more stability than the mobile spacer technique in patients with severe bone loss.5,8 ) the main advantage of this technique is the maintenance of a normally aligned lower limb during the interval period . this maintains knee stability in combination with early muscle strengthening exercises , including quadriceps setting exercise , and enables the patient to comfortably dress and manage him / herself during the intervening period . the cement rod and static spacer provide a stable gap between the femur and tibia , thereby minimizing soft tissue contracture and shortening of the lower limb . in addition , symmetric maintenance of the soft tissue of both medial and lateral gutters requires no additional soft tissue balancing at the second - stage reimplantation . the additional cost of a metal nail , however , and the difficulty in infection control due to biofilm formation around the metal nail can be troublesome . in addition , a metal nail can not be removed easily at the second stage reimplantation due to its hardness , and soft tissue adhesion of the femoral or tibial medullary canals . on the other hand , an antibiotic - impregnated cement rod enjoys advantages , such as inexpensive antibiotic delivery to the marrow spaces and easy removal by using a hercules cutter . in addition , a static spacer is anchored to the cement rod , which can prevent spacer migration and bone erosion . this feature is believed to generate less cement wear debris than with the conventional static spacer or mobile articulating spacer technique . during the conduct of the antibiotic - impregnated cement rod technique , antibiotic - impregnated cement was applied to the proximal tibia , distal femur , joint gap space , suprapatellar pouch , and both gutters in a stepwise manner . this technique enables easy removal of the cement and reduced soft tissue adhesion at second - stage reimplantation .

the two - stage exchange arthroplasty ( one- or two - stage ) is believed to be the gold standard for the management of infections following total knee arthroplasty . we herein report a novel two - stage exchange arthroplasty technique using an antibiotic - impregnated cement intramedullary nail , which can be easily prepared during surgery using a straight thoracic tube and a steinmann pin , and may provide additional stability to the knee to maintain normal mechanical axis . in addition , there is less pain between the period of prosthesis removal and subsequent reimplantation . less soft tissue contracture , less scar adhesion , easy removal of the cement intramedullary nail , and successful infection control are the advantages of this technique .

a 52-year - old man presented to our hospital with complaint of painless , progressive decrease in vision in both eyes for 6 months . there was no history of trauma , recurrent redness or any ocular surgery . the patient was born with a bilateral cleft lip and cleft palate , for which surgical repair was done in childhood and he was prescribed an obturator for the small residual cleft in the palate [ fig . 1 ] . on examination , the patient was orthophoric , all ocular movements were full and free , and pupillary reactions were also normal . the applanation tonometry by golmann applanation tonometer revealed an intraocular pressure of 18 mm in both eyes . the fundus examination revealed bilateral odp inferotemporally with maculopathy with hyperpigmentation at the macula [ fig . telecanthus and hypertelorism were ruled out by measuring inner canthal distance , outer canthal distance and interpupillary distance . showing repaired bilateral cleft lip ( blue arrow ) and palate with residual fistula ( red arrow ) fundus of both eyes showing optic disc pit inferotemporally with maculopathy the fundus flourescein angiography showed a normal arterio - venous filling with window defects at the macula but no leakage [ fig . the spectral domain optical coherence tomography of the right eye revealed an odp with maculoschisis with thinning of the retinal layers , with a neurosensory detachment not communicating with the pit in the right eye while the left eye showed an odp with maculoschisis with thinning of the retinal layers . there was also hyper - reflectivity of retinal pigment epithelium - choriocapillaries complex in both eyes [ fig . the magnetic resonance imaging of the brain and spine done to rule out any other midline or neurological anomalies were within normal limits . ultrasonography of the abdomen and pelvis was also done to rule out any renal abnormality and was unremarkable . fluorescein angiography of both eyes showing window defects at macula , but no leakage spectral domain optical coherence tomography of right eye showing schisis and neurosensory detachment ( a ) and of left eye showing only maculoschisis ( b ) the patient was not advised surgery in view of poor visual prognosis due to retinal thinning and pigmentary changes at macula . he was also referred to the department of plastic surgery , where he was advised to continue using the obturator . the optic disc pit is small , gray - white , oval depression found at the optic nerve head . it is a congenital defect that occurs due to imperfect closure of superior edge of the embryonic fissure . it appears as a crater like indentation on the surface of optic nerve head usually with a steep temporal wall . however , variants of optic disc colobomas especially morning glory syndrome have been associated with the papillorenal syndrome and basal encephaloceles . papillorenal syndrome , also known as renal - coloboma syndrome is an autosomal dominant disorder consisting of bilateral optic disc anomalies associated with hypoplastic kidneys , implicating pax2 and pax6 at chromosome 10 as the causative genes . these genes play an important role in the normal development of kidney , mid - brain , hind - brain , ears and eyes . developmental anomalies of the optic disc have also been seen in patients with basal encephalocele associated with cleft lip and palate . these include the morning glory syndrome , pale discs , coloboma of the optic nerve head , megalopapilla , optic nerve dysplasia , peripapillary staphyloma and odp . the occurrence of basal encephalocele with mid - facial clefting is known as frontonasal dysplasia . it has a wide clinical spectrum consisting of hypertelorism , primary telecanthus , a broad nasal tip which is frequently cleft , median cleft upper lip and premaxilla , median cleft palate , anterior or basal encephalocele , and agenesis of the corpus callosum . the pathogenesis is unknown , but a nonseparation theory , which assumes that during closure of the neural tube , the ectodermal elements fail to separate , has been implicated . the cleft lip and palate occurs due to nonfusion of frontonasal , maxillary and mandibular prominences . itakura et al . , have suggested that if the sphenoid encephalocele prevents fusion of the palate , which precedes formation of the optic nerve , then the later development of the optic nerve could be abnormal . the co - existence of cleft lip and palate with odp in the absence of basal encephalocele can not be explained by the above - mentioned theory , and the only common pathway in the pathogenesis of these two independent disorders is the gestational age of 68 weeks , at which the frontonasal , maxillary and mandibular processes fuse and the embryonic fissure in the primitive eye closes . hence , it may be hypothesized that an insult at this time may have caused these two anomalies to co - occur . to the best of our knowledge , there is only one case of odp with maculopathy , with cleft lip - palate with basal encephalocele reported in the literature . this is the first case report of odp with maculopathy with cleft lip and palate without a basal encephalocele found incidentally in the same patient or there might be a possible unexplained association . thus , a possibility of odp should be kept in mind , in a patient of cleft lip and palate with visual complaints , irrespective of the presence or absence of basal encephalocele . the various options for management of maculopathy associated with odp include gas tamponade with or without laser barrage and surgically with pars plana vitrectomy with or without internal limiting membrane peeling with or without gas tamponade . it has been seen that multilayer schisis pattern of maculopathy has poorer visual prognosis and may require multiple surgeries as compared with serous detachment pattern .

optic disc pit ( odp ) is small , gray - white , oval depression found at the optic nerve head . it is a congenital defect that occurs due to imperfect closure of superior edge of the embryonic fissure . cleft lip and palate are also congenital midline abnormalities occurring due to defect in the fusion of frontonasal prominence , maxillary prominence and mandibular prominence . there is only one case report describing the occurrence of odp in a young patient with cleft lip and palate who also had basal encephalocele . we describe a 52-year - old patient with congenital cleft lip and palate with bilateral odp with maculopathy but without any other midline abnormality .

evaluation focused on a sample of 10 representative counties and consisted of personal and media surveys . the personal survey assessed knowledge , behavior , and attitudes about wnv ( 8) . knowledge was measured by asking respondents how wnv is transmitted , who is most vulnerable , and what self - protection measures are available . behavior was measured by asking what respondents had done during the past week to protect themselves from mosquito bites . attitude was measured by asking respondents their perceived risk of contracting wnv and for concerns or comments about recommended protective measures . a total of 2,329 calls were made reaching 779 eligible respondents ; 534 ( 69% ) respondents participated in the survey . compared to kansas ' census 2000 data , the sample 's demographics were comparable to the general population . ninety seven percent of the sample had heard of wnv , 94% knew that it is transmitted through mosquitoes , and 70% knew that persons > 50 years of age were most likely to become severely ill from it . among the 17 spanish - speaking respondents , there was significantly less awareness ( p<0.001 , chi - square test ) ; only 7 , ( 41% ) had heard of wnv . among respondents who had heard of wnv , 89% knew > 1 personal protective measure , 59% knew to avoid mosquitoes , 47% knew to use insect repellent , and 21% specified the use of repellent with deet ( table 1 ) . fewer respondents used repellent than those who had cited this measure ( p<0.001 , chi - square test ) . more respondents wore protective clothing ( p<0.001 , chi - square test ) , eliminated standing water ( p<0.001 , chi - square test ) , and maintained window screens ( p<0.001 , chi - square test ) than those who had cited these measures . * deet , n , n - diethyl - meta - toluamide ; na , not available . more than one third expressed concerns about deet , mostly about health and safety ; 26% stated that wearing long clothing outside at dawn and dusk was uncomfortable , and 16% cited difficulties eliminating standing water . respondents estimated the risk of contracting wnv ; 55% considered the risk to be low and 8% considered it to be high . to assess the process and outcome of the kdhe campaign , respondents were asked to list their most recent sources of wnv information . most respondents cited mass media and word - of - mouth , few cited magazines or web sites , and even fewer cited healthcare providers or brochures ( table 2 ) . every newspaper , radio station , and television station in the 10-county sample was contacted by phone or email . all were asked about receipt of kdhe wnv materials and if and how materials were used . no television station broadcasted psas or scripted stories provided by kdhe ; only half recalled receiving the materials . kdhe campaign materials were used minimally by local media ; persons were likely informed from national news , cdc , or news releases when local cases of wnv were reported . low awareness levels in spanish - speaking respondents indicated that prevention messages from any source were not reaching this population segment . three factors appeared to influence the degree to which wnv prevention messages affected respondents ' knowledge , attitudes , and behavior : message content , media used , and method of delivery . more respondents knew they should be using repellent than actually used it . knowledge and awareness risk perceptions may be a moderating factor . despite 90 confirmed cases of wnv , a 4-fold increase from 2002 , and 731 reported presumed cases , most respondents perceived little risk of acquiring the illness . thus , they likely were not motivated to use protective measures , especially those seen as deleterious or unpleasant . more respondents took other protective measures ( wore protective clothing , removed standing water , maintained screens ) than cited them . clearly some took these measures for other reasons , unaware that they provided protection from wnv . mass media and word - of - mouth were the most successful methods of providing wnv information to respondents . brochures were least successful , indicating that they may be ineffective for this type of communication , or that difficulties with their distribution occurred . timing and campaign material delivery methods were critical factors . materials were sent in the spring before the peak of wnv incidence . by the time our survey was conducted during peak wnv season , news media considered wnv a " hot topic . " media respondents often did not recall receiving wnv materials , yet asked our surveyors for materials . news media look for current materials and do not likely store information for later use . we recommend the following practices for public health disease prevention campaigns for wnv and other emerging diseases : 1 ) reduce barriers to desired behavioral changes . 2 ) distribute materials by email with provisions to assure recipients that materials are virus - free . send explanatory letters by the postal service before and after any email . provide a a web site for direct access to campaign materials . 4 ) research ways to influence and promote word - of - mouth , an important source of information . 7 ) design campaigns for a linguistically and culturally diverse population ( 10 ) and to reach vulnerable population subgroups such as the elderly and immunocompromised for wnv ( 1115 ) .

we evaluated the 2003 kansas west nile virus public education campaign . awareness was widespread but compliance was low . spanish - speaking persons were poorly informed . relevant factors included population segment variability , campaign content , media choice , and materials delivery methods .

restuans mosquitoes collected by mosquito surveillance programs in 2001 and 2002 in nassau ( 89 identified/100 tested ) , orange ( 66/87 ) , rockland ( 83/96 ) , and westchester ( 20/20 ) counties and in 2005 and 2006 in tompkins county ( 46/52 ) ( 1 ) . baited cdc light traps and gravid traps were used to capture host - seeking and ovipositing females , respectively . seventy percent of mosquitoes were collected from traps located in public places such as parks , preserves , woodlots , cemeteries , and golf courses ( hereafter , parks and preserves ) . the remaining 30% were collected on residential properties , near storm water basins and sewage treatment plants , and at a university composting facility and dairy barn . genomic dna was extracted from each mosquito by using dnazol - bd ( molecular research center , cincinnati , oh , usa ) or dneasy blood & tissue kits ( qiagen , germantown , md , usa ) . we subsequently used dna sequencing with cytochrome b primers as follows : cyt f 5-gchgayachwvhhyhgchttytchtc-3 and cyt h 5-cccctcagaatgatatttgtcctca-3 , in which w = a or t , h = a , c , or t , y = c or t , and v = a , c , or g. cycling conditions were 94c for 2 min , followed by 55 cycles at 94c for 45 s , 50c for 50 s , and 72c for 1 min with a final extension at 72c for 7 min . 300-bp pcr products were purified with an exonuclease - alkaline phosphate kit ( exo sap - it , usb corporation , cleveland , oh , usa ) . samples were sequenced at the biotechnology resource center ( cornell university , ithaca , ny , usa ) with a 3730 dna analyzer ( applied biosystems , foster city , ca , usa ) . sequences were identified by using blastn searches in the genbank database to compare fragments ( 8) . pipiens blood meals ) , mammals ( n = 12 , 6.5% ) , and a northern brown snake ( storeria d. dekayi ) ( n = 1 , 0.5% ) . cx . restuans fed exclusively on birds . avian host species were similar to those previously reported ( 3,4 ) , except that northern cardinals ( cardinalis cardinalis ) , not american robins , were the principal hosts throughout the season , and feeding patterns differed somewhat , depending on the habitat of the trap site . northern cardinal , gray catbird ( dumetella carolinensis ) , american robin , and blue jay ( cyanocitta cristata ) accounted for 64% of the identifications . on residential properties , 52% of the blood meals were from cardinals . american robin blood meals accounted for only 12% of the blood meals and were found only in parks , preserves , and residential and storm water catch basins habitats . crows ( corvus spp . ) accounted for 26% of the blood meals from storm water catch basins and sewage treatment plant sites but only 2% of the collections from parks and preserves . american crows ( c. brachyrhynchos ) and fish crows ( c. ossifragus ) are found where crow - fed mosquitoes were collected . mammalian blood meals were identified in june ( human , white - tailed deer , and raccoon ) , july ( deer and virginia opossum ) , and august ( human , 3 white - tailed deer , and 2 eastern gray squirrels ) . the percentage of northern cardinal and american robin blood meals was relatively constant throughout the summer ( p = 0.261 , fisher exact test ) ( table ) . derived blood meals increased somewhat late in the summer ( p = 0.668 , fisher exact test ) . however , data on breeding bird communities were available for mosquito trap locations , and all species detected in blood meals were known to be present there ( 9,10 ) . in tompkins county , 10-min point - count censuses within a 50-m radius of mosquito traps were conducted 23 times each month from june through september 2006 , totaling 140 counts . sites included 8 residential properties , a university composting facility , and a wooded area . of the 84 avian species recorded , the most frequent were northern cardinal ( n = 110 ) , black - capped chickadee ( poecile atricapillus ) ( n = 109 ) , american robin ( n = 103 ) , blue jay ( n = 102 ) , and american crow ( n = 100 ) . although the relative frequency of northern cardinals and american robins was approximately the same at tompkins county sites , northern cardinals were 7.7 times more likely than american robins to be selected at those sites . we found northern cardinals , rather than american robins , to be the predominant hosts of cx . restuans in all habitat types except storm water catch basins , where crows were identified most frequently . pipiens fed on mammals , similar to findings of a study in connecticut ( 4 ) . the infrequent identification of crow - derived blood meals relative to their local abundance is an enigma ( 3,4 ) . however , the spatial and temporal distribution and social behavior of crows have never been considered . unless mosquito traps are located where crows are present at dusk or sleeping , the probability of collecting a crow - fed mosquito in the area sampled is low . this caveat is particularly relevant for mosquitoes with relatively short flight ranges such as cx . restuans , which presumably would not travel far to find suitable hosts . why american robins were the predominant hosts found in host - feeding studies in connecticut , maryland , and washington , dc ( 4,5 ) and why northern cardinals were the preferred hosts in our study are not clear . at the tompkins county , new york , sites , thus , host abundance does not explain the frequency of cardinal - derived blood meals , at least at those sites . cardinals and robins are common , share similar habitats , and are capable of amplifying wnv ( 11,12 ) . wnv seroprevalence rates in northern cardinals , american robins , and other birds differ across geographic areas from year to year ( 13 ) . whether host - feeding patterns parallel those findings is not known . pipiens fed on humans in june and august and on deer throughout the summer . in areas experiencing recurrent human wnv infection , future blood meal analyses should focus on peridomestic populations of culex spp . to better understand their predilection for avian and/or mammalian feeding and the spatial and temporal dynamics of their host - feeding activities .

mosquito feeding patterns identify vertebrate species potentially involved in the amplification of west nile virus . in new york , northern cardinals ( cardinalis cardinalis ) were the predominant hosts in most habitats . crow ( corvus sp . ) blood meals were most frequently identified from sewage treatment plant and storm water catch basin habitats .

lymphangioma circumscriptum ( lc ) or microcystic lymphatic malformation is a hamartomatous malformation of the lymphatic channels of the skin . treatment of lc is difficult because of the persistent nature of the disease due to deeper subcutaneous cisternal connections . we report here a case of lc treated effectively with radiofrequency ablation without any recurrence . a 16-year - old male with fitzpatrick skin type v presented to our clinic with partially fluid - filled lesions on left upper arm with slight local swelling . the patient had these lesions since the age of 2 years and had been repeatedly treated with antibiotics for local infection . examination showed a well - defined plaque on left upper arm with grouped vesicular lesions , giving the typical appearance of a a biopsy was taken from the edge of the lesion and histopathology showed multiple thin - walled , dilated lymphatic spaces in the papillary dermis and these spaces contained lymph and few erythrocytes . the overlying epidermis was thin , and there were elongated rete ridges that appeared to surround the lymphatic channels . the patient was given a systemic antiobiotic , cefadroxil 500 mg twice daily for 5 days , to treat the infection including oozing from the lesions and to decrease the inflammation . radiofrequency ablation was done a week later ( basco radiofrequency device , model rf - b2 , high frequency 2 mhz , power < 150 w ) , in cut and coagulate mode with wire loop electrode , under local anesthesia . the patient was advised to clean the area with betadine lotion and apply topical antibiotic mupirocin on the lesions . three sessions were required at weekly intervals for the lesions to clear as some deeper components were left untreated at the first two sessions . one week after last treatment , the area had partially healed with slight depigmentation . at 1 month , the lesions had completely healed and swelling had subsided [ figure 1 ] . no recurrence has occurred in the past 1 year and the patient is still under surveillance . ( a ) lc lesion on the left upper arm ; ( b ) lesions being treated with radiofrequency ablation ; ( c ) immediate post treatment red erythematous area ; ( d ) complete healing of the lesions at 1 month lc is benign ectasia with two components : the clinically obvious , dermal vesicular component , visible on the skin , and the deeper subcutaneous cisternal element . whimster described the pathogenesis and said that lc arises from the subcutaneous muscle - coated lymphatic cisterns which receive lymphatic flow from the surrounding tissue , but this is not drained to the normal lymphatic system . these dilated cisterns conduct the lymph through communicating channels into the dermal thin lymphatics , which balloon out into the epidermis . treatment modalities include surgical excision , lasers and sclerotherapy with varying success.[35 ] we tried the radiofrequency ablation to treat lc , which produced near - complete clinical ablation with coagulation of lesional and perilesional skin leading to fibrosis of the perivesicular lymphatics . the follow up was longer in our case , i.e. , 1 year and we are encouraged to do a case series to determine the efficacy of radiofrequency in this notorious condition .

lymphangioma circumscriptum ( lc ) , a hamartomatous lymphatic malformation , is a therapeutic challenge for the dermatologist . various modalities like surgical excision , lasers , and sclerotherapy have been used in the past to treat this notorious skin condition . we report the efficacy of a radiofrequency ablation in a patient with lc . the treatment efficacy of radiofrequency was satisfactory in our patient with no recurrence during 1 year follow - up period . the radiofrequency technique is a safe and economic treatment for management of lc .

in november 2009 , a bat was found on the ground in bokeloh , lower saxony , germany ( 522513.99n ; 92331.56e ) . it was given mealworms and water ad libitum supplemented with minerals and vitamins . in february 2010 , the bat began to act aggressively , directly approaching any moving object , vigorously trying to bite , and screaming ferociously . this agitated stage lasted for 7 days and was followed by general weakness , lethargy , and paralysis . after the first 3 days of the clinical course the bat was submitted for testing , and rabies diagnosis was performed by using immunohistochemical analysis . lyssavirus antigen was detected in numerous neurons of the cerebral cortex , cerebellum , and especially the nucleus funiculi lateralis and the nucleus olivaris of the medulla ( figure 1 ) . organs other than the central nervous system , e.g. , the salivary glands , did not contain lyssavirus antigen . after the first cell passage in rabies tissue culture infection test ( 9 ) , virus was isolated from brain tissue . antigenic typing performed with a panel of 10 antinucleocapsid monoclonal antibodies ( 10 ) clearly differentiated the isolated virus from all other tested lyssavirus species ( table ) . immunohistochemical analysis of brain of natterer s bat for lyssavirus antigen by using the avidin biotin complex method . cytoplasmic granular - to - diffuse staining for rabies antigen is visible in the perikarya and neuronal processus . b ) medulla and neurons of the nucleus funiculi lateralis showing strong cytoplasmic staining for rabies antigen . bblv , bokeloh bat lyssavirus ; rabv , rabies virus ; lbv , lagos bat virus ; mokv , mokola virus ; duvv , duvenhage virus ; eblv , european bat lyssavirus ; ablv , australian bat lyssavirus ; + + + , strongly positive ; , negative . results of discriminatory reverse transcription pcr results for eblv-1 and eblv-2 ( 11,12 ) were negative , and only a generic reverse transcription pcr ( 13 ) yielded a 605-bp amplification product similar to that of the positive control . the nucleotide sequence was determined by using standard methods ( primers and protocols are available upon request ) . sequence analysis of the nucleoprotein gene performed with mega version 4.0 software ( www.megasoftware.net/mega4/mega.html ) showed that bblv differed from all other published lyssavirus sequences with the highest nucleotide identity to khuv ( 80% ) , followed by arav ( 79% ) , eblv-2 ( 79% ) , australia bat lyssavirus ( 77% ) , eblv-1 ( 77% ) , irkut virus ( 76% ) , shimoni virus ( 76% ) , rabv ( 73 - 75% ) and duvenhage virus ( 75% ) . lagos bat virus ( 72 - 74% ) , mokola virus ( 72% ) , and west caucasian bat virus cbv ( 72% ) showed the highest divergence to bblv . also , phylogenetic analysis based on concatenated n - p - m - g - l nucleotide sequences showed that bblv is most closely related to khuv , followed by eblv-2 ( figure 2 ) . phylogenetic tree inferred from concatenated n - p - m - g - l sequences of bat lyssaviruses . the neighbor - joining method ( kimura 2-parameter ) was used as implemented in mega4 software ( www.megasoftware.net ) . rabv , rabies virus ; ablv , australian bat lyssavirus ; arav , aravan virus ; khuv , khujand virus ; bblv , bokeloh bat lyssavirus ; european bat lyssavirus ; irkv , irkut virus ; duvv , duvenhage virus ; shibv , shimoni bat virus ; lbv , lagos bat virus ; mokv , mokola virus ; wcbv , west caucasian bat virus . we report the discovery of a lyssavirus ( designated as bblv ) from a natterer s bat that died with rabies - like clinical signs . initially , a distinctive pattern in the reaction with a panel of antinucleocapsid monoclonal antibodies indicated the presence of an antigenically atypical isolate . the differentiation from other lyssavirus species was confirmed by phylogenetic analysis ( figure 2 ) . bblv is pathogenic because it caused a fatal disease in the natterer s bat that was similar to the clinical picture of rabies seen in other bats . viral antigen was present in many locations of the brain ( figure 1 ) but surprisingly not in the salivary glands . since the exact date of infection is unknown , the incubation period can only be estimated as > 4 months . whether the natterer s bat is the natural reservoir species of bblv or whether it was bats ( eblv-2 from m. daubentonii , m. dasycneme , khuv from m. mystacinus , and arav from m. blythii ) indicating that myotis spp . if one considers the history of bat rabies in europe , it seems unlikely that bblv had spread from a distant origin into central europe or that the bat itself was translocated over long distances . the fact that bblv has been identified only in 1 bat is puzzling , considering the relatively high level of surveillance in germany . also , of 63 natterer s bats tested during 19992010 in a retrospective study , none tested positive for rabies ( t. mller et al . germany is the only country where several bat species other than serotine bats , i.e. , pipistrellus nathusii , pipistrellus pipistrellus , and plecotus auritus , have been found infected with eblv-1 during this study ( t. mller et al . data ) , and this is the second discovery in recent years of a new lyssavirus species through routine passive bat rabies surveillance . also , in 2007 a daubenton s bat found on the ground was taken to a rehabilitation center , where it died and subsequently tested positive for eblv-2 ( 7 ) . in both cases , the person who took care of the animal had completed the full preexposure vaccination , as a required risk - mitigating measure . an encounter with a bblv - infected natterer s bat could lead to a fatal outcome because bat lyssaviruses have caused several human cases of infection ( 4 ) . in europe , species conservation and research require the handling of bats by bat workers . during 20002010 , a total of 37,140 handlings were recorded for the natterer s bat ( bat marking centre , saxon state office for environment and geology , dresden , germany ) , underlining the need for adequate prophylaxis for bat handlers . if one considers the close phylogenetic relationship between bblv and eblv-2 humans who receive rabies prophylaxis however , recent studies of the antigenic relationships of lyssaviruses have shown the difficulty of interpreting antigenic differences by using sequences alone ( 14 ) . thus , in vitro and in vivo cross - neutralization and protection studies with current anti - rabv vaccines are urgently required for assessing the public health risk posed by this new lyssavirus .

a virus isolated from a natterer s bat ( myotis nattererii ) in germany was differentiated from other lyssaviruses on the basis of the reaction pattern of a panel of monoclonal antibodies . phylogenetic analysis supported the assumption that the isolated virus , bokeloh bat lyssavirus , may represent a new member of the genus lyssavirus .

intramucosal melanotic nevi with multiple polypoid presentation in oral cavity are rare though solitary nevi are not uncommon . in 1943 , , 1967 adopted the less anatomically specific term , intramucosal nevus which clinician understand easily . white adults have ten to forty cutaneous nevi on an average , but intraoral lesions are rare . oral nevi follow the same classification as that of cutaneous nevi however ; the term intradermal is replaced by intramucosal . although little doubt exist that nevus cells arise from the neural crest , whether the cells represent true melanocytes or are closely related . melanocytes are located suprabasally in the epithelium , are dendritic cells and transfer melanin to the adjacent keratinocytes . on the contrary nevus cell has rounded cytoplasm and lack the dendritic processes , typical of melanocytes . normally melanin is retained by nevus cells and not transferred to adjacent keratinocytes . the intramucosal nevus is composed of a bulk of nevus cells in the mucosal epithelium . melanotic nevi can be present at birth , or they may appear shortly after birth . although little doubt exist that nevus cells arise from the neural crest , whether the cells represent true melanocytes or are closely related . melanocytes are located suprabasally in the epithelium , are dendritic cells and transfer melanin to the adjacent keratinocytes . on the contrary nevus cell has rounded cytoplasm and lack the dendritic processes , typical of melanocytes . the intramucosal nevus is composed of a bulk of nevus cells in the mucosal epithelium . melanotic nevi can be present at birth , or they may appear shortly after birth . a 26-year - old male presented at the outpatient department with the chief complaint of irritation from lower anterior teeth and a mass present on upper front region of jaw [ figure 1 ] . tumor was present since birth , was red in color initially and it gradually increased to its present size . preoperative view before extraction patient sustained an accident one year back , which caused loss of right , lateral incisor and following accident the color of the mass changed to black . clinical examination revealed an indurate , black nodular lesion of about 8 - 10 cm in diameter , firm in consistency and rough textured with irregular margins . periodontal probe was used to detect any false or true pocket but there was no evidence of periodontal disease . patient was advised extraction of right central incisor [ figures 2 and 3 ] ( in consultation with department of prosthodontic to rule out its interference with fixed prosthesis fabrication . ) following histological report of nevus , gingivectomy was undertaken with adequate alveoloplasty [ figures 4 and 5 ] . intra operative view ( after gingivectomy ) post operative view ( after one month ) h and e section revealed parakeratinized stratified squamous epithelium . pigmented nevus cells were seen in circumscribed groups ( theques ) in the connective tissue subjacent to the epithelium . histopathologic view ( h and e 100 ) histopathologic view ( h and e 400 ) the patient remained uneventful almost one year following operation till date and is advised follow up . pigmented nevus cells were seen in circumscribed groups ( theques ) in the connective tissue subjacent to the epithelium . histopathologic view ( h and e 100 ) histopathologic view ( h and e 400 ) the patient remained uneventful almost one year following operation till date and is advised follow up . nevi are benign lesion , present commonly on the skin but also occur in oral mucosa . they may present as round or oval well circumscribed ; slightly raised in 65 - 80% cases . oral nevi are usually smooth and rarely have a papillated or rough surface . in present case nevi was neither well circumscribed nor round and smooth but had irregular margins and was multi polypoid in nature . the intramucosal type of oral nevus is most common by far and represents 63 to 70% of all oral nevi , most common on the hard palate ( 40% ) . second most common location is the buccal mucosa ( 20% ) , 10% of all types of oral nevi are found on gingiva . among all nevi the present case of intramucosal nevi was on gingival surface , a rare finding . about 75% of the nevi smaller than 0.6 cm . the present case is unique with an exceptional large size of 8 - 10 cm . in general , the larger nevi are considered to be congenital akin to the present case . although congenital nevi in the oral cavity have been reported , they are extremely rare , none underwent malignant transformation . further gingival surface nevi , an exceptional giant size is unique to the present case .

intramucosal melanotic nevus with multiple polypoid presentations in oral cavity is rare ; though single nevus is not uncommon . nevi are benign proliferations of nevus cells either in the epithelium or in the subepithelial stroma . they are best categorized as hamartomas rather than true neoplasm . we present a case of intramucosal melanotic nevi in a 26-year - old male patient , which clinically resembled hereditary fibrous gingival enlargement .

traditionally , respiratory monitoring has concentrated on static and summary measures of mechanics and gas exchange . resistance and compliance , plateau pressure , auto - positive end - expiratory pressure ( auto - peep ) , tidal flows and volume , ventilatory dead space and oxygenation indices provide useful diagnostic information and treatment targets , but all characterize global performance , provide few clues to the nature of any abnormality they report , and do not inform us directly of regional distortions of lung topography ( for example , caused by atelectasis , pneumothorax , pleural effusion , and compressive intrathoracic lesions . ) a recently published study appearing in this journal by lev and colleagues again illustrates the potential added value of acoustic dynamic imaging for the acute care setting . sound - based patient monitoring appears close at hand , but a few questions remain before such methods can be confidently deployed and their data unequivocally interpreted . could some updated version of the venerable stethoscope an instrument that , unlike thoracic ultrasound , passively acquires rather than injects sonic energy eventually join other emerging technologies ( for example , electrical impedance tomography ) to address needs for dynamic regional imaging and surveillance of the diseased lung ? although the highly portable and cost - effective stethoscope has served medicine admirably and with relatively little conceptual modification for the better part of two centuries , our computer - aided ability to detect , filter , classify and record sonic information has progressed immeasurably beyond what the stethoscope can do . what we identify as an audible wheeze , rhonchus , or crackle signs that often prompt us to initiate or modify treatments possess acoustic ' frequency signatures ' amenable to categorization , quantification , and display . to a lesser extent , the same can be said of bronchial breath sounds and the relative acoustic silence of non - ventilated or poorly aerated zones . the value of today 's stethoscope depends on the observer 's ears , brain and memory for interpretation as it moves from site to site . an intriguing alternative is to deploy a topographically dispersed array of miniaturized microphone pickups , linked by electronic circuitry , that quantifies the amplitude , classifies the nature of the sound or absence of it and displays an acoustic map of the structural or functional abnormalities that gave rise to that distribution of spontaneously generated sonic energy . one such system , the vibration response imaging used in lev and colleagues ' study , appears to be nearing the point of commercial entry into the clinical arena . noninvasive , well tolerated , and providing near - continuous recording , the information from vibration response imaging and other devices for sonic surveillance can theoretically benefit critical care giving in ways other than by providing a changing acoustic outline . the nature , timing , and distribution of acoustic energy are each important . a few examples : crackles , especially those that blossom late in the inspiratory cycle , suggest the need for added peep ( either for improving gas exchange or preventing ventilator induced lung injury ) . acoustic profiling might prove a logical and time - efficient alternative to measures of gas exchange or mechanics in avoiding tidal recruitment . sudden changes in the geographic distribution of acoustic information in the context of deteriorating gas exchange or respiratory distress may suggest inadvertent mainstem bronchus intubation , pneumothorax , or mucus plugging of a major airway . a widely distributed transformation of the amplitude or nature of the acoustic signature suggests the emergence of hypopnea , pulmonary edema , or bronchospasm . newly audible rhonchi heard with disproportionate loudness over the trachea or major bronchi warn of secretion retention and the need for airway suctioning . ( conversely , the absence of rhonchi may restrain the caregiver from unproductive airway suctioning , with its attendant consequences of patient discomfort , mucosal trauma , deteriorated gas exchange , bronchospasm or arrhythmia induction . ) in fact , acoustic monitoring of airway sounds by a single pick - up mounted near the endotracheal tube holds interest as a simple means for timing when to suction the intubated airway . as these examples suggest , rather than discard auscultation in favor of other advanced imaging technologies , it may be time at last to re - visit and upgrade our old pocket companion . significant practical details must be worked through to unleash the full potential of acoustic monitoring . the depth and pattern of breathing influence airway opening and alter the amplitude and profiles of flow - generated breath sounds . position alters not only lung volume but also the distribution of tidal airflow , crackles , and wheezes . chest wall anatomy and airspace filling may degrade or enhance the projection of sonic energy . as shown in the present communication by lev and colleagues , peep alters the vibration response distribution resulting from a fixed tidal breath in most patients , re - configuring the acoustic map . the authors correctly point out the importance of knowing how the sonic image normally responds to a common therapeutic intervention before inferring pathologic response at the bedside . perhaps other passively derived filtered and conditioned acoustic information , such as whether acoustic monitoring ( passive signal reception ) could be usefully coupled to thoracic ultrasound ( active signal injection ) has not yet been addressed . finally , as we have learned with non - invasive ventilation , the concept may be unassailable while the interface determines clinical acceptance . in routine clinical practice , deploying a stable and appropriately positioned array of microphonic pick - ups for extended periods may prove cumbersome or unachievable . despite such challenges , new methods for sonic evaluation these emerging options complement our ' static / global ' monitoring with dynamic regional information long missing from the optimal care of the ventilated patient with critical illness .

vesicular breath sounds , wheezes , rhonchi , and crackles possess acoustic ' signatures ' amenable to detection , quantification , and moment - by - moment visual display . despite technical hurdles , new methods for sonic evaluation , once perfected , should offer innovative diagnostic and monitoring tools that add clinical value . these emerging options complement current ' static / global ' monitoring of mechanics and gas exchange with dynamic regional information long missing from the optimal care of the ventilated patient with critical illness .

diagnosis of cutaneous tuberculosis ( ctb ) is complicated and requires a full work - up , including a detailed history and physical examination , careful consideration of clinical presentation , skin biopsy with histological analysis , and special staining methods for identification of acid - fast bacilli ( afb ) and the use of other diagnostic tests , such as chest x - ray and sputum culture.[24 ] we selected 30 patients who were clinically suspected to have cutaneous tuberculosis . to rule out tuberculosis in other organs , chest x - ray and sputum - smear examination for afb on three consecutive days skin biopsy was performed in all cases and examined after staining with hematoxylin and eosin . skin biopsy , mantoux test , chest x - ray , haemogram , and serum biochemistry were performed on these patients . other tests including fine needle aspiration cytology , lymph node biopsy , and radiological imaging were conducted when clinically indicated . in our study , maximum ( 50% ) patients were between 2130 years , 20% patients were between 3140 years , 10% patients were between 1120 years , and 4150 years each and 5% patients were between 010 years and 5160 years each . males outnumbered females and male to female ratio was 1.5 : 1 . commonest clinical variant of cutaneous tuberculosis in our study was lupus vulgaris [ figure 1a and b ] seen in 55% patients followed by scrufuloderma [ figure 2 ] seen in 25% patients followed by orificial tuberculosis [ figure 3a and b ] , tuberculosis verrucosa cutis , papulonecrotic tuberculid , and erythema induratum seen in 5% each [ table 1 ] . the commonest site of involvement was limbs seen in 50% patients followed by neck seen in 25% patients , face in 15% and trunk in 10% patients . maximum percentage of patients ( 55% ) had duration of cutaneous tuberculosis between 612 months followed by 35% between 1324 months , 5% had duration of cutaneous tuberculosis less than 6 months , and rest 5% had duration more than 24 months . the commonest histopathological feature in our study was tuberculoid granuloma with epithelioid and langhans giant cells seen in 70% patients , hyperkeratosis was seen in 15% patients and afb bacilli were seen in 5% patients [ table 2 ] . the mantoux test positivity was seen in ten patients and varied from 10 - 24 mm in diameter . plaque of lupus vulgaris on the knee with central atrophy histopathology of lupus vulgaris showing noncaseasting granuloma with epithelioid and langhans giant cells ( h and e stain 100 ) scrufuloderma below the ear photomicrograph of perianal swelling showing hyperkeratosis and acanthosis with multiple lymph spaces in upper dermis ( h and e stain , 100 ) clinical variants of cutaneous tuberculosis the histopathological feature of cutaneous tuberculosis to conclude , although the incidence of ctb is rare , it should be considered in patients presenting with atypical skin lesions suggestive of an underlying infectious etiology . microbiological tests such as direct microscopy and culture are usually negative in cutaneous tuberculosis because it is paucibacillary . histopathological findings are characteristic but not pathognomonic and are shared by other granulomatous diseases including leprosy , sarcoidosis , leishmaniasis , and subcutaneous fungal infections .

extrapulmonary tuberculosis constitutes about 10% of all cases of tuberculosis , and cutaneous tuberculosis makes up only a small proportion of these cases . despite prevention programs , tuberculosis is still progressing endemically in developing countries . commonest clinical variant of cutaneous tuberculosis in our study was lupus vulgaris seen in 55% patients followed by scrufuloderma seen in 25% patients followed by orificial tuberculosis , tuberculosis verrucosa cutis , papulonecrotic tuberculid , and erythema induratum seen in 5% each . the commonest site of involvement was limbs seen in 50% patients followed by neck seen in 25% patients , face in 15% , and trunk in 10% patients . maximum percentage of patients ( 55% ) had duration of cutaneous tuberculosis between 612 months followed by 35% between 1324 months , 5% had duration of cutaneous tuberculosis less than 6 months , and the rest 5% had duration more than 24 months . the commonest histopathological feature in our study was tuberculoid granuloma with epitheloid cell and langhans giant cells seen in 70% patients , hyperkeratosis was seen in 15% patients and afb bacilli were seen in 5% patients .

preoperative co - morbidities , long duration of surgery , large fluid shifts , and delayed correction of metabolic derangements by the transplanted liver are the common factors responsible for preventing primary extubation after liver transplantation . moreover , until very recently , a postoperative period of mechanical ventilation was considered a standard of care for anyone undergoing liver transplantation as it was believed that reducing the stress associated with arousal from anaesthesia and the resumption of spontaneous ventilation contributed to ensuring a soft and controlled transition from the surgical to the postoperative recovery phase . however , now there is a substantial body of evidence proving that patients who undergo large and complex surgeries including transplants can be extubated immediately after surgery with few complications and no effect on 1 or 3 year graft survival . the first patient was a 45-year - old male hepatitis c related cirrhosis with hepatocellular carcinoma , child grade c , with refractory ascites , coagulopathy and mild hepatorenal syndrome . the second patient was a 64-year - old male with alcoholic liver disease that had decompensated with refractory ascites and coagulopathy . preoperatively both the patients were conscious and well oriented having stable cardiovascular , respiratory , and renal systems . standard monitoring was applied consisting of invasive blood pressure measurement , central venous pressure , pulmonary artery pressure , urine output , temperature and bispectral index in addition to routine monitoring . rapid sequence induction using fentanyl 2 mcg / kg , propofol 1.5 mg / kg and scoline 1.5 mg / kg , and was followed by fentanyl infusion 2 mcg / kg / hr , atracurium infusion 0.5 mg / kg / hr and patient ventilated with isoflurane in oxygen air mixture . the average time from reperfusion to completion of hepatic artery anastomosis was 45 min . at the end of hepatic artery anastomosis and after confirmation of good flow on doppler ultrasound isoflurane propofol infusion was started for maintenance of anaesthesia and infusion rate titrated to maintain bispectral index between 40 and 60 . the range of propofol infusion dose required was 2 to 6 mg / kg / hr . we planned to give bolus doses of atracurium 5 to 10 mg , if clinically the need for muscle relaxation was felt , but both the patients did not require any additional doses of atracurium . during bile duct anastomosis , the patient was evaluated for feasibility of immediate post - operative extubation using standard criteria . good donor liver function was defined as normal ph , no clinical bleeding with an acceptable prothrombin time as judged by the anaesthetist . because a need for massive transfusion is known to be associated with a negative outcome in liver transplantation , transfusion requirement of less than 10 u of packed red blood cells was necessary . haemodynamic stability was defined as no need for noradrenaline infusion more than 200 nanogram / kg / min . our patients fulfilled all of these criteria ( see tables ) . the average time taken after hepatic artery anastomosis to the completion of closure of skin in the two cases was 90 minutes . at the closure of the skin standard reversal was given and propofol infusion stopped . during the time dressing and cleaning was being done , breathing was manually assisted with 100% oxygen . after about 20 minutes when all the routine criteria for extubation were met ( viz . , breathing spontaneously , fully awake and able to follow simple commands ; respiratory rate less than 35 breaths / min , and tidal volume was greater than 5 ml / kg ; and no sign of respiratory distress , heart rate not more than 20% above baseline ) , the patient was extubated . then humidified oxygen was given by facemask and patient shifted to recovery for observation . later , after about one hour the patient was transferred to the intensive care unit ( icu ) in a stable condition . both the patients continued to do well without any adverse event related to early extubation and finally discharged home in a satisfactory condition . fast tracking is an attempt to make efficient use of resources and to improve recovery of the patient . clinical advantages include lower risk of post - operative infection and improved haemodynamic conditions promoting hepatic venous drainage and graft circulation . on basis of our experience and after going through literature there was a consensus that early awakening could be achieved by reducing the total dose of fentanyl infused . fentanyl has a long context sensitive decrement time , and therefore , on the basis of our clinical experience we decided to reduce the infusion dose early and stop it altogether when good vascular flows were confirmed in the transplanted liver . residual levels of fentanyl continue to provide analgesia for long time after prolonged infusion for several hours . remifentanil can be a better alternative to fentanyl for fast tracking because of its rapid elimination . desflurane may be a better alternative because of its low solubility coefficient but isoflurane has the theoretical advantage of maintaining better hepatic blood flow . drugs having a faster elimination facilitate fast tracking , but more important is the optimal anaesthetic management and a good surgical technique . in order to achieve our goal and at the same time diverting minimally from our routine protocol , we planned to continue our routine anaesthetics till hepatic artery anastomosis . then all routine anaesthetics were stopped and propofol infusion started using bispectral index as a guide to maintain anaesthesia . this protocol provided sufficient time for reduction of the levels of fentanyl , isoflurane and atracurium so that we had an awake , stable patient twenty minutes after cessation of propofol ready for extubation . moreover , adult right lobe living donor liver transplant tends to be technically more difficult and of longer duration intraoperatively , and to have more post - operative complications than straightforward full size orthoptic liver transplantation . under specified conditions , using strict criteria early extubation is a safe procedure . we selected our patients carefully , they did not have any pre - operative contraindication for fast tracking , viz . , acute liver failure , encephalopathy , morbid obesity , pre - operative need for mechanical ventilation or re - transplantation . moreover , intraoperatively the feasibility of fast tracking was done applying standard criteria strictly [ table 1 ] . recently safe operating room extubation after liver transplantation score ( sorelt score ) has been suggested to select the patients for extubation in operating room . we use morphine 1.5 to 3 mg boluses i. v. on as and when required basis in the transplant icu . analgesic requirements in patients with end - stage liver disease undergoing liver transplantation appear to be significantly decreased compared with other major abdominal surgery . the neuropeptide metenkephalin , which is involved in pain modulation , has been shown to be significantly elevated in liver transplant patients compared with the control population . the exact mechanism of this clinical observation is unknown , and perioperative administration of large doses of steroids may play some role . postoperatively , the patients did not have any morbidity related to fast tracking and were discharged in a satisfactory condition . immediate extubation after liver transplantation is possible in a substantial percentage of cases ; confidence , habit and a spirit of emulation are decisive factors in encouraging anaesthetists to extend this practice to the largest possible number of patients . with more and more experience it is possible that such patients be shifted directly to an high dependency unit settingsetting thus saving costs further . a successful immediate extubation may be an important indicator of perioperative quality of care in liver transplantation .

liver transplantation is a dynamic field undergoing continuous changes in management . prolonged postoperative mechanical ventilation has been a norm but now there is a trend towards early extubation . we developed a protocol for early extubation based on bispectral index monitoring . this protocol was applied in two cases with satisfactory outcome .

lung cancer is one of the most frequent and commonly diagnosed cancers worldwide , with a high mortality rate . the most common sites for distant metastases of lung cancer are adrenal glands , liver , brain , and bone . we present a case of a 75-year - old nonsmoker male who presented with an ischioanal mass . the biopsy showed adenocarcinoma without any colorectal mucosal lesion , which prompted a positron emission tomography ( pet ) computed tomography ( ct ) scan evaluation , leading to the diagnosis of stage 4 lung cancer with metastasis to the ischioanal fossa and adrenal glands . a 75-year - old male , nonsmoker , diabetic , hypertensive , postcoronary bypass was referred to our hospital with complaints of burning sensation in perianal area with a mass - like sensation causing hindrance to sit . there was no history of constipation , bleeding per - rectum , pain or mass per - abdomen or weight loss . on examination , . per - rectum revealed a growth on the left lateral part around the anal region , no growth felt in the rectal mucosa , and the upper extent of the tumor could not be delineated . contrast - enhanced ct of the abdomen and pelvis done outside showed a 3.7 cm 4.2 cm 2.8 cm mass in the perianal region , medially extending up to the external sphincter close to the anal verge . the patient had undergone a biopsy from the mass outside , which was suggestive of moderately differentiated adenocarcinoma . no immunochemical ( ihc ) evaluation was done . with a suspicion of a skip lesion from a higher growth , we performed a sigmoido - colonoscopy which showed a hard mass on the left side of perianal region with no clear growth arising from the rectal or anal mucosa . carcinoembryonic antigen was 205.7 ng / ml . in view of unusual site of adenocarcinoma in the perianal region , a pet / ct scan was done which revealed a 2.6 cm 2.3 cm mass in the right lower lobe of lung with hilar and axillary lymphadenopathy , bilateral lung nodules with a small adrenal nodule along with a 4.8 cm 3.5 cm mass in the left ischioanal fossa [ figures 1 and 2 ] . we finally concluded that the patient has stage 4 adenocarcinoma lung with metastases to ischioanal fossa , bilateral lung , and adrenal gland . epidermal growth factor receptor ( egfr ) and anaplastic lymphoma kinase ( alk ) mutation analyses were negative . after two cycles of pemetrexed - carboplatin , the patient did not have any benefit . hence , subsequently , his chemotherapy was changed to paclitaxel - carboplatin and after the first cycle itself the mass began to shrink . positron emission tomography computed tomography showing fluorodeoxyglucose avid lesion in the ischioanal fossa positron emission tomography computed tomography showing fluorodeoxyglucose avid lung primary here , we present a case of lung adenocarcinoma with a rare presentation of an ischioanal mass in a nonsmoker which was diagnosed on pet / ct . some rare sites of metastasis published in the literature are subcutaneous nodules , thyroid gland , intracranial tumor - meningioma , and multiple cavitary lesions in a patient with wild - type egfr . angiomyxoma is a rare neoplasm which can also present with a well - defined lobulated mass in the ischiorectal fossa as in our case . lung cancer is generally believed to be smoker 's disease as compared to nonsmoker 's which many at times leads to delayed diagnosis in nonsmokers . in our patient , detailed imaging excluded primary origin in the abdominal cavity as well as from epithelial lining of the rectal and anal mucosa . the histopathology report suggested moderately differentiated adenocarcinoma which led to the suspicion of skip lesion , and later on , pet scan was done which showed the origin in the lung with metastasis to adrenal too . it is essential to distinguish pulmonary adenocarcinoma with intestinal differentiation from metastatic colorectal carcinoma because of critical differences in therapeutic strategies and prognosis , which can be done by ihc and egfr analysis . egfr mutations seem to influence the site of metastasis with a positive egfr status favoring pleural metastasis in pulmonary adenocarcinoma . since egfr and akl mutation were found to be negative in our case , the treatment was started on pemetrexed ( folate antagonist)-carboplatin chemotherapy and later on shifted to paclitaxel - carboplatin therapy which showed more effectiveness in suppressing the mass . overall , this case emphasizes that consideration should be given to wide range of diagnosis in atypical cases of anorectal masses . there are no similar reported cases of primary lung adenocarcinoma presenting as ischioanal fossa mass and this case represents a challenge in both diagnosis and long - term management . there are no case reports of lung cancer presenting as an ischioanal fossa mass as the initial presentation . this case report emphasizes the varied forms of lung cancer presentation which is a diagnostic challenge , especially in nonsmokers .

lung cancer metastasis commonly involves the adrenal glands , liver , bone , and brain . however , it can have some rarer forms of metastatic presentation making diagnosis difficult , especially in nonsmokers . we describe a rare case of lung cancer with metastasis to the ischioanal fossa . overall , this case emphasizes that consideration should be given to wide range of diagnosis in atypical cases of anorectal masses . lung cancer presenting as an ischioanal mass is not reported so far .

ashy dermatosis is a hypermelanotic disorder of the idiopathic variety characterized by bluish - grey macules in healthy individuals . it is a controversial entity and is sometimes considered as a variant of lichen planus . etiology of ashy dermatosis is mostly unknown and it usually affects the face , arms , neck , and trunk . ashy dermatosis usually has a symmetrical distribution but cases with unilateral presentation have also been observed . lichen planus pigmentosus , occupational dermatosis with hyperpigmentation , drug - related dermatoses , universal acquired melanosis , and familial progressive hyperpigmentation are the common entities confounding diagnosis . our case was a 20 year - old indian male who presented with slowly progressive , diffuse darkening of the face , arms , neck , and trunk seen over the last two years [ figures 1 and 2 ] . he had no previous history of skin diseases and was not on any kind of medication during this two - year period . laboratory investigations suggested normal blood counts , blood glucose level , normal liver and kidney function test and normal acth stimulation ( sensitive ) test results . bluish black discoloration of face , chest , and upper extrimity bluish black discoloration of neck and back oral mucous membrane and palate are not involved it has been a controversial topic that has showed a tendency to appear mostly in dark colored individuals and also in asians . confusion also arises because the disease is also known by many different names like erythema dyschromicum perstans and lichen planus pigmentosus . others have suggested that ashy dermatosis presents clear clinical characteristics but that histopathological findings are not specific . our differential diagnoses revolved around lichen planus pigmentosus , occupational dermatosis with hyperpigmentation , drug - related dermatoses , universal acquired melanosis , allgrove 's syndrome , dermatomyositis , and familial progressive hyperpigmentation syndrome . absence of occupational exposure ruled out occupational dermatosis with hyperpigmentation ; dermatomyositis is a condition of muscle weakness , and allgrove syndrome is characterized by alacrima , achalasia , and acth insensitivity . but the patient did not show any of these symptoms and signs . a normal creatinine phosphokinase ( cpk ) level ruled out the chances of dermatomyositis , and a normal barium meal x - ray and acth sensitivity test ruled out allgrove syndrome . the patient had not taken any drugs in this period.so drug - related dermatosis was ruled out . the histopathological study was not conclusive enough to differentiate from lichen planus pigmentosus but the absence of pruritus , the lack of involvement of the oral mucosa , and the bluish - black discoloration in our patient , a dark colored indian in his second decade of life support our diagnosis in favor of ashy dermatosis of the idiopathic variety . the only treatment in this condition resulting in considerable improvement in pigmentation is clofazimine at a dose of 100 mg three times per week for three to five months .

we present here the case of a young indian male with slowly progressive , diffuse darkening of the face , arms , neck , and trunk . the patient was not taking any medication and there was no history of any previous skin disease and the mucous membrane was not involved . these findings are consistent with a diagnosis for ashy dermatosis of unknown etiology .

psammomatous melanotic schwannoma ( pms ) is a very rare pigmented tumor composed of schwann cells capable of melanogenesis . the histopathogenesis of this tumor is debatable considering the common neuroectodermal origin of melanocytes and schwann cells . pms arises most frequently from the spinal nerve roots and sympathetic ganglia , but other primary sites such as visceral organs and skin have been reported . in half of the cases , the tumor may occur within the carney complex , or it can be isolated . although most of the cases follow a benign clinical course , some malignant variants with possible local relapses and metastases have been reported . the totally excised tumor obtained from the patient for diagnostic purpose was fixed in formalin , embedded in paraffin , cut at 5 m and stained with hematoxylin - eosin . an immunohistochemical study was performed with the avidin - biotin immunoperoxidase technique on deparaffinized sections using commercially available antibodies to melan - a / mart-1 , hmb45 , cd34 , cd117 , cytokeratin , ema , cd68 and s100 . here , we describe the case of an isolated pms in a 35-year - old female patient localized on the buttocks , clinically simulating a pilonidal cyst . the tumor had been noticed by the patient since she was 12 years old and slowly increased in size during the 3 years before it was surgically removed . histological examination showed circumscribed subcutaneous proliferation of spindle - shaped cells with rounded ovoid nuclei , frequent nuclear grooves and prominent intracytoplasmic melanin pigment . mitoses were quite infrequent , and < 1 mitosis per 10 fields of high magnification could be seen . 1 ) . the spindle cells stained positive for s-100 , melan - a and hmb-45 ( fig . 2 ) but were negative for cd34 , cd117 , cytokeratin , ema and cd68 . no clinical evidence of any association with the carney complex was present as assessed by full meticulous skin examination and cardiac echography in order to exclude intracardiac myxoma . the family history of the patient was positive for graves disease , but no other endocrine disease was present . the malignant nature of the tumor could not be initially excluded based solely on the abovementioned morphology and the lack of significant mitotic activity . therefore , the patient underwent additional skin excision with 1 cm margin , and a follow - up for high - risk malignant melanoma was initiated . unless occurring within an already recognized carney complex , the diagnosis of pms relies on histological examination . the main histological differential diagnosis includes malignant melanoma , which shares common features such as melanin synthesis and positive staining for melanocytic markers . predominantly spindled ( rather than epithelioid - plasmacytoid ) morphology , heavy melanin pigmentation , psammoma bodies , vacuolated ( adipocyte - like ) cells and striking nuclear pleomorphism with a relatively low mitotic rate suggest pms . to our knowledge , 20 cases of isolated cutaneous or subcutaneous pms have been reported , with most cases being clinically described as a slow - growing cutaneous or subcutaneous mass in the upper parts of the body . in our patient , the tumor did not occur within the carney complex and was clinically considered as a pilonidal cyst both because of its location and its volume which had remained unchanged since childhood , but finally increased during the last 3 years before it was removed . because of the clinical context and the uncertainty of the biological behavior of this rare tumor which can undergo malignant progression in about 10 - 35% of a limited number of cases , its malignant potential can not be formally ruled out . recently , some authors have even suggested that the malignant potential of melanotic schwannomas ( with or without psammoma bodies ) is underestimated . therefore , a careful follow - up for a potentially high - risk malignant tumor should be recommended . distinguishing pms from malignant melanoma can be challenging for dermatopathologists who should be aware of this rare pigmented cutaneous tumor .

psammomatous melanotic schwannoma ( pms ) is a rare pigmented tumor that can be part of the carney complex . here , we describe the case of a 35-year - old female patient presenting an isolated subcutaneous pms . histopathological analysis could not formally exclude the malignant nature of the tumor . the challenging histological diagnosis and consequently the management of the patient are described .

one of the more important effects of our recent study may be to call in to question a widely held assumption about the significance of csf - tau in ad pathogenesis that elevated csf - tau levels typically seen in ad are caused by passive release of tau from dead neurons . even in the earliest accounts of elevated csf - tau in ad in the mid 1990s , the death - based origin for csf - tau was generally accepted at that time because it was plausible , consistent with the known progression of neurofibrillary degeneration to extracellular ghost tangles and was unopposed by other explanations . also , the lack of tauopathy models and of accurate data on the timecourse of neuron death in ad made acquiring direct evidence for alternative csf - tau biogenesis mechanisms impractical . since then , this assumption has been repeatedly ( if casually ) asserted in the medical literature despite the lack of evidence for a causal link between antecedent neuronal cell death and elevated csf - tau levels in ad . the continued plausibility of the death - induced hypothesis of csf - tau in ad appears to be based on analogy with episodic conditions ( head trauma , stroke , severe seizures ) in which the time course of csf or blood tau levels can be measured relative to a single generative event . in each of these conditions , csf and/or serum tau levels undergo a large transient rise that is directly correlated with both event severity and with direct measures of neuronal loss . the analogy with ad - induced neuron loss is strengthened by the presence of excitotoxic features in the neuron loss in all of these conditions , although this does not rule out a role for active secretion , since ca fluxes also play a critical role in most unconventional secretion mechanisms . another situation where neuron death remains a highly plausible ( if still unproven ) source for elevated csf - tau may be prion diseases such as creutzfeldt jacob disease ( cjd ) , which typically features much higher csf - tau levels than does ad together with massive neocortical neuron loss over a shorter timecourse after diagnosis . in the case of ad , however , indications from studies performed in the past decade have generally been either ambiguous or inconsistent with the death tau hypothesis . the advent of quantitative elisa - based studies comparing csf - tau levels in early and late ad cases ( including ours ) show that the well - established neuropathological braak sequence of ad development does not anticipate the elevation of csf - tau levels and thus conflicts with the death origin hypothesis ( see figure 1a ) . limbic stage ad ( braak stages 34 ) , when neurofibrillary pathology is confined to limbic regions of the temporal lobe that represent less than 10% of brain volume , while csf - tau levels are rising sharply to their maximal levels . moreover , csf - tau levels remain largely stable or may even fall in late stage ad , even as neurofibrillary pathology and neuron loss become widespread in the brain . in this context , our demonstration that tau , particularly in its phosphorylated form , is associated with a secretion marker in csf from early ad patients provides an alternative mechanism to neuron death , and thus may prompt a broad reassessment of the origin of csf tau in ad . figure 1 . elevated csf levels of total tau and phosphotau in early ad are better explained by secretion of misprocessed tau from neurons and glia rather than a consequence of massive neuronal death . ( a ) csf - tau in ad consists largely of 1 ) n - terminal fragments between 2035kd apparent molecular weight with a variable admixture of higher mw species that appear to represent near full length tau . these match the secreted tau species seen in both in situ and cell culture models of tau secretion . the image at right shows an identified neuron ( abc ) in the lamprey brain expressing 4r0n human tau with the p301l tauopathy mutation after 20 d of expression immunolabeled with tau12 ( n - terminal mab red channel ) and the gfp tag ( green channel ) . this image illustrates the multiple possible secretion routes for tau that ultimately accumulates in the csf . tau described in the lamprey model consists largely of n - terminal fragments that lack the mtbr , whereas the focal route requires the presence of the mtbr . both secretion routes in the lamprey model either introduce tau to the interior surfaces of the ivth ventricle ( periventricular tau ) or cross it entirely . ( b ) the respective time courses of neuronal death and csf - tau elevation in ad are inconsistent with postmortem passive leakage of tau into the csf , with the highest levels of csf - tau occurring well before the onset of widespread cerebral occurrence of neurofibrillary degeneration in the so - called isocortical stages ( braak 56 ) of ad , and failing to increase with disease severity . the likelihood that tau secretion is involved in the genesis of csf tau is fundamentally important to critical questions relating to ad diagnosis and treatment , since it raises broad issues of the timing and distribution of degenerative changes in the brain . mechanism of csf - tau pathogenesis implies that tau misprocessing is fatal to affected neurons earlier in the disease than is suggested by a it therefore suggests a more pessimistic outlook than the latter for the development of prospective diagnostics and effective therapeutics for ad . it is a truism that the staying power of powerful and compelling ideas is better linked to their plausibility rather than to the actual evidence supporting them a well known example being the miasmatic theory of infectious disease . by presenting the first direct evidence for an alternative mechanism , this study may crystallize the existing evidence that antecedent neuron death is not currently a plausible mechanism for csf - tau biogenesis in ad this provides a new perspective on ad pathogenesis that opens unexplored avenues to improving both the diagnosis and treatment of this devastating and widespread condition .

our recent identification of an exosomal route for tau protein secretion1 marks a key similarity between tau and other aggregation - prone proteins implicated in neurodegenerative disease pathogenesis and is to some extent congruent with the popular idea that tau pathology spreads between neurons via a prionlike template - mediated protein misfolding mechanism in ad and other tauopathies . however , the observation that much of the phosphotau in csf samples from early ad patients is exosomal ( and thus likely to have been secreted ) calls into question a very widely held and plausible assumption - the idea that the elevated csf - tau in ad is due to the passive release and accumulation of tau in the csf as a consequence of widespread neuronal death . here we examine this issue directly and explore some of the broader implications of this study for our understanding of ad pathogenesis and the prospects for improving its diagnosis and treatment .

all solvents used for catalysis were dried over and distilled from sodium ( toluene , tetrahydrofuran , diethyl ether ) or cah2 ( dichloromethane , methanol , acetonitrile ) . all other chemicals were purchased from commercial suppliers ( sigma aldrich , acros or strem ) and used without further purification . nmr spectra ( h , and c{1h } ) were measured by using a bruker av400 , av300 , drx 500 or drx 300 spectrometer . individual peaks are reported as : multiplicity ( s = singlet , d = doublet , t = triplet , q = quartet , m = multiplet ) , integration , coupling constant [ hz ] . ms system , and the corresponding hrms data were recorded by using a jeol accutof 4 g with a direct injection probe using either ei or esi . the gc used for isomer separation was a shimadzu 17a with a supelco spb tm1 fused silica capillary column with a length of 30 m , a diameter of 0.32 mm and a film thickness of 2.0 m . [ co(metaa ) ] , [ co(mephtaa ) ] and [ co(bzmetaa ) ] were synthesised according to reported procedures.20 [ co(tpp ) ] and [ co(salen ) ] were purchased from sigma aldrich and used without further purification . under a n2 atmosphere , the solid was dissolved , and the additive ( 0.05 equiv . ) and alkene ( 1.0 equiv . then , the diazo compound ( 1.2 equiv . ) was added , and the solution was stirred for 1 h. the resulting mixture was concentrated , and the residue was purified by flash chromatography ( silica gel ) or extracted into pentane . an equimolar mixture of the corresponding aldehyde and ntosylhydrazide was placed in a roundbottomed flask and dissolved in methanol ( 2 ml mmol ) . the white precipitate was collected by filtration and washed with cold methanol and hexane to obtain the pure product . the formed ntosylhydrazone was then deprotonated in methanol with naome ( 1 equiv . ) . after the evaporation of methanol , the pure product was obtained as a white powder . under a n2 atmosphere , the respective ntosylhydrazone salt ( 1.0 equiv . ) , catalyst ( 0.03 equiv . ) and aliquat336 ( 0.15 equiv . ) were added to a flamedried schlenk tube in a glovebox . the schlenk tube was then placed in an oil bath and heated to 50 c under n2 for a set time . the resulting mixture was concentrated , and the residue was purified by flash chromatography ( silica gel ) or extracted into pentane . all solvents used for catalysis were dried over and distilled from sodium ( toluene , tetrahydrofuran , diethyl ether ) or cah2 ( dichloromethane , methanol , acetonitrile ) . all other chemicals were purchased from commercial suppliers ( sigma aldrich , acros or strem ) and used without further purification . nmr spectra ( h , and c{1h } ) were measured by using a bruker av400 , av300 , drx 500 or drx 300 spectrometer . individual peaks are reported as : multiplicity ( s = singlet , d = doublet , t = triplet , q = quartet , m = multiplet ) , integration , coupling constant [ hz ] . ms system , and the corresponding hrms data were recorded by using a jeol accutof 4 g with a direct injection probe using either ei or esi . the gc used for isomer separation was a shimadzu 17a with a supelco spb tm1 fused silica capillary column with a length of 30 m , a diameter of 0.32 mm and a film thickness of 2.0 m . [ co(metaa ) ] , [ co(mephtaa ) ] and [ co(bzmetaa ) ] were synthesised according to reported procedures.20 [ co(tpp ) ] and [ co(salen ) ] were purchased from sigma aldrich and used without further purification . under a n2 atmosphere , catalyst ( 0.05 equiv . ) was added to a flamedried schlenk tube . the solid was dissolved , and the additive ( 0.05 equiv . ) and alkene ( 1.0 equiv . then , the diazo compound ( 1.2 equiv . ) was added , and the solution was stirred for 1 h. the resulting mixture was concentrated , and the residue was purified by flash chromatography ( silica gel ) or extracted into pentane . an equimolar mixture of the corresponding aldehyde and ntosylhydrazide was placed in a roundbottomed flask and dissolved in methanol ( 2 ml mmol ) . the white precipitate was collected by filtration and washed with cold methanol and hexane to obtain the pure product . the formed ntosylhydrazone was then deprotonated in methanol with naome ( 1 equiv . ) . after the evaporation of methanol , under a n2 atmosphere , the respective ntosylhydrazone salt ( 1.0 equiv . ) , catalyst ( 0.03 equiv . ) and aliquat336 ( 0.15 equiv . ) the schlenk tube was then placed in an oil bath and heated to 50 c under n2 for a set time . the resulting mixture was concentrated , and the residue was purified by flash chromatography ( silica gel ) or extracted into pentane . as a service to our authors and readers , this journal provides supporting information supplied by the authors . such materials are peer reviewed and may be reorganized for online delivery , but are not copyedited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors .

abstracta new protocol for the catalytic synthesis of cyclopropanes using electrondeficient alkenes is presented , which is catalysed by a series of affordable , easy to synthesise and highly active substituted cobalt(ii ) tetraaza[14]annulenes . these catalysts are compatible with the use of sodium tosylhydrazone salts as precursors to diazo compounds in onepot catalytic transformations to afford the desired cyclopropanes in almost quantitative yields . the reaction takes advantage of the metalloradical character of the co complexes to activate the diazo compounds . the reaction is practical and fast , and proceeds from readily available starting materials . it does not require the slow addition of diazo reagents or tosylhydrazone salts or heating and tolerates many solvents , which include protic ones such as meoh . the coii complexes derived from the tetramethyltetraaza[14]annulene ligand are easier to prepare than cobalt(ii ) porphyrins and present a similar catalytic carbene radical reactivity but are more active . the reaction proceeds at 20 c in a matter of minutes and even at 78 c in a few hours . the catalytic system is robust and can operate with either the alkene or the diazo reagent as the limiting reagent , which inhibits the dimerisation of diazo compounds totally . the protocol has been applied to synthesise a variety of substituted cyclopropanes . high yields and selectivities were achieved for various substrates with an intrinsic preference for trans cyclopropanes .

although cerebral hyperperfusion syndrome ( chs ) is well documented after carotid endarterectomy and carotid artery stenting , only a few cases have been described after intracranial stenting . after the stenting versus aggressive medical therapy for intracranial arterial stenosis and vitesse stent ischemic therapy trials demonstrated the inferiority of intracranial stenting compared to aggressive medical treatment , this procedure has been largely abandoned . cerebral hyperperfusion is defined as a > 100% increase in cerebral blood flow ( cbf ) compared to the baseline and it is generally associated with postprocedural hypertension . chs has an estimated incidence of 0.4%2.7% after ce and usually presents with ipsilateral headache or migrainous phenomena , seizures , or intracerebral hemorrhage ( ich ) . i would like to report an unusual case of chs following middle cerebral artery ( mca ) stenting . a 71-year - old man presented to us with fluctuating motor aphasia of 3 h duration . magnetic resonance imaging of the brain showed multiple acute infarcts in the left mca territory and he was started on antiplatelets and statins . by the next day morning , he had developed global aphasia and transient right - sided weakness . his blood pressure ( bp ) was 150/90 mm hg and he was taken up for a four - vessel digital subtraction angiography which showed a possible dissection with a thrombus in the distal left mca [ figure 1 ] . after obtaining consent , a 4 mm 15 mm solitaire ab neurovascular modeling device ( ev3 , irvine , usa ) was placed across the lesion into the superior mca division with good recanalization . postprocedure , the patient was sedated and ventilated , but had severe hypertension , exceeding 240/140 mm hg which was difficult to control even with multiple antihypertensives . the next morning , a routine computed tomography ( ct ) brain ( 12 h later ) showed two discrete intracerebral hematomas ( ich ) in the left frontal and temporal areas [ figure 1 ] . transcranial doppler ( tcd ) showed elevated mean flow velocities of > 130 cm / s in the left mca . coagulation parameters were normal . on examination , now he had a dense right hemiplegia and global aphasia . two weeks later , a repeat ct showed resolution of the ich and no fresh infarcts . the patient had a residual wernicke 's aphasia and right hemiplegia at follow - up even 6 months later . ( a ) top left panel shows an irregularity in the left middle cerebral artery m1 segment , suggestive of dissection . ( c ) bottom panels ; computed tomography scan images showing left temporal and frontal intracerebral hematomas risk factors for chs include age > 75 years , preexisting hypertension , high - grade stenosis with poor collateralization , decreased cerebrovascular reactivity , and increased peak flow velocities . reperfusion of ischemic territories can also lead to reperfusion injury , wherein oxidant production , complement activation , and increased microvascular permeability result in an impaired blood chs is a devastating complication because of the high morbidity and mortality of nearly 60%80% associated with this condition . after cerebral revascularization , the advent of severe headache , seizures , or focal neurological deficits after cerebral revascularization should be presumed to signify chs unless proved otherwise . tcd studies are helpful in monitoring elevated peak systolic velocities in the intracranial arteries as a marker of impending chs . in about 15% of patients , in such patients , near - infrared spectroscopy may be a useful option to monitor cbf . all critical care physicians should be aware of this entity for better monitoring and prevention of this postprocedural complication in the icu .

cerebral hyperperfusion syndrome ( chs ) is a rare complication following cerebral revascularization . it presents with ipsilateral headache , seizures , and intracerebral hemorrhage . it has mostly been described following extracranial carotid endarterectomy and stenting and it is very unusual after intracranial stenting . a 71-year - old man with a stuttering stroke was taken up for a cerebral angiogram ( digital subtraction angiography ) , which showed a dissection of the distal left middle cerebral artery . this was recanalized with a solitaire ab stent . after 12 h , the patient developed a right hemiplegia and aphasia . computed tomography brain showed two discrete intracerebral hematomas in the left hemisphere . this is the first reported case of chs following intracranial stenting from india .

we designed and conducted a retrospective , descriptive study to examine trends in ltbi and tb disease rates among homeless persons at the selected sites . our dataset was limited to the following categories : age , sex , race / ethnicity , prior tst status , hiv test status , and ltbi treatment history . those with no previous tst , prior negative tests , or unclear prior test results were offered a tb evaluation . tst was not offered to those with a convincing past history of tb or a documented or convincing history of a previous positive tst result ( explanation in the technical appendix ) . we classified each person as follows : tst negative , tst positive as tested , tst positive by history , tb disease , and noncompliant with skin testing reading . the number of single adult homeless persons identified by the yearly census of the new york city department of homeless services ranged from 27,846 in 1992 to 29,348 in 2005 ( 2 ) , while the number and proportion of tst screenings by our program increased from 972 ( 3% of new york city total ) in 1992 to 4,093 ( 13.9% ) in 2005 , the last complete year of our data . among the 32,108 attempted tb screenings , 28,835 persons ( 89.8% ) completed the screening process ; 11,385 had positive tst results or history ( table 2 ) . we stratified tst data from all sites and compared those from site 1 ( 58.1% of observations ) to those from sites 28 combined , for all years . using a nonparametric test for trend across ordered groups ( developed by cuzick as an extension of the wilcoxon rank - sum test ) , we found the 4 testing groups each had statistically significant negative trends by year : site 1 test only , z = 3.64 , p<0.001 ; site 1 test and history , z = 3.35 , p = 0.001 ; sites 28 test only , z = 2.91 , p = 0.004 ; sites 28 test and history , z = 2.95 , p = 0.003 ( stata 10.1 manual : nptrend test ) ( 4 ) . the statistically significant decreasing trends for the tst and tst positive by history groups for both site 1 and the other sites combined , from the inception of the data collection , are shown in figure 1 . * tb , tuberculosis ; tst , tuberculin skin testing ; na , not applicable . thus , in the technical appendix table 4 , the percentage of such persons is na . tuberculin skin test positivity by site and year , new york , ny , usa , january 1992june 2006 . overall , when the categories of administered tst and tst positivity by history were combined as indicators of ltbi , results decreased from 58.1% to 30.9% ( 19922006 ) at site 1 and from 57.3% to 30.8% at sites 28 combined ( 19972006 ) ( technical appendix table 1 ) . since few persons with a history of tst provided documentation , we examined ltbi rates among those persons actually tested . by this criterion , tst positivity decreased from 40.1% to 9.8% at site 1 ( 19922006 ) and from 30.4% to 13.3% at sites 28 combined ( 19972006 ) . tb disease rates at all 8 sites combined ( figure 2 ) also decreased in the screened population over the study period . sixty - three persons with tb disease were identified from january 1992 through june 2006 . in 1992 , these rates are far greater than for the general new york city population ( 13.0/100,000 ) and the united states population ( 4.4/100,000 ) in 2007 ( 5 ) . from january 2005 through june 2006 the percentage of persons with a history of positive tst and who received > 6 months of treatment trended upward , from 50.0% in 1996 through 1997 to 84.2% in 2006 ( technical appendix figure ) . tuberculosis disease case rates ( per 100,000 ) and infection rates ( as tested ) by year , new york , ny , usa , 19922006 . atb , active tuberculosis ; ltbi , latent tuberculosis infection . using logistic regression , we modeled the risk factors ( technical appendix tables 14 ) , and the probability of being tb positive ( by test or history ) and of not having the tb test read . for tb positivity , the adjusted odds ratio ( or ) for each age group compared with that for the youngest age group was significant and increased linearly with age . in general , the or increased by a factor of 2 for each advancing age group ( technical appendix table 3 ) . regarding compliance in tst reading , being in an older group was protective ( technical appendix table 3 ) . we were able to assess changes in hiv - positivity rates from january 2001 through june 2006 . the stage of hiv disease ( from asymptomatic hiv - antibody positive to aids ) was not recorded . for comparison , during this period in new york city , the number of persons who received a diagnosis of aids each year decreased from 5,616 to 3,672 ( 6 ) . because the percentage of hiv antibody positivity among those screened was essentially constant during the study period , we believe that the decreasing ltbi rates ( represented by tst positive as tested ) are real and not due to increasing numbers of persons with advanced hiv disease who are unable to mount an appropriate skin test response . our acceptance of a compelling history of prior positive tst rather than retesting may have resulted in inaccurate reporting of ltbi rates . however , we decided to accept compelling histories on the basis of decades of clinical experience in caring for homeless persons , experience in completing forms in the same way over the study years , and by a desire to do no harm . our population is not a random sample and may not represent the total homeless population within the city , raising concern about the generalizability of our findings . also , because the results of all tst screenings were included in our analysis , persons who were screened multiple times are overrepresented . also , the number of screenings at each site over the years varied , depending on changing requirements of the shelter program . in the past 2 decades , major public health efforts have been made to evaluate and treat persons with both tb disease and ltbi . our analysis offers evidence that these attempts to control tb in the homeless population have been beneficial ( 79 ) . although case rates of tb disease are carefully measured by public health authorities throughout the united states , this is not true for ltbi rates . therefore , we can not directly compare the rates of ltbi among these homeless persons to those among the general population . however , the rates of ltbi and tb disease observed in this study may serve as a valuable resource for tb control planning .

we conducted a retrospective study to examine trends in latent tuberculosis infection ( ltbi ) and tb disease rates among homeless persons in shelters in new york , ny , 19922006 . although tb case rates fell from 1,502/100,000 population to 0 , a 31% ltbi rate in 2006 shows the value of identifying and treating tb in the homeless .

pneumorrhachis is defined as air localized within the spinal canal : in the extradural space ; in the intradural space ; or in the subarachnoid space . it is a rare condition and is usually incidentally detected during radiological investigations.1 in the radiology practice , it is often associated with severe spinal trauma or is iatrogenic . pneumorrhachis tends to remain localized and resolves spontaneously.1 common causes of pneumorrhachis include : penetrating trauma ; an invasive procedure like an epidural analgesia or a lumbar puncture ; spontaneous or traumatic pneumomediastinum and pneumothorax ; degenerative disc disease ; or extradural abscess . bronchial asthma that causes pneumorrhachis is a very rare condition.16 to our knowledge , very few cases of this association are reported in the published literature.16 pneumorrhachis secondary to interstitial lung disease was reported by sandhya et al in 2011.7 a case of pneumorrhachis related to the common flu was recently reported.8 pneumorrhachis secondary to peanut aspiration was also reported.9 we present a rare case of pneumorrhachis , pneumomediastinum , pneumothorax , and surgical emphysema secondary to an acute attack of bronchial asthma . an 18-year - old female arab , a known asthmatic , presented to the emergency department of our hospital with complaints of chest pain and a nonproductive cough of 1-hour duration . there was no previous history of pulmonary tuberculosis , recent trauma , surgery , or other intervention . a chest radiograph was obtained , which revealed surgical emphysema along the upper part of the right lateral chest wall and the right side of the neck . a loss of volume of the right lung was noted with a shift of mediastinum to the right and elevated right diaphragmatic dome ( figure 1 ) . the portable bedside chest radiograph revealed increased severity of pneumomediastinum , surgical emphysema , right lung collapse , and mediastinal shift to the right ( figure 2 ) . computed tomography ( ct ) imaging of the thorax was also performed , which confirmed the dissection of air into the mediastinal and subcutaneous spaces ( figure 3 ) . a ct scan also revealed air within the posterior spinal extradural space in the thoracic spine ( figures 4 and 5 ) , minimal pneumothorax on the right , and obstruction of the segmental right upper lobe bronchus by mucus plugs ( figure 6 ) . she was hospitalized and treated with antibiotics , bronchodilators , oxygen inhalation , and other conservative measures . a bronchoscopic removal of mucus plugs and thick secretions was also performed . after only 5 days the chest radiograph revealed resolution of the pneumomediastinum and surgical emphysema and a significant improvement of the right lung collapse and mediastinal shift to the right ( figure 7 ) . she improved rapidly during her stay in the hospital and was discharged after 7 days . pneumorrhachis can be classified by etiology into traumatic , nontraumatic , and iatrogenic types.1 pneumorrhachis usually does not cause any symptoms and is , most of the time , incidentally detected . pneumorrhachis has been described secondary to spontaneous or nontraumatic pneumomediastinum or pneumothorax.10 there are very few reports of the combined presence of pneumomediastinum and extradural pneumorrhachis that are not associated with thoracic injury in the published literature . our patient developed pneumorrhachis , pneumomediastinum , pneumothorax , and surgical emphysema without any trauma . it may be detected in the cervical , thoracic , or lumbosacral regions or the entire spinal canal . pneumorrhachis commonly remains localized.1 in our case , pneumorrhachis was extradural and localized in the lower cervical and upper thoracic spine . pneumorrhachis is primarily a clinical imaging diagnosis , and clinicians do not play any role in its diagnosis , as pneumorrhachis is almost always asymptomatic . a ct scan is the investigation of choice in its diagnosis.1,811 in our case , also , the pneumorrhachis was asymptomatic and incidentally detected on a chest ct scan . a violent cough can sometimes occur in bronchial asthma , may cause sudden elevation of intra - alveolar pressure , and consequently may lead to a rupture of the peripheral pulmonary alveoli.1 the leaked air dissects through the perivascular interstitium of the lung and may traverse through the fascial planes from the retropharyngeal space or the mediastinum . air traversing through the fascial planes may pass through the intervertebral neural foramina into the spinal canal.1 there are no barriers along the fascia to prevent this spread of air from the chest to the spinal canal.1 the patient collapsed immediately after obtaining the first radiograph likely due to an acute lung collapse , which in turn may have been caused by an obstruction by a mucus plug or a blood clot . the severe collapse of a lung as a result of large mucus plugs occluding major airways has been described in many studies on different lung diseases , including bronchial asthma.12 occluding large mucus plugs may cause reduced gas exchange , increasing inspiratory pressure , and breathing difficulty.12 in most cases , extradural pneumorrhachis is self - limiting and resolves spontaneously when the etiological entity is taken care of . in our case also , the pneumorrhachis resolved spontaneously . in conclusion , we present a very rare case of extradural pneumorrhachis due to pneumomediastinum , which in turn was secondary to bronchial asthma . however , it is essential for the treating physician to study carefully the associated disease conditions and neurological status of the patient , as neurological deficits may occur in some cases.11

air localized within the spinal canal is called pneumorrhachis . in the case of pneumorrhachis , air can be present in the extradural , the intradural , or the subarachnoid space of the spinal canal . the air within the soft tissue of the posterior mediastinum may dissect along fascial planes , through the intervertebral neural foramina , and into the extradural or the subarachnoid space . nontraumatic pneumorrhachis is a rare presentation . most of the time , pneumorrhachis is asymptomatic , remains localized , and resolves spontaneously . there are very few reports of combined presence of pneumomediastinum and extradural pneumorrhachis not associated with thoracic injury in the published literature . we report a rare case of pneumorrhachis , pneumomediastinum , pneumothorax , and surgical emphysema in an adult female patient developed after a bout of violent cough related to bronchial asthma .

empyema of the gallbladder can occur due to obstruction of the cystic duct by a malignant mass such as a cholangiocarcinoma . here , we describe a 59-year - old man who presented with recurrent hiccups and was found to have cholangiocarcinoma causing obstruction to cystic duct drainage . this patient was managed successfully by percutaneous transhepatic cholecysto - duodenal self - expandable covered metal stent ( secms ) insertion . a 59-year - old man presented with complaints of upper abdominal pain , pruritus , and jaundice of 2 months duration . on ultrasonography ( usg ) , bilobar intrahepatic biliary radical dilatation ( ihbrd ) with segmental separation of the biliary radicals was noted . contrast - enhanced computed tomography ( ct ) scan of the abdomen showed bilobar ihbrd , with a block at the level of the hilum but no appreciable mass lesion . the patient underwent three - segment ( iii , vi , viii ) percutaneous transhepatic biliary drainage . because of recurrent cholangitis , he was started on intravenous antibiotics ( based on culture sensitivity ) . he developed cholecystitis with raised counts and intractable hiccups ; for this , he was reviewed by usg , which showed empyema of the gallbladder . metallic stenting of segments iii , vi , and viii was done accordingly , and the cholecystostomy tube was removed . after 1 month , the patient presented again with fever and hiccups . he again underwent cholecystostomy for relief of the sepsis . due to the inconvenience he experienced , the patient requested for the removal of the cholecystotomy tube . we first tried percutaneous internal biliary drainage through the cystic duct into the common bile duct , but were unable to cannulate though this route . we then attempted cholecysto - duodenal fistula creation by directly puncturing the gallbladder neck and the adjacent second part of the duodenum ( under usg and fluoroscopic guidance ) . after puncturing [ figure 1 ] the wall of the gallbladder [ using a neff percutaneous access set with a 22-gauge , 15-cm , hydrophilic - coated needle - 15 cm ( cook , bloomington , usa ) ] and the second part of the duodenum , we passed a 150-cm , 0.035 hydrophilic - coated angled - tip guidewire ( terumo europe , belgium ) [ figure 2 ] . we then exchanged [ figures 3 and 4 ] the guidewire for a 180-cm , r 3 mm , 0.035 amplatz ultra - stiff guidewire ( cook , bloomington , usa ) using a 40-cm kmp , 0.038 exchange catheter ( cook , bloomington , usa ) . finally , a 40 10-mm secms ( boston scientific , usa ) , having a 5-mm uncovered portion at each end [ figure 5 ] , was deployed with the proximal end in the gallbladder and the distal end in the duodenum . post procedure , the patient developed mild ascites , but this improved after few days and he was finally discharged . digital subtraction fluoroscopy image shows previously placed metallic stents in the biliary radicals ( arrows ) and puncture ( arrowhead ) of the gallbladder wall digital subtraction fluoroscopy image shows passage of a terumo guidewire ( arrow ) across the gallbladder ( arrowhead ) and into the second part of the duodenum ( curved arrow ) digital subtraction fluoroscopy image shows the distal end of the stiff guidewire ( arrow ) at the duodeno - jejunal junction digital subtraction fluoroscopy image shows passage of a 10-f arterial sheath ( arrow ) up to the duodenal wall ( arrowhead ) digital subtraction fluoroscopy image shows the cholecysto - duodenal stent ( arrow ) with passage of contrast instilled into the gallbladder lumen ( arrowhead ) into the duodenal loop ( curved arrow ) across the self - expandable , covered metal stent empyema of the gallbladder is usually managed successfully by operative removal of the gallbladder . in unresectable cases or in patients with comorbid conditions , different methods of treatment have been described , eg , percutaneous transhepatic cholecysto - duodenal stent ( with passage through the cystic duct into the duodenum ) or endoscopically placed stents , either transpapillary , across a pre - existing cholecysto - duodenal fistula , or across a fistula created endoscopically between the antrum of the stomach and the gallbladder.[58 ] we were unable to find any references in the literature describing the percutaneous creation of a fistula between the gallbladder and the second part of the duodenum , which we successfully performed in our patient . we first negotiated the guidewire across the cystic duct into the duodenum , but were unable to achieve access into the common bile duct ( due to obstruction by the cholangiocarcinoma ) . our patient had recurrent episodes of hiccups that had been successfully managed on the first occasion by cholecystostomy . we wanted to achieve internal drainage , and therefore attempted to create a cholecysto - duodenal fistula between the gallbladder and the adjoining second part of the duodenum , followed by deployment of secms . as the cystic plexus of the nerve supplying the gallbladder has branches from the phrenic nerve , we assumed that the cause of the recurrent hiccups was empyema of the gallbladder and that successful management of the empyema would provide relief . in an earlier report , a ureteric stent has been used for the management of empyema of the gallbladder . it is our firm belief that percutaneously placed secms is appropriate for this purpose as it has good long - term patency rate and less probability of displacement as compared to endoscopically placed plastic stents . in our patient , metallic stents had been initially deployed in the intrahepatic biliary radicals , and the common bile duct and endoscopic transpapillary drainage of the cystic duct was not possible . therefore , we attempted the creation of a cholecysto - duodenal fistula via the percutaneous route . we hope that no further intervention will be required in this patient , but , if necessary , the stent could be exchanged either via a percutaneous route or via a combined approach .

empyema of the gallbladder develops when the gallbladder neck is obstructed in the presence of infection , preventing pus from draining via the cystic duct . treatment options include cholecystectomy or , in patients with comorbidities , drainage via percutaneous cholecystostomy , later followed by cholecystectomy . here , we describe a 59-year - old man who presented with complaints of recurrent hiccups and was found to have cholangiocarcinoma causing obstruction to cystic duct drainage . the patient was managed successfully by percutaneous transhepatic cholecysto - duodenal self - expandable covered metal stent .

at hcb , as part of the routine workup for febrile patients , serum samples were collected , stored at 20c , and transported in liquid nitrogen to quito for pcr . hospital personnel also tested these samples by using a dengue igm / igg - capture elisa with high specificity and sensitivity ( panbio , waltham , ma , usa ) . at the snem laboratory , 24 drops of whole blood were collected on filter paper ( whatman 903 , kent , uk ) from persons spontaneously seeking or referred for malaria diagnosis . filter papers were left to dry overnight , stored at 0c in a zipper bag , and transported to quito for analysis . denv was amplified from total rna from blood spots and serum as described ( 12,13 ) . pcr products were sized in 1.5% agarose gel electrophoresis and sybr safe dna gel stain ( invitrogen , carlsbad , ca , usa ) ( 1:10,000 ) under uv light . pcr product was sent to functional biosciences ( madison , wi , usa ) for sequencing . the study was approved by institutional review board committees at the universidad san francisco de quito ( quito , ecuador ) and the university of michigan ( ann arbor , mi , usa ) . from july 2010 through february 2011 , a total of 77 samples ( 36 serum , 41 blood spot ) were collected from febrile patients . of these 36 hospital patients , 10 were from borbn and 26 were from the surrounding communities ; patients were 274 years of age ( median 19 years ) , and fever duration was 320 days ( median 6 days ) . six ( 17% ) of the 36 serum samples and 7 ( 17% ) of the 41 blood spots were positive for dengue by pcr ; whereas 10 ( 29% ) of the 34 serum samples tested by elisa were positive for dengue igm ( table ) . the ages of the 10 patients with positive results by elisa were 363 years ( median 38 years ) , and fever duration was 413 days ( median 6.5 days ) . although positive pcrs are sufficient indicators of acute infection , the positive igm reflects a cumulative incidence over 6090 days . therefore , the 17% pcr - positive estimate is a lower bound , and the 42% estimate by pcr or elisa is an upper bound . the denvs in the 13 samples that were positive by pcr were either serotype 2 or 3 ; samples from 1 patient contained both serotypes , probably resulting from a co - infection . each institution ( hcb and snem ) submitted samples from the same 2 patients , but only 1 was positive for dengue by pcr . during this same period , denv-1 , -2 , and -4 were detected in coastal cities in other regions of ecuador ( denv-3 has not been reported in ecuador since 2009 ) . colombia is a likely source , given the proximity of the study region to colombia and the fact that denv-3 was circulating in colombia ; but without sequence data , the geographic location of the source can not be confirmed . * only 34 serum samples were tested by elisa ; only 1 of the 10 positive samples was also positive by pcr . this study provides evidence of a transition of febrile disease etiology from plasmodium spp . , other possible fever - causing agents for which we did not test include leptospira spp . given that malaria has historically been the predominant cause of fever in the developing world , febrile patients are often triaged toward malaria treatment , especially in resource - poor areas . moreover , the awareness of malaria is embedded culturally and behaviorally in these communities : having a fever is equated with having malaria . of the 40 febrile patients who sought treatment for malaria , none had malaria but 17% had dengue ( positive for denv by pcr ) . further research is needed to refine this estimate and explore how the ministry of health and the general population should be directed to manage cases of fever during this etiologic transition . the need to bring attention to this transition is exemplified by our finding of denv-3 in our study site ; this serotype has not been isolated in other parts of ecuador since 2009 . esmeraldas , therefore , may be a major source of newly introduced dengue serotypes into ecuador .

in tropical areas , the predominant cause of fever has historically been malaria . however by 2011 , among febrile patients in northwestern ecuador , dengue was identified in 42% and malaria in none . this finding suggests a transition in the cause of fever from malaria to other illnesses , such as dengue .

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 .

although isolated cases of endomyocardial fibrosis ( emf ) and apical hypertrophic cardiomyopathy ( aphcm ) have been frequently reported in the prior literature there is only one other case report of the coexistence of both entities in the same patient . a 48yearold man from west africa with no family history of cardiac disease or sudden cardiac death was evaluated for chronic dyspnea . a transthoracic echocardiogram showed a thickened left ventricular ( lv ) apex ( 21 mm ) with an echolucent mass at the lv apex surrounded by a dense ridge of tissue ( figure 2 ) . doppler echocardiography showed restrictive hemodynamics ( figure 3 ) and twodimensional speckle tracking myocardial longitudinal strain assessment showed reduced apical longitudinal strain ( figure 4 a ) . given he was of west african descent , an initial diagnosis of endomyocardial fibrosis was entertained . however , because careful doppler interrogation demonstrated intramyocardial coronary blood flow ( figure 4 b ) at the hypertrophied apex , the possibility of aphcm with a possible calcified apical thrombus also was considered . cardiac magnetic resonance imaging ( cmr ) showed a thickened myocardium with apical cavity obliteration and endomyocardial calcification ( figure 5 a ) , and delayed imaging demonstrated two distinct patterns of hyperenhancement : one with marked bright computed tomography revealed marked calcification in the lv apex with apical hypertrophy and no coronary stenosis ( figure 6 ) . holter monitoring revealed several episodes of nonsustained ventricular tachycardia ( nsvt ) , and the patient had a hypotensive blood pressure response with runs of nsvt on treadmill testing . the patient subsequently underwent a prophylactic defibrillator placement for primary prevention of sudden cardiac death . an extensive workup for known disorders of cardiac calcification , including hypercalcemia , myocarditis , myocardial infarction , prior radiation therapy or renal disease , was negative . the electrocardiogram shows normal sinus rhythm with left ventricular hypertrophy and inverted t waves in the anterolateral leads . the echocardiogram ( a ) without contrast and ( b ) with contrast shows calcium ( white arrows ) and a thick ridge of tissue surrounding the calcium ( arrowheads ) . ( a ) the mitral inflow pattern shows a deceleration time of 144 ms . ( a ) color doppler with a nyquist limit of 12 cm / s shows the intramural coronary artery ( arrow ) . ( b ) a bull'seye view of the left ventricular longitudinal strain shows decreased strain of the apex . cardiac magnetic resonance imaging ( a ) ssfp 4ch cine image and ( b ) late gadolinium enhancement images show calcification ( green arrows ) . the red arrow points to the subendocardial fibrosis , and the arrowheads point to the area of patchy gadolinium enhancement . computed tomography of the heart ( a ) without contrast and ( b ) with contrast shows calcification in the endomyocardium of the left ventricular apex . obliterative fibrosis and calcification of the lv is known to occur in emf a disease first described by davies et al . in uganda in 1947.1 the pathologic hallmark of emf is scarring and fibrosis of the endocardium and inner third of the myocardium ; five types of emf , based on the different regions of the heart involved , have been described . although biopsy is the mainstay of diagnosis , contemporary imaging modalities ( e.g. , cmr , computed tomography ) with their high contrast and spatial resolution are very valuable for tissue characterization of the underlying fibrosis and calcification and preclude routine biopsies in suspected cases of emf.2 aphcm , on the other hand , is a phenotypic variant of hcm in which hypertrophy is localized to the lv apex with or without midsegment involvement ( mixed morphologic subtype ) and with or without the formation of an apical aneurysm . aphcm patients with paradoxic jet flow gradients are prone to apical mural thrombus formation ( which may calcify over time ) with subsequent systemic thromboembolism . myocardial fibrosis as evidenced by late gadolinium enhancement is commonly observed in aphcm,3 and although endomyocardial calcification in aphcm is reported , it is rare . the diffuse nature of intramyocardial fibrosis in aphcm differentiates it from the dense subendocardial hyperenhancement in emf . initially , the differential diagnosis for the bright hyperenhancement was emf vs trapped contrast . however , the absolute absence of blood flow established by color doppler , contrast echocardiogram , and computed tomographic contrast in the left ventricular apical cavity between the calcium and apical hypertrophied muscle favored emf as the diagnosis . careful multimodality imaging ( computed tomography , cmr , and color doppler ) did not show any regional dysfunction , midcavitary obstruction , or paradoxic jet flow although reduced apical longitudinal strain with grade iii diastolic dysfunction were noted . judicious evaluation by color doppler with a low nyquist limit clearly showed intramural coronary arteries in a hypertrophied apical segment , and the diagnosis of emf was considered to be less likely until cmr clearly hinted at the presence of type1 emf . since the etiopathogenesis of emf remains elusive , it remains to be determined if aphcm is a contributor or just an incidental finding . moreover , as cmr techniques continue to mature , it is conceivable that more such synchronous cardiomyopathies may be able to be diagnosed in the future .

abstracta 48yearold man from west africa was evaluated for dyspnea . echocardiography showed an echolucent mass at the left ventricular apex surrounded by a dense ridge of tissue , suggesting endomyocardial fibrosis ( emf ) . doppler echocardiography showed restrictive hemodynamics and intramyocardial coronary blood flow at the hypertrophied apex , suggesting apical hypertrophic cardiomyopathy ( aphcm ) with calcified thrombus . cardiac magnetic resonance imaging showed a thickened myocardium with apical cavity obliteration and endomyocardial calcification , and gadolinium contrast demonstrated marked bright subendocardial and diffuse patchy intramyocardial hyperenhancement in the hypertrophied apical wall segment , confirming coexistence of emf and aphcm . workup for known disorders of calcification was negative .

idiopathic and familial forms of pulmonary arterial hypertension ( pah ) continue to carry a poor prognosis despite significant improvements in the treatment of these and related conditions over the past 15 years . existing therapies are based on the replacement of prostanoids , inhibition of the endothelin pathway , or enhancement of nitric oxide signaling . although these therapies have improved symptoms and possibly survival of some patients , additional approaches founded on a more thorough understanding of the cell and molecular pathobiology of pah are required . nearly 10 years ago , heterozygous germline mutations in the gene encoding bone morphogenetic protein type ii receptor ( bmpr - ii ) , on chromosome 2q33 , were identified in families affected by pah . to date , mutations in bmpr - ii have been identified in nearly 80% of affected families . in addition , 10 - 40% of apparently sporadic cases of idiopathic pah have been found to harbour mutations in bmpr - ii . mutations have been identified in almost all of the coding exons of the bmpr2 gene . approximately 30% of mutations are missense , causing substitution of highly conserved amino acids in important functional domains of the receptor ( e.g. , the ligand - binding or kinase domains ) . the remaining ( approximately 70% ) comprise nonsense , frameshift , and splice - site defects , and gene rearrangements . these predict premature termination of the transcript with likely loss through the process of nonsense - mediated decay ( nmd ) . this important observation suggests that , although heterozygous mutation in bmpr - ii increases the risk for pah more than 10-fold , some additional environmental or genetic factor seems to be a requirement for disease manifestation . evidence for genotype - phenotype correlations is slowly emerging in that missense mutations have been associated with earlier age of onset and increased penetrance compared with other mutations . in addition , certain low - penetrance alleles seem more likely to occur in idiopathic pah or disease associated with other known triggers . bmpr - ii is a type ii receptor member of the transforming growth factor - beta ( tgf- ) superfamily . as with other tgf- family members , the type ii receptor is a constitutively active serine - threonine kinase , which in the presence of ligand phosphorylates the type i receptor . the type i receptor then phosphorylates a family of proteins termed smads , which can bind to dna either directly to alter gene transcription or in the presence of dna - binding partners . bmps typically activate smads 1 , 5 , and 8 , whereas the tgf- receptors typically activate smads 2 and 3 . smad 4 is a common partner smad that lacks a dna - binding domain but is necessary for entry of the receptor - activated smads to the nucleus . in lung tissue from patients with heritable pah , bmpr - ii protein expression and phospho - smad1 expression are reduced . of note , expression of these key parts of the bmp signaling pathway is also reduced in pah patients who have no identifiable mutation in bmpr - ii . in pulmonary artery smooth muscle cells ( pasmcs ) isolated from patients with bmpr - ii mutations , phospho - smad1/5 activation in response to bmps is suppressed , as is the activation of key bmp target genes , including the inhibitors of differentiation ( i d ) genes . the bmp / bmpr - ii / smad1/id gene axis appears to be growth - suppressive in pasmcs and pro - apoptotic . overexpression of mutant bmpr - ii in vascular smooth muscle cells of transgenic mice appears sufficient to induce the development of pulmonary hypertension in these animals , whereas heterozygous bmpr2-null mice have no clear phenotype . these findings likely indicate the need for a critical reduction in the bmpr - ii activity below a threshold for the manifestation of disease . it is possible that additional triggers necessary for disease manifestation may further disrupt expression of key components of this pathway or indeed bmpr - ii itself . immunohistochemistry and in vitro studies suggest that bmpr - ii is most highly expressed on the vascular endothelium . in contrast to pasmcs , bmps via bmpr - ii / smad1/5 and id1 are thought to enhance proliferation and reduce apoptosis of endothelial cells . conditional knockout of endothelial bmpr - ii is sufficient to cause pulmonary hypertension in a proportion of mice . in terms of the translational value of the molecular findings , two major questions arise . first , can the restoration of bmpr - ii function or expression prevent , or preferably reverse , the development of pulmonary hypertension ? second , what are the consequences to the cell of reduced bmpr - ii expression or function and can these be targeted ? we now know that reduced bmpr - ii expression is a key feature of the two most commonly used rat models of pah : chronic hypoxia and exposure to the plant alkaloid , monocrotaline . prevention of the reduction of bmpr - ii expression by adenovirally transduced lung endothelial targeting of bmpr - ii ameliorates the development of pulmonary hypertension in chronically hypoxic rats . the same targeted approach is successful in the monocrotaline model , although transduction via the airways failed to have an effect . agents that improve translational read - through of the transcript would therefore be useful for mutations in which the resulting protein would retain some function . many of the missense mutations occur in the ligand - binding domain of bmpr - ii and involve the substitution of important cysteine residues that provide tertiary structure to the molecule . these cysteine - substituted mutants fail to traffic normally to the cell surface and are held up within the endoplasmic reticulum . though mutated , these receptors retain kinase activity , can associate with type i receptors , and retain some ligand - binding capacity . it is possible to use chemical chaperones to enhance mutant bmpr - ii trafficking to the cell surface and restore bmp signaling in addition , it is possible that the endoplasmic reticulum stress response may be activated in the presence of these mutations , which could also be a target for intervention . one example of a pathway that is altered as a consequence of reduced bmp signaling is the tgf- pathway via the tgf- type 1 receptor , activin receptor - like kinase 5 ( alk-5 ) . several studies have now confirmed that alk-5 inhibition can prevent or reverse established pulmonary hypertension in rodent models . another consequence of reduced bmpr - ii function appears to be the increased expression of pro - inflammatory cytokines and inflammation . further advances are required to develop a robust mouse model of bmpr - ii mutation that consistently leads to pulmonary hypertension and vascular remodeling . this will depend on the identification of a trigger or second hit that precipitates disease . the unique conditions faced by the lung circulation and the localization of disease to that vascular bed are likely clues to solving this enigma . such models will allow the testing in vivo of novel therapies designed to target bmpr - ii or the bmp signaling pathway . a further challenge is to more fully understand the consequences to the vascular cell of bmpr - ii mutation . evidence is emerging that non - canonical signaling or additional hitherto unknown functions of bmpr - ii may provide further insight into pathobiology and ultimately therapy .

pulmonary arterial hypertension ( pah ) is usually a devastating condition with a poor prognosis . nearly 10 years ago , the underlying molecular basis of heritable pah was elucidated with the identification of mutations in the gene encoding the bone morphogenetic protein type ii receptor ( bmpr - ii ) . this discovery is now beginning to suggest novel approaches to therapy in heritable pah . moreover , recent studies provide evidence that dysfunction of the bmpr - ii pathway is a feature of non - familial forms of pah , broadening the scope for intervention in this pathway .

electroporation , a nonthermal phenomenon , is used to enhance the permeability of biological cells and tissues [ 14 ] . here , an attempt has been made to study the electric field 's effect on tumor tissues thereby leading to the efficacy of electroporation . electroporation involves the rapid structural rearrangement of membrane , in response to an electrically applied electric field . a noticeable effect is a rapid increase in electrical conductivity attributed to the formation of pores in the bilayer lipid membrane . literatures have shown significant trend of progressive electrical changes according to the proliferative characteristics of breast epithelial cells . physiologists also further postulated that malignant transformation resulted from sustained depolarization and a failure of the cell to repolarize after cell division , making the area where cancer develops relatively depolarized when compared to their nondividing or resting counterparts . it leads to the rupturing of membrane wall which can be either reversible or irreversible . electroporation generally depend upon the magnitude and the duration of the voltage , and the field applied . the membrane potential vm is given as ( 1)vm=1.5ercos , where r is the cell radius and is the angle between the electric field e and the radius vector . a detailed study of electric field distribution is necessary for an effective understanding of the tissue 's behavior when subjected to electric field . in this study the behavior of tissue and the effect of electric field on them are noted in each case . literature has indicated that changes in the electrical properties of abnormal breast are more significant compared to the breast normal tissues . the surface potentials are sensitive to the presence of tumour , location and placement of the electrodes . the results can be used as a complement to experimental analysis , essential for effective manipulation of tissues for practical , real - life applications , such as electroporation - mediated gene therapy and enhancement of chemo - drug delivery ( electrochemotherapy ) [ 14 ] . for fast and accurate simulation results , we chose the maxwell 's fem software from ansoft corporation , usa . for this simulation study , a slightly modified version of the more detailed electrical model of a tumor tissue reported by surowiec et al . three - dimensional models of breast lobe with single tumor and normal cell , with two tumor cells and two normal cells , are simulated for both needle and plate electrode configurations . the maxwell simulator is an interactive package that uses finite element analysis ( fea ) to solve three - dimensional electrostatic problems . the normal and the tumor cell permittivity and conductivity parameters used for the model are shown in table 1 [ 9 , 10 ] . a high voltage of the order of 1200 v / cm is applied at 1 khz frequency . the electric field across the tissue model for plate electrodes configuration is shown in figures 2 and 3 for normal and tumor cell tissues . the electric field intensity is more for the normal cell tissue than the tumor cell tissue . this could be due to change in membrane structure , composition , and minerals in the tumor cell compared to the normal cell . similar results were obtained also for needle electrode configuration ( figure 4 ) . from this electric field distribution values , the transmembrane potential is calculated for the applied voltage . also , from the 3d simulated model of different tissue model the capacitance value is noted and this value is applied to the electrical model using matlab . for this simulation study , a slightly modified version of the more detailed electrical model of a cell reported by schoenbach 's team [ 12 , 13 ] is used . the entire breast lobe with tissues is assumed as a single cell , and simulation is done . here , the tissue is modeled as a homogenous conductive medium ( cytoplasm ) surrounded by a leaky dielectric membrane . in the above electrical model , the capacitance of the normal cell is replaced by the capacitance value obtained from the ansoft model of the cancer cell developed in this study . to this electrical model , a pulsed electric field of the order of 1200 v / cm is applied with a pulse width of 100 sec and for a time period of one second . the variation in voltage ( y - axis ) across each element with respect to time ( x - axis ) is shown in figures 610 for various tissue models studied using plate electrode configuration . figure 6 shows the voltage across various cell elements , such as nucleus , plasma , and conductive cytoplasm for tissue with a normal cell and a tumor cell . figure 7 shows the voltages for a tissue with two normal cells and figure 8 shows that of a tissue with two tumor cells ( plate electrodes ) . there is noticeable difference between the voltages and their profiles for various elements between these two electrode configurations indicating the effect of electrode on the electroporation efficacy [ 14 , 15 ] . figure 10 shows the influence of the electric field orientation on the transmembrane potential ( tmp ) . the orientation is varied from 0 to 70 degrees , and the tmp is evaluated for the applied voltage between the electrodes . it can be inferred that the transmembrane potential tends to decrease with increase in orientation . also , the transmembrane potential of tumor tissue is less than that of the normal tissue . this could also be attributed to the altered cell membrane and other cell parameters of the tumor cell compared to the normal cell . table 2 shows the influence of the electric field orientation on the nuclear membrane potential ( nmp ) . the orientation is varied from 0 to 70 degrees , and the nmp is evaluated for the applied voltage between the electrodes . also , the nmp of tumor tissue is less than that of the normal tissue . this could also be attributed to the altered cell membrane and other cell parameters of the tumor cell compared to the normal cell . a healthy cell membrane potential is strongly linked to the control of cell membrane transport and proliferation mechanisms as well as dna activity , protein synthesis , and aerobic energy production . since cancer cells can not maintain a normal membrane potential , they will have electronic dysfunctions that will impede repair and the reestablishment of normal metabolic functions . therefore , a key therapeutic method for cell repair and cancer treatment would be to reestablish a healthy membrane potential in the body 's cells . in our research , the electric field distribution in normal and tumor tissues was investigated using 3d finite element analysis for plane and needle electrode configurations . the tumor tissues shows lower intensities of electric field compared to the normal tissues , possibly due to the altered characteristics of membrane potential , its composition and minerals such as potassium , magnesium , sodium , and calcium . these results demonstrate the susceptibility of malignant cells to the electric field application and the relative robustness of the normal cells , illustrating the enhanced efficacy of the electrochemotherapy using lower drug doses . the field analysis results can be used for assessing effective treatment parameters of tumor tissues . the electrical characteristics of the membrane and the cytoplasm , such as the conductivity and permittivity of the membrane and the cytoplasm , as well as membrane thickness also govern the response due to electroporation in addition to the intensity and distribution of the electric field applied . our results indicate that electric field analyses could be used for selecting suitable parameters for effective treatment of tumor tissues , since these parameters need to be optimized for various tumors / tissues and cells .

an attractive alternative treatment for malignant tumors that are refractive to conventional therapies , such as surgery , radiation , and chemotherapy , is electrical - pulse - mediated drug delivery . electric field distribution of tissue / tumor is important for effective treatment of tissues . this paper deals with the electric field distribution study of a tissue model using maxwell 3d simulator . our results indicate that tumor tissue had lower electric field strength compared to normal cells , which makes them susceptible to electrical - pulse - mediated drug delivery . this difference could be due to the altered properties of tumor cells compared to normal cells , and our results corroborate this .

knowledge of the anatomical variations of the axillary region has become more relevant with increasing surgeries of this region for breast cancer , reconstruction procedures and axillary by - pass . lager 's arch or the axillary arch ( aa ) is the best - known variant structure in the axilla . it is a muscular or fibromuscular slip of varying dimensions , extending from the latissimus dorsi ( ld ) muscle about the middle of the posterior axillary fold , and crosses over the neurovascular structures , to join the under surface of the tendon of the pectoralis major , the coracobrachialis , or the fascia over the bicepsbrachii [ 1 , 2 ] . a 60-year - old female presented to our breast clinic with a left breast lump sized 3 2.5 cm incidentally felt since 3 months . it was gradually increasing in size and was not associated with any other breast complaints . she was evaluated with mammography that suggested a birads 3 lesion at 12 oclock position . subsequently , her metastatic work - up included abdominal pelvic ultrasound , chest computed tomography and bone scan . intra - operatively , during the axillary lymph node dissection , we encountered an unusual muscle slip crossing the axilla from the ld muscle to the posterior surface of the pectoralis major muscle anterior to the axillary vein . all neurovascular structures and lymphoid tissue were lying posterior to this abnormal muscle ( fig . 1 ) . figure 1:aa muscle extending from ld muscle to under surface of pectoralis major tendon in the left axilla crossing over axillary neurovascular structures ( in view ) . aa , axillary arch ; pm , pectoralis major ; ld , latissimus dorsi muscle ; av , axillary vein ; tnb , thoracodorsal neurovascular bundle ; ltn , long thoracic nerve . aa muscle extending from ld muscle to under surface of pectoralis major tendon in the left axilla crossing over axillary neurovascular structures ( in view ) . aa , axillary arch ; pm , pectoralis major ; ld , latissimus dorsi muscle ; av , axillary vein ; tnb , thoracodorsal neurovascular bundle ; ltn , long thoracic nerve . the lymph nodes lateral and beneath the arch were successfully dissected , and the arch itself was left undisturbed . the procedure was uneventful , and the patient had a good post - operative recovery . on follow - up , 21 months after surgery , the patient was alive and free of known disease . however , it was karl langer in 1846 who gave a more accurate description of this variant , so thereafter , it was named after him [ 24 ] . throughout the literature , several terms have been used to describe the muscular variant running from the ld muscle towards the pectoralis major muscle : aa muscle , axillopectoral muscle and also their translations in different languages . in the following text , the anatomical description of the aa is variable among authors . according to testu 's classification ( 1884 ) , the complete aa extended between the ld and the tendon of the pectoralis major near its insertion on the humerus ; the incomplete one extended from the ld to the axillary fascia , biceps brachii muscle , coracobrachialis muscle , the distal end of the bicipital groove and the inferior edge of pectoralis minor muscle or coracoid process . the case we encountered was of unilateral complete aa . according to many anatomic texts , however , it has been recognized in only 0.25% during axillary surgical procedures [ 1 , 2 , 4 , 5 ] . the difference in surgical and anatomical incidence reflects a failure of reporting or identification during surgery . also , this discrepancy may be attributed to the specific aim of cadaveric studies to identify such anatomic anomalies . this should be kept in mind as it can be confused with axillary lymphadenopathy or soft tissue tumour [ 1 , 3 ] . aa can act as entrapment site for the neurovascular bundle during some arm movements causing circulatory deficiency , chronic pain and paraesthesia . simple division of the arch is curative in such cases [ 2 , 5 ] . jelev , through his extensive work , introduced a new definition of clinical aa as a variant muscular structure in the axilla that is a possible entrapment site for the nerves and vessels . , the existence of a superficial or deep aa could be suspected according to the vessels or nerves mostly affected . it can positively correlate its presence with neurovascular entrapment symptoms . also , it can assess its anatomic relations [ 1 , 5 ] . the surgical significance of the aa is 2-fold : ( i ) it may hide some axillary nodes , and ( ii ) it may mislead the dissection into a supra axillary plane . a group of lateral axillary nodes may be concealed under the aa while crossing over the axillary vein . missing these nodes during axillary node dissection imposes a risk for local recurrence in patients with breast cancer and melanoma . this also can lead to inaccurate staging , which in turn could negatively affect adjuvant and systemic therapy decisions for breast cancer . this may lead the surgeon to dissect in a plane above the axillary vein increasing the risk of injury to the axillary artery and brachial plexus . during sentinel node biopsy , the aa can pose difficulty as it stretches in the hyper abducted position shifting the nodes higher . in order to clearly identify , the anatomic landmarks the arch can be divided at the level of the axillary vein . furthermore , some authors suggest division of the arch in all cases to prevent possible post - operative axillary vein compression and associated lymphoedema [ 3 , 4 ] . in our case , there was no added morbidity related to dissection of nodes beneath and lateral to the arch . the presence of the aa may precipitate lymphoedema in cases where ld myocutaneous flap is used for breast reconstruction . for this reason , the aa should be divided if there is a possibility of a ld flap being required in the future . as in our case , most reported clinical cases describing the aa have been identified during axillary surgical procedures [ 2 , 4 ] . it can cause confusion during routine axillary surgery for breast cancer , which can both affect procedure safety and misguide further treatment decisions [ 3 , 4 ] .

langer 's arch is the best - known anatomic variant of definite surgical implication in the region of the axilla . this rare anomaly is a muscular slip extending from the latissimus dorsi ( ld ) muscle to the tendons , muscles or fasciae around the superior part of the humerus . in this report , we present a rare case of left axillary arch . during modified radical mastectomy for breast cancer , we encountered an abnormal muscle slip crossing the axilla from the ld muscle to the posterior surface of the pectoralis major muscle anterior to the neurovascular structures . preoperative knowledge is essential to identify such unusual anomaly and avoid potential complications both intra- and postoperatively .

they learn how to overcome their fears and how to minimize the delivery side effects . the classes are nine sessions , held at the 21 to 37 week of pregnancy . each session contains 45 min theoretical lessons , 15 min question and answers , 30 min practical exercises and 15 min visiting the delivery ward . the physical practices are used to achieve practical relaxation without any medicine . in physiologic delivery these interferences can include simple actions such as shaving , enema , serums , hourly vaginal touch , and obligatory bed rest . in physiologic delivery , vaginal massages , perineal wet and warm exercise can be used instead of episiotomy . concerning the mentioned facts and advantages of physiologic delivery , in this field trial , all pregnant women who were involved in physiologic delivery program in besat hospital ( sanandaj ) were evaluated during 2010 - 2011 . the inclusion criterion was willingness to participate in physiologic labor program and exclusion criteria included : absence of prom , fetal post date , cephalopelvic disproportion , multi - fetal pregnancy , induction , meconium stain , blood pressure above 140/90 , placenta previa , and history of cesarean . first , women received the necessary trainings that had been standardized according to the national guidelines . then , pregnant women entering labor blocks were enrolled in the study as non - physiologic delivery group . an assistant midwife conducted some interviews and examinations and helped the women to fill out a questionnaire that included demographic information , questions about the physiologic labor , their satisfaction and delivery outcomes . apgar score and babies status were recorded . in order to eliminate any ethical conflict in the study , in case of any indication for cesarean the data was then entered into spss 16 software . for comparing vaginal laceration , episiotomy and apgar score between two groups chi - square test and fisher exact test were used . there were 73 persons in physiologic delivery group and 69 in the non - physiologic delivery group . mean age was 27.3 ( 4.9 ) years , median of gravity was one ( 1 to 5 ) and median of parity was 0 ( 0 to 4 ) . no difference in age , residency , and educational level was observed between two groups . median of parity was higher in physiologic delivery group than non - physiologic delivery group ( p = 0.013 ) . twelve persons ( 16.4% ) in physiologic delivery group and 27 persons ( 39.1% ) in non - physiologic delivery group needed episiotomy ( p = 0.002 ) . ten patients ( 13.7% ) in physiologic delivery group and seven persons ( 10.1% ) in non - physiologic delivery group suffered from vaginal laceration ( p = 0.51 ) [ table 1 ] . no statistically significant difference was found between the apgar scores of the two groups . comparing the non - physiologic and physiologic delivery group regarding the demographic features and the outcomes of the delivery after delivery , 95.5% of women were immediately satisfied with physiologic labor and had no delivery complication . the percentage of mothers satisfaction in physiologic delivery group at the time of delivery , 10 days and 40 days after delivery based on the results of this study , a lower percentage of participants in physiologic delivery group , compared with non - physiologic delivery group , need episiotomy ; nevertheless , the vaginal laceration was the same in both groups . moreover , women were highly satisfied with the physiologic delivery and their satisfaction increased in the later days following delivery . it is more important in iran because the number of caesarean section cases is very high in this country and it even reaches up to 50% in some regions of the country . apparently , it is a good alternative for pregnant women and they may be motivated to practice physiologic delivery . the main purpose of physiologic delivery is to relay on the mother 's body for delivery with minimal intervention . pregnant women learn how to overcome fear and pain ; consequently they will suffer less from negative aspects of vaginal delivery . one of the main advantages of physiologic delivery is the lack of additional procedures such as shaving , enema , serums , and obligatory bed rest . the hourly vaginal touch for controlling the patient and the fetus is not required and the examinations are done once every four hours . routine application of lithotomy position which is used in non - physiologic delivery group , may increase the chance of trauma and the duration of bed rest and it is only essential when delivery assisted tools are used . based on the conducted studies , in classic delivery the episiotomy which is conducted for nullipara pregnancies does not make any particular advantage in exiting the fetus . in physiologic delivery , vaginal massages and very few studies have been done in the field of physiologic delivery and the first study in this field was published in iran . in a few number of studies some of its components have been investigated . in a survey conducted by mehdizadeh et al . , eight sessions of theoretical and neural - muscle exercises reduced the pelvic pain and fatigue during pregnancy and increased daily activities . the active phase and the second step of delivery were shorter in trail group ; however , the level of prescribed drugs or oxsytosin , anti spasm , pain killers , perineal laceration , the weight at birth , and apgar scores were similar in both groups . in another study by hosseini et al . , the effect of prenatal education on anxiety , pain and duration of labor was evaluated . based on the results , the anxiety , the labor pain , and duration of pain in the intervention group were significantly less than other groups ( p < 0.001 ) . taavoni et al . , investigated how exercising with birth ball can affect the pain , duration of active phase , and contractions during delivery . according to the study , average pain score on ball group was significantly lower than the control group ( p < 0.05 ) . the mean duration of uterine contractions , the contractions interval and the duration of active phase in the two groups were not significantly different . we did not evaluate duration of labor phase and we have focused on vaginal laceration , episiotomy and apgar score . due to the shortage of research in this area , more research is needed .

background : the main purpose of physiologic delivery is to rely on mother 's body for childbirth . in physiologic delivery method pregnant women attend delivery preparation classes and they learn how to overcome fear and pain . this study compares delivery outcomes among women who participated in physiologic delivery with those who had undergone non - physiologic delivery.methods:all patients referred for physiologic delivery were assessed . exclusion criteria were lack of prom , post date , cephalopelvic disproportion , multi - fetal pregnancy , meconium stain , blood pressure above 90/140 , placenta previa and previous record of cesarean . data was entered in spss 16 software and fisher and chi - square tests were used to compare vaginal laceration , episiotomy and apgar score between two groups.results:twelve out of 73 pregnant women ( 16.4% ) in physiologic delivery group and 27 out of 69 pregnant women ( 39.1% ) in non - physiologic delivery group needed episiotomy ( p = 0.002 ) . ten patients ( 13.7% ) in physiologic delivery group and seven persons ( 10.1% ) in the non - physiologic delivery group were suffering from vaginal laceration ( p = 0.51 ) . there was no significant statistical difference between newborns apgar score in two groups.conclusions:physiologic delivery can reduce the need for episiotomy without any further complications .

according to the world health organization ( who ) classification , odontogenic tumors are considered to be tumors of the odontogenic mesenchyme , with or without the presence of odontogenic epithelium . myxomas of head and neck are divided into two forms : i ) deriving from facial bone which has also been subdivided into osteogenic myxoma and odontogenic myxoma ; ii ) deriving from soft tissue which originate from perioral soft tissues , parotid glands , ears and larynx . patients may also complain of malocclusion , loss of tooth and palatal swelling . from a histological aspect , odontogenic myxomas include spindle like cells , star shaped cells with elonged cytoplasms and , in some cases , small masses of inactive odontogenic epithelium . radiographically , the tumors present as unilocular or multilocular radiolucent lesions . the lesions usually have well - defined borders and are described as honeycombed or soap bubble shaped . differential diagnosis must be made with ameloblastoma dentiginous cysts , fibrous dysplasia , osteosarcoma , chondrosarcoma and odontogenic fibroma . although local trauma has been thought to be the cause , the etiology is unknown . there are high recurrence rates after surgical excision . therefore , wide local excision is mandatory for treatment . in this case report we discuss these tumors with examples from literature because they are very unusual in childhood and have high recurrence rates . the patient was a 9-year old girl presenting with swelling on the right facial region . physical examination of the patient revealed that the mass had obliterated the right nasolabial groove and caused swelling of the right facial region . the computerized tomography ( ct ) examination revealed that the mass was originating from the right maxillar bone and the maxillary sinus antrum was filled by the tumor . medial and anterior wall of the sinus was displaced because of the growing mass ( figures 1 and 2 ) . an incisional biopsy was made through the nasolabial groove and was reported to be odontogenic myxoma . surgical removal of the mass including wide periincisional tissue was performed via a right superior gingivo - buccal incision . during the operation it was seen that the mass was white in color , completely encapsulated and was completely filling the sinus antrum . the anterior wall of the maxillary sinus was thinned , partially destructed and pushed anteriorly . figure 1axial tomographic image of the myxoma showing obliteration of the right maxillary sinus and bone destruction with finger like projections into maxilla . axial tomographic image of the myxoma showing obliteration of the right maxillary sinus and bone destruction with finger like projections into maxilla . figure 2coronal tomographic images of the myxoma showing obliteration of the right maxillary sinus and bone destruction with finger like projections into maxilla . coronal tomographic images of the myxoma showing obliteration of the right maxillary sinus and bone destruction with finger like projections into maxilla . the patient was followed up for two years and there has been no evidence of recurrence . histological examination of both masses removed during the two surgical interventions revealed hypocellular tumoral tissues with myxoid stromas and scattered stellate fusiform cells with hyperchromatic nuclei ( figures 3 and 4 ) . figure 3hypocellular tumoral tissue with myxoid stroma and scattered stellate and fusiform cells with hyperchromatic nuclei ( hematoxylin & eosin , 200 ) . hypocellular tumoral tissue with myxoid stroma and scattered stellate and fusiform cells with hyperchromatic nuclei ( hematoxylin & eosin , 200 ) . figure 4tumor tissue showing the same morphology in every field including the bone trabeculae ( hematoxylin & eosin , 200 ) . tumor tissue showing the same morphology in every field including the bone trabeculae ( hematoxylin & eosin , 200 ) . thoma and goldman separated myxomas of the mandible and maxilla from other myxomas . in 1948 , stout redefined the histological criteria for myxomas as benign neoplasms of mesenchymal origin . ghosh et al . defined only 10 osseous myxomas in a review of 8723 primary bone tumors ; 6 in the mandible and 4 in the maxilla . although it is claimed that maxilla and mandible are equally involved , others noted a more frequent involvement of the mandible . however , there is a theory that they arise from odontogenic mesenchyme , especially from the molar and premolar region of the maxilla . stromas of myxomas are hypocellular and they include mucopolysaccharides , hyaluronic acid , and chondroitin sulfate molecules . these substances are thought to be the cause of the locally aggressive behavior of the myxomas . histologically , these tumors may be confused with myxoid degeneration , malignant nerve sheath tumors and myxoid chondrosarcoma . enucleation is performed for protecting the facial growth centers and this approach prevents facial asymmetry . it is suggested that enucleation may be performed in small tumors , but recurrence rates are higher than partial maxillectomy . therefore , wide surgical excision and close follow up is mandatory in osseous myxomas . in our patient , recurrence was confirmed four months after the operation and partial maxillectomy had to be performed . recurrence rates are high and a long follow - up period over years is essential after treatment for patients with these tumors .

myxomas are mostly seen in the 2th and 3rd decades . they rarely occur in childhood and maxillofacial region is rarely involved . the recurrence incidence is high . we report this unusual case occurring in a 9-year - old girl in the maxillofacial region and recurrence four months after initial treatment .

the ehlers danlos syndrome ( eds ) is a connective tissue disorder characterized by hypermobility of the joints as well as hyperextensibility of the skin . classic eds ( type i ) is an autosomal dominant disorder with a defect in type v collagen . hypermobility eds ( type iii ) is autosomal dominant and has a defect in tenascin x. these patients have classic severe joint hypermobility problems . vascular eds ( also known as type iv ) is an autosomal dominant disease , which is well known to the surgical community because of its propensity to cause spontaneous rupture of organs and arteries . in this variant , ocular b scoliotic eds ( type vi ) is known for severe curvature of the spine . patients have a marfanoid - type body habitus . because of the defect in procollagen b lysine 5 dioxygenase activity , minor trauma to the eye can cause globe rupture . these patients can also have rupture of the great vessels ( table 1 ) . to our knowledge , this is the first report of a traumatic dissection in a patient with eds type vi . because this patient was relatively well known in the medical community , institutional review board approval was obtained for this case report . table 1:eds classification.typetypical featuresinheritanceprotein defectclassic ( eds i and ii)skin hyperextensibility and fragility , joint hypermobility , tissue fragility manifested by widened hypertrophic scarringautosomal dominantcollagen vhypermobile ( eds iii)joint hypermobility , moderate skin involvementautosomal dominanttenascin xvascular ( eds iv)spontaneous rupture of internal organs including major arteries and intestines ; skin is thin and translucent with extensive bruising ; hypermobile minor jointsautosomal dominantcollagen iiix - linked edssimilar to classic typex - linked recessiveunknownocular scoliotic eds vimuscular hypotonia , progressive kyphoscoliosis , marfanoid habitus , osteopenia , occasional rupture of eye globe and great vessels . our patient is a 24-year - old male with the eds type vi who had undergone rod fixation of his spine for scoliosis , ocular surgery for a ruptured globe and ligation of his popliteal artery after an attempt was made to repair his aneurysm . the patient was being followed at duke eds clinic where he underwent an extensive workup , and a definitive diagnosis was established . he presented to the emergency room ( er ) after being kicked in the abdomen during a martial arts class . the patient went home after the incident and then developed nausea , vomiting and diaphoresis . he was hemodynamically normal in the er . his groin pulses were slightly diminished compared with his radial pulses . the patient underwent a computed tomography ( ct ) scan of the chest , abdomen and pelvis with intravenous contrast . the patient was found to have traumatic aortic injury ( fig . 1 ) . he was started on esmolol intravenously , and diltiazem was added in order to keep his mean arterial pressure around 60 . after 2 days in the icu , the patient was transitioned to medications by mouth . he was allowed to ambulate on the fourth day and discharged on the eighth day after a long discussion with him and his family . repeat ct scan revealed extension of the aortic injury in the abdominal aorta with no flow in the iliac ( figs 24 ) . the patient was emergently taken to the operating room ( or ) where the aorta , iliac and femoral vessels were unable to hold sutures . post - operatively , we spoke with the family , and the patient was allowed to expire . figure 3:no contrast is seen in the abdominal viscera . figure 4:note contrast in the distal aorta but no contrast in the iliac arteries . the eds type vi has ocular , vascular and musculoskeletal manifestations . complications of the disease continually plague patients throughout their lives . cross linking at the lysine and hydroxylysine is a key step in order for the fibrils to form . the defect in the eds type vi is reduced activity of the lysyl hydroxylase enzyme . this seems to lead to muscle hypotonia , joint laxity , kyphoscoliosis , poor wound healing , ocular fragility and arterial rupture . the major problem in eds is the patient 's tissue - paper - like vessels . this can be helpful , but sometimes the tissue is too fragile for even pledgets . because the vessels are so delicate , endovascular stents may be out of the question . all stents have some sort of anchor or hooks which hold the stents in place . these hooks would tear the brittle vessels in the eds patient and therefore would not be useful . however , there have been a couple of recent case reports [ 5 , 6 ] and one small retrospective series suggesting that endovascular stents may have a role in selected patients with eds . in retrospect , it is hard not to look at this case and see that this patient had few viable options when he originally presented to the er . taking this patient to the or was futile , as his vessels were unable to hold suture with or without pledgets . this caused more stress on his aorta through increased shearing forces . because of the patient 's inability to lay down normal collagen , he probably needed more time to heal this injury . nonoperative therapy was the best option for the patient . maybe keeping this patient in the hospital and making sure that his blood pressure and heart rate were under better control would have given this patient a better chance at survival .

a 24-year - old male with the ehlers danlos syndrome ( eds ) type vi ( ocular scoliotic ) who was kicked in the abdomen presented to the emergency room ( er ) with abdominal pain . he was found to have a blunt traumatic aortic injury . the patient was treated nonoperatively . he was stable and discharged home on the eighth day . the patient returned to the er several days later hypotensive and tachycardic . the patient was taken immediately to the operating room , but vascular repair was not possible . the patient expired . we discuss the challenges of taking care of a patient with eds and offer suggestions that might improve future patient 's outcome .

operating room ( ors ) fires related to anaesthesia ventilator mishaps are extremely rare events , but when they do occur , result in serious and sometimes mortal consequences . cardiac arrest associated with ventilator fire has not been reported in the published english literature . we report a near - fatal incident of cardiac arrest following ventilator mishap and successful revival of a patient who underwent subtotal thyroidectomy . a 65-year - old 60 kg asa grade i female patient underwent subtotal thyroidectomy for diffuse multinodular colloid goiter . pre - anaesthetic check up revealed normal cardiorespiratory systems . all investigations including electrocardiogram ( ecg ) , echocardiography and chest x - ray were within normal limits . routine general anaesthesia was administered and maintained using o2/n2o / isoflurane / fentanyl / vecuronium and ippv with an electrically driven volume - controlled anaesthesia ventilator . during the operation , intravenous fluids were administered based on haemodynamic parameters . at the end of near - completion of surgery , a moderately loud explosive sound this was followed within seconds by the appearance of smoke and an orange flame from the control panel of the ventilator . within minutes , both the smoke and the flame increased significantly and engulfed the ventilator , leading to complete melting of its parts [ figure 1 ] . the patient was disconnected immediately from the ventilator and ventilated with an ambu resuscitation bag . meanwhile , oxygen , nitrous oxide and electric supply of the anaesthesia apparatus and ventilator were disconnected and the fire was extinguished by spraying water . the anaesthetic and surgical teams shifted the patient out of the fire area to another adjacent operation theatre along with the ambu bag . in the or , the patient was reconnected to the monitor and another anaesthesia work station and ventilation was started with 100% oxygen . the approximate time between disconnection of endotracheal tube ( ett ) and ventilation with 100% oxygen was 23 min . meanwhile , we noticed absence of pulse and oxygen saturation with ecg showing tracings of asystole . cardiopulmonary resuscitation ( cpr ) was started and the lungs were ventilated with high flows ( 12 l / min ) of 100% oxygen . following 34 min of cpr and i.v . atropine 3 mg and adrenaline 2 mg ( 1 mg + 1 mg ) , the patient showed return of spontaneous circulation ( rosc ) . thereafter , the patient maintained a heart rate of 110120 bpm , bp 100/70 mmhg and oxygen saturation of 9394% . a 12-lead ecg , serum troponin a , serum electrolytes and abg were obtained to rule out other causes of cardiac arrest , and were within normal limits . once the patient 's circulation was restored and maintained for 1520 min , the remaining part of the surgery was allowed to complete . after the completion of the procedure , the neuromuscular blockade was antagonized with neostigmine 3.0 mg and glycopyrrolate 0.4 mg . she was observed and monitored in the post - anaesthesia care unit ( pacu ) for 24 h and then discharged on the fifth post - operative day . she was followed - up after 2 weeks and later monthly with no reported adverse sequelae of the event . the incident was notified to the manufacturer of the ventilator and is under an investigation stage to determine the cause of the incident . among all or fires , equipment - related fires are extremely rare incidents , probably because of strict electrical safety standards , good design of equipment and routine inspection and preventive maintenance . however , when these occur , the consequences are often disastrous for both the patient and the or personnel , particularly in poorly equipped hospital set - ups . historically , or fires or explosions caused by anaesthesia equipment were attributable to flammable anaesthetic agents.[25 ] berry et al . have reported combustive destruction of the anaesthetic circuit expiratory valve and explosions within the anaesthesia machine were reported by castro et al . normally , they create some smell or vapors , and these are controlled by stopping the flow of electricity to the device . sometimes , the fire can flare up without these warnings , as noted in our case . to cause fire , an oxidizing agent , a source of heat and a flammable material or fuel must be present . in the present case , sparks due to friction or electrical short circuit might have acted as the source of the ignition , which led to fire and explosion in the oxygen - rich environment . fire mishaps in ventilators are prevented by routine pre - use checkups and device service as per minimum standards mentioned in the user manual . cardiac arrest following ventilator fire is also a rare incident . because this mishap occurred intraoperatively , the first priority was to immediately shift the patient out of the danger area to protect from further thermal damage . although we disconnected the patient from the ventilator immediately , some smoke - rich gases were delivered by the ventilator . as other causes of cardiac arrest were ruled out , we suspected carbon monoxide toxicity as one of the causes for severe hypoxaemia and cardiac arrest . although cooximeter analysis helps in the estimation of carboxyhaemoglobin ( cohb ) , it is not routinely available in sub district - level hospital set ups . the half - life of cohb is between 4 and 6 h with room air , which further drops to 4090 min and 1530 min if the patient is receiving normobaric 100% oxygen and hyperbaric oxygen , respectively . although hyperbaric oxygen is the treatment of suspected co poisoning , high - flow normobaric 100% oxygen can still be life saving . timely and effective resuscitation helped us to revive the patient successfully . in conclusion , ventilator fires , although infrequent , can be disastrous . although the patient did not suffer thermal injury , the or team should be prepared to handle any eventuality arising out of such disaster . prevention of fires requires attention from everyone in the or to hospital authorities who make purchasing decisions . the knowledge and vigilance of the or teams in preventing fire and a quick response during such incidents appears a necessity . having a stringent quality control and ensuring electrical safety of medical equipment

operating room fires are rare events , but when occur they result in serious and sometimes fatal consequences . anaesthesia ventilator fire leading to cardiac arrest is a rare incident and has not been reported . we report a near catastrophic ventilator fire leading to cardiac arrest in a patient undergoing subtotal thyroidectomy . in the present case sparks due to friction or electrical short circuit within the ventilator might have acted as source of ignition leading to fire and explosion in the oxygen rich environment . the patient was successfully resuscitated and revived with uneventful recovery and no adverse sequelae . the cardiac arrest was possibly due to severe hypoxia resulting from inhalation of smoke containing high concentrations of carbon monoxide and other noxious gases .

a 71-year - old woman presented to our clinic for evaluation of right ocular pain and loss of visual acuity for the previous week . on ophthalmic examination , visual acuity was 20 / 50 in the right eye ( od ) . there was an anterior chamber reaction ( + + ) and a vitreous cell reaction ( + ) in the od . fundus examination revealed disc swelling , peripheral serous retinal detachment , and edema at the site of a macular lesion ( fig . posterior scleral thickening , choroidal effusion , and serous retinal detachment were demonstrated on ocular ultrasonography , suggesting posterior scleritis ( fig . the patient was treated with prednisolone ( 1 mg / kg orally ) and topical prednisolone ( 1% ) . after three days of treatment , the serous and choroidal detachment worsened , and her visual acuity decreased to hand movement . the patient agreed to proceed with intravitreal bevacizumab treatment ( 1.25 mg/0.1 ml ) after informed consent for the off - label use of this drug was obtained . one day later , the ocular pain and serous macular detachment were considerably reduced ; after one month , the scleritis had completely remitted ( fig . further improvement was noted , and the patient remained stable during six months of follow - up with a visual acuity of 20 / 40 in the od . concentrations of vegf and il-8 were measured using suspension bead array technology on a luminex tm 100 is system ( luminex corp . aqueous humor and blood samples from ten healthy controls undergoing cataract surgery were processed using an identical method . the aqueous humor and serum levels of vegf and il-8 from the patient were 880.51 pg / ml and 4,531.5 pg / ml , respectively , which were significantly higher than those of the healthy control group ( 65.1 42.9 pg / ml and 132.4 62.6 pg / ml , respectively ; p < 0.001 ) . the plasma levels of vegf and il-8 from the patient were 105.51 pg / ml and 5.91 pg / ml , respectively , which did not significantly differ from those of the healthy control group ( 255.7 198.9 pg / ml and 17.8 14.6 pg / ml ; p = 0.416 and p = 0.328 , respectively ) . data were compared using student 's t - test with bonferroni 's correction using spss ver . 12.0 ( spss inc . , posterior scleritis is a common form of scleritis that should be suspected in patients who present with periocular pain , visual loss , or any of the other signs of posterior scleritis . the pathophysiology of posterior scleritis is not fully understood ; however , during scleral inflammation multiple factors , including vegf , may increase vascular permeability by altering gap formation between endothelial cells . there have been numerous reports regarding its safety and efficacy in the off - label treatment of choroidal neovascularization and other ischemic - proliferative retinopathies . however , no studies using intravitreal bevacizumab as an adjuvant in treating posterior scleritis have been published to date . vegf , a powerful angiogenic substance , significantly increases vascular permeability and is associated with inflammation and immune - mediated pathology . therefore , we hypothesized that vegf is elevated in posterior scleritis . to test this hypothesis , we measured the aqueous humor and plasma levels of vegf in an affected patient . the current case describes the benefits of using intravitreal anti - vegf therapy in combination with systemic treatment . we observed an increased level of vegf in the aqueous humor of an affected patient without a corresponding increase is serum level . we suggest that the increased vegf was locally expressed and was not associated with increased systemic production . the increased levels of vegf and il-8 in the aqueous humor provide a rationale for the use of intravitreal anti - vegf therapy . although systemic steroid therapy may have a role in disease treatment , we demonstrated that an intravitreal bevacizumab injection could bring on prompt resorption of subretinal fluid , which may be associated with rapidly improved vision . the elevated aqueous humor levels of vegf suggest that it plays an important role in intra - ocular inflammation and increased vascular permeability in posterior scleritis .

we report a case of posterior scleritis effectively managed with intravitreal bevacizumab . a 71-year - old woman was diagnosed with posterior scleritis . although she was initially treated with systemic steroids , her clinical presentation deteriorated . she was then treated with a single intravitreal injection of bevacizumab and aqueous humor collection . the aqueous level of vascular endothelial growth factor prior to the intravitreal injection was 880.51 pg / ml , greater than that in the healthy control group ( p < 0.001 ) . one month later , the scleritis was completely resolved , and the patient remained stable during six months of follow - up . intravitreal bevacizumab appears to be an effective adjuvant therapy for patients with posterior scleritis .

they occur in roughly 1 in every 200 identical twin pregnancies and are always identical . the incidence ranges from 1 in 50 000 to 1 in 100 000 live births . because this situation carries high risk , early diagnosis and management of delivery is extremely important . a 31-year - old multigravid woman was referred to our university hospital at an 11-week gestation because of a conjoined twin ( thoracopagus ) diagnosed by ultrasonography . sonography was performed and two fetuses with 2 arms , 2 legs , and 2 heads were visualized . there was a single umbilical cord , and only one fetal heart was observed ( figure 1 ) . the placenta was localized anteriorly , and one artery and one vein were seen in the umbilical cord . on the basis of these findings , the diagnosis of terata anacatadidyma , thoracopagus , conjoined twins was made ( figures 2(a ) and 2(b ) ) , and the parents were informed about the malformation and the twins ' poor chance for survival . a written informed consent was taken from the family , and the termination of pregnancy was approved by the medical ethics committee . the next two days , after induction of labor with prostaglandin , a vaginal delivery of the conjoined twins was achieved without complication . conjoined twins are classified according to the most prominent site of conjunction : thorax ( thoracopagus ) , abdomen ( omphalopagus ) , sacrum ( pygopagus ) , pelvis ( ischiopagus ) , skull ( cephalopagus ) , and back ( rachipagus ) . depending on the aspect of the embryonic disc , the most common types are thoracopagus ( 19% ) ( table 1 ) . its etiology is unknown , but an incomplete division of the zygote between 13th and 15th days after fertilization probably occurs . the condition is more frequently found among females , with a ratio of 3 : 1 . two theories have been proposed to explain this observation : the process of x - inactivation overlaps with the timing of monozygotic twinning and thus may directly contribute to development of monozygotic twins , and the xx karyotype may confer a survival benefit . the traditional theory is fission , in which the fertilized egg splits partially and conjoined twins represent delayed separation of the embryonic mass after day 12 of fertilization . the second theory is fusion , in which a fertilized egg completely separates , but stem cells ( which search for similar cells ) find like - stem cells on the other twin and fuse the twins together [ 4 , 6 , 7 ] . conjoined twins share a single common chorion , placenta , and amniotic sac , although these characteristics are not exclusive to conjoined twins as there are some monozygotic but nonconjoined twins that also share these structures in utero [ 4 , 6 ] . early diagnosis of conjoined twins was previously reported , but not before the 10th week of gestation . on careful transvaginal sonography and serial scanning , there appears to be an inability to separate between the anatomical parts of the fetuses . once conjoined twins have been diagnosed , characterization of the type and severity of the abnormality can be performed with ultrasound , three - dimensional ultrasound , computed tomography , or magnetic resonance imaging [ 9 , 10 ] . , the diagnosis has been performed in the first trimester , and because the family has chosen termination of this pregnancy , further diagnostic intervention has not been considered . surgery to separate conjoined twins may range from relatively simple to extremely complex , depending on the point of attachment and the internal parts that are shared . conjoined twins are associated with a high perinatal mortality ; therefore , making an early diagnosis with ultrasonographic examination of conjoined twins gives the parents a chance to elect pregnancy termination .

objective . conjoined twin is a rarely seen congenital anomaly together with severe mortality and morbidity . the more common types of conjoined twins include the thoracopagus type , where the fusion is anterior , at the chest , and involves the heart . we are reporting one case of conjoined thoracopagus twins diagnosed by ultrasonography at 11 weeks . case report . in a multigravid pregnant woman who has been admitted to our clinic with a diagnosis of conjoined twins , thoracopagus , by ultrasonography at an 11-week gestation , termination of the pregnancy was performed . conclusion . making an early diagnosis with ultrasonographic examination gives the parents a chance to elect pregnancy termination .

airborne - contact dermatitis ( abcd ) denotes an unique type of contact dermatitis originating from dust , sprays , pollens or volatile chemicals by airborne fumes or particles without directly handling this allergen . this form of dermatitis commonly involves face , neck , v - area of chest and eyelids . exposed as well as nonexposed skin can be affected . airborne dermatoses often cause diagnostic problems and create a puzzle not only to the patient but also to the doctor . as per previous reports abcd in indian patients has been attributed exclusively by pollens of the plants like parthenium hysterophorus , xanthium strumarium , chrysanthemum coronarium , helianthus annus ( sunflower ) and dahlia pimrata . in recent years the above scenario has been changing rapidly in urban and semi\urban perspective especially in developing countries . organic compounds that are used or generated anthropogenically in large quantities in the cities can be the source of human contact allergens . abcd may be caused by : a ) cement and wood dust , causing irritant as well as sensitization reactions b ) fibrous materials like grain dust , glass fiber and rock wool causing mechanical dermatitis c ) aerosols of mineral oils inducing irritant reaction d ) pollens or dust containing particles from plants such as parthenium hysterophorus , ragweed or certain types of woods or medicaments by the process of delayed hypersensitivity . in a study by ghosh among 64 patients(36 m , 28 f ) age ranging from 10 to 67 years suffering from abcd in urban perspective 64.1% ( n=41 ) had urban residency whereas 35.9% ( n= 23 ) had semiurban . pattern of allergens contributory to abcd detected in the study were as follows : potassium dichromate 39.7% ( n=25 ) , fragrance mix 28.1% ( n=18 ) , epoxy resin 26.6% ( n=17 ) , colophony 17.8% ( n=12 ) , formaldehyde 13.2% ( n=7 ) and parthenium 9.4% ( n=6 ) . cement , perfumes or deodorants , volatile paints and synthetic glues have become commonest allergens contributing to abcd in urban and semiurban areas . in urban and semiurban area of india incidence of abcd due to parthenium has been gradually become lowered as compared to previous reports due to rapid urbanization and reduction in open land required for the growth of these plants . abcd to cement ( chromate ) has been already published by different workers.[1114 ] extensive housing development projects and construction works in recent years in developing country like india have caused very high allergic sensitivity rate to potassium dichromate contained in the cement . even by non - occupational contact housewives are also commonly involved . in china a high proportion ( 19% ) of patch test positive reaction to chromate has been reported possibly reflecting the exposure to cement due to china 's very active construction programs . fragrance allergy leading to abcd has been reported by many authors.[1618 ] in the recent years increased self - image and beauty consciousness due to media and film influence has contributed to the increased use of perfume , deodorants , room fresheners among urban and semiurban people . increased incidence of epoxy resins and colophony allergy has been caused by increased household decoration , newer occupations and various newer personal hobbies . abcd originated by paints , epoxy resin , colophony and formaldehyde has been reported by some previous workers.[1922 ] epoxy resin systems are important sensitizers and often responsible for occupational airborne dermatitis . airborne dermatitis resulted from exposure to metaproterenol ( alupent ) used by respiratory therapist to treat patients . psyllium , primarily used as a stool softener , comes from the seed of the genus plantago . abcd appears on areas of the skin where the dust or fibers can be trapped , e.g. , on the eyelids , neck ( under a shirt collar ) , forearms ( under cuffs ) or lower legs ( inside trouser legs ) . contact dermatitis from prolonged , repeated exposure to relatively small quantities of airborne allergens , such as pollens , dusts and vapors , produces diffuse , dry and lichenified eruptions with vesiculations . the exposed portions of the body as well as wrinkles and folds are most markedly involved . household sprays , insecticides , animal hairs and occupational volatile chemicals can produce eyelid dermatitis . the handling of large amounts of carbonless copy paper and laser printed paper can cause irritation of the mucous membrane of the nose and eyes and pruritus on exposed skin . various cutaneous symptoms , including pruritus and paresthesia , have been described after long - term exposure to computer screens , but few patients exhibit diagnostic skin lesions . a chronic eczema on exposed areas is usually not due to photosensitivity but is the result of abcd . abcd characteristically involves the upper eyelids and extends below the chin and behind the ears , but does not always do so . airborne and photoallergic contact dermatitis have a similar clinical expression acute or subacute dermatitis on exposed areas . they differ from toxic dermatitis because they have a more polymorphic clinical picture , not precisely limited to exposed areas . however , as stated with irritant type , there are some locations spared in photodermatitis , which may be affected in airborne type , such as upper eyelids , under the chin , behind the ears , the back of neck , or even the scalp . airborne irritant contact dermatitis predominates in exposed areas , but , as opposed to photosensitive dermatitis it does not spare areas such as the upper eyelids , retroauricular folds or submental area . abcd may result from exposure to sawdust even associated with leukoderma , cutting oils and even jewellery the airborne mci / mi ( chloromethyl- and methylisothiazolinone ) dermatitis may appear in the face of sensitized individuals who stay in newly painted rooms , and the diagnosis is easily missed unless specifically considered . dental practitioners and their associates may develop dermatitis on face , eyelids and other exposed skin areas by airborne contact . these have been largely reported as an occupational problem in health workers with hypersensitivity to latex proteins from rubber gloves made with natural latex ( usually derived from hevea brasiliensis muell . airborne transmission of latex allergens is enhanced by their adsorption onto the cornstarch ( derived from zea mays l. , family gramineae ) used as glove powder . airborne contact urticaria reported in a warehouseman resulted from exposure to dust derived from cinchona bark ( cinchona spp . the sensitizing potential of trivalent chromium salts remains high as they form complexes with proteins in the upper layers of the skin . the trivalent salts are , however , not common sensitizers due to their low penetration into the skin . in contrast hexavalent chromium salts , a nonsensitizer by nature , can penetrate the skin and could be reduced to trivalent salts subsequently and the latter may lead to sensitization by acting as hapten . in some countries ferrous sulphate is added to cement to transform hexavalent chromates into trivalent ones to reduce the incidence of sensitization . otherwise a special type of cement namely portland blast furnace slag cement ( pbfsc ) of low hexavalent chromate content may be used to reduce cement sensitivity .

airborne - contact dermatitis ( abcd ) represents a unique type of contact dermatitis originating from dust , sprays , pollens or volatile chemicals by airborne fumes or particles without directly touching the allergen . abcd in indian patients has been attributed exclusively by pollens of the plants like parthenium hysterophorus , etc . , but in recent years the above scenario has been changing rapidly in urban and semiurban perspective especially in developing countries . abcd has been reported worldwide due to various type of nonplant allergens and their clinical feature are sometimes distinctive . preventive aspect has been attempted by introduction of different chemicals of less allergic potential .

it has a peak incidence between 10 and 14 year of age and only 30% of all osteosarcomas occur in individuals aged > 40 . osteosarcoma is a rare disease , with an annual incidence rate of approximately 4.4 per 10 for people aged 024 years . several subtypes of osteosarcoma can be distinguished , of which conventional high - grade central , or intramedullary osteosarcoma , is by far the most common ( 75% of the cases ) . osteosarcoma is characterized by the production of osteoid matrix and is located mostly at the metaphysis of long bones . in addition to surgery patients receive intensive pre- and post - operative chemotherapy . although neo - adjuvant chemotherapy has markedly improved outcome , since its introduction in the 70ties survival has reached a plateau of about 6070% . therefore , new treatment options are needed . as osteosarcoma is a rare disease , international collaborations are essential for the conduction of clinical trials . the european and american osteosarcoma study group ( euramos ) , started its first trial in 2005 , in which 2260 patients from 326 centres across 17 countries were enrolled . this largest osteosarcoma study to date could be achieved by a committed collaboration between four well established study groups . however , due to the absence of consensus and regional differences in compound approval , a second study has not emerged yet , which is especially discouraging now this successful worldwide network has been established . to see how the quantity of osteosarcoma in vitro studies developed overtime , we set out to systematically identify all the drugs that have been tested on osteosarcoma cells in vitro in the past two decades . a pubmed search strategy was compiled which can be found in supplementary data 1 . to our surprise it struck our attention that the number of publications on treatment of osteosarcoma cell lines with various compounds has increased almost exponentially ( fig . after importing these pubmed hits in endnote x7 , we obtained an indication of how the amount of publications developed in china , the usa , india , australia , canada and europe ( defined as countries that are in the schengen area and/or the european union ) in the past few years by searching for these countries in the authors address box . the amount of publications from the usa showed a minor increase , from 45 in 1996 to 73 in 2015 , whereas the amount of publication from europe increased substantially from 35 in 1996 to 176 in 2015 . strikingly , the amount of publications from china rose from 1 to 359 , thereby mainly being responsible for the huge increase in publications observed in the last few years . china has been the leading country since 2012 , and 53% of the publications from 2015 involved chinese institutes ; this is a much higher proportion than reported for other research areas such as haematology research . we read all the abstracts of the hits of the past three years ( n=1755 ) , and categorized them based on non - osteosarcoma ( n=297 , many studies on other cancers metastasizing to the bone ) , no in vitro study ( n=179 ) , no drugs study ( n=596 , many studies performed sirna knockdown only ) and no inhibitory effect ( n=126 ) , leaving us with 560 studies from the last three years , a relatively large number when considering the rareness of this disease . interestingly , approximately 1/3 of the compounds could be classified as traditional medicine , of which over 80% was published by chinese authors . for example , we encountered several compounds such as evodiamine , a chemical extracted from the tetradium genus of plants , and crude extracts of rheum palmatum l. , the root of chinese rhubarb . remarkably , many studies were performed with only one cell line , either u-2 os or mg-63 . due to the high heterogeneity of osteosarcoma , studying a panel of cell lines instead of a single cell line is essential for eventual clinical applicability . u-2 os and mg-63 are both atcc cell lines established in 1964 and 1977 respectively . searching pubmed for u-2 os ( and u2os / u2-os / u-2-os ) and mg-63 ( and mg63 ) identified respectively 1449 and 2564 publications from 1996 to 2015 , while the combination only resulted in 163 pubmed hits . determining the amount of publications per year and per country for these cell lines as described above further demonstrated the almost exponential increase in publications with osteosarcoma cell lines attributable to studies from chinese institutes ( fig . 1b ) . to compare these results with another atcc sarcoma cell line with a comparable amount of total publications , we performed an identical search for ht-1080 ( fibrosarcoma ) , in which we did not see this trend ( fig . 1b ) , demonstrating that this is not a trend observed in all atcc sarcoma cell lines . u-2 os and mg-63 are ubiquitously applied also outside the osteosarcoma field for general cell biology studies because they are among the few human cell lines that are relatively susceptible to transfection . in addition , these cells grow rapidly facilitating experimental application but also boosting drug responsiveness . this probably explains why so many in vitro studies have been published for this relatively rare disease . there may be a jewel hidden in this avalanche of studies , but it is difficult to discern due to the huge quantity of papers using questionable designs . if in vitro studies are performed , researchers should always include a panel of cell lines to represent the tumour heterogeneity in osteosarcoma patients . as a researcher , it is impossible to keep track of all the research that is being published , which may lead to missing promising therapeutic targets . the publication of these relatively easy executable studies is obviously fed by the incentive of publish or perish , but it keeps scientists occupied with often irrelevant work , it usurps financial budgets and obscures relevant investigations . other major drivers of the enormous increase in research papers is the substantial increase in the number of academic journals . aggressive editor 's requests to submit manuscripts to new journals keep filling a scientist 's mailbox , which can be quite disturbing . this trend to prevail quantity over quality is occupying precious time from editors and reviewers . currently , the science citation index is used for medical career evaluation in the majority of large chinese hospitals , resulting in a huge pressure of chinese medical doctors to publish articles and an increase in number of publishing scientists , . therefore , it is essential that the evaluation system on research performance will be changed with the focus shifted from quantity to quality as was recently again advocated that bibliometrics are warping science . our analysis of in vitro osteosarcoma studies illustrates the effect of the increased publication pressure since the convenience of osteosarcoma cell lines renders them into low hanging fruit but results in studies with limited scientific value , which constrains solutions for this deadly disease that affects young patients .

osteosarcoma is a primary malignant bone tumour , for which no improvement in survival rate has been made since the nineteen seventies . we set out to systemically identify the in vitro studies performed in the past two decades describing potential future therapies . strikingly , we obtained a total of 5282 pubmed hits on this subject . the amount of publications has increased almost exponentially over the past few years . studies from chinese institutes are mainly responsible for this huge increase , accounting for 53% of the publications in 2015 . approximately 1/3 of all drugs described in the past three years could be classified as traditional medicine . furthermore , it struck our attention that even though in such studies multiple cell lines are essential to represent the heterogeneity in patients , many studies were performed with only one or two cell lines , i.e. u-2 os or mg-63 . these cells are fast growing , facilitating rapid experimental application but also boosting drug responsiveness . this probably explains why so many in vitro studies have been published for this relatively rare disease . furthermore , it illustrates the current publication pressure , especially in china .

we discuss the management of a patient after its recurrence , involving the upper respiratory tract i.e. nasopharynx and oropharynx , which compromised the airway . the patient was referred for anesthesia on three different occasions with different presentations owing to the recurrence of symptoms . the presence of an oropharyngeal membrane with a small opening made airway management a challenge . rhinoscleroma is a chronic , granulomatous infection , caused by klebsiella rhinosleromatis , affecting the nasopharynx , oro - pharynx , larynx , trachea and bronchi . it is common in the second and third decade of life , with females more frequently affected . treatment consists of prolonged antibiotic treatment , surgery to remove the obstruction and laser therapy to treat airway compromise and tissue deformity . this progressive infection , involving the upper respiratory tract , may pose a challenge in airway management . however , he had no long - term relief and the symptoms progressed . in the last six months , he developed difficulty in breathing and swallowing . oral examination revealed a membrane at the level of uvula covering the oropharynx with a central opening of approximately 8 mm diameter through which he managed swallowing [ figure 1 ] . ct scan and mri scan showed a concentric narrowing at the level of the oropharynx [ figures 2 and 3 ] with sparing of the lower respiratory tract . flexible fiber - optic bronchoscopy ( with a 6 mm scope ) under la revealed uninvolved vocal cords , but patient had discomfort and was unable to hold his breath during the procedure . oro - pharyngeal membrane visible at the level of uvula covering the oropharynx with a central opening of approximately 8 mm diameter mri of the airway sagittal section showing the membrane in the oropharynx and no involvement of the airway below mri coronal view showing narrowing of the oropharynx due to the membrane ( shown by arrow ) premedication with 20 mg omeprazole and glycopyrrolate 0.2 mg intramuscularly was given . after preoxygenation , anesthesia was induced with 120 mcg fentanyl , propofol 1mg / kg and sevoflurane in titrated doses . after ensuring adequate mask ventilation , succinylcholine 1.5mg / kg was given . although an ideal laryngoscopy could not be performed , moving the tongue gently with the laryngoscope helped visualize the membrane . a 15 fr bougie was inserted via the hole in the membrane and tracheal rings were well felt . a non - laser shielded 5 mm i d endotracheal tube ( ett ) was negotiated , over the bougie , through the opening . membrane was resected with diode contact laser and the tissue was sent for histopathology evaluation . the induction was done as in the previous instance but we were unable to negotiate the bougie , and two attempts at blind intubation with 5 mm i d ett and an attempt with a smaller ett were unsuccessful . post operatively , the tracheostomy was kept and patient discharged on fourth postoperative day with tracheostomy tube in situ . rhinoscleroma leads to fibrosis of the airways with consequent deformity , atresia or complete obstruction of the airway . diagnosis is made on the basis of clinical presentation , histopathology , bacteriological culture and serological investigations . the extent of oropharyngeal and tracheobronchial involvement can be accurately assessed with ct or mri scans , although very few studies have described imaging features of rhinoscleroma.[79 ] the nasal cavity is the most often affected ( 95 - 100% ) , but the lesions may also involve larynx ( 15 - 40% ) , nasopharynx ( 18 - 43% ) , oral cavity , paranasal sinuses ( 26% ) , soft tissues of lips , nose , trachea ( 12% ) and bronchi ( 2 - 7% ) . sharing the airway with the surgeon is of utmost concern to an anesthesiologist . in the case reported , a trial at oral intubation guided by a gum elastic bougie was done as the patency of the pharynx distal to the membrane on mri and ct scan was confirmed [ figures 24 ] . we avoided blind nasal intubation since the nares seemed blocked and the ct image showed some synechiae in the nasal passage . the feel of the tracheal rings by the bougie guided us the insertion of the ett . a fiberoptic bronchoscope would have helped in visualizing the membrane , as it done in the ent clinic , but we only had a 6 mm scope , which would have permitted only a larger ett over it . trauma to the membrane or bleeding had to be avoided . a supraglottic airway could not be used . jet ventilation would have made the patient prone to barotrauma as airway pressures can not be controlled with its use . retrograde intubation would have been tedious as passing the guide wire through the small opening would have been very difficult . as the pharyngoplasty took only fifteen minutes , ett was not changed to a bigger size later . ct scan showing narrowing of the oropharynx due the membrane ( shown by arrow ) fatal airway obstruction has been reported after evading tracheostomy in a patient who seemed to be improving following antibiotic treatment . pharyngoplasty is often a day care procedure performed using laser , and is associated with minimal blood loss , edema , and quick recovery . routinely , it does not need the patient to have a tracheostomy , as lubricated airways , post - surgery , maintain the airway patency well . in our patient , at the second instance , the opening in the oropharyngeal membrane was smaller . we were however reluctant to do a tracheostomy knowing that the symptoms would be relieved on resection of the membrane . despite three attempts with smaller sized ett we did not expect recurrence , as the patient had undergone laser and electrical cautery resection , but there was recurrence . the third time , the patient presented with respiratory distress that warranted an immediate tracheostomy . he had not responded to prolonged antibiotics , anti - inflammatory drugs , steroids or even surgery and finally needed a permanent tracheostomy . close observation for prolonged periods of time is essential to recognize reactivation of quiescent lesions . trauma caused by excision and laser can incite more fibrosis and lead to recurrence of the primary problem with a vengeance . the recurrence rate of rhinoscleroma has been cited to be up to 25% of the treated cases in 10 years . in patients with an oropharyngeal membrane with a solitary opening , the size of the opening , pathology and involvement of the oropharynx , nasopharynx and the tracheobronchial tree must be evaluated . it is important to consider the site of airway obstruction and ensure availability of equipment to secure the airway . fiberoptic bronchoscope is an important tool in assessing the airway patency but can precipitate respiratory distress and a bougie may be helpful . tracheostomy should be performed if the opening is small or if the airway is affected at multiple levels .

rhinoscleroma is a rare entity encountered in anesthesia practice . we discuss the management of a patient after its recurrence , involving the upper respiratory tract i.e. nasopharynx and oropharynx , which compromised the airway . the pateint was referred for anesthesia on three different occasions with different presentations owing to the recurrence of symptoms.the presence of an oropharyngeal membrane with a small opening made airway management a challenge . the patient was successfully managed on all three occasions . imaging facilitated assessment and subsequent airway management .

the species of cryptococcus genus have been identified from different environmental sources such as air , water , soil , wood , and pigeon excreta . cr . this kind of yeast was reported from soil of tabriz in iran as well , . cr . friedmannii and some of the yeast species were isolated from the atacama desert , with high daily temperature variations a 57-year - old man was admitted to our department in october 2015 ( at day 0 ) with distal subungual hyperkeratosis clinical type of onychomycosis on the first right toenail ( fig . 1 ) . the patient did not have disease like diabetes , psoriasis , immunodeficiencies or any chronic disease . however , four months ago ( at day 4 months ) , the patient had a history of ungueal trauma and small traumatic lesion was emerged on toenail . three direct microscopic examinations ( at day 0 ) of nail scrapings , with 20% potassium hydroxide revealed single or budding yeast cells . three nail specimens were cultured on sabourauds dextrose agar plates with chloramphenicol ( at day 0 ) , and incubated at 2025 c , which were produced creamy and smooth colonies after a few days ( fig . microscopic examinations ( at day 7 ) of the colonies with chinese ink were shown single or budding cells with a thin capsule ( fig . the yeast was cultured on yeast extract peptone dextrose agar and incubated at 2025 c.fig . 2fig . 3budding cells with a thin capsule with chinese ink wet mount ( 400).fig . mount slide of colonies ( 400).fig . 4 distal subungual thickening and hyperkeratosis of patient . genomic dna was extracted using qiagen tissue kit ( germany ) ( at day 11 ) . the its1 - 5.8s - its2 region was amplified with its1 ( tcc gta ggt gaa cct gcg g ) and its4 ( tcc tcc gct tat tga tat gc ) universal primers by the following profile : 98 c ( 5 min ) , 40 cycles of 98 c ( 30 s ) , annealing temperature 56 c ( 30 s ) , and 72 c ( 30 s ) , followed by a final extension of 72 c ( 5 min ) . amplification of the isolate with its1 and its4 primers yielded 500 bp fragment ( at day 11 ) . sequence analyzes was compared with the reference sequences of genbank database using blast ( basic local alignment search tool ) ( http://www.ncbi.nlm.nih.gov/blast ) . friedmannii ( naganishia friedmannii ) with the accession number km243311.1 ( at day 23 ) . the sequence of the its region was submitted to the genebank as the accession number kx268322 ( fig . 5).fig . 5the sequence of the its region was submitted to the genebank as the accession number kx268322.fig . 5 the sequence of the its region was submitted to the genebank as the accession number kx268322 . the antifungal susceptibilities were conducted according to the clinical and laboratory standard institute method ( document m27-s3 ) . friedmannii to fluconazole , itraconazole and amphotericin b was determined at 72 h. the mics results revealed this isolate was susceptible to these drugs with mic values of 0.25 , 0.125 and 0.25 g / ml for fluconazole , itraconazole and amphotericin b , respectively ( at day 30 ) . the patient was treated with oral itraconazole at the dosage of 200 mg daily . direct microscopic examinations of nail scrapings with 20% potassium hydroxide had not revealed single or budding yeast cells and culture of the nail sample was negative . the yeast cr . friedmannii was first reported as a new species of basidiomycetous yeast of antarctic in 1985 . this increased may reveal enhanced immunocompromised patients with impaired cell - mediated immunity , organ transplantation , diabetic patients , azole prophylaxis , and etc . humicola were reported as opportunistic pathogens over the last few years , . a case of cr . also , prothoteca spp was reported as the first causative agent of onychomycosis in brazil which was the 3rd case in the world . furthermore , onychomycosis is related to the host ones such as age , occupation , chronic diseases , nail care and lifestyle .

yeasts are common etiologic agents of onychomycosis . this study reported a case of onychomycosis due to cryptococcus friedmannii ( naganishia friedmannii ) . this yeast was isolated of the right great toenail of 57-year - old man . microscopic examination of nail scrapings showed budding cells with thin capsule . sequence analyzes of the internal transcribed spacer regions was closely related to cryptococcus friedmannii . the results of susceptibility testing showed the cryptococcus friedmannii to be sensitive to fluconazole , itraconazole and amphotericin b.

mycoplasma is the smallest free - living organism and is unique among prokaryotes in that it lacks a cell wall . this feature is largely responsible for particular biologic properties including lack of a gram stain reaction and nonsusceptibility to many commonly prescribed antimicrobial agents , including beta lactams . mycoplasma pneumoniae is a common pathogen that first linked to respiratory infections in 1898 when roux and nocard isolated the organisms from bovine pleuropneumonia specimens . initially mycoplasma species were thought to be viral in nature because of their size , and this was disproved by the presence of both mycoplasma dna and rna . mycoplasma pneumoniae can be communicated through close personal contact via respiratory droplets and has an increased prevalence in autumn and winter.2 mycoplasma pneumoniae is predominantly a respiratory pathogen but may also involve other systems . exanthems and gastrointestinal symptoms are quite common,3 whereas mycoplasma - associated carditis ( myo- or pericarditis ) is an uncommon complication , occurring in only 1 - 5% of patients . we report a child with acute myocarditis due to m. pneumoniae and analyse all documented cases of mycoplasma infection in our hospital over a one year period . our patient , a 6 year old boy , was admitted to hospital in july 2004 with a 4 day history of pyrexia up to 104f , headache , loose stools and lethargy together with a one day history of shortness of breath . he had been started on miocamycin ( a newer macrolide ) by his general practitioner one day prior to admission . he was very pale , sweaty and tachypnoiec with a temperature of 99.8f and a regular heart rate of 155bpm . the first and second heart sounds were normal and there was a loud third sound . his leukocyte count was normal and his c - reactive protein was significantly increased ( 223mg / l ) . a chest x - ray showed cardiomegaly and pulmonary oedema and an echocardiogram showed decreased fractional shortening ( 25% ) and mitral incompetence . a working diagnosis of myocarditis with decompensated shock was made and he was started on peripheral dobutamine and transferred to intensive care where he was ventilated , intravenous ceftriaxone was added and oral miocamycin continued . he developed a persistent maculopapular rash , ceftriaxone was changed to meropenem and the rash subsided . blood , urine and csf cultures were negative and an elisa test for mycoplasma pneumoniae igm was positive . coxsackie a , coxsackie b , and echovirus antibodies were negative . over the next few days , the child 's condition improved , the shortening fraction increased from 25% to 40% over a ten day period and mitral regurgitation disappeared . miocamycin was stopped after fourteen days of treatment when the c - reactive protein had returned to normal . six months later , he was off all treatment other than inhaled steriods for asthma . a review of all cases of documented mycoplasma infections in our hospital in the year 2004 showed no other cases of carditis , 29 cases of respiratory infections , 13 cases investigated for pyrexia of unknown origin and 5 miscellaneous cases . mycoplasma infection affects mostly children and adolescents but the mean age of patients with mycoplasma carditis in the literature is higher ( 32 years).45 it is thought that pneumonia with associated myocarditis is commoner in adults while extrapulmonary manifestations , such as arthritis and central nervous system complications , are commoner in the paediatric age group.6 the clinical spectrum of respiratory infections caused by m. pneumoniae ranges from a complete absence of symptoms to frank pneumonia.3 only 7 - 11% of patients develop pneumonia , while 5 - 20% may develop pleural effusion.78 however , in patients with mycoplasma carditis , the rate of pneumonia and pleural effusion is higher ( 43% and 19% respectively).5 alternatively , some of the cases of mycoplasma - carditis manifesting without pneumonia may remain undiagnosed and classified as idiopathic carditis.9 the ecg is a sensitive and inexpensive tool for the initial evaluation of suspected cases since the diagnosis of carditis may be unclear due to lack of specific cardiac symptoms . for example , tachycardia was found in only 43% , and chest pain in 38% of the patients with carditis . in contrast , ecg abnormalities were found in 100% of reported ecgs.5 complete heart block due to mycoplasma carditis has also been reported.10 echocardiography is naturally useful to quantify cardiac function and monitor progress . elisa ( enzyme linked immunosorbent assay ) based methods are the laboratory methods of choice and utilize an enzyme immunoassay for mycoplasma pneumoniae specific igm . this igm is found in 80% of mycoplasma pneumoniae cases within 1 week of infection . culture of mycoplasma species usually requires 1 - 2 weeks3 and is successful in only 40 - 90% of cases.6 successful treatment of mycoplasma carditis hinges on promptly considering mycoplasma as a potential etiologic agent , obtaining proper diagnostic tests for its detection , and providing appropriate antimicrobial coverage . macrolides are the agents of choice as they inhibit mycoplasma growth , possibly by blocking dissociation of peptidyl trna from ribosomes , causing rna - dependent protein synthesis to arrest . long - term sequelae are not infrequent in mycoplasma carditis . a significant reduction in cardiac sequela has been observed . in the earlier review done by ponka et al in 1979 , 43% of the patients had cardiac sequelae , whereas potasman et al in 2003 described a complication rate of less than 30% and this may have been due to better antibiotic coverage.5 respiratory syndromes other than pneumonia caused by this organism are reported to be 10 - 20 times more frequent than pneumonia . since most patients with mycoplasma carditis present solely with respiratory symptoms , an ecg may be a useful screening test in suspected cases of mycarditis . appropriate and timely treatment is essential and therefore serological testing for mycoplasma pneumoniae should be part of the routine work - up of myocarditis .

mycoplasma pneumoniae is primarily a respiratory pathogen but may affect exhibit a diverse range of presentations from asymptomatic infection to life threatening conditions . myocarditis of varying severity is an unusual complication . we report a 6 year old with mycoplasma myocarditis , a rare age for such a presentation , and who responded well to treatment with no sequelae . serological testing for mycoplasma pneumoniae should be part of the routine work - up for myocarditis .

a 16-year - old male presented with asymptomatic , slowly progressive abnormality of skin color , beginning when he was 1 year old . the lesions were first noticed on his chest and back , and subsequently involved his entire body except the palms and soles . at the age of 14 the definitive cause of renal failure could not be determined because of late presentation of the patient . many of his family members have similar skin dyspigmentation , as shown in the family pedigree ( fig . 1 ) . the onset of lesions in all involved members occurred in childhood , as in our patient . there was no family history suggestive of renal disease . physical examination revealed generalized symmetrical hypopigmented and hyperpigmented macules , varying from 2 to 5 mm in size , on the face , trunk , extremities and dorsum of both hands and feet , sparing the palms and soles ( fig . dyschromatosis universalis hereditaria ( duh ) is a rare inherited dyschromatosis , characterized by the appearance of both hypopigmented and hyperpigmented macules that can involve almost all parts of the body . the disease is usually autosomal dominant inheritance , with a few autosomal recessive and sporadic cases reported . recently , a mutation in the abcb6 gene was identified as the pathologic gene in duh . however , not all duh patients have the abcb6 mutation . it is possible that duh is a disease of genetic heterogeneity [ 1 , 2 , 3 ] . the main feature of duh is a mixture of hypopigmented and hyperpigmented macules , distributed symmetrically . the lesions can occur anywhere on the body , but rarely involve the palms and soles . the lesions usually appear in infancy or early childhood and stop spreading before adolescence , after which the lesions will last for life [ 4 , 5 , 6 ] . the differential diagnoses of duh are shown in table 1 . except for skin lesions , there is no other common associated condition in duh ; however , there have been various reports of an association with short stature and high - tone deafness , seizure , mental retardation , hair and nail abnormalities , ocular abnormalities and thrombocytopenia [ 4 , 6 , 7 , 8 ] . furthermore , there have been no reports of malignant transformation of the lesions in duh patients . histologically , hyperpigmented lesions of duh contain more melanin than either normal or hypopigmented macules . in both hypopigmented and hyperpigmented lesions , based on electron microscopic examination , a difference in the amount of fully melanized melanosomes in hypopigmented and hyperpigmented lesions was found . however , there was no difference in melanocyte number and tyrosinase activity . therefore , duh is not a disorder of melanocytes , but rather a defect of melanosome synthesis or transport [ 9 , 10 ] . a definitive treatment has not been established for duh . in most cases , patient education and reassurance are recommended . although in a recent report hyperpigmented macules were successfully treated with a q - switched alexandrite laser , longer follow - up of the result is needed . in the present case , however , since the patient is scheduled for kidney transplantation , there is a question of malignant transformation of his skin lesions . in our opinion , the lesions of duh should not increase the risk of skin cancer for the average transplant patient , and indeed duh has thus far never been associated with such a risk . however , since the pathogenesis of duh still remains to be elucidated , we plan to follow up on the patient 's condition in the future . thus , our case gives further support to the previous evidence that duh is an autosomal dominant disease . furthermore renal failure , which occurred in our case , has never been previously reported in the literature . however , renal biopsy was not performed due to the late presentation of renal failure in this case . therefore , whether the occurrence of renal failure is a true association or a coincidence remains inconclusive . the authors declare that they have no conflict of interest and that they received no funding or support .

dyschromatosis universalis hereditaria ( duh ) is a rare autosomal dominant inherited dermatosis which usually appears during childhood and is characterized by dyspigmentation , with both hypopigmented and hyperpigmented macules . we report a case of duh with unexplained childhood - onset renal failure . the association between duh and renal failure is yet to be proven by further studies .

a 45-year - old male presented to the emergency department with alleged history of getting hit over the left side of neck by some air - borne object while standing on the roadside . this was followed up with severe , piercing pain in the neck region associated with bleeding from the wound site . he also gave history of transient loss of consciousness but had no neurological sequelae thereafter . there was no history of difficulty in breathing , change in voice , or swelling over the neck or face . on examination , his vitals were stable . there was a 2 cm 1 cm linear lacerated wound on the left side of neck at the junction of upper 1/3rd and lower 2/3rd of the sternomastoid muscle on its anterior border . an x - ray of the cervical region showed a radio - opaque foreign body in the left side of neck suggestive of a pellet ( figure 1 ) . a ct scan was ordered before taking up the patient for an exploration and removal of the foreign body . the scan confirmed the position of the pellet as being medial to the sternomastoid around the level of the glottis ( figures 2 and 3 ) . on going medial to the sternomastoid , a thrill was palpable over the carotid sheath proximal to the foreign body . the pellet was identified within the carotid sheath partially piercing the internal jugular vein such that a part of it was outside the vessel and half of it was within the lumen . the bleed was controlled with local pressure , and the vein was ligated and transfixed both proximal and distal to the site of injury . the postoperative period was uneventful , and the patient is asymptomatic in his follow - up visits . ktesbias ii of egypt first used compressed air to propel a projectile around 250 bc . airguns were known as wind chambers , and used an air reservoir connected to a cannon barrel was used . these weapons were used in the napoleonic wars in the late 17th and early 18th centuries . the modern high - powered rifles can propel a pellet beyond 1100 ft / s ( 330 m / s ) , approximately the speed of sound , and produce a noise similar to a .22-calibre rim - fire rifle . petroleum oil placed in the barrel ( dieseling ) and ignited by the heat produced by the passing pellet results in an explosion which imparts greater velocity and more penetrating power to the pellet . this is a wasp - waisted projectile flared at the base , with a variety of head styles . these relatively low - energy missiles produce direct effects on tissues such as laceration and crushing within the missile tract as was also seen in our case . the critical velocity required for the penetration of human skin by an air rifle pellet is around 125230 ft / s ( 3870 m / s ) , which is well within the muzzle velocities of many air rifles available in the market . the risk involved with these injuries increases because it is mostly the head and neck region that is affected . there are vital neurovascular bundles , major vessels , trachea , oesophagus , and spinal cord in this region which makes an early diagnosis and immediate management important . holland et al . have reported three cases of penetrating airgun injuries to the neck : two had the pellet removed and one was managed conservatively . david also published a case involving penetrating injury to the neck in a young adult who had the pellet removed from the posterior oesophageal wall . the universally accepted protocol is that these injuries need to be managed in a systematic manner . first and foremost the airway needs to be established and the cardiocerebral perfusion needs to be maintained . it is after this that a detailed evaluation of the site and severity of the wound needs to be done . immediate exploration is warranted in the presence of active bleeding , and diagnostic studies should be reserved for those patients who are haemodynamically stable . injury of major vessels might be tamponaded by foreign bodies ; therefore , blind removal of the objects may cause life - threatening hemorrhage . preoperative plain radiographs , ct scans , and mri scans are helpful in giving an idea about the nature and site of injury . they also provide information about any associated complications , forgotten and retained foreign bodies . radiopaque markers can be used in conventional radiographs in 2 planes as this allows fast , intraoperative localization of radiopaque foreign bodies within soft tissue . van as et al . have proposed the use of selective angiography in management of gunshot wounds to the neck , along with careful clinical examination particularly so in wounds of the neck and base of skull . also , if a pellet can not be seen in the missile tract , there is a possibility of its embolisation to a distant site making angiography important to establish a diagnosis . as noted in our case , the plain radiograph and ct scan helped in localizing the pellet and in planning our approach for surgical removal . some authors have recommended a no - intervention policy in pellet injuries to the neck . we propose that it should be mandatory to explore all cases with penetrating neck injuries in the light of our patient 's findings which suggest that the entry wound might be small enough to make the injury trivial but the missile could be lodged in a vital structure such as the internal jugular vein .

penetrating neck injuries are dangerous and deserve emergency treatment by virtue of the vital structures present underneath . there is a potential risk of unrecognized vascular injury and retained foreign bodies with their associated complications in these wounds . therefore , an early diagnostic workup to localize the site of injury and an immediate neck exploration are important .

left ventricle non - compaction ( lvnc ) or persistence of spongy myocardium is a rare form of congenital cardiomyopathy which presents with cardiac failure , thromboembolic events , arrhythmia and sudden death . we report a family with two deceased children and two alive offspring diagnosed with left ventricular ( lv ) non - compaction . a 9-year - old boy and a 16-year - old girl of our reported family suddenly died following exercise and emotional provocation . both had a history of convulsion and syncope , with the latter taking anticonvulsant medication . the remaining two offsprings , one boy and one girl were diagnosed as having isolated lvnc . syncope and convulsion can be first manifestations of lvnc and heralding signs for sudden death in patients with lvnc . isolated left ventricular non - compaction ( lvnc ) is one of the rare genetic heart diseases recently known , and characterized by heterogeneous defects in endocardium accompanied by increased trabeculation due to abnormal embryogenesis of the normal myocardium . in this disease , the myocardium is composed of two layers : spongy or non - compacted and normal or compacted ones . the clinical manifestations include symptoms and signs of left ventricular failure ( common ) , those of right ventricle ( rare ) , ventricular arrhythmias , sudden death , mural thrombi and embolic events with cardiac origin . we report a family having the history of two offspring deaths , at the ages of 9 and 16 , with two live ones suffering from lvnc . we reported sudden death of a 9-year old boy with a history of two episodes of unprovoked convulsion and syncope in school and his 16-year old sister due to sudden death while she was getting back home after a feast . a 12year - old boy and a 7-year - old girl were referred to pediatric cardiology clinic for cardiac evaluation following occurrence of sudden death in their siblings . the first pregnancy of the mother ended in abortion at the age of two months of gestation , and the second offspring was a girl who died one week after birth following an operation to repair esophageal atresia . the first victim of suspected lvnc in this family was a nine year old boy with a history of two episodes of unprovoked convulsion and syncope in school . the first attack was in break time with spasm of neck and body , ended uneventfully . the next one was during exercise , with sudden fall but no urinary incontinence , eye deviation or sialorrhea . the electrocardiogram ( ecg ) , electroencephalography and lab tests showed no abnormalities at that time . the family lost their 16-year old daughter due to sudden death while she was getting back home after a feast . she also had experienced two seizure episodes associated with loss of consciousness , one at the age of 9 during exercise at school and the other at the age of 10 on vacation . both episodes had ended uneventfully , and brain ct scan with contrast demonstrated no pathologic finding . the 12-year - old boy had no history of seizure , syncope , easy fatigability , exertional dyspnea or hospitalization . on 2d transthorasic echocardiography , the parasternal short axis and four chamber views demonstrated increased left ventricular ( lv ) wall thickness accompanied by trabeculations and deep recesses that were indicative of lv non - compaction . four chamber and short axis views demonstrating the ratio of non - compacted to normally compacted segments the coronary arteries were normal and no pericardial effusion and intracavitary thrombi were detected . the 7-year - old girl also had no positive history of hospitalization , seizure , easy fatigue . her ecg was normal , however , her 2d echocardiograms were compatible with the diagnosis of lv non - compcation , based on the diagnostic criteria already reported by frischknecht et al , with increased lateral , inferior and apical wall thickness and deep recesses and trabeculations . the coronary arteries were normal and no pericardial effusion and intracavitary thrombi were detected ( fig . parasternal long axis view and m - mode echocardiography showing abnormal trabeculation and spongy pattern of left ventricle the parents were evaluated clinically and by echocardiography . this case report highlights the importance of syncope and seizure as heralding signs for sudden death in two deceased children of a family with two offspring having documented lv non - compaction . although syncope and sudden death have been previously reported in adults with lvnc but to date , as to best of our knowledge , sudden death with prior heralding sign of syncope and seizure has not been reported in children with lv non - compaction . in our reported family , both of the unexpected deaths occurred after previous episodes of uneventful seizure and syncope . considering the common embryologic origins of central nervous system and myocardium , occurrence of syncope and seizure in lvnc could be explained . lv non - compaction or persistence of spongy myocardium , first described in 1984 , is a rare form congenital cardiomyopathy with a prevalence of 0.05 - 0.24/year . the limitation of our report is lack of echocardiographic evidence for confirmation of diagnosis in the two deceased and not timely - referred and timely - diagnosed children . we suggest careful biannual follow up ( ecg , holter monitoring , echocardiography ) and anticoagulation therapy ( aspirin , dose : 3 - 5mg/ kg / daily ) for alive sibling . unexplained seizure and syncope in a child , particularly in a familial pattern , may warrant further echocardiographic evaluation for early diagnosis of left ventricular non - compaction to prevent catastrophic events . although the numbers of our patients are limited , but it seems that seizure and syncope can be considered as warning signs in those patients with lvnc who are at high risk for sudden death .

backgroundleft ventricle non - compaction ( lvnc ) or persistence of spongy myocardium is a rare form of congenital cardiomyopathy which presents with cardiac failure , thromboembolic events , arrhythmia and sudden death.case presentationwe report a family with two deceased children and two alive offspring diagnosed with left ventricular ( lv ) non - compaction . a 9-year - old boy and a 16-year - old girl of our reported family suddenly died following exercise and emotional provocation . both had a history of convulsion and syncope , with the latter taking anticonvulsant medication . following their demise , the other members of the family were evaluated by echocardiography . the remaining two offsprings , one boy and one girl were diagnosed as having isolated lvnc.conclusionsyncope and convulsion can be first manifestations of lvnc and heralding signs for sudden death in patients with lvnc . echocardiography can be helpful for early diagnosis .

she presented with long - standing essential hypertension that was resistant to pharmacological therapy with five different antihypertensive drugs , namely irbesartan 300 mg / day , triazide 25 mg / day , amlodipine 10 mg / day , spironolactone 100 mg / day and nebivolol 5 mg / day . fundoscopy revealed grade 2 hypertensive retinopathy . due to the uncontrolled nature of the resistant hypertension and progression of target organ damage , the patient was eligible for percutaneous renal denervation treatment . under local anesthesia , the femoral artery was accessed in standard technique , 5000 iu uf heparin was given intravenously and fluoroscopic angiography was performed to visualize the renal artery . angiography showed normal configuration of the right renal artery ( diameter > 4 mm , length > 20 mm , no stenosis ; figure 1 ) . while there was a well developed accessory renal artery on the left side [ figure 2 ] . the diameter of both left renal artery and left accessory renal artery were greater than 4 mm and their length was greater than 20 mm [ figure 3 ] . renal angiography is showing right renal artery renal angiography is showing left accessory renal artery renal angiography is showing left renal artery to prevent renal artery spasm iv nitrate was injected directly to renal artery . then the specially designed and commercially available radiofrequency ablation catheter ( symplicity , ardian , medtronic ) was inserted into both renal arteries , and accessory left renal artery . denervation was performed with application of 6 low - power radiofrequency treatments along the proximal portion of the vessels . radiofrequency ablation was applied to both renal arteries and accessory left renal arteries without apparent procedural complications . after the procedure , the patient was followed in the coronary care unit for one day . immediately after the procedure the patient was discharged at the third day with nebivolol 5 mg / day and amlodipine 10 mg / day . her blood pressure was 120/80 mmhg at office and ambulatory blood pressure monitoring was repeated which revealed an average systolic and diastolic blood pressure of 119/63 mmhg one month later . resistant hypertension is defined as uncontrolled blood pressure despite the use of optimal doses of three antihypertensive agents , of which one is a diuretic . the sympathetic innervation of the kidney is implicated in the pathogenesis of hypertension and resistant hypertension through effects on renin secretion , increased plasma renin activity that leads to sodium and water retention , and reduction of renal blood flow . recently , catheter - based renal sympathetic denervation has been shown to be fairly safe and effective in patients with resistant hypertension . renal sympathetic denervation is devoid of the adverse effects of surgical sympathectomy , due to its localized nature , is minimally invasive , and provides short procedural and recovery times . multicenter studies have shown significant differences in blood pressure changes from baseline between patients treated with catheter - based renal sympathectomy and those treated medically . percutaneous catheter based renal denervation has been shown to reduce blood pressure and the sequel of hypertension via interference with both efferent and afferent sympathetic nerves function and potentially further central mechanisms . symplicity htn 1 is the pilot feasibility trial carried out in patients with resistant hypertension evaluating the efficacy of renal denervation on blood pressure compared to a group treated with medical products . a significant blood pressure reduction at one month follow - up of 14 and 10 mm hg ( systolic and diastolic , respectively ) was followed by a sustained response with a pronounced systolic and diastolic blood pressure reduction of 27 and 17 mmhg , respectively , at 12 months . in symplicity htn-2 ( renal sympathetic denervation in patients with treatment - resistant hypertension ) trial , 106 patients with resistant hypertension were randomized to catheter - based therapy in addition to conventional antihypertensive medications versus antihypertensive medications only . in the renal denervation group of 52 patients , office blood pressure drop was evident as early as one month post - procedure and a statistically significant decrease of 32/12 mmhg was present at six months , whereas in the control group no changes in blood pressure were observed . in both of the trial mentioned above , the reason for exclusion of such patients might be due to potential risk of complications during the procedure as suitable arteries are considered to be with diameter < 4 mm . in our case , we believed that if we omitted the well developed accessory renal artery , we would not have maintained adequate blood pressure control . the immediate decrease in blood pressure suggested that application of the procedure to the accessory artery was beneficial . in all of the studies of renal artery denervation , patients with accessory renal arteries are excluded . thus , it can not be assumed that renal denervation in the main renal arteries will translate into a similar beneficial effect in patients who have accessory renal arteries . we presented a young female patient with resistant hypertension who successfully underwent percutaneous renal denervation of the both renal arteries together with left accessory renal artery .

renal sympathetic denervation is safe and effective in patients with resistant hypertension . in all of the studies of renal artery denervation , patients with accessory renal arteries are excluded . so there is not any data regarding renal sympathetic denervation applied to the accessory renal arteries . we present a young female patient with resistant hypertension despite use of five different antihypertensive drugs . the patient had a well developed ( diameter > 4 mm ) left renal accessory . we believe that if we omitted the well developed accessory renal artery , we would not have maintained adequate blood pressure control . thus , we applied radiofrequency ablation to both renal arteries and left accessory artery . immediately after the procedure , the patient 's blood pressure was reduced to 110/60 mmhg and this effect was continued during the first month of follow - up .

he was diagnosed with lymphoblastic lymphoma and treated with a chemotherapeutic regimen ( hyper - cvad ) . ten days after the chemotherapy , he became agitated and exhibited temporary whole - body tremor that made him unable to stand still . on examination , he appeared dull and apathetic , and his gait was slow and characterized by short steps , shuffling , the paucity of arm swing , and difficulty in turning of the body . his posture was stooped forward , and he complained of a sense of heaviness and clumsiness in his activities of daily living . there were bilateral mild - to - moderate postural and action tremors , symmetric and moderate rigidity with bradykinesia , and moderately shuffling gait in a stooped posture according to the unified parkinson 's disease rating scale ( updrs).4 laboratory findings were inconclusive . cerebrospinal fluid ( csf ) findings were as followed : pleocytosis ( 90 wbcs / mm , 70% mononuclear cells ) , no red blood cells , mild elevation of protein ( 51.9 mg / dl ) , and normal glucose ( 72 mg / dl ) . pcr of csf samples for mycobacterium tuberculosis and an antibody against fungus produced negative results . t2-weighted axial mri showed numerous disseminated hyperintense lesions in the whole brain , mainly in both basal ganglia , thalamus , cerebral cortex , white matter , brainstem , and cerebellum . 1 ) . we used a steroid to treat lg because the patient and his family did not allow us to perform a brain biopsy . pulse therapy with methylprednisolone ( 1000 mg / day ) for 5 days resulted in most of the disseminated lesions disappearing in follow - up brain mri , and they had completely resolved 2 months later ( fig . 2 ) . whilst mild shuffling of the gait remained ( mild severity according to the updrs4 ) , the parkinsonian features in the limbs of the patient such as tremor , rigidity , and bradykinesia were no longer present after the therapy . cognitive evaluation using the korean version of wechsler adult intelligence scale ( kwais ) had initially showed a lower - than - average iq and dissociation between verbal and performance iq . two months later , he showed better cognitive function and an average iq on the kwais . we experienced a patient who presented only with subacute - onset symmetric parkinsonism associated with disseminated multifocal enhanced lesions in the brain . multiple disseminated lesions in the subcortical gray matter , including the basal ganglia and thalamus , might have been responsible for the parkinsonism and slowing of thought processing in this patient . cns complications of hematologic neoplasm are caused either by the primary disease or by the effects of therapy.5 lg is one of the rare diseases that causes cns complications in patients with hematologic neoplasm . multifocal gadolinium - enhanced lesions in the brain can be caused by infiltration of primary hematologic disease or opportunistic infection with disseminated tuberculosis or fungus , so clinicians should differentiate lg and infectious causes . neither malignant cells nor microorganisms in the csf were found or grown in the present case . also , pulse therapy with a steroid was effective for the parkinsonian symptoms and the brain lesions without the use of antituberculous and antifungal agents . the known cns complications of hyper - cvad are only related to steroids,6 and hence the present subject represents a novel case . mri is more sensitive than csf cytologic analysis or flow cytometry for detecting cns involvement from lg.7 therefore , we considered the cns lesion in this case to be lg since there was no evidence of opportunistic infections or complications of chemotherapy , and the patient showed specific mri findings of lg and a good response to steroid therapy . despite these findings , we were unable to make a definitive diagnosis due to the lack of pathologic data . lg presents diverse neuroimaging features , such as multiple punctuate or linear enhancements , ring - like enhancements , large enhanced mass lesions , leptomeningeal involvement , and choroid plexus involvement.7,8 disseminated multifocal enhancement in the present case is a typical pattern of angiocentric involvement with lg . the clinical features of its cns involvement also are variable , including headache , seizure , blindness , cranial nerve palsies , hemiparesis , ataxia , spastic gait , dementia , and altered consciousness.2,3 parkinsonism is a rare presenting symptom of lg.9 parkinsonism could be the only presenting manifestation of cns involvement of lg , and it is worth applying steroid therapy in cases with clinical suspicion because the prognosis of lg involved cns is variable , ranging from spontaneous resolution to rapid fatality.10

lymphomatoid granulomatosis ( lg ) is a potentially malignant lymphoproliferative disorder . the lung is the most common involved site , followed by the skin and nervous system . however , lg of the central nervous system presenting with parkinsonism is very rare . we report a patient with lg who presented with parkinsonian features such as bilateral rigidity , bradykinesia , and agitation . brain magnetic resonance imaging showed multifocal punctuate enhanced lesions in both supra- and infratentorial areas . steroid pulse therapy resulted in a dramatical improvement in the symptoms and mri abnormalities .

its frequency increases during childhood but it usually resolves by the age of 30 years . acetylation is a metabolic pathway in a number of drugs , which exhibits a genetically controlled bimodal distribution within any given population which is phenotyped as slow or rapid acetylators . studies had been done to determine acetylation phenotype in middle east population,[58 ] which showed slow acetylator predominance . therefore , we examined ad in this population to find any possible association with the disease severity . thirty - six pediatric patients , 21 males and 15 females , aged from 8 to 11 years ( mean 9.660.9 sd ) besides , 42 healthy children , 27 males and 15 females , aged from 7 to 11 years ( mean 8.931.1 sd ) as a control group , participated in this prospective and open study . approval to conduct this study , was granted by the appropriate ethical committee in baghdad college of medicine . the participants were recruited from the outpatient clinic of department of dermatology of baghdad teaching hospital from october 2007 to december 2008 . the nature of the trial was explained to the children 's parents and their consent was obtained . after an overnight fast , each individual ( patient and control ) received a single oral dose of dapsone 1.54 mg / kg body weight . a blood sample ( 5 ml ) was taken in a test tube containing heparin , 3 hours after the drug intake . plasma was separated within 1 hour of collection and then high performance liquid chromatography ( hplc ) was used to estimate plasma concentrations of dapsone and its metabolite ( monoacetyldapsone ) . individuals were considered slow acetylators if their acetylation ratio ( ratio of monoacetyldapsone to dapsone ) was less than 0.30 and rapid acetylators if their acetylation ratio was greater than 0.30 . twenty - six of the 36 ad pediatric patients ( 72.2% ) were slow acetylators compared with 29 of 42 control individuals ( 69.4% ) , and this was found to be a statistically non - significant result [ table 1 ] . in ad patients , a significant relationship appeared between familial history of allergy and slow acetylators who represented 73% ( 19 out of 26 slow acetylator patients ) [ table 2 ] . application of hanifin - rajka scoring system revealed that 30.5% ( 11 of 36 ad patients ) were severe cases and all were slow acetylators [ table 3 ] . in the ad patients , eczematous lesions which presented in the limbs ( elbows , knees , hands and feet ) were found mostly in slow acetylators who represented 84.6% ( 22 out of 26 eczematous patients ) , whereas lesions that presented in the face and neck were found mainly in rapid acetylators who represented 60.0% ( 6 out of 10 rapid phenotypes ) . frequency distribution of acetylation phenotype in ad patients and control the acetylation phenotype and history of allergy in ad patients the acetylation phenotype and hanifin - rajka scoring system in ad patients the acetylation phenotype and distribution of eczematous lesions in ad patients this study demonstrated that there is a predominance of slow acetylators in ad patients as compared with the control group . the results are in accordance with those of studies that showed a predominance of ad patients carrying the allele for slow acetylation.[58 ] however , our study succeeded to show a relation between acetylator status and different aspects of the disease course . a significant association was found between the severity of ad and slow acetylator status in which hanifin - rajka scoring system determined that a large number of slow acetylator ad patients had scores ( 50 points ) which means severe cases , while no one is a rapid acetylator . this indicates that n - acetylation phenotype variation in human skin could account for variation in the disease severity . this result agreed with that of a study on acetylator phenotype among children with allergic contact dermatitis in which an association was found between the site of allergic lesions and acetylator status . in a population of slow acetylators , it appears that the slow acetylatation phenotype can be considered as a genetic predisposing state for ad and is a clue for severity of the disease .

background : few studies have been done on the relation between acetylator status and allergic diseases.aim:to determine any possible association between acetylating phenotype in pediatric patients with atopic dermatitis ( ad ) and the disease prognosis.patients and methods : thirty - six pediatric patients and forty two healthy children as a control group were participated in the study . all participants received a single oral dose of dapsone of 1.54 mg / kg body weight , after an overnight fast . using high performance liquid chromatography ( hplc ) , plasma concentrations of dapsone and its metabolite ( monoacetyldapsone ) were estimated to phenotype the participants as slow and rapid acetylators according to their acetylation ratio ( ratio of monoacetyldapsone to dapsone).results:72.2% of pediatric patients with ad showed slow acetylating status as compared to 69.4% of control individuals . also , 73% of ad patients with slow acetylating phenotype had familial history of allergy . the severity of ad occurred only in slow acetylator patients . the eczematous lesions in slow acetylators presented mainly in the limbs , while in rapid acetylators , they were found mostly in face and neck.conclusion:this study shows an association between the n - acetylation phenotype variation and clinical aspects of ad .

vitamin c , also known as ascorbic acid , like other vitamins is an organic substance , which is required by the body in small amounts to maintain life and health . it acts as a catalyst in the formation of hormones , enzymes , blood cells , neurotransmitters , and genetic materials . it is also essential to complete the metabolism of carbohydrates , proteins , and fats . vitamin c has antioxidant properties and as such either blocks the initiation of free radical formation or inactivate ( scavenge ) free radical . vitamin c levels in the third trimester has been shown to be lower than the levels in the first and second trimester due to physiological changes in pregnancy leading to hemodilution and deficiency of vitamin c may be associated with some complications in pregnancy . vitamin c supplementation has been shown in some studies to reduce the risk of premature rupture of placental membranes and premature births , gestational hypertension , intrauterine growth retardation , and gestational diabetes in addition to other health benefits . furthermore , because vitamin c enhances iron absorption , the low serum ascorbate can lead to a decrease in the absorption and subsequent utilization of iron which is required for the proper maintenance of pregnancy and fetal growth . the purpose of this study was to determine serum vitamins c levels among pregnant women attending antenatal care at a general hospital in dawakin kudu , kano , nigeria , and this can help further research to determine the place of vitamin c supplementation in pregnancy . this was a prospective study of 400 pregnant women at various maternal ages , gestational ages and parities done between 31 november 2009 and 30 march 2011 . ethical approval for the research was obtained from general hospital , dawakin kudu , kano , nigeria . dawakin kudu is a rural community in kano state , nigeria , and about 10 km from kano , the commercial nerve center of northern nigeria . research structured questionnaire was administered to 400 respondents randomly selected and this showed various sociodemographic indices . documented prevalence of 32.26% ( 20 out of 62 ) from previous study was used . participants with confounders such as hypertensive diseases and diabetes mellitus were excluded . whole blood sample ( 5 ml ) was collected from the 400 participants and drawn directly into a plain blood sample container . determination of serum vitamin c level , according to roe and kuether , 1943 , and normal range was 0.52 mg / dl . were compared using one - way anova and p < 0.05 was considered statistically significant . results are shown in tables 13 . out of 450 participants , 400 completed the study . participants who could not be followed - up or who developed confounders such as hypertensive diseases or diabetes mellitus were dropped . majority of the women were aged 2039 years with a mean of 23.67 6.11 . seventy - nine and half percentage ( 79.5% ) of the women had vitamin c deficiency . the values for vitamin c were 0.20 0.18 mg / dl during the first trimester , 0.50 0.99 in the second trimester , and 0.35 0.36 mg / dl in the third trimester . the differences between the vitamins from one trimester to the other were statistically significant ( p < 0.05 ) . age and parity distribution serum vitamins c levels of the study sample pattern of serum vitamins c levels in mg / dl across trimesters the present study reports that majority of the women were aged 2039 years and a mean of 23.67 6.11 was reported . the association between the status of vitamin c and maternal age has been studied , and the highest levels were found among the age group 2225 years and the lowest levels in the age group 3437 years . some local studies have reported that the serum vitamin c levels decrease with parity because multiparous women in our environment may have depleted vitamin storage from frequent pregnancies at short intervals . the present study reports low serum vitamin c levels among this cohort of pregnant women and this was significant across the three trimesters . a previous study from the northwestern part of nigeria reported a lower prevalence of 32.3% . this difference may be related to the high parity , inadequate nutrition , and nutritional taboos among northern nigeria pregnant women . contrary to other studies , plasma vitamin c decline during pregnancy did not follow a linear trend with time . vitamin c deficiency may be accounted partly by the physiological hemodilution of pregnancy , inadequate intake , and the use of vitamin c to combat the oxidative stress of pregnancy . this study has shown deficient vitamin c status among pregnant women attending antenatal clinic at general hospital dawakin kudu , kano , and there is a significant reduction across trimesters . although data on vitamin c supplementation in pregnancy are conflicting , vitamin c supplementation can be suggested during pregnancy , especially for those whose fruit and vegetable consumption is inadequate because of aforementioned benefits . vitamin c supplementation could also help to prevent the development of such complications of pregnancy such as gestational hypertension , intrauterine growth retardation , and gestational diabetes , conditions all known to be associated with high levels of oxidative stress . studies from less - developed economies where vitamin c deficiency among pregnant mothers is prevalent showed significant benefit of vitamin c supplementation during pregnancy in reducing low birth weight and small for gestational age births . it has also been shown that supplementation with vitamins c and e after preterm premature rupture of membranes ( pprom ) is associated with a statistically significant increase in difference in the number of days before delivery . however , another study was of the contrary and does not support vitamin c use for management or prevention of pprom . decision as to which micronutrients are of greatest concern in developing countries requires a more systematic and comprehensive approach . there is a significant reduction in the serum vitamins c concentration throughout the period of pregnancy with the highest levels in the second trimester therefore , vitamin c supplementation is suggested during pregnancy , especially for those whose fruit and vegetable consumption are inadequate .

background : vitamin c levels are low in pregnancy . the purpose of this study was to determine serum vitamins c levels among pregnant women attending antenatal care at a general hospital in dawakin kudu , kano , and this can help further research to determine the place of vitamin c supplementation in pregnancy.methods:this was a prospective study of 400 pregnant women who presented for antenatal care in general hospital dawakin kudu , kano , nigeria . research structured questionnaire was administered to 400 respondents . determination of serum vitamin c was done using appropriate biochemical methods.results:vitamin c deficiency was found in 79.5% of the participants . the values for vitamin c were 0.20 0.18 mg / dl during the first trimester , 0.50 0.99 mg / dl in the second trimester , and 0.35 0.36 mg / dl in the third trimester and p = 0.001.conclusions:there is a significant reduction in the serum vitamins c concentration throughout the period of pregnancy with the highest levels in the second trimester . therefore , vitamin c supplementation is suggested during pregnancy , especially for those whose fruit and vegetable consumption is inadequate .

sewing needle is an uncommonly ingested foreign body which may perforate though the stomach to reach pancreas and other surrounding organs . once inside the pancreas , it has potential to create fatal complications like pancreatitis , pancreatic abscess and pseudo aneurysm , so it should be removed once detected.[15 ] most of these cases were managed by open surgical method and till date only two cases have been managed laparoscopically . we hereby report a young lady with sewing needle inside the pancreas which was removed laparoscopically . a 28 -year - old lady presented with pain in the epigastric region for 3 months which was not associated with heartburn , vomiting , fever , jaundice , haematemesis , melena , etc . her physical examination and routine blood tests including haemogram , renal function test , liver function test , serum amylase and lipase were normal . x - ray of the abdomen ( ap view ) revealed a linear radio - opaque shadow in across t11 and t12 vertebrae [ figure 1 ] . her cect abdomen showed a 3.8 cm sized linear metallic density object inside the head of pancreas [ figure 1 ] . her endoscopic examination , with both end and side viewing scopes , failed to localise any object inside the stomach and duodenum . patient was planned for laparoscopic removal of the foreign body , lesser sac was approached through the gastro colic ligament , stomach and first part of duodenum dissected away from the pancreas , after that tip of the object could be felt by the instrument . careful dissection was done to visualise the object and once in sight , it was removed with the help of maryland dissector under vision and bleeding was controlled by pressure with a gauge [ figure 2 ] . post - operative period was uneventful and the patient was allowed orals after 6 hours and discharged on second post - operative day . ( b ) ct picture ( left ) showing hyperdense body ( arrow ) in the pancreatoduodenal groove region . ( right ) enlarged reconstructed image showing linear hyperdensity ( arrow ) traversing duoenopancreatic groove into the head of pancrease intra - operative picture with extracted needle shown in inset sharp foreign bodies like fish bone , chicken bone , tooth pick and sewing needle may be ingested accidentally or otherwise . the cricopharyngeal sphincter , pylorus , c - loop of duodenum , duodenojejunal junction and ileocaecal junction are common sites of perforation , ileocaecal region being the commonest . occasionally , these objects can perforate through the wall of the stomach or duodenum and may reach surrounding solid organs like liver and pancreas . once inside the pancreatic or hepatic parenchyma , they can lead to development of abscess which can further lead to pseudo aneurysm formation ; they can also produce direct injury to blood vessel ( portal vein , splenic vein ) and sometimes may mimic other diseases affecting these organs . the diagnosis of this condition is not always easy as most of the patients ( like in our case also ) dont remember the incident ; history of surgical intervention in the past may raise the suspicion of iatrogenic cause and organic objects may produce picture mimicking carcinoma.[35 ] the diagnosis of the foreign body inside the abdomen may be suspected on roentgenogram of abdomen but computed tomography is a must to know exact location of the foreign body and the presence of complications due to it . on the basis of findings on ct , endoscopic removal may be attempted which may be successful in cases where some part of needle can be seen inside the lumen of stomach or duodenum , but it is not the case usually . most of the reported cases have been dealt surgically by open method ( except two cases).[25 ] in the modern era of minimally invasive surgery , laparoscopic removal of these foreign bodies should be attempted in all such cases before opting for open method , because it avoids incision of exploratory laparotomy and offers advantage of surgery under magnification and other benefits of laparoscopic modality . we could find two case reports regarding laparoscopic removal foreign bodies from pancreas and hereby presenting a third case . laparoscopic removal of pancreatic foreign bodies is possible and should be tried before open surgical removal .

foreign bodies inside the pancreas are rare and usually occur after the ingestion of sharp objects like fish bone , sewing needle and toothpick . most of the ingested foreign bodies pass spontaneously through the anus without being noticed but about 1% of them can perforate through the wall of stomach or duodenum to reach solid organs like pancreas or liver . once inside the pancreas they can produce complications like abscess , pseudoaneurysm or pancreatits . foreign bodies of pancreas should be removed by endoscopic or surgical methods . we hereby report our experience of successful removal one a sewing needle from pancreas .

paroxysmal nocturnal hemoglobinuria ( pnh ) is a disease characterized by intra - vascular hemolysis , thrombosis , and bone marrow failure . the disease is associated with mutations in the pig - a gene in hematopoietic stem cells , resulting in a deficiency of glycosylphosphatidylinositol ( gpi)-anchored proteins.1 this deficiency results in loss of cd55 and cd59 , which are believed to be the main gpi - anchored proteins that serve to protect red blood cells ( rbcs ) from complement - mediated destruction.2 this rare disease , estimated at two to five new cases per million us inhabitants , has led to the development of multiple hypotheses that seek to explain the role of pig - a gene mutations and the survival , and clonal expansion , of cd55/cd59 cells ( pnh cells).1 these hypotheses seek to understand whether there is either an extrinsic permissive environment or an intrinsic survival benefit to pnh cells that allows for the clonal expansion within the bone marrow compartment.1,3,4 additionally , the identification of cd55/cd59 cells is not pathognomonic for clinical pathology , as pnh cells have been identified in normal individuals , thus further complicating the understanding of pnh and the role of pig - a.5,6 while early hypotheses of pnh pathophysiology considered the entity as part of a myelofibrosis ( mf)/myelodysplastic syndrome , these conceptualizations largely fell out of favor until recently with the advent of new high - throughput genetics and deep sequencing.7 deep sequencing studies have identified acquired somatic mutations in genes associated with myeloid neoplasms not only in hematologic malignancies but also in aging and in nonmalignant hematologic diseases such as aplastic anemia , suggesting that the development of a malignant process is bridged by the acquisition of multiple genetic mutations.8,9 recent data have identified the concurrence of pig - a mutations with genetic mutations associated with myeloproliferative disorders such as jak2 , hmga2 , and bcr - abl , thus further supporting the hypothesis that in some occurrences of pnh , the development of clinically significant pnh is the result of a stepwise progression of multiple genetic mutations similar to other myelodysplastic or myeloproliferative syndromes.1012 here , we report for the first time in the literature the development of clinically significant pnh in a patient with jak2v617f - negative , calr - positive essential thrombocythemia ( et ) . the patient was initially diagnosed with et in 2005 following the incidental finding of elevated platelets . the patient s initial bone marrow examination was consistent with a myeloproliferative neoplasm ( mpn ) . in 2011 , the patient was noted to have ongoing thrombocytosis ( platelets 795 k / mm ) but developed anemia ( hgb 9.0 g / dl ) , elevated lactate dehydrogenase ( 1,440 u / l ) , and marked reticulocytosis ( absolute reticulocyte count 197.3 k / mm ) ( figure 1c ) . a repeat bone marrow biopsy showed megakaryocyte hyperplasia with myelofibrosis , consistent with post - et myelofibrosis . the patient had a normal karyotype and a negative jak2v617f mutation but was found to have calr p.k385fs*47 , an acquired somatic mutation strongly associated with the development of mpn.13 his hemoglobin improved following iron supplementation , but hemolysis persisted with ongoing elevated lactate dehydrogenase , reduced haptoglobin , and reticulocytosis . urinalysis , which had previously been normal , revealed hemoglobinuria , 56 rbc/l , and 4 + hemosiderin . high - resolution karyotype with a single - nucleotide polymorphism array revealed hemizygous loss of xp22.2 , an area of the genome that contains the pig - a gene ( figure 1a ) . this microdeletion , which has been previously described , is a genetic aberration associated with the development of pnh.14 peripheral blood samples were used for multiparametric flow cytometry analysis based on fluorescent inactive aerolysin and the gpi - anchored proteins cd59 on rbcs and cd14 on monocytes and granulocytes . flow cytometry identified loss of gpi - anchored proteins ( pnh clone ) comprising 14% of rbcs , 60% of granulocytes , and 73% of monocytes , thus confirming his diagnosis of pnh ( figure 1b ) . though the development of pnh has been documented to be associated with a number of genetic aberrations associated with mpn and myelodyplasia , this is the first description of the development of pnh in a patient with a calr mutation.14 the progressive quality of his disease , initially from et to post - et myelofibrosis with eventual evolution of clinically significant pnh driven by microdeletion of xp22.2 , which encompassed the pig - a gene , illustrates the evolving nature of myelodysplastic / myeloproliferative conditions and supports the hypothesis that multiple genomic hits may occur in order to develop clinically significant pnh . while not fully elucidated , the calr mutation has been shown to lead to excessive cell proliferation.15 we hypothesize that the calr mutation conferred the survival benefit needed for clonal expansion and survival benefit within the bone marrow stem cell compartment of pig - a mutant cells , thus cooperating to generate the pnh phenotype . this case also importantly illustrates the utility of genomic testing outside the research setting and its utility in diagnosis when embedded within the clinical milieu . this patient s normal karyotype coupled with his calr mutation status allowed for appropriate identification of disease driving lesions and prognostication in et . as his disease continued to evolve , single - nucleotide polymorphism microarray appropriately identified the etiologic cause of his worsening anemia and changing clinical presentation , thus demonstrating how the clinical availability of sensitive genetic testing leads to more accurate diagnosis , pathogenic understanding of disease process , and the development of more targeted and personalized treatments.16

paroxysmal nocturnal hemoglobinuria ( pnh ) , a disease characterized by intravascular hemolysis , thrombosis , and bone marrow failure , is associated with mutations in the pig - a gene , resulting in a deficiency of glycosylphosphatidylinositol - anchored proteins . many hypotheses have been posed as to whether pnh and pig - a mutations result in an intrinsic survival benefit of cd55/cd59 cells or an extrinsic permissive environment that allows for their clonal expansion within the bone marrow compartment . recent data have identified the concurrence of pig - a mutations with additional genetic mutations associated with myeloproliferative disorders , suggesting that some presentations of pnh are the result of a stepwise progression of genetic mutations similar to other myelodysplastic or myeloproliferative syndromes . we report for the first time in the literature the development of clinically significant pnh in a patient with jak2v617f - negative , calr - positive essential thrombocythemia , providing further support to the hypothesis that the development of pnh is associated with the accumulation of multiple genetic mutations that create an intrinsic survival benefit for clonal expansion . this case study additionally highlights the utility of genomic testing in diagnosis and the understanding of disease progression in the clinical setting .

nail fragility , nail thickening and onycholysis may considerably reduce ability to manipulate small objects and can be a serious handicap , for example , to jewelers , musicians or illusionists . we report the case of mario , an eccentric 23-year - old man , a card illusionist who had alopecia areata ( aa ) universalis for the last 15 years . he had accepted his hair loss and was not seeking treatment for it . in january 2007 , he consulted us because he developed severe abnormalities of all his fingernails . at clinical examination , the fingernails were yellow gray colored and showed severe onycholysis , involving the whole nail plate and nail bed hyperkeratosis [ figure 1 ] . the patient asked for treatment as the nail changes did not permit him to continue his work as card illusionist . he was treated with intramuscolar triamcinolone acetonide 0.5 mg / kg / month , for 3 months [ figure 2 ] . severe onycholysis with distal to proximal detachment of the nail plate , nail bed hyperkeratosis regression of the nail changes after systemic triamcinolone acetonide for 3 months aa most commonly affects the scalp but it may involve beard , eyelashes , eyebrows , pubic , axillary , body hair . in patients with aa , nail abnormalities were found in 10 - 66% of the patients . hence , nail changes due to nail matrix inflammation are common and usually not severe ; geometric pitting affects up to 34% of patients , others alterations include trachyonychia , punctate leukonychia , mottled lunulae and onychomadesis . the nails are useful tools in many occupations and their cosmetic appearance is important in all occupations where personal contact occurs . in mario 's case the nail abnormalities were severe and affected the nail bed with symptoms that are not typical of nail aa . systemic steroids were very effective and treatment was justified by the important impact of the nail changes on the patient 's job .

in patients with alopecia areata ( aa ) , nail abnormalities due to nail matrix inflammation are common and usually not severe . we report the case of a 23-year - old man with aa universalis , who developed severe abnormalities of all his fingernails . systemic steroids improved the onycholysis that had an important impact on the patient 's job , as he was a card illusionist .

a 77-year - old woman with a history of hypertension was referred to our clinic in september 2006 for a 2-week history of blurred vision in her right eye . she had received an intravitreal injection of 4 mg of triamcinolone acetonide in her right eye for macular edema due to central retinal vein occlusion ( crvo ) 4 months previously . her right eye visual acuity was significant for light perception only , and ophthalmic examination of the right eye showed many cells in the anterior chamber and vitreous , multiple retinal hemorrhages and peripheral circumferential retinitis ( fig . serologic tests for infectious uveitis caused by herpes zoster virus ( hzv ) , herpes simplex virus ( hsv ) , cmv , toxoplasmosis , and syphilis ( vdrl ) , and a test for human immunodeficiency virus , were performed . the patient tested seronegative for hzv , hsv , cmv , toxoplasma , and hiv , and vdrl was non - reactive . before starting an oral corticosteroid , intravenous injection of acyclovir ( 2000 mg / day 4 times a day ) was started . because of a presumed diagnosis of acute retinal necrosis or cmv retinitis , diagnostic anterior chamber paracentesis was performed , and an aqueous humor sample was sent for analysis by polymerase chain reaction ( pcr ) for hzv , hsv , cmv and toxoplasmosis . an intravitreous gancyclovir injection ( 1.7 mg ) five days after the gancyclovir injection , the number of inflammatory cells in the anterior chamber decreased to trace amounts only , and the vitreous was cleared . argon laser photocoagulation between the area of retinitis and the normal retina was performed on the patient 's right eye . three weeks after the first gancyclovir injection , the patient presented with an aggravated retinal lesion and chamber reactions in the right eye . an additional two intravitreal gancyclovir ( 1.7 mg ) injections were performed at 2 weeks and 6 weeks after the second injection . two weeks after the final gancyclovir injection , examination of the right eye revealed much improved peripheral retinal necrosis with persistent retinitis at the inferior periphery . nine weeks after the last injection ( 4 months after the patient 's first visit to our clinic ) , the retinitis was completely resolved . the patient 's final resultant vision in her right eye was significant for hand motion . cmv is a ubiquitous human virus and 50 - 80% of adults in the united states harbor anti - cmv antibodies.22,3 seroprevalence among lower socioeconomic groups , residents of developing countries , and homosexual men can exceed 90%.4 acquisition of the virus occurs through placental transfer , breast feeding , saliva , sexual contact , blood transfusions , and organ or bone marrow transplants . infection with cmv leads to life - long persistence ; however , in healthy individuals , the virus becomes dormant and remains latent.1 reactivation occurs in patients with immature or compromised immune systems.1 in iatrogenically immunosuppressed patients after organ or bone marrow transplantation , cmv retinitis is a rare complication.5,6 recently , 4 cases of cmv retinitis after intravitreal steroid application in immunocompetent patients have been reported.7 - 9 in comparison with these previously published cases , our patient had no medical problems such as diabetes mellitus or behcet 's disease that could have impaired her immunity.7 - 9 local immunosuppression may be strong enough to allow cmv to replicate and lead to retinitis . in our case , symptomatic retinitis developed 4 months after the injection of intravitreal triamcinolone . the local immunosuppressive effect of ivta is thought to persist up to 8 months after injection . the poor visual outcome in this case was thought to be mainly due to the patient 's baseline disease . timely treatment with intravitreal injection of gancyclovir until local immune recovery may be effective for local immunosuppressioninduced cmv retinitis . ophthalmologists using intravitreal triamcinolone injections should be aware of the potential risk of subsequent cmv retinitis . early diagnosis and treatment with intravitreal injections of gancyclovir until recovery is obtained may prevent further complications .

to report a case of cytomegalovirus ( cmv ) retinitis after intravitreal injection of triamcinolone acetonide ( ivta ) . a 77-year - old woman with macular edema due to central retinal vein occlusion ( crvo ) developed peripheral retinitis 4 months after ivta . a diagnostic anterior chamber paracentesis was performed to obtain dna for a polymerase chain reaction ( pcr ) test for viral retinitis . the pcr test was positive for cmv dna . other tests for infective uveitis and immune competence were negative . four months after presentation , gancyclovir was intravitreously injected a total of 5 times , and the retinitis resolved completely . cmv retinitis is a rare complication of local immunosuppression with ivta . it can be managed with timely injection of intravitreal gancyclovir until recovery from local immunosuppression .

lymphedema is a type of edema that occurs due to an abnormal accumulation of fluids and other substances in the tissues resulting from a failure of the lymphatic system associated with insufficiency of extralymphatic proteolysis of proteins in the cell interstice and mobilization of macromolecules , for example hyaluronic acid . the treatment recommended for lymphedema is a combination of therapies including : lymph drainage , , exercising , , , hygienic care , psychological support and more recently the association of occupational activities with compression mechanisms and cervical stimuli , . the exercises used to treat lymphedema should be programmed controlled muscle activities to improve the physical condition without competitive objectives , . even so , it is very important to consider the principles of biomechanics , velocity , duration and positioning with this approach to therapy . however , one of the difficulties related to exercising is controlling how they are carried out : the development of facilitating devices may assist in this aspect and establish a specific plan of exercises for the patient . the objective of the present study was to evaluate the reduction in volume of arm lymphedema resulting from cancer treatment utilizing a specific exercise facilitating device . a total of 21 women with clinical diagnosis of arm lymphedema were randomly selected by order of arrival in a rehabilitation group . all participants reported that they had been submitted to radiotherapy after surgery for breast cancer . the time from surgery until this study varied between 2 and 12 years and none of the patients had been submitted to any type of physical rehabilitation within this period . evaluation of the edema was achieved by water displacement volumetry immediately before and after each experiment . the patients were submitted to a one - hour session of active exercising , divided in 12-minute stints with intervals of 3 minutes , utilizing a facilitating device . the active exercises in this study were characterized by active and conscious participation of the patient with voluntary command of the muscles involved in the movements . the patient independently performed the exercises without help from the therapist : the apparatus has no type of manual or mechanical resistance . the intervention was only to control the time and rest intervals , and guidance about posture . the patients remained sitting with alignment of the vertebral column and used a cotton - polyester compression sleeve on the lymphedematous limb . an active exercising device , denominated mobile flexion bar , was developed ( figure 1 ( fig . it is fixed on a metal base at a height of 30 cm from the tabletop and at a distance of 10 cm from the body of the patient ( figure 2 ( fig . the paired student t - test was utilized for statistical analysis with an alpha error of 5% ( p - value 0.05 ) being considered acceptable . the study was approved by the research ethics committee ( instituto de biocincias letras e cincias exatas , campus de so jos do rio preto , brazil protocol no . the initial and final mean volumes were 2,089.9 ml and 2,023.0 ml , respectively giving a mean loss of 66.9 ml ( p - value < 0.001 ) . 1 ) illustrates the volume loss before and after the activities and the variations for each patient . the current study adopted a pedal arrangement with the objective of facilitating , programming and controlling exercises of patients with arm lymphedema and showed that these exercises are efficacious in reducing the volume of edema . there are no publications analyzing the use of devices with these characteristics in lymphedema treatment . the device was developed after a pilot study of lymphedematous upper limbs which evaluated the working pressures of the main muscle groups which are involved in flexion and stretching movements and cause the greatest working pressure variations . the main difficulty in respect to myolymphokinetic exercises is the control of how they are carried out . exercises utilize muscle contractions and these cause external compression on the blood vessels ; this compression on veins and lymphatic vessels favors drainage . however , exercising demands a higher blood flow to the region and consequently increases the capillary filtration and requires greater lympho - venous drainage . thus , exercising may lead to an increase in the volume of the limbs or a reduction depending on the filtration demand versus drainage . in the treatment of lymphedema , the main objective is the reduction in edema ; hence exercises should be performed so that there is a resulting reduction . the authors suggest the term myolymphokinetic therapy for exercises and activities that lead to greater drainage than filtration and thus a reduction in the size of the limb . . however , active exercises are important to assist in maintaining the muscle trophism and maintaining the efficacy of contractions . the development of active exercises that can be controlled will constitute an advance in the treatment of lymphedema in respect to exercising . it will be possible to establish , for each patient , an individually adapted device that leads to a reduction in the lymphedema . this is a new research line that will help to better understand exercising , a low cost therapy which is easy to perform . another advantage is that exercises can be performed in any place giving greater independence to these patients . exercising will not constitute the only therapy for lymphedema , but will be part of the combination of therapies . the development of myolymphokinetic apparatuses may facilitate the indication of more specific and efficacious exercises in the treatment of lymphedema of the upper limbs . the authors declare that they have no competing interests ( political , personal , religious , ideological , academic , intellectual , commercial or any other ) in relation to this manuscript . the authors declare that they have no competing interests ( political , personal , religious , ideological , academic , intellectual , commercial or any other ) in relation to this manuscript .

the aim of this study was to evaluate the reduction in volume of arm lymphedema secondary to breast cancer therapy utilizing an exercise facilitating device . twenty - one women with arm lymphedema resulting from the surgical and radiotherapeutic treatment of breast cancer were randomly selected . evaluation was made by water - displacement volumetry before and after each session . the patients were submitted to a series of active exercises using a facilitating device for four 12-minute sessions with intervals of 3 minutes between sessions in the sitting position with alignment of the spinal column . the lymphedematous arm was maintained under compression using a cotton - polyester sleeve . the active exercising device used was a mobile flexion bar fixed on a metal base at a height of 30 cm from the tabletop and at a distance of 10 cm from the patient s body . the paired t - test was utilized for statistical analysis with an alpha error of 5% ( p - value 0.05 ) being considered significant . the initial mean volume of the arms was 2,089.9 and the final volume was 2,023.0 ml with a mean loss of 66.9 ml ( p - value < 0.001 ) . in conclusion , active exercises utilizing facilitating devices can contribute to a reduction in size of lymphedematous limbs .

a 66-year - old woman with sjgren syndrome presented with a 5-year history of bilateral shoulder pain that was significantly worse on the right than the left side . the pain was reported to be constant in nature but worse at night , and completely prohibited activities above shoulder height . examination of the right shoulder revealed a globally restricted range of movement at the glenohumeral joint . treatment with copeland resurfacing hemiarthroplasty was performed in june 2007 through an anterosuperior ( mackenzie ) approach . . 1 interrupted pds ( polydioxanone ) sutures were used for reattachment of the anterior border of the osteo - periosteal sleeve to the acromion . the sutures were placed transosseously through the acromium on one side and through the deltoid fascia , incorporating an osteo - periosteal sleeve , on the other [ figure 2 ] . preoperative radiograph demonstrating severe osteoarthritis radiograph taken in the immediate postoperative period showing a copeland resurfacing hemiarthroplasty passive elevation past 90 could be achieved on the first postoperative day . a shoulder immobilizer was worn for 3 weeks and the patient was instructed to avoid active elevation . the patient had returned to aerobics and table tennis by the 4 postoperative month , at which point increased pain in the shoulder was reported . at the end of the 1 postoperative year , significant impingement symptoms were reported and x - rays demonstrated a new bony spur on the anteroinferior edge of the acromion [ figure 3 ] . an ultrasound scan showed a bony spur indenting the supraspinatus , but there was no accompanying cuff tear . the pain continued to worsen and diagnostic arthroscopy was performed in july 2009 , which confirmed the presence of the spur at the anteroinferior edge of the acromion and excluded the presence of significant glenoid arthrosis or adhesions as contributing factors to the patient 's symptoms . radiograph at 1 year showing new bony spur on the inferior surface of the acromion appearance following arthroscopic resection of the spur the mackenzie anterosuperior approach has been popularized for several types of shoulder arthroplasties . in this approach the anterior deltoid is commonly reflected with an osteo - priosteal sleeve . we postulate that the bony spur responsible for the impingement symptoms in our patient was formed by malunion of the osteo - periosteal sleeve . at the time of arthroscopy , a sharp spur of bone of the same size and shape as the osteo - periosteal sleeve was found to be united in the correct position on the anterior acromion but , from its shape , it had apparently rotated 90 from the original orientation . the onset of symptomatic impingement along with new x - ray findings at 4 months postoperatively is consistent with rotation of the fragment during healing following the patient 's return to sporting activity . full resolution of the patient 's symptoms following resection of the spur also supports this conclusion . intra - articular factors are the most common reasons for postoperative pain following copeland resurfacing hemiarthroplasty and are due to the nonanatomical shape of the prosthesis , which does not accurately recreate the original shape of the humeral head . as our patient was initially pain free with good shoulder function , we carried out other investigations , including diagnostic arthroscopy , to look for other causes for her pain preoperative investigation to establish the diagnosis of subacromial impingement could include an injection of local anesthetic under aseptic technique into the subacromial space . immediate pain relief would be convincing evidence of the existence of subacromial impingement . to the best of our knowledge , this is the first report of formation of an acromial spur following the mackenzie approach . complications of the copeland resurfacing hemiarthroplasty have been reported as infection , aseptic loosening , periprosthetic humeral fracture , and osteolysis . subacromial impingement has been reported in patients after this procedure and the symptoms have necessitated subacromial decompression , but this has not previously been reported to be associated with a malunited osteo - periosteal sleeve . nonunion ( or fibrous union ) has been reported by previous authors following surgical access using the mackenzie approach but they did not report symptomatic subacromial impingement . in our patient , simple arthroscopic excision of the bony spur proved curative . this case has altered our practice , as we have now abandoned the osteoperiosteal sleeve technique and instead opt for subperiosteal dissection of the anterior deltoid . we conclude that the cause for the delayed , severe impingement symptoms in this patient following successful copeland resurfacing hemiarthroplasty was malunion of the osteo - periosteal sleeve that was made as part of the mackenzie approach . all symptoms resolved following arthroscopic resection of the spur .

we report the case of a patient with end - stage osteoarthritis who received a successful copeland resurfacing hemiarthroplasty through a mackenzie anterosuperior approach , which involves taking the anterior portion of the deltoid attachment from the acromion along with an osteo - periosteal sleeve . the patient went on to develop severe subacromial impingement symptoms 4 months postoperatively . x - rays revealed a large anteroinferior acromial osteophyte that had not been present preoperatively and was deemed to represent a malunited osteo - periosteal sleeve from the mackenzie approach .

the reca gene was first identified in escherichia coli more than 40 years ago , and hundreds ( if not thousands ) of papers have shown this gene to be centrally important to both the recombination and repair of dna . while genetic recombination helps create genetic diversity and therefore increases the fitness of a population , pathways for genetic recombination appear to have arisen as a mechanism for the repair of dna , using an identical or homologous stretch of one dna molecule to repair a second dna molecule that has been damaged . the reca protein is produced quite copiously in bacteria after massive dna damage and actually can be the single most abundant protein in the cell . in addition , pure reca protein in vitro can catalyze a remarkable reaction in which two dna molecules exchange a strand . these reactions have served as models for the action of rad51 , the eukaryotic homolog of reca . the active forms of both reca and rad51 are helical protein polymers formed on dna , and this has made many high - resolution structural studies difficult or impossible . electron microscopic and topological studies had shown that reca has a profound effect on dna structure when it binds : the dna is stretched by ~50% , and the dna is untwisted by almost a factor of two , from ~10 to ~19 base pairs per turn . since the human rad51 protein has been shown to induce similar changes in dna , it is reasonable to believe that this unusual dna structure is important for the mechanism of genetic recombination . a crystal structure of reca protein had been solved many years ago , but based upon electron microscope observations , the filament within the crystal appeared to be in a compressed inactive conformation . furthermore , the crystal did not contain dna , so it provided few clues about how reca induced this unusual dna conformation . modeling studies for stretched dna have been attempted , but these are relatively unconstrained by detailed experimental observations . a very challenging study using nuclear magnetic resonance ( nmr ) was undertaken to look at oligonucleotides complexed with reca , but the interpretation of those results appears to have depended upon the assumption that the structure is actually uniform , with every base in the same conformation . a new crystal structure of a complex between reca and dna has been solved , and one of the most surprising observations is that there is no uniform stretched dna structure . three bases adopt a fairly b - like conformation ( figure 1 ) , with stacking of the bases to exclude solvent within these triplets , and then there is a very large stretch and a left - handed twist to reach the next set of triplets . the left - handed twists interspersed between the triplets in right - handed b - like conformations account for the global untwisting that has been measured , whereas the stretching of ~7.8 between triplets accounts for the global average of ~5.1 rise per base or base pair ( from ~3.4 per base pair in b - dna ) . in addition to giving us the first high - resolution picture of this unusual dna conformation ( and one that is likely to be conserved from bacteria to humans ) , the crystal structure is a technical tour de force . the problem with many helical polymers is that , unless there are exactly two , three , four , or six units per turn , the polymer can not be crystallized so that every subunit is in an identical environment . polymerization can also be competing with crystallization , so that under the conditions of high protein concentrations needed for crystallization many polymeric proteins will polymerize . pavletich and colleagues solved this problem for reca by engineering a reca polyprotein containing four , five , or six copies of reca linked together , with the ends modified to prevent polymerization . the new crystal structure also shows that reca subunits have the ability to rotate in the filament from the position seen in the first crystal filament , consistent with predictions made using both electron microscopy and spectroscopy . the subunits of the active filament are bound to atp , whose hydrolysis releases the dna from the filaments . this rotation brings atp molecules bound to one subunit into a cleft between adjacent subunits where they can be hydrolyzed . three bases are stacked and have a b - like twist but are separated from adjacent triplets by regions of left - handed twist and extreme stretching . this conformation appears to be the basis of a search for homology with a second dna molecule that will locally have a b - like conformation . although the new crystal structure provides a major advance in understanding how reca - like proteins function , many questions still remain . however , these questions now can be examined in a framework that is very different from the one that has existed previously . it has been known that a second dna molecule can be untwisted by the complex of reca bound to a first dna molecule , but the new crystal structures do not provide direct information about how dna is untwisted at this second binding site . models can be built , and the new framework provides many constraints that will aid in designing experimental tests . all of this will advance our understanding of how the fundamental biological process of homologous genetic recombination takes place , and will undoubtedly have an impact on human health as well . diseases like cancer can be caused by defects in the repair of damaged dna , so a molecular understanding of how proteins such as human rad51 act in the repair of dna will be crucial for many advances .

the reca protein has been the most intensively studied protein involved in homologous genetic recombination , but until recently very little has been known about the molecular details of how reca can bring two dna molecules into juxtaposition and switch strands between them . a recent reca - dna crystal structure provides some striking new insights .

odontogenic ghost cell carcinoma ( ogcc ) is a rare odontogenic tumor characterized by the presence of ghost cells . it can appear as a de novo tumor or may arise in a preexisting calcifying odontogenic cyst ( coc ) . until now , only 31 cases of ogccs have been reported in literature . because of the limited number of published cases , the clinical behavior of the tumor is not well - understood . a 54-year - old male presented with pain in the left malar prominence and epistaxis . on examination , there was tenderness in the malar region . intraorally left gingivobuccal sulcus showed a smooth swelling measuring 3 cm 3 cm . imaging showed irregular soft tissue density mass in the left maxillary antrum measuring 4.6 cm 4.5 cm 3.8 cm with destruction of the wall . microscopy showed a neoplasm composed of islands of odontogenic epithelium resembling that of ameloblastoma [ figure 1 ] and epithelial cells transforming into ghost cells [ figures 24 ] . focal cellular areas composed of pleomorphic cells with increased nuclear cytoplasmic ratio and hyperchromatic nuclei were noted . photomicrograph showing ameloblastoma - like epithelial proliferation and hemorrhagic areas ( h&e stain , 100 ) photomicrograph showing islands of epithelial cells admixed with ghost cells ( h&e stain , 100 ) photomicrograph highlighting the features of ghost cells with loss of nuclei and preserved cell outlines ( h&e stain , 200 ) higher power of the ghost cells ( h&e stain , 400 ) area of high cellularity with increased number of mitotic figures ( h&e stain , 200 ) the patient was given postoperative radiotherapy . biopsy of the lung mass showed the similar morphology as the maxillary tumor with ghost cells [ figure 6 ] . tumor cells were positive for cytokeratin and p63 and were negative for ttf1 and ck7 [ figure 7 ] . lung biopsy showing ghost cells ( h&e stain , 200 ) immunohistochemistry on lung tumor showing ( a ) cytokeratin positivity ( ihc stain , 100 ) , ( b ) p63-positivity ( ihc stain , 200 ) ( c ) ck7-negativity(ihc stain 200 ) and ( d ) ttf1-negativity ( ihc stain , 200 ) the peak incidence occurred in the fourth decade with age ranging from 13 to 72 years . ogcc is believed to be one end of the spectrum of a heterogeneous entity known as coc also known as gorlin cyst , first identified by gorlin in 1962 . in the initial years , coc was considered a nonneoplastic cyst . however , later , some of these lesions showed a solid component also . in 1981 , praetorius et al . they further classified the cystic type into three subtypes such as simple unicystic , odontoma - producing type and ameloblastomatous proliferating type . the neoplastic ( solid ) type was called dentinogenic ghost cell tumor because of its tendency to produce dentinoid material . proposed the term epithelial odontogenic ghost cell tumor ( eogct ) to these neoplastic solid types and these authors classified the neoplastic form of coc into ameloblastoma ex coc , peripheral eogct ( which occurred in gingival or alveolar mucosa ) and central eogct ( which occurred intraosseously ) . divided the calcifying cystic odantogenic tumors into four subtypes which included simple cystic , odontoma associated , ameloblastomatous proliferating and ccot associated with benign odontogenic tumors other than odontomas . they separated the dentinogenic ghost cell tumor into central aggressive dgct and a peripheral nonaggressive counterpart . the who considered all coc as neoplastic and termed the cystic form as calcifying cystic odontogenic tumor and the neoplastic solid form as dentinogenic ghost cell tumor whereas ghost cell odontogenic carcinoma is a malignant odontogenic epithelial tumor with features of one or both of these lesions . in 1985 , ikemura et al . described the first well - documented case of malignancy arising in a coc . in their case report the histological features of ogcc are an ameloblastoma - like epithelial proliferation , ghost cells that may be calcified , admixed with areas of atypical features such as increased cellularity , pleomorphism , mitosis , necrosis and infiltrative growth pattern . the accurate diagnosis of ogcc requires extensive sampling of the specimen as the features of malignancy can be focal and the other areas may show benign histology . they are large polygonal epithelial cells with eosinophilic cytoplasm that have lost their nuclei but maintain a faint outline of cellular and nuclear membrane . the intracytoplasmic keratin preserves the cell outline and the corresponding previous site of the nucleus . levy proposed that the formation of ghost cells is due to squamous metaplasia of odontogenic epithelium caused by ischemia . in general , the cell outlines of ghost cells are well - defined but , in some cases , it may be blurred . in such cases , groups of ghost cells that suggested some of the cytokines produced by ghost cells play roles in the bone resorption . it can behave as slowly growing locally aggressive neoplasm or rapidly growing highly invasive tumor . the overall 5-year survival rate is estimated to be 73% . in the first case of ogcc described by ikemura et al . review of literature shows only three previous cases of metastatic ogcc . in the case described by grodjesk et al . , the patient died due to lung metastasis . in the second case , the patient developed metastasis in the skin , lung and brain . the third case was reported by cheng et al . where the patient developed metastasis in the cranium . in our case , 2 years after the initial diagnosis , the patient developed metastasis in the lung . because of the unpredictable biological behavior of the tumor , a long - term follow - up is recommended .

odontogenic ghost cell carcinoma ( ogcc ) is an exceptionally rare malignant odontogenic epithelial tumor . it is characterized by ameloblastic - like islands of epithelial cells with aberrant keratinization in the form of ghost cells with varying amounts of dysplastic dentin . malignant histological characteristics include infiltration , cellular pleomorphism , numerous mitosis and necrosis . its biological behavior varies from slow - growing locally invasive lesions to rapidly growing highly aggressive tumors . ogcc metastasizing to distant sites is extremely rare . only three cases of metastasis have been reported in literature . we are reporting the case of a 54-year - old male patient who presented with tender swelling in the malar region . histopathological examination revealed ogcc and he received postoperative radiotherapy . two years later , he presented with a lung mass . biopsy from the lung lesion showed the same morphology as that of maxillary tumor with scattered ghost cells . this case points to the aggressive behavior of ogcc and its metastatic potential . it also highlights the need for long - term follow - up of these patients .

spinal tumors are known to be relatively rare among neoplastic diseases . but as the expected length of life extends every year and due to the rapid development in diagnostic tools , the incidence of spinal tumors is increasing markedly . as a result , many studies on spinal tumors are under progress . spinal tumors often do not accompany symptoms , but as it progresses , it may accompany muscle weakness , pain , or even serious disability such as quadriplegia . therefore , like other tumors , early discovery and treatment may have an absolute impact on the prognosis of the patient2,6 ) . generally , for spinal tumors , metastatic spinal tumor is known to be much more common than primary spinal tumor . therefore , once a spinal tumor is identified on imaging studies such as ct scan or mri , full metastasis work up for finding a probable primary location of the tumor is essential . especially more in case of patients with a previous cancer history ( lung cancer , breast cancer , or else ) . it is easier to regard the spinal tumor as metastatic lesion from the existing tumors of other organs . an abdominal ct scan was taken of a 57-year - old male patient who had sacral and right buttock and thigh pain , and revealed with a tumor - like lesion at the t12 vertebrae . previously in 2007 , the patient had been diagnosed with colon cancer , confirmed as adenocarcinoma by open biopsy . targeting the cancer lesion , only endoscopic mucosal resection was executed at that time and was considered as a cure . after a period of 3 years , on a follow up large intestine endoscope , a recurred lesion was identified , thus abdominal low anterior tumor resection with colostomy was performed immediately . the patient was also diagnosed with liver cancer in 2009 , which was confirmed as hepatocellular carcinoma . about this hepatic lesion the t12 level tumor mass was first discovered in the abdominal ct which was taken to confirm the hepatic lesion , and in the follow - up abdominal ct executed 6 months later , the diameter of tumor mass was increased from 1.5 cm to 4 cm ( fig . 1 , 2 ) . first , it was presumed that the lesion might be a metastatic lesion originated from the primary colon or liver cancer considering the previous cancer history of the patient . as a treatment for the vertebral lesion , total laminectomy , right hemi - vertebrectomy of t12 and tumor resection was performed , and pedicle screw fixation of t10 , t11 , l1 , and l2 vertebral bodies were done . observed intra - operatively , the tumor was found to be a brownish , hypervascular , and friable mass compressing the thecal sac on right side of t11 - 12 level , and additional erosion of the t12 lamina was also identified . on the final pathologic report , however , it was confirmed as plasmacytoma ( fig . 3 , 4 ) , which was completely different pathologically from previously diagnosed colon cancer or liver cancer . on additional immunostaining , the tumor cells also showed a monoclonality for lambda immunoglobulin in its light chain . in conclusion , the patient was finally diagnosed to have triple primary - origin tumors of adenocarcinoma , hepatocellular carcinoma , and vertebral plasmacytoma . generally , spinal tumors are mostly metastatic tumors , and those that often cause metastasis to spine include lung cancer , breast cancer , and prostate cancer . on the contrary , primary spinal tumor is very rare so that among the most representative of such , multiple myeloma is found in 1 - 2 persons per 100,0001 ) , and chordoma is found in 0.5 persons per 100,0003 ) . therefore , when a patient is found with a lesion suspicious of a tumor in the spine , the expectation is that it is a metastatic lesion and the metastatic examination and treatment are conducted , and in most cases the future biopsy results are consistent . under such circumstances , when a lesion suspicious of spinal tumor is found in a patient already diagnosed with tumors in other organs , the probability and the suspicion that this lesion is a spinal metastasis from an existing tumor are bound to be even greater . as in our case above , however , there clearly is the case where the spinal lesion is primary and a completely different type of tumor is diagnosed despite having two different types of tumors in different organs , and the treatment directions may differ completely depending on this . for example , when a lesion suspicious of tumor is found in spine from the imaging study executed with the backache as the main symptom for a lung cancer patient , generally it is considered the spinal metastasis of the lung cancer and only palliative radiation therapy may be executed . if the actual spinal lesion was chordoma , however , the treatment method must be completely different - it is resistant to general radiation therapy , so the treatment direction should be surgical removal and proton - beam radiation4,5 ) . for this reason , it is emphasized that even if the discovered spinal lesion is suspicious of being a metastatic lesion , histological confirmation should be executed when possible . triple primary - origin tumor is a very rare case across the world ; this report intended to cover the case report and also the necessity of histological confirmed diagnosis of spinal tumor . so far , it is difficult to make a perfect differential diagnosis with imaging study alone without a biopsy for modern technology , and this may be resolved with development of imaging and interpretation technologies in the future . with this report , we wish to emphasize the necessity of pathologic confirmation and adequate further treatment even in a patient with known malignancies .

generally , among the extradural spinal tumors , metastatic spinal tumor is much more common than primary spinal tumors . thus , in the case of a spinal tumor patient with cancer history ( such as lung cancer , breast cancer , etc . ) , we used to infer that the spinal lesion is the metastasis from , primary malignancy . we introduce an experience of a case of triple primary origin tumor in a 57-year - old man . when the spinal lesion was found on the abdominal computed tomography scan , he already had a history of colon cancer and liver cancer . initially , it was thought that the lesion would probably be a metastatic tumor from the liver or colon cancers , and the operation was performed accordingly . in the pathologic final report , however , the mass was proven to plasmacytoma - the third primary lesion . the patient underwent chemotherapy after surgery . globally , the triple primary origin tumor has been reported very rarely . with this report , we wish to emphasize the necessity of pathologic confirmation and adequate treatment even in a patient with known malignancies .

it is characterised by a rapidly progressive glomerulonephritis due to circulating anti - glomerular basement membrane ( anti - gbm ) antibodies . the subject of this report developed acute pulmonary aspergillosis following exposure to fungal spores in mouldy tree bark whilst gardening and this led to goodpasture 's syndrome . we believe that this is the first presentation of aspergillosis induced goodpasture 's syndrome to be reported in the medical literature . a 69 year old retired man with no significant medical history was admitted to hospital with a 5 week history of increasing dyspnoea and intermittent haemoptysis . antibiotics in the community had not improved his symptoms . he was a lifelong smoker of 30 cigarettes per day . on admission ( day 0 ) , his temperature was 37.2 c , his pulse was 72 , his respiratory rate 22 per minute and his blood pressure was 120/69 mmhg . initial blood tests revealed raised inflammatory markers ( crp 225 mg / l and leucocyte count 19.510/l with a neutrophilia ) . spirometry on day+5 was as follows : fev1 1.69 l ( 55% predicted ) ; forced vital capacity 2.59 l ( 65% predicted ) : fev1/fvc ratio 65% . on day+6 , a high resolution ct of his thorax revealed widespread fine nodularity , maximal in the midzones and ill - defined peribronchial inflammatory shadowing . there was bronchiectasis ( which had improved on a follow - up scan 2 months later ) and patchy tree - in - bud change , but no radiological features of pulmonary haemorrhage . at bronchoscopy on day+7 , endobronchial biopsies showed non - specific inflammatory changes , with no granulomata seen . transbronchial biopsy was not possible as the patient 's oxygen levels fell and so the procedure was abandoned . serum ana was weakly positive at 1/100 ( speckled pattern ) with negative ena and anca . he had elevated igg to aspergillus fumigatus of 47 mga / l ( reference range up to 40 a diagnosis of acute invasive pulmonary aspergillosis ( ipa ) was made and he was discharged home on day+13 , on oral itraconazole , 200 mg twice daily . his discharge creatinine was 80 mol / l . at clinic on day+27 , his respiratory symptoms had improved substantially following treatment . he was able to climb 20 steps and the saturation did not fall below 90% . spirometry was greatly improved at 2.4/3.9 ( fev1 78% predicted , vital capacity 90% predicted , fev1/fvc ratio 61% ) . direct questioning revealed that his symptoms had developed about 2 weeks after spreading eight , 40 l bags of foul smelling mouldy tree bark on the garden . this material was subsequently cultured in the national aspergillosis centre and it grew a. fumigatus , rhizopus spp . , sporobolomyces spp . and bacteria ( fig . a renal immunology screen showed positive anti - glomerular basement membrane ( anti - gbm ) antibodies with a titre of 111 u / ml ( elisa assay ) ( reference range<15 u / ml ) . retrospective analysis of a blood sample from day 3 of his first hospital admission showed an anti - gbm titre of 67 u / ml at that time . renal biopsy demonstrated necrotising crescentic glomerulonephritis with linear deposition of igg along the basement membrane , consistent with anti - gbm disease . on day+28 , he was commenced on haemodialysis , pulsed methylprednisolone 500 mg once daily for 3 days , cyclophosphamide 750 mg ( once monthly dose ) and plasma exchange . subsequent anti - gbm antibody titres were significantly lower ( 20 u / ml 6 weeks post - presentation , 8 u / ml at 8 weeks and < 7 u / ml at 5 months post - presentation ) . aspergillus igg 6 weeks after his acute respiratory presentation had fallen to 7 mga / l , and after 3 months total ige was normal . unfortunately the patient remained frail and housebound despite haemodialysis and he died from severe sepsis and acute pneumonia 10 months after his first presentation . invasive pulmonary aspergillosis has specifically been reported in healthy individuals after spreading rotting tree bark whilst gardening [ 13 ] . in previous cases , massive inhalation of spores there is diagnostic difficulty in these cases and diagnosis is often made at post - mortem , because blood and sputum cultures have poor sensitivity . serological testing for aspergillus igg antibodies can be used in the diagnosis of ipa . in a study of patients developing ipa following bone marrow transplant , an igg response to acute infection was noted . anti - gbm antibody disease is characterised by a rapidly progressive glomerulonephritis due to circulating anti - gbm antibodies . the target of these antibodies is the non - collagenous domain of the 3 chain of type iv collagen . there is a body of evidence to suggest that certain human leucocyte antigen ( hla ) molecules , notably hla - dr 15 and hla - dr 4 , are associated with the development of anti - gbm disease . subsequent analysis of our patient 's hla type revealed hla - dr 17 and dr 4 . hypothetically certain epitopes that are normally immunologically privileged can become exposed and perceived as foreign , leading to antibody development . a. fumigatus conidia bind to type iv collagen ( and fibrinogen ) , a process inhibited by free sialic acid and in particular n - acetylneuraminic acid . whether the binding of a. fumigatus to collagen iv in the lung altered the allergenicity of this major structural protein , allowing auto - antibodies to be formed , remains conjecture . it has been hypothesised that exposure to certain environmental factors may affect the molecular structure of 3nc1 domain , making antibody binding more likely . development of goodpasture 's syndrome has been reported following exposure to inhaled chemicals , drugs and in association with infectious disease . we hypothesise that our patient contracted invasive pulmonary aspergillosis due to heavy exposure to fungal spores whilst gardening . this led to epitope exposure in the alveoli with subsequent development of gbm auto - antibodies and acute renal failure , in an individual with pre - existing genetic risk factors . we have no conflicts of interest in the publication of this article , including financial ones to declare .

a non - immunocompromised man developed acute aspergillus pneumonia after spreading mouldy tree bark mulch . despite normal renal function at presentation , he developed rapidly progressive glomerulonephritis with acute kidney injury due to anti - glomerular basement membrane antibodies ( anti - gbm ) 4 weeks later . he remained dialysis dependent and died of sepsis 10 months later . we hypothesise that he contracted invasive pulmonary aspergillosis from heavy exposure to fungal spores , leading to epitope exposure in the alveoli with subsequent development of gbm auto - antibodies .

fibrous dysplasia of bone is characterized by the replacement of medullary bone with fibro - osseous tissue . this results in the distortion and overgrowth of bone , leading to characteristic deformities . based on the bony involvement , fibrous dysplasia is divided into three types : monostotic , polyostotic , and mccune albright syndrome ( mas ) . mas is characterized by a triad of monostotic / polyostotic fibrous dysplasia , caf-au - lait macules ( calms ) , and endocrine hyperfunction . the disease is congenital but not hereditary and is due to an activating mutation in g protein - coupled receptor . it manifests usually in childhood , with recurrent fractures , distorted bones , precocious puberty , acromegaly , or hyperthyroidism . untreated disease leads to permanent disfigurement , and the disease is classified as paucibacillary or multibacillary depending on the proliferation of the bacilli . the risk factors for the disease are living in endemic areas with poor hygiene conditions and defects in cell - mediated immunity . we recently encountered a patient with mas who presented with cutaneous features of hansen 's disease . we report the same for the unusual association and to highlight the relevant review of the literature . a 30-year - old man presented with hypoesthetic , depigmented patches over the skin of the chest and back of 1 year duration . he gave history of recurrent fractures since the age of 4 years with shortening of right leg . the parents gave history of hyperpigmented macules over the trunk since birth and denied similar features in family members . the patient attained puberty at the age of 14 years and denies history suggestive of acral enlargement , thyrotoxicosis , cushing 's syndrome , and swellings in any part of the body . examination revealed ( height 152 cm ) asymmetry of the face with expansion of right maxilla and lower jaw and short right leg ( 82 vs 86 cm ) [ figures 1 and 2 ] . cutaneous examination revealed a large calm over the back , extending across the midline and multiple anesthetic patches over scapula and lower back [ figure 3 ] . there was no evidence of goiter , acromegaloid features , and thickened nerves , and the rest of the examination was normal . facial photograph showing craniofacial dysplasia legs showing short right leg ( arrow ) with expansile lesion of tibia ( arrow head ) skin over the back showing a large calm crossing midline ( long arrows ) with depigmented hypoesthetic patches ( short arrow ) hormonal profile revealed normal thyroid adrenal and gonadal axes evaluation . skeletal survey revealed expansile osteolytic lesion over right maxilla , right hip , and shoulder . skin biopsy specimens were obtained from ear lobes , legs , and depigmented lesions over the back , avoiding areas of calm . specimens revealed the presence of acid - fast bacilli along with noncaseating granulomas consistent with the diagnosis of tuberculoid leprosy . the diagnosis of fibrous dysplasia is made by the presence of bone pains , recurrent fractures , deformity of bone , and radiological evidence of fibro - osseous tissue showing expansile lytic lesion . biopsy and tc - mdp scan of the bone were not considered necessary to establish the diagnosis in this classical case . other laboratory workup showed elevated alkaline phosphatase ( 388 u / l ) with normal calcium , phosphorus , parathyroid hormone , and 25-hydroxy vitamin d levels . he was treated with triple drug regimen for leprosy and also given oral calcium carbonate 1.5 g daily along with the first dose of zoledronic acid 4 mg as an intravenous infusion . mas is characterized by the triad of polyostotic fibrous dysplasia , calm , and endocrinopathy . the diagnosis of fibrous dysplasia is based on classical radiological findings supported by histopathology and bone scan . hyperfunctioning of endocrine glands in mas presents with precocious puberty , hyperthyroidism , acromegaly , or cushing 's syndrome . our patient had only two features of the triad and did not have any evidence of endocrine hyperfunction syndromes . the calm is unusual in our patient in that it crossed the midline and was seen on both sides of the body . the calms in mas do not cross the midline and follow the developmental lines of blashko , thus differentiating from those in neurofibromatosis . our patient had an exceptionally large calm that crossed the midline interspersed with anesthetic depigmented macular lesions of hansen 's disease . hansen 's disease is caused by mycobacterium leprae , and the disease spreads via respiratory droplets between close personal contacts over a prolonged duration . immunocompromised situations are the predominant risk factors for the disease , and defects in cell - mediated immunity are implicated in persons with genetic predisposition . the mode of acquisition of hansen 's disease in our patient is possibly due to frequent stay in the hospitals due to multiple fractures and contact with a patient . screening of the persons involved in personal care of the patient did not reveal features of hansen 's disease . the association of hansen 's disease with mas appears coincidental as there is no evidence that mas predisposes to the infectious diseases or leads to immunosuppressed state . extensive literature search did not reveal any previous reports of association between hansen 's disease and mas . they are given as intravenous or oral preparation and act by suppressing the osteoclast activation . treatment of mas involves bisphosphonate therapy to reduce fracture rate apart from treating any associated endocrinopathy . to conclude , we present an interesting case of mas without associated endocrinopathy who had coexisting hansen 's disease . this unusual combination was not reported earlier in world literature .

mccune albright syndrome ( mas ) comprises a triad of fibrous dysplasia of bone , caf - au - lait macule , and endocrinopathy . the disease is due to activating mutation of g protein - coupled receptor leading to hyperfunction of glands . hansen 's disease is caused by infection with mycobacterium leprae and is seen with underlying immunosuppressed conditions in genetically predisposed individuals . we recently encountered a patient with hansen 's disease along with underlying mas and report the same in this report .

vaginal tumors are rare and include papilloma , hemangioma , mucus polyp , and rarely leiomyoma . vaginal leiomyomas remain an uncommon entity with only about 300 reported cases since the first detected case back in 1733 by denys de leyden . bennett and erlich found only nine cases in 50,000 surgical specimens and only one case in 15,000 autopsies reviewed at johns hopkins hospital . we report a case of primary leiomyoma of vagina arising from anterior wall and presenting with lower abdominal pain , bleeding , and a feeling of something coming out of vagina . a 38-year - old female gravid 2 , para 2 presented to the outpatient department with complaints of lower abdominal pain , abnormal vaginal bleeding , and dyspareunia since 8 months . there was no history of dysuria , increased frequency , or any feature of urinary retention . the patient complained that she noticed something appeared to come down her vagina for the last 2 months . a pervaginal examination revealed a mass in the vagina , but the upper limit of the mass could not be delineated . an ultrasonography was performed which showed a 6 4 cm hypoechoic mass in the upper part of vagina and a possibility of pedunculated cervical fibroid was made . the tumor was then sent for histopathological examination with a peroperative diagnosis of vaginal leiomyoma . gross examination revealed a 6 5 cm solid mass with a whorling appearance in the cut section [ figure 1 ] . microscopic examination revealed a well - circumscribed leiomyoma underlying the squamous epithelium , consistent with the diagnosis of vaginal leiomyoma [ figure 2 ] . photograph showing the whorling pattern on cut section of the vaginal tumor microphotograph showing the leiomyoma ( arrow ) with the overlying vaginal squamous epithelium ( right side ) ( hematoxylin and eosin stain , 100 magnification ) tumors of vagina are rare and there are only around 300 reported cases of vaginal leiomyomas since the first described case in 1733 by denys de leyden . leiomyomas in female genital tract are common in the uterus and to some extent in the cervix followed by the round ligament , utero - sacral ligament , ovary , and inguinal canal . vaginal leiomyomas are commonly seen in the age group ranging from 35 to 50 years and are reported to be more common among caucasian women . they usually occur as single , well - circumscribed mass arising from the midline anterior wall and less commonly , from the posterior and lateral walls . they may be asymptomatic but depending on the site of occurrence , they can give rise to varying symptoms including lower abdominal pain , low back pain , vaginal bleeding , dyspareunia , frequency of micturation , dysuria , or other features of urinary obstruction these tumors can be intramural or pedunculated and solid as well as cystic . usually these tumors are single , benign , and slow growing but sarcomatous transformation has been reported . preoperatively , diagnosis by ultrasonography may be difficult , but magnetic resonance imaging usually clinches the diagnosis . in magnetic resonance imaging , they appear as well - demarcated solid masses of low signal intensity in t1- and t2-weighted images , with homogenous contrast enhancement , while leiomyosarcomas and other vaginal malignancies show characteristic high t2 signal intensity with irregular and heterogeneous areas of necrosis or hemorrhage . however , histopathological confirmation is the gold standard of diagnosis and also beneficial to rule out any possible focus of malignancy . surgical removal of the tumor through vaginal approach , preferably with urethral catheterization to protect the urethra during surgery , is usually the treatment of choice . in case of large tumors

leiomyomas are common benign tumors in the uterus . however , vaginal leiomyomas remain an uncommon entity with only about 300 reported cases . here , we report a case of a 38-year - old multigravida who presented with lower abdominal pain and vaginal bleeding . a physical examination and ultrasonography were performed , and a diagnosis of cervical fibroid was made . pervaginal removal of the tumor was performed and subsequent histopathology revealed a vaginal leiomyoma . although a rare tumor , vaginal leiomyomas may present with a variety of clinical features and may be mistaken preoperatively for cervical fibroid . removal of tumor by vaginal route , wherever possible , with subsequent histopathological examination appears to be the optimum management plan .

early identification of the source is a critical step in the management of any patient with sepsis as it allows the timely administration of appropriate antibiotic therapy . in the elderly the usual culprits are the respiratory and urinary systems , however this case highlights the importance of keeping an open mind when assessing such patients as diagnostic prejudice can lead to delays in treatment and worsening of the clinical picture . acute cholecystitis is a common abdominal cause of sepsis , however the signs and symptoms may not be initially apparent in the elderly . an 87 year - old lady presented to the emergency department with a head injury following a fall with a transient loss of consciousness . her past medical history was notable for idiopathic parkinson s disease , ductal adenocarcinoma of the breast , primary hypertension , osteoarthritis and age - related macular degeneration . on examination she was haemodynamically stable , but pyrexic at 38.8 c , with a saturation of 92% on two litres of supplemental oxygen via nasal cannulae . her initial physical examination revealed only widespread inspiratory crepitations , with no other significant abnormalities . blood tests showed a white cell count of 31.4 109 l with a differential neutrophil count of 30.5 109 l , and a crp of 133 units . following auscultation and a chest x - ray showing mild consolidation she was diagnosed with chest sepsis complicated by mild acute kidney injury in the emergency department , and was transferred to a medical ward where she received intravenous amoxicillin , fluids , and respiratory support . it was thought that the fall was a consequence of her pre - existing co - morbidities and concurrent acute illness . on the second day of admission nursing staff noticed an undocumented firm , tender , dark red swelling , approximately 1 cm in diameter , on her right flank . this was initially felt to be a haematoma resulting from her fall , however the lump rapidly expanded over the course of the day , and a surgical opinion was sought . at the time of review the lump had a diameter of 5 cm , it was hot and erythematous with surrounding cellulitis and skin induration . a ct scan of the patient 's abdomen demonstrated a thick walled gallbladder with free fluid in the gallbladder fossa , and adjacent fat stranding in keeping with acute cholecystitis . moreover , the gallbladder fundus was seen extending close to the posterior abdominal wall where a 6 cm overlying soft tissue collection was identified , however there was no convincing communication between the two cavities . these radiological appearances were indicative of acute cholecystitis with a traumatic haematoma of the abdominal wall . as radiologically guided drainage was not available , the patient underwent surgical incision and drainage of the abdominal wall collection where 125 ml of bile - stained pus was released . a pus swab grew escherichia coli , and the patient completed a five - day course of intravenous co - amoxiclav . she made an excellent recovery and the drain was removed on the eighth post - operative day . a follow - up ultrasound scan showed a thin - walled gallbladder contracted around a solitary 21 mm calculus . additionally , a track of fluid was seen extending from the gallbladder fundus to the drain site , conclusively demonstrating a cholecystocutaneous fistula . the patient was reviewed in clinic four weeks later , the drain had been removed and the patient had made a full recovery and back to her premorbid state . as the gallbladder had ruptured and drained itself percutaneously this natural course of events will suffice as treatment and no further management such as a cholecystectomy is currently required . as radiologically guided drainage was not available , the patient underwent surgical incision and drainage of the abdominal wall collection where 125 ml of bile - stained pus was released . a pus swab grew escherichia coli , and the patient completed a five - day course of intravenous co - amoxiclav . she made an excellent recovery and the drain was removed on the eighth post - operative day . a follow - up ultrasound scan showed a thin - walled gallbladder contracted around a solitary 21 mm calculus . additionally , a track of fluid was seen extending from the gallbladder fundus to the drain site , conclusively demonstrating a cholecystocutaneous fistula . the patient was reviewed in clinic four weeks later , the drain had been removed and the patient had made a full recovery and back to her premorbid state . as the gallbladder had ruptured and drained itself percutaneously this natural course of events will suffice as treatment and no further management such as a cholecystectomy is currently required . spontaneous rupture of the gallbladder is a well - documented complication of acute cholecytitis . in 1890 , courvoisier described 499 cases of gallbladder perforation , of which 169 had cholecystocutaneous fistulae , however , as few as 25 cases have been reported in the literature in the past 50 years . this decline in incidence is likely due to improvements in imaging techniques , surgical treatments , and antibiotic availability in the intervening period . predisposing factors include biliary surgery , cholangiocarcinoma , trauma , or acute cholecystitis as in this case . when they do occur , external biliary fistulae are usually found in the right hypochondriac and lumbar regions , however other locations such as the right breast , groin , and gluteal region have been reported . a recent report estimates morbidity and mortality of gallbladder perforation at 57.7% and 9.5% respectively . given the high complication rate of the condition , ultrasound scanning is the preferred imaging modality for both cutaneous collections and the biliary tree , however our department did not have access to sonography out - of - hours . as a result , fortunately this did not preclude the patient from receiving the appropriate treatment , illustrating the importance of empirical intervention without relying on pre - operative imaging which can introduce unnecessary delay . additionally , this case highlights the importance of a full head - to - toe approach to physical examination when assessing any unwell patient , particularly in the context of sepsis . percutaneous abscesses arising from the gallbladder are a rare but potentially serious consequence of acute cholecystitis , and may present in a wide variety of locations here we present a case of silent cholecystitis which is a rare but significant cause of sepsis . we demonstrate the paramount importance of conducting a full body inspection in the septic patient , even when a source has been identified as there may be a dual source of sepsis as was evident in our patient . early surgical intervention is invaluable in suspected abscesses , regardless of the availability of pre - operative imaging .

highlightspercutaneous abscesses arising from the gallbladder are a rare but potentially serious consequence of acute cholecystitis , and may present in a wide variety of locations.silent cholecystitis is a rare but significant cause of sepsis.it is imperative to conduct a full body inspection in the septic patient , even when a source has been identified.early surgical intervention is invaluable in suspected abscesses , regardless of the availability of pre - operative imaging .

graves disease is a prevalent autoimmune disease that affects approximately 0.5% of the population and is the most common cause ( 50% to 80% ) of hyperthyroidism . antithyroid drugs have been used as standard therapy for graves disease and interfere with thyroid hormone synthesis . these drugs , however , have various side effects , including rash , joint pain , hepatic inflammation , and agranulocytosis . use of thionamides , either propylthiouracil or methimazole , causes agranulocytosis in 0.1% to 0.3% of treated patients . guillain - barre syndrome ( gbs ) is an acute paralytic illness that affects children and adults of all ages . the incidence of the disease worldwide is 0.6 to 4 cases per 100,000 . about two - thirds of cases have been associated with infection occurring 1 to 13 weeks prior to symptom onset , particularly respiratory infection and gastroenteritis . we describe a 57-year - old female patient with graves disease who suffered from methimazole - induced agranulocytosis and postinfectious gbs . a 57-year - old female presented with fever , abdominal pain , and diarrhea for 3 days . she had been diagnosed with graves disease 25 years prior and was taking methimazole , the dose of which had been increased from 5 to 20 mg twice a day , as of 10 weeks prior . when the patient visited a primary care hospital , her laboratory findings revealed leukopenia and anemia with a white blood cell ( wbc ) count of 570/ml , absolute neutrophil count of 10/ml , hemoglobin of 9.4 g / dl , and platelet count of 161,000/ml . the physician diagnosed her with methimazole - induced agranulocytosis and stopped methimazole . during the neutropenic period , the patient developed fever and cough . the pathogen of infection was not confirmed , and she took empirical antibiotics for pneumonia . clinical features were not improved , and the physician considered fungal pneumonia based on the findings of chest computed tomography . ten days after onset of respiratory symptoms , she suddenly presented with symmetric weakness of the lower extremities , which progressed to the upper extremities . a nerve conduction study ( ncs ) showed axonal - type motor polyneuropathy . intravenous immunoglobulin ( ivig ) was started for probable gbs , and she was referred to our hospital for further management . when the patient first came to our emergency room , a neurologic examination showed quadriplegia , flaccid dysarthria , and aflexia , all of which were worse than 5 days before . the findings of spinal tap were 218.9 mg / dl protein and 10/ml wbc in the cerebral spinal fluid , known as albuminocytologic dissociation , which supported gbs . the patient showed maximum weakness during the first 2 weeks after admission to the intensive care unit , but artificial ventilation was not needed . neurologic examination and follow - up ncs improved a month after the onset of weakness ( fig . the patient faced an impending thyrotoxic crisis with free thyroxine of 6.59 ng / dl ( reference range , 0.89 to 1.8 ) , thyroid - stimulating hormone ( tsh ) of 0.01 miu / ml ( reference range , 0.35 to 5.5 ) , and tsh receptor antibody of 107 the patient had been admitted for 40 days and received physical rehabilitation . with gradual neurologic improvement , she could ambulate using a wheelchair when discharged . after discharge , she maintained rehabilitation therapy for 6 months . the patient could walk without orthotics ; however , she felt fatigue after a long distance walk . gbs is an acute flaccid paralysis syndrome characterized by ascending weakness and sensory loss , usually provoked by antecedent infection , vaccination , and/or surgery . about two - thirds of patients have symptoms of an infection in the 6 weeks prior to the onset of gbs . in most studies , although the pathogen of infection is not often identified , the most frequently reported agents are campylobacter jejuni , epstein barr virus , cytomegalovirus , and mycoplasma pneumoniae . among these , c. jejuni is the most common cause of infection , reported in 30% to 40% of cases . molecular mimicry seems to be related to gbs development after infection , through the synthesis of autoantibodies against gangliosides of nerves . autoimmune reactions are found only in a small proportion of all exposed individuals , depending on host factors . host factors , including genetic polymorphisms , might influence the severity of gbs ; however , neither human leukocyte antigen class ii alleles nor single nucleotide polymorphisms have shown a consistent association with gbs . then , patients experience a plateau phase , which varies from days to several weeks or even months . the clinical outcome is usually favorable with a spontaneous and complete recovery , although 10% to 20% of patients show residual motor deficits . even 3 to 5 years after onset of gbs , about one - third of patients have to change their lifestyle due to residual disabilities . careful monitoring and control of vital signs are essential , and infections have to be prevented . van der meche and schmitz showed that treatment with ivig was at least as effective as plasmapheresis in acute gbs . currently , the american academy of neurology practice guidelines recommend that either plasmapheresis or ivig be applied for the treatment of immobile patients with gbs . two infectious events , which are considered precipitating factors for gbs , occurred within 3 weeks before the onset of weakness , and no pathogen was indentified . we presume that methimazole - associated agranulocytosis induced an opportunistic infection , which may have evoked gbs . the patient showed maximum weakness during the first 2 weeks , and neurologic signs improved after 4 weeks . even after her recovery for over a year , she still felt fatigue with daily activities . to our knowledge , there is no other case report of postinfectious gbs in a patient with graves disease .

both graves disease and guillain - barre syndrome ( gbs ) are autoimmune disorders caused by impaired self - tolerance mechanisms and triggered by interactions between genetic and environmental factors . gbs in patients who suffer from other autoimmune diseases is rarely reported , and the development of postinfectious gbs in a patient with graves disease has not been previously reported in the literature . herein , we report a patient with graves disease who developed postinfectious gbs during a course of methimazole - induced agranulocytosis .

seasonality is noted in various aspects of human behavior and functioning which have led to an increasing interest in their seasonality in the recent years . rectal foreign body insertion has been extensively described in the literature , with the earliest description dating back as long as the sixteenth century ( haft and benjamin ) and earliest case report published in 1919 . the incidence is increasing with up to 589 cases reported in the literature , and many more unreported cases presenting to the hospital . a variety of human behaviors such as sexual gratification ( most common ) , criminal assault or accident , and self - treatment of anorectal disease have been implicated . various theories on the effect of climatic changes including changes in air pressure , temperature , solar activity , and humidity have been postulated to affect human behavior and disorders relating to these . we aimed to examine the seasonal variation in the incidence of rectal foreign bodies in the us using a large inpatient database . we used the nationwide inpatient sample ( nis ) database to identify patients aged 18 years admitted with the primary diagnosis of the rectal foreign body ( international classification of diseases , 9 revision , clinical modification code 937 ) from 2009 to 2011 . nis is the largest publicly available all - payer inpatient care database in the united states and is sponsored by the agency for healthcare research and quality as a part of healthcare cost and utilization project . we used the edwards recognition and estimation of cyclic trend method to study the seasonal variation of the incidence of rectal foreign body and z - test to compare the seasonal incidences . edwards 's method was used to generate a fitted curve to a time series of monthly frequencies and generate the estimates of the seasonal intensity of occurrence ( peak - to - low ratio ) . a total of 3359 hospitalizations with the primary diagnosis of rectal foreign body were reported from 2009 to 2011 . the peak incidence of rectal foreign bodies was seen in october ( peak / low ratio 1.20 , 95% ci : 1.101.32 ) [ figure 1 and table 1 ] . seasonal trend for rectal foreign body admissions , 20092011 monthly distribution of rectal foreign body admissions , 2009 - 2011 one of the first studied patterns was a higher number of suicides and hospitalizations for affective disorders described in the spring , followed by the fall . similarly , the onset of affective episode in bipolar patient and use of electroconvulsive therapy were also found to be more common during the same time . rapid changes in the length of the days might disturb the circadian and sleep - wake cycles and lead to disruptive behaviors in the at - risk individuals . furthermore , interestingly , one of the studies found the highest frequency of sexual intercourse in spring and summer ; and lowest frequency in winter . whether rectal foreign body insertion as a means of sexual gratification occurs due to less sexual activity in the fall is a hypothesis that would require further study . further studies would be required to verify whether our findings of a higher incidence in the fall season are reflective of acute changes in the length of the days , climate , sleep - wake cycle , or decreased sexual intercourse at this time of the year . high suspicion at this time of the year may help promptly diagnose and avoid unnecessary investigations .

background : seasonality is noted in various aspects of human behavior and functioning which have led to an increasing interest in their seasonality in the recent years.aims:we aimed to examine the seasonal variation in the incidence of rectal foreign bodies in the us using a large inpatient database.methods:we used the nationwide inpatient sample database to identify patients aged 18 years admitted with a primary diagnosis of the rectal foreign body from 2009 to 2011 . we used the edward 's recognition and estimation of cyclic trend method to study the seasonal variation of the incidence of rectal foreign body and z - test to compare the seasonal incidences.results:a total of 3359 hospitalizations with primary diagnosis of the rectal foreign body were reported from 2009 to 2011 . the peak incidence of rectal foreign bodies was seen in october ( peak / low ratio 1.20 , 95% confidence interval [ ci ] : 1.101.32).conclusion : data on seasonal variation of rectal foreign bodies are extremely limited . further studies would be required to verify whether our findings of a higher incidence in the fall season are reflective of acute changes in the length of the days , climate , sleep - wake cycle , or decreased sexual intercourse at this time of the year . high suspicion at this time of the year may help promptly diagnose and avoid unnecessary investigations .

nevus lipomatosus cutaneous superficialis ( nlcs ) is a rare benign hamartomatous condition , which usually presents at birth or manifests in the first two decades of life . the classical presentation is with multiple painless soft pedunculated , yellowish cerebriform masses commonly located on the pelvic and gluteal region . we report here a case of nlcs with huge swellings on the back and prominent peau - d orange appearance at places . a 10-year - old boy presented with multiple humps on the upper and lower back , present for the preceding 2 years . starting as a single swelling on the upper back , it gradually increased in number and size to attain the present dimension . the surface showed fine wrinkling and peau - d orange appearance at places [ figure 2 ] . there was no evidence of ulceration or comedo - like plugs associated with the lesions . there was no underlying developmental anomaly , caf-au - lait macule , neurological abnormality or evidence of any systemic disease . histological examination showed beneath a normal epidermis , aggregates of mature adipocytes in the upper dermis [ figure 3 ] . the patient was counseled and referred to department of plastic surgery but was subsequently lost to follow - up . note the swellings over the lower back also close - up photograph showing fine wrinkling and peau - d orange appearance . besides , there are smaller satellite nodules in the surrounding skin photomicrograph showing a normal epidermis , increased melanization of the basal layer , aggregates of mature adipocytes in the upper dermis , normal vascularity and lack of infiltrate . nlcs is a rare hamartoma that is characterized by the presence of ectopic isolated adipocytes or mature adipose tissue in the dermis . morphologically , the lesions of classical nlcs are asymptomatic , soft , skin colored to yellow papulo - nodules , often coalescing to form plaques . the surface may be smooth , wrinkled , cerebriform , and associated with comedones and peau dorange texture . in our case , the lesions showed prominent peau dorange appearance . the distribution may be linear , systematized , zosteriform or along the lines of skin folds . the lesions are usually located on the pelvic girdle , lumbar area , buttocks and upper thighs , with rare instances of involvement of the scalp , face , shoulder , thorax and abdomen . the disorder may coexist with pigmentary conditions like cafe - au - lait macules , hypertrichosis , leukoderma , capillary hemangioma and trichofolliculoma . however , electron microscopic appearance of lipocytesin in close association with the capillaries suggests hamartomatous origin from the pericytes . we considered the clinical differential diagnoses of plexiform neurofibroma , smooth muscle hamartoma and leiomyoma cutis . the characteristic histopathological finding is the presence of ectopic fat cells in dermis , mostly around blood vessels . goltz syndrome is characterized by the absence of collagen and associated underlying deformities . the pedunculated appearance and later onset in life help to distinguish lipofibroma from nevus lipomatosus . our case had a few unique findings like multiple huge swellings on the back mimicking smooth muscle hamartoma and plexiform neurofibroma , presence of fine wrinkling and peau - d orange appearance at places .

nevus lipomatosus cutaneous superficialis ( nlcs ) is a benign dermatosis , histologically characterized by the presence of mature ectopic adipocytes in the dermis . we hereby report a case of a 10-year - old boy who presented with multiple huge swellings on the scapular regions and lower back . the lesions were surmounted by small papules , along with peau - d orange appearance at places . histology showed features consistent with nlcs . the case is being reported for the unusual clinical presentation .

in october 2011 , the u.s . national science advisory board for biosecurity ( nsabb ) was asked to review two papers for their potential as dual - use research of concern ( durc ) . these papers contained results on the adaptation of the highly pathogenic avian influenza a / h5n1 virus to mammalian hosts such that it could be transmitted via respiratory droplets from animal to animal . we found that this work had great potential for harm or misuse and recommended that the general conclusions highlighting the novel outcome be published , but that the manuscripts not include the methodological and other details that could enable replication of the experiments by those who would seek to do harm the recommendation not to publish scientific results was highly unusual and the first such recommendation by the nsabb membership . we are primarily a group of actively practicing basic research scientists , and we have consistently advocated for open publication practices . as per our advisory nature to the u.s . there was agreement by nsabb voting members for these recommendations , though the rationale of individual members as they arrived at the same conclusions varied . we had to judge the beneficial attributes of these research results against their potential to cause harm . over the last 7 years , nsabb has studied the issues associated with dual - use research , including risk / benefit assessments , and developed principles and tools to guide the deliberative process . much of this has been formalized in a series of reports and recommendations that are available at a public website ( http://oba.od.nih.gov/biosecurity/biosecurity.html ) . despite this experience and carefully crafted guidance , there are points in the deliberations where uncertainties and even contradictory information necessitate subjective decisions . is there a clear and bright line to be crossed or is this a more nebulous and fuzzy region of yes or no for this research ? i will present only my personal rationale and how i came to the strong conclusion that this work had the potential to be very dangerous and that its communication should be restricted at this time . i heard from members of the influenza research community and reviewed the world health organization ( who ) data indicating that this avian virus had a very high mortality rate in humans . while the influenza a / h5n1 virus rarely infects humans , when it does it causes catastrophic disease . we are all aware of the rapid global spread of human - adapted influenza both on a yearly basis and during less common pandemics . the documented devastation of the 1918 influenza pandemic , even with its lower mortality rate , was a testament to the powerful potential of influenza . the thought of combining the high human mortality of influenza a / h5n1 with a highly transmissible human - adapted phenotype was sobering . a pandemic by such a pathogen could reasonably be concluded to cause such devastation that it should be prevented at all costs . i carefully considered how restricting the information would compromise scientific research progress and even how it would hinder public health efforts to prevent such a horrific pandemic . i know from firsthand experience that the free flow of information is part of the best and most productive research endeavors and that any restrictions burden the progress . the conclusion that this virus could be adapted to mammal - to - mammal respiratory transmission was , in my mind , the foremost beneficial part of the research . with this firm conclusion in hand , policy makers , granting agencies , public health officials , and vaccine and drug developers should have both the motivation and a compelling argument to move forward to improve our influenza - fighting infrastructure . the details of the research , on the other hand , would add little to this short - term effort and could enable someone to replicate the work in a short period of time . the short - term negative consequences of restricting experimental details seemed small in contrast to the large consequences of facilitating the replication of these experiments by someone with nefarious intent . current public health surveillance and public health responses would be enhanced little by these details . this comes not only from my own professional experience in globally tracking dangerous pathogens but also from personally watching the 2009 h1n1 influenza pandemic spread globally . it was impossible to contain , and i believe that the same would be true for an h5n1 influenza pandemic . we were lucky in that the h1n1 virus has low virulence , but the best current data suggest that this would not be the case for the h5n1 virus . publishing a detailed experimental protocol on how to produce a highly transmissible h5n1 virus in a highly regarded scientific journal is a very bad idea . since our recommendations were announced in mid - december , there has been considerable response from scientists , policy makers , funding agencies , and global health organizations . there have been criticisms that restriction of the publications was insufficient and that even performing such experiments should be restricted . the debate has touched upon both biosafety and biosecurity aspects , with some calling for the destruction of the virus or for moving all such research to the highest safety level , biosafety level 4 ( bsl-4 ) . the nsabb has not yet offered specific recommendations concerning these statements , and my personal opinions are relatively unimportant . what is gratifying and essential is that the debate is occurring ; it is occurring on an international stage , and it is occurring rapidly . in the midst of nsabb deliberations and formulation of our recommendations , the need for a global debate to develop policy has always been in our discussions . why should the nsabb be telling the world what to do ? why has not the world already had these discussions and debates ? how could the nsabb stimulate the process such that global leaders in science , policy , and public health engage in a broad - based conversation on these issues ? the specific nsabb recommendations seem to have been accepted and are being implemented by two research groups and two scientific journals ; more importantly , the research issue of adapting an avian virus to mammals , potentially humans , is a topic that is being widely discussed . the who has agreed to participate and facilitate in policy development . and the u.s . research and public policy will be developed from this global engagement process , a process that should increase the public s confidence in the scientific endeavor , in scientists ethical behavior , and in the transparency that a free research environment embraces .

abstractthe national science advisory board for biosecurity ( nsabb ) has recommended that two scientific papers concerning the laboratory adaptation of avian h5n1 influenza virus to mammal - to - mammal respiratory transmission restrict their content to prevent others from replicating their work . after hearing from experts in the field of influenza research and public health , the benefits of the research were deemed less important than the potential negative consequences . the evaluation followed established nsabb procedures and prior policy recommendations for identifying dual use research of concern ( durc ) . this recommendation was received by the united states government , endorsed and forwarded to the research teams and scientific journals involved with the publications .

in the previous issue of critical care , friesecke and colleagues demonstrate that the survival rate of patients with severe lactic acidosis due to metformin accumulation can be strikingly higher than expected based on the initial clinical evaluation . metformin is nowadays the first - line drug of choice for the treatment of adults with type 2 diabetes . this drug is the sixth most frequently prescribed in the usa ( > 50 million prescriptions in 2009 ) and is taken by almost 1.5% of the italian population . metformin is a safe drug when correctly used in properly selected patients . in particular , no cases of lactic acidosis ( a relatively common side effect of other biguanide compounds ) were reported in 347 trials with 70,490 patient - years of metformin use . real life can differ from research settings , however , and lactic acidosis has been repeatedly , although rarely , observed in patients treated with metformin . the number of inquiries to the swedish poison information centre for metformin intoxication has increased 10 times during the past decade , with 25 cases of severe lactic acidosis reported in 2007 and 2008 . according to the american association of poison control centers forty - nine cases of lactic acidosis and accidental metformin accumulation were reported to the poison control centre of pavia ( italy ) from january 2005 to august 2010 , resulting in 11 deaths . since metformin use is constantly increasing - there has been a 10 to 15% rise in prescriptions per year in the usa and italy - related cases of lactic acidosis may become less rare . the term metformin - associated lactic acidosis refers to any case of lactic acidosis that develops in a patient treated with metformin , with no further mechanistic insight . in most of the cases , however , lactic acidosis can not be directly attributed to metformin use but rather depends on concomitant low cardiac output , anemia , hypoxemia or liver failure . the term metformin - induced lactic acidosis specifically refers to cases that can not be explained by any major risk factor other than metformin overdose . the distinction between these two entities is sometimes very subtle and metformin accumulation may coexist with other risk factors , all contributing to the pathogenesis of lactic acidosis . the present case series includes 10 patients admitted to intensive care with lactic acidosis and metformin accumulation due to renal failure . at admission , arterial ph was 6.75 0.13 and lactatemia was 19 5 mmol / l . the simplified acute physiology score ii was 88 23 and the predicted mortality was 96% . eight ( 80% ) patients had a cardiac arrest during their stay in intensive care . treatment consisted of vital function support and renal replacement therapy . despite the dramatic severity of clinical presentation , hospital survival was 50% . conversely , there were no survivors out of 31 patients with similarly severe lactic acidosis from other causes ( mainly cardiogenic , septic or hemorrhagic shock ) who were admitted to the same institution during the same period of time . this finding is in line with previous observations . in 49 patients treated with metformin who developed severe lactic acidosis , survival was 17% among those with no drug accumulation ( that is , lactic acidosis was actually due to another precipitating event ) and was 71% in those with metformin accumulation , despite a similar severity of hyperlactatemia . in another series , one out of 10 ( 10% ) patients with lactic acidosis probably due to metformin accumulation actually died despite an initially predicted mortality of around 55% . we have recently reviewed the data for 24 critically ill patients with lactic acidosis and proven or probable metformin intoxication . despite an expected mortality of 70% , observed mortality was 21% . even patients with initial arterial ph down to 6.62 , lactatemia up to 33 mmol / l or simplified acute physiology score ii as high as 87 managed to survive to hospital discharge . that lactic acidosis carries lactic acid per se , however , is unlikely to be the explanation for this association . this response provides some energy and a chance for cells to survive , even when oxygen availability or utilization are defective . cancer cells in a way provide the best evidence for lactate overproduction being an efficient response to hypoxia . by mainly relying on anaerobic metabolism , malignant cells can not only survive but even proliferate in a hypoxic environment , so that tumor growth can exceed angiogenesis . according to the theory of lactate shuttles proposed by brooks acidosis itself may arise as an adaptive response to inadequate energy provision and may extend cellular viability . the prognosis of lactic acidosis primarily depends on the underlying mechanism and on its reversibility . when lactic acidosis is due to metformin accumulation , then renal replacement therapy can efficiently remove the toxic substance ( that is , metformin and not lactate ! ) and prognosis can be surprisingly good . the situation can be much more complex and less easily reversible when lactic acidosis is primarily due to severe hypoxia or tissue hypoperfusion . based on present and past observations , one may conclude that the decision to treat ( or not to treat ) a patient with suspected metformin - induced lactic acidosis can not be based only on the severity of clinical presentation . we personally believe that treatment of the critically ill patient should always include drug removal , as long as metformin accumulation is thought to be responsible for severe lactic acidosis . since a plasma metformin dosage is rarely available in most centers , intoxication should be considered highly probable whenever lactic acidosis and renal failure are uncommonly severe , other primary explanations are not evident and chronic metformin use is reported .

metformin is a safe drug when correctly used in properly selected patients . in real life , however , associated lactic acidosis has been repeatedly , although rarely , reported . the term metformin - induced lactic acidosis refers to cases that can not be explained by any major risk factor other than drug accumulation , usually due to renal failure . treatment consists of vital function support and drug removal , mainly achieved by renal replacement therapy . despite dramatic clinical presentation , the prognosis of metformin - induced lactic acidosis is usually surprisingly good .

hemoglobinopathies are important inherited disorders with high prevalence in many tropical countries ( atweh et al 2003 ) . in structurally abnormal hemoglobins , the following mechanisms can be invoked : single nucleotide base substitutions leading to amino acid replacement or chain termination variants ; nucleotide deletions ( or additions ) leading to deletion and frameshift variants ; and nonhomologous crossing over leading to the production of fused globin chains ( forget 1979 ) . the molecular basis of the hemoglobinopathies , disorders characterized by the absence of , or decreased , synthesis of alpha globin or beta globin chains , is quite heterogeneous ( forget 1979 ) . the mutation in the gene coding for alpha globin or beta globin chains is the underlying pathogenesis of hemoglobinopathies ( atweh et al 2003 ) . clinical manifestations of these disorders vary from mild to severe presentations ( atweh et al 2003 ) . predicting protein nanostructure and function is a great challenge in proteomics and structural genomics . identifying the point vulnerable to mutation is a new trend in research on disorders at the genomic and proteomic level ( levin et al 2002 ; lee and wang 2005 ) . generally , disordered regions in proteins often contain short linear peptide motifs that are important for protein function . identification of the peptide motifs in the amino acid sequence can give a good prediction of the weak linkages in a protein ( levin et al 2002 ; lee and wang 2005 ) . a bioinformatics analysis was peformed to determine positions that tend to correspond with peptide motifs in the amino acid sequence of alpha globin and beta globin chains . the database expasy ( gasteiger et al 2003 ) was used for searching the amino acid sequence of normal human alpha globin and beta globin chains . the derived sequences were then used to identify the weak linkage . to identify the weak linkage in alpha globin and beta globin chains , a new bioinformatics tool , globplot ( linding et al 2003 ) , was used . globplot is a web service that allows the user to plot the tendency within the query protein for order / globularity and disorder ( linding et al 2003 ) . it successfully identifies interdomain segments containing linear motifs , and also apparently ordered regions that do not contain any recognized domains ( linding et al 2003 ) . the database expasy ( gasteiger et al 2003 ) was used for searching the amino acid sequence of normal human alpha globin and beta globin chains . to identify the weak linkage in alpha globin and beta globin chains , a new bioinformatics tool , globplot ( linding et al 2003 ) , was used . globplot is a web service that allows the user to plot the tendency within the query protein for order / globularity and disorder ( linding et al 2003 ) . it successfully identifies interdomain segments containing linear motifs , and also apparently ordered regions that do not contain any recognized domains ( linding et al 2003 ) . twenty - two positions were identified for the alpha globin chain ( figure 1 ) . the disorders were found at positions 38 , 3842 , 4651 , and 75 - 79 . forty - six positions were identified for the beta globin chain ( figure 2 ) . the disorders were found at positions 61146 . identified positions ( in capitals ) that correspond with peptide motifs in amino acid sequence of alpha globin . identified positions ( in capitals ) that correspond with peptide motifs in amino acid sequence of beta globin . structural aberration is believed to be the main underlying pathogenesis in hemoglobinopathy ( atweh et al 2003 ) . some disorders are described as a single substitution with other effects on the sequence frame ; other disorders are mentioned as a frameshift ( atweh et al 2003 ) . there are many reported mutations of globin and there are many undetermined ones . in the present study , an algorithm was used to identify the positions in the amino acid sequences of alpha globin and beta globin chains that can mutate . many positions were identified ; some are known and others are newly discovered . of interest , more points with known mutations have been reported for beta globin than for alpha globin ( atweh et al 2003 ) . the present study shows that weak linkages in the alpha globin and beta globin chains can be identified and can provide good information for predicting possible new mutations that can lead to new hemoglobin disorders .

hemoglobinopathies are important inherited disorders with high prevalence in many tropical countries . prediction of protein nanostructure and function is a great challenge in proteomics and structural genomics . identifying the point vulnerable to mutation is a new trend in research on disorders at the genomic and proteomic level . a bioinformatics analysis was performed to determine the positions that tend to correspond with peptide motifs in the amino acid sequence of alpha and beta globin chains . to identify the weak linkage in alpha globin and beta globin chains , a new bioinformatics tool , globplot , was used . for the alpha globin chain , 22 positions were identified : the disorders were found at positions 38 , 3842 , 4651 , and 7579 . for the beta globin chain , 46 positions were identified : the disorders were found at positions 61146 . the study showed that weak linkages in alpha globin and beta globin chains can be identified and provide good information for predicting possible new mutations that could lead to new hemoglobinopathies .

tenofovir , a nucleotide reverse transcriptase inhibitor is approved by us food and drug administration for treatment of human immunodeficiency virus ( hiv ) infection in adults . it is generally well tolerated ( except for flatulence ) . however , rare episodes of acute renal failure and fanconi syndrome have been reported . fanconi syndrome is a generalized defect in proximal renal tubule transport involving amino acids , glucose , phosphate , uric acid , potassium , bicarbonate and proteins a 43-year old , hiv positive man was treated with stavudine , lamivudine and nevirapine as per national aids control organization ( naco ) guidelines for 30 months . however , his cd4 count ( 56 cells/l ) and plasma viral load ( 1,27,734/mm of blood ) failed to improve . hence the patient was advised the second line antiretroviral therapy consisting of tenofovir 150 mg plus lamivudine 150 mg twice a day along with boosted lopinavir ( lpv ) 200 mg + 50 mg twice a day . he was also prescribed co - trimoxazole 960 mg once a day , along with multivitamins and folic acid . after a year on this therapy , patient complained of increased frequency of urination , ankle edema and knee pain . on investigations , g / l ) and glycosuria ( 30 mmol / l ) on two subsequent investigations on dates 28/09/2010 , 27/10/2010 . his blood pressure was 118/78 mm of hg , rbs was 132 mg / dl and radiological appearance of kidneys and urinary bladder was also normal . considering the clinical presentation and time course of events tenofovir was suspected to be the causal drug ( stopped on 5 january 2011 ) and patient was switched on alternative regimen consisting of abacavir 300 mg and lamivudine 150 mg , five tablets orally , twice a day , along with didanosine 400 mg at bed time on 5 january 2011 . after 5 months , increased urinary frequency , ankle edema and pain in knees were resolved and serum phosphate returned to normal level ( 2.8 mg / dl on 30/5/2011 ) . glycosuria become absent 1-month after the drug stopped , as investigations were done one dates 3/2/2011 , 28/2/2011 and 27/6/2011 . causality assessment of the adverse drug event was carried out using who- uppsala monitoring centre ( umc ) criteria and naranjo 's scale . further , the preventability assessment carried out using modified schumock and thornton criteria showed that the adr was probably preventable . it is available as tenofovir disoproxil ( prodrug ) that has better oral bioavailability . in this case , the patient developed glycosuria , albuminuria and hypophosphatemia after receiving tenofovir based antiretroviral therapy for 1 year . the laboratory and routine clinical examination had ruled out the chronic kidney disease , diabetes and hypertension . a possibility of primary fanconi syndrome was ruled out since the patient had no history suggestive of this condition during the past . tenofovir was discontinued and a regimen consisting of abacavir , lamivudine and didanosine along with lopinavir - ritonavir ( lpv / r ) combination was started . the patient recovered and renal functions returned to normal , hence , suggesting the possibility of tenofovir induced fanconi syndrome . confirmed cases of fanconi syndrome due to tenofovir have been reported worldwide . in india also teneofovir associated renal dysfunction have been reported . the mean duration of therapy with tenofovir before developing fanconi syndrome is reported to be 11 months and it was discontinued in all these cases and subsequently renal function tests were normalized . an important observation made in all these patients was the concomitant treatment with boosted lpv . the risk of developing nephrotoxicty in patients prescribed tenofovir is nearly 4 times higher with boosted lpv than with nucleoside reverse transcriptase inhibitor ( nrti ) based therapy . pharmacokinetic studies have shown that concomitant therapy with lpv / r increases the plasma concentration of tenofovir . tenofovir is predominantly secreted from the primary renal tubule via multidrug resistance ( mdr-2 ) protein . ritonavir inhibits mdr-2 protein and leads to accumulation of tenofovir in primary renal tubules resulting in toxicity . proposed mechanism for this drug - induced proximal renal tubular toxicity include epithelial cell mitochondrial dna depletion and/or direct tubular cytotoxicity . hence , it is hypothesized that drug interaction between tenofovir and lpv / r combination may be responsible for this adverse drug reaction ( adr ) . india has a large pool of hiv infected patients and naco has recommended tenofovir as a second line antiretroviral drug . a substantial number of patients are prescribed this drug in combination with a protease inhibitor . it is therefore , recommended that patients receiving this combination should be screened for renal functions and electrolyte balance from the start of therapy and periodically during first year .

tenofovir was introduced as a second line drug for the treatment of human immunodeficiency virus ( hiv ) infection in india in december 2009 . although rare , renal toxicity is a recognized adverse drug reaction ( adr ) of this drug , especially when administered with boosted lopinavir - ritonavir . in this case , an hiv positive patient receiving tenofovir based antiretroviral therapy ( art ) for last 1 year developed albuminuria , glycosuria and hypophosphatemia . renal function tests and random blood sugar were within normal limits . he was diagnosed as a case of tenofovir induced fanconi syndrome . tenofovir was discontinued and patient was prescribed an alternate regimen . five months later clinical symptoms and renal functions returned to normal . a pharmacokinetic interaction between tenofovir and ritonavir may have resulted in the toxicity . a periodic monitoring of renal functions is desirable in patients on tenofovir based art .

since standard preclinical models have notoriously overestimated the clinical potential of her tkis , we challenged the traditional approach to evaluating tkis in these models . traditionally , signaling inhibitors are thought to have a continuous suppressive effect through rapid and sustained inhibition of their direct molecular targets and downstream signaling events . this notion of drug therapy may be too simplistic . clearly , continuous exposure to a growth factor stimulus does not produce continuous high output downstream signaling . rather , it leads to a sequelae of signaling events , programmed by negative and positive feedback signaling , until establishment of a new steady state in the presence of continued stimulus . we find here that continuous exposure to tkis similarly leads to a sequence of signaling events that manifest over time , until a new steady state is reached . with this new perspective , we report that her3/pi3k / akt signaling is not effectively inhibited by current tkis . in particular , the allocation of kinase and signaling functions to different members within the her family allows the signaling substrate her3 to restore signaling activity despite significant inhibition of her2 kinase , in effect buffering her3/pi3k / akt signaling against an incomplete loss of her2 kinase function . this inherent signal buffering capacity allows tumor cells to evade the pro - apoptotic effects of tkis resulting in a significant loss of their anti - tumor activity . the highly effective treatment of her - driven cancers may require drugs with much higher potency or drugs that completely inactivate her kinase function . irreversible tkis , although more potent , are subject to similar limitations . due to their reactive groups and reduced selectivity , future highly selective irreversible inhibitors may turn out to be more effective . until highly specific and fully inactivating drugs can be designed , combination treatment strategies designed to undermine the resiliency of her family signaling may offer the most promising approach in the near future . in addition , inhibition of autophosphorylation activity deceptively overstates the efficacy of tkis and is a poor in vivo biologic marker . the signal buffering capacity endowed by the separation of kinase and signaling functions to different family members in the her kinase family attests to an evolutionary advantage conferred by the loss of catalytic activity in the her3 protein kinase . this can shed light on why approximately 10% of the human kinome appears to be catalytically inactive 28 . reagent sources are detailed in supplementary materials . for immunofluorescence studies , cells grown on fibronectin coated cover slips were treated as indicated , fixed in 4% paraformaldehyde , permeabilized , and stained with the indicated primary antibodies and fitc conjugated secondary antibodies . apoptotic cells were identified and quantified by analysis of annexin v binding using the annexin v - fitc apoptosis detection kit ( calbiochem ) according to the manufacturer s instructions , or by their sub - g1 dna content and quantified by facs analysis as previously described 30 . all experimental arms were done in duplicate and displayed as averages with standard of deviation error bars . cells were seeded at a density of 300,000 cells per well in 12-well plates and transfected the following day . for sirna transfections 100300nmol of sirna ( dharmacon ) was premixed with lipofectemine2000 in opti - mem media and then added to each well . for plasmid transfections , 2 ug of plasmid dna was premixed with lipofectamine2000 in opti - mem media and added to wells for 6 hours . freshly prepared sulfo - nhs - ss - biotin was added to the final concentration of 0.5 mg / ml in pbs . following 45min incubation at 4c cells cells were rinsed twice with pbs and incubated with 10 m of freshly prepared h2dcfda in phenol - red free media for 45 min at 37c . reagent sources are detailed in supplementary materials . for immunofluorescence studies , cells grown on fibronectin coated cover slips were treated as indicated , fixed in 4% paraformaldehyde , permeabilized , and stained with the indicated primary antibodies and fitc conjugated secondary antibodies . apoptotic cells were identified and quantified by analysis of annexin v binding using the annexin v - fitc apoptosis detection kit ( calbiochem ) according to the manufacturer s instructions , or by their sub - g1 dna content and quantified by facs analysis as previously described 30 . all experimental arms were done in duplicate and displayed as averages with standard of deviation error bars . cells were seeded at a density of 300,000 cells per well in 12-well plates and transfected the following day . for sirna transfections 100300nmol of sirna ( dharmacon ) was premixed with lipofectemine2000 in opti - mem media and then added to each well . for plasmid transfections , 2 ug of plasmid dna was premixed with lipofectamine2000 in opti - mem media and added to wells for 6 hours . freshly prepared sulfo - nhs - ss - biotin was added to the final concentration of 0.5 mg / ml in pbs . following 45min incubation at 4c cells cells were rinsed twice with pbs and incubated with 10 m of freshly prepared h2dcfda in phenol - red free media for 45 min at 37c .

oncogenic tyrosine kinases have proven to be promising targets for the development of highly effective anticancer drugs . however her family tyrosine kinase inhibitors ( tkis ) show only limited activity against her2-driven cancers despite effective inhibition of egfr and her2 in vivo 18 . the reasons for this are unclear . signaling in trans is a key feature of this multimember family and the critically important pi3k / akt pathway is driven predominantly through transphosphorylation of the kinase - inactive her3 9,10 . we report that her3 and consequently pi3k / akt signaling evade inhibition by current her family tkis in vitro and in tumors in vivo . this is due to a compensatory shift in her3 phosphorylation - dephosphorylation equilibrium driven by increased membrane her3 expression driving the phosphorylation reaction and reduced her3 phosphatase activity impeding the dephosphorylation reaction . these compensatory changes are driven by akt mediated negative feedback signaling . although her3 is not a direct target of tkis , her3 substrate resistance undermines their efficacy and has thus far gone undetected . the experimental abbrogation of her3 resistance by sirna knockdown restores potent pro - apoptotic effects to otherwise cytostatic her tkis , re - affirming the oncogene - addicted nature of her2-driven tumors and the therapeutic promise of this oncoprotein target . however , since her3 signaling is buffered against an incomplete inhibition of her2 kinase , much more potent tkis or combination strategies are required to effectively silence oncogenic her2 signaling . the biologic marker to guide her tkis should be the transphosphorylation of her3 .

the tropical medicine foundation of amazonas is a tertiary care center for infectious diseases in manaus ( 38s , 601w ) . in 2001 and 2002 , a total of 13,056 cases of malaria were diagnosed in this institution ( 11,251 p. vivax ) , representing 65.1% of the total cases from manaus . during the same period , 358 ( 3.2% ) a retrospective analysis was performed of case - patients who fulfilled the malaria severity criteria of the world health organization ( who ) ( 8) . these patients had an exclusive diagnosis of p. vivax malaria by thick blood smear ( reviewed 2 times by experienced microscopists ) and pcr , according to the technique described elsewhere ( 9 ) . pcr was performed on whole blood from all patients with p. vivax malaria , confirmed by microscopy and any p. falciparum severity criterion recommended by who . full clinical information was available from the patients charts , and serologic tests for dengue virus , leptospira spp . , and hepatitis a , b , and c viruses were performed on available serum samples stored at 20c . patients were routinely discharged only after parasitologic clearance and clinical recovery . until 2006 , chloroquine was still prescribed for patients with severe cases at a dose of 10 mg / kg on the first day and 7.5 mg / kg on the second and third days , followed by primaquine ( 0.5 mg / kg / day for 7 days ) , according to the brazilian ministry of health guidelines . in 2006 , who formally recommended the treatment of severe vivax malaria to be the same as that for severe falciparum malaria , because of the risk for an unrecognized mixed infection ( 8) . seventeen patients were included in the analysis , and their clinical and laboratory data are shown in table 1 and table 2 , respectively . all patients received chloroquine ( orally or through a nasogastric tube ) and primaquine . acute respiratory distress syndrome ( ards ) ( diffuse interstitial and alveolar infiltrate by chest radiograph and partial o2 pressure 40 mm hg by arterial gas analysis ) developed in patient 11 two days after she received chloroquine , and she died 3 days later . this patient had a negative thick blood smear from day 3 of treatment with choloroquine . none had clinical symptoms of malaria , and all thick blood smears were negative at days 7 , 14 , and 28 . * who , world health organization ; icu , intensive care unit ; hav , hepatitis a virus ; ards , acute respiratory distress syndrome ( tachypnea , shortness of breath , and signs of hypoxemia ) . hemoglobin < 7 g / dl in adults and < 5 g / dl in children . who , world health organization ; ast , aspartate aminotransferase ; alt , alanine aminotransferase . the patients in whom complications developed exhibited a remarkably wide age range ( 28 days80 years ) . this age range is similar to that seen in other case series from latin america , such as in hospitalized children from venezuela with severe anemia that required blood transfusions ( 10 ) and in adults from rondnia ( a state in the western brazilian amazon ) who had severe anemia , jaundice , acute renal failure , ards , and shock ( 11 ) . p. vivax malaria with ards has been reported in travelers who acquired the infection in manaus ( 12,13 ) . the finding of severe anemia in 4 of 7 children highlights the relevance of this complication in p. vivax infection ( figure ) , as shown in a prospective study from papua , indonesia ( 14 ) . nine patients sought treatment for cholestatic jaundice ; for 8 , jaundice was the only complication . 1 ) with severe anemia ( hemoglobin level 3.6 g / dl ) , showing intense pallor , compared with the hand of a healthy physician . photograph provided by authors . the concomitant diagnosis of hepatitis a virus infection in patient 3 ( table 1 ) indicates that other infectious diseases should be excluded when characterizing severe p. vivax malaria . also of note is the presence of thrombocytopenia in 15/17 patients ( none had clinical bleeding ) , which suggests that this hematologic complication may be a surrogate marker of severity . the wide range of parasitemia found in our patients does not enable us to comment on the value of this variable as a determinant of severity . sixteen patients recovered without the use of antimicrobial drugs ; therefore , it is highly improbable that bacterial sepsis was a factor for severity in our case series . in unstable transmission areas ( < 0.1 autochthonous case per 1,000 persons per year ) , malaria in older patients may pose an additional problem because chronic diseases ( e.g. , arterial hypertension and diabetes ) may predispose a patient to clinical decompensation . in vivo chloroquine resistance was not detected in any of the cases that were followed up , despite recent confirmation of the phenomenon in this same locality ( 15 ) . because a reliable molecular marker of chloroquine resistance is lacking and parenteral artemisinin derivatives are recommended for treatment of patients with severe p. vivax malaria , studies that assess clinical severity and chloroquine resistance would be unethical . however , our findings suggest that chloroquine resistance would be a problem for individual patients and that the determinants of this resistance need to be clarified . clearly , areas with chloroquine - resistant p. vivax also report severe p. vivax malaria , but we believe that these studies are not able to establish any firm causality . the finding of both phenomena in some areas may simply reflect high transmission of this species . our retrospective review illustrates the spectrum of severe p. vivax malaria in manaus , and these results parallel the increasing clinical severity described in malaria - endemic areas such as papua ( indonesia ) and india . these severe p. vivax cases contribute to increased public health costs because of increased hospitalization and the need for intensive care and blood transfusions . the major complications in patients who required hospitalization were jaundice and severe anemia , although whether these complications were responsible for deaths is undetermined . however , who criteria formerly defined for p. falciparum malaria seem to be applicable to most of the severe p. vivax malaria cases reported in hospital - based studies in the literature . pcr should be performed to rule out mixed infections and other common infectious diseases so that reports from different parts of the world are comparable . despite the small number of patients , our data corroborate previous findings of severe disease found in areas where chloroquine - resistant p. vivax is being reported but suggest that establishing direct causality is not straightforward . we urgently need to know which clinical complications in p. vivax malaria are associated with death to validate severity criteria . a valid biomarker for chloroquine resistance would also enable associative studies to determine the association between resistance and severity .

we describe a case series of 17 patients hospitalized in manaus ( western brazilian amazon ) with pcr - confirmed plasmodium vivax infection who were treated with chloroquine and primaquine . the major complications were jaundice and severe anemia . no in vivo chloroquine resistance was detected . these data help characterize the clinical profile of severe p. vivax malaria in latin america .

global digital pathology networks between pathology laboratories , academic centers and commercial entities have capitalized on whole slide imaging ( wsi ) technology , the internet and cloud services . at the university of pittsburgh medical center ( upmc ) we launched a telepathology consultation service with kingmed diagnostics laboratory in guangzhou , china . wsi submitted for consultation resided on the client 's server ( hammamatsu ndp.serve ) in china . pathology consultants from pittsburgh in the usa used the web portal to securely access these images on the client 's server . workflow ( e.g. , case triage and transcription ) and reporting was incorporated into this web - based application . with the aforementioned information technology client - specific infrastructure , we were able to initially avoid lengthy transfers of large wsi files over the internet . however , after 2 years of practice network latency issues increased that negatively impacted viewing of wsis and hence interpretation of digital consultation cases . reasons for the delay in processing network data were often hard to determine and , therefore , resolve . ping tools identified decreased download and upload speeds for connections to servers in china compared with those located locally . although the current telepathology workload is manageable , the delays experienced by pathologists ( lengthy time waiting for images to open , pixelated images when panning and zooming ) were frustrating . therefore , the aim of our study was to explore various image file transfer solutions to improve the viewing experience of digital consult cases . to solve ongoing latency issues , two attempts were made to transfer wsi files from china to an image server at upmc in our data center . the first solution employed an open source product ( fast data transfer [ fdt ] , by cern . a command line utility was established to facilitate a batch transfer process of image files [ figure 1 ] . aspera uses user datagram protocol ( udp ) , does not involve data compression , and permitted immediate file transfers that did not need to be initiated by a user [ figure 2 ] . the aspera software was configured using a hot folder for automated file transfer . with this set up , every time a file was dropped into the folder on the server in china it was immediately transferred over to the upmc server . since aspera can be configured to take up as much of the sender 's bandwidth network pipe as needed , our team set it up to use 80 mbps of the client 's 100 mbps internet connection to transfer files off business hours . once images were successfully transferred to the usa , when consultants logged into the web - based portal to access their digital pathology cases they were offered the option to view digital slides launched either from the server in china or locally in pittsburgh . process steps involved using an open source tool to transfer images process steps involved using aspera to transfer images table 1 compares file sizes , transfer times , and image quality parameters for the two transfer methods used . transferring files with the open source product fdt provided fast transfer speeds of 23 mbps , but suffered from intermittent dropped connections . although these interruptions varied throughout the day , they were most marked at 6 am in pittsburgh ( eastern time zone ) . the image transfers with fdt required 515 min of extra processing time to zip files and involved a batch process . it was also noted that the open source zip utility did not compress files much more than they were already being compressed by the nanozoomer scanner ( nanozoomer 2.0-ht , hamamatsu ) . employing the commercial file transfer software , aspera permitted much faster ( 75100 mbps ) transfer speeds . use of hot folders did not add any extra processing time to the transfers and avoided files having to sit in a queue . in addition , the file sizes being transferred with fdt were larger because the open source software zipped up multiple images ( anywhere from 10 to 30 files ) into one file , whereas aspera sent over one image file at a time . fdt was used to transfer 8 cases ( 101 slides ) including hematopathology and breast / gynecologic consults . all of these cases comprised large specimens that contained anywhere from 8 - 15 slides , except for 1 biopsy that included 2 slides . the open source software file sizes represent multiple whole slide images batched together , whereas only one file at a time was transmitted with the commercial software successful global telepathology requires dedicated image management , which includes fast and reliable movement of digital data . traditional transmission of data over the internet can be slow due to congestion , degradation , erratic transfer speed , and bottlenecks ( e.g. , packet loss ) . attempts in radiology to improve data transmission time between medical imaging systems have been based mainly on image compression . according to the american telemedicine association ( ata ) clinical guidelines for telepathology , compression technology may be applied with telepathology so long as it does not compromise the image for clinical use . the guidelines state that reversible ( lossless ) compression may always be used as there is no impact on the image . however , irreversible ( lossy ) compression may be used to reduce transmission time or storage space only if the resulting quality is sufficient to reliably perform the clinical task . fortunately , prior studies have shown that image compression does not appear to noticeably affect image quality and diagnostic accuracy , at least for store - and - forward telepathology . use of compression methods to improve data transmission time may not always be effective in high - speed networks . newer transmission methods and bulk data transport tools , such as aspera , which use alternative technology ( e.g. udp - based application - level protocols vs. traditional tcp - based transport ) offer innovative solutions . for example , some investigators were able to improve radiology image transmission time by using parallelism ( increased number of parallel network streams ) without compression . it is important to be aware , however , that overwhelming a network with too many streams may cause congestion and therefore actually have a negative effect on throughput achieved . despite the fact that transferring files from china to our local server delayed the availability of images for consultants to view by up to 24 h , this measure improved the overall turn - around time of digital consultations because pathologists found it easier to work with locally stored wsis . although we resolved the latency issue impacting our consulting pathologists , the exact reason causing this latency has not been clarified . network latency is not limited to file transfers between china and the usa , but can be an issue anywhere in the world , even within the usa . although biological materials ( slides and blocks with human tissue ) can not leave china to be sent to our institution , we are not aware of any regulations restricting the movement of images out of china . it is unclear how our telepathology experience was impacted by the golden shield project ( i.e. great firewall of china ) , which is china 's censorship of the internet . using a combination of firewalls and proxy servers at internet gateways china are able to analyze and manipulate internet traffic . nonetheless , transfer of digital files helped us overcome network latency issues , which in turn enhanced the viewing experience for end - user digital consultants .

background : telepathology practice across international borders has become increasingly popular . our telepathology consultation service with a laboratory in china was hampered by latency issues when viewing whole slide images.objective:the aim was to explore data transfer solutions to improve the viewing experience of digital consult cases.methods:whole slide image files residing on a server in china were transferred to our data center in the usa using an open source product ( fast data transfer ) . a faster more automated commercial high speed file transfer software solution ( aspera ) was also tested.results:transferring files with the open source product provided transfer speeds of 23 mbps , but suffered from intermittent dropped connections . employing commercial software permitted more reliable transmission of digital files with 75100 mbps transfer speeds.conclusions:successful global telepathology requires dedicated image management . transfer of files to local servers by employing high speed data transfer tools helped overcome network latency issues , improved the overall turn - around time of digital consultations , and enhanced the viewing experience for end - user digital consultants .

a 15-year - old female developed fever , stinging eyes and headache , followed one day later by sudden appearance of flaccid blisters on the face with subsequent dissemination to more than 70% of the whole integument and development of mucosal erosions . thirty days before , she had been operated on the nose and medicated with cefuroxime ( for 8 days ) , paracetamol ( for approx . 10 days ) and metamizol ( for approx . 10 days ) , the latter of which was later identified by lymphocyte transformation test as the most likely causative compound . four days before admission , she had taken acetylsalicylic acid and paracetamol for flu - like symptoms including conjunctival irritation and rhinitis . upon physical evaluation , disseminated flaccid blisters filled with serous liquid were present on 70% of her skin surface . her eye- , mouth- , pharyngeal- and genital mucosae were also affected by erosive lesions . she received intravenous immunoglobulins ( ivigs ) , in total 3 g / kg body weight over three consecutive days , hydration and nutritional support as well as careful wound care . topical therapy included silver - coated dressings on erosions , and after reepithelialization , skin washes with water and wax emulsion were performed , followed by the application of hydrocortisone 0.5% in hydrophilic unguent . from day 1 after onset of ivig therapy onwards , no new development of blisters was observed . during the clinical course , desquamation of dusky areas of skin leaving an intact epidermis below was observed . we noted frequent spontaneous bleeding upon changes of the silver - coated dressings during reepithelialization period in the second week . the remaining detached skin fragments that overlied the progressively regrowing epidermis as of day 7 were progressively shed between day 7 and day 28 . the patient was discharged from the intensive care unit ( icu ) at day 28 after admission , with almost complete skin reepithelialization . at the last follow - up control 6 months later , the patient showed full recovery , except for residual alopecia and dry eyes . to date , no specific treatment with a high evidence level of efficacy has been reported for ten . the standard of care consists of best supportive therapy in an icu setting , and includes hydroelectrolytic and nutritional support as well as regular wound care and the appropriate detection and treatment of infectious complications . whereas best supportive care is an accepted standard of care for ten patients , none of the specific treatment strategies described to date , including ivig ( adequately dosed at 3 g / kg body weight ; there is an apparent dose dependence , as the reduction in mortality appears to be greatest for doses of 3 - 4 g / kg ) , corticosteroids , and infliximab , has shown solid evidence in support of a survival advantage in ten patients . to date , only one prospective , randomized - controlled clinical trial has been reported in ten , demonstrating no therapeutic benefit for thalidomide in the treatment of ten . ivig is a safe therapeutic modality that has been shown in several case series to potentially provide a benefit in ten . controversy as to the exact efficacy does , however , exist . in the recently established guideline for the use of high - dose immunoglobulins in dermatology , early administration of high - dose immunoglobulins ( 3 g / kg ) indeed , several published studies reporting the use of ivig for the treatment of ten have shown this therapy to potentially provide a survival benefit . the studies published to date are unfortunately heterogeneous , and often of limited size , retrospective nature , and noncontrolled . on the other hand , ten is a rare disease , and randomized prospective controlled studies analyzing the effect of ivig are very difficult to perform , and do not exist to date . eight of the 11 studies published to date reporting the use of ivig in ten suggest a positive effect of ivig on mortality if compared to the mortality predicted by scorten where applied , or the 25 - 35% average mortality rate for ten reported in the literature ( table 1 ) . it must be kept in mind , however , that as for many other therapies , the total dose ( in g / kg body weight ) of ivig administered may have an effect on the therapeutic outcome . indeed , a recent publication by trent et al . , analyzing in detail the studies published to date , showed that a dose - response relationship likely exists : per 1-g / kg increase in ivig dose , there was an observed 4.2-fold increase in patient survival . moreover , no mortality was observed amongst the 30 patients that had received 3 g / kg ivig or more . taking into account the lack of a proven specific therapy , the severity of ten , the safety of ivig , and the data to date concerning the efficacy of ivig in ten , we are of the opinion that in the absence of proven superior therapies , ivig therapy should be considered in patients with ten .

toxic epidermal necrolysis is a rare but clinically well - described dermatological pathology . however , clinical pictures of this disorder in text books do not reflect its dynamic evolution . usually , the desquamative post - bullous stage is represented , neglecting the initial bullous stage as well as the skin healing . with one clinical case , we provide a day - after - day illustration of the evolution of a patient suffering from toxic epidermal necrolysis . during one month , a skin area of a limb was regularly photo - documented .

we used the google trends database to obtain the proportion of all google searches that contained the words mrsa or staph . staph was included because many news stories refer to mrsa as antibiotic resistant staph . methicillin - resistant staphylococcus aureus was too infrequently searched to be useful . google trends reports search activity relative to the average number of similar queries in february 2004 . we extracted counts of us newspaper , wire service , and radio and television stories mentioning mrsa or staph from the lexisnexis academic database . we spot - checked stories with the word staph to confirm they were about mrsa . we hypothesized that the volume of news coverage captured the relative effect of the story on search behavior . we used quarterly hospital discharge data from the university healthsystems consortium clinical database , which includes > 90% of us academic medical centers , to calculate the proportion of hospitalizations including an mrsa diagnosis . we used the diagnostic code for mrsa from the international classification of disease , 9th revision ( v09.0 ) . mrsa hospitalizations include ca - mrsa infections that led to hospitalization and infections that developed during a hospitalization . this database includes < 99 codes per discharge , more than other national hospital discharge databases . the likelihood of recording an mrsa diagnosis increases with longer lists of codes because of the many concurrent conditions in complex hospitalizations . we adjusted hospitalization rates for the maximum number of codes submitted by each medical center each year . data after the 3rd quarter of 2008 were not included because of implementation of a nationwide coding change for mrsa . we related quarterly variation in mrsa hospitalizations to quarterly variations in search queries and news stories in a linear regression model . because of the effect of the 2007 cdc report on mrsa awareness , we tested 2 indicator variables : 1 to capture the spike in search activity during the 4th quarter of 2007 , and 1 to account for higher levels of search activity in subsequent quarters ( 10 ) . these 2 indicators enable the model baseline to differ during the quarters before , during , and after the 4th quarter of 2007 , while keeping the relationship between hospitalization rates and internet searches and news counts the same during the 3 periods . all statistical analyses were performed in stata version 10.0 ( statacorp lp , college station , tx , usa ) . they range from 4 to 130 before the october 2007 peak of 719 , related to the cdc report , the effect of which appears to linger . the prior peak of 130 in april 2005 was related to articles in the new england journal of medicine describing necrotizing fasciitis associated with mrsa and the emergence of ca - mrsa in 20012002 ( 11,12 ) . weekly counts of news coverage ( newspaper stories , wire service stories , and television and radio news transcripts ) that mention mrsa ( methicillin - resistant staphylococcus aureus ) or in addition to the spike , there was a subsequent change in the relative frequency of search term mrsa compared with note that the news count peak in 2005 is not seen in the google searches , and the peak in the google searches in the 3rd quarter of 2006 is not apparent in the news counts . actual and predicted hospitalization rates per 1,000 hospitalizations with an international classification of disease , 10th revision , diagnostic code for methicillin - resistant staphylococcus aureus ( mrsa ) and the fraction of google search queries for mrsa or staph ( relative to the fraction of february 2004 ) , 20042008 . google queries were a useful predictor of mrsa hospitalizations and explained 33% of quarterly variation when used alone . adding news counts to the model resulted in increasing the percentage of explained variation only modestly to 41% . the news counts were not a significant addition to the model ( p = 0.18 ) . our final model , which includes search queries and the 2 temporal indicator variables , but not the news counts , is shown in the table . although data after 2007 are insufficient for definitive comparison , a better prediction before than after the 4th quarter of 2007 is suggested ( figure 2 ) . * uhc , university healthsystems consortium ; mrsa , methicillin - resistant staphylococcus aureus ; ci , confidence interval . the overall model f(3,15 ) was 29.69 ( p<0.0001 ) , r 0.8559 , and adjusted r 0.8270 . we report an ip surveillance model for mrsa incidence . we hypothesized that news coverage for such an unfamiliar disease would strongly influence search activity . however , news coverage did not affect the relationship between search queries and hospitalization rates before the 2007 cdc report . the congruence of the internet search activity and the hospital discharge data suggest that their temporal pattern represents the actual trend in mrsa : an increasing incidence during 20042007 , with a suggestion of seasonal variation , and no increase in 2008 . this pattern is not the same pattern documented by the abc surveillance data for invasive mrsa infections ( 13 ) . searches using the phonetic misspelling mersa show a parallel trend to searches using mrsa , although they are less frequent , and the correctly spelled methicillin hospitalized mrsa infections include hospital - associated mrsa infections and the more serious ca - mrsa infections . because evidence has shown that invasive hospital - associated mrsa infections decreased during the study period ( 13 ) , the generally upward secular trend in mrsa hospitalizations is more likely to represent the trend in ca - mrsa , especially because we now know that most mrsa infections have onset in the community ( 3 ) . the inability to distinguish community and health care infections is nonetheless a limitation of the google and the hospitalization data . the lack of any true standard for mrsa incidence is why ip surveillance is potentially useful .

the internet is a common source of medical information and has created novel surveillance opportunities . we assessed the potential for internet - based surveillance of methicillin - resistant staphylococcus aureus and examined the extent to which it reflects trends in hospitalizations and news coverage . google queries were a useful predictor of hospitalizations for methicillin - resistant s. aureus infections .

at the first medical examination , the sister was 7 years 8 months old , and the brother was 5 years 3 months old . neither sibling had any specific birth history . slit lamp microscopic examination revealed no abnormalities in the anterior segments of either eye , in either patient . the best corrected visual acuities ( bcva ) were 0.1 ( right eye ) and 0.8 ( left eye ) in the sister , and 0.7 ( right eye ) and 0.1 ( left eye ) in the brother . the cycloplegic refractive powers in the sister were : -15.50 diopter ( dpt ) , cylinder ( cyl ) + 4.50 dpt ax 85 in the right eye and -1.00 dpt cyl . the differences in spherical equivalents between the two eyes were -12.50 diopters in the sister and -6.875 diopters in the brother . full - time right occlusion therapy was performed in both patients for three months , then four to six hours a day for two years . the sister was prescribed atropine for the left eye after six hours right - sided occlusion therapy a day for a year . three years later , the bcva in the brother 's left eye had improved from 0.1 to 0.7 . the bcva in the sister 's left eye improved from 0.1 to 0.7 during the first year ; however , she showed no further improvement after that time . the refraction and the radius of the anterior corneal curvature were measured using an autorefractokeratometer ( speedy - k ; nikon , tokyo , japan ) and a topographer ( orb - scan ; bausch & lomb , rochester , ny , usa ) . a - mode ultrasonography ( cinescan ; quantel medical , clermont - ferrand , france ) was performed . the results of a - mode ultrasonography and orb - scan are presented in table 2 . this condition is often associated with amblyopia , both in the presence of and in the absence of strabismus [ 6 , 7 ] . the prevalence of anisometropia reported in school - based and population - based studies of school - aged children is typically 5% , but this figure varies depending on the manner in which anisometropia is defined . myopic anisometropia is usually accompanied by strabismus , especially exotropia in 30 - 60% of patients . this suggests that the development of binocular vision might be affected by mild infantile exotropia . when high myopia of one eye is more than -5 to -6 diopters , or the difference in spherical equivalents of both eyes is more than 5 diopters , then anisometropia may be responsible for amblyopia . , the present case is without any obvious complication and shows mirror image similarly . in the study of 78 monozygotic twins and 40 dizygotic twins , sorsby et al . reported that the concordances of corneal power , axial length , and vertical ocular refraction were higher in monozygotic twins than in dizygotic twins . interestingly , patients in the present study had similar axial lengths in their myopic eyes . in conclusion , we believe that severe myopic anisometropia may be genetically determined , and further investigation is recommended .

we report a case of one sister and brother with mirror image myopic anisometropia . one sister and brother complained visual disturbance . the sister was 10 years 11 months old , and brother was 8 years 4 months old . full ophthalmic examinations were performed , including slit lamp examination , intraocular pressure , keratometry , anterior chamber depth , axial length , fundus examination and the cycloplegic refraction . the cycloplegic refractive power was -15.50 dpt cyl.+4.50 dpt ax 85 ( right eye ) , -1.00 dpt cyl.+0.50 dpt ax 90 ( left eye ) in the sister ; -1.75 dpt cyl.+2.25 dpt ax 90 ( right eye ) , -9.50 dpt cyl.+4.00 dpt ax 80 ( left eye ) in the brother . the co - occurrence of severe myopic anisometropia in a sister and brother is extremely rare . the present case suggests that severe myopic anisometropia may be related by genetic inheritance .

osteosarcoma is the most common type of bone tumor in children and the lung is the most frequent site for metastatic osteosarcoma . histologically conventional osteosarcoma , once metastasized to the lung , generally causes a rapid and fatal outcome . we report herein a case of osteoblastic osteosarcoma with exceptionally unique features : sporadic lung metastases and delayed metastases to unusual sites with long - term survival . an 18-year - old female patient presented with a history of pain in the left knee in august 2002 . magnetic resonance imaging and she was treated with wide resection of the tumor and perioperative chemotherapy , including cysplatin , doxorubicin , and methotrexate . however , 2 years later pulmonary metastasis was detected and treated with surgical resection and ifosfamide chemotherapy in october 2004 . then , she was treated for 5 more events of pulmonary metastasis by repeated operations and adjuvant conventional chemotherapies for sarcoma , including ifosfamide , etoposide , and gemcitabine ( july 2005 , may 2007 , january 2008 , june 2008 , january 2012 ) . anteroposterior and lateral mri of the left knee reveal a bone tumor of the proximal tibia ( a and b ) . mri = magnetic resonance imaging . in november 2011 , she consulted a general hospital complaining of tarry stools . subsequently , total gastrectomy was performed . in september 2012 , she was referred to our emergency department with abdominal pain and vomiting . the size of the jejunum tumor was 2 cm 2 cm 2 cm ( c ) . the patient written informed consent was waived due to the retrospective nature of the presented case . the most common site for metastatic osteosarcoma is the lung , occurring in more than 90% of cases . other sites of metastases include the bones , pleura , brain , and intraabdominal solid viscera . 5 were to the stomach , 3 were to the duodenum , 8 were to the jejunum , and 3 were to the ilium . the metastasis localized in the stomach presented as anemia , hematemesis , and tarry stools . in 5 cases , patients underwent a resection of the metastatic masses endoscopically or using a laparotomy or laparoscopy to determine each tumor 's size and localization . the metastasis in the jejunum presented as abdominal pain and vomiting , and in 7 of 9 cases intussusception occurred . chandramohan et al reported that they could not conservatively cure their patient of intussusception caused by osteosarcoma metastasis to the jejunum , so they concluded that surgical management should be considered because of the risk of gangrene and perforation . recent aggressive therapy and increased long - term survival have brought about a change in the natural history of osteosarcoma . this , in turn , might have led to a recent increase in reports on osteosarcoma metastasis to the gastrointestinal tract . giuliano et al addressed the fact that advances in therapy such as multi target chemotherapy have altered the pattern of recurrences and metastasis in patients treated for osteosarcoma . the mean survival of the latter patients was about 3 years from the last recurrence , with the maximum relapse or recurrence rate being 7 . the patient described here survived 11 years after the first recurrence and experienced 8 relapses . this patient was very unusual in terms of a long - term survival and metastatic sites , suggesting the importance of vigilance and thorough follow - up for patients with conventional osteosarcoma .

abstracthistologically conventional osteosarcoma , once metastasized to the lung , generally causes a rapid and fatal outcome . osteosarcoma metastasis to the gastrointestinal tract is extremely rare.we report herein a case of osteoblastic osteosarcoma with exceptionally unique features : sporadic lung metastases and delayed metastases to the stomach and the jejunum with long - term survival . she received multiple operations and chemotherapies , but consequently died of peritoneal dissemination . a review of the literature on osteosarcoma metastasis to the gastrointestinal tract is presented.this patient was very unusual in terms of a long - term survival and metastatic sites , suggesting the importance of vigilance and thorough follow - up for patients with conventional osteosarcoma .

it is well known that patients with long dialysis vintage have low cardiac output for various reasons including dilated cardiomyopathy , which is otherwise known as uraemic cardiomyopathy. although the aetiology has still not been clearly defined , uraemic states have been associated with sympathetic overactivity and autonomic neuropathy . have shown that end - stage renal disease ( esrd ) patients manifest abnormal myocardial i - metaiodobenzylguanidine ( i - mibg ) uptake that has been used to evaluate cardiac sympathetic innervations . mibg provides a means to evaluate the cardiac adrenergic nerve activity , because mibg is subject to the same uptake and storage mechanisms as norepinephrine . esrd patients with decreased left ventricular ejection fraction ( lvef ) have not usually been referred for transplantation , because they are considered at increased risk of perioperative morbidity and mortality , although kidney transplantation significantly decreases those risks . indeed , it has been reported that expectations are low for patients with longer dialysis vintage to improve their cardiac function after kidney transplantation . we successfully performed living kidney transplantation for a patient with a long dialysis vintage of 17 years and dilated cardiomyopathy . his cardiothoracic ratio ( ctr ; the ratio of the transverse diameter of the heart to the internal diameter of the chest at its widest point ) had increased and the symptoms of heart failure gradually exacerbated ( nyha class iii ) . cag showed no coronary artery disease but diffusely hypokinetic left ventricular wall motion without hypertrophy . haemodynamic data showed maintained cardiac index and relevant pulmonary capillary wedge pressure ( pcwp ) but extremely low systolic function ( cardiac index 2.81 , pcwp 12 mmhg , lvef 18% ) leading to the diagnosis of dilated cardiomyopathy . the laboratory results before the transplantation were as follows : haemoglobin 11.1 g / dl ; brain natriuretic peptide ( bnp ) 1046 pg / ml and ctr 61.4% . echocardiography showed the left ventricular diastolic diameter ( lvdd ) of 84 mm , left ventricular systolic diameter ( lvds ) of 71 mm and ejection fraction ( ef ) of 28% . after obtaining informed consent and clearance from cardiology consult , we performed living kidney transplantation . his serum creatinine level decreased to 1.10 mg / dl by the 10th postoperative day . although his blood pressure ( bp ) was very low without antihypertensives , it rose postoperatively and renin angiotensin system inhibitors could be started . one year after the operation , ctr and bnp had decreased from 61% to 54% and 1047 pg / ml to 75 pg / ml , respectively , and the nyha functional class improved to i ii . his body weight never decreased post - transplant , rather it increased , which suggests that volume overload was not present before transplantation . despite this clinical improvement ( shown in figure 1 ) , his lvef improved only modestly from 28% to 31% . to evaluate his cardiac function in more detail , we performed i - mibg scintigraphy . the area showing the i - mibg uptake reduction or absence markedly decreased over time . the late heart - to - mediastinum ( h / m ) ratio in i - mibg scintigram , indicating the normal myocardial uptake of mibg , rose to be within the normal range ( 2.35 ) compared to before transplantation ( 1.3 ) , which provides evidence for significant improvement of his cardiac autonomic nerve function . the post - inferior wall showed moderate radioisotope uptake reduction , indicating the presence of viable myocardium except in this region . although after the operation body weight increased , bnp and ctr decreased , indicating that the circulating volume has decreased . ( a ) cardiac i - mibg uptake and ( b ) tl uptake 1 year after transplantation . the coloured areas indicate isotope uptake and black areas show the absence of isotope uptake . there are arguments for and against kidney transplantation in esrd patients with significantly decreased systolic function , although transplantation generally decreases cardiac mortality . in particular , long dialysis vintage is regarded to be associated with irreversible cardiac damage . in this report first , sequential i - mibg scintigraphy can be used as an evaluation tool for the improvement of cardiac sympathetic function . secondly , even in esrd patients with a long dialysis history , severely impaired systolic function may be at least partially reversible . uptake reduction in the i - mibg scintigram suggests structural and functional cardiac , microvascular , and neurological anomalies and interstitial fibrosis that is documented in patients with esrd . have shown that patients with a long history of dialysis ( 45.1 19.9 months ) were prone to have little or no improvement in lvef assessed by echocardiography . although lvef in this patient has not shown marked improvement during the first year after transplantation , parameters such as ctr and serum bnp levels , together with mibg parameters , have improved . in addition , agarwal et al . demonstrated that significant autonomic nerve dysfunction in patients who developed hypotension during haemodialysis and marked reversal of autonomic dysfunction was observed following kidney transplantation . kurata et al . reported that kidney transplantation provided the improvement of uraemic cardiac sympathetic neuropathy assessed by i - mibg scintigraphy imaging . in this patient , history of frequent heart failure due to interdialytic weight gain when lvef was still normal is indicative of volume overload . however , he was not volume overloaded , as a result of intensive dry weight and blood pressure control , after lvef deteriorated . this implies that amelioration of uraemia itself , not amelioration of chronic volume overload , improved cardiac function in this patient , which in turn indicates that it was the uraemic condition that caused myocardial depression . the uptake of thallium scintigram means that the cardiac muscle still has a capacity for recovery . findings from the cardiac scintigram in this patient ( i.e. the discrepancy between the patterns of tl and i - mibg distribution ) suggest still denervated , but , nonetheless , viable myocardium , supporting the idea that even with long dialysis vintage , cardiac function can improve after removal of uraemia . kidney transplantation for esrd patients with severely impaired cardiac function due to dilated cardiomyopathy or uraemic cardiomyopathy is safe and effective under careful monitoring during and after transplantation , irrespective of dialysis vintage . sequential i - mibg scintigraphy can be used as an evaluation tool for the improvement of cardiac sympathetic function .

patients with long dialysis vintage have low cardiac output for various reasons . although kidney transplantation is known to improve cardiac mortality , patients are sometimes evaluated as contraindicated for transplantation because of cardiac risk . we successfully performed kidney transplantation for a patient with a long dialysis vintage and dilated cardiomyopathy . sequential 123i - metaiodobenzylguanidine ( 123i - mibg ) scintigraphy suggested that amelioration of uraemia improved cardiac function . kidney transplantation for patients with severely impaired cardiac function is safe and effective under careful perioperative monitoring irrespective of dialysis vintage . sequential 123i - mibg scintigraphy can be used as an evaluation tool for the improvement in cardiac function .

a 19-year old female presented to our dermatological clinic with hyperpigmented , indurated and atrophic patches on a zosteri - form distribution extending from her left sub - mammary region ( figure 1 ) through to her back ( figure 2 ) . the patient denied any personal or family past medical history of interest , except for an episode of herpes zoster on the same location two years before . blood cell count , general biochemistry , urinalysis , thyroid profile , antinuclear antibodies , erythrocyte sedimentation rate , c reactive protein , chest x - ray and serological tests for borrelia burgdoferi showed no abnormalities . serology for varicella - zoster virus tested negative for igm but positive for igg . histopathological examination showed thick bundles of collagen in reticular dermis orientated parallel to the skin surface . cutaneous appendages were reduced . a perivascular inflammatory infiltrate composed of plasma cells and lymphocytes could also be observed . thus , our case was consistent with zosteriform morphea as an expression of isotopic wolf response following an episode of herpes zoster . the patient was then started on a calcipotriol / betamethasone gel , with only a mild therapeutic response . the term zosteriform is commonly used to describe the morphological pattern of a skin dermatosis resembling the distribution of herpes zoster . lichen planus , porokeratosis , common warts , fungal infections , naevus and skin metastases are some of the conditions that have been described as following this pattern . on the other hand , several types of cutaneous lesions have previously been described at the site of herpes zoster scars . this phenomenon , which is characterized by the occurrence of a new skin condition at the site of a previous one , was named isotopic response by wolf et al . even though the cutaneous eruptions described in herpes zoster scars are variable , granuloma annulare and other types of granulomatous disorders are the most commonly reported reactions . it has been hypothesized that the viral infection might change local immunity , thus inducing a delayed - type hypersensitivity reaction to herpes zoster viral antigen or an immune suppression . we agree with lopez et al . that a different dermatosis can be expressed according to the cytokine pattern of the inflammatory response . conversely , it is to be remembered that other conditions , such as zosteriform lichen planus , have been interpreted as a manifestation of koebner 's phenomenon . this pattern would be an expression of a viscerocutaneous reflex mechanism within the affected segments consequent to a radicular irritation caused by abnormalities in the spine .

we report the case of a 19-year old female who presented to our dermatological clinic with hyperpigmented , indurated and atrophic patches on a zosteriform distribution , extending from her left submammary region through to her back . our case was consistent with a zosteriform morphea as an expression of an isotopic wolf response following an episode of herpes zoster . we discuss the pathogenic mechanisms and review the clinical cases previously reported in the literature .

a 25-year - old caucasian male patient presented with a three - week history of a red right eye . a prominent vascularized iris lesion located at 7 o'clock was present in the right eye in addition to mutton - fat keratic precipitates , predominantly in arlt 's triangle , anterior chamber cells , and mixed conjunctival and ciliary injection ( figure 1(a ) ) . neither fundoscopy of the right eye nor examination of the left eye disclosed any pathological findings . an ultrasound biomicroscopy ( ubm ) of the right eye revealed a prominent iris process with extension into ciliary body which measured 4.7 4.0 1.8 mm with middle internal reflectivity ( figure 1(b ) ) . chest computed tomography ( ct ) revealed bilateral hilar lymphadenopathy and reticulonodular parenchymal involvement . to confirm the suggested diagnosis of sarcoidosis , conjunctival biopsy was performed . histopathological work - up showed granulomatous epithelioid cell inflammation with insular central necrosis without acid - fast bacilli ( figures 1(c ) and 1(d ) ) . extensive systemic checkup , including bronchoscopy , bronchoalveolar lavage ( bal ) with cd4/cd8 ratio evaluation , and transbronchial biopsy , revealed no evidence of acid - fast organisms . systemic and topical steroid therapy was initiated with oral prednisolone 100 mg daily and prednisolone acetate 1% eye drops hourly . under this treatment eight weeks after the first presentation , no signs of intraocular inflammation were detectable , the iris tumor resolved completely , and the patient was free of any complaints . sarcoidosis is a chronic multisystem granulomatous disorder of unknown origin [ 1 , 2 ] . sarcoidosis occurs worldwide but is predominant in certain ethnic and racial groups ( e.g. , scandinavians and us blacks ) and usually develops before the age of 50 years with the incidence peaking at 20 to 39 years . the highest annual incidence of sarcoidosis has been observed in northern european countries ( 5 to 40 cases per 100,000 people ) . sarcoidosis is characterized by the formation of noncaseating granulomas in affected organs , predominantly in the lungs and thoracic lymph nodes ( more than 90% of patients ) and skin ( 25% of patients ) , and might have either self - limited ( two thirds of patients ) or chronic course ( up to one third of patients ) [ 2 , 5 ] . the most common ocular manifestations are uveitis ( 3070% ) and conjunctival nodules ( 40% ) . classic sarcoid associated anterior uveitis may present either as acute iridocyclitis , which is mostly seen in lfgren 's syndrome , or as a chronic granulomatous uveitis with mutton - fat keratic precipitates . in the chronic type of the disease , the granulomatous nodules of the iris and in the anterior chamber angle are sometimes seen ( the so - called koeppe and busacca nodules ) . in rare cases , iris sarcoid granulomas can simulate other prominent iris lesions such as an amelanotic melanoma of the iris or a carcinoma metastasis [ 6 , 7 ] such as in our case . in the absence of the known causative agent , chest computed tomography has been reported to be more sensitive than radiography and can show hilar adenopathy in combination with interstitial lung disorder . measurements of serum angiotensin converting enzyme ( ace ) level reflect the disease activity but are not specific enough for diagnostic properties ; normal serum ace levels do not exclude the diagnosis of sarcoidosis , especially not in case of isolated ocular manifestation . clinical features together with the presence of noncaseating epithelioid cell granulomas on tissue biopsy are usually pathognomonic for the diagnosis of sarcoidosis . tissue biopsy might be obtained from lung , skin , lymph node , or other affected tissues such as conjunctiva . conjunctival biopsy has been shown to be positive in 66.7% in patients with and in 31.4% without conjunctival follicles . although noncaseating granulomas are not pathognomonic , tissue examination is essential to differentiate sarcoidosis from infections or malignancies [ 1 , 9 ] . in our case , a similar case of patient with scrotal sarcoid granulomas with central necrosis , leading to presumption of tuberculosis , has also been reported . the ideal therapy for sarcoidosis is not well defined ; therapeutic decisions are dictated by the localisation and severity of the disease . nevertheless , oral corticosteroids are the mainstay of treatment . for refractory course and in some cases of ocular involvement ,

introduction . we report a case of a male patient presented with sarcoid lesions of the iris and conjunctiva , mimicking tuberculosis due to epithelioid cell granulomas with small central necrosis in conjunctival biopsy . patient . a 25-year - old man was referred to our department for further management of an iris tumor with iridocyclitis in his right eye . initial examination showed an isolated vascular tumor of the iris and ciliary body with anterior uveitis and mutton - fat keratic precipitates , suggesting the diagnosis of a granulomatous disease . conjunctival biopsy revealed granulomatous epithelioid cell inflammation with small central necrosis without acid - fast bacilli . extensive systemic examination , including bronchoscopy and transbronchial biopsy , provided the diagnosis of sarcoidosis stage 2 with pulmonary involvement , thus ruling out tuberculosis . systemic and local steroid therapy was initiated , leading to complete recovery of our patient with complete disappearance of the iris lesion and improvement of the pulmonary function . conclusion . although noncaseating epithelioid cell granulomas are typical for sarcoidosis , small central necrosis can be found in some granulomas , leading to presumption of tuberculosis . extensive systemic checkup in cooperation with other specialists is essential to confirm the correct diagnosis and to initiate the appropriate therapy .

presence of rv antigen on brain tissue was confirmed by the direct fluorescent antibody test ( www.cdc.gov/ncidod/dvrd/rabies/professional/publications/dfa_diagnosis/dfa_protocol-b.htm ) and direct rapid immunohistochemical test ( 3 ) ( figure 1 ) . antigenic typing was performed with a panel of anti - rv nucleoprotein ( n ) monoclonal antibodies as described ( 46 ) . comparison of the human sample with established reaction patterns of rv variants showed that the closest antigenic match was among insectivorous bat patterns , specifically a unique rv variant in colorado myotis sp . and several tadarida brasiliensis variants ( appendix table ) . patterns obtained from hematophagous bat- , canine- , and terrestrial carnivore associated rv variants were not consistent with the pattern obtained from the patient . detection of rabies virus antigen in brain impressions of the patient by direct fluorescent antibody test counterstained with evans blue , 200 total magnification : a ) positive control ; b ) negative control . direct rapid immunohistochemistry test counterstained with hematoxylin , 400 total magnification : c ) positive control ; d ) negative control . total rna was extracted from infected tissue , and the entire n gene was amplified by reverse transcription pcr in 2 overlapping amplicons , as described ( 7 ) . phylogenetic analyses were conducted by comparing full and partial rv n sequences with sequences derived from major extant rabies enzootics in both dogs and vampire bats in mexico , as well as sequences associated with rvs maintained by other bat species and wild terrestrial carnivores from the united states and the americas ( 810 ) ( figure 2 ) . mega and bioedit software were used to perform the phylogenetic reconstructions and sequence analyses ( 11,12 ) . phylogenetic tree of complete lyssavirus nucleoprotein genes , comparing the patient isolate with representative rabies virus variants associated with common new world animal reservoirs . the map shows the locations of representative samples associated with rabies transmitted by tadarida brasiliensis and vampire bats used in the analysis . rabid dogs and vampire bats are the most common sources of exposure for humans in mexico ( www.salud.gob.mx/unidades/cdi/documentos/rabia.pdf ) . residual canine rabies enzootics persist in central and southeastern mexico , whereas vampire bat rabies is found throughout a wide geographic focus , particularly in the tropical and subtropical areas ( 8,10 ) . in addition , at least 20 different lineages of rv that are associated with at least 9 bat species have been described in mexico ( 8) . nevertheless , phylogenetic analyses of the rv obtained from the brain sample of the patient did not support a close relationship with any of the rv variants previously described . the isolate was found to be most closely related with those from mexican free - tailed bats ( t. brasiliensis ) ; overall average identity was 95% but clearly segregated in an independent lineage ( figure 2 ) . given that the average percentage of genetic divergence among previously sequenced members of the t. brasiliensis rv clade ranges between 2.4% for the full n over a 20-year period and 1% for the partial n over a 40-year period , the extent of genetic divergence ( 5% ) between the oaxaca sample and the t. brasiliensis rv clade suggests that this isolate represents a new rv variant . additionally , although the oaxaca sample shares a distinctive molecular signature with the t. brasiliensis rv clade ( i.e. , conserved amino acid sequence alanine , aspartic acid , and threonine located at positions 377379 within the n gene ) , the histidine at position 321 , which is unique and highly conserved in members of the t. brasiliensis rv lineage , was changed to glutamine in the oaxaca patient . although this patient s history indicated that he had been bitten near his home ( san vicente coatlan , district of ejutla , oaxaca ) by a costoche ( 2 ) ( gray fox , urocyon cinereoargenteus ) , the genetic and phylogenetic analyses did not support a close relationship to any known rv associated with terrestrial carnivores . rvs of major rabies epizootics associated with dogs and other terrestrial carnivores in mexico and the united states are genetically distinct ( average genetic distance 14%16% ) from those in bats throughout north america . also , although the rv associated with the human case was nested within the monophyletic assemblage of bat rv variants , rv variants phylogenetically closest to this case were still genetically distant . rv variants associated with north american tadarida and vampire bat rabies in mexico were from 5% to 7% divergent from that of the human case . results of partial rv n gene sequence analyses indicated that at least 2 other human rabies cases one in california in 1995 and the other in nuevo leon , mexico , in 1999were associated with the t. brasiliensis variant . these cases segregated within the monophyletic assemblage that includes enzootic rabies in t. brasiliensis bats collected over a period of 40 years in the united states and mexico ; the oaxaca human case sample fell outside the t. brasiliensis clade , forming an independent lineage that was statistically supported in both the partial and full n phylogenetic reconstructions . these results plus the amino acid change found at position 321 in the rv associated with this case reinforced the concept of a new rv lineage associated with an unknown animal reservoir . in 2008 , a mexican immigrant with a history of fox bite ( 2 ) died in california of infection with an rv variant most closely associated with rvs associated with insectivorous bats ( t. brasiliensis ) . both the molecular and phylogenetic characterizations of this rv suggest that this is a new lineage . although the primary reservoir or most likely origin of this rv was determined to be an insectivorous bat ( unknown species ) , the history of carnivore exposure suggests that a secondary transmitter ( vector ) could have been involved in the transmission chain , as has been reported in other cases ( 13 ) . one can not , however , rule out the possibility that the unknown reservoir species of this new rv lineage is , in fact , a different bat species ( which could have been involved in the primary transmission after an unnoticed or cryptic exposure ) or a terrestrial carnivore ( e.g. , the biting fox ) . the establishment of an insectivorous bat - derived rv variant in a terrestrial reservoir ( i.e. , striped skunk ) in northern arizona has been described ( 14 ) . enhanced epidemiologic surveillance and intensified research to characterize rv variants and their reservoirs in the region are needed to resolve this intriguing discovery . comparative monoclonal antibody ( mab ) reactivity of rabies viruses from the patient and likely reservoir host species *

a novel rabies virus was identified after death in a man who had immigrated from oaxaca , mexico , to california , usa . despite the patient s history of exposure to domestic and wild carnivores , molecular and phylogenetic characterizations suggested that the virus originated from insectivorous bats . enhanced surveillance is needed to elucidate likely reservoirs .

the developmental disturbances affecting the shape of tooth include gemination , fusion , and concrescence . gemination is an attempt at division of a single tooth bud by an invagination with incomplete formation of two teeth whereas fusion is union of two or more teeth . the number of teeth is reduced by one or more in fusion and the same remains unaltered in gemination . concrescence is cemental union of teeth which affects only the mesodemal layer and may be diagnosed only post - extraction . these may be joined through fusion , gemination , concrescence or a combination of fusion and gemination . although , union of two teeth by concrescence is reported in permanent and primary teeth , three such teeth , involving primary maxillary incisors and a supplemental incisor , are very rare . a 7-year - old boy complained of palatally erupting upper front tooth and a retained primary tooth . an examination revealed palatal eruption of permanent maxillary left central incisor . also , visible was an erupted supplemental tooth bearing resemblance to a miniature incisor . it was present between the deciduous maxillary left central and lateral incisors ( 61 and 62 respectively fdration dentaire internationale ( fdi ) notation ) . the teeth 61 and 62 were carious and lacked mobility . also , the tooth 61 was black in color . history revealed trauma to the upper anterior region when the child was 1 year of age . a radiograph revealed cariously infected 61 and 62 with a supplemental tooth in between [ figure 1 ] . it was decided to extract all the three teeth taking into consideration age of the child , presence of infected teeth and eruptive status of succedaneous teeth . attempts at removal of a single tooth resulted in extraction of all the three teeth en bloc . examination revealed that these teeth were joined together by the roots [ figures 2 and 3 ] . an intra - oral periapical radiograph showing carious 61 , 62 and the supplemental tooth labial aspect of concrescent teeth-61 , supplemental tooth , 62 lingual aspect of three concrescent teeth the specimen was thereafter , sent for histopathology . the teeth were decalcified in 3% nitric acid and the prepared sections ( 5 m ) stained with hematoxylin and eosin . the sections revealed the union of teeth by cementum [ figures 4 and 5 ] . dentin and cementum ( decalcified section [ h and e , 40 ] ) union of teeth by cementum ( decalcified section [ h and e , 40 ] ) a missing permanent tooth is suggestive of partial anodontia ; or fusion of primary incisors and a permanent tooth . absence of any missing tooth is indicative of fusion involving primary incisors and a supernumerary tooth ; or a combination of fusion and gemination of primary teeth . gemination is seen as a bifid crown but usually has a single pulp chamber and a single identifiable root canal . in the present case , well - demarcated grooves separated the crowns of incisors and supernumerary tooth when viewed from the labial and lingual aspect of extracted triple teeth . moreover , mesial caries on both the incisors made it difficult to evaluate enamel fusion , if any . a radiographic image also confirmed separate pulp chambers and root canals of all the three teeth . also , there was no missing primary or permanent tooth . fusion and gemination involve a confluence of dentin whereas concrescence involves union by cementum only . in our case , union was by cementum in the cervical - middle third of the roots and dentin of the teeth was separate . also , morphological topography of the roots of triplets was distinguishable post - extraction which is indicative of complete root formation prior to union . the union by cementum was also confirmed histologically . although , the etiology of concrescence is largely unclear , trauma , crowding of teeth , excessive occlusal forces , periradicular infection , proximity of roots , systemic diseases , and genetic factors are some of the factors . concrescence is classified as developmental or true if it occurs before root formation when roots of the adjacent teeth are in close proximity ; and post - inflammatory or acquired if it occurs after chronic inflammation in relation to a non - vital tooth . clinical detection of concrescent teeth is often difficult as radiographs usually fail to detect them . it is unusual to find the union of primary maxillary incisors and a supplemental incisor by cementum . the reported prevalence of a supplemental tooth in the deciduous dentition is 0.3 - 0.8% . the present case had carious infected teeth and the etiology of concrescence is likely post - inflammatory in nature . the close proximity of roots of triple teeth along with an excessive cementum formation during repair of periradicular lesions might have resulted in resorption of the interdental bone thus , triggering union by cementum . also , trauma sustained to the tooth 61 in early life , during the period of root formation , might have resulted in early cemental union of these three teeth . triple teeth complicate endodontics , oral surgical procedures , and periodontal treatment apart from being unaesthetic . primary triple anterior teeth may prevent or delay eruption of succedaneous and adjacent teeth , cause ectopic eruption , root deviation or root resorption of adjacent teeth . in the present case , the permanent tooth bud was displaced palatally , thus increasing the possibility of anterior cross bite . attempts at removal of a single tooth will facilitate removal of other teeth involved by concrescence which was so in this case as well . the heroic efforts to extract triple teeth , particularly when permanent molars are affected can lead to jaw fractures or oro - sinus communications . concrescence should be suspected if the roots of retained primary anteriors are in close proximity and are accompanied by a cariously infected pulp with or without a previous history of trauma . a clinical and multiple - angled radiographic examination of the conjoined triplets may establish the diagnosis . an appropriate treatment plan has to be decided thereafter , to minimize the risk of complications .

odontogenesis is a complex process wherein more than 200 genes are known to play a significant role in tooth development . an imbalance can lead to an abnormality in the number , size , shape or structure of the developing tooth / teeth . the presence of an extra dental lamina forms a supernumerary tooth . the supernumerary teeth are of two types : a rudimentary tooth where the supernumerary tooth does not resemble any tooth in the normal series or a supplemental tooth in which this anomalous tooth resembles one in the normal series . it is also very rare to encounter triple teeth in primary dentition . the union of these teeth may be through fusion , gemination , concrescence or a combination of fusion and gemination . presented is a rare case of concrescence involving maxillary deciduous incisors and a supplemental tooth in a 7-year - old boy . the differential diagnosis , etiology , and complications of primary anterior triple teeth are discussed .

nonurothelial tumors of the bladder are rare and account for less than 5% of all bladder malignancies . more than 100 cases of leiomyosarcoma have been reported , which represent 0.1% of all nonurothelial tumors . consensus is lacking regarding the definitive treatment of this type of bladder sarcoma , and little is known about its natural history and prognosis . herein we present the case of a young women in whom a low - grade leiomyosarcoma lying near the bladder neck was diagnosed . the patient has been doing well for 12 months of follow - up with no evidence of local or distant recurrences . a 22-year - old young woman presented with dysuria and lower urinary tract symptoms ( american urological association , 12 ) for 6 months . her results on renal function tests , urinalysis , and urine culture sensitivity were within the normal limits . the bladder ultrasound revealed a single bladder mass approximately 2.9 cm2.7 cm3 cm in size near the bladder neck . the results of urine cytology for malignant cells were negative . a contrast - enhanced computed tomography ( ct ) scan showed a well - defined , homogeneous , enhancing endophytic soft tissue lesion near the bladder neck ( fig . the histopathological examination revealed a tumor composed of proliferated elongated or spindle - shaped cells disposed in bundles or fascicles or an interlacing pattern ( fig . 2 ) . the cells enclosed ovoid nuclei and fair amounts of lightly stained cytoplasm . the immunohistochemical staining showed that the whole specimen was strongly positive for muscle actin , strongly positive for desmin , and negative for pancytokeratin ( fig . the results of the histopathology with immunohistochemical staining were consistent with a low - grade leiomyosarcoma . six cycles ( 21 days for each cycle ) of ifosfamide and doxorubicin were administered . the therapeutic response was monitored by contrast - enhanced ct and cystoscopic examination , which showed a partial response . next , external beam fractionated radiotherapy was given ( total 60 grays , 2 grays / d , 5 days / wk ) . the patient has been doing well for 12 months of follow - up , with no evidence of either local or distant recurrences . nonurothelial tumors of the bladder are rare and account for less than 5% of all bladder malignancies . more than 100 cases of leiomyosarcoma have been reported , which represent 0.1% of all nonepithelial tumors . consensus is lacking regarding the definitive treatment of this type of bladder sarcoma , and little is known about its natural history and prognosis . the most common clinical presentation is gross hematuria , which is reported in 81% of cases , followed by pollakiuria ( 28% ) and dysuria ( 19% ) , respectively . our case presented in the early third decade of life with lower urinary tract symptoms and dysuria . the presentation in our case was at a relatively earlier age than in other cases [ 3 - 5 ] . surgery with a tumor - free margin is the basic surgical principle for the treatment of leiomyosarcoma . tumors of a high grade and advanced stage should be treated with radical cystectomy and urinary diversion . partial cystectomy is reserved for tumors that present at an early stage and a low grade . in addition , local invasiveness , tumor size , and tumor grade are other important prognostic factors . the overall local recurrence rate of leiomyosarcoma is about 16% , and most recurrences are seen in the pelvis . although there is no general consensus on the treatment of leiomyosarcoma , minimally invasive approaches such as transurethral resection of the tumor and adjuvant chemoradiation are used for patients with small lesions . long - term survival rates were shown to not differ significantly compared with those in cases who undergo more radical surgery . partial cystectomy with sole resection of the mass , even when tumor - free margins are achieved , is just a palliative treatment . the main treatment consists of radical cystectomy , including removal of the uterus , cervix , and vaginal cuff in women . the procedure should include wide resection margins with a 2 to 3 cm depth free from tumor invasion . the role of adjuvant chemotherapy remains questionable . in case of metastatic disease , combination chemotherapy ( doxorubicin , ifosfamide , cisplatinum , and docetaxel ) salvage therapy is ineffective , with a median survival of 20 months after surgery . in the present case , we selected transurethral resection of the bladder tumor followed by sequential chemoradiation . the reasons for this choice were the small size and low grade of the tumor , the lack of radiological evidence of local or distant metastasis , and the location of the tumor near the bladder neck . the patient was young and unmarried and she did not agree to the radical surgery . we are also highlighting the fact that the minimally invasive modality is highly effective and can be adopted in young patients desiring bladder preservation .

a 22-year - old young woman presented with dysuria and lower urinary tract symptoms that had persisted for 6 months . she was diagnosed with a tumor near the bladder neck . transurethral resection was done under anaesthesia . the histopathological examination with immunohistochemical staining showed the tumor to be a low - grade leiomyosarcoma . adjuvant chemoradiation was given , and the patient has been doing well for 12 months of follow - up . nonurothelial tumors of the bladder are rare and consensus is lacking regarding their definitive treatment . furthermore , little is known about the natural history and prognosis of this type of bladder sarcoma . we present a minimally invasive treatment for this relatively rare tumor in which bladder preservation was achieved with no evidence of local or distant recurrences during the follow - up to date .

reagents were received from sigma aldrich chemical co. ( bangalore , karnataka , india ) and used without further purification . solvents were purchased from commercial sources from hyderabad , telangana , indiabased companies and purified by reported protocols . h and c nmr spectra were recorded on bruker 300 mhz and 500 mhz machines and calibrated against tetramethylsilane ( tms ) . mass spectrometric data were acquired by an electrospray ionization ( esi ) technique on a qtofmicro quadruple mass spectrometer . the stock solutions ( 110 m ) of ndin and ndina were prepared in chcl3 . an aliquot of it was transferred to various ratios of chcl3/mch in different volumetric flasks ( final volume of 2 ml ) and allowed to equilibrate for 2 h prior to the uv / vis absorption measurements . all experiments were performed upon excitation at 350 nm in a quartz cell with a 1 cm path length . the stock solutions were prepared in a similar manner as for the absorption study and employed for emission measurements . the stock solutions were prepared in chcl3 in a similar manner as for the uv / vis study . sem images of ndin and ndina were recorded on an fei nova nanosem ( hillsboro , or usa ) operating at high vacuum . for sem imaging , the samples of ndia and ndina were sputtercoated with gold for 10 s at 0.016 ma ar plasma after dropcasting the solutions on glass coverslip and solvent evaporation at rt . tem samples were prepared by the paper blotting method followed by solvent evaporation on a holey carboncoated copper grid . the liquid sample in chcl3/mch ( 5:95 , v / v ) was dropcasted and solvent was allowed to evaporate on the surface naturally . reagents were received from sigma aldrich chemical co. ( bangalore , karnataka , india ) and used without further purification . solvents were purchased from commercial sources from hyderabad , telangana , indiabased companies and purified by reported protocols . h and c nmr spectra were recorded on bruker 300 mhz and 500 mhz machines and calibrated against tetramethylsilane ( tms ) . mass spectrometric data were acquired by an electrospray ionization ( esi ) technique on a qtofmicro quadruple mass spectrometer . the stock solutions ( 110 m ) of ndin and ndina were prepared in chcl3 . an aliquot of it was transferred to various ratios of chcl3/mch in different volumetric flasks ( final volume of 2 ml ) and allowed to equilibrate for 2 h prior to the uv / vis absorption measurements . all experiments were performed upon excitation at 350 nm in a quartz cell with a 1 cm path length . the stock solutions were prepared in a similar manner as for the absorption study and employed for emission measurements . the stock solutions were prepared in chcl3 in a similar manner as for the uv / vis study . sem images of ndin and ndina were recorded on an fei nova nanosem ( hillsboro , or usa ) operating at high vacuum . for sem imaging , the samples of ndia and ndina were sputtercoated with gold for 10 s at 0.016 ma ar plasma after dropcasting the solutions on glass coverslip and solvent evaporation at rt . tem samples were prepared by the paper blotting method followed by solvent evaporation on a holey carboncoated copper grid . the liquid sample in chcl3/mch ( 5:95 , v / v ) was dropcasted and solvent was allowed to evaporate on the surface naturally . as a service to our authors and readers , this journal provides supporting information supplied by the authors . such materials are peer reviewed and may be reorganized for online delivery , but are not copyedited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors .

abstractin the present work , two new naphthalene diimide ( ndi ) amphiphiles , ndin and ndina , were successfully synthesized and employed to investigate their selfassembly and optical properties . for ndina , which contains an amide group , aggregationinduced emission enhancement ( aiee ) was demonstrated in the presence of various ratios of methylcyclohexane ( mch ) in chloroform , which led to the visual color changes . this new amidecontaining ndina amphiphile formed nanobelt structures in chloroform / mch ( 10:90 , v / v ) and microcuplike morphologies in chloroform / mch ( 5:95 , v / v ) . the closure of these microcups led to the formation of vesicles and microcapsules . the structural morphologies gained from the solvophobic control of ndina were confirmed by various complementary techniques such as infrared spectroscopy , xray diffraction , and scanning and transmission electron microscopy . in the absence of the amide moiety in ndin , no selfassembly was observed , indicating the fundamental role of hbonding in the selfassociation process .

subacute sclerosing panencephalitis ( sspe ) is a progressive disorder of central nervous system ( cns ) . there is a latent period of around 6 to 8 years before sspe manifests clinically . cognitive decline ( such as memory loss ) and myoclonus coupled with personality , behavioral and intellectual changes are common initial clinical features of sspe seen in around 80 - 97% of cases . other neurological features like seizure , blindness and hemiplegia tend to occur as illness progresses . in advanced stages of the disease , individuals may lose the ability to walk , as their muscles stiffen or spasm . there is progressive deterioration to a comatose state , and then to a persistent vegetative state . the diagnosis of sspe is based on signs , symptoms and typical changes observed in electroencephalograph ( eeg ) . additionally , there is elevated anti - measles antibody ( igg ) in the serum and cerebrospinal fluid . however , the presence of additional signs and symptoms during initial stages make the case challenging clinically and can delay the diagnosis . catatonia is not a usual clinical presentation of sspe , especially in the initial stages of illness . however , there is only one reported cases of sspe presenting as catatonia among children . in this report , however , there were sspe - specific changes found on eeg and the catatonia failed to respond to lorazepam . we describe a case of sspe in a child presenting as catatonia that presented with clinical features of catatonia and did not have typical eeg findings when assessed at first contact . he responded to lorazepam and eeg changes emerged during the course of follow - up . a 14-year - old schoolboy was brought to department of psychiatry at a tertiary care general hospital in india . the parents reported an insidious onset illness with a progressive course of 6 months duration with no apparent precipitating factor . the presenting complaints included reduced interaction , minimal responsiveness to questions and occasional mimicking of utterances of others . he would keep standing at one spot for long periods of time without any apparent reason , make poor eye contact and would resist attempts at moving him . the parents reported that these features followed a brief initial phase characterized by poor school performance , withdrawn behavior and decreased interaction with others . there was no history of any prolonged high - grade fever or history of abnormal body jerky movements or history of fits . there was no history to suggest motor , sensory , and bladder or bowel involvement . there was no history of headache , vomiting , loss of consciousness , dimness of vision or jaundice . there was no history of use of psychoactive substances . on examination , he was conscious and afebrile . application of bush francis catatonia rating scale ( bfcrs ) revealed a score of 8 . he was found to have signs of mutism , posturing , echolalia , grimacing , rigidity and negativism . bio - chemical variables including complete hemogram , liver functions and renal functions were with - in normal range . electroencephalogram ( eeg ) showed generalized slowing and ct brain also did not reveal any abnormality . catatonic signs and symptoms partially responded to lorazepam with a reduction in bfcrs score to 4 . he again visited department of psychiatry after 4 months with myoclonus , episodes of generalized tonic - clonic movements and neurological deficits . eeg was characterized by periodic complexes consisting of bilaterally symmetrical , synchronous , high - voltage bursts of polyphasic , stereotyped delta waves [ figure 1ac ] . catatonia is a distinct motor syndrome first described in 1874 by the german psychiatrist karl ludwig kahlbaum . various studies have reported psychiatric causes of catatonia ranging from 70% to 80% and organic causes of catatonia ranging from 20% to 30% . also , responses to lorazepam treatment among catatonic patients have been reported in some studies , mainly among psychiatric cases . catatonia has not been reported as a usual clinical manifestation of sspe during early stages of the illness . states of minimal conscious progressing to akinetic mutism are usually seen only in the advanced stages of sspe . there are only two earlier published reports of sspe presenting as catatonia in the initial stages . the case presented with features of catatonia and the diagnosis of sspe could be confirmed based on typical changes on eeg , mri and serological findings at time of first presentation . in the current case , however , eeg changes were not suggestive of sspe at the time of first presentation . only a non - specific generalized slowing was observed on eeg . consequently , the case could not be identified as that of sspe and was managed symptomatically for catatonia . unlike the earlier reported case , the current case responded to lorazepam during the initial few days and a reduction in catatonic features was observed . the diagnosis of sspe was later confirmed based on usual neurological manifestation , eeg recordings and serological findings . interestingly , a history of measles infection earlier during childhood could not be established as well in this case . failure to elicit past history of measles infection has been reported in earlier reported cases of sspe among children as well . the case highlights the importance of considering possibility of viral encephalitis as a possible cause of catatonic presentation during childhood . such a consideration is warranted even if the history of viral illness earlier during childhood is not evident . relevant investigations need to be repeated during the course of follow - up even if the earlier findings were non - contributory . also , a trial of lorazepam can be considered for catatonic features during earlier stages . the case is of particular relevance as annual prevalence of sspe has been reported to be high at 21 cases per million people in some settings . while the prevalence has been reported to be lower in developed countries , sspe is of relevance to these countries as well in context of the migrated population . cases of sspe have been reported among immigrants even years after resettlement . also , eeg is a cost - effective tool in establishing diagnosis of sspe in such settings . it can be repeated at periodic intervals if the clinical features fail to resolve . neuroimaging techniques such as mri and serological investigations are more expensive and not widely available in many settings . in conclusion therefore , pediatricians , neurologists as well as psychiatrists should be aware of this possibility .

catatonia is not a usual clinical presentation of subacute sclerosing panencephalitis ( sspe ) , especially in the initial stages of illness . however , there is only one reported case of sspe presenting as catatonia among children . in this report , however , there were sspe - specific changes on eeg and the catatonia failed to respond to lorazepam . we describe a case of sspe in a child presenting as catatonia that presented with clinical features of catatonia and did not have typical eeg findings when assessed at first contact . he responded to lorazepam and eeg changes emerged during the course of follow - up .

electrical failure during cardiopulmonary bypass ( cpb ) is an undesired situation with possible catastrophic consequences in the operating room . its incidence is estimated to be 1 per 1000 cases , fortunately with low morbidity and mortality . during 2000 routine cpb cases in our institution within the period of 4 years , 1 case of electrical failure was observed . different mechanisms of electrical failure have been reported , including mains failure , generator failure , and uninterrupted power supply ( ups ) failure [ 1 , 2 ] . since these kinds of equipment failure and accidents are very rare , little attention is given to preventative measures concerning electrical supply and backup batteries . operators should be informed during their education about this life - threatening scenario , since taking the wrong action during a crisis may lead to serious consequences . , we report a case involving electrical failure during cpb due to a ups failure , which was managed successfully by the cardiac surgical team . a 51-year - old , 84-kg male patient with low ejection fraction was undergoing cpb during one - vessel coronary bypass surgery concomitant with the repair of a huge left ventricular aneurysm . suddenly , the heart - lung machine and the heat exchanger stopped . the other pieces of equipment , including the anesthetic machine , lights , and monitors , remained functional . the console of the pump showed no power supply . only the power to the protected sockets was interrupted . soon , it became apparent that a new neurosurgical navigation device had been used for the first time , which led to the ups failure . luckily , when the heart - lung machine and the heat exchanger were shut down , the patient 's core temperature was 34c , the operative procedures were completed , and the aortic cross clamp had already been released . however , the temperature and hemodynamic parameters were not satisfactory enough to wean the patient from cpb . in the first place , the venous line was clamped , and hand - cranking was initiated simultaneously with adjustment of venous clamping in order to maintain the reservoir level . the sockets were replaced with standard sockets , but the machines did not function . therefore , hand - cranking was performed for 10 minutes . surface heating was conducted , inotropic support was initiated to increase blood pressure , and , finally , the patient could be weaned with a core body temperature of 35c . electrical failure during cpb leads to the shutdown of the heart - lung machine , which may not be restored immediately depending on the mechanisms of the failure and the technical status of the hospital . this possibly devastating scenario may only be managed with the help of a ready surgical , perfusionist , and technical team . despite the low rates of mortality and morbidity , in a large survey reporting 200 interrupted cases , the key point is that , even when the pump stops , the venous return to the reservoir continues , so the first step should consist in clamping the venous line . the venous return should be controlled , and the reservoir level should be maintained [ 1 , 4 ] . this duty may be performed by some other members of the team to allow the perfusionist to deal with the restoration of systemic perfusion . if the heart is contracting when the pump stops , only the occlusion of the venous line may restore systemic perfusion , sometimes with the help of inotropic support . if the aorta is clamped , the only solution is hand - cranking [ 1 , 2 , 4 , 5 ] . hand - cranking is effective in terms of restoring systemic perfusion , but the universally accepted time limit for a single person is 15 minutes , to prevent exhaustion [ 1 , 4 ] . even when hand - cranking was performed for only 1 minute , the flow rate achieved in the second half of that minute was not as high as desired . in the same study , tomizawa et al . documented that the target flow rate could be achieved without practice , but adjustment of the venous reservoir level by clamping required practice . it is recommended that the surgeon should intermittently palpate the aorta in order to evaluate the efficacy of hand - cranking . if it is not possible to restore the electrical supply immediately , the aortic cross clamp should be released as soon as possible even at the expense of incomplete surgery . if the heat exchanger is also affected , warming should be ensured by other means . at the same time , battery and other sources of power supply to monitors , anesthetic machines , surgical lamps , and defibrillators should be provided . we clamped the venous line first , performed hand - cranking , and weaned the patient from cardiopulmonary bypass as soon as possible . the electrical supply of the institution should be dual , so that if one element shuts down , the other will continue to function . the ups should be situated in an adequate environment to prevent overheating , and the battery condition should be checked periodically . backup batteries for pump consoles should be supplied if not present , and should be checked frequently . a separate , portable , petrol - driven generator with extension cables may be kept close to the operation room [ 1 , 4 ] . electrical failure during cpb may result in devastating injury to the patient and the surgical team if no preventative measures are taken and no management strategies are developed . taking action without panic and adhering to a previously designed algorithm is essential for all surgical teams .

electrical failure during cardiopulmonary bypass is a crisis situation for the cardiac surgical team . fortunately , it has a low incidence with low morbidity and mortality rates . notwithstanding , institutional preventative and management measures should be taken . here , we report a case of electrical failure during cardiopulmonary bypass , which was successfully managed during the surgery , allowing the patient to recover uneventfully . these unwanted complications can only be managed by promoting awareness and putting in place strategies against them .

wegener granulomatosis ( wg ) is a rare multisystem autoimmune disease of unknown etiology.1 2 it is a systemic vasculitis , affecting small and medium - sized vessels of the upper and lower respiratory tract and kidneys , including necrotizing granulomatous inflammation.2 3 wg has a spectrum of clinical presentations that includes recurrent respiratory infection , renal manifestations , and nonspecific systemic symptoms . otologic manifestations are occasionally the first to appear in 20 to 60% of cases of wg , and serous otitis media is the most common presentation in ear disease.4 5 6 however , wg is not a common diagnosis in ear , nose , and throat ( ent ) practice . we describe a case of a 50-year - old woman with severe bilateral hearing loss as the first symptom of the disease . the differential diagnosis of wg with otologic manifestations may include tuberculous otitis media , cholesteatoma , langerhans cell histiocytosis , neoplastic diseases , and other forms of vasculitis , sarcoidosis , and systemic lupus erythematosus . tuberculous otitis media is characterized by painless otorrhea that fails to respond to the usual antimicrobial treatment in a patient with evidence of tubercle infection elsewhere , followed by multiple tympanic membrane perforations , abundant granulation tissue , bone necrosis , and preauricular lymphadenopathy . deafness is out of proportion with the apparent degree of development of disease seen in the otoscopy . an ear exam may show a pocket or perforation in the eardrum often with drainage when cholesteatoma occurs . known previously to have sarcoidosis , this disease should be seriously considered . in patients presenting with otologic disorders and associated facial nerve paralysis or other neuropathies , uveitis , granulomatous meningitis , or diabetes insipidus , sarcoidosis should be suspected . an examination of the eyes as well as a chest x - ray is imperative . the patient presented with complaints of severe and progressive bilateral hearing loss with onset 6 months previously . symptoms evolved with otorrhea and pain refractory to broad - spectrum antibiotics and nonsteroidal anti - inflammatory drugs . during ent examination , otoscopy showed bilateral thickening and retraction of the tympanic membrane and fluid in the middle ear , with no other clinical findings . after carrying out the audiometry ( fig . 1 ) and after 1 month , the patient complained of weight loss ( 7 kg / mo ) , lack of appetite , fevers , night sweats , asthenia , and dry cough . laboratory findings revealed mild normochromic normocytic anemia , westergren erythrocyte sedimentation elevated rate , elevated c - reactive protein , nonreactive mantoux tuberculin skin test , negative sputum smear , and negative hiv antibody . computed tomography of the temporal bone ( fig . chest computed tomography showed the presence of pulmonary nodules and masses with excavation areas in the left upper and lower lobes , with moderate pericardial effusion ( fig . 3 ) . bronchoscopy with transbronchial biopsy showed inconclusive pathologic result , with the presence of discrete fibrous thickening and septal fibrosis nodular focus . chest computed tomography showed the presence of pulmonary nodules and masses with excavation areas in the left upper and lower lobes and moderate pericardial effusion . the patient was also referred to the department of rheumatology for antineutrophil cytoplasmic antibodies testing , which was positive , and then antiproteinase 3 antibody testing , which was also positive , confirming the diagnosis . with the onset of steroid ( prednisone 60 mg / d ) , the patient 's symptoms improved and hearing thresholds recovered significantly after 1 week of treatment ( fig . the patient currently uses cyclophosphamide monthly and corticosteroids daily with good clinical and laboratory control . wg is a rare idiopathic disease , immunologically mediated , which affects the small arteries of the upper and lower respiratory tracts and the kidneys , causing inflammation with necrosis , granuloma formation , and vasculitis in these organs.1 2 3 4 the average age of diagnosis is usually between 20 and 40 years , and males are affected more than females ( 1.5:1.0).5 otologic manifestation varies widely , occurring in 20 to 60% of the affected patients , and includes serous otitis media , chronic otitis media , sensorineural hearing loss , vertigo , tinnitus , and facial palsy.4 6 treatment should be started early for a better hearing outcome.7 pulmonary manifestations occur in 45% of cases at initial presentation and 87% during the course of the disease.8 9 ocular involvement in wg can be part of the initial presentation of the disease in 8 to 16% of cases . the majority of studies have reported initial manifestations in ent , followed by lung , skin , and kidneys.3 10 immunosuppressive drugs are the first - line therapy.1 2 5 in cases of acute ear manifestations with or without hearing loss and with poor response to usual treatments , wg should be included among the possible etiologies . as the prognosis depends on early diagnosis and appropriate treatment , the otolaryngologist plays a decisive role in reducing the morbidity and mortality rate in this disease .

introduction wegener granulomatosis is a systemic vasculitis affecting small and medium - sized vessels of the upper and lower respiratory tract and kidneys . objective to describe a case of wegener disease with atypical manifestation . resumed report we describe the case of a 50-year - old woman with chronic otitis media and sensorineural hearing loss as the primary symptoms , without other manifestations . conclusion in cases of acute ear manifestations with or without hearing loss and with poor response to usual treatments , wegener granulomatosis should be included among the possible etiologies . after adequate diagnoses and treatment of this rare disease , there was favorable evolution .

infection itself is often asymptomatic but long - term can lead to the development of cirrhosis and hepatocellular carcinoma . since the molecular cloning of hcv in 1989 , significant research into potential treatments for chronic hcv infection has been carried out . the current standard of care is therapy with pegylated interferon ( peg - ifn2a or peg - ifn2b ) in combination with ribavirin for between 24 and 48 weeks . in genotype 2 and 3 infections , a sustained virological response ( svr ) , effectively a cure , the svr rates in the other genotypes are less favourable , especially the common genotype 1 infection in which svr rates are less than 42 - 46% . the question then arises of how to treat those patients who do not achieve an svr despite full compliance with therapy . potential strategies include dose optimisation , extended duration , additional treatments , and specifically targeted antiviral therapies for hcv ( stat - c ) . current work suggests that retreatment of individuals who have failed prior therapy may be beneficial in specific subgroups . a number of studies have shown that individuals who are relapsed responders ( rrs ) to ifn and ribavirin as opposed to non - responders ( nrs ) are more likely to respond to retreatment regimens , as are those who have received prior standard ifn rather than peg - ifn . in these studies , the svr rates for rrs treated with standard ifn and ribavirin were 42 - 45% as opposed to 8 - 17% for nrs and , in the epic ( efficacy of peg - ifn in chronic hepatitis c ) study , 36 versus 4% for rrs and nrs , respectively , when treated with peg - ifn and ribavirin . studies that have made combined analyses on individuals treated with ifn monotherapy or combination therapy have shown a pronounced effect of genotype on outcome , with svr rates of 57 - 60% for genotype 2/3 as compared with 14 - 17% for genotype 1 . higher doses of ribavirin and ifn have been tested and look most promising for difficult - to - treat groups . weight - based dosing of ribavirin is important in individuals with genotype 1 infection treated with either peg - ifn2a or peg - ifn2b . increasing the dose of ribavirin from 13.3 to 15.2 g / kg per day ( maximum dose of 1,600 mg ribavirin / day ) can also improve svr rates . prolonging the duration of therapy from 48 to 72 weeks may be beneficial in patients who are slow - responders ( that is , remain pcr ( polymerase chain reaction ) positive at week 4 ) . initial data from the repeat ( retreatment with pegasys in patients not responding to peg - intron therapy ) study suggested that induction with high - dose peg - ifn2a ( 360 g ) may be beneficial in prior nrs , but it now appears that this enhanced benefit is more likely to be related to extending the duration of therapy . disappointingly , a trial of consensus ifn and ribavirin in peg - ifn and ribavirin nrs gave svr rates of only 6.9% ( 9 g consensus ifn ) and 10.7% ( 15 g ) on intention - to - treat analysis . stat - c agents , given in combination with peg - ifn and ribavirin , offer the greatest promise in the retreatment of prior nrs or relapsers to current optimal treatment regimens . however , viral resistance is common when they are given as monotherapy , hence the necessity of combination treatment . two drugs , telaprevir and boceprevir , both ns3-ns4a protease inhibitors , have entered phase iii testing . in phase ii studies performed in combination regimens with peg - ifn and ribavirin , telaprevir achieved svr rates of 61 and 67% [ results from the phase 2 study of vx-950 , pegasys , and copegus in hepatitis c ( prove ) ] and boceprevir achieved an svr rate of 57% [ results from sprint ( serine protease inhibitor therapy ) ] in ifn - nave patients [ 16 - 18 ] . these agents induce a rapid decrease in hcv rna , which in current peg - ifn - based regimens is associated with svr . prove 3 is currently studying telaprevir in previously treated individuals , it also shows greater efficacy at the end of treatment in the relapsers to prior treatment as opposed to nrs . of note is that these agents can generate significant side effects , including fatigue , anaemia , and rashes ( telaprevir ) . further studies of nucleoside polymerase inhibitors and non - nucleoside polymerase inhibitors are under way [ 20 - 23 ] . whilst the emerging data on these new agents are exciting , viral resistance to them has been described as early as day 8 . this has highlighted the need to avoid monotherapy and combine them either with drugs with nonoverlapping resistance profiles or with peg - ifn and ribavirin . the concept of suppressing or halting disease progression using low - dose maintenance peg - ifn has been evaluated in three long - term trials : co - pilot ( colchicine versus pegintron long - term ) , epic , and halt - c ( hepatitis c antiviral long - term treatment against cirrhosis ) . the rates of clinical outcomes and histological progression were , in general , similar between treated and untreated control groups , and therefore this strategy does not represent a viable treatment option for the majority of virologic nrs to current therapy . the concept of suppressing or halting disease progression using low - dose maintenance peg - ifn has been evaluated in three long - term trials : co - pilot ( colchicine versus pegintron long - term ) , epic , and halt - c ( hepatitis c antiviral long - term treatment against cirrhosis ) . results from the halt - c trial were published recently . the rates of clinical outcomes and histological progression were , in general , similar between treated and untreated control groups , and therefore this strategy does not represent a viable treatment option for the majority of virologic nrs to current therapy . current studies are beginning to report successful retreatment with peg - ifn and ribavirin in specific subgroups of individuals . individuals who are rrs may benefit from retreatment with optimised dosages and durations of peg - ifn and ribavirin . the key to successful treatment is to ensure adherence to the regimen , which can be achieved with supportive nursing care . induction with peg - ifn or use of higher and weight - based dosing regimens of ribavirin may require additional haematological support with granulocyte - macrophage colony - stimulating factor and erythropoietin . however , true nrs are unlikely to gain benefit from a further course of peg - ifn and ribavirin . stat - c agents in combination with peg - ifn and ribavirin should become the mainstay of treatment for this group of individuals . however , the optimal dosage schedules for using them have yet to be determined . at present , telaprevir and boceprevir represent the most likely therapies to emerge on the market in the near future . until then , inclusion in trial protocols may represent the best option for these individuals , with the caveat that there is a theoretical risk of selecting for resistant viral variants if these patients can not be made to be rapid responders .

the standard of care for treatment of individuals chronically infected with hepatitis c virus is pegylated interferon in combination with ribavirin . efficacy is closely related to viral genotype . this review outlines potential therapeutic strategies for treatment failures and discusses some of the newer agents currently in development .