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. they can be either pedunculated or sessile and are more common in the extremities . we present a case of 18 year female , who came with a swelling in right groin since 2 years which was diagnosed to be osteochondroma on x - ray and magnetic resonance imaging . excision biopsy was done as the patient wanted it to be removed for cosmetic purpose and confirmed it to be non - malignant osteochondroma . thus osteochondroma of the pelvis should be kept in mind as a differential diagnosis when evaluating mass in pelvis . . they can be either pedunculated or sessile and are more common in the extremities , i.e. distal femur , proximal tibia and proximal humerus in decreasing order . indications for excision are cosmetic deformity , pressure symptoms on neuro - vascular bundle or malignant transformation to chondrosarcoma which is rare . osteochondroma of the pubic ramus is rare entity and the actual incidence is not known . it can present as a solitary lesion or as a part of multiple hereditary exostosis . pelvic osteochondromas can present as compressive neuropathy or compressive symptoms on urethra , bladder or other vital structures and so on . on the contrary a pubic bone mass may need to be removed in young females which might be prominent at labia for cosmetic reasons as in our case . an 18 year female came to the out - patient department with complaints of swelling in right groin since 5 years which was insidious in onset , small in size initially but grew over last 5 years and was noticeable to the patient . , there was a bony hard swelling 3 5 cms in size in the groin at the pubic tubercle of the right side . plain x - ray s of pelvis ap , inlet and outlet view ( fig.1 to 3 ) and magnetic resonance imaging ( fig 4 & 5 ) showed bony growth of 543746 mm in size in transverse , craniocaudal and anteroposterior dimension which was arising from right superior pubic ramus and was extrapelvic in situation with a cartilage cap of 4 mm . 6 ) was taken and as the soft tissue was retracted cartilage cap of the osteochondroma was seen ( fig . manual palpation was done and one more piece was found which was then excised ( fig . 9 ) . inguinal ligament was closed in layers maintaining the external iliac ring with continuous sutures to prevent future inguinal hernia ( fig . osteochondromas are benign tumors which have an unknown etiology . it is considered as a developmental physeal abnormality rather than a primary bone neoplasm . a few theories have been suggested which include virchow theory , muller theory , keith theory , and a few more . the most common sites are metaphysis of long bones like distal femur , proximal tibia and proximal humerus . osteochondromas can also be found as a part of multiple hereditary exostosis which is thought to be associated with ext1 and ext 2 gene . osteochondromas are as such an incidental finding in patients and only a few are symptomatic . it is usually present in growing age and the growth of the mass stops after skeletal maturity . various studies have mentioned about the size of cartilage cap as a predictor for malignancy with a cartilage cap of more than 2 cm after skeletal maturity indicative of malignant transformation . pre operative investigations and planning in patients presenting with a bony neoplasm must be done . pre - operative x - rays and mri were done for our patient to see the extent and measure the cartilage cap of the osteochondroma . pelvic osteochondroma involving ilium has been reported in literature which caused nerve root compression and had to be removed . osteochondroma of the pubic symphisis has been reported which was removed due to bladder outlet obstruction . thus with a thorough search in literature we concluded that it is a rare entity and it was diagnosed due to the compressive symptoms caused by it . here in our case the swelling near the private part was the cause for the patient to seek medical help . there were no compressive symptoms either on vessels or on urinary tract which was confirmed by arterial doppler and micturating cysto - urethrography . a similar case was reported by qaisrani gh and associates which was also present on superior pubic ramus and was removed for cosmetic deformity . complete en - bloc removal of the mass was done in our case for cosmetic reasons and she is being followed up regularly . even after 1 year there has not been any recurrence of the lesion . benign osteochondromas are usually incidental findings and are removed most commonly for cosmetic purposes with a very low incidence of recurrence if removed after skeletal maturity . also pelvic osteochondromas are rare entity but it has to be kept in mind for any bony mass when looking for differentials . pelvic osteochondromas are rare entity but it has to be kept in mind for any bony mass when looking for differentials .

introduction : osteochondroma are benign neoplasms which arise from small cartilage nodules within the periosteum . they can be either pedunculated or sessile and are more common in the extremities . they rarely develop in bones like scapula , feet , hands and pelvis . management of the lesion is by en - bloc excision.case report : we present a case of 18 year female , who came with a swelling in right groin since 2 years which was diagnosed to be osteochondroma on x - ray and magnetic resonance imaging . excision biopsy was done as the patient wanted it to be removed for cosmetic purpose and confirmed it to be non - malignant osteochondroma . there has been no recurrence even after 1 year of follow up.conclusion:thus osteochondroma of the pelvis should be kept in mind as a differential diagnosis when evaluating mass in pelvis . also these have to be removed when they pose cosmetic problems .

cancer of the gastric stump in patients previously operated on for benign disease was first mentioned by balfour in 1922 and was subsequently described by several authors . today , cancer of the gastric stump is no longer the great rarity it was once considered to be . although the question whether gastric resection for ulcer disease implies an increased risk for subsequent cancer remains a matter of dispute . many authors in western europe agree that there is evidence of increased risk compared with the normal population . although stomach cancer is the most common malignancy of adults in korea , there has been one report of 3 case of stump cancer . a 69-year - old man was transferred to our hospital with the chief complaints of hematemesis and melena . about 5 days before admission he had received 5 pints of blood at a private clinic because of hypovolemic symptoms . he had a history of subtotal gastrectomy 20 years ago due to a bleeding duodenal ulcer . two years before admission he checked ugis at opd but there was no evidence of a filling defect or ulceration on the remnant stomach and anastomosis . on physical examination , the patient was pale and presented a chronically ill appearance . his blood pressure was 110/70 , pulse rate 110/min , respiration rate 25/min and temperature was 36.5c , the sclera was not icteric but the conjunctiva was slightly anemic . on abdomen no organomegaly or palpable mass was detected and the surgical scar was noted . all routine laboratory tests were normal with the exception of hemoglobin and hematocrit ( 8.1 g / dl , 27.1 % respectively ) , the liver function tests were normal . an upper gastrointestinal series revealed a large filling defect with central ulceration , about 63 cm in size on the anterior wall side of the residual stomach body ( fig . a large nodular mass was noted on the anterior wall and lesser curvature aspect of the body 2 cm above the stoma . 2 ) . the abdominal ct revealed no evidence of regional metastasis to liver , spleen , pancreas and no demonstrable lymphadenopathy in perigastric , retroperitoneal and mesenteric group . the tumor measured 7.55.0 cm in cross diameter and was located 8.5 cm from the proximal resection margin . sections from the gastro - jejunostomy site showed moderately well differentiated adenocarcinoma of the stomach , which directly extended into the anastomosis site of the jejunum ( fig . when defining cancer of the gastric stump , two criteria must be fulfilled ; first , the previous surgery ( partial gastrectomy or gastroenterostomy ) should be for benign disease , and second , to rule out the presence of an occult carcinoma at the time of the surgery a time interval of at least five years should have elapse since the original gastric resection . although the interval between resection for ulcer and the appearance of gastric stump cancer varied , it increased to six to eight times as much between the 15th and 30th years after the initial surgery . in our case the interval was about 20 years , in 1966 the patient underwent a subtotal gastrectomy due to massive upper gi bleeding . the incidence of stump cancer varies considerably with geographical location , with a high incidence in certain parts of scandinavia as well as in central europe . contrary to these findings this form of malignancy is seldom observed in great britian or in the united states . in a controlled retrospective study of 630 cases of gastric cancer , the frequency of previous gastric surgery for ulcer was increased to about six times more than the control for those patients operated on 25 years previously . in southern germany griesser and schmit , reported the frequency of stump cancer was 13.3% among 580 patients after partial gastrectomy for gastric ulcer . most authors agree to a causal relationship of partial gastrectomy and an increased risk of cancer in the gastric remnant . however some investigators did not observe a higher frequency of stump carcinoma than expected in the normal population with intact stomachs . but in korea , there has been one report of 3 cases of stump cancer , although stomach cancer is the most common malignancy in adults , stump cancer is very rare . the reasons are not well established , but , one of which is that billroth ii resection was introduced about 30 years ago in this country , therefore , the incidence of stump cancer maybe increase if regular examination has been performel . although the etiology of stump cancer has not been determined , clinical and experimental observations have pointed to the important role of the duodenogastic reflux . bile , the main component of the doudenogastric reflux is known to act as a detergent thereby damaging the mucosal barrier of the stomach . atropic gastritis , intestinal metaplasia , and cystification of the mucosal glands are common findings in the vicinity of a gastroenteric anastomsis . the prominence of a billroth ii anastomosis or a gastroenterostomy rather than a billroth i gastroduodenal anastomosis undoubtedly reflected the more frequent use of the former procedures in the earlier era . however a latter study of 74 patients with a billroth i anastomosis found stump cancer in 5.4 per cent , suggesting that the risk was present regardless of the type of previous ulcer surgery . griesser and schmidt , reported the frequency of stump cancer was 13.3% among 580 patients after partial gastrectomy for gastric ulcers , but when the indication for stomach resection was a duodenal ulcer , only 6.25% of the patients developed a cancer . however other investigators reported that there is no difference in the incidence of cancer of the stump as related to the primary ulcer site . the main problem in stump cancer , as in any gastric cancer , is related to early diagnosis . most patients come too late for treatment , because the symptoms are misinterpreted by the patients , and often by their doctors , too , as benign postgastrectomy symptoms . one should be especially aware of the possibility of cancer in patients , who , after a long symptomless interval , complain of dyspepsia and other nonspecific gi symptoms . in our patient , the x - ray pictures taken 2 years before admission , showed no evidence of malignancy , but had gastroscopy been performed at that time , we could have had different information about the remnant stomach . x - rays are often difficult to interpret , as benign postoperative changes may be difficult to distinguish from cancer , so gastroscopy is , in our opinion , the best diagnostic method . although carcinoma of the gastric stump is either exophytic or appears as an ulcer , exophytic tumors are more common . the direction of growth is mainly along the minor site of the gastric remnant from distal to proximal . studies concerning the localization of cancer of the gastric stump have pointed to the stoma as a specific area . hammar , studied 65 autopsy specimens and provided strong evidence for a typical site of cancer growth within the billroth ii stoma . the only treatment for stump cancer as well as gastric cancer , is surgical . from various reports , saegesser & waridel , recommended subtotal gastrectomy by this method , because total gastrectomy is a greater trauma to the patient , and leads to more serious postoperative complications . saegesser & waridel claim that the prognosis in the cases which can be radically operated , is not worse than for operable gastric cancers in general . the etiology of cancer in the gastric stump is still obscure , but the risk of developing cancer increases considerably with increasing time , all patients who have undergone gastric resection should be regularly followed up by gastroscopy .

carcinoma of the gastric stump as a late complication for resection of benign disease is a well recognized clinical entity.the risk of stump carcinoma , at least in western europe , is estimated to be increased twofold compared with the normal population.but in korea there has been one report . recently we experienced a case of carcinoma of the stump which developed about 20 years after a gastro - jejunostomy for a duodenal ulcer .

fungal meningitis is a rare cause of meningitis and results from the spread of fungi to the cerebrospinal fluid ( csf ) . the most common causes of fungal meningitis include , cryptococcus neoformans , histoplasma capsulatum , blastomyces dermatitidis , and coccidioides immitis / posadasii . hiv / aids , solid organ transplantation , high dose steroid use , malignancy , and other primary and secondary immunosuppressed states are associated with a higher risk of coccidioides meningitis than in immunocompetent patients . , , we present a case of meningitis with cerebral infarction from vasculitis as one of the manifestations of coccidioidal meningitis in a patient with acute lymphocytic leukemia ( all ) . a 23-year - old woman with a history of b - cell all and cns involvement presented to the emergency department with severe headache , nausea , vomiting , fatigue , worsening mental status , and fever for approximately one week . her other chemotherapy regimen included 6-mercaptopurine , vincristine , and prednisone 100 mg oral daily for 5 days at the start of the month . the patient did not have a prior history of coccidioidomycosis and no prior coccidioides serological testing . moreover , her medical history included diabetes mellitus , deep vein thrombosis , and depression . past surgical history included an insertion of omaya reservoir nine months before admission for intrathecal chemotherapy , which was removed due to postoperative complications including altered mental status , intracranial , and ventricular hemorrhage . on admission , the patient was obtunded : opening eyes to verbal and tactile stimuli , following simple commands intermittently , but was otherwise unable to perform more thorough testing . neurological examination showed intact strength and sensation in the right upper and lower extremities , but diminished strength in the left upper extremity and left lower extremity on plantar flexion ( 4/5 ) . she had diminished reflexes in upper extremities 1 + throughout bilaterally , and 0 in lower extremities bilaterally , with flexor plantar reflexs . lumbar punctures were performed on hospital days 1 , 8 , 22 and 23 and the results are summarized in table 1 . brain magnetic resonance imaging ( mri ) showed extensive small vessel deep infarctions involving both cerebral hemispheres , the midbrain and cerebellum ( see fig . 1 , fig . 2 ) . a right distal portion infarct of the middle cerebral artery was present . serum coccidioides antibodies ( igm and igg ) by enzyme - linked immunosorbent assay ( eia ) were positive . the patient was administered liposomal amphotericin b ( 5 mg / kg ) and was continued on intravenous fluconazole ( 800 mg daily ) . on day 8 , due to the lack of clinical response and mental status deterioration , a repeat lumbar puncture ( see table 1 ) and mri/ magnetic resonance angiogram ( mra ) were done . mri / mra showed : subacute infarcts involving the bilateral temporoparietal lobes , left lentiform nucleus , left medial temporal lobe , portions of the caudate head on hemisphere , right thalamus , right basal ganglia , and right insular cortex ( see fig . 2 ) . characteristic enhancing basilar leptomeninges and ring - like irregular enhancing focal lesions were also seen ( see fig . a ct angiogram of the head and neck confirmed suspicion for vasculitis by demonstrating caliber variation of several intracranial vessels ( see fig . micafungin and prednisone ( 60 mg daily ) were added ( on day 14 and 17 , respectively ) after a discussion at a multidisciplinary conference . she would open her eyes to verbal stimuli and was able to say short two - three word sentences . her strength had improved to 4/5 in all of her extremities ; however , she still had severe cognitive deficits and significant impairments of activities of daily living . coccidioidomycosis is the most common cause of fungal meningitis in arizona , california , new mexico , and western texas . primary coccidioidomycosis affects the lung , but may spread to other organs in 0.6% of the cases . patients with dissemination are severely sick and treated with amphotericin b and/or a triazole antifungal . the use of an echinocandin in combination with amphotericin b deoxycholate has also been shown to increase survival and decrease tissue burdens of coccidioides in mice models . . the most common presentation of cns disease is headaches , decreased cognition , and basilar meningitis . , in a retrospective analysis of 60 patients with coccidioidal meningitis by mathisen et al . , headache was the most common presenting symptom ( approximately 80% of patients ) and signs of increased intracranial pressure ( nausea / vomiting , papilledema ) were seen in about 50% of patients - which were initial complaints of the patients . mri post - contrast can show enhancement of cervical subarachnoid space , basilar , sylvian , and interhemispheric cisterns with focal parenchymal signal abnormalities indicating ischemia or infarction . . complications of meningitis related to coccidioidomycosis include hydrocephalus , infarction , vasculitis , and abscess . vasculitis is life threatening and is characterized by cerebral infarction due to inflammatory changes in the walls of small and medium size cerebral arteries and veins leading to vascular insufficiency and neurologic deficiencies resembling stroke . williams pl et al . , reported 10 cases of vasculitis due to coccidioidal meningitis . the time to onset was less than 1 month in 5 cases , 12 months in 3 cases , and greater than 2 months in 2 cases . drake et al . reported 71 cases of coccidioidal meningitis with 31% of those cases showing parenchymal brain lesions which most were believed to be secondary to vasculitis . . choice of therapy providing the most favorable outcome in coccidioidal cns vasculitis resulting in infarction remains unsettled . this was prior to discovering that azoles could be used to treat meningeal disease . the minimum dose is 400 mg daily , but higher doses are preferred initially 800 mg was used in our patient . the lipid preparation of amphotericin b has been shown to increase benefit in animal studies to treat coccidioidomycosis meningitis . limited data exist regarding the use of caspofungin , duration of therapy and the role of steroids in the treatment of vasculitis in patients with coccidioidal meningitis . , . currently , the use of steroids in the setting of vasculitic infarction is controversial although the updated infectious diseases society of america guidelines for the treatment of coccidioidomycosis do mention their use . , there were no clinical studies showing clear efficacy of steroid use in the management of coccidioidal meningitis , but rather only anecdotal evidence , case reports , and expert opinion . reported using intravenous dexamethasone in conjunction with amphotericin b , typically within hours to days of onset of symptoms , with one reported case showing brief clinical improvement . thompson et al . showed in a multicenter retrospective study that adjunctive corticosteroid therapy , given after a documented cerebrovascular accident ( cva ) attributed to coccidioides meningitis , reduced the rate of subsequent cvas and was well tolerated with few adverse events . kern medical center uses dexamethaxone with a gradual taper . in our case , the patient did eventually show minor improvements in mental status after the initiation of steroids , although she did not return to her baseline mental status and continues to display significant cognitive deficits . response to therapy can be monitored by cf titer and lumbar punctures should be obtained every six to twelve weeks . a low ( < = 1:4 ) or undetectable titer suggests control of disease . however , vasculitic complications may occur despite stable cerebrospinal fluid ( csf ) parameters . mri should be used to establish a baseline and monitor the course of illness especially if new neurological symptoms occur . the incidence of abnormalities detectable by imaging studies has been reported to be as high as 93% for patients with coccidioidal meningitis . at the university of arizona , it is suggested to perform imaging at the time of diagnosis , at 3 month , 6 months , and 1 year , and every 6 months thereafter until clinical and imaging stability is achieved . it is recommended that these patients be on triazole therapy for life , given the high relapse rate when therapy is discontinued . coccidioidal meningitis has a high morbidity and mortality and should be considered in the differential in immunocompromised patients who present with altered mental status or meningitis - like symptoms and live or traveled to an endemic region . furthermore , patients should be screened for coccidioidomycosis prior to starting immunosuppressive therapy , and fluconazole prophylaxis may be considered in patients actively receiving treatment for hematologic malignancies or solid organ transplantation with positive serology . the authors declare that there is no conflict of interest regarding the publication of this paper .

central nervous system ( cns ) vasculitis is the most common life - threatening complication of coccidioidal meningitis . it is manifested by cerebral ischemia , hemorrhage , and infarction . we report a case of cns vasculitis in a patient receiving chemotherapy and review of the literature on coccidioidal meningitis . the patient was treated with combination antifungal therapy and a short course of high dose corticosteroids with a modest improvement in her neurological examination after initiation of steroids .

during 20092014 , we identified 20 persons who were admitted to 2 tertiary - care hospitals in rennes and paris , france , with culture - positive xdr tb infections . patients were identified through hospital database searches ; patient data were extracted from medical charts . for each patient , we performed direct examination of sputum smears ; cultures on lowenstein - jensen medium ; genotypic resistance profiling ( genotype mtbdr plus ; hain lifescience , nehren , germany ) ; and in vitro drug susceptibility testing ( dst ) on lowenstein - jensen medium , according to the proportions method . all patients were isolated in negative - pressure rooms until their respiratory sample culture results converted from positive to negative ( hereafter referred to as culture conversion ) . medical and surgical therapeutic options were determined during multidisciplinary meetings involving infectious diseases , respiratory diseases , microbiology , and thoracic surgery departments . in agreement with world health organization guidelines ( 3 ) , we selected anti - tb drug therapy on the basis of results from previously used agents or genotypic and phenotypic dst . throughout hospitalization , treatment toxicity was carefully monitored through clinical assessments , routine laboratory tests , therapeutic drug monitoring , audiograms for patients on aminoglycosides , and weekly electrocardiograms . treatment efficacy was monitored through thoracic imaging and monthly examination of respiratory samples . for patients with nondisseminated pulmonary tb , surgery was considered at the initiation of medical treatment if success of the treatment was deemed unlikely because of extensive lesions or after 3 months of optimized medical treatment if sputum conversion was not achieved . in agreement with procedures implemented by the french information protection commission the 20 xdr tb patients ( table 1 ) had recently arrived in france from georgia ( n = 17 ) , armenia ( n = 2 ) , and the russian federation ( n = 1 ) ; median duration between arrival and hospitalization was 2 ( interquartile range [ iqr ] 17 ) days . median delay from admission to initiation of any anti - tb treatment was 18 ( iqr 1125 ) days . loss of > 5% of total bodyweight . body temperature > 38c during at least 3 weeks . during the intensive phase of treatment , each patient all patients required long - term central venous access for administration of amikacin or carbapenems . duration of medical treatment was individualized but continued a minimum of 12 months after culture conversion . median length of stay in the acute - care setting was 67 ( iqr 55124 ) days . * the following grade 3 or 4 treatment - associated adverse events ( common terminology criteria for adverse events , http://evs.nci.nih.gov/ftp1/ctcae/ctcae_4.03_2010-06-14_quickreference_5x7.pdf ) were reported in 18 patients : digestive side effects ( 14 patients ) , hepatitis ( 1 patient ) , peripheral neuropathy ( 7 patients ) , neuropsychiatric side effects ( 3 patients ) , and hearing impairment ( 3 patients ) . no grade 3 or 4 nephrotoxicity or cytopenia or significant qt interval prolongation were reported . adverse events related to anti - tb agents were managed by a wide range of symptom treatments . thoracic surgery was performed in 8 patients ( lobectomy in 5 , pneumonectomy in 3 ) , of whom 2 had severe postsurgical complications . six of these patients were culture - positive before surgery , and their cultures converted a median of 25 days postsurgery ( iqr 2033 days ) . after a median follow - up of 22 ( iqr 1527 ) months , sputum cultures had converted for 19 patients , 4 of whom had completed treatment and a median of 38 ( iqr 2940 ) months of posttreatment follow - up . median time from treatment initiation to culture conversion was 100 ( iqr 75114 ) days . this small series of xdr tb cases managed in a high - income country illustrates the potential safety and efficacy of multidisciplinary and individualized treatment with a multidrug regimen that includes new anti - tb agents ( e.g. , bedaquiline ) ; innovative use of older agents ( e.g. , linezolid ) ; and the combination of imipenem plus amoxicillin / clavulanate . the final outcome could not be ascertained for most study patients because they are still receiving antimycobacterial therapy ; however , the 90% survival rate after a median follow - up of 22 months after treatment initiation is reassuring and compares favorably with survival rates of 66% , 54% , and 38% in the united states ( 4 ) , south africa ( 5 ) , and the united kingdom ( 6 ) , respectively . the high rate of microbiologic conversion in our study ( 95% ) also reflects the potentially achievable treatment efficacy , even in the context of previously treated xdr tb cases . our findings should be interpreted cautiously because of the small number of patients and the relatively short follow - up at the time of this writing . however , the overall figures of culture conversion are more satisfactory than those previously reported in high - income countries , where conversion rates ranged from 46.7% to 76.1% ( 4,610 ) , and in high - prevalence settings , where conversion rates are lower ( 5,11,12 ) . preliminary results from a study conducted in south africa were more favorable : samples from 48 ( 76% ) of 63 patients with 6 months follow - up were culture - negative ( 13 ) . postsurgery sputum conversion was rapidly achieved for patients in our study ; thus , pulmonary resection surgery , although risky , may also have contributed substantially to treatment successes . patients were referred to our centers soon after arriving in france , causing communication difficulties for patients with a limited understanding of french and english . medical histories were long and complex , and most patients were in advanced stages of pulmonary tb . the numerous side effects observed during prolonged anti - tb regimens must be optimally and intensively managed ; otherwise , patients may not complete treatment . because of the limited number of potentially active anti - tb agents , drugs with documented long - term toxicities must also be included in multidrug regimens . the high incidence of breakthrough candidemia cases ( 5/20 patients [ 25% ] ) was not anticipated , although prolonged exposure to broad - spectrum antimicrobial drugs and long - term central venous access are acknowledged risk factors for candidemia . this risk must be taken into account when considering treatment of xdr tb with carbapenems and amoxicillin / clavulanate . the overall good tolerability of linezolid may be a result of the low dosage ( routinely , 600 mg / d initially , decreased to 300 mg / d if toxicity is suspected , even with limited evidence ) . financial , social , and cultural aspects of the management of vulnerable and marginalized patients are also essential and time - consuming . prolonged hospital stays were necessary for patients in our study , resulting in high healthcare costs , as previously reported in south africa ( 14 ) . . however , failure to adequately address these issues would translate into additional xdr tb transmission in the community and increased illness and death , which could result in a much higher societal burden . previous experience in high - income countries has documented that comprehensive care of tb patients is cost - effective , even in the most vulnerable and marginalized populations , especially when multidrug - resistant or xdr tb are involved ( 15 ) . our results reflect the situation in a high - income setting with free access to all potentially active drugs , extensive investigation of responsible strains ( e.g. , using dst and genotypic tests ) , daily monitoring of adverse events , regular multidisciplinary meetings to tailor treatment to any new event and evaluate the need for thoracic surgery in selected cases , dedicated medical and paramedical staff , and psychosocial support . unfortunately , the situation may not be the same in the countries most affected by xdr tb .

we report 20 cases of extensively drug - resistant tuberculosis managed in france . treatment was individualized and included bedaquiline and linezolid for most patients and surgery in 8 patients . at last follow - up ( 22 months ) , 19 patients had achieved conversion from positive to negative on culture testing . these promising results of comprehensive management obtained in a small series deserve confirmation .

scrub typhus was suspected by clinical manifestations such as febrile illness or fever with rash or eschar . after giving informed consent , patients filled out questionnaires about potential chigger exposure and symptoms or signs consistent with scrub typhus . blood samples were taken from all patients for total blood cell count , biochemical analysis , serologic diagnosis , and molecular assays . when they sought treatment , 5 patients had been symptomatic for 5 to 7 days , 14 had been symptomatic for 8 to 14 days , and the remaining 2 had been symptomatic for 18 to 25 days . blood samples were collected at the time of admission to the hospital , and no serial assays were performed . all patients with clinical features that suggested scrub typhus received antirickettsial drugs ( doxycycline / azithromycin ) empirically . two serologic tests were used to confirm infections . the weil - felix proteus agglutination assay with proteus vulgaris ox-19 and ox-2 and p. mirabilis ox - k strains ( wellcome diagnostics , dartford , uk ) was performed on each sample ; a titer > 80 was considered positive . serum specimens were tested by mif assay with a panel of 11 rickettsial antigens , including spotted fever group ( sfg ) rickettsiae ( rickettsia japonica , r. helvetica , r. slovaca , r. conorii subsp . indica , r. hone , r. heilongjangensis , and r. felis ) , r. typhi , and orientia tsutsugamushi ( gilliam , karp , kato and kawasaki strains ) ( 3 ) . the mif assay was considered positive if antibody titers were > 128 for igg and > 64 for igm or if seroconversion was demonstrated ( 9,10 ) . dna was extracted from the blood sample ( buffy coat ) by using qiaamp dna mini kit ( qiagen gmbh , hilden , germany ) according to the manufacturer 's instructions . two amplification reactions were performed : 1 ) a real - time quantitative pcr with a taqman probe targeting the 47-kda outer membrane protein with primers and probe previously described ( 11 ) and 2 ) a standard pcr targeting the 56-kda protein with forward and reverse primers ( otsuf : 5-aattgctagtgcaatgtctg-3 and otsur : 5-ggcattatagtaggctgag-3 ) . the success of the amplification was confirmed by resolution of the products by electrophoresis on 1% agarose gel ( sigma chemical co. , saint louis , mo , usa ) in 1 tris borate edta buffer for products of the 56-kda gene . the sizes of the pcr - amplified products were determined by comparison with a molecular weight standard ( boehringer , manheim , germany ) under uv light after ethidium bromide staining . the pcr products were purified by using the qiaquick pcr purification kit ( qiagen ) according to the manufacturer 's instructions . sequencing reactions were performed with a dna sequencing kit , drhodamine terminator cycle sequencing ready reaction mix ( applied biosystems , foster city , ca , usa ) . the sequences were identified by comparison with sequences available in genbank by using the blast software ( http://www.ncbi.nlm.nih.gov/blast/ ) . in the mif assay , samples from 21 patients showed positive antibody titers ( both igg and igm ) to o. tsutsugamushi ( gilliam , karp , kato , and kawasaki strains ) . twenty - eight of 51 serum samples had titers 80320 to proteus oxk antigen on weil - felix test , of which only 13 had titers on mif . moreover , samples from 15 patients with titers on weil - felix did not show titers on mif , and samples from 8 patients without titers on weil - felix showed titers on mif . real - time quantitative pcr to o. tsutsugamushi was positive in anticoagulated blood of 3 patients , and this result was confirmed by using primers for the 56-kda antigen gene of o. tsutsugamushi . dq530440 ) that matched the karp type , close to strain la-1 isolated in 1993 in malaysia from mites ( 12 ) . the sequence obtained from patient 2 ( genbank accession no . dq530441 ) matched the sequence between the jg type and a recently described new subtype called saitama , described in japan ( 13 ) . the results of mif assays are shown in table 1 . the clinical features and laboratory abnormalities found in these 21 patients igm was considered positive at a titer of 64 ; igg was considered positive at a titer of 128 . elevated protein level and increased lymphocyte count . by mif assay , 11 of 21 samples had positive titers of both igg and igm ; 3 were positive for igg ( but not igm ) and were positive on pcr . these 14 patients had acute infection and are considered to have had scrub typhus , whereas the remaining 7 patients with only igg titers are considered as probable scrub typhus case - patients . in cases of primary infection with o. tsutsugamushi , igm appears at the end of the first week , whereas igg appears at the end of the second week . however , in the case of reinfection with o. tsutsugamushi , igg is detectable by day 6 , and igm titers are variable . the absence of igm in 10 samples can be attributable to previous antigenic conditioning from reinfection ( 9 ) . moreover all 3 patients with positive pcr results had igg titers but not igm titers , which suggests that some of the remaining 7 patients with only igg might also have been acutely infected . we confirmed the diagnosis of scrub typhus in 21 patients from the himalayas with several validated assays . pcr was performed in a few cases to further confirm o. tsutsugamushi , and we found that pcr was a good tool for molecular diagnosis , as recently reported ( 6 ) . to the best of our knowledge , this is the first molecular detection of o. tsutsugamushi in southern asia . the result was confirmed by using 2 different target genes in 2 different pcr assays . in our study , > 2 different genotypes were identified ; the phylogenetic position of 1 is between karp and jp-1 , and the other is between saitama and jg type ( figure ) . therefore , isolating these strains is recommended to increase understanding of the epidemiologic features of scrub typhus in india ( 12 ) . in our study , an eschar , which is formed in few secondary infections ( 2 ) , eschars are rare in southeast asian patients , and indigenous persons of typhus - endemic areas commonly have less severe illness , often without rash or eschar ( 14 ) . the variation in cutaneous immunity has also been suggested as a possible explanation for the absence of an eschar in certain instances of scrub typhus ( 15 ) . phylogenetic tree produced by unweighted pair - group method with arithmetic means that shows the positions of ihs i and ihs ii genotypes based on the partial 56-kda sequence homologies . numbers at nodes indicate bootstrap values , and the scale bar shows genetic distance of 0.02 . the literature mentions this disease in hilly regions of the himalayas and the shimla region in himachal pradesh ( 5,7,15 ) , but specific data are not available . the disease must have been present in the area but was not noticed because , in the past , most cases of fever were treated with drugs like tetracycline and chloramphenicol , which effectively treat scrub typhus also . the incidence of pyrexia of unknown origin with multiple organ involvement has increased for the past few years , which prompted us to conduct this study . increasing prevalence of scrub typhus has been reported from some asian countries , which coincides with the widespread use of -lactam antimicrobial drugs and urbanization in rural areas ( 14 ) .

himachal pradesh state of india is situated in the outer himalayan ranges . during the rainy season , several cases of acute febrile illness of unknown origin occurred . orientia tsutsugamushi was identified as the causative agent by microimmunofluorescence and pcr . two new genotypes of o. tsutsugamushi were identified in the region .

disulfiram ( dsf ) is one of the recommended aids in the management of selected cases of alcohol dependence . drug and alcohol de - addiction / rehabilitation centers utilize dsf in selected patients , sometimes surreptitiously , as an alcohol deterring agent . for more than 55 years it is a unique medication that relies on psychological threat to avoid dsf - ethanol reactions . dsf toxicity may present the different clinical aspects , though the mechanism of toxicity ( direct or idiosyncratic ) remains unclear . dsf ( 125 - 500 mg/ day ) related hypertension has been documented in very few earlier reports to cause reversible , dose - dependent stage - i and stage - ii hypertension within 2 - 3 weeks of administration , while a systematic review observed no change in blood pressure ( bp ) with 6 weeks of dsf ( 250 mg / day ) therapy . surprisingly , most of the related articles were during the period between 1950s and 1980s . this shows the need for research especially , in the indian context , when alcohol population and its wide use in de - addiction centers are considered . we report a 6 month prospective study of a normotensive case with the comorbid alcohol and tobacco dependence that developed hypertension in temporal association to dsf administration that showed a dose - dependent reduction and reversal to normal bp on discontinuation of dsf . a brief review of relevant literature has been undertaken to compile information on possible mechanism of dsf induced hypertension . hypertension , blood pressure , and relevant articles were retrieved supplemented with a manual search of the cross references . a 39-year - old married adult male , from urban and middle socio - economic background , presented with a history of daily alcohol consumption ( 92 - 123 g of ethanol / day ) and chewing of tobacco ( 15 - 20 packets ) since 10 years with the dependence pattern since 4 years . he was diagnosed as alcohol dependence syndrome , and tobacco dependence syndrome in uncomplicated withdrawal state as per icd-10 diagnostic criteria . he had no prior medical history of hypertension , diabetes , heavy metal exposure , epilepsy , neurological deficits , or any drug intake . family history of alcoholism , but not hypertension was noted in his father and brother . on admission , vital parameters showed marginal alcohol withdrawal sympathetic activity with pulse rate of 96 beats / min and bp of 140/90 mm of hg . his general physical and the systemic examination revealed no other abnormal findings , except for fine tremors of both hands and mild hepatomegaly . patient had pre - occupations with alcohol , anxious mood with preserved cognitions , and grade-4 insight . after alcohol detoxification , his bp had stabilized to 120/84 mm of hg on day-8 of admission . hematological and biochemical investigations such as complete blood count , blood glucose ( 105 mg / dl ) , blood urea ( 25 mg / dl ) , and serum creatinine ( 1.0 mg / dl ) were within normal limits . liver function tests were normal except for elevated liver enzymes ( gamma - glutamyl transferase 96 units / l ; serum glutamic oxaloacetic transaminase 120 units / l ; serum glutamic pyruvic transaminase his ultrasound abdomen showed mildly enlarged liver with grade-2 fatty infiltration . considering frequent relapses , patient , and spouse were explained about the nature of illness , and its various treatment modalities available including dsf . written informed consent for dsf therapy was taken and a dose of 500 mg / day was initiated . patient was discharged with dsf ( 500 mg/ day ) , and multi - vitamin supplementation . at discharge , his vital parameters were stable with pulse of 86 beats / min , and bp of 130/80 mm of hg . a fortnight later , patient complained of gradual onset occipital headache and giddiness with pulse rate of 86 bpm and bp of 146/100 mm of hg . on week-4 of dsf therapy , his complaints of headache , giddiness worsened , and bp increased to 170/110 mm of hg . in view of recent inclusion of dsf , with the absence of prior medical illnesses or drug history contributing to hypertension , possibility of drug induced ( dsf ) hypertension was suspected . subsequently , dsf was reduced to 250 mg / day and bp reduced to 150/96 mm of hg a week later . dsf was further reduced to 125 mg / day following this observation and antihypertensive agents such as telmisartan 40 mg and hydrochlorothiazide 12.5 mg / day were also initiated on the physician 's advice . a month later ( week-8 ) , patient reported with increased giddiness and physical fatigue with bp of 90/60 mm of hg despite abstinent . anti - hypertensive agents were withdrawn and dsf was discontinued completely . fortnight later ( week-10 ) , patient had reached his premorbid levels of bp to 110/70 mm of hg . psycho education about medical illness , life style modifications such as regular exercises and dietary measures were advised . six months later , patient had maintained complete abstinence from alcohol as well as tobacco , and his bp was 130/80 mm of hg [ figure 1 ] . systolic and diastolic blood pressure variations in an abstinent patient diagnosed with alcohol dependence on disulfiram ( dsf ) therapy ( htz - hydrochlorothiazide ) dsf , an alcohol deterring agent that is relatively nontoxic substance when administered alone , markedly alters the intermediary metabolism of alcohol . it acts by inhibiting aldehyde dehydrogenase , alcohol dehydrogenase and dopamine beta - hydroxylase ( dbh ) . dsf along with its two metabolites , diethyldithiocarbamate , and carbon disulphide inhibit dbh activity , a norepinephrine ( ne ) biosynthetic enzyme , which normally catalyzes the formation of ne from dopamine . this increases urinary excretion of the main dopamine metabolite homovanillic acid and decreases urinary excretion of ne and its major metabolite vanillylmandelic acid . furthermore , side - effects of dsf such as fatigue , tremor , reduced sexual potency , headache , and dizziness can be mediated by sympathetic nervous system where ne is the neurotransmitter . central nervous system alpha adrenergic receptors modulate peripheral autonomic activities both , which regulate bp . possibly , changes in central or peripheral ne activity are responsible for the increase in bp . peripheral synthesis of ne is probably not affected by the dsf as it is noted to have no effect on the pressor effect of tyramine and ne , as also plasma levels of ne increase following long - term high - dose ( > 500 mg/ day ) dsf therapy . however , dsf increases the nitro - glycerine induced postural hypotension while decreasing the accompanying tachycardia . this implies that dsf impairs the bp regulation through central nervous system by inhibition of the central dbh activity resulting in decreased central ne synthesis , which may interfere with the central alpha - adrenergic activity at the bulbar sympathetic cardio - accelerator , and vasomotor centers , resulting in increased bp , opposite of which is noted with antihypertensive agents like central alpha agonists ( clonidine , methyldopa , reserpine , and guanfacine ) . dsf has an inhibitory effect on certain cytochrome p450 ( 2e1 , 2c9 , 3a4 , 3a5 ) enzymes . nicotine also has an inhibitory effect on many cytochrome p450 enzymes ( 1a1 , 1a2 , 2a6 , 2a13 , 2b6 , 2c8 , 2c9 , 2c19 , 2d6 , 2e1 , 3a4 ) . comorbid tobacco dependence in patients on dsf therapy may have a role in drug level alteration as both share common cyp 450 enzyme system for metabolism ( 2c9 , 2e1 , and 3a4 ) , possibly leading to more chances of side - effects . dose of dsf in our middle aged patient who had fatty liver was 500 mg / day . reduction of dose in our case showed mild reduction in bp may suggest dose - dependent neurovascular side - effect of dsf . however , even low - doses of dsf ( 125 mg / day ) in the presence of cirrhosis of the liver have been quoted to reduce metabolism of dsf leading to hypertension . however , this was not the case in our patient whose abstinence and compliance was ensured by supervised medication as also the finding of temporal association of side - effect , gradual persistent increase in bp over time and a dose - dependent reduction in the bp with a return to normal values following the discontinuation of dsf may reflect it to be drug related hypertension . an awareness of the adverse effect is useful to keep a follow - up and sustain patient compliance with the drug . hypertension may be a clinically significant , dose - dependent and usually reversible side - effect of dsf therapy . in our opinion , an index of suspicion for vascular side - effects of dsf in cases with the comorbid alcohol and tobacco dependence may detect and also prevent misdiagnosis of essential hypertension . we suggest that in detected individuals , reduction of dose may be advised along with life style modification , dietary measures , and regular monitoring of bp . regular monitoring of bp at least fortnightly for 1 3 months , followed by monthly for next 3 months , and later once in 3 months , may possibly detect

disulfiram ( dsf ) is one of the recommended aids in the management of alcohol dependence . hypertension may be a clinically significant , dose - dependent , and usually reversible adverse event of dsf therapy . we report 6 month prospective study of normotensive case of comorbid alcohol and tobacco dependence that developed reversible stage - ii hypertension within 2 - 4 weeks of dsf therapy . we suggest that regular monitoring of blood pressure at least fortnightly for 1st 3 months , followed by monthly for next 3 months , and later once in 3 months , may possibly detect silent adverse event of dsf hypertension .

cough is one of the most common symptoms that doctor faces in working with pediatric population , and according to some characteristics of cough , doctors can often conclude the localization , and sometimes even the nature of the disease that causes it ( 1 ) . cough is one of the most common symptoms for which patients seek medical attention from primary care physicians and pulmonologists ( 2 ) . in children , it is the second symptom of respiratory disease after runny nose , with 46 - 56% representation depending on the age of the child . the literature states that the infant in a day inhales 1260 , and schoolchild 6640 liters of air ( 3 ) . it represents a protective reflex that wants to free the airways from pathological foreign content , from irritating substances , bronchial secretion , inflammatory products and products of circulatory congestion . cough is , therefore , not only the physiological defense reaction , but a symptom of a disease . considering the contents wet cough is a specific feature of exudation phase , except in lower respiratory diseases it can be found as productive cough or sore throat lasting secretion of hypertrophic and chronically inflamed adenoid vegetations . according to duration it can be acute , chronic and recidivist , recurrent and persistent , strong or discreet , caused by changes in body position and changes in outside temperature . pediatric chronic cough ( i.e. , cough in children aged < 15 years ) is defined as a daily cough lasting for > 4 weeks ( 5 ) . cough has three acts first is a deep inspiration , second act is expiratory when glottis is closed and the third is a quick gasp of air when the glottis is open . center for coordination is in the medulla oblongata , near the center of breathing . outburst of convulsive dry cough in attacks that supplements strong sound inspiration , is a feature of whooping cough . two - part ( bi - tonal ) cough is rare but important sign of the stenosis of main bronchus and trachea by swollen lymph glands or by foreign body , and is marked by the simultaneous appearance of one deep hoarse tone and one high - pitched tone . restrained cough occurs in a child in difficult dyspnea or with pleural pain , and is identified by a distinct effort of a child to suppress cough reflex ( pleuropneumonia ) . mucoid mucus , purulent a sign of bacterial superinfection and severe allergic reactions ) or pneumonia , as well as chronic pulmonary disease like cystic fibrosis , bronchiectasis ( purulent or very purulent ) etc . smelly expectoration suggests anaerobic infection of the lungs , lung abscess , unlike cystic fibrosis , where the sputum , although purulent , rarely has unpleasant smell . sometimes , for differentiation , culture of sputum is necessary , other than specific diagnostic tests of immune or alergology type , with x - ray diagnostics of respiratory and sometimes digestive system . if there is a productive cough , it is usually caused by the presence of secretion in the respiratory system . in pediatric population pneumonia is the most common cause of productive cough . pneumonia , is an acute inflammation of the lung parenchyma caused by various bacteria , viruses , fungi and parasites . pathoanatomically it is divided into lobar , lobular , alveolar and interstitial , pathogenetically to bronchogenic and hematogenous , as well as in immuno competent and immunocompromised , and clinically on the local and inpatient ( 72 hours after hospital admission ) . typical pneumonia is mostly bacterial and atypical is caused by mycoplasma , chlamydia , legionella and viruses . in a typical pneumonia onset is sudden , it begins with temperature and fever ( temperature suddenly rises above 39 degrees ) . pain occurs in the chest on the side of inflammation , then tachypnea and cough . cough is initially unproductive , and eventually , in three days , it becomes productive with purulent , sometimes bloody sputum . atypical pneumonia , begins gradually , with general symptoms , poor dry and non - productive cough , accompanied by a temperature not exceeding 39 degrees . sudden and turbulent start is in favor of typical pneumonia . by auscultation bronchial breathing , the primary diagnostics is radiological , posterior to anterior ( p - a ) and lateral footage of the chest . laboratory findings in typical pneumonia , are characterized by leukocytosis , neutrophilia and shift of blood image to the left . the basic bacteriological diagnosis is sputum gram s stain and culture of sputum . in atypical pneumonia , leukocytes are usually in the normal range , and it is necessary to do serological tests ( igm and igg antibodies ) . the main symptom of bronchiectasis ( permanent , irreversible enlargement of the bronchi ) is cough with higher amounts of muco - purulent sputum ( coughing with full mouth , which occurs with abundant secretion in the morning after waking up ) , hemoptysis , and recurrent pneumonia . the appearance and quantity of sputum depends on bacterial superinfection , and its cause . in bronchial asthma , in case that attack of obstruction is not suppressed relatively quickly , it usually leads to secretion in the bronchi , which often causes , other than productive cough , vomiting of thick , viscous mucus . distribution of cough according to type in cystic fibrosis , an integral part of the clinical picture is the chronic cough with expectoration , which is usually firstly mucoid and later purulent . clinically with exacerbations of the lung disease , by new strain of a pathogen or previous cause , intensifies the cough , with a change of color and consistency of the ejected content . in these stages , other than expectorants and secretolytic agents , intensive respiratory physical treatment is used ( 1 ) . the role of doctors in primary health care is auscultation differentiation of murmurs with confirmation of doubt , if there is pathological findings by laboratory tests and treatment , depending on the type of cough . productive cough can be treated with expectorants , secretolytic agents , having previously applied non - pharmacological measures , in the form of hydration , positioning drainage , physiotherapy and inhalation of water steam or aerosol . in smaller children in addition to secretolytic agents , mobilized secretion can be evacuated with implementation of mechanism like coughing , gasping ( huffing ) and suction . except bromhexine ( bromhexine derivative ambroxol hydrochloride ) and acetylcysteine , for secretolytic agents as pharmacotherapeutic agents today no firm scientific evidence for clinical activity is available ( 3 ) . in all cases of expectoration , other than expectorants , secretolytic agents , especially in children , it makes sense to make expectoration easier with extracts of plantain , primrose , thyme , in the form of large spectrum of syrups or making tea with the aforementioned extracts .

cough is one of the most common symptoms that doctor faces in working with pediatric population , and according to some characteristics of cough , doctors can often conclude localization , and sometimes even the nature of the disease that causes it . cough is not only the physiological defense reaction , but a symptom of a disease . according to duration it can be acute , chronic and recidivist , recurrent and persistent , strong or discreet , caused by changes in body position and changes in outside temperature . pathoanatomically it is divided into lobar , lobular , alveolar and interstitial , pathogenetically to bronchogenic and hematogenous , as well as in immuno competent and immunocompromised , and clinically on the local and inpatient ( 72 hours after hospital admission ) . considering the contents , cough can be productive with secretion from the respiratory tract , and unproductive - dry , without secretion . by auscultation bronchial breathing , rattle and crepitus can be heard . the primary diagnostics is radiological , posterior to anterior ( p - a ) and lateral footage of the chest . laboratory findings in typical pneumonia , are characterized by leukocytosis , neutrophilia and shift of blood image to the left . sedimentation is accelerated and c - reactive protein is elevated . the basic bacteriological diagnosis is sputum gram s stain and culture of sputum . in atypical pneumonia , leukocytes are usually in the normal range , and it is necessary to do serological tests ( igm and igg antibodies ) . the role of doctors in primary health care is auscultation differentiation of murmurs with confirmation of doubt if there is pathological findings by laboratory tests and treatment , depending on the type of cough . treatment is essentially pharmacological , with irrefutable importance of non - pharmacological measures .

chronic constipation is a common disease in the western world , especially among the elderly population.1 this condition can usually be treated conservatively with lifestyle changes and laxatives.2 nonetheless , occasionally patients with no previous history of gastrointestinal disease develop severe chronic constipation , often refractory to conservative treatment . this condition is also called chronic intestinal pseudoobstruction ( cip ) and is often classified as idiopathic.3 since the pathogenesis in some of these cases is due to a neuropathy involving the enteric nervous system , diseases that involve autonomic neuropathy , eg , diabetes mellitus , alcohol abuse , and paraneoplastic syndrome , are known causes of cip.3 in this case report we describe a case of sudden onset cip due to chronic lyme neuroborreliosis ( lnb ) , which is known to cause neurological disorders , but has never before been described as the cause of cip . a 66-year - old woman , with no major medical history was hospitalized due to urinary retention and lower back - pain radiating to the right lower extremity and lower abdomen . the patient lived in an area where lyme disease is endemic and had been bitten by ixodes ticks previously . physical examination on admission , including clinical neurological examination , was normal . blood tests , including white blood cell count and c - reactive protein , were normal . spinal mri revealed a suspected right - sided paramedian disc prolapse at l4/l5 with impingement of the l5 nerve root and a small disc prolapse at l5/s1 . while the urinary retention resolved spontaneously , the pain intensified and the patient developed severe constipation , unresponsive to laxatives . abdominal x - ray and ct scan suspected colonic ileus with some dilation of the colon ( figure ) . absence of intestinal obstruction was confirmed by barium x - ray and the condition was interpreted as intestinal pseudoobstruction resulting from opioid therapy . treatment with an acetylcholinesterase inhibitor resulted in defecation and flatulence , but the effects were only temporary . colonoscopy revealed a flaccid , poorly - prepared bowel , but no other pathology was found . more than 6 months after onset of symptoms the patient only defecated sporadically , even with twice daily transanal irrigation , supplemented with high dose osmotic and peristaltic stimulation . by this time lumbar puncture was performed and investigation of the cerebrospinal fluid ( csf ) showed csf lymphocytosis with spinal leucocyte count on 103 10/l , 100% mononuclear , elevated igg - index , elevated total spinal protein content , positive oligoclonal bands and intrathecal borrelia antibody synthesis , igg as well as igm . since the symptoms had lasted for more than 6 months this was consistent with chronic lnb.4 no other bacteria or malignant cells were found in the csf . the patient received a course of intravenous ceftriaxone 2 g administered once daily for 3 weeks . the frequency of transanal irrigation was reduced 4 days after onset of antibiotic therapy and 2 weeks later she had daily defecation without transanal irrigation , with decreased use of laxatives . following improvement in gastrointestinal function after 3 weeks of antibiotic therapy , intensity of the pain slowly subsided with subsequently reduced need for analgesia . three months after antibiotic treatment the patient was having a daily bowel movement with no need for laxatives . the pain was now of low intensity ( visual analog scale 12 ) when treated with secondary analgesics . in a repeated lumbar puncture , the spinal leucocyte count had decreased to 9 10/l , spinal protein content had decreased and there was a dramatic decrease in intrathecal synthesis of anti - bb igm and igg . the sensory evoked potentials showed bilateral peripheral affection of the upper extremities and the motor evoked potentials showed bilateral peripheral affection to musculus abductor pollicis brevis . lnb is a nervous system disorder caused by borrelia burgdorferi ( bb ) , a tick - borne spirochete . america , borreliosis occurs mainly in the north eastern states but chronic lnb is almost solely reported in europe.4 lnb is divided into early and chronic disease . chronic lnb is defined as disease duration of more than six months , csf inflammation and bb specific intrathecal igg synthesis . less than 12% of patients with lnb develop chronic lnb.4 borreliosis often presents as erythema migrans and if untreated approximately 5% will develop lnb in 26 weeks . the most common manifestation of early lnb is a subacute painful meningoradiculitis called bannwarths syndrome and consists of csf inflammation , painful radiculitis and palsies . bannwarths syndrome comprises more than 80% of lnb cases but approximately 30% of these patients present without motor signs as seen in the present case . characteristically , the pain is migrating , burning , often located in the back and radiating to the upper and lower extremities , abdomen and/or chest . approximately 50% have cranial nerve involvement , predominantly a peripheral facial nerve palsy . in the chronic stage , patients typically present with headache , malaise , significant weight loss , sensorineural hearing loss or a progressive spastic - ataxic gait disturbance.4 autonomic dysfunction is rarely seen in lnb.4 if lnb is suspected , investigation of anti - bb in the serum must be made . in the first stage of lyme borreliosis , 2050% of the patients will be anti - bb igm positive . twelve weeks after onset of neurological symptoms , all patients will have detectable anti - bb igg in the serum.4 if the blood sample is positive for anti - bb the csf must be examined . specific csf antibodies appear during the second week after onset of neurological symptoms and are detectable in 100% of patients 8 weeks after onset . disease duration for more than 6 months , csf inflammation and bb specific intrathecal igg synthesis is diagnostic of chronic lnb.4 chronic lnb seems not to be self - limiting , but antibiotic therapy arrests disease progression and patients recover significantly . there is no evidence of improved outcome when treating lnb patients with antibiotics for more than 2 weeks.4 the patient in the present case , initially experienced radicular pain , but she also developed urinary retention and severe intestinal pseudoobstruction as manifestations of autonomic dysfunction . the results of the nerve conduction studies were regarded as insignificant since the patient had no neurological symptoms of the upper extremities during the course of disease . urinary retention in lnb is described previously.57 intestinal pseudoobstruction in patients with acute lnb has been described in three patients , two of whom had symptomatology very similar to the patient in the present case , with urinary retention in addition to the intestinal pseudoobstruction.5,8 to our knowledge , the present case report is the first reported case of cip due to chronic lnb . cip is associated with poor quality of life and high morbidity.3 pathophysiological aspects of the condition remain obscure and treatment options are limited and often unsatisfactory.9 consequently , it is crucial that all physicians and gastroenterologists in particular , are aware of the non - idiopathic causes , and especially those that can be treated successfully . infection with bb can manifest as cip and all of the 3 patients described , with acute lnb and intestinal pseudoobstruction , experienced complete remission after 23 weeks of antibiotic therapy . in the present case , 3 weeks of antibiotic treatment was effective even though the patient had developed chronic lnb . in conclusion , bb infection must be suspected in patients with sudden onset , severe constipation or intestinal pseudoobstruction , in particular in patients with simultaneous emergence of symptoms such as palsies , radicular pain , arthritis , and myocarditis , and in patients living in an endemic area .

chronic intestinal pseudoobstruction is often classified as idiopathic . the condition is associated with poor quality of life and high morbidity , and treatment options are often unsatisfactory . a case of chronic intestinal pseudoobstruction in a 66-year - old woman , presenting with back and abdominal pain , urinary retention and severe constipation is described . the patient lived in an area in which lyme disease is endemic and had been bitten by ixodes ticks . intrathecal synthesis of anti - borrelia igm and igg and lymphocytosis in the cerebrospinal fluid was found , consistent with chronic lyme neuroborreliosis since symptoms had lasted for more than six months . the patient s gastrointestinal function recovered and the pain subsided significantly following treatment with antibiotics . lyme neuroborreliosis ( lnb ) often results in palsy , but rarely affects the autonomic nervous system . three patients have been described with intestinal pseudoobstruction due to acute lnb . however , this is the first described case of intestinal pseudoobstruction due to chronic lyme neuroborreliosis . lnb must be suspected in patients with intestinal pseudoobstruction , in particular in patients who have been bitten by an ixodes tick and in patients living in an endemic area .

diabetes mellitus represents an extreme disturbance in glucose metabolism with severe hyperglycemia and insulin deficiency . diabetes mellitus is the fifth most common chronic condition and the sixth most frequent cause of death among the elderly . tissue repair is affected and dysfunction of the oral mucosa occurs due to alterations in salivary flow and constituents , changes in nutrition and reduced immune defenses leading to changes in microbial oral flora and a greater tendency to infections . as a result , xerostomia ; candidiasis ; increased incidence of dental caries , gingivitis and periodontitis ; periapical abscess ; parotid enlargement and burning mouth syndrome are prevalent in diabetics . therefore , early diagnosis of the diabetes mellitus is an important aspect of health care . glycogen fails to stain with conventional hematoxylin solutions and only stains weakly , if at all , with eosin . diastase is the commonly employed form of glycogen digestion enzyme as it is easy to use , stable and comparatively cheap . the aim of our study was to study the effects of diastase enzyme on the glycogen content of the epithelial cells of mucosa of normal and diabetic patients in exfoliative cytology and to compare the staining quality in mucosa of normal and diabetic patients using hematoxylin and eosin ( h and e ) stain ; papanicolaou ( pap ) stain , periodic acid schiff ( pas ) and pas - diastase ( pas - d ) stains , respectively . it is a case - control study involving a total of 20 subjects ( 10 cases and 10 controls ) . diagnosed cases of diabetes were selected . the method used to estimate the values of blood sugar levels ( bsl ) ( fasting and postprandial [ pp ] ) was glucose oxidase method . patients with habits ( tobacco chewing and smoking ) , other systemic diseases / malignancies / taking medications other than the diabetic medications were excluded . smears were taken from the mucosa of normal ( control ) and diabetic ( study ) patients using a wooden spatula and transferred onto clean glass slides . the glass slides ( 40 ) were then immediately fixed in 95% ethyl alcohol and stained using h and e ( 10 slides ) , pap ( 10 slides ) , pas ( 10 slides ) and pas - d ( 10 slides ) stains for both the groups . for pas - d , the slides were first incubated in diastase solution at 37c for 1-h , washed and then stained with pas stain . the staining quality in the cells and their glycogen content was studied in both the groups and then compared . it is used to detect both hypoglycemia and hyperglycemia and helps in diagnosis of diabetes . glucose oxidase is an enzyme highly specific for glucose and does not react with blood saccharides . the principle used in pas - d stain was that diastase ( or -amylase ) acts on glycogen to depolymerize it into smaller sugar units , maltose and glucose , that are washed out of the section . glycogen will be stained magenta on pas [ figure 1 ] stained slide and will be absent on the pas - d [ figure 2 ] stained slide because of glycogen digestion by the diastase enzyme . photomicrograph of buccal exfoliated cells ( pas stain , 400 ) photomicrograph of buccal exfoliated cells ( pas - d stain , 400 ) on comparison of the mean and standard deviation values during fasting and pp , we found that high bsls were seen in the study group as compared to that of the control group [ table 1 ] . by applying student 's unpaired t - test , there was a highly significant difference between mean values of bsl when compared to control versus study group ( i.e. , p < 0.01 ) . also , it was seen that the mean values of bsl both fasting and pp was more in the study group as compared to the control group [ table 2 ] . by applying student 's unpaired t - test , there was a highly significant difference between mean values of bsl when compared to fasting versus pp in both control and study group ( i.e. , p < 0.01 ) [ table 3 ] . mean and standard deviation values of blood sugar level in control and study group comparison of mean values of blood sugar level in control and study group comparison of mean values of both fasting and post - prandial blood sugar levels in control and study group the study group exhibited nuclear changes such as binucleation [ figure 3 ] , decreased cytoplasmic / nuclear ratio , nuclear enlargement [ figure 4 ] and enucleation [ figure 5 ] in pap stained slides as compared to that of control group . photomicrograph of exfoliated cells exhibiting binucleation ( h&e stain , 400 ) photomicrograph of exfoliated cells exhibiting nuclear enlargement ( pas stain , 400 ) photomicrograph of exfoliated cells exhibiting enucleation ( h&e stain , 400 ) diabetes mellitus , a complex metabolic disorder , is a syndrome characterized by abnormalities in carbohydrates , lipid and protein metabolism that results either from a profound or an absolute deficiency of insulin ( type i ) or from target tissue resistance to its cellular metabolic effects ( type ii ) . although many of the pathological processes affecting the oral mucosa are clinically distinguishable , most lesions require a definitive diagnosis before the appropriate therapy may be commenced . the most accepted clinical technique for the diagnosis of lesions of the oral mucosa is an incisional or excisional biopsy . in specific clinical conditions , such as diabetes , a great many invasive techniques lose viability as a result of variations in blood glucose and the disease itself . in these cases a cytologic smear is an advantageous diagnostic procedure because it is noninvasive , relatively painless , inexpensive and requires a minimum of technical skill . it is useful when a patient refuses to have a biopsy performed or when medically compromised patients would be exposed to unnecessary surgical risks and anxious patients can be reassured quickly about the nature of oral mucosal changes , especially when a fear of cancer or a family history of cancer accounts for their apprehension . in a study developed in sudan , the oral cytologic analysis is proposed as a useful early diagnostic method for epithelial atypia and therefore also for malignant oral lesions . in our study , we compared the slides of h and e , pap , pas , pas - d in both control and study group and found that the cells in the study group exhibited binucleation , decreased cytoplasmic / nuclear ratio , nuclear enlargement , enucleation and inflammation as compared to that of control group , which is similar to the findings of jajarm et al . alberti et al . who also found that diabetes mellitus can produce alterations in oral epithelial cells , detectable by microscopy and cytomorphometry , which can be used in evaluation of this disease . our study evaluated whether diabetes diagnosis can be made by analysis of the glycogen content of the oral epithelial cells in diabetics . we compared the mean values of bsl in control and study group and found that mean values of bsl fasting and pp is more in study group as compared control group which is highly significant with a p < 0.01 . because of the increased glucose in diabetics , their epithelial cells showed less staining when stained with pas - d , since glycogen is digested by the diastase enzyme treatment prior to pas staining . in our study , the oral smears obtained from diabetic and control groups contained cellular representatives of all the epithelial strata , from nonkeratinized cells to the completely keratinized ones . these patients presented cellular alterations , both quantitative and qualitative , at all differentiation levels . we found that nuclear changes were significantly higher in the diabetic group than in the control group that was similar to the findings of jajarm et al . decreased cellular turnover might be a secondary reaction to ischemia caused by atherosclerosis in diabetic patients . thus as a result of ischemia , cellular turnover would decrease and limited production of young cells would mean that the majority of cells are old or aged . we found a significant increase in inflammation in the diabetic group in comparison with the control group . this might result from decreased salivary flow in diabetes , due to hypofunction of the salivary glands secondary to adverse hormonal , microvascular and neuronal changes . conner et al . , reported a decrease in the salivary flow of diabetic patients , probably related to systemic dehydration ( polyuria ) , medicament interference ( diuretics ) and/or membranopathy of the ducts . from our study , we can say that exfoliative cytology is useful as an additional tool to aid in the diagnosis of diabetes mellitus . furthermore , studies with greater sample size and comparison to other conditions causing similar cytomorphometric changes are needed to determine the predictive value of this method . thus , from our study , it can be said that exfoliative cytology can be used as a tool for diagnosis as well as for screening the patients for diabetes using pas - d stain . however , larger sample size studies should be performed to come to a definite conclusion .

background : diabetes mellitus is the fifth most common chronic condition and the sixth most frequent cause of death among the elderly . the objective of this research was to develop a new method for diabetes diagnosis by analysis of the glycogen content of the oral epithelial cells.materials and methods : ten control subjects and ten diabetic patients ( study group ) were taken , four oral smears for both control and study group from the buccal mucosa were taken and stained with hematoxylin and eosin stain , papanicolaou ( pap ) stain , periodic acid schiff ( pas ) stain and pas - diastase ( pas - d ) stain.results:the results showed that in the diabetic group : ( i ) the epithelial cells stained with pap stain exhibited figures of binucleation and occasional karyorrhexis , ( ii ) the epithelial cells treated with pas - d showed that glycogen containing cells did not take up the stain as compared to the other cells.conclusion:the results associated with clinical and histological observations suggest that diabetes mellitus can produce alterations of oral epithelial cells as well as in their glycogen content .

primary lymphedema is usually idiopathic , without a family history , and defined by the age of onset1 , 2 . it is characterized by swelling of the tissues and thickening and hardening of the skin and soft tissue3 , 4 . the first indication of primary lymphedema is usually swelling of the feet and ankles , and is predominant in women5 . the prevalence is difficult to determine and estimates vary considerably6 . up to half of all cases of lymphedema lymphedema has adverse physical , psychological , and socioeconomic impact , and treatment is continued for life5 . the best practice management of lymphedema uses a holistic , multidisciplinary approach that includes exercise / movement , swelling reduction and prevention ( compression and/or massage ) , skin care , risk reduction , and pain and psychosocial management6 . matrix rhythm therapy ( mrt ) provides vibromassage and aims to induce correct metabolism through a specific physiological pulse . the mrt device activates and rebalances specific vibration in skeletal muscles and the nervous system . the device produces an oscillating rhythm that maximizes lymphatic venous perfusion of the extracellular space in which the anti - edematous effects originate8,9,10 . there are few studies describing clinical experiences and the effectiveness of mrt , and there is a low level of evidence for its effectiveness11,12,13 . a 36-year - old female ( height : 160 cm , weight : 55 kg , body mass index : 21.5 kg / m ) with no history of trauma or surgery had symptoms in the left lower limb for 9 years and was diagnosed with primary lymphedema . she had used knee - high compression hosiery for 4 years , but had not received any treatment for lymphedema or any medication to reduce edema . measurements are taken at fixed anatomical points along the limb and repeated at different levels15,16,17 . circumference was measured before and at the end of treatment , and 1 and 3 months later , to assess lymphedema . the lower limb was measured at 9 levels ( metatarsophalangeal joint , ankle , 10 , 15 , and 20 cm above the ankle , knee , and 10 , 15 , and 20 cm above the knee ) . both lower limbs were measured for comparison of circumferences at the same anatomic locations . circumferential measurements are entered into a formula for calculation of limb volume based on a conical frustrum , to aid in diagnosis and monitor the effect of treatment5 . for management of lymphedema , mrt is applied with an electrically powered oscillator ( resonator ) . the mechanical oscillations produce a visually detectable longitudinal motion in the musculature9 , 10 . mrt was applied to the thoracic and lumbar spine , abdominal area , and affected limb in elevation . during treatment , a resonator is used to reactivate cell and tissue metabolism by inducing deep distention at 812 hz . twenty treatment sessions ( 5 days / week ) were performed by a physiotherapist trained and certified in the mrt program . the patient was allowed to continue use of the same compression hosiery during working hours . the patient was educated about the risks of lymphedema , daily living recommendations , and use of appropriate compression garments . she was also given preventive advice , including proper skin care and was advised to be more active . the global rating of change ( grc ) scales were used to evaluate patient satisfaction and quantify improvement . the grc scales offer a flexible , quick , and simple method for charting self - assessed clinical progress18 . the patient would rate her condition compared to the beginning of treatment as improved significantly ( 2 ) , improved slightly ( 1 ) , stayed the same ( 0 ) , deteriorated slightly ( 1 ) , or deteriorated significantly ( 2 ) . this case study complied with the ethical standards of the declaration of helsinki ( 1975 , revised 1983 ) . circumferential measurements taken at 9 levels before treatment showed more than 2 cm of fixed lymphedema at the metatarsophalangeal joint , ankle , and 10 and 15 cm above the ankle . the volumetric value of the left lower limb was 1,573.28 ml before treatment , 1,573.13 ml at the end of treatment , 1,516.70 ml 1 month later , and 1,441.61 ml 3 months later . reduction is determined by subtracting the lymphedema volume of the affected limb at the end of treatment from the volume before treatment . volume reduction was 0.15 ml . percent reduction is calculated as volume reduction divided by baseline volume multiplied by 100 . when measurements at 1 and 3 months were compared with baseline measurements , there was a decrease in the lymphedema ( 3.59% and 8.36% , respectively ) . the patient reported satisfaction with the treatment , reduction in the sense of stiffness and heaviness , and eased mobility in the ankle ; the baseline edema was reduced and softened during the treatment process . we hypothesized that mrt could be an alternative or additional treatment option for patients with primary lymphedema because it has anti - edematous effects . based on the results in this case , we could not conclude that mrt is effective in reducing lymphedema , but it may show a positive effect by reducing edema in the long term . the presence and severity of swelling is measured objectively by comparing the circumference or volume of the affected limb to that of the unaffected limb19 . in the current study , water displacement and optoelectronic measurements , which are other valid methods , were not preferred for the evaluation of lymphedema because of time , cost , difficulty of use , and equipment requirements6 , 19 . instead , circumferential measurement , which is a simple , inexpensive , non - invasive , and easy method , was preferred to evaluate lymphedema . similar to massage , which has beneficial effects on circulation , edema , and lymphatic drainage , mrt can cause afferent stimulation through the effect of vibration20 . although mrt seems appropriate for musculoskeletal injuries , because of implementation by direct skin contact , it could affect the superficial lymphatic system . however , there are only a few studies on the effectiveness of mrt . mrt for burns , sports injuries , and circulation has been reported in the literature10,11,12,13 . investigated the acute effects of mrt on blood circulation in comparison with conventional massage , and reported that mrt was more effective11 . the findings can also be interpreted as the sustained long - term effect of mrt at the cellular level . although there was only a slight difference in lymphedema volume at the end of treatment , there was a decrease at follow up . using the percentage difference in limb volume is likely to be most appropriate , because this takes into account the inter - individual differences in limb size . there is agreement among reviews that complex decongestive physiotherapy ( cdp ) is effective at reducing limb volume23 , 24 . it is an intensive treatment program involving manual lymphatic drainage ( mld ) , skin care , compression therapy , and/or prescribed exercises23 . since these techniques can also be offered separately , it would be useful to determine the effectiveness of each component19 . mld is a specialized form of light massage that is used to assist the flow of lymph from distal areas of stasis to proximal , normally functioning lymphatic vessels19 . mld seems to be effective when used with compression therapy , but the available evidence does not support its use as a stand - alone treatment strategy3 , 23 . compressive bandages must be left in place 21 to 24 hours per day for optimal volume reduction26 . however , in the current study , mrt was applied for only one hour a day and bandaging was not used during the day . the extremity was managed with compression hosiery for only a few hours , less than half of the day , which is inappropriate for lymphedema . compression hosiery is used mainly for the treatment and prevention of recurrent venous leg ulcers and applies relatively low levels of static compression to the lower leg ( up to a maximum of 46 mmhg at the ankle ) . however , when used as part of lymphedema management , higher levels of compression may be required , involving the use of hosiery capable of achieving at least 49 mmhg at the ankle27 . despite the use of compression hosiery for years , the swelling continued to increase before the patient contacted us , so its continued use would not provide compression sufficient to achieve a volumetric difference . in order to observe the pure effects of mrt , additional compression therapy was not administered . greater reductions might be demonstrated when the use of mrt is combined with compression therapy for the entire day . additionally , due to similar application time , application technique , and the effect on the lymphatic system for mrt and mld , comparative research should be performed to determine whether mrt could be an alternative to mld . unfortunately , this is only a case report and there was no control group for comparison . in conclusion , based on the results of the present case , mrt was not found to be effective in reducing lymphedema when used alone . however , mrt might positively affect lymphedema , which is a chronic process , if it is applied for a longer term and repeated often . to determine the effects of mrt , it would be useful to conduct further follow - up studies with a larger sample size . furthermore , investigations of mrt compared with mld are necessary to determine the actual effect . mrt may be combined with compression therapy to manage lymphedema , and could provide a positive contribution to the cdp approach .

[ purpose ] primary lymphedema occurs because of genetic predisposition and developmental insufficiency of the lymphatic system . matrix rhythm therapy was developed as an external and dynamic method that supplies rhythmic mobilization of the fluids in tissues . the aim of the study was to investigate the effects of matrix rhythm therapy in primary lymphedema . [ subject and methods ] a 36-year - old female with left lower limb lymphedema was evaluated . leg circumference was measured before and at the end of treatment , and 1 and 3 months later . the circumferences were converted to volumetric values . twenty sessions of matrix rhythm therapy ( 5 days / week ) were applied to the affected leg , spine , and abdominal regions . patient satisfaction was assessed with the global rating of change scale . [ results ] volumetric values were 1,573.28 ml before treatment , 1,573.13 ml at the end of treatment , 1,516.70 ml 1 month later , and 1,441.61 ml 3 months later . at the end of treatment , the volumetric reduction was not significant ; however , when compared with baseline , measurements at 1 and 3 months decreased by 3.59% and 8.36% , respectively . the global rating of change score was 2 . [ conclusion ] matrix rhythm therapy could not reduce lymphedema when used alone , but long - term treatment may show positive effects .

a 50-year - old woman presenting with back pain was referred to our center with a 2.5-cm nodule in the right middle lung field on a chest x - ray . the patient had a past history of surgical excision of an odontogenic tumor at a local dental clinic 17 years previously . a chest computed tomography ( ct ) scan revealed a 2.6-cm lobulated , heterogeneous enhancing nodule and a 1.5-cm satellite nodule in the anterior segment of the right upper lobe ( rul ) ( fig . 1 ) . therefore , we performed ct - guided percutaneous needle biopsy for the tissue diagnosis of the main nodule . the specimen showed a cohesive tumor island composed of squamoid cells , with central keratin pearl - like material . bronchoscopy , brain magnetic resonance imaging , and positron emission tomography scanning were performed for further evaluation and staging , based on the impression of primary lung cancer . then , we performed a planned rul lobectomy and mediastinal lymph node dissection through thoracotomy upon the diagnosis of clinical stage ia ( t1bn0 ) or iib ( t3n0 ) lung cancer . however , the histopathological diagnosis after the operation was different from that of preoperative biopsy . these tumor islands showed peripheral palisading and loosely arranged central cells , which resembled stellate reticulum . we contacted the patient 's former dentist and requested her medical records , but we could not obtain any information related to the odontogenic tumor . finally , the diagnosis of metastasizing ameloblastoma was made based on the patient 's past history and histopathological studies . although the patient had no associated symptoms , panoramic radiography and facial ct were performed after consulting a dentist to identify local recurrence at the oral cavity . there was fibrotic scar formation but no evidence of recurrence at previous odontogenic tumor site . the patient was doing well without any evidence of recurrence or metastasis during regular follow - up . ameloblastomas are rare odontogenic epithelial tumors and account for 1% of all tumors and cysts of the jaws . they are classified as benign and characterized by slow growth , local invasiveness , and a high rate of recurrence . in contrast with its high recurrence rate ( up to 50% to 72% ) , the metastasizing ameloblastoma ( ma ) is uncommon . the incidence of malignancy / metastasis in relation to ameloblastoma has been reported to be only 2% . to our knowledge , this is the first report of a patient who was diagnosed with metastasizing pulmonary ameloblastoma in south korea . the odontogenic tumors are classified according to the current world health organization histological classification published in 2005 . ma is defined as an ameloblastoma that metastasizes despite a benign histological appearance and shows no specific features different from those of ameloblastomas that do not metastasize . thus , the diagnosis of metastasizing ameloblastoma can only be made in retrospect , after the event of metastasis . ameloblastic carcinoma is defined as a rare odontogenic malignancy that combines the histological features of ameloblastoma with cytological atypia , even in the absence of metastases . mas mostly occur in the lungs , although there are some reports of ma arising in the regional lymph nodes , bones , liver , and brain . van dam et al . reported a summary of clinical findings of mas after reviewing 27 previously published reports and 3 of their cases . there are 74% of primary tumors with purely plexiform , follicular , or mixed patterns . the lungs ( 78% ) are the most common site of metastasis , of which 71% are bilateral . the average interval from the diagnosis of a primary tumor to the diagnosis of metastasis is 18 years , with a range of 3 to 45 years . because of the rare occurrence of mas , the clinical course and the appropriate treatment are not yet well established . in most of the reported cases , close observation , surgical resection , and chemo / radiotherapy can be considered treatment options . scannell et al . also suggested radiofrequency ablation as a possible treatment option for mas . however , most authors recommend a complete surgical resection as the treatment of choice , particularly in the cases of operable pulmonary lesions . chemo / radiotherapy can be reserved to relieve symptoms and to offer palliative care for inoperable lesions . of course , meticulous follow - up for recurrence after adequate resection of primary tumors should take precedence . in summary the diagnosis was made on the basis of the patient 's past history of surgical excision for an odontogenic tumor and the histopathological features of ameloblastoma .

ameloblastomas are rare odontogenic epithelial tumors that occur mainly in the mandible . despite their benign histologic appearance , they are locally aggressive with a high recurrence rate . however , a metastasizing ameloblastoma has been rarely reported . according to the current world health organization classification system , the definitive diagnosis of metastasizing ameloblastoma can only be carried out in retrospect , after the event of metastasis . this case report describes a patient with metastatic pulmonary ameloblastoma , 17 years after the surgical excision of an odontogenic tumor , preoperatively misdiagnosed as primary squamous cell carcinoma .

numerous syndromes of a suspected infectious origin remain of unknown microbial aetiology even after investigation by a thorough microbial diagnostic assessment that includes the use of broad - range bacterial pcr targeting the 16s rrna encoding gene on normally sterile samples . however , this technique fails to detect bacteria from the chlamydiales order because of the highly different chlamydiales 16s rrna sequences compared to bacteria from other orders . we thus wondered whether members of the chlamydiales order may be implicated in the occurrence of cryptogenic infections . in this study , we performed a pan - chlamydiales pcr on all samples received in our laboratory between 11 may 2012 and 11 march 2013 and all samples that tested negative by 16s rrna pcr analysis . a total of 107 samples from 69 patients were investigated by our homemade pan - chlamydiales pcr in duplicate , as previously described . dna sequencing was not successful in any of these samples , probably because of the low amount of targeted dna . ( dna was detected between a range of 36.2 to 44.7 cycle threshold ( ct ) , corresponding to 3160 and 8 copies of dna / ml respectively ) . the first patient , a 60-year - old woman who had undergone several knee joint replacements and who had metabolic syndrome , was admitted to the emergency ward with fever , dyspnoea and an increasing systemic inflammatory response syndrome . joint infection was documented by a knee arthrocentesis revealing a high amount of polymorphonuclear cells . concomitantly , the patient received a treatment with intravenous amoxicillin / clavulanic acid , which was switched to an oral therapy of rifampicin and doxycycline for 3 months because of the high suspicion of prosthesis intracellular bacterial infection due to the negative cultures and broad - range bacterial 16s rrna pcrs . interestingly , the pan - chlamydiales pcr was positive for two samples from this patient ; one sample was taken from the prosthesis , and the other was a sample of synovial fluid obtained 3 weeks after spacer implantation . the infection could have been of nosocomial origin because the last prosthesis replacement was performed 7 months before the patient 's presentation to the hospital . chlamydia spp . could have been the cause of the infection even though these bacteria are more likely to cause reactive arthritis , . the second patient , a 41-year - old man with no relevant medical history , experienced flulike symptoms while he was in south africa . two months later , back in switzerland , he developed two episodes of bronchopneumonia with fever , cough , dyspnoea , chest pain and a radiologic infiltrate that was located at the left superior lobe . a bronchoscopy was performed after the second episode of bronchopneumonia , revealing a stenosis of a segmental bronchi . all the cultures remained sterile , whereas both the 16s rrna pcr and the broad - range mycobacterial pcrs were negative on all tested lower respiratory tract samples . the bronchial biopsy sample showed signs of chronic inflammation and fibrosis without any signs of neoplasia . the patient had a good clinical outcome with a treatment of amoxicillin / clavulanate ( 16 days ) and clarithromycin ( 17 days ) and after stenting the bronchi with a metallic stent . our work suggests a role for chlamydiales in orthopaedic prosthesis infections and in the pathogenesis of chronic bronchial stenosis or bronchial stenosis superinfection . this relies on the absence of any alternative identified pathogen despite multiple in - depth investigations , a favourable outcome after beginning empirical therapy with antibiotics with intrinsic activity against most pathogens of the chlamydiales order ( i.e. doxycycline , rifampicin and clarithromycin ) and the plausibility that the infectious syndromes were caused by intracellular bacteria . in that regard , several chlamydiaceae and chlamydia - related bacteria have already been associated with pulmonary infections , , . the value of this work is limited by the absence of identification of the aetiological agent at the species level . however , this work shows the added value of pan - chlamydiales pcr in such cases of infections of unknown aetiology and suggests a role of some member of the chlamydiales order as an agent of prosthetic infection and in the pathogenesis of bronchial stenosis or bronchial stenosis superinfection . further studies should be done in order to precisely identify the chlamydiales species involved in these syndromes .

since routine eubacterial 16s rrna pcr does not amplify members of the chlamydiales order , we tested all samples received in our laboratory during a 10 months period using a pan - chlamydiales real - time pcr . 3 of 107 samples ( 2.8% ) revealed to be positive , suggesting a role of some chlamydiales in the pathogenesis of chronic bronchial stenosis or bronchial stenosis superinfection and as agents of orthopaedic prosthesis infections .

we report an unusual case of normotensive pheochromocytoma detected incidentally , presenting a pre - operative management problem . a 40-year - old lady with vague abdominal symptoms was initially discovered with a left adrenal incidentaloma by ultrasound abdomen , which was also revealed in computed tomography ( ct ) . after exclusion of all the causes with possible necessary investigations , pheochromocytoma was confirmed with elevated 24 hour urinary metanephrine and normetanephrine . she was attempted to be prepared with combined alpha and beta blockade but could not tolerate this regimen due to symptomatic hypotension . subsequently , surgical preparation was planned cautiously with alpha - adenergic blockade only . with intensive monitoring pre - operative preparation in these patients can be achieved with alpha - adrenergic blockade , adequate hydration , and liberal salt intake . although hypertension , sustained or paroxysmal , is usually a cardinal feature of pheochromocytoma , normotensive presentation is unusual . symptoms of orthostatic hypotension may dominate the presentation in patients with epinephrine- or dopamine - predominant tumors . in this case report , we describe a normotensive patient with pheochromocytoma who initially presented as adrenal incidentaloma and the management dilemma regarding this case . a 40-year - old , menstruating , mother of one child , was referred to the outpatient department of endocrinology of n.r.s medical college and hospital , kolkata , with an ultrasound abdomen report suggestive of enlarged left adrenal gland . on enquiry , she gave history of vague abdominal discomfort for prolonged duration without any other positive complaints . her blood pressure ( recorded on multiple occasions ) was around 110/70 mmhg with pulse rate 76 - 84/min in sitting and 106/70 mmhg with pulse rate 82 - 90/min in standing position . she did not have any features of marfanoid habitus or any evidence of mucosal neuroma , caf - au - lait spots , or any features of hyperandrogenism . general physical and systemic examinations were non - contributory . her routine blood investigations ( complete hemogram , blood sugar , urea , creatinine , urine routine examination , e.c.g , chest x - ray ) were within normal limits . subsequently , computed tomography abdomen also confirmed a left adrenal adenoma with dimension of 48 mm 47 mm , round shape , smooth contour with sharp margin [ figure 1 ] . serum cortisol ( 8 am ) and dexamethasone suppression test did not reveal any abnormality . urinary metanephrine and normetanephrine levels were : 6986.56 g/24 hrs ( 8963.33 g / gm of creatinine ) and 7496.50 g/24 hrs ( 9617.56 g /gm of creatinine ) , respectively . having thus diagnosed , left adrenal pheochromocytoma , the patient was being prepared for surgery with volume repletion and administration of extended release prazosin ( 2.5 mg ) at night ( since phenoxybenzamine was not available ) and propranolol ( 30 mg ) in divided doses . computed tomography abdomen showing left adrenal adenoma ( 48 mm 47 mm ) however , she had symptomatic hypotension with this combination so much so that cardiologist was keen on stopping both the anti - hypertensives , and the anesthesiologist wanted to withhold prazosin . she was cautiously put on extended release prazosin ( 2.5 mg ) only with intensive monitoring as a preparation for surgery . subsequently , she underwent an open left adrenalectomy under general anesthesia , which she tolerated well . the tumor was well - encapsulated , and histopathology also confirmed the diagnosis of pheochromocytoma . though hypertension ( attributed to norepinephrine secretion ) episodic or sustained is common , hypo to normotensive presentation , as a possibility , should also be kept in mind . in 2008 , gonzalez - pantaleon and simon presented a case of normotensive pheochromocytoma along with its challenges in diagnosis and management . the intra - operative mortality in patients with unsuspected pheochromocytoma may approach -50% . as a result , extreme care in the pre - operative preparation and the intra - operative management should be taken . in normotensive patients , for example , our patient developed symptomatic hypotension during combination ( alpha- and beta - blocker ) therapy but tolerated well the low - dose alpha - blocker therapy only . again , in absence of hypertension , use of combination ( alpha- and beta - blocker ) therapy may cause precipitous fall in blood pressure and , therefore , these agents should be used cautiously in such patients .

introduction : we report an unusual case of normotensive pheochromocytoma detected incidentally , presenting a pre - operative management problem.case note : a 40-year - old lady with vague abdominal symptoms was initially discovered with a left adrenal incidentaloma by ultrasound abdomen , which was also revealed in computed tomography ( ct ) . after exclusion of all the causes with possible necessary investigations , pheochromocytoma was confirmed with elevated 24 hour urinary metanephrine and normetanephrine . her blood pressure was in low to normotensive range all throughout . she was attempted to be prepared with combined alpha and beta blockade but could not tolerate this regimen due to symptomatic hypotension . subsequently , surgical preparation was planned cautiously with alpha - adenergic blockade only . with intensive monitoring , she underwent uneventful left adrenalectomy , and surgical pathology was consistent with pheochromocytoma.conclusion:this case illustrates an unusual presentation of normotensive pheochromocytoma as adrenal incidentaloma . pre - operative preparation in these patients can be achieved with alpha - adrenergic blockade , adequate hydration , and liberal salt intake .

this hypothesis drew great attention as it necessitated antibacterial treatment for morphea . in the following years , serological , immunohistochemical and culture approaches were performed to determine the role of borrelia burgdorferi in the pathogenesis of morphea ( 2 - 5 ) . however , these studies concerning the relation between b. burgdorferi and morphea have had conflicting results . in recent years , several authors have used polymerase chain reaction ( pcr ) to detect b. burgdorferi in skin lesions of patients with morphea , but the relationship between morphea and this organism has still remained controversial ( 6 - 10 ) . the most acceptable reason for this confliction is the possible geographical variations and different borrelia subspecies which affect the relationship , as borrelia has frequently been detected in european and asian patients , but not in cases from the usa or scotland ( 10 - 13 ) . the present study was designed to record the occurrence of b. burgdorferi among skin biopsies of patients with morphea . if the link is firmed , the next studies can focus on the role of antibiotic therapy in morphea . this was a case series study performed on skin biopsy specimens of patients with clinical and pathological diagnoses of morphea . by reviewing the records of the pathology department of imam reza and ghaem hospitals as the two main university hospitals in northeast of iran during october 2003 to october 2009 after reconfirmation of histological diagnosis , five to eight sections ( 5 m ) were cut from each formalin - fixed , paraffin - embedded ( ffpe ) tissue block and were deparaffinized by adding xylene ( sigma - aldrich , llc ) . thereafter , dna was extracted from those tissue samples using commercial dna isolation kit for ffpe ( qiaamp dna ffpe tissue kit ; qiagen gmbh , hilden , germany ) according to the manufacturer s instructions ( qiaamp dna ffpe tissue procedure ) . the quality of the dna sample and the absence of pcr inhibitors were checked in all the samples by amplification of a part of the human b - actin gene . afterwards , the presence of borrelia dna was tested by pcr in a techne gradient thermal cycler ( tc-5000 gradient thermal cycler , techne , uk ) . this study was performed by a pcr kit ( genepak dna pcr test , isogene lab ltd . russia ) which could detect three species of borrelia ( b. burgdorferi , b. garini , b. afzelii ) ( 14 ) . the amplification condition comprised an initial denaturation step of two minutes at 95c and then 43 cycles as one minute at 95c , 50 seconds at 58c , and one minute at 72c , with the final extension step prolonged to two minutes at 72c to ensure complete amplification of the target . pcr products were visualized by ethidium bromide ( etbr ) staining under uv light . visualizing the 445-bp fragment the patients consisted of 40 females ( 60.6% ) and 26 males ( 39.4% ) , with a mean age of 28.39 17.28 years . the youngest patient in this study was one and the oldest was 76 years old at the diagnosis time . the mean duration from the onset of lesions to the time of biopsy was 15.5 23.86 months . in 26 patients ( 39.4% ) , biopsies were taken mainly from the trunk ( n = 38 , 57.6% ) and lower extremities ( n = 14 , 21.2% ) ; 7 ( 10.6% ) were from the upper extremities and 7 ( 10.6% ) from the head and neck area . the lesions were more frequent on the trunk ( abdomen , n = 6 ; back , n = 18 ; chest , n = 10 ; flank , n = 4 ) , than leg ( n = 14 ) , arm ( n = 7 ) , head ( forehead , n = 4 ; scalp , n = 2 ) and neck ( n = 1 ) . the results are shown in table 1 . ( % ) . according to the classification of peterson , the clinical manifestations of morphea were of the plaque type in 59 ( 89.4% ) , linear in 6 ( 7.6% ) and frontoparietal morphea in 2 ( 3% ) patients ( 16 ) . isolation of sufficient dna with regard to quality and quantity was shown in all the clinical specimens by successful amplification of a part of the human b - actin gene . no borrelia dna was detected in skin biopsies of 66 patients with morphea with pcr ( figure 1 ) . nc , negative control ; pc , positive control ; samples 11 to 29 are negative . the present study was designed to determine the frequency of borrelia spp . in morphea lesion in our region and showed no relationship between borrelia infection and development of morphea . pcr was performed in 66 cases with confirmed morphea to detect borrelia dna in skin biopsies . all the 66 cases were negative for borrelia - specific dna , despite successful amplification of appropriate positive controls in every test , demonstrating the lack of evidence for an association between borrelia infection and morphea . in reviewing other studies , initial studies used serological methods for investigation the correlation between borrelia infection and morphea . in several studies , all the tested patients with morphea were seronegative , while some other studies found specific antibodies against borrelia in 6 - 54% of unselected patients with morphea ( 2 , 5 - 8 , 17 - 26 ) . since negative serology does not exclude previous infection with borrelia and positive serology may merely represent coincidental infection , other studies sought more definite evidence of a causal link by seeking to demonstrate the organism in biopsies of skin lesions taken from patients with morphea . attempts to visualize borrelia infected organisms directly in histological sections after appropriate staining have demonstrated spirochaetes in only a small number of cases ( 2 , 3 , 19 - 21 , 23 , 27 , 28 ) . several studies using culture of borrelia from biopsies of morpheic lesions have shown completely negative results ( 2 , 17 , 18 , 25 , 27 ) , while in a small number of cases positive results have been achieved ( 4 , 20 , 22 , 23 , 28 ) . in view of these conflicting results , studies reporting a positive association between borrelia infection and morphea have shown evidence of the organism in 26 - 100% of cases ( 8 , 10 , 26 , 29 , 30 ) , whereas in further 10 reports including our current one , no positive case has been identified ( 5 , 7 , 9 , 11 - 13 , 18 , 25 ) . isolated studies have reported a positive association in countries such as italy , switzerland , puerto rico , turkey , and japan , and negative association in spain , finland , holland , the usa , some parts of germany and france ( 2 , 3 , 10 , 18 , 25 - 27 , 29 , 30 ) . all the pcr examinations were thoroughly controlled by the use of positive and negative controls . based on these procedures , there is a high probability that we would have been able to detect borrelia dna , had it been present . fujiwara and coworkers suggested that morphea might be caused by certain subspecies of b. burgdorferi which are endemic , exclusively in certain geographical areas ( 10 ) . since the literature suggests that there is a strong geographical relation between borrelia infection and morphea , the results of the present study , which was the first study concerning the association between infection with borrelia spp . and morphea in northeast of iran , suggests that morphea is probably not associated with borrelia spp . in northeast of iran . these results indicate that in northeast of iran , there is no association between infection with borrelia spp . and the subsequent development of morphea . the reason for the inconsistent results in studies using pcr could be the low number of microorganisms found in the tissue , ie , below the detection threshold for this technique ( 5 - 7 , 11 , 25 , 31 ) . other explanations include previous antibiotic treatment , old stage of the disease , wrong biopsy site ( eg , from the negative sclerotic area ) , or wrong fixation of tissue specimens leading to dna cross - linking ( e.g. , with inadequately buffered formalin ) . in this study , we used ffpe tissue blocks , so the abovementioned points could have caused some limitations in our study . in conclusion , pcr examination showed no evidence for borrelia infection in our group of patients with morphea . therefore , we found consistent evidence for absence of b. burgdorferi infection in patients with morphea in northeast of iran . the result of this study showed no relationship between borrelia infection and morphea lesions and in other word indicated that morphea , at least in iran , is not caused by borrelia spp . this study proposed a geographical relationship between different borrelia subspecies as causative agents of morphea , which was absent in our region . if the link is firmed , the next studies can focus on the role of antibiotic therapy in morphea .

background : the etiology of morphea is still unknown . borrelia spp . as a causative agent of morphea has been discussed since 1985 , but the relationship remains uncertain.objectives:we aimed to find the frequency of borrelia in morphea lesions by polymerase chain reaction ( pcr ) in northeast of iran.patients and methods : sixty six patients with morphea were prospectively included in the present study . for each patient , formalin - fixed , paraffin - embedded tissue blocks of skin lesion biopsies were examined for borrelia spp . dna using pcr.results:no borrelia dna was detected by pcr in skin lesions of patients with morphea.conclusions:the result of this study showed no relationship between borrelia infection and morphea lesions and in other word indicated that morphea , at least in iran , is not caused by borrelia spp .

the spherical aberration of the cornea is positive and that of the lens is negative in the young , healthy eye , and these differences have a compensatory relationship [ 1 , 2 ] . decreased optical quality occurs in the aging eye as the spherical aberration of the lens becomes gradually positive and thus loses its ability to compensate for the corneal aberration , which changes little with increasing age [ 15 ] . conventional spherical intraocular lenses ( iols ) act as an aging lens in which positive spherical aberration can not compensate for the corneal aberration . aspheric iols can decrease the total amount of ocular spherical aberration after cataract surgery due to their introduction of negative spherical aberration . it has been shown that aspheric aberration - correcting iols effectively reduce ocular aberration and improve contrast sensitivity in patients with age - related cataracts [ 615 ] . however , little is known about the safety and effectiveness of aspheric iols in patients with extreme myopia . therefore , we performed the current study to evaluate the clinical effects of aspheric iol implantation in cataract patients with extreme myopia by comparing the objective and subjective visual quality achieved with that achieved in nonextreme myopic eyes . we chose the mc x11 asp lens ( humanoptics ag ) as our experimental iol because it is currently the only aspheric iol with a negative power . the mc x11 asp lens is a one - piece hydrophilic acrylic iol with a prolate posterior surface that introduces negative spherical aberration to the ocular system . the optic diameter varies from 5.5 mm to 7.0 mm depending on the power of the iol . iols with a power of 18.0 diopter or less have an optic diameter of 7.0 mm . this prospective study included 33 eyes of 22 cataract patients ( 12 males and 10 females ) who were scheduled to undergo phacoemulsification and iol implantation surgery between june 2008 and march 2009 at the eye & ent hospital , fudan university , china . exclusion criteria included a history of previous ocular surgery , ocular disorders other than cataract , myopia , or macular degeneration , and patient refusal or inability to maintain followup . patients were divided into two groups according to their ocular axial length . those with an axial length longer than 28.0 mm were included in the extreme myopia group , and the others were included in the nonextreme myopia group . the study was approved by the ethics committee of eye & ent hospital , fudan university . after topical anesthesia , a 2.2 mm superior clear corneal incision was made , and a 5.56.0 mm continuous curvilinear capsulorhexis was created . after hydrodissection , endocapsular phacoemulsification of the nucleus and cortical aspiration were performed using the intrepid micro - coaxial system on the infiniti ( alcon laboratories inc . ) . preoperative measurements included visual acuity , intraocular pressure , axial length , and corneal endothelial cell density . at 1 day , 3 days , 2 weeks , and 1 month after surgery , visual acuity and slit - lamp examination were performed . six months postoperatively , visual acuity , refraction , contrast sensitivity , wavefront aberration , and subjective visual quality were assessed . complications such as posterior capsule opacification ( pco ) and retinal detachment were recorded at the last follow - up visit . subjective visual quality was evaluated using the self - administered edition of the national eye institute visual functioning questionnaire-25 ( nei vfq-25 ) . this 25-item questionnaire was designed to assess vision - related quality of life ( vrql ) . it includes one general health rating question and 11 vision - targeted subscales as listed in table 2 . , the answer was converted to a 0-to-100-point score according to the manual , with higher scores representing better vrql . contrast sensitivity was measured using the contrast glare tester cgt-1000 ( takaci ) under mesopic illumination ( 10 cd / m ) at a 350 mm testing distance . contrast sensitivity was defined as the reciprocal of the contrast threshold , and this value was converted to log contrast sensitivity for statistical analysis . after mydriasis , high - order aberrations were measured with the hartmann - shack aberrometer ( wasca analyzer , carl zeiss meditec ) . three consecutive measurements were performed on each eye . the lateral coma ( z3 ) , vertical coma ( z3 ) , and spherical aberration ( z4 ) as well as the root mean square ( rms ) values of the total high - order aberrations and 3rd - order to 7th - order aberrations over a 6.0 mm pupil diameter were automatically calculated by the aberrometer . independent t - test was used to compare demographic data , questionnaire scores , contrast sensitivity , and wavefront aberrations between the two groups . logarithm of the minimum angle of resolution ( log mar ) visual acuity values were tested by the wilcoxon rank - sum test . comparison of snellen visual acuity before and after surgery was performed using the cmh chi - square test . however , 7 eyes ( 38.9% ) in the extreme myopia group had preexisting maculopathy before surgery , including 6 eyes with degenerative myopic maculopathy and 1 eye with macular schisis . six months after surgery , 77.8% of eyes in the extreme myopia group achieved a bcva of 20/40 or better , including 22.2% of eyes with 20/25 or better . four eyes demonstrated poor vision of less than 20/60 due to severe macular degeneration or macular schisis . in the nonextreme myopia group , 86.7% of eyes achieved a bcva of 20/40 or better , including 80.0% of eyes with 20/25 or better . the postoperative bcva of both groups was significantly better than the respective preoperative bcva values ( = 16.36 , p = 0.0001 ; = 20.94 , p = 0.0000 ) , and the nonextreme myopia group performed significantly better than the extreme myopia group ( = 5.98 , p = 0.0144 ) . however , evaluation of the vfq-25 subscale scores revealed that the nonextreme myopia group performed significantly better than the extreme myopia group in terms of mental health and dependency . data related to driving were not analyzed , because none of the patients in the extreme myopia group and only four patients in nonextreme myopia group drove . as illustrated in figure 2(a ) , contrast sensitivity without glare did not differ between the groups at each spatial frequency . however , patients in the nonextreme myopia group showed better contrast sensitivity with glare at intermediate frequencies ( visual angle of 2.5 degrees , p = 0.0277 and 1.6 degrees , p = 0.0181 ) ( figure 2(b ) ) . for a 6 mm pupil , the average spherical aberration ( z4 ) was 0.03 0.11 m in the extreme myopia group and 0.07 0.07 m in the nonextreme myopia group , and total high - order aberrations were 0.50 0.17 m and 0.46 0.15 m , respectively . there were no significant differences in lateral coma , vertical coma , spherical aberration , total high - order aberrations , or 3rd - order to 7th - order aberrations ( figure 3 ) . one patient complained of glare in one eye ( 5.6% ) in the extreme myopia group , and three eyes ( 20% ) were associated with complaints of glare in the nonextreme myopia group , which did not represent a statistically significant difference ( p = 0.340 ) . the average follow - up period was 6.94 1.47 months ( range 6 to 10 ) in the extreme myopia group and 6.60 1.59 months ( range 6 to 12 ) in the nonextreme myopia group . at the last followup , two eyes in each group ( 11.1% and 13.3% , resp . ) had moderate pco but did not require further treatment . one eye in the extreme myopia group developed capsular block syndrome , and the eye achieved a final visual acuity of 20/30 following anterior capsulotomy . it is well known that myopia is more common in asia than in america , europe , and africa with a prevalence of 32.3% in the urban adult chinese population reported by the latest epidemiological study published in 2009 . high myopia prevalence also varies geographically , ranging from 1.7% to 3.3% in europe , while it affects up to 24% of university students in south - east asia . in this study , we carried out phacoemulsification and aspheric iol implantation with low or negative power on cataract patients with extreme myopia . we report the visual performance of aspheric iols in terms of functional vision in cataract eyes with extreme myopia in comparison to that achieved in patients with nonextreme myopia . our results show that aspheric iol implantation provided good visual outcomes in most eyes with extreme myopia , although some patients with extreme myopia had relatively worse retinal status than nonmyopia patients . when the seven eyes with maculopathy in the extreme myopia group were excluded from the data analysis , postoperative visual outcomes were similar between the two groups ( = 1.45 , p = 0.2288 ) . for the seven excluded eyes , visual acuity improved after surgery anyway : one improved from hand moving to 20/400 , one improved from 20/2000 to 20/250 , and the other 5 improved 2 to 8 lines ( snellen chart ) . in these patients , after objective visual acuity measurements , we assessed the subjective visual quality of the patients using the nei vfq-25 . this questionnaire was designed to capture the impact of visual problems on physical functioning , emotional well - being , and social functioning . it has been widely used to evaluate health - related quality of life in patients with various eye diseases and treatments [ 1925 ] . the score from the extreme myopia group was similar to that reported by lin et al . , who implanted the aspheric iq iol ( sn60wf , alcon laboratories inc . , interestingly , although the nonextreme myopia group had better postoperative bcva in the present study , the two groups reported similar subscale scores for near and distance activities ; that is , the patients ' perception of their visual function was similar . this might be attributed to the preoperative visual status of the patients with extreme myopia who always had poor visual function . therefore , the removal of the cataract along with the correction of the refractive errors likely resulted in a high level of patient satisfaction in terms of visual outcome . however , the subscale scores of mental health and dependency were significantly lower in this group , suggesting that these patients worried more about their eyesight and that their quality of life was more affected by vision . , we found that patients with nonextreme myopia had better contrast sensitivity at intermediate spatial frequencies under glare conditions . these data are in agreement with stoimenova 's findings , which showed that myopes exhibited reduced sensitivity to contrast in comparison to emmetropes and that contrast sensitivity decreased with an increasing degree of myopia . this difference may contribute to the aberrations of the myopic eyes or functional / morphologic changes in the retina of myopic eyes . we also compared high - order aberrations between the groups and found that postoperative ocular spherical aberration ( z4 ) was near zero in the two groups , which fulfilled the aim of compensating the corneal spherical aberration with an iol . the total effect of all monochromatic optical aberrations represents the optical quality of the eye . because the spherical and cylindrical refractive errors were fully corrected and high - order aberrations were similar between groups , the optical quality of the ocular system in the extreme myopia group was as good as that in the nonextreme myopia group . however , the extreme myopia group showed worse visual acuity and contrast sensitivity , mainly because of the poor retinal status . in the absence of macular degeneration , the eyes with extreme myopia would have achieved visual acuity as good as that of eyes with nonextreme myopia . glare disturbance occurred in 5.6% of patients in the extreme - myopia group and 20% of patients in the nonextreme myopia group , and this difference was consistent with the results of previous studies . franchini reported that glare occurred in 20% of patients who received the aspheric tecnis z9000 iol ( abbott laboratories ) . in the study by johansson et al . , 21.1% of patients who received an akreos adapt ao iol ( bausch & lomb laboratories inc . ) in one eye and a tecnis z9000 iol in the other eye experienced glare . in the current study , a possible cause may be that the macular disorder of some of the eyes was so severe that the patients could not detect the glare . in terms of the pco and retinal detachment the aspheric iol used in this study was the mc x11 asp , which features a large optic diameter ( 7.0 mm ) for middle to low iol powers . it has been shown that greater optic diameter can reduce postoperative glare [ 30 , 31 ] . larger optic diameter can also facilitate postoperative peripheral retinal examination and treatment , because eyes with high myopia are at high risk of lattice degenerations , retinal holes and tears , and retinal detachment . because of the larger optic diameter , a larger capsulorhexis of 6.0 to 6.5 mm was required . one patient developed capsular block syndrome , which may have been caused by a relatively small capsulorhexis opening . in conclusion , aspheric iols can provide good visual outcomes for cataract patients with extreme myopia . also , preoperative evaluation of the severity of maculopathy is very important and should be carefully performed in eyes of patients with extreme myopia before surgery .

objective . to evaluate the postoperative visual quality of cataract patients with extreme myopia after implantation of aspheric intraocular lenses ( iols ) . methods . thirty - three eyes were enrolled in this prospectivestudy . eighteen eyes with an axial length longer than 28 mm were included in the extreme myopia group , and the other 15 eyes were included in the nonextreme myopia group . phacoemulsification and aspheric iol implantation were performed . six months after cataract surgery , best - corrected visual acuity ( bcva ) , contrast sensitivity , and wavefront aberrations were measured , and subjective visual quality was assessed . results . the bcva improved significantly after surgery for both groups , and patients in the nonextreme myopia group achieved better postoperative bcva due to better retinal status of the eyes . the evaluation of contrast sensitivity without glare was the same in both groups , whereas patients in the nonextreme myopia group performed better at intermediate spatial frequencies under glare conditions . the two groups did not show a significant difference in high - order aberrations . with regard to subjective visual quality , the composite scores of both groups did not differ significantly . conclusions . aspheric iols provided good visual outcomes in cataract patients with extreme myopia . these patients should undergo careful evaluation to determine the maculopathy severity level before surgery .

anxiety disorders are thought to be the most prevalent psychiatric disorders in the general population . sympathetic activation and parasympathetic ( vagal ) withdrawal.1 among various anxieties , panic disorder ( pd ) typifies the occurrence of sudden , recurrent and unexpected panic attacks , reaching a peak in approximately 10 minutes.2 according to the etiopathogenesis of anxiety disorders , clinicians are used to choosing antidepressants or sedatives to treat pd . the panic attack symptoms of patients , described as palpitations , trembling or shaking , sensations of shortness of breath or smothering , faint , fear of dying , and hot flashes , gradually disappear within the periodic treatment . however , there are few records on the special modality of pd , which shows a totally reversed pathogenesis vagal activation occupying the leading role . mrs jyh , a 41-year - old , married , chinese female , has been suffering from sudden episodes of tingling , numbness , sensations of shortness of breath , and giddiness since the age of 33 . she has been treated with many kinds of anxiolytics for a sufficient amount of time but with little effect . recently , her symptoms were exacerbated with the occurrence of two daily episodes of attacks ; she also began to experience the feeling of impending death , and sometimes even fainted , eyes closed . after the attack , she was able to recall the whole process and complained of fatigue and poor sleep with the fear of recurrence which restricted her social functioning markedly . there were no abnormalities on the physical examination and laboratory tests including the tilt - table testing . her symptoms were reckoned to be common pd according to the diagnostic criteria of the international classification of diseases ( icd)-10 . therefore , she began treatment with paroxetine 20 mg / day until the dose increased to 40 mg / day and clonazepam 3 mg / day . however , her symptoms did not improve except for the sleep quality . during her hospitalization , we happened to find her heart rate was 55 beats per minute during a panic attack . based on the variation of her heart rate , we prescribed atropine to control her bradycardia occurring during these episodes . she was treated with atropine 0.6 mg / day , increased to 1.8 mg / day after 1 week . because of her signs of worry and hopelessness between the intervals of attacks , we did not cease the treatment with paroxetine . through the treatment for 5 weeks , the patient had remission of pd and her basic heart rate also increased to 76 beats per minute but no obvious somatic discomfort was observed . as a result , she was discharged from hospital . we were glad to find that she had recovered her normal life with nearly no panic attacks at all . pd usually has a lifetime prevalence of 1% to 3% and sudden attacks of fear accompanied by cardiac symptoms such as palpitations , chest pain , and tachycardia.3 in modern reviews , pd , also the first anxiety disorder to which heart rate variability analysis was applied due to the salience of tachycardia,4 is dominated by a focus on sympathetic aberrations such as tonic sympathetic nervous system hyperarousal.5 however , there has been a tendency to emphasize the sympathetic nervous system and neglect the parasympathetic function . according to the report of massana et al , they also found that some pd patients showed symptoms of bradycardia and generalized sweating , which they called pseudoneurological symptoms . according to their research , they concluded that pd may be a heterogeneous condition and can be sorted into different subtypes.6 we hypothesize that the reason atropine , used on this specific patient , was effective could be due to the activation of vagus nerve during her panic attack , which was similar to the special subtype of pd mentioned above . as is known to all , the vagus nerve , innervating the sinoatrial node and atrioventricular node , could cause a greater reduction in heart rate when stimulated.7 the patient in this case just showed related inhibitive symptoms such as fainting and bradycardia instead of tachycardia during episodes . considering this , we assumed that her pd is triggered by the vagus nerve hyperarousal . as a result , we treated her with atropine , a potent cardiac parasympatholytic blocking agent , which could increase the heart rate and is widely used to treat bradycardia.8 to our delight , the fact demonstrates the efficacy of atropine combined with paroxetine in curing this specific case of pd . our case just suggests that the pathogenesis of pd might be the imbalance between the sympathetic and parasympathetic tone , whereas the imbalance could be manifested by the activation of either sympathetic nervous system or parasympathetic nervous system . hence , when we are confronted with patients with pd , we should pay attention to the variation of their heart rate to differentiate the type of pd and prescribe the pertinent medicine .

panic disorder is often associated with the autonomic nervous system pattern sympathetic activation and parasympathetic ( vagal ) withdrawal . however , we present one special case here to show a totally reversed pathogenesis vagal activation occupying the leading role , which requires atropine to cure the patient s symptoms . through this report , it is reasonably proven that panic disorder may be a heterogeneous condition , whose mechanism might be the imbalance between the sympathetic and parasympathetic tone .

activator protein-1 ( ap1 ) is a transcription factor that consists of either homo- or heterodimers of the jun and fos family proteins . it regulates gene expression in response to a variety of stimuli , including environmental stresses , uv radiation , cytokines , and growth factors . ap1 in turn controls a number of cellular processes including proliferation , transformation , inflammation , and innate immune response . the jun and fos proteins share similar amino acid sequences that comprise the basic dna - binding sequence and the adjacent leucine zipper region by which these proteins dimerize [ 24 ] . the ap1 transcription factor binds specifically to 12-o - tetradecanoylphorbol-13-acetate ( tpa ) responsive element 5-tgag / ctca-3 which is commonly referred to as the ap1 site [ 5 , 6 ] . c - fos and c - jun genes are autoregulated ; the transcription of c - jun is stimulated by its own product , and in contrast c - fos is negatively autoregulated [ 79 ] . ap1 has been found constitutively active in many cancers including breast , ovarian , cervical , and lung . numerous studies have shown that inhibition of ap1 has a profound effect on the behavior of cancer cells and tumors suggesting that ap1 could be a promising target for cancer therapy . curcumin , a dietary spice derived from the plant turmeric ( curcuma longa ) , is used as a traditional medicine for inflammatory conditions . further , curcumin has been reported to have anti - inflammatory , anti - oxidant , and anticancer effects [ 1215 ] . in vivo administration of curcumin was found to reduce the incidence and size of tumors in mice [ 1619 ] . moreover , curcumin was reported to inhibit proliferation and cell cycle progression in cancer cells . curcumin suppresses constitutive ap1 activity in hl-60 , raji , and prostate cancer cell lines ( lncap , pc-3 , and du145 ) [ 2125 ] . curcumin was also reported to suppress lps - induced cyclooxygenase-2 gene expression by inhibiting ap1 dna binding in bv2 microglial cells . it was confirmed that curcumin directly interacts with jun - fos dimer and inhibits its binding to dna ( ap1 site ) . some synthetic curcumin derivatives have been discovered as inhibitors of jun - fos - dna complex formation [ 2830 ] . however , no information on the site of interaction is reported yet . in the present study we investigate the interaction of curcumin derivatives with jun - fos complex by molecular docking studies . to investigate the interaction with jun - fos complex , curcumin natural derivatives ( figure 1 ) , synthetic curcumin - based inhibitors ( table 1 ) , and other known inhibitors of jun - fos - dna complex formation ( figure 2 ) were drawn and 3d optimized using marvinsketch ( free academic license ) and saved in protein data bank ( pdb ) file format . these molecules were prepared for molecular docking by merging nonpolar hydrogens , assigning gastegier charges , and saving them in pdbqt file format using autodock tools ( adt ) 1.5.6 . x - ray crystal structure of jun - fos - dna complex ( pdb i d : fos1 ) was obtained from the protein data bank ( http://www.rcsb.org/pdb ) . for molecular docking dna and other heteroatoms ( water , ions , etc . ) gasteiger charges were assigned , and jun - fos complex was saved in pdbqt file format using adt . grid and docking parameter files were prepared using adt , and molecular docking was performed with autodock 4.2.1 ( scripps research institute , usa ) considering all the rotatable bonds of curcumin derivatives as rotatable and jun - fos complex as rigid . grid box size of 90 90 90 with 0.375 spacing was selected that include the whole basic dna - binding sequence and the adjacent leucine zipper region of jun - fos complex . empirical - free energy function and lamarckian genetic algorithm , with an initial population of 150 randomly placed individuals , a maximum number of 2,500,000 energy evaluations , a mutation rate of 0.02 , and a crossover rate of 0.80 , were used to perform molecular docking . curcumin derivative - jun - fos complex for lowest free energy of binding ( g ) confirmation from the largest cluster was written in pdbqt format and converted to pdb file format using ucsf chimera 1.6.1 . further , these complexes were analyzed using pymol 0.99 for possible polar and hydrophobic interactions . all the docking studies were performed at intel(r ) xeon(r ) cpu ( 3.2 ghz ) with linux - based operating system fedora 15 . x - ray crystal structure of jun - fos - dna complex shows that arg140 , asn147 , lys153 , ser154 , arg155 , arg158 , arg268 , asn271 , arg272 , and ser278 are the key residues by which jun - fos complex binds to dna through hydrogen bonding ( figure 3 ) . to predict the interaction of curcumin derivatives with jun - fos complex , natural curcumin derivatives and other known inhibitors of jun - fos - dna complex formation were docked over dna - binding region ( dbr ) of jun - fos complex , and results were summarized in table 2 . amongst all the natural curcumin derivatives docked to jun - fos complex curcumin sulphate bound with g of 8.20 kcal / mol and predicted ki of 976.64 nm followed by cyclocurcumin and demethoxycurcumin which bound with g of 5.75 and 5.72 kcal / mol and predicted ki of 61.42 and 63.86 m , respectively ( figure 4(a ) ) . the binding mode of curcumin sulphate depicted that sulphate and nearby methoxy group present at one aromatic ring of the molecule were in polar contact range with lys282 ; however methoxy group present at the other side formed polar contact with side chain of lys280 ( figure 4(b ) ) . keto group present in the linker region was in polar contact range with side chain of arg158 . the binding mode of cyclocurcumin showed that hydroxyl group present at one aromatic ring of the molecule formed polar contact with side chain of arg155 ; however at the other side it formed polar contacts with arg158 ( figure 4(c ) ) . when demethoxycurcumin docked to jun - fos complex , hydroxyl and neighboring methoxy group present at one aromatic ring formed polar contact with side chains of arg155 and arg279 , respectively , while hydroxyl group present at other side of the molecule formed polar contact with side chain of ser276 ( figure 4(d ) ) . in the linker region of the molecule keto and hydroxyl groups were in polar contact range with arg158 and arg279 , respectively . amongst the synthetic curcumin - based inhibitors chc011 bound to jun - fos complex with g of 9.59 kcal / mol and predicted ki of 93.25 nm followed by chc009 and chc007 which docked with g of 9.52 and 9.15 kcal / mol and predicted ki of 104.26 nm and 196.96 nm , respectively ( figure 5(a ) ) . similar results were observed in the in vitro studies by hahm et al . in 2002 . the binding mode studies depicted that no2 group present at one aromatic ring of the chc011 molecule formed polar contact with side chain of arg272 while at the other side of the molecule it interacted with lys282 ( figure 5(b ) ) . when chc009 docked to jun - fos complex , keto group present in the linker region of the molecule formed polar contact with side chain of arg158 ( figure 5(c ) ) . hydroxyl and no2 group present at one aromatic ring of the chc007 molecule formed polar contacts with backbone of arg155 and side chain of lys282 , respectively , while the hydroxyl group present in the linker region of the molecule showed polar contact with side chain of arg158 ( figure 5(d ) ) . amongst the other known inhibitors t5224 [ 3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxybenzo [ d]isoxazol-6-yl)methoxy)phenyl)propanoic acid ] bound to jun - fos complex with g of 9.96 kcal / mol and predicted ki of 49.64 nm followed by dihydroguaiaretic acid and resveratrol which docked with g of 4.43 and 4.20 kcal / mol and predicted ki of 569.58 and 829.30 m , respectively ( figure 6(a ) ) . the binding mode studies of t5224 depicted that oxygen atom of cyclopentyloxy group formed polar contact with side chain of arg158 ; however nearby hydroxyl group formed polar contact with arg279 . hydroxyl group of 3-hydroxybenzo [ d]isoxazol-6-yl)methoxy group formed polar contact with asn271 ; however oxygen atom of its methoxy group formed polar contact with ser278 . acid group of the t5224 molecule was in polar contact range with lys282 ( figure 6(b ) ) . when docked to jun - fos complex neighboring hydroxyl and methoxy groups present at one side of the dihydroguaiaretic acid molecule formed polar contacts with ser278 and arg279 respectively , whereas the hydroxyl group present at the other side of the molecule formed polar contact with backbone of arg279 ( figure 6(c ) ) . when docked to jun - fos complex neighboring hydroxyl groups attached to one of the aromatic ring of resveratrol molecule formed polar contacts with ser 154 and side chain of lys282 , respectively ( figure 6(d ) ) . we observed that curcumin derivatives form polar contacts preferentially with residues like arg155 , arg158 , lys276 , arg279 , lys280 , and lys282 when docked to dbr of jun - fos complex amongst which arg155 and arg158 are the key residues by which jun - fos complex binds to dna . the results suggested that interaction of curcumin derivatives with residues like arg155 and arg158 could be the possible mechanism by which curcumin derivatives inhibit jun - fos - dna complex formation . ala151 , ala275 , leu283 , and ile286 were the hydrophobic residues present at binding site contributing to hydrophobic contacts with inhibitor molecules . the present molecular docking study provides insights into the inhibition of jun - fos - dna complex formation by curcumin derivatives . the involvement of residues like arg155 , arg158 , lys276 , lys280 , and lys282 seems to play a key role in binding of curcumin derivatives to jun - fos complex through polar contacts which prevents its binding to dna ( ap1 site ) . ala151 , ala275 , leu283 and ile286 were the important hydrophobic residues present at binding site . most of the curcumin derivatives were predicted to be more potent than inhibitors like resveratrol and dihydroguaiaretic acid . curcumin sulphate was predicted to be the most potent inhibitor amongst all the natural curcumin derivatives docked .

activator protein-1 ( ap1 ) is a transcription factor that consists of the jun and fos family proteins . it regulates gene expression in response to a variety of stimuli and controls cellular processes including proliferation , transformation , inflammation , and innate immune responses . ap1 binds specifically to 12-o - tetradecanoylphorbol-13-acetate ( tpa ) responsive element 5-tgag / ctca-3 ( ap1 site ) . it has been found constitutively active in breast , ovarian , cervical , and lung cancers . numerous studies have shown that inhibition of ap1 could be a promising strategy for cancer therapeutic applications . the present in silico study provides insights into the inhibition of jun - fos - dna complex formation by curcumin derivatives . these derivatives interact with the amino acid residues like arg155 and arg158 which play a key role in binding of jun - fos complex to dna ( ap1 site ) . ala151 , ala275 , leu283 , and ile286 were the residues present at binding site which could contribute to hydrophobic contacts with inhibitor molecules . curcumin sulphate was predicted to be the most potent inhibitor amongst all the natural curcumin derivatives docked .

it is well established that nonpharmacological management using cognitive behavioral therapy ( cbt ) is effective for the management of depression and anxiety [ 13 ] , and for maintaining quality of life ( qol ) in cancer patients . given the limited availability of therapists , the access is a challenge . low - intensity working with less practitioner time may contribute to a wider use of cbt . guided self - help defined as a self - administered intervention facilitated by healthcare professionals using a range of books or evidence - based self - help manuals for specific purposes , was recently recommended in the national institute for health and clinical excellence ( nice ) guidelines for the management of depression in adults with a chronic physical health problem . psychological need is one of the highest unmet supportive needs of cancer patients , and increases with longer time from diagnosis . surviving cancer usually means enduring sequential combinations of treatment modalities , including surgery , radiotherapy , chemotherapy , and hormonal treatment . it is stressful for most women to confront not only the burden of treatment , but also the fear of recurrence and death . the prevalence of depression , anxiety , or both is two - fold higher in women with early breast cancer than in the general female population . women with breast cancer need support to cope with the psychological consequences of the disease , but many feel insufficiently informed about psychological support options . despite the recognition that early preventive intervention against psychological distress soon after cancer diagnosis is critical , there are few management strategies . through our development of people - centered care to promote patient self - help and to establish the best possible care system as part of the 21st century center of excellence program , we found that women with breast cancer often faced psychological challenges during the treatment process . chemotherapy has a significant impact on qol of women with breast cancer , and may increase the risk of depression and anxiety [ 7 , 14 ] . professional - led support groups for cancer patients have been shown to have positive effects on the psychosocial functioning of their members . oncology nurses are the most valuable clinical contact , and can provide the initial education and psychological support to cancer patients [ 1719 ] . in this study , we investigated the effectiveness of the oncology nurse - guided self - help intervention compared with usual care in preventing the development of depression or anxiety in women with breast cancer in addition to support group programs in outpatient chemotherapy settings . patients were invited to join the study at an outpatient appointment before their chemotherapy commenced at an ambulatory treatment center in a general hospital in tokyo , japan . we included women diagnosed with primary breast cancer who were younger than 80 years of age , had been surgically treated and were awaiting adjuvant therapy ( 4 cycles of epirubicine combined with cyclophosphamide : ec therapy ) . participants were excluded if they had relapsed , were pregnant , or had a history of mental disorder . we assigned patients receiving ec therapy for the first year of the study to the control group and those receiving therapy for the second year to the intervention group . the intervention group received a 12-week guided self - help intervention ( table 1 ) . we developed a self - help kit as a self - learning package of necessary preparatory information during a period of outpatient chemotherapy . the self - help kit aimed at helping patients develop cognitive representations based on rehearsing the outpatient chemotherapy procedure ; improving patients ' belief in their ability to manage side effects ; and helping patients build problem - solving skills . an orientation was given by the nurse , and all participants saw the video on chemotherapy procedure before the initial adjuvant chemotherapy . the participants received self - learning reading materials ( basic knowledge on chemotherapy , side effects , and problem - solving skills ) , and kept diaries for self - management . to reinforce participant learning , the nurse in attendance monitored and facilitated the patient 's progress using the diary during the patient 's chemotherapy , which was administered every 3 weeks . we also provided professional - led support groups for patients to attend at least two to three times during the study period to promote effective management of psychological and emotional responses through interaction with peers in support groups . a small support group meeting comprising about five members was held once a week in the communication lounge next to the treatment room on outpatient visit day . on the basis of a prepared scenario , two topics were discussed in the support group ( for example , how do you talk about your cancer to the people close to you ? or each support group meeting was facilitated by one of the investigators and the nurse from an ambulatory treatment center and lasted 70 minutes . women assigned to the control group received usual care from the nurse using a simple chemotherapy education leaflet which was different from that for the intervention group . the leaflet included information on adverse events and management , and emergency contact ( e.g. , in case of fever ) . we completed all outcome measures within the same timeframe as that of the intervention group . to assure the quality of the intervention , the 13 nurses who provided interventions attended a 2-day training session consisting of two workshops . the purpose of the first session was to teach the nurses the theory and practical method of the guided self - help program . to assess the nurses ' level of understanding of the instruction method , we conducted pre- and posttests using a computer - assisted learning . the nurses answered 18 true or false questions on the knowledge and information necessary to improve coping processes in daily living and with side effects during chemotherapy . posttest scores were significantly higher ( p < .01 ) than pretest scores , and the knowledge base of the nurses who participated in the session was deemed sufficient , as we reported elsehwere . the purpose of the second session was to teach the nurses how to facilitate the support group . the nurses were divided into small groups of 2 or 3 , and each nurse roleplayed discussion on how to cope with treatment and living . patients ' reports of depression symptoms were evaluated by the center for epidemiologic studies - depression ( ces - d ) scale , a 20-item self - report questionnaire to measure depression symptoms in four domains ( depression affect , somatic complaints / activity inhibition , positive affect , and interpersonal difficulties ) on a four - point scale during the week prior to evaluation . higher scores on this measure indicate higher levels of depressive symptomatology , with scores equal to or greater than 16 indicating an increased risk of clinical depression . we used the japanese version of the ces - d , which is a common tool to for psychological assessment of patients with breast cancer in japan . the spielberger state - trait anxiety inventory ( stai ) contains two 20-item forms used to measure state anxiety ( the level of present anxiety ) and trait anxiety ( the general level of anxiety experienced ) . we used the japanese version of the stai scale , since it is widely used to assess psychological distress of patients with breast cancer in japan . the short form-36 ( sf-36 ) health survey is a generic questionnaire used to measure two major health concepts ( physical and mental health ) with 36 questions and 8 multiitem scales : physical functioning , role functioning physical , bodily pain , general health , vitality , social functioning , role functioning emotional , and mental health . we used the japanese version of the sf-36 because of a reliable self - reporting tool for patient populations in japan . toxicity was graded according to adverse events of chemotherapy assessed by administering the japanese version of nci - common toxicity criteria nci - ctc v2.0 . data were collected at baseline ( t1 ) , 1 week ( t2 ) , 3 months ( t3 ) , and 6 months ( t4 ) . the data at baseline and 1 week were collected on site , while the participants returned completed questionnaires at 3 months and 6 months by mail . we used the chi - square test and the student t - test to examine differences between the two groups . we performed repeated measures analysis of variance ( anova ) to test the effects of the intervention on the measures over time . all statistical analyses were performed using two - tailed tests , and the significance level was set at 0.05 . of the 110 female patients who received postoperative adjuvant systemic therapy , 95 met the eligibility criteria for recruitment . thirteen patients refused to participate ; thus , a total of 82 patients ( 46 in the intervention group and 36 in the control group ) consented to participate . at the time that t4 questionnaires were completed ( 6 months postinvestigation ) , 7 patients ( 15.2% ) had withdrawn from the intervention group , leaving a total of 39 , and 8 ( 22.2% ) had withdrawn from the control group , leaving 28 . the reasons for withdrawal in the intervention group included discontinued treatment ( n = 2 ) , psychological condition potentially hampering compliance with the study protocol ( n = 2 ) , and no reply ( n = 3 ) . similarly , in the control group , discontinued treatment ( n = 2 ) , psychological condition potentially hampering compliance with the study protocol ( n = 3 ) , loss of a family member ( n = 1 ) , and no reply ( n = 2 ) were the reasons for withdrawal ( figure 1 ) . there were no significant differences in patient demographic or medical characteristics ( age , employment , education , stage of cancer , and treatment ) at baseline between the intervention and control groups ( table 2 ) . adverse events included mucositis , fatigue , emesis , nausea , and alopecia , and there were no significant differences in toxicity between the two groups . table 3 shows the mean scores for anxiety and depression symptoms at t1 , t2 , t3 , and t4 in the intervention and control groups . at baseline , there were no significant differences between the intervention and control groups on the trait anxiety or state anxiety scales , and the repeated measures anova revealed no significant differences in the state anxiety or trait anxiety scales between the two groups over the study period . although the depression levels on the scales decreased markedly in the intervention group over time , none of these bivariate relationships were significant . , there were no significant differences between the intervention and control groups on any sf-36 subscales ( table 4 ) . although only the mental subscale scores showed a significant difference between the two groups over the study period , the effect size was small ( f = 7.48 , p = .008 , = 0.004 ) . in this study , the guided self - help intervention was not significantly more effective than the usual care , although all depression and anxiety measures and qol measures were improved in both the intervention and control groups . there are possible explanations for the present results , including sample size , the severity of disease , placebo effect , and number of contact . patients who experience clinically significant depression , may be more likely to be benefit from the intervention . report that women with a high depression burden had the greatest gains in psychological adjustment with five 6-week self - help interventions , and pitceathly et al . also demonstrated that a 3-session ( face - to - face and telephone ) program by nonspecialists was an effective intervention for cancer patients at high risk of developing anxiety or depressive disorder . therefore , in a population that does not have a high risk of depression but does have a primary diagnosis of cancer , a larger sample size or a longer followup may be needed to detect significant differences in the stai and ces - d . repeated contact with the same nurse might have provided those in the control group with a feeling of security , even though they received no intervention but only routine chemotherapy sessions with the standard explanations . the contact number of the nurse was six in the intervention group , which was within the range of no less than three contacts and no more than six recommended by the nice guideline . although the effects of follow - up telephone calls for cancer patients were demonstrated in other studies [ 31 , 32 ] , the nurse talked to the patient only during the injection of anticancer drug at the ambulatory treatment center in this study due to the limited staffing . furthermore , the instruments we used in the present study are common for measuring changes in depression and anxiety , and qol . these instruments , however , are not designed specifically for use in cancer patients , and this may have undermined the results of this study . as the role of oncology nurses is on the rise , how the oncology nurse can contribute to prevention and management of depression and anxiety remains a challenge . , there is a movement to implement a standardized screening tool for distress by oncology nurses on a routine basis . a randomized nursing intervention using a stepped care approach , in which the basic concept is similar to this study , is planned in sweden . assessment and intervention for depression and anxiety in cancer patients by oncology nurses , guided self - management in particular , needs further research . the findings of the present study need to be interpreted in the context of several limitations . we did not randomly assign individual patients to groups in order to avoid a possible influence that could be caused by two or more patients visiting the same outpatient clinic on the same day . since the intervention group data was collected after the control group data , there exists the possibility of threatening external validity due to changes over time . our recruitment rate was lower than initially planned and resulted in the relatively small sample size , because we recruited patients by strict inclusion criteria of chemotherapy regimen ( ec therapy only ) . and finally , the nurses ' intervention in the patient 's self - help was limited to chemotherapy sessions , and the intensity of intervention therefore might not have been sufficient . the present study found that the guided self - help intervention for depression and anxiety was not significantly more effective the usual care , although all depression and anxiety measures and qol measures were improved in both groups .

depression and anxiety are prevalent in women with breast cancer . we developed a self - help kit as a self - learning package of necessary preparatory information ( basic knowledge on chemotherapy , side effects , and problem - solving skills ) . we provided an oncology nurse - guided self - help kit with a cognitive behavioral therapy approach to 46 women with breast cancer in the intervention group and usual care to 36 in the control group in outpatient chemotherapy settings . the oncology nurse monitored and facilitated the patient 's progress using the diary during the patient 's chemotherapy . we also provided professional - led support group programs . depression , anxiety , and quality of life were measured at baseline , 1 week , 3 months , and 6 months . the chi - square test and t were used to examine differences between the two groups , and repeated measures analysis of variance was used to test the effects of the intervention on the measures over time . all depression and anxiety scores were improved in both the intervention and control groups , but there were no significant differences between the two groups . further studies are needed to evaluate the effectiveness of an oncology nurse - guided self - help approach for cancer patients .

viral meningoencephalitis leading to hydrocephalus is an extremely rare entity with only few documented cases , predominantly due to hsv-2 infection . herpes simplex virus type 1 ( hsv-1 ) infection of central nervous system present in the majority of the cases as encephalitis . an 11-year - old boy was presented to the emergency pediatric department with high fever ( 38.5c ) , coughing and a 3 day vomiting history . he was initially admitted to the pediatric department and underwent a thorough examination with chest x - ray , full blood count and abdomen ultrasound , which were uneventful . within the next hours severe headache , confused mental status with gcs score to 13 , photophobia and neck stiffness were shown . figure 1:ct scan of the brain showed acute hydrocephalus with massive dilatation of lateral and third ventricles ( at mesencephalon and thalamus levels , respectively ) . ct scan of the brain showed acute hydrocephalus with massive dilatation of lateral and third ventricles ( at mesencephalon and thalamus levels , respectively ) . cerebrospinal fluid analysis of the intraoperative sample revealed 27 cells/l , with < 20 mg / dl glucose and 61 mg / dl albumin concentration , respectively . moreover , cerebral spinal fluid ( csf ) was sent for polymerase chain reaction ( pcr ) examination of hsv-1,-2 , varicella zoster virus , enteroviruses , west nile and dengue viruses . the magnetic resonance imaging ( mri ) of brain showed massive occlusive hydrocephalus ( fig . 2 ) . he received treatment for hsv-1 encephalitis with acyclovir ( 30 mg / kg / d ) for 21 days . several attempts to wean off the ventricular drain were unsuccessful and he underwent a ventriculo - peritoneal shunt on the 25th day ( table 1 ) . figure 2:mri of brain enhanced with contrast agent showing ventricular dilatation with aqueducts occlusion ( axial and sagittal sequences , respectively ) . daycsf cells27/l5/l5/l10/l12/l2/l0/l glucose<20 mg / dl68 mg / dl50 mg / dl57 mg / dl54 mg / dl60 mg / dl54 mg / dl albumin61 mg / dl48 mg / dl<20 mg / dl<20 mg / dl20 mg / dl<20 mg / dl<20 mg / dlgram - stainnegativenegativenegativenegativenegativenegativenegativepcr+ for hsv1 mri of brain enhanced with contrast agent showing ventricular dilatation with aqueducts occlusion ( axial and sagittal sequences , respectively ) . due to the fact that aqueduct is the narrowest segment of csf pathway , it is the commonest site of intraventricular obstruction . there are two peaks of distribution of age , one in the first year of life and the second in adolescence . often it may be tolerated for years in a condition described by oi et al . as arrested hydrocephalus used for patients who may harbor an undetected stenosis . to these mechanisms accounted a partially occluded aqueduct , employment of alternative csf pathways and alteration in csf production . it is also suggested that head injuries , subarachnoid hemorrhages or viral infections may worsen the occlusion . in viral infections , the mechanism is attributed either to an ependymitis leading to desquamation of ependyma with subsequent mechanical obstruction or to a cross linking between ependymal cells caused by viral particles bridges . at the aqueduct location , where continuous csf bathing with released viruses takes place in addition to that the pathological findings and subsequently the radiological ones do not prove a gliosis compared to the bacterial infections . the majority of the documented cases of viral infection and hydrocephalus development are mostly attributed to hsv-2 infection , which causes usually meningitis and shows a more benign course compared with the hsv-1 . one characteristic case of hsv-1 encephalitis and hydrocephalus was described by tyagi et al . . due to the infection presence and the prolonged hospitalization period of the child who might be burdened with a potential reoperation of stoma obstruction after a third ventriculo - stomy , the ventriculo - peritoneal shunt implantation was preferred . epitomizing the aforementioned issues , it could be concluded that by the presence of hydrocephalus without a gross obstructing intracranial lesion the suspicion of subclinically manifested viral encephalitis should be raised and thus the pcr for hsv-1 should also be included in the diagnostic tests as well , defining on the same time the optimal surgical treatment .

abstractherpes simplex virus type 1 ( hsv-1 ) is a human neurotropic virus causing encephalitis , corneal blindness or several peripheral nervous system disorders . herpes simplex encephalitis ( hse ) is the most devastating clinical syndrome with severe morbidity and mortality . hydrocephalus associated with viral meningoencephalitis is an extremely rare entity with only few documented cases , predominantly due to hsv-2 infection . hsv-1 infection of central nervous system present in the majority of the cases as encephalitis . we report a rare case of an 11-year - old child suffering from hsv-1 infection of central nervous system causing hydrocephalus without evidence of encephalitis .

diagnostic and therapeutic measures , especially against intoxication with cholinesterase inhibitors , require eliminating the toxic agents as rapidly as possible . the therapy consists of gastric lavage ( in the case of oral intake ) , support of ventilation unitl respirator is introduced , administration of atropine and pralidoxime when necessary . in the early period of poisoning , inhibition is reversible and may be reactivated by oximes . late reports contain data on the use of extracorporeal elimination of poisons in the management of these intoxications . we have recently treated successfully three patients suffering from severe poisoning with cholinesterase inhibitors by hemodialysis and hemoperfusion . 1 ) a 28-year - old patient ( s.k . , male ) , because of a traffic accident with material loss , had swallowed about 100 ml of quinalfos ( oral ld50 for rats amounts to 66 mg / kg ) in a suicidal attempt . on the way to the hospital , the patient lost consciousness and was admitted to the department 50 minutes after poisoning . on admission , he was cyanotic with white foam on his mouth , dyspneic , hypotonic , in deep coma and was not responsive to stimulation prothrombin time measured from 16s ( 50% ) to 17s ( 44% ) , and from 15.5s ( 53% ) to 12s ( 100% ) . treatment was begun with gastric lavage , introduced subclavian catheter , inserted arteriovenous shunt on the left leg and extracorporeal hemodialysis administration with hemodialyzer of 1.4 m. immediately after that , hemoperfusion over amberlite resin ( xad-4 ) for 4 hours by means of general heparinization was started . the procedure began at 6.15 p.m. , and at 7.30 p.m. the patient responded to verbal instructions . blood flow through the hemoperfusion system was kept at 200 ml / min . at the end of the procedure , macrohematuria , with low platelet values ( 48.2% lower from the initial levels ) and prolonged prothrombin time took place , and the hemoperfusion was stopped . on the next day , the patient was treated with atropine and pralidoxime and his blood - cholinesterase activity on the 13th hospital day was 50% of normal . three days after hospitalization , abstinence symptoms appeared and he was given clomethiazole and meprobamate . in 16 days the psychiatric finding showed that the patient was critical towards the attempted suicide and it appears as a shortlasting affective reaction of an hysteric personality . 2 ) a 48 year - old patient ( j.b . , male ) had a long history of ulcer disease . in 1971 the patient underwent surgical procedure because of duodenal ulcer perforation ( suture ) while , in 1974 , a gastric resection was done . in 1979 , however , the disease recurred and , since 1980 , the patient is drinking greater quantities of alcohol every day . the patient , while drunk , consumed an unknown quantity of quinalfos and , a few minutes after that , lost consciousness . on admission he was comatose , sweated , flushed , with plenty secretion in his mouth , with pinpoint pupils not reactive to light , shallow respiration and cyanotic extremities . the white - cell count was 10.4 - 7.610/l with 10 - 3 percent of nonsegmented cells . the blood - cholinesterase was 68u / l , and the platelet count was 372;166;146 and 12610/l . minutes after arriving at the hospital the patient was treated with gastric lavage and , due to the progression of respiratory insufficiency , endotracheal intubation was done . the hemodialysis , with a capillary hemodialyzer of 1.3 m , was immediately started and , after that , hemoperfusion over amberlite resin ( xad-4 ) was performed . the patient s respiration improved and eight hours later he was extubated . on the next morning , the patient regained consciousness . during the procedure , he was treated with atropine and pralidoxime and , on the third day , with meprobamate as well , due to the development of abstinence syndrome . in 12 days 3 ) the third case was a 29-year - old man ( j.s . ) . it was discovered that , in 1982 , the patient attempted suicide by cutting the blood vessels of his left forearm and , in march 1983 , he again made an attempt to commit suicide by stabbing himself in the region near the heart . he underwent urgent surgery . in the same year , after having family problems , the patient consumed about 150 ml of quinalfos . after that , he was taken to a local health institution , where he was given 40 mg of atropine intravenously , and he was admitted to our department of medicine about 9 hours after poisoning . there are data that he was consuming about 1 liter of brandy per day . on admission , the platelet count was 145 and 6010/l , and prothrombin time , after hemoperfusion , was 15s ( 46% ) . due to the serious clinical state of the patient , treatment was started immediately . a subclavian catheter was inserted and extracorporeal hemodialysis was attempted with a capillary hemodialyzer of 1.3 m. shortly thereafter , hemoperfusion over resin ( xad-4 ) was initiated and it lasted for 2.5 hours . heparin was administered and the blood flow held constant at 200 ml / minute . during , and immediately after , the procedure the patient regained consciousness and became somnolent . atropine and pralidoxime continued to be administered and on the second hospital day , due to the development of abstinence symptoms , infusion of clomethiazole was given , followed by meprobamate . on the eight day after admission , he was transferred to the department of psychiatry for further treatment of psychogenic depressive reaction , the third suicidal attempt . today in the treatment of severe poisoning , various methods are used including hemodialysis and hemoperfusion . hemoperfusion is the passage of blood through a column packed with granules of amberlite resin which act as absorbents . in this procedure , physicochemical properties of an absorbent are used , while in hemodialysis there is a concentrational gradient between the blood and the solvent across the dialysis membrane . the method of hemoperfusion is effective in an experiment , in which amberlite resin is used for elimination of organophosphorus poisons . however , there is little experience with its use , particularly with the application of activated charcoal and dialysis in cholinesterase inhibitor poisoning . hemoperfusion is when removing liposoluble substances which are bound to plasma proteins and have smaller molecular weight , as well as when the blood flow through the apparatus is greater . however , this procedure has its disadvantages , including side - effects such as thrombocytopenia and , therefore , it is reserved for most severe poisoning . three patients with methylparathion intoxication , treated with plasma perfusion through activated charcoal , have been reported . the method of hemoperfusion with activated charcoal has been described in the treatment of a 25-year - old patient after an attempted suicide , and the procedure was undertaken 25.5 hours after intoxication . the patient died as the result of coma . in the comparison of in - vitro hemodialysis and hemoperfusion , analysing the clearance of organosphosphorus compounds and nitrostigmine proved to be nondialyzable , while its clearance values for hemoperfusion with activated charcoal amounted to 59.2 ml / min . demeton - s - methyl - sulfoxide and dimethoate had higher clearance rates by hemoperfusion than by dialysis ( 83.7:60.0 ml / min and 87.8:59.1 ml / min , respectively ) . seyffart , in his publication , quoted malathion of organophosphorus poisons and reported that effective methods for its elimination are forced diuresis ( + ) , peritoneal dialysis ( + ) , hemodialysis ( + + ) and hemoperfusion over activated charcoal , while he gave no data on hemoperfusion with amerlite resin . a 34-year - old female patient , who ingested an organophosphorus poison intending to commit suicide , has been presented . there are also individual studies on the simultaneous use of these two methods : hemoperfusion with activated charcoal and hemodialysis . fifteen patients intoxicated with various sedative - hypnotic agents treated with this combination have been reported . however , the use of combined hemoperfusion - hemodialysis therapy is a matter of debate in the treatment of organophosphorus poisoning , so , in the literature , this method is not discussed . our report describes three patients whose clinical picture was very severe . in one of the patients , mechanical ventilation was institiuted and all three were in deep coma . in each case , the combined use of dialysis and hemoperfusion over amberlite resin was effective , but this management is considered as yet an unproven form of therapy . all our three patients had completely resolved after a relatively short period of time : one regained full consiousness at the end of the procedure , the other became somnolent and the third , who was in a state of apnea , established spontaneous breathing followed by extubation , and his consciousness gradually restored . there are the studies carried out in - vitro that speak in favour of hemoperfusion with amberlite resin in intoxications : the clearance value for parathion with acrylhydrogel charcoal is 59.2 ( relative clearance in percentage for a drug or pesticide at a blood flow rate of 1.25 ml / min ) and 81.3 with amberlite resin . we conclude that each patient , poisoned with organophosphorus compounds , should be treated in an intensive care unit with monitoring of all vital functions , where the quoted therapeutic methods may be applied in the case of most serious poisoning .

three patients with cholinesterase inhibitor poisoning have been presented . the patients were in a deep coma and , in one of them , artificial mechanical respiration was instituted . all three cases were treated by a procedure combining hemodialysis and hemoperfusion with amberlite resin ( xad-4 ) , and the clinical picture improved over a short period of time . after the end of procedure , the platelet count was approximately 41% of normal , some aspects of these intoxications are discussed .

livedoid vasculopathy ( lv ) is a chronic prothrombotic disease of cutaneous microcirculation resulting in cutaneous ischemia and infarction . as a rare disease , lv has an estimated incidence of ten cases per million.1 lv mostly appears in late adolescence up to the age of 30 years , and patients with lv have an average age of 45 years.2 lv shows a distinct female preference and affects three times as many females as males.1 not only correct diagnosis but also effective treatments are very difficult for patients with lv.3 due to the lack of large - scale studies in this rare disease , lv poses a great challenge to the doctors , and existing treatment has always been an individual attempt with off - label application . the main goals in the treatment of patients with lv are to avoid the repeated occurrence of active cutaneous lesions and prevent painful ulceration and irreversible scarring . as an important result of recent data , lv has been defined as a coagulation disease and systemic anti - coagulant drugs , especially the rivaroxaban , have been shown to be effective as a treatment for patients with lv.4 as the first multi - center study , rivaroxaban for livedoid vasculopathy ( riliva ) trial has been published by weishaupt et al5 and suggested that rivaroxaban is a suitable treatment option for patients with lv . the current report describes the cases of three chinese patients with lv receiving the treatment of rivaroxaban and observes the treatment effect of rivaroxaban during the follow - up . written informed consents were provided by the three patients to have the case details and any accompanying images published . female patient , 38 years old , visited our hospital on november 17 , 2014 . she complained of repeated skin eruptions with sting and tenderness in both lower limbs for 4 months . red skin eruptions did not fade under pressure , first having the appearance of tip , then gradually expanding and deeply bursting and finally coalescing and leaving the shrinkage and pigmentation , with high skin temperature ( figure 1a and c ) . no abnormality was found by cardiopulmonary physical examination , and the electrocardiogram and chest x - ray were normal . laboratory analyses revealed elevated levels of erythrocyte sedimentation rate ( esr , 24 mm / h ) , carbohydrate antigen 125 ( ca125 , 48.75 u / ml ) , and ca724 ( 19.97 u / ml ) , normal levels of c - reactive protein ( crp ) , homocysteine , alanine aminotransferase ( alt ) and creatinine , and negative antinuclear antibody , antineutrophil cytoplasm antibody , rheumatoid factor , tuberculosis antibody , autoantibody , and anticardiolipin antibody . skin biopsy revealed neutrophils , lymphocytes , or plasmacytes in a few small vessel walls ( figure 2a ) . meanwhile , not only no thrombus was seen in the vessel lumen , but no fibrinoid necrosis was noted in the vessel wall as well ( figure 2b ) . she used the glucocorticoid , immunosuppressant , and other externally used drugs , and skin eruptions appeared repeatedly . after being admitted to our hospital , glucocorticoid was gradually decreased and then finally ceased , immunosuppressant was ceased , and rivaroxaban 10 mg / d was regularly taken once a day . skin eruptions disappeared after 3 months and had not recurred after 23 months ( figure 1b and d ) . female patient , 30 years old , visited our hospital on july 9 , 2015 . red skin eruptions first had the appearance of tip and then gradually expanded . for these skin eruptions , it was easy to burst but difficult to coalesce . scarring and pigmentation were formed due to the repeated appearance of skin eruptions ( figure 3a and c ) . she had medical history of chickenpox appearing at the same time of skin eruptions , 4 years ago . laboratory analyses showed normal levels of blood platelet count , esr , crp , alt , and creatinine and negative autoantibody and tuberculosis antibody . the patient used prednisone acetate , thalidomide , colchicine , and hydroxychloroquine . due to the lack of treatment effect , prednisone acetate was ceased , and other drugs were not regularly used . after being admitted to our hospital , rivaroxaban was taken for 6 months , and skin eruptions had not recurred after 18 months ( figure 3b and d ) . female patient , 39 years old , visited our hospital on october 9 , 2013 . skin eruptions were dark red with sting , tenderness , and high skin temperature ( figure 4a ) . swelling and pain were not seen , and movement was not restricted in lower limbs and all joints . laboratory analyses showed elevated levels of white blood cell count ( 11.8810/l ) , blood platelet count ( 35310/l ) , esr ( 32 mm / h ) , crp ( 0.4 mg / dl ) , ca125 ( 65.24 u / ml ) , and ca724 ( 13.13 u / ml ) and normal levels of hemoglobin , alt , creatinine , immunoglobulin , and complement . skin biopsy showed chronic inflammation of cutaneous tissue . there were eosinophils in the superficial layer of dermis , inflammatory cells in vessel walls , and fibrinoid necrosis in a few vessel walls ( figure 5 ) . she used methylprednisolone , levofloxacin , and indomethacin , and skin eruptions recurred after ceasing methylprednisolone . immunosuppressant , immunoglobulin , ii recombinant human receptor antibody fusion protein of tumor necrosis factor ( rhrptn ) , and adalimumab were also added to treat the skin eruptions . however , due to the recurrence of tuberculosis , methylprednisolone and immunosuppressant were ceased , and rivaroxaban was regularly taken for 3 months . female patient , 38 years old , visited our hospital on november 17 , 2014 . she complained of repeated skin eruptions with sting and tenderness in both lower limbs for 4 months . red skin eruptions did not fade under pressure , first having the appearance of tip , then gradually expanding and deeply bursting and finally coalescing and leaving the shrinkage and pigmentation , with high skin temperature ( figure 1a and c ) . no abnormality was found by cardiopulmonary physical examination , and the electrocardiogram and chest x - ray were normal . laboratory analyses revealed elevated levels of erythrocyte sedimentation rate ( esr , 24 mm / h ) , carbohydrate antigen 125 ( ca125 , 48.75 u / ml ) , and ca724 ( 19.97 u / ml ) , normal levels of c - reactive protein ( crp ) , homocysteine , alanine aminotransferase ( alt ) and creatinine , and negative antinuclear antibody , antineutrophil cytoplasm antibody , rheumatoid factor , tuberculosis antibody , autoantibody , and anticardiolipin antibody . skin biopsy revealed neutrophils , lymphocytes , or plasmacytes in a few small vessel walls ( figure 2a ) . meanwhile , not only no thrombus was seen in the vessel lumen , but no fibrinoid necrosis was noted in the vessel wall as well ( figure 2b ) . she used the glucocorticoid , immunosuppressant , and other externally used drugs , and skin eruptions appeared repeatedly . after being admitted to our hospital , glucocorticoid was gradually decreased and then finally ceased , immunosuppressant was ceased , and rivaroxaban 10 mg / d was regularly taken once a day . skin eruptions disappeared after 3 months and had not recurred after 23 months ( figure 1b and d ) . female patient , 30 years old , visited our hospital on july 9 , 2015 . red skin eruptions first had the appearance of tip and then gradually expanded . for these skin eruptions , it was easy to burst but difficult to coalesce . scarring and pigmentation were formed due to the repeated appearance of skin eruptions ( figure 3a and c ) . she had medical history of chickenpox appearing at the same time of skin eruptions , 4 years ago . laboratory analyses showed normal levels of blood platelet count , esr , crp , alt , and creatinine and negative autoantibody and tuberculosis antibody . the patient used prednisone acetate , thalidomide , colchicine , and hydroxychloroquine . due to the lack of treatment effect , prednisone acetate was ceased , and other drugs were not regularly used . after being admitted to our hospital , rivaroxaban was taken for 6 months , and skin eruptions had not recurred after 18 months ( figure 3b and d ) . female patient , 39 years old , visited our hospital on october 9 , 2013 . skin eruptions were dark red with sting , tenderness , and high skin temperature ( figure 4a ) . swelling and pain were not seen , and movement was not restricted in lower limbs and all joints . laboratory analyses showed elevated levels of white blood cell count ( 11.8810/l ) , blood platelet count ( 35310/l ) , esr ( 32 mm / h ) , crp ( 0.4 mg / dl ) , ca125 ( 65.24 u / ml ) , and ca724 ( 13.13 u / ml ) and normal levels of hemoglobin , alt , creatinine , immunoglobulin , and complement . there were eosinophils in the superficial layer of dermis , inflammatory cells in vessel walls , and fibrinoid necrosis in a few vessel walls ( figure 5 ) . she used methylprednisolone , levofloxacin , and indomethacin , and skin eruptions recurred after ceasing methylprednisolone . immunosuppressant , immunoglobulin , ii recombinant human receptor antibody fusion protein of tumor necrosis factor ( rhrptn ) , and adalimumab were also added to treat the skin eruptions . however , due to the recurrence of tuberculosis , methylprednisolone and immunosuppressant were ceased , and rivaroxaban was regularly taken for 3 months . the pathogenesis of lv is cutaneous ischemia and infarction caused by the occlusion of capillary microcirculation.6 although there are lv - like changes in autoimmune and neoplastic diseases , they develop as secondary lesions.7,8 perivascular inflammatory infiltration is secondary to the inflammation in an advanced stage and less prominent compared with coagulation function.9 lv is almost exclusively located on both lower limbs , particularly the surrounding region of ankle and dorsal aspect of feet . characteristic appearances of lv include one or more of triad livedo racemosa , ulceration , and atrophie blanche . disturbed perfusion of cutaneous microcirculation leads to livedo racemosa , and the latter appears in a precursor stage to ulceration . the localized sensation of pain rather than fatigue appears in this stage and is of great importance as an early warning of continuously cutaneous ischemia and infarction with ulceration and scarring . due to an inadequate blood supply to the cutaneous layers , ulceration develops as the result of cutaneous ischemia in the acute stage of lv.3 atrophie blanche is an irreversible scarring representing the remnants of cutaneous infarction at the end of the restructuring process and accompanying postinflammatory pigmentation the main goals in the treatment of patients with lv are to avoid the repeated occurrence of active cutaneous lesions and prevent the progressive ulceration . effective treatment of lv is difficult , and limited options of drugs are available . in light of the coagulation disease , systemic anticoagulation drugs , such as low - molecular - weight heparin ( lmwh ) and warfarin , have been reported as treatment options.10 as has been the experience of european doctors , the treatment effect can be satisfactorily achieved for most patients with the application of lmwh.11,12 based on previous literature , warfarin is also deemed as an option with the regular monitoring of international normalized ratio.13 however , lv is a chronic disease , and patients with lv complain about daily injections of lmwh and repeated monitoring of international normalized ratio . meanwhile , the application of a fibrinolytic drug has strict indications due to severe risk of massive hemorrhages.14 although experimental observation has also reported the benefit of immunoglobulin in patients with lv , it inevitably results in economic burden on patients with lv.15 recent data have suggested that rivaroxaban , an oral direct inhibitor of factor xa inhibitor , has the potential to alleviate the intractable pain and cutaneous ischemia and prevent the occurrence of ulceration and scarring in patients with lv.16 as the first multicenter study , riliva trial has been published by weishaupt et al5 and has suggested that rivaroxaban is a suitable treatment option for patients with lv . as an injection - free alternative to lmwh and monitoring - free alternative to warfarin , rivaroxaban improves the quality of life and enhances the compliance of patients.17 all patients consider rivaroxaban as more tolerable than previous drugs and , therefore , they continue the application of rivaroxaban , effectively improving the treatment effect of the drug and successfully avoiding the repeated occurrence of active cutaneous lesions . the current report presented three chinese cases with lv receiving rivaroxaban treatment and confirmed the treatment benefit of rivaroxaban in patients with lv during the follow - up . treatment application of rivaroxaban in chinese patients with lv successfully avoids the recurrence of active cutaneous lesions and prevents the progressive ulceration and scarring .

livedoid vasculopathy ( lv ) is a chronic prothrombotic disease of cutaneous micro - circulation resulting in cutaneous ischemia and infarction . as a rare disease , lv has an estimated incidence of ten cases per million . not only correct diagnosis but also effective treatments are very difficult for patients with lv . due to the lack of large - scale studies in this rare disease , lv poses a great challenge to the doctors , and existing treatment has always been an individual attempt with off - label application . the main goals in the treatment of patients with lv are to avoid the repeated occurrence of active cutaneous lesions and prevent painful ulceration and irreversible scarring . the current report describes the cases of three chinese patients with lv receiving rivaroxaban treatment , an oral direct inhibitor of factor xa inhibitor , and observes the treatment effect of rivaroxaban during the follow - up . as an injection - free alternative to low - molecular - weight heparin ( lmwp ) and monitoring - free alternative to warfarin , rivaroxaban improves the quality of life and enhances the compliance of patients . all patients consider rivaroxaban as more tolerable than previous drugs and , therefore , continue the application of rivaroxaban , effectively improving the treatment effect of drugs and successfully avoiding the repeated occurrence of active cutaneous lesions . treatment application of rivaroxaban in chinese patients with lv successfully avoids the recurrence of active cutaneous lesions and prevents the progressive ulceration and scarring .

the gluteus maximus ( gm ) plays a major role in functional activity as a trunk and hip extensor . weakness of the gm could cause dysfunction in the pelvic and hip joints and back pain1 . prone hip extension ( phe ) is an exercise that can activate the gm effectively and is popularly used in clinics2 . however , unwanted substitution motion , such as pelvic anterior tilt or excessive lumbar extension , could happen during phe due to stiffness of the hip flexor , dominance of the erector spinae ( es ) , weakness of the gm , and so forth3 . therefore , recent studies have focused on controlling unwanted substitution motion of the pelvis and lower back during phe4,5,6 . many previous studies about phe have been performed at the 0 hip flexed position8,9,10 . some other studies have used starting positions varying from 20 to 90 hip flexion for people with hip flexor contracture6 , 7 , 11 . . however , little information exists concerning whether hip joint angles during phe selectively change the emg activity of the gm . therefore , the purpose of this study was to examine the effects of initial hip joint position on the muscle activity of the es , gm , and biceps femoris ( bf ) as measured by electromyography ( emg ) of the hip extensor as well as the effect of the angle of pelvic anterior tilt . through this process , we sought the most effective position for selective gm muscle activation during phe . fifteen healthy adults were enrolled in this study ( age , 26.73.7 years [ meansd ] ; height , 167.19.2 cm ; mass , 58.111.7 kg ) . exclusion criteria were neuromuscular or musculoskeletal dysfunction of the lower back and both legs , lower back or hip pain , contracture of the hip flexor , or a hip extensor strength below fair . all subjects agreed to participate and signed an informed consent form approved by the inje university ethics committee for human investigations . prior to testing , kinematic data of the pelvis were recorded at 100 hz using an eight - camera vicon mx - t20 motion capture system ( vicon motion systems ltd . , the respective muscle activities of the bilateral es , unilateral gm , and biceps femoris bf were collected using a delsys trigno wireless emg system ( delsys inc . , natick , ma , usa ) , which was synchronized with a vicon motion system . the emg signals were sampled at 2,000 hz and filtered at 20 to 450 hz , and the root mean square values of the signals were calculated . the emg data were expressed as a percentage relative to the maximal voluntary contraction for normalization . a newly developed two - segment model consisting of the lumbar spine and pelvis was used to measure the angle of pelvic anterior tilt . the lumbar segment was defined with four markers located on the subject s l1 and l2 spinous processes , and 1 cm lateral from the l2 spinous process on both sides . the pelvic segment was defined with three markers located on the mid - point of the posterior superior iliac spine and the bilateral anterior and superior iliac spines . the subjects lifted their right legs during phe at three starting positions arranged in random order ( 0 , 20 , and 45 hip flexed position ) . with phe at 0 hip flexion , each subject was positioned prone on a table consisting of 2 segments that were jointed in a way that it was possible to adjust the table s position so the subject s hip could be positioned at an initial hip flexion of 20 or 45. a bar placed over the table would come in contact with the achilles tendon when the subject s hip was extended to 30 from the initial position . emg activities and pelvic kinematics were measured when subjects extended from their initial position . all subjects performed 3 repetitions with a 10-second rest between trials and rested for 2 minutes between each testing position . pasw statistics for window ( ver . 18.0 ; spss inc . , chicago , il , usa ) was used to analyze differences in muscle activities and pelvic kinematics . repeated measures anova and bonferroni - adjusted post hoc comparisons were used to compare the respective muscle activities of the es , gm , and bf and the amount of pelvic anterior tilt among the three initial positions . there were significant differences in es , gm and bf muscle activity on the left side among the three positions during phe . muscle activity for the es on the right side did not show any difference in emg among the three positions . the amount of pelvic anterior tilt showed a significant decrease at the 20 hip flexion position compared with that at the 0 angle ( table 1table 1.normalized emg data and amount of pelvic anterior tilt ( n=15)variableship joint position ( meansd)02045lt . es ( % mvic)49.515.344.112.431.713.2rt . bf ( % mvic)36.59.433.39.638.711.1pelvic anterior tilt ( )7.42.05.92.47.32.8bf : biceps femoris ; es : erector spinae ; gm : gluteus maximus ; lt . bf : biceps femoris ; es : erector spinae ; gm : gluteus maximus ; lt . : left ; mvic : muscle voluntary isometric contraction ; rt . : of the three positions , active phe at 45 resulted in a significant decrease in muscle activity of the contralateral es compared with the other positions . the role of the es as a global stabilizer was reduced at 45 because alteration of this position from the initial position to 30 hip extension induced pelvic anterior tilt . therefore , we consider that the 45 flexed position would be able to effectively prevent excessive lumbar motion and maintain an upright pelvis alignment we think that the 45 hip flexed position decreased internal momentum due to the short lever arm in comparison with other positions12 . although the muscle activity of the contralateral es tended to decrease at 20 , this decrease was not significant . this investigation revealed that the 20 hip flexed position needs an additional 10 hip extension for a total of 30 extension during phe , which may result in contraction of the es . however , this position increased gm activity compared with the other positions and decreased bf activity compared with that occurring with the 45 hip flexion angle . additionally , the amount of pelvic anterior tilt at 20 was lower than those at 0 and 45. we consider that the pelvic anterior tilt provided by 20 hip flexion led to the optimal length by elongation of the gm , which may contribute to increases in gm activity12 . worrell et al.7 demonstrated that gm activity was greatest at the 0 angle and that hs muscle activity did not differ among all the positions they studied , which was not in line with the results of our study . they examined gm and bf activity with changes in hip and knee joint angles during maximal voluntary isometric contraction , whereas we investigated muscle activities with initial positions to 30 extensions of the hip joint during active phe with knee extension . chance - larsen et al.9 reported that restraint of pelvic anterior tilting during phe decreased the length of the bf and influenced the synergistic relationship between the gm and bf . of three positions , 0 could negatively impact the lumbar segment by increasing the es activity and 45 did not activate the gm in spite of the reduction of es activity . hence , the 45 position could be recommended for persons who need to minimize the weight - bearing load on the lumbar spine . in conclusion , we suggest that 20 is the optimal position to activate the gm selectively by minimizing additional pelvic anterior tilt . first , our sample size was small , so it is difficult to generalize the findings to all subjects . second , we examined the changes in emg - measured muscle activity at only three joint angles ; it is possible that the results do not indicate the optimal position for phe . therefore , further studies are needed to investigate the changes at the various phe joint angles .

[ purpose ] the aim of this study was to identify the effects of initial position of the hip joint with changes in the hip joint angle on the respective muscle activities of the bilateral erector spinae ( es ) , unilateral gluteus maximus ( gm ) , and biceps femoris ( bf ) and the amount of pelvic anterior tilt during prone hip extension ( phe ) . [ subjects ] fifteen healthy volunteers were enrolled in this study . [ methods ] the subjects performed phe in three positions : neutral , 20 , and 45 flexed hip joint . the activities of the es , gm , and bf were measured using surface electromyography , and kinematic values for pelvic anterior tilt were calculated using a motion capture system . [ results ] there was a significant decrease in muscle activity of the contralateral es at 45 , and an increase in the gm muscle activity and decrease in the bf muscle activity at 20. the amount of pelvic anterior tilt was lower at 20. [ conclusion ] these results suggest that a hip flexion position of 20 would have an advantage over the other measured positions .

celiac artery stenosis is a relatively common condition with an incidence estimated to be between 10 and 25% of the adult population . however , many patients remain asymptomatic until the arterial blood flow is reduced by 6070% , due to the development of extensive collateral pathways . during pancreaticoduodenectomy , the gastroduodenal artery and its collaterals are ligated , and if not managed properly , catastrophic complications , such as hepatic and/or anastomotic ischemia , may result . in this study , we present an elderly patient with pancreatic adenocarcinoma and severe atherosclerosis who successfully underwent pancreaticoduodenectomy with bypass grafting between the supraceliac aorta and the common hepatic artery . his medical history was significant for lung cancer , bladder cancer , coronary artery disease and history of femoral popliteal bypass surgery for severe peripheral vascular disease . on initial presentation , the patient was afebrile , normotensive and in sinus rhythm . the biochemical studies were significant for a total bilirubin of 5.3 mg / dl , a direct bilirubin of 4.5 mg / dl and an alkaline phosphatase of 561 abdominal ultrasound showed a 17-mm common bile duct ( cbd ) dilatation and moderate intrahepatic ductal dilatation . magnetic resonance imaging showed a high - grade stricture of the distal cbd , resulting in markedly dilated intrahepatic bile ducts , with 2.6 cm by 1.9 cm soft - tissue fullness at the level of the pancreatic head ( fig . abdominal angiography showed moderate narrowing at the origin of the celiac artery ; however , the distal celiac , superior mesenteric and inferior mesenteric arteries were patent ( fig . computed tomography showed no recurrent disease of lung and bladder cancer and no significantly abnormal uptake within the pancreatic lesion . endoscopic retrograde cholangiopancreatography was performed with sphincterotomy , cbd dilatation and concurrent placement of a 7-cm , 10-fr stent . figure 1:(a ) mri of the abdomen demonstrated marked intrahepatic biliary dilatation due to an abrupt high - grade stricture of the distal cbd at the level of the pancreatic head . ( b ) ct angiography of the abdomen showed patent celiac artery despite moderate narrowing at the origin of the celiac artery . ( a ) mri of the abdomen demonstrated marked intrahepatic biliary dilatation due to an abrupt high - grade stricture of the distal cbd at the level of the pancreatic head . ( b ) ct angiography of the abdomen showed patent celiac artery despite moderate narrowing at the origin of the celiac artery . with no evidence for systemic disease , pancreaticoduodenectomy was recommended . the mobilization , dissection and division of the jejunum , stomach and pancreas were performed in the standard fashion . manual compression of the gastroduodenal artery did not show any evidence of loss of blood flow to the common hepatic artery . after the neck of the pancreas was divided , the tumor appeared to be adherent to the right lateral wall of the portal vein . thus , the portal vein was dissected above and below the area of the tumor , and the sidewall of the portal vein was excised and repaired . after the completion of pancreaticojejunostomy , the hepatic artery was found to be soft and nonpulsatile , with significantly diminished blood flow on doppler ultrasound . however , there was no evidence of arterial injury and no evidence of gross visceral ischemia . at this time after completion of the anastomoses , the hepatic artery continued to be nonpulsatile . therefore , a bypass from the supraceliac aorta to the common hepatic artery was created to prevent potential postoperative complications , including anastomotic ischemia and breakdown . the supraceliac aorta was dissected . after the patient was given intravenous heparin , a 6-mm gore - tex graft was anastomosed to the aorta and to the hepatic artery in an end - to - side fashion . surgical pathology showed stage iib poorly differentiated pancreatic adenocarcinoma with extensive perineural invasion , focal lymphovascular invasion and metastatic carcinoma in 1 of 30 lymph nodes . the patient had an uneventful postoperative course and was discharged 7 days after the operation . up to 5% of patients undergoing pancreaticoduodenectomy are estimated to have celiac artery stenosis . in these patients , extensive collaterals develop from the superior mesenteric artery to provide retrograde flow from the gastroduodenal artery to the liver . although the vast majority of these patients are asymptomatic , the collaterals and gastroduodenal artery are transected during pancreaticoduodenectomy and may cause hepatic and/or anastomotic ischemia , unless intervention is undertaken in a timely fashion [ 2 , 3 ] . classically , the gastroduodenal artery occlusion test has been performed to assess for adequate blood flow , as this artery represents the communication between the celiac axis and the superior mesenteric artery . if visceral ischemia becomes evident upon occlusion of the gastroduodenal artery , a revascularization procedure is necessary . unfortunately , there are times when this test is negative and visceral ischemia is seen only after the pancreatic resection , due to the interruption of collateral flow from pancreaticoduodenal blood supply . machado et al . proposed an additional maneuver of occluding pancreatic flow at the pancreatic neck after the portal vein dissection . this maneuver interrupts collateral vessels between the pancreatic body and the splenic arterial system and may increase the sensitivity of the gastroduodenal artery occlusion test . the first case of successful pancreaticoduodencetomy in the setting of celiac occlusive disease was reported in 1980 , using a splenic - to - superior mesenteric artery reimplantation technique . these authors also noted that the gastroduodenal artery occlusion test is not always a reliable test and recommended preoperative arteriographic evaluation . since pancreaticoduodenectomy is the only potentially curative option for pancreatic cancer , patients with significant mesenteric arterial disease and pancreatic cancer others have reported creation of an anastomosis between the superior posterior pancreaticoduodenal artery and the posterior inferior pancreaticoduodenal artery , anastomosis between the middle colic artery and the gastroduodenal artery , and transposition of the celiac artery onto the superior mesenteric artery [ 68 ] . in our case , bypass grafting between the supraceliac aorta and the hepatic artery proved to be a successful option for our patient .

patients with celiac artery stenosis often remain asymptomatic due to formation of extensive collateral pathways . hepatic or anastomotic ischemia may occur when the gastroduodenal artery and these collaterals are ligated during pancreaticoduodenectomy . here , we present a patient with severe atherosclerotic disease of the celiac axis who successfully underwent pancreaticoduodenectomy with aorto - hepatic bypass .

osteopetrosis ( op ) has also called with its historical names as a albers - schnberg disease , which was firstly described by a german radiologist [ 1 , 2 ] . the main cause of the disease is osteoclastic activity defect , which results hypersclerotic fragile bone [ 3 , 4 ] . autosomal recessive op ( aro ) has a two subtype , which are infantile malignant op and intermediate type . infantile malignant aro has diagnosed within the first year of the life that has fatal clinical progression due to the bone marrow deficiency and infection . important neurological symptoms are cranial verve palsies due to the obliteration of cranial nerve foramina such as vision loss , deafness , and facial paralysis . the most common neurological finding is visual loss due to the optic nerve compression within the optic channel . in contrast to the aro , autosomal dominant op ( ado ) is described as adult benign type due to the normal life expectancy [ 2 , 3 , 7 ] . ado diagnosis is given easily by recurrent bone fracture history , osteomyelitis , radiologic and laboratory findings , and genetic examination . the typical signs are bone within the bone on the end bones , sclerotic appearances on the long bone and multiple previous fracture lines . other radiological findings are hypoplastic maxillary sinus , teeth deformity and multiple carious . the genetic mutation in the chloride channel 7 ( clcn7 ) gene has been shown . clcn7 gene mutations are heterogeneous , but the result is osteoclastic activity failure [ 4 , 6 ] . she was evaluated with magnetic resonance imaging ( mri ) , which showed chiari i malformation with a 7 mm descent of cerebellar tonsils ( fig . 1 a and b ) . computed tomography demonstrated diffuse calvarial thickening and loss of the medullary space ( fig . 2 ) . her past medical history was consistent with left eye surgery due to amblyopia when she was a child and she was blind in her left eye . radioactive i treatment had been given due to the graves disease and hyperthyroidism ; therefore , she was hypothyroidic and was using levothyroxine daily . her physical examination revealed prominent occipital area and midfacial hypoplasia . increased cortical thickness in her long bones c ) . there were no abnormal findings on neurological examination except of left eye amorozis . large enough posterior fossa craniectomy with c1 laminectomy was performed with ssep and mep monitoring . she developed superficial wound infection , which was treated with simple washout and antibiotics . figure 1:(a ) sagittal t2-weighted image showing cerebellar tonsillar herniation and diffuse thickening of the occipital bone . ( b ) axial t1-weighted image showing compression on the upper cervical spinal cord ( green arrow ) and cerebellar tonsillar herniation ( red arrow ) . figure 2:axial ct image ( bone window ) showing diffuse calvarial thickening and loss of the medullary space . figure 3:patients ' picture showing midfacial hypoplasia on the face ( a ) , x - ray graphy of the right femur ( b ) and x - ray of left femur ( c ) showing diffuse cortical thickening . ( a ) sagittal t2-weighted image showing cerebellar tonsillar herniation and diffuse thickening of the occipital bone . ( b ) axial t1-weighted image showing compression on the upper cervical spinal cord ( green arrow ) and cerebellar tonsillar herniation ( red arrow ) . axial ct image ( bone window ) showing diffuse calvarial thickening and loss of the medullary space . patients ' picture showing midfacial hypoplasia on the face ( a ) , x - ray graphy of the right femur ( b ) and x - ray of left femur ( c ) showing diffuse cortical thickening . op is a rare and hereditary skeletal disease , which resulting from destructive or absence of osteoclastic activity . over this case is the second ado case associated with chiari type i , which presented with hindbrain headache and numbness on the upper extremity without other cranial nerve compression sign . mri revealed brain stem compression , tonsillar herniation , occipital bone thickening and shallow posterior fossa . the first diagnosis was chiari type i , but detailed history , endocrinologic and radiologic work - up yielded as an ado , which was a final diagnosis . reported that untreated aro patients died by the age of 4 years because of the pancytopenia and recurrent infection , which had a 75% rate . there are two type describe , which have different clinical , biochemical and histological manifestation . type i has osteosclerosis on the cranial vault , while type ii has end - plate thickening of vertebral body ( rugger jersey spine ) and end bones in the pelvis . both the types are strictly family related and seen in late childhood [ 3 , 10 ] . the fracture frequency is increased in type ii and normal type i [ 1 , 2 , 4 , 8 , 10 ] . de oliveira et al . reported that there is no need to perform genetic study to confirm the disease . tohidi and bagherpour suggest that ado is rare condition , which can be asymptomatic . therefore , accurate diagnosis can be achieved with the proper clinical , endocrinologic and radiologic investigation . calcium , phosphorus and alkaline phosphatase levels are usually within the normal limits in the benign op [ 7 , 10 ] . dlouhy and menezes proposed in their report that even if their report is the first case ado with chiari , further study is needed . in their report , the cause of the chiari malformation in the op explained as unclear . moreover , the absence of the osteoclastic activity leads to underdeveloped occipital bone , and this results in a smaller posterior fossa . in conclusion , however , patients can present with only chiari symptoms without other cranial nerves compression symptoms ; therefore , ado can be overlooked for differential diagnosis . symptomatic chiari malformation needs surgical intervention , but it should be kept in mind that the patients with chiari malformation should investigate differential diagnosis for ado . whole skeletal survey must be done , whether there are sclerotic chances , thickening skull base , bone within the bone appearance , rugger jersey spine , erlenmeyer flask deformity on the long bone and fracture line on the bone .

osteopetrosis ( op ) is hereditary x - linked , autosomal recessive ( aro ) , or autosomal dominant ( ado ) skeletal disease . aro has two subtypes , which are infantile malignant and intermediate type . aro and x - linked op have poor clinical outcome . ado is called adult benign type because of the normal life expectancy , which has type i and type ii . here , the authors present an ado patient with chiari type i. concomitant ado with chiari type i malformation is an extremely rare condition . literature research yielded only one case report to date .

cysteines may be reduced ( free , where sulfur occurs in the reactive sulfhydryl form ) or oxidized ; the latter may be involved in a disulfide bond , i.e. a half - cystine , or instead covalently bound to a metallic ligand that is part of a prosthetic group . experimental determination of cysteine species ( free , half - cystine , ligand - bound ) is non - trivial , and often only the knowledge of the three - dimensional structure indicates the species . for this reason , cysteine classification is an important bioinformatics problem that may be approached by using machine learning methods . in this paper , we apply support vector machines ( svm ) to the ternary cysteine classification problem , to determine whether a given cysteine is free , a half - cystine or ligand - bound . to the best of our knowledge it is reasonable to assume that each species of cysteine resides in a distinct micro - environment which influences the cysteine redox potential and its steric accessibility . this hypothesis is confirmed and exploited in several machine learning approaches for cysteine classification that , while different , share the common feature that the discrimination is based on the analysis of the cysteine sequence context , using a symmetric sequence window of length w centered about each cysteine . particular effort has been spent on the binary classification problem to discriminate intra - chain half - cystines from free cysteines , the latter being the most represented species . for this problem , nevertheless , other species of cysteines exist namely ligand - bound cysteines and half - cystines involved in inter - chain disulfide bonds . such cysteines reside in possibly different micro - environments , hence may be discernable from other species . only one attempt has been made to discriminate ligand - bound cysteines ; specifically , passerini and frasconi ( 3 ) obtained prediction accuracy of 90% for the binary classification problem of distinguishing ligand - bound cysteines from half - cystines . dianna 1.1 is the only software which performs ternary cysteine classification ; all other cysteine classification web servers consider only the binary classification problem of discriminating free cysteines from intra - chain half - cystines . in this paper , we apply a svm with ( a variant of ) the spectrum kernel ( 4 ) to classify cysteines into three different species : free , half - cystine or ligand - bound . for predicted ligand - bound cysteines , we further refine the classification by predicting the bound ligand to be iron , zinc , cadmium or carbon . although we have some results concerning inter - chain disulfide bonds ( data not shown ) , the dianna web server is intended only for use with single - chain proteins . to test and train a ternary svm predictor for cysteine classification , it was necessary to build a dataset , in which each cysteine species is well represented . this was done as follows . from the protein data bank ( 5 ) , we extracted the set of single - chain proteins containing ligand - bound cysteines , and produced a non - redundant collection by using the program uniqueprot ( 6 ) with hssp distance set to 0 . this produced a list of 202 chains , denoted by up . to enrich the small number ( 60 ) of half - cystines examples ( which is probably not representative ) , we considered the 967 non - redundant protein chains used in ( 1 ) for training and testing a neural network to predict cysteine oxidation state prediction ( dataset ma ) . we merged the up and ma datasets , and re - applied uniqueprot to eliminate redundancy between the two lists . from each redundancy cluster , we selected one member containing ligand - bound cysteines , if available ( if not , we selected the representative member proposed by uniqueprot ) . in this fashion , we obtained a dataset ( denoted upma ) of 526 chains , with adequate representation of each of the three cysteine classes . table 1 displays the number of cysteines in each species , and table 2 presents the number of chains containing each species . from each protein in upma , we extracted symmetric windows of size w centered around each cysteine . different values of w were tested , and the best results were obtained for w = 17 [ the same value led to the best performance in ( 3 ) ] . svms were introduced by vapnik within the context of a mathematically rigorous statistical learning theory for a very clear exposition of this topic see ( 7 ) . often demonstrating better prediction accuracy than neural networks , svms have become increasingly popular in bioinformatics , with applications ranging from translation initiation site determination ( 8) , remote homology detection in proteins ( 9 ) , viral protease cleavage site prediction ( 10 ) , fast computation of z - scores for minimum free energy of rna ( 11 ) and so on . to apply svms to the ternary cysteine classification problem , we use the spectrum representation ( 4 ) which describes an amino acid sequence by specifying the vector of k - mers which occur ; i.e. for peptide p , define k(p ) = a(x):a ak , where a(x ) is the number of occurrences of the k - mer a in p , and a is the set of 1-letter codes of amino acids . more rigorously speaking , these authors actually apply classical kernels [ e.g. the linear kernel in ( 4,13 ) ] for new representations of amino acid sequences the spectrum representation , mismatch representation , profile - based spectrum representation . in this paper , we obtained the best results when k = 3 , so that the amino acid sequence p in each size w window is encoded by the vector 3(p ) of 8000 coordinates , giving the number of occurrences of each 3-mer in p. with the spectrum representation , we used the software libsvm ( 12 ) with a degree 2 polynomial kernel , such that the cost parameter c = 1for explanation of these parameters see ( 12 ) . to train and test the svms we used 5-fold cross - validation , splitting positive and negative datasets into five random subsets of approximatively the same size . using libsvm , the svm multiclass classifier outputs , for each cysteine in the input sequence , the probability of being a free cysteine ( fc ) , a half - cystine ( hc ) and ligand - bound ( lc ) . to measure the performance of the algorithm we used the q3 score , which is the ratio between correctly predicted examples and the total number of examples . the q3 score is commonly used for the performance evaluation of three states ( sheet , helix , coil ) secondary structure predictors e.g . see ( 15 ) . additionally , we computed the qp score , which is the fraction of proteins for which all cysteines are correctly classified . the results ( table 3 ) show that the highest q3 and qp scores are obtained using for the spectrum representation with a degree 2 polynomial kernel ( scores of 0.78 and 0.53 , respectively ) . although the papers ( 13 ) and ( 14,16 ) report that the mismatch and profile - based kernels outperform the spectrum kernel in protein classification experiments , we found that this is not the case for cysteine oxidation state prediction . additional data describing the results of binary classification experiments can be found in the web supplement at the dianna web site . table 4 displays the number of examples in dataset upma for each distinct ligand type in ligand - bound cysteines . for the cases for which we have at least 39 examples ( i.e. zn , fe , cd , c ) we investigated whether machine learning can be used to discriminate the atomic species bound experiments were performed where the positive set consisted of amino acid sequences symmetrically flanking those cysteines bound to a specific ligand ( say iron ) , while the negative set consisted of sequences flanking cysteines bound to a different ligand . in the case of cadmium ( cd ) and carbon ( c ) , we randomly resampled the positive training set ( which is substantially smaller than the negative training set ) until the number of positive and negative examples was the same ( note that the test set is unchanged ) . as in ternary cysteine classification , we found that the best discrimination was obtained in using the degree 2 polynomial kernel with the spectrum representation . dianna 1.1 has a simple user - friendly web interface , which allows the user to obtain a prediction of the state ( free , half - cystine or ligand - bound ) for each cysteine in an input protein . the ternary svm predictor outputs the highest probability class , and , for those cysteines predicted as ligand - bound , the most likely ligand is displayed ( among iron , zinc , cadmium , carbon ) , by a winner - takes - all decision . additionally , as described previously ( 17,18 ) , dianna 1.1 uses a state - of - the - art method to predict the disulfide connectivity i.e . which cysteines form a disulfide bond with which other cysteines . a screen shot of the dianna 1.1 web server output for a ternary classification prediction is shown in figure 2 . additionally , dianna 1.1 allows all possible binary classification predictions for the three cysteine classes ( free , half - cystine , ligand - bound ) . the upper panel of figure 2 displays the input form , including the pull - down menu , which allows the user to choose the classifier used for cysteine state prediction ( ternary classifier , or one of three binary classifiers ) . the lower panel of figure 2 displays the output of the ternary cysteine state classifier , indicating the probability of each class ( half - cystine , free cysteine , ligand - bound ) . in the case of predicted ligand - bound cysteines , the predicted ligand is listed in the right - most column . the user enters a protein in fasta format , possibly including a fasta comment , and chooses either to predict the cysteine state for each cysteine , or to determine the disulfide connectivity . given the amino acid sequence of a protein , dianna ( 17 ) is a state - of - the - art method to predict disulfide connectivity topology . version 1.0 of the dianna web server , described in ( 18 ) , additionally predicts the oxidation state of each cysteine ( free or half - cystine ) , by using our implementation of the neural network of fariselli et al . ( 19 ) . in version 1.1 of the dianna web server , described in this paper , we replace the binary classifier of ( 19 ) by a svm with degree 2 polynomial kernel for the spectrum representation ( 4 ) . using libsvm , we obtain a ternary classifier , capable of discriminating between free cysteines , half - cystines and ligand - bound cysteines . moreover , for the latter , dianna 1.1 predicts the type of ligand . to the best of our knowledge , this is the first application of string - based kernels to sequence windows ; until this paper , such kernels had been used only for protein classification . [ for an explanation of receiver operating characteristic ( roc ) curves see ( 20 ) ] . upper panel : the dianna web - server update allows the user to choose between disulfide connectivity prediction and cysteine classification ( ternary cysteine classification is only available in the 1.1 update ) . in the latter case , the user can type or paste a fasta sequence in a text box , then choose among four different classification predictions by means of a drop down menu ( i.e. the ternary lc versus hc versus fc classification , and the three binary classifications lc versus hc , lc versus fc and hc versus fc ) . lower panel : output for the ternary classification . for each cysteine in the submitted sequence , the svm model predicts the probability of being half - cystine , free cysteine or ligand - bound . the class having the highest probability is highlighted . if a specific cysteine is predicted as ligand bound , a tentative prediction about the putative ligand ( out of four possible ligands ) is attempted . total number of different cysteine species in datasets considered in this paper the description of each dataset can be found in the section dataset. legend : ia , intra - chain disulfide bonds ; ie , inter - chain disulfide bonds ; hc , half - cystines ; fc , free cysteines ; lc , ligand - bound cysteines . breakdown of protein chains which contain at the same time half - cystines ( hc ) , free cysteines ( fc ) and ligand - bound cysteines ( lc ) , for each of the three datasets considered in this paper performance measure ( q3 and qp scores ) for the three - class prediction of lc , hc , fc using different kernels and input representation the q3 score is the ratio between correct prediction and total number of examples . the qp score is the fraction of proteins for which all cysteines are correctly predicted . q3 and optimal values of the c parameter and the parameter for the radial basis function ( rbf ) kernel are estimated by a grid search . legend : spr spectrum representation ; mmr mismatch representation ; prfr profile representation . total number of distinct atomic ligands found covalently bound to cysteine residues in the upma dataset . performance measures for the prediction of cysteines bound to specific ligands legend : acc accuracy ; sen sensitivity ; spe specificity ; mcc matthew 's correlation coefficient ; auc area under the roc curve .

dianna is a recent state - of - the - art artificial neural network and web server , which determines the cysteine oxidation state and disulfide connectivity of a protein , given only its amino acid sequence . version 1.0 of dianna uses a feed - forward neural network to determine which cysteines are involved in a disulfide bond , and employs a novel architecture neural network to predict which half - cystines are covalently bound to which other half - cystines . in version 1.1 of dianna , described here , we extend functionality by applying a support vector machine with spectrum kernel for the cysteine classification problem to determine whether a cysteine is reduced ( free in sulfhydryl state ) , half - cystine ( involved in a disulfide bond ) or bound to a metallic ligand . in the latter case , dianna predicts the ligand among iron , zinc , cadmium and carbon . available at : .

it is now being replaced by low - molecular weight heparin ( lmwh ) because of certain advantages like equal efficacy , increased bioavailability , and less frequent dosing interval . also , monitoring of activated partial thromboplastin time is not required . the major adverse effects of these drugs are bleeding , thrombocytopenia , alopecia , and osteoporosis . a rare adverse effect of heparin reported insufficient and conflicting data are available regarding the effects of lmwh ( enoxaparin ) on serum potassium levels . hence , this study was carried out to compare the effect of heparin and lmwh on serum potassium levels and also sodium . the protocol was approved by the institute human ethics committee and written informed consent was obtained from all the study patients . it was a single blind and parallel study conducted at a tertiary care hospital in kolar from march to december 2010 . sixty patients of either sex in the age group of 4060 years suffering from angina , myocardial infarction , and stroke were included in this study . patients with first and recurrent attacks of angina , myocardial infarction , and cortical venous thrombosis were enrolled . patients with baseline serum potassium < 3.5 and > 5 meq / l and serum sodium levels < 135 and > 145 meq / l were excluded . the serum potassium and sodium levels were estimated at the time of admission ( baseline level ) and on the fifth day after therapy in both the groups . gault formula , and the patients were excluded if crcl was < 30 ml / min . sample size was determined by power analysis with power of 0.95 and was found to be 30 in each group . data are expressed as mean standard deviation ( sd ) for continuous variables and as percentages for categorical variables . predictor variables for hyperkalemia were evaluated using the logistic regression in both univariate and multivariate models , and odds ratio with 95% confidence intervals were computed . for the analysis of potential risk factors for hyperkalemia , continuous variables were dichotomized . known risk factors from the literature were included in a multiple logistic regression model to analyze the independent association of these risk factors with a higher risk of the development of hyperkalemia . variables independently associated with higher risk in multiple logistic regression were defined as major risk factors . sample size was determined by power analysis with power of 0.95 and was found to be 30 in each group . data are expressed as mean standard deviation ( sd ) for continuous variables and as percentages for categorical variables . predictor variables for hyperkalemia were evaluated using the logistic regression in both univariate and multivariate models , and odds ratio with 95% confidence intervals were computed . for the analysis of potential risk factors for hyperkalemia known risk factors from the literature were included in a multiple logistic regression model to analyze the independent association of these risk factors with a higher risk of the development of hyperkalemia . variables independently associated with higher risk in multiple logistic regression were defined as major risk factors . in our study , we had 41 males and 19 females , and they were age matched [ table 1 ] . there were 20 ( 67% ) male and 10 ( 33% ) female patients in heparin group , and lmwh group had 21 ( 70% ) male and 9 ( 30% ) female patients . eleven ( 37% ) and 10 ( 33% ) patients had diabetes in heparin and lmwh groups , respectively . there was no significant difference in serum k and na on fifth day when compared with baseline with heparin p=0.715 and 0.897 and with lmwh p=0.773 and 0.057 , respectively . age distribution and kidney functions of the patients at baseline subcutaneous heparin and lmwh are commonly used in the treatment of angina , myocardial infarction , cortical venous thrombosis , and deep vein thrombosis [ table 2 ] . in this study , males were predominant , and majority of females were diagnosed as cortical venous thrombosis ( 17% ) . neither of the drugs increased serum potassium levels significantly after 5 days of therapy [ table 3 ] . the k exceeded 5 meq / dl in two and four cases , which received heparin and lmwh respectively , and this was statistically significant ( p=0.001 ) . patients who received lmwh had high levels of k at baseline and on fifth day [ table 3 ] , but insignificant . the serum sodium levels were significantly higher with lmwh [ table 3 ] at baseline ( p=0.04 ) and it lowered on fifth day . these findings prove the role of heparin and lmwh in inhibiting the aldosterone physiology thereby leading to increase in serum potassium levels and natriuresis . it can also be observed that patient receiving lmwh have significant alteration of the electrolytes , which indicates relatively more interference with aldosterone , and this effect was related to basal serum potassium ( p=0.001 ) and did not show correlation with age , gender , and diagnosis ( p>0.05 ) . indications for heparin and lmwh serum k and na values in both groups on the basis of univariate analysis , patients who received heparin developed hyperkalemia which was significant . the odds of developing hyperkalemia is eight times more with heparin if the baseline k was > 4.3 the odds ratios ( ors ) and p values are shown in table 4 and 5 . multivariate - adjusted ors in the logistic regression model were 43.10 for baseline potassium in case of heparin ( 95% ci : 1.4045.76 ; p=0.02 ) and 0.06 for crcl for enoxaparin ( 95% ci : 0.061.41 ; p=0.05 ) . there were no significant correlations between increase in potassium levels with age , diabetic status , and blood urea in the two groups . the univariate and multivariate analysis report for k levels on day 5 in both heparin and lmwh group is presented in tables 4 and 5 . univariate analysis of parameters with k levels on day 5 multivariate analysis of parameters with k levels on day 5 heparin - induced hyperkalemia is mediated by a reversible effect on aldosterone through blockage of an enzymatic step in the synthesis and angiotensin ii receptors in adrenal gland . the most important mechanism of heparin - induced hypoaldosteronism involves the reduction in both number and affinity of angiotensin ii receptors in the zona glomerulosa . prolonged administration of heparin has caused marked reduction in the width of adrenal zona glomerulosa thereby leading to hyperkalemia and natriuresis . this reversible suppression of aldosterone occurs within a few days of initiation of therapy and is independent of either the anticoagulant effect or the route of administration . lmwhs have similar effects on aldosterone as unfractionated heparin or there may be a different risk of hyperkalemia which is still unsettled . this could possibly be because of the heterogeneity of the populations studied and the regimens of heparin used . the inhibitory action is specifically on the glomerulosa zone of the adrenal cortex thereby other corticosteroids are spared . our findings confirm the role of renal insufficiency ( measured as crcl ) in development of hyperkalemia . we found a marginally significant correlation between the development of hyperkalemia and basal potassium level , and similar findings have been reported by gonzalez - martin et al . as baseline potassium level reflects pretreatment aldosterone level , its value has a predictive role for susceptibility to develop hyperkalemia . the various risk factors for the development of hyperkalemia according to univariate and multivariate analysis were found to be baseline potassium and crcl ( p0.05 ) . the other risk factor identified was diabetes , which is not seen in this study . our results concur with those of monreal et al . who reported increase in serum potassium > 5 meq / l in 7% receiving heparin and 15% lmwh among 30 patients . the practical implications of these findings are that routine monitoring of serum potassium concentration may be necessary . although aldosterone suppression is reported to occur within a few days of heparin treatment , the time needed to develop hyperkalemia may be extremely variable among patients , depending on their clinical background . this observation underlines the potential risk associated with an unmonitored treatment for a period longer than that used in our study . the short - term treatment with lmwh induces a significant increase in serum potassium level , but the related risk of clinically relevant hyperkalemia remains low . the limitations of the study are that the confidence interval of various parameters in univariate and multivariate analysis is wide ( i.e. , difference between lower and higher value is more ) and it is less than 1 . so a large sample size more than 30 will actually predict the risk of hyperkalemia . serum creatinine is not a risk factor in multivariate analysis because some other factor is masking its effects in predicting hyperkalemia . lmwh - induced aldosterone suppression leading to hyperkalemia and hyponatremia ( natriuresis ) is more than heparin . serum potassium should be monitored periodically in patients on heparin or lmwh for five or more days , especially in high - risk patients for hyperkalemia .

introduction : to study the effects of heparin and low - molecular weight heparin ( lmwh ) on potassium and sodium levels in patients with cardiovascular diseases ( cvds ) and stroke.materials and methods : sixty patients were recruited with 30 patients each receiving heparin and enoxaparin . patients with cvd and stroke receiving heparin and lmwh were compared for their demographic profile and laboratory data , and this was analyzed by descriptive statistics . risk factors associated with the development of hyperkalemia were analyzed using multiple logistic regression model.results:there was an increase in potassium levels and decrease in sodium levels compared with baseline in both the groups . the difference between the groups with respect to sodium and potassium levels was not statistically significant . on analysis , the risk factors for development of hyperkalemia were baseline potassium levels , serum creatinine , and creatinine clearance . the change in sodium and potassium levels on the fifth day of therapy was increased with lmwh compared with heparin , although not statistically significant.conclusions:the clinician should anticipate hyperkalemia especially in patients with renal impairment receiving these drugs .

heart transplantation has revolutionized end - stage heart failure therapy and is presently regarded as the gold standard of treatment . looking back on its history , it is now over 45 years ago , on december 3 , 1967 , that the world was riveted by news of the first transplantation of a human heart , performed in cape town , south africa , by the late dr . we have progressed considerably since that time and great advances have been made even in the field of pediatric heart transplantation since the first unsuccessful effort in a 17-day - old child suffering from a severe form of ebstein s anomaly by dr . adrian kantrowitz in brooklyn , new york , also in december 1967 , which was the first human heart transplant in the usa . in germany , heart transplantation was first performed in munich in 1969 and was resumed there in 1981 by its two centers , followed by hannover in 1983 as performed by our group . after carrying out 72 heart transplants within 2 years ( several of these patients survived for more than 20 years and one for more than 28 years ) our group moved to berlin where we embarked upon a very active heart transplant program at the deutsches herzzentrum berlin in april 1986 , performing a total of 1762 heart transplantations ( 181 pediatric heart transplants ) , including 51 re - transplantations and 101 combined heart and lung transplantations , by september 2012 . it was in 1980 that cyclosporin a after heart transplantation was first used in a clinical trial in stanford group with high dose of cyclosporin a and steroids . in 1984 the group in paris used quadruple therapy with antithymocyte globulin and steroids , delayed cyclosporin a and early cessation of azathioprine . our group in 1984 started the quadruple therapy with antithymocyte globulin and cyclosporin a , azathioprine and steroids . presently , our immunosuppression protocol consists of an induction therapy designed to reduce the incidence of early rejection and is started 6 hours post - heart transplantation with intravenous anti - thymocyte globulin 1.5 mg / kg on the first 3 days accompanying intravenous prednisolone at 2.5 - 5 mg / kg / day . cyclosporin is started immediately preoperatively at 6 mg / kg orally and is continued at 2 mg / kg intravenously or 6 mg / kg orally to target a trough level of 250 ng / ml . mycophenolate mofetil ( mmf ) is started preoperatively at 1000 mg orally and is continued at 1000 mg twice daily either orally or intravenously . this triple therapy with cyclosporin / mmf / steroids is alternatively applied with everolimus ( 2x0.75 mg orally daily , target trough levels 3 - 8 ng / ml ) instead of mmf if there are no contraindications to everolimus . the original biatrial anastomosis technique has been abandoned by many groups in favor of bicaval anastomoses because of seemingly less tricuspid incompetence . however , if the biatrial anastomosis technique is performed exactly as demonstrated by the stanford group in the 1970s , there is almost no tricuspid incompetence either . the heterotropic heart transplantation technique has been generally abandoned because of less favorable results , although quite a number of patients live long term with the additional grafts . monitoring of graft rejection we employ mostly non - invasive techniques of rejection monitoring , in particular the intramyocardial electrogram ( imeg ) and echocardiograph . the remote monitoring imeg system which has been developed by our group since 1986 [ 3 , 4 ] and has become the major diagnostic tool in our facility , has an implanted telemetric pacemaker that allows daily long - distance surveillance of the electrocardiogram and records changes consistent with both cellular and humoral rejection in a highly reliable manner . rejection is assumed when a drop of > 10% of the mean qrs amplitude paralleled by an increase of heart rate in both leads on 3 consecutive days occurs . anti - rejection therapy is immediately initiated when tissue doppler echocardiography in a pulsed - wave mode reveals impairment of early diastolic left ventricular wall relaxation concomitant with qrs amplitude loss . a new doppler imaging technology is echocardiographic strain and strain rate imaging which enables more reliable and comprehensive assessment of myocardial function with its ability to differentiate between active and passive movement of myocardial segments , quantify intraventricular dyssynchrony and evaluate longitudinal myocardial shortening . its high sensitivity in the assessment of myocardial viability is helpful in detecting acute allograft rejection and early occurrence of transplant coronary artery disease after heart transplantation . histologic studies from right ventricular biopsy specimens are performed for detection of leukocyte infiltrations , endocardial demarcation and myocyte damage and depiction of small vessels . immunohistology is performed to generate and analyze leukocyte subsets in cellular rejection and is a prerequisite for the detection of humoral rejection with analysis of complement fractions and endothelial markers . endomyocardial biopsy is , however , infrequently used in pediatric transplant patients , since they normally require sedation before the procedure . treatment of graft rejection graft rejection episodes are treated based on the severity . a schema of additional oral steroids for severe acute rejections , patients are admitted to the hospital and are given high - dose steroid treatment with 3 - 5 x 500 mg methylprednisolone daily combined with antibiotics and cytomegalovirus prophylaxis . in those with grade iii rejection or in the presence of adverse effects on hemodynamics , anti - thymocyte globulin infusion 2.5 mg / kg / day given every 4 hours is added . other drugs , such as okt3 , cyclophosphamide , methotrexate and rituximab , or procedures like plasmapheresis , immunoadsorption or radiation are seldom required and are performed exclusively in the transplantation centers . late graft - associated diseases and sequelae of immunosuppression therapy transplant vasculopathy . development of cardiac allograft vasculopathy ( cav ) has become a major concern in the long - term follow - up of transplant patients . vasculopathy is the main cause of cardiac allograft loss and a leading cause of mortality after the first post - transplantation year . it was detected in 57 transplanted hearts in our pediatric series that freedom from cav was 75% at 5 years , 50% at 10 years , and 25% at 15 years . localized or focal stenosis was diagnosed in 48.9% of patients with cav leading to interventional treatments . cav was the main cause for re - transplantation in 10 patients after a median post - transplant time of 12.25 ( 0.3 - 17.45 ) years . it has been well - documented that the early onset of cav is a predictor of rapid development of severe forms of cav , while patients with late onset cav have much delayed course . post - transplant lymphoproliferative disease post - transplant neoplasia , primarily lymphoma and other forms of post - transplant lymphoproliferative disease ( ptld ) , remains a challenging long - term problem for patients undergoing cardiac transplantation . ptld appears to be largely the result of the effectiveness of current agents used for long - term immunosuppression , and the neoplasms typically harbor the epstein barr virus ( ebv ) genome , which is presumed to play a major role in neoplastic transformation . children are potentially at greater risk for developing ptld than adults because of the frequency which with they are seronegative for ebv at the time of transplant . there has been some concern that induction therapy might increase the risk of cytomegalovirus ( cmv ) disease or the development of ptld , driven by the ebv . however , no relationship has been found between the reported rate of cmv disease according to donor / recipient status combinations and the use of induction therapy . post - transplantation , new diseases may occur or there may be worsening of preexisting diseases . in the first post - transplant year , 75% of patients develop hypertension and this increases to up to 95% by 5 years after transplantation . renal insufficiency develops among 35% of patients until 5 years after transplantation , and 10% have a creatinine value of > 2.5 mg / dl . at this time , 2 - 3% require chronic dialysis and some eventually undergo renal transplantation . the renal insufficiency occurring after heart transplantation is dependent on cyclosporin a , arterial hypertension , athereosclerosis and humoral consequences of denervation of the graft . thirty - five percent of patients develop diabetes mellitus 2 - 5 years post - transplantation . this occurs in approximately 4 - 5% of patients on cyclosporin therapy and in 10 - 15% of patients on tacrolimus . eight years post - transplantation , 25% have developed malignant skin tumors and epithelial carcinoma . osteoporosis , hip necrosis and other musculoskeletal diseases as well as neurological tremors , epilepsy and focal neurological seizures may develop . use of mechanical circulatory assist device as a bridge to transplantation . mechanical circulatory support as a bridge to transplantation was successfully introduced by our group in 1987 [ 8 , 9 ] . the ensuing routine use of assist devices to keep patients alive until transplantation paved the way to their clinical use as an established treatment for end - stage heart failure by itself . this has become essential in the face of the increasing donor organ shortage , with many patients receiving permanent assist devices and fewer receiving heart transplants . after the epochal achievement of the stanford group in the early 1980s , the survival rate of transplant patients reached a level almost as good as that of today based on the 2011 ishlt report . during the 25-year period , mean duration of follow - up was 16.080.8 ( range 8 months - 26 years ) . our overall survival rates are 68.3% , 52.8% , and 22.4% at 5 , 10 and 20 years , respectively . in those transplant patients who lived longer than 10 years , 68.12.6% lived more than 16 years and 45.54.7% survived for more than 20 years . in recent years , the results have rather become worse because many patients are transplanted because of complications of assist device support such as device infections or stroke , which by themselves are high risk factors for the transplantation . in addition , patients have to go through a long waiting time under intensive care treatment where they gradually deteriorate . furthermore , donor age has significantly increased because of organ shortage , and grafts of less than optimal status are being accepted . pyschosocial development in the heart transplant patient based on psychological analyses in a larger series of 182 patients of the impact of receiving heart transplantation , the side effects of chronic immunosuppression play a great role , such that its burden results in depression in conjunction with an uncertain perspective towards certain social interactions . overall , the transplant patients do well in all socio - psychological aspects and the results are comparable to those of the general population . however , a certain percentage of patients have a difficult time adjusting to work and tend to have significant impairment in their functional activity compared to that of their healthy peers . with time , patients tend to develop graft vasculopathy and would require re - transplantation to remain alive . the results of re - transplantation are definitely inferior than those of the primary transplantation and , in the face of organ scarcity , serious ethical considerations become an issue . a potential solution for this problem for the time being is the use of mechanical circulatory support devices , which in cases of pump failure can be easily exchanged . rapid progress in the technology of these devices may ultimately lead to them being used more extensively for long - term support , as we are already doing presently in the elderly .

heart transplantation is an established procedure with acceptable , predictable long - term results and good quality of life for more than 20 years . however , it is only available for a limited number of patients . the fate of the patients is determined by the side effects of immunosuppressive drugs , increased tumor incidence and chronic vascular transplant disease . patients living 10 to 20 years after heart transplantation show physical status equal to that of patients with various chronic illnesses . they suffer from chronic side effects of long - term medication and mainly report fears of renal insufficiency followed by osteoporosis - associated pain , cortisone - induced myopathy and risk for tumors . only moderate psychological impairment is reported despite somatic problems . in the period 10 - 20 years post - heart transplantation , there is even a surprising increase in emotional well - being . the 20-year survivors are active and satisfied with daily life . they experience their own life as meaningful and have good partner , family and social relations . heart transplantation , the most ambitious project in medicine in the 20th century has been made a reality . its development has the strongest impact on cardiac surgery , immunology , pharmacology , medical logistics , defining life and death , ethics in medicine , acceptance of medical progress by the public and by health care systems . it has provided a strong solidarity among politicians , sociologists , physicians and citizens . ethical concerns will last and will make heart transplantation an important , yet temporary episode in human medicine . it has stimulated research and development of mechanical circulatory support systems as an alternative to treat end - stage heart failure .

the use of dietary supplements , including multivitamins has increased substantially in the past few decades . on an average 20 - 30% of the population in developed countries use such vitamin supplements . industries involved in their manufacture are reported to be one of the world 's fastest growing industries . although , the use of multivitamin supplementation may provide benefits in terms of increased nutrient intake , there are potential adverse effects also due to high intake . although certain benefits , like that of folic acid supplementation and protection against neural tube defects in specific populations is well - established , but results of some large scale randomized trials have shown that for the majority of the population multivitamin supplements are ineffective . sesso et al . in a randomized controlled trial conducted in 14,641 participants in usa revealed that daily multivitamin supplement did not reduce cardiovascular events , myocardial infarction or stroke in men . in today 's scenario with more literate and health conscious patients who are capable of making their own decisions regarding their health care coupled with wide availability of such supplements , present study was conducted to explore pattern of use , public knowledge and attitude toward consumption of these multivitamin supplements . a descriptive cross - sectional population based study was conducted from january to june 2013 among the general public . subjects included were patients and other hospital attendees like patients ' family members / relatives or friends , of either sex aged 18 years or older while they were waiting in the outpatient department . study participants were assured of confidentiality and anonymity of the information and written informed consent was obtained from them . a total of 120 participants were interviewed and information was collected in a structured questionnaire . the questionnaire was based on previous studies undertaken among adults about their attitude toward multivitamin supplementation and it was suitably modified for the present setting . the survey questions in addition to questions covering demographic , education level ( primary , secondary or above ) , alcohol drinking status , contained questions regarding awareness of multivitamin supplements , its consumption ( frequency , duration of usage ) , reasons for usage ( self - medication , physician advice ) and its effect . at the end of the study pearson chi - square test was applied to see the association between genders and educational status with the use of multivitamins . of the 120 study participants , 66 were males ( 55% ) and 54 were females ( 45% ) . mean age of the males was 43.85 15.44 years and of females was 38.75 12.87 years . no association was found between gender and use of multivitamins ( p = 0.969 ) . regarding educational status , approximately ( 58 ) 48% were graduates , ( 13 ) 11% postgraduates , ( 36 ) 30% had completed secondary education and ( 7 ) 6% had covered only primary education while ( 6 ) 5% were illiterate . educational status of the participants did not show any association with the use of multivitamins ( p = 0.583 ) . source of awareness of vitamin supplement use was a family doctor , relatives or friends and media , e.g. newspaper / internet [ table 1 ] . percentage of participants with different sources of information regarding multivitamins about 68.33% ( 82 ) of the participants were either current or former users of multivitamin supplements while 31.66% ( 38 ) claimed that they had never taken multivitamins . out of these users , 18.2% ( 15 ) admitted taking multivitamins of their own , 69.5% ( 57 ) consumed on the advice of their physicians while 12.1% ( 10 ) relied on the advice of family or friends . among the users , 70.73% ( 58 ) considered multivitamin supplements to be helpful . study respondents when queried as to whether they had experienced any health problem due to the use of such supplements , only one reported diarrhea which he believed to be related to multivitamin supplement use . majority of the participants were unaware of the harmful effects of multivitamin supplements or their possible interactions with other drugs . nearly 12% ( 14 ) of study participants were alcoholics and all of them were multivitamin supplement users . out of these , only three said that there is a benefit of taking these supplements along with alcohol while seven considered no benefit in consuming supplements along with alcohol . reasons quoted for the self - medication use of multivitamins are depicted in figure 1 . physician prescribed reasons were multiple , like in mouth ulcers , with concurrent antibiotic prescription , arthritis , hypotension , weakness , leg pain etc . reasons for the use of multivitamin supplements among self - medicated users there was a variable response regarding frequency of vitamin supplementation . out of the self - medication group , approximately 10 consumed multivitamin on a daily basis while 3 consumed 2 times a day . some of them reported consuming them 4 times weekly or some even mentioned taking for 4 weeks after every 6 months [ table 2 ] . frequency of usage of multivitamins by self - prescribed users majority of the participants were unaware regarding the correct indications for the multivitamin supplementation . study participants who were aware of the multivitamin use when asked about the opinion whether these drugs can be self - medicated , 60% ( 50 ) responded affirmatively . regarding knowledge about the natural sources of these vitamins , as many as 76% ( 64 ) showed ignorance . in the present scenario of high prevalence of nutrient supplementation use world - wide , present study was conducted to examine multivitamin consumption in the general adult population . our study depicted multivitamin use by 68.33% of the participants . similarly , national health and nutrition examination survey 2003 - 2006 reported use of dietary supplements by 53% of the respondents and out of which most frequently used supplement was multivitamin . a survey conducted in columbia on the estimate of use of dietary supplements revealed 73% users , out of which 85% reported using multivitamin supplements . likewise , a study conducted in 11,929 men in germany reported use of vitamin or mineral supplements by 40% of population . moreover , internet sites and television are flooded with advertisements depicting increased energy with the use of such supplements . health conscious people now - a - days feel happy to consume such supplements thinking they are actively taking care of their health . most common source of information regarding vitamin supplement use , in our study was doctors , 69.1% users consumed multivitamins on the advice of doctors . these results are in concordance with the study conducted in karachi , which revealed recommendation of vitamin supplement by doctors to be 66.2% . number of self - prescribed multivitamin users consuming multivitamins on a daily basis was high which is consistent with results from other studies where dietary supplement was consumed on a daily basis by more than 50% of multiple dietary supplement users . this is an area of concern as it has been seen in some other studies as well . a study conducted in america among five ethnic groups found that the median daily nutrient intake from multivitamin / minerals among users were above the recommended daily allowance for some vitamins such as a , b-6 , b-12 and e , thiamin , riboflavin , niacin , pantothenic acid and folate . this is more so a problem in the country like ours where there is the wide availability of supplements without physician prescription , which can clearly lead to excessive use of vitamins and hence possible adverse effects or interactions . furthermore , nutrient composition of multivitamins is extremely variable which in some cases can lead to excessive use . in india , chughchugh and lhamo have shown that the majority of the supplements available in the market contained nutrient amounts higher than the recommended dietary intakes . various studies such as alpha - tocopherol , beta - carotene cancer prevention study reported increased risk of hemorrhagic stroke by 50% with the use of alpha tocopherol for 6 years and selenium and vitamin e cancer prevention trial revealed that vitamin e supplements could increase the risk of prostate cancer among healthy men . reasons quoted for using vitamin supplements by self - prescribers were similar to study conducted by dickinson et al . where maintaining wellness was the top reason for personal use . similar reasons were seen in studies by neuhouser and eldridge and sheenan though there is no conclusive evidence that vitamin supplementation is beneficial in persons with adequate dietary intake . results of the meta - analysis have revealed that for the majority of the population multivitamin supplements are not effective . notable ones are meta - analysis of five randomized control trials which found no significant beneficial effect of such supplementation and data from eight prospective studies did not support the hypothesis that use of folate , vitamin a , c , e and multivitamins reduce the risk of lung cancer . ignorance of the participants regarding potential deleterious effects of over supplementation reflected their false belief that these medications are safe . hence , physicians should ask direct questions to their patients regarding use of self - prescribed multivitamins and educate them toward harmful effects and potential interactions with prescription medication . interaction between vitamin e and aspirin leading to additive antithrombotic effect and between vitamin e and warfarin leading to increased risk of bleeding are available in the literature . similarly , large doses of antioxidants such as vitamin e and alpha lipoic acid can decrease the effectiveness of radiation or chemotherapy for cancer . there are certain limitation of this study , which needs to be acknowledged like its cross - sectional design and its conductance at the single hospital . furthermore , association between different variables can not be established as it is a descriptive cross - sectional study . findings from this study suggest that multivitamin use is highly prevalent and the majority of the participants were ignorant of any possible harm or drug interactions . in light of this , there is a need to adopt certain educational interventions to minimize self - directed supplement use . at the same time health care professionals should take extra care to know about their patients multivitamin use and hence should counsel them about the correct use .

background and objective : the use of supplements has increased substantially in the past few decades . the present study is an effort to explore pattern of use , knowledge and attitude toward consumption of multivitamin supplements among the general public.materials and methods : a descriptive cross - sectional study on 120 adult participants from the general public was conducted . the participants were interviewed and information was collected in a predesigned structured questionnaire . the data was analyzed and expressed as counts and percentages.results:of the 120 study participants , 66 were males and 54 were females . results revealed that 68.33% ( 82 ) of the participants were users of multivitamin supplements . out of the users , 69.5% ( 57 ) participants consumed on the advice of doctors , 18.2% ( 15 ) were self - prescribers while 12.1% ( 10 ) relied on advice of family or friends . among the users , 70.96% considered such supplements to be helpful . reasons quoted for self - medication use of multivitamins were multiple such as maintenance of general health ( 55% ) , to allay weakness or fatigue ( 20% ) , to improve appetite ( 15% ) etc . majority of the participants were unaware regarding the correct indications for multivitamin supplementation . regarding knowledge about the natural sources of these vitamins , as many as 76% showed ignorance.conclusion:finding from this study suggests that multivitamin use is highly prevalent and the majority of the participants were ignorant of any possible harm or drug interactions . in light of this , there is a need to adopt certain educational interventions to minimize self - directed supplement use and increase awareness regarding their correct usage .

psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of epidermal keratinocytes and resulting in scaly , red and well - demarcated skin lesions . hyperproliferation is driven by the additive and synergistic activities of a plethora of cytokines and growth factors ( baliwag et al . , 2015 ) acting on , and driving changes in the architecture of the epidermis , keratinocytes , resident and infiltrating immune cells as well as fibroblasts and vascular endothelium in the dermis ( elder et al . , 2010 ) . in this issue of the journal , sun et al . add another ingredient to the inflammatory recipe responsible for driving this disease ; they report that the expression of ccn1 , a multifunctional non - structural protein found in the extracellular matrix ( ecm ) , is elevated in the skin of patients with psoriasis , as well as in psoriasis - like mouse models . importantly , blocking ccn1 function by either lentiviral - based sh - rna knockdown of ccn1 or anti - ccn1 neutralizing antibodies attenuated the epidermal hyperplasia and inflammation seen in the psoriasis - like mouse models . thus , they concluded that ccn1 participates in the pathogenesis of psoriasis and that targeting ccn1 could be an important therapeutic strategy . although the mechanisms by which ccn1 promotes epidermal hyperplasia and inflammation are not fully understood , sun et al . ccn1 is a secreted protein that interacts with the ecm , making it a member of a large family of matricellular proteins . based on structural homology , ccn proteins comprise a family of six members , ccn1 - 6 ( perbal , 2004 ) . the ccn acronym is taken from the names of the first three members of the family to be discovered : cyr61/ccn1 ( cysteine - rich protein 61 ) , ctgf / ccn2 ( connective tissue growth factor ) and nov / ccn3 ( nephroblastoma overexpressed gene ) . members of the ccn family exhibit diverse cellular functions , such as regulation of cell proliferation , chemotaxis , apoptosis , adhesion , motility , ion transport , and ecm regulation ( chen and lau , 2009 ) . ccn1 has been reported to regulate cell adhesion , migration , chemotaxis , inflammation , cell - matrix interactions , synthesis of ecm proteins , and wound healing in a variety of cells in culture ( jun and lau , 2010 ; lau , 2011 ) . ccn1 exerts this range of functions through interaction with multiple integrins in a cell - type and context - dependent manner [ figure 1 ] ( lau , 2011 ) . during embryonic development , ccn1 plays a critical role in vascular development and blood vessel formation in the placenta . ccn1 knockout in mice is embryonic lethal primarily due to a failure in vascular development caused by impaired ecm homeostasis . studies in animal models and in patients have confirmed that deregulation of ccn1 protein is found in several diseases associated with chronic inflammation and/or tissue injury , including rheumatoid arthritis , atherosclerosis , diabetes - related nephropathy and retinopathy , and many forms of cancer ( chen and lau , 2009 ; kular et al . , 2011 ) . the study by sun et al . reveals elevated ccn1 in the skin of patients with psoriasis and its potential role as a driving force for epidermal hyperplasia and inflammation . obviously , their findings raise the question of what drives the sustained elevation of ccn . several recent studies have shown that the ccn1 expression is regulated directly by the transcriptional co - activator yes - associated protein ( yap ) , a major downstream effector of the hippo signaling pathway . in mouse skin , yap plays a critical role in regulating keratinocyte proliferation , differentiation , and survival through up - regulation of ccn1 ( zhang et al . , 2011 ) . in the human skin cancer , basal cell carcinoma ( bcc ) , yap and its downstream transcriptional target ccn1 this inhibition of proliferation and survival is rescued by restoration of ccn1 expression ( quan et al . , 2014 ) . these data provide evidence that up - regulation of yap promotes aberrant keratinocyte proliferation through up - regulation of ccn1 in bcc . although the expression of yap in psoriasis is unknown , these data suggest that yap may be involved in up - regulating ccn1 in psoriasis . additionally , a positive feedback loop between ccn1 and the cytokine network may also contribute to the sustained elevation of ccn1 in psoriatic skin . ccn1 not only promotes the production of cytokines ( qin et al . , 2014 ) , it is also induced by cytokines , growth factors and environmental stressors ( chen and lau , 2009 ) , suggesting that a positive feedback loop may contribute to sustained elevation of ccn1 found in psoriatic skin . therefore , targeting ccn1 could be an effective therapeutic strategy by inhibiting such a positive feedback loop in psoriasis ccn1 could be an important regulator in skin biology since it impacts both epidermal keratinocytes and dermal fibroblasts . in normal adult human skin , ccn1 is substantially elevated in the dermis by aging , as well as under the influence of ultraviolet ( uv)-irradiation ( quan and fisher , 2014 ) . elevated expression of cyr61/ccn1 in the dermis leads to reduced collagen production by impairing tgf- signaling ( quan and fisher , 2014 ) and increasing collagen fibril fragmentation through the production of multiple matrix metalloproteinase proteins ( mmps ) ( quan and fisher , 2014 ) . thus , elevated ccn1 promotes skin thinning and fragility , two prominent features of aged skin , but interestingly this is not seen in long - standing psoriasis , suggesting the involvement of other mitigating factors , as well . abnormal regulation of ccn1 expression has been observed in several skin diseases , including wound healing and fibrosis ( jun and lau , 2010 ) . studies in a mouse model have demonstrated that ccn1 exerts anti - fibrotic activity via induction of dermal fibroblast senescence during cutaneous wound healing . elevated ccn1 may also have significant impact on the delayed wound healing seen in elderly patients . laser ablation , which causes partial thickness wounding , rapidly and markedly induces ccn1 in human skin dermis in vivo ( quan and fisher , 2014 ) . timing of the elevated ccn1 levels corresponds to the inflammatory phase ( ecm breakdown ) , and the timing of cyr61/ccn1 diminution corresponds to the ecm remodeling phase ( collagen production ) of wound healing responses . also of note , ccn1-regulated factors such as proinflammatory cytokine ( il-1 ) , collagen - degrading mmps ( mmp-1 , mmp-3 , and mmp-9 ) , and type i procollagen are well - known components of the wound healing response . these data suggest that ccn1 may play a critical role in regulating wound repair in human skin . further support comes from mouse studies , which have reported that ccn1 is induced by cutaneous wounding and that it participates in both the inflammatory and remodeling phases of repair ( jun and lau , 2010 ) . therefore , the constitutive elevation of ccn1 in aged human skin may delay wound healing by extending the inflammatory phase and delaying the remodeling phase . these findings highlight ccn1 as a possible therapeutic target , not only for psoriasis , but also for improving wound healing in the elderly and in skin cancer . the results reported by sun et al . in this issue reveal the potential role of ccn1 in the pathogenesis of psoriasis . this study , together with other emerging data , suggests that ccn1 may function as an important regulator in skin biology , by modulating key functions of keratinocytes and fibroblasts . clearly , there remains much to be learned about the regulation of ccn1 and its functions in skin physiology and pathology . it should be noted that ccn1 is one of six members of the ccn family . however , little is known regarding the roles of ccn3 - 6 in skin biology . certainly the article by sun et al . should spur new appreciation of the importance of the ccn family of proteins in skin biology .

the complex pathogenesis of psoriasis is still not fully understood . the study by sun et al . ( sun et al . , 2015 ) in this issue of the journal suggests that cyr61(now named ccn1 ) , a secreted matricellular protein , plays a role in the pathogenesis of psoriasis , and thus targeting ccn1 represents a potential therapeutic strategy in its treatment .

pulmonary tuberculosis is a common infection worldwide . in iran , particularly in the eastern part , fluctuations in tuberculosis prevalence are seen due to the migration of people from afghanistan . in smear - positive pulmonary tuberculosis , currently , the follow - ups are performed at the end of months 2 , 4 , and 6 via sputum smear study looking for acid - fast bacilli ( afb ) . in patients whose sputum smear does not become negative after the fifth month of treatment , treatment failure is suggested . the aim of this study is to evaluate the time of sputum smear conversion after treatment initiation and to study possible affecting factors in those whose smear does not become negative . this prospective ( descriptive - analytic ) study was carried out on all pulmonary tuberculosis patients who attended birjand tuberculosis center during 2010 - 2011 . the diagnostic criteria for pulmonary tuberculosis were at least two positive sputum smears , or a positive sputum smear and a suspicious radiography , or a positive smear along with a positive culture . the exclusion criteria were drug resistant , relapse cases and patients with hiv infection , death during treatment , inability to collect sputum , and transfer to other institutions . prior to participation , a questionnaire was filled out for each patient containing demographic information , pre - existing medical illness ( diabetes , cancer , heart disease , etc . ) and copd , the time of pulmonary tuberculosis diagnosis , treatment initiation time , and the number of live bacilli in sputum sample before the treatment followed by 1 , 2 , 3 , 4 , 5 , and 6 months after treatment . the time of sputum smear conversion was recorded for each patient considering the treatment initiation time . this study was performed on 85 smear - positive pulmonary tuberculosis patients with the mean age of 65.616.7 years , ranging from 15 to 93 . there were 38 male patients ( 44.7% ) , 47 urban residents ( 55.3% ) , and only 6 patients ( 7.1% ) from afghanistan . regarding primary bacilli density before treatment , 25 patients ( 29.4% ) were 1 + , 21 patients ( 24.7% ) were 2 + , and others ( 45.9% ) were 3 + . this time was also prolonged in those with pre - existing medical illness in comparison with others ( table 1 ) . in addition , with increased bacilli density in the primary sputum sample , the time to sputum conversion after treatment was longer ( table 2 ) . with increased age , the time it took for sputum to become negative was longer , but this relationship was not significant based on spearman correlation coefficient ( r=0.15 , p=0.17 ) . comparison of mean sputum conversion time after treatment initiation in the studied patients copd : chronic obstructive pulmonary diseases , sd : standard deviation , significance at alpha=0.05 comparison of sputum conversion after starting treatment in the studied patients based on the primary bacilli density significance at alpha=0.05 in this study , the mean time of sputum conversion in smear - positive pulmonary tuberculosis patients was about 2 months . in addition , it was revealed that the time that sputum became negative was longer in males and in those with pre - existing chronic disease . with increased bacilli density prior to treatment initiation , the time to sputum conversion was longer . these findings are comparable to a study from portugal that was carried out in 2012 . furthermore , 64.7% of patients showed smear conversion until the end of the second month and this figure reached 91.8% at the end of the third month . at the end of the fourth month , 98.8% showed smear conversion . in a study performed by soudbakhsh in 2001 , 74.6% of patients had negative smears at the end of the second month of treatment and until the end of the third and fourth months , 83.9% and 85.3% had negative smears , respectively . tahir et al , demonstrated that tuberculosis organism smear and culture have a significant relationship , but culture is time consuming and may not show the organisms in case of low sputum volume . the rate of smear negativity at the end of the second month ( 64.7% ) was in agreement with a study done in oman , but different from studies in bangladesh ( 85% response ) and india ( 91% response ) . in this study , it was revealed that with increased initial sample bacilli density , the time to smear negativity was prolonged . in addition , patients whose pulmonary involvement was evident on two or more views , the time to smear negativity was longer , which is consistent with studies by soudbakhsh and guler . noted that the presence of cavity in pulmonary tuberculosis patients is associated with delayed smear negativity . although some of our patients had cavity in their lungs , but no significant relationship was found between the presence of cavity and smear conversion . this is in agreement with a study in oman . in patients with high load of bacilli , tissue destruction is more prominent , which is due to a weak immune system to control the disease . furthermore , antibiotics have limitations in accessing organisms . in our study , those with pre - existing disease ( diabetes , chronic obstructive pulmonary disease ( copd ) , and chronic cardiac diseases ) showed delay in smear negativity compared with those without pre - existing medical illness . according to similar studies , different results have been reported regarding the relationship between time to sputum conversion and diabetes and copd . in an indian study , although patients with diabetes showed more conversion in comparison with non - diabetic patients , however , such relationship was not reported by the study in oman . supervision and control of diabetes can decrease the difference between well - controlled diabetes and non - diabetic patients . in our study , the time to sputum smear conversion was significantly longer in males compared with females . however , in a study by balasubrasekaran et al , it was reported that males experience more treatment failures . although in older patients the time to smear conversion was prolonged , the relationship was not significant . in a study by al - mamari in canada as well as a study from oman however , a study by arora et al . from india , showed that older patients had less sputum conversion compared with the youth . pre - existing illnesses in older patients and non - compliance in this age group could explain the cause of lower response rate . the main limitations of the present study were the small sample size ( limiting our ability to detect significant associations ) and potential inaccuracies in completing the records ( leading to bias in data collection ) . to minimize inaccuracies , the authors carefully reviewed all clinical files and available examination results . in this study , it was revealed that pre - existing illness , smoking , bacilli density in initial smear , and severe involvement of the lung on radiography could be associated with delay in sputum smear conversion . it is recommended that ( i ) in future , such study should be done using sputum culture , ( ii ) pre - existing illnesses of tuberculosis patients should be treated or controlled , ( iii ) dots should be done with more accuracy , specifically in patients with addiction , males , and those with pre - existing illnesses , and finally ( iv ) more studies with larger sample size in at risk groups should be carried out .

pulmonary tuberculosis is a common infection worldwide . in the eastern part of iran , fluctuations in tuberculosis prevalence are seen due to the migration of people from afghanistan . the aim of this study was to evaluate the time of bacteriologic sputum conversion after treatment and affecting factors in those whose smear does not become negative . this study was carried out on 85 smear - positive pulmonary tuberculosis patients with the mean age of 65.616.7 years . there were 38 male patients ( 44.7% ) , 47 urban residents ( 55.3% ) , and only 6 patients ( 7.1% ) from afghanistan . the mean time of sputum conversion after starting treatment was 1.991.06 months . the mean time of sputum conversion was significantly higher in males ( p=0.046 ) , increased bacilli density in the primary sputum sample ( p<0.0001 , r=0.507 ) , and pre - existing medical illness ( p=0.001 ) . in this study , it was revealed that pre - existing illness , bacilli density in initial smear , and severe involvement of the lung on radiography , could be associated with delay in sputum smear conversion .

neuromyelitis optica ( nmo ) is a rare , female predominance disease associated with recurrent autoimmune and demyelinating spectrum with cardinal manifestations . the diagnosis of nmo requires the following criteria : presence of optic neuritis , myelitis , involvement of spinal cord lesions in 3 or more segments by magnetic resonance imaging ( mri ) , initial mri of the brain not meeting the criteria of multiple sclerosis , and seropositive aquaporin-4 antibodies ( aqp4-abs ) . highly specific biomarker antibodies targeting the water channel protein aqp4 provided an insight into the immunopathology of nmo , which also served to predict relapse ratio . an interesting finding is that this group showed no female predominance , a higher proportion of caucasian ethnicity , monophasic disease , and younger age at the time of presentation . in addition , seronegative nmo patients also present with simultaneous optic neuritis and myelitis at the beginning of the disease , less severe visual impairment , and common mri finding consistent with deep gray matter involvement . there are indications that seropositive and seronegative patients might differ with regard to clinical presentation or prognosis . according to the marignier series , all seronegative patients had relapsed ; however , they also had milder visual impairment . the clinical spectrum of nmo as defined by wingerchuk et al . includes cases of simultaneous optic neuritis and myelitis , in which the two events do not develop simultaneously . we present a 37-year - old hispanic male with a past medical history of 2 episodes of bilateral optic neuritis and new onset of lower extremity weakness . he had previous admission with working diagnosis of multiple sclerosis and was treated with steroids . beside the lower extremity weakness , neurological exam revealed right lower extremity muscle power of 3/5 , and 2/5 in the left lower extremity . hyporeflexia was noted in both upper extremities , and babinski 's sign was positive bilaterally , with clonus at the right ankle . mri of thoracic spine demonstrated multiphasic demyelinating process involving the thoracic spinal cord ( fig . 1 , fig . 2 ) . mri of the brain also showed nonspecific changes with evidence in t1 imagining as noticed in fig . multiple sclerosis was still in the differential diagnosis ; however , mri of the brain showed hyperintense signal and faint hyperenhancement within the intracanalicular and intracranial segments of the optic nerves bilaterally ( fig . our patient met the diagnostic criteria for optic nmo by having two of the absolute criteria ( optic neuritis and myelitis ) and two of the supportive criteria ( brain mri not meeting criteria for multiple sclerosis diagnosis , and longitudinally extensive transverse myelitis on t2-weighted imaging on mri ) . the patient was started on methylprednisolone 250 mg every 6 h for 5 days . due to the severity of nmo with no improvement after steroids after two treatment sections , the patient 's condition improved and he regained his lower extremity strength . he completed five cycles of plasma exchange and was discharged with steroid therapy with follow - up in neurology clinic . nmo , also known as devic 's disease , is a rare condition that can be associated with systemic autoimmune disorders such as sjgren 's syndrome , systemic lupus erythematosus , thyroid autoimmune diseases , and myasthenia gravis . it was previously considered a variant of multiple sclerosis but the discovery of aqp4-ab grouped it as a separate diagnosis with different entity . imaging studies usually reveal longitudinally extensive transverse myelitis with t1 hypointensity , periependymal brainstem changes , and perivenous white matter lesions . it was also estimated that there is a correlation between segmental length of spinal cord lesions and expected disability . the traditional treatment for acute attacks in seropositive nmo is intravenous corticosteroids with or without plasma exchanges achieving almost 60% recovery rate . nmo is highly associated with relapse rate ( high aqp4-ab titers ) , requiring the need to use a maintenance immunosuppressive therapy . azathioprine with or without low - dose oral steroids is considered reasonably effective in reducing the frequency of attacks . treatment for seronegative nmo is similar to the seropositive patients ; however , recent studies showed rituximab to be an effective therapy for resistant or seronegative nmo patients and some consider it to be the first line of therapy . nmo should be thought of in the differential diagnosis in any patient presenting with transverse myelitis and or optic neuritis regardless of the gender and race . negative aqp4-ab can not exclude the diagnosis , but rather should trigger further evaluation of pathophysiology , manifestation , and prognosis . treatment is similar between seropositive and seronegative nmo ; however , new studies showed promising results using rituximab as an alternative first - line therapy . future studies and research are still needed to evaluate the prognostic outcome of both groups .

abstractneuromyelitis optica ( nmo ) is a rare disease , common in white females and rarely reported in hispanic males . it is usually associated with recurrent demyelinating spectrum that is autoimmune in nature . the diagnosis is usually confirmed by antibody biomarkers ; however , they can be negative and lead to more dilemma in diagnosis . furthermore , the course of disease and prognosis are different in seronegative as compared to seropositive nmo . treatment is similar in both subgroups with new approaches under investigation for seronegative nmo patients . we present an interesting case of a 37-year - old hispanic male who presented with sudden onset of lower extremity weakness , numbness , blurry vision , and urinary retention . magnetic resonance imaging ( mri ) of the thoracic spine showed multiphasic demyelinating process involving the thoracic spinal cord . his brain mri also revealed changes suggesting optic neuritis . the patient met the criteria for diagnosis of nmo by having optic neuritis and myelitis by imaging studies despite having negative aquaporin-4 antibodies ( aqp4-ab ) . his condition improved after plasma exchange . nmo can be difficult to distinguish from acute multiple sclerosis in the early stages of the disease . having aqp4-ab testing is important for diagnosis with imaging studies ; however , negative antibody results can not exclude the diagnosis , but rather group it in seronegative subtype . ongoing studies and research suggest that seronegative nmo might have a different pathophysiology , manifestation , and prognosis .

cloacal exstrophy ( ce ) is the most complex congenital , ventral , abdominal wall defect with an incidence of less than 1 in 200,000 live births . conventionally surgical repair consisted of a multiple staged approach ; however here we describe a primary approach in a male neonate undertaken by two surgical specialties . a male neonate was born at 39 weeks ' gestation by normal vaginal delivery to nonconsanguineous parents . antenatally , bladder exstrophy was suspected at week 21 due to nonvisualisation of the bladder on foetal ultrasonography and the decision was made to continue the pregnancy . the remainder of the gestation and labour were unremarkable and he has a healthy brother aged 3 years old . immediate management consisted of dressing the defect to minimalize fluid losses and the risk of infection . he was then transferred , on day 1 of life , from a district general hospital to a tertiary pediatric unit , where intravenous antibiotics were given . neurological examination and spinal ultrasound scan did not find evidence of myelocystocele . on full examination we found an imperforate anus , bifid scrotum , and pubic symphysis diastasis . the small omphalocele was tied as shown in figure 1 . on day 9 of life the patient was taken to theatre where primary closure of cloacal exstrophy with bilateral oblique pelvic innominate osteotomies was undertaken . firstly the orthopaedic team performed pelvic osteotomies , followed by the pediatric urology team closing the exstrophied caecum with anastomosis to the hind gut , creating an end colostomy , and closing the omphalocele with excision of the appendices . the abdominal wall was then closed ventrally with a catheter placed in the neck of the bladder and a drain placed in each hemibladder wall . the patient was started on total parenteral nutrition on his return to the urology high dependency unit ; urine output was monitored closely along with the other vital signs . the catheters were removed ; he was discharged home three weeks following surgery and then seen in clinic when he was eight weeks old ( figure 2 ) . future surgical treatment will involve a bladder neck reconstruction with epispadias repair and a pull through procedure if the external anal sphincter is found to be functioning with electrical stimulation . ce has an incidence of between 1 in 200,000 and 1 in 400,000 live births ; there is no known genetic component to the aetiology . in normal embryology , the cloaca is a common tract which at around week four separates , by growth of the urogenital membrane , into the anorectal canal and the urogenital sinus . the urogenital membrane then differentiates into the perineal body . at around the same time , the cloacal membrane which separates the cloaca from the amniotic fluid is invaded by lateral mesodermal folds . ce occurs when this invasion of mesoderm fails resulting in rupture of a weakened cloacal membrane before 4 weeks ' gestation . typical features of this defect are two exstrophied bladder plates separated medially by an exstrophied caecal plate , an omphalocele , intussusception , and herniation of the ileum , hemiphalli , imperforate anus with a variable length of shortened hindgut , and diastasis of the pubic symphysis in western countries the majority of cases of ce are diagnosed in the prenatal period following foetal ultrasound scanning . due to the complexity of the defect and lack of long term data , prenatal counselling the first case of a patient surviving ce beyond the neonatal period was published in 1960 . surgical , medical , and nutritional advances over the following decades have brought present day survival to between 83 and 100% in the western world . this includes the use of intensive care units after surgery , improved nutritional care including total parental nutrition , and developments in antibiotics [ 1 , 5 ] . traditionally surgery is undertaken as a multiple staged approach . in the first procedure the intestine the next procedure involves closure of the hemibladders ventrally but this can require multiple procedures to gain full closure . the patient then returns to theatre at around 6 months of age for closure of the abdominal wall , which can also require multiple attempts to gain full closure . outcomes from this approach have been undesirable with reports of only 5 out of 10 and 1 out of 10 of the surviving fourteen patients achieving urinary and faecal continence , respectively . in this case , surgery was undertaken as a primary repair under the care of two surgical specialties resulting in full bladder and abdominal wall closure within the first few days of life . indications for primary closure are that the patient is haemodynamically stable , there is adequate pulmonary function to cope with the increased abdominal pressure , the omphalocele is small , and the pubic diastasis is small . so far there is no long term data on this approach ; however short term observations are that the patient leaves hospital faster and avoids the burden of multiple operations in the early stages of life . the risks of multiple procedures in an infant include infection , tracheal stenosis , hypothermia , electrolyte imbalance , coagulopathy , and death . ce represents a significant reconstructive surgical challenge with the aims of preventing upper urinary tract damage , achieving urinary and faecal continence , and leaving an acceptable cosmetic appearance . as more long term data is collected it is anticipated that this will be shown to be the desired surgical approach in the properly selected patient . patients with large omphaloceles , open myelomeningoceles , and other life threatening issues need to have these problems addressed initially .

cloacal exstrophy is the most complex congenital , ventral , abdominal wall defect . traditionally surgery consists of a staged approach to repair which takes place on many separate theatre visits . in this case a primary approach was undertaken resulting in a relatively short inpatient stay and a reduced risk from multiple surgical procedures under general anaesthesia .

they most often result from accidental neck injuries , or from intraoperative insults in the context of oropharyngeal surgery , mostly tonsillectomy . there is no case reported whereby an internal carotid artery endovascular stent was removed accidentally during a lateral pharyngeal mass biopsy , and without bleeding . hereby we present such a case , as a reminder to be kept in mind of the proximity of the great vessels to the lateral pharyngeal wall , especially in the setting of an irradiated neck with a foreign material prosthesis or stent . the patient is a 54-year - old man who first presented to our department in 1988 with an adenocarcinoma of the right mandible . he underwent a right hemimandibulectomy , neck dissection , and reconstruction using iliac bone and pectoralis major flap , with postoperative chemotherapy and 70gy radiotherapy . he did well until 2006 when he was found to have a right internal carotid artery near total occlusion , most probably post radiation in origin , with a 40% contralateral stenosis . he underwent consequently a right carotid artery angiography and endovascular stenting , and was started on anticoagulation . on his last follow up in our clinic , he was found to have a nonhealing 5 3 cm necrotic mass occupying the right oropharyngeal space . therefore , he was scheduled for debridement of the ulcer and biopsy of the mass in the operating room to rule out the possibility of tumor recurrence . preoperative computed tomography scanning ( ct ) showed the irregular ulcer at the right oropharyngeal space , with the right carotid artery stent completely occluded with no distal perfusion ( figure 1 ) , and it was encased in the mass of necrotic tissue . in the operating room , under general anesthesia , the oropharyngeal lesion was inspected endoscopically transorally ( figure 2 ) . using a punch biopsy forceps , a specimen was taken from the ulcer for pathological examination . however , the mass was so rubbery and consistent that a large piece was excised , with a net - shaped cribriform metallic object encased within . on inspection , the carotid endovascular stent was identified , invaded , and surrounded by the mass of necrosis that was filling the lateral oropharyngeal wall ( figure 3 ) . the vascular surgery team was consulted into the operating room , to assess the possibility of any secondary bleeding . they recommended close surveillance of the patient for 72 hours since there was no evidence of bleeding and since the ica was already completely obstructed , with practically a very minimal risk of vessel rupture . most cases have been described in the context of head trauma or oropharyngeal surgery , mainly in relation to tonsillar surgery [ 1 , 2 ] . in our report , we go beyond tonsillectomy to describe the first case of a carotid endovascular stent removal during a lateral oropharyngeal mass biopsy . we have performed a medline literature review dating back to 1950 , and to the best of our knowledge , there is no similar reported case . physicians , in particular otolaryngology residents in training , have always been warned about the potential risk of digging deep in the tonsillar fossa while doing an extracapsular tonsillectomy , and advised to stick to the tonsillar capsule for more safety . the reason is that the icas are relatively superficially located posterolateral to the lateral pharyngeal wall or tonsillar fossa . in fact , there are multiple studies describing the relative location of the ica with respect to the tonsillar fossa . hendrix et al found that the ica was located anterior to the posterior pillar by a distance that is grossly equivalent to 40% the width of the tonsillar fossa . deutsch et al . described this distance to be roughly around 25 mm in the adult population , but it can occasionally be much smaller . this means that any incidental movement with a sharp instrument during oropharyngeal interventions might potentially injure the ica , and cause severe hemorrhage . if we add to this the incidence of carotid course anomalies such as kinking , tortuosity , or coiling ( 466% ) , we can see that a seemingly simple surgery might sometimes unwillingly turn disastrous . after performing so many uneventful simple tonsillectomies , our meticulous sharp attention as surgeons might sometimes be blunted , and a tiny pulsating mass in the lateral pharyngeal wall might escape our detection . though our patient received his neck radiation therapy 20 years ago , delayed effects of radionecrosis have been described up to 50 years later . radiation necrosis , with the high dose of 70gy that was administered to our patient , is probably the cause of the ulcer 's poor healing capacity . some authors have even suggested that radiation arteritis might be a contraindication to stenting , because these vessels often restenose , such as in our patient whose right ica was stented only two years ago . described a 22% prevalence of more than 70% stenosis of the carotid artery lumen in radiated necks compared to 4% in controls . on preoperative contrast enhanced ct scans done 1 month before our biopsy , our patient 's right ica had a normal course with no apparent tortuosity , coiling , or kinking . however , he had a total occlusion of his stent with no flow into the distal carotid on the right side , the contralateral circulation probably taking over the blood supply of the occluded side . the biopsy was done in the operating room under general anesthesia , in anticipation of any complications that might occur , considering the patient 's complex medical background . the mass of necrosis had apparently engulfed the ica and invaded it , contributing to the obstruction of the endovascular carotid stent and of the ica . the previous radiation therapy that the neck was exposed to had probably played its role in thrombosing the stent , causing a distal carotid wall necrosis , following which the stent had become denuded and adherent to the bulk of the invading oropharyngeal mass . our patient was lucky that the carotid was already totally occluded , as could be seen preoperatively on the scan , and that stent removal happened uneventfully without any bleeding . in retrospect , it would have been better to use a scalpel to sharply biopsy the lesion , avoiding the traction made by a punch biopsy forceps . . we should be careful and always remember the proximity of the great vessels when working laterally in the pharynx , such as while performing a tonsillectomy or tonsillar biopsy , especially in radiated necks . computed tomography and magnetic resonance imaging are key , giving us spatial information on the surrounding structures . it is of great importance to recognize the position of the ica prior to performing the surgery , especially in cases where anatomy is distorted by a neoplastic or necrotic invasive process . it is mainly because this is a very rare occurrence , which is often lethal short of aggressive action to stop the bleeding . in this paper , it is not our aim to discuss the treatment of such scenarios . this case highlights the impact of radiation - induced necrosis and draws our attention to the importance of close follow up of endovascular stents or other cervical instrumentation in the setting of an irradiated neck . the increased risks of surgical interventions in adjacent areas are to be kept in mind , and especially during manipulation of the pharyngeal wall , being a boundary to some underlying vital structures such as the ica .

a 54-year - old male patient , with a history of a right mandibular adenocarcinoma , previously excised , and treated with post operative chemo- and radio - therapy , presented with a right oropharyngeal necrotic mass of several months duration . his history is pertinent for a right internal carotid endovascular stenting 2 years prior to presentation . during biopsy of his oropharyngeal lesion , a specimen of tissue was retrieved , with the carotid stent within . there was no bleeding . to the best of our knowledge , there is no such case reported in the literature . we present this case as a reminder on the importance and risks of radiation - induced necrosis and its distortion of the surrounding anatomy , especially in the presence of foreign bodies or protheses .

3-methylcrotonyl - coenzyme a carboxylase ( 3mcc ) deficiency is a rare defect of l - leucine metabolism1 ) . the urinary excretion of 3-hydroxyisovaleric acid ( 3-hiva ) and 3-methylcrotonylglycine ( 3-mcg ) is increased . 3mcc deficiency is one of the most common inborn errors of metabolism detected in neonatal screening programs ( 1/36,000 births ) using tandem mass spectrometry2 ) . although the manifestation of 3mcc deficiency is variable , most infants detected by tandem mass screening are asymptomatic and remain healthy during the follow - up , and a number of apparently asymptomatic mothers have been diagnosed with 3mcc deficiency through their infant 's newborn screen3,4 ) . recently , there have been an increased number of cases of 3mcc deficiency in korea after tandem mass spectrometry was introduced as the newborn screening test5,6 ) . however , there is only one case report about maternal 3mcc deficiency in korea7 ) . we identified a case of asymptomatic maternal 3mcc deficiency detected by her son 's tandem mass spectrometry . a 14-day - old boy was referred to our endocrinology and metabolic disease clinic because of increased levels of 3-hydroxyisovaleryl carnitine on a neonatal screening test performed at one week of age . his birth weight was 3.2 kg , and he did not have immediate perinatal problems . there were no complaints of nausea , vomiting , or poor oral feeding . his height was 54 cm ( 0.26 standard deviation score ) , weight was 3.8 kg ( -1.22 standard deviation score ) , and head circumference was 37 cm ( 50 - 75 percentile ) . his blood pressure was 80/49 mmhg , pulse rate was 142 beats / min , respiratory rate was 31 breaths / min , and body temperature was 36.6. the physical exam was unremarkable . he was alert and showed normal findings on the neurologic examination , and his muscle tone was not hypotonic . leucine - free formula feeding and carnitine ( 100 mg / kg / day ) supplementation was started because we suspected he had a 3mcc deficiency . the laboratory studies showed a normal complete blood count , normal electrolytes , and normal renal and liver function test results . in addition , there was no acidosis on the venous blood gas analysis , and his ammonia level was also within the normal range . metabolic investigations showed normal serum amino acids and normal concentrations of free and total carnitine . 3-mcg and we then suspected maternal 3mcc deficiency , and a urine organic acid analysis of the patient 's mother was performed . the 3-mcg level was increased ( 227.98 mmol / mol cr , control : not detectable ) in her urine ( fig . there were no abnormal findings on her physical examination , and she was not lethargic and had no specific symptoms of acute illness according to her past medical history . we recommended further evaluation such as a plasma amino acid analysis , enzyme activity test and genetic study . after maternal 3mcc deficiency was diagnosed , the leucine - free formula and carnitine supplementation for her baby was stopped , and breast milk feeding was started . after 3 months , the mother and her baby were doing well , and they had no symptoms associated with 3mcc . it is induced by mutations in the mccc1 and mccc2 genes encoding the and subunits , respectively8 ) . 3-hiva and 3-mcg are increased in the urine of 3mcc deficiency subjects . additionally , 3-hydroxyisovalerylcarnitine is also high in the blood and urine , and it is detected by the neonatal screening test . signs / symptoms previously described in 3mcc deficiency include poor feeding , vomiting , hypotonia , seizures , failure to thrive , developmental delay , and hypoglycemia1 ) . however , the neonatal screening test using tandem mass spectrometry , which has become quite prevalent recently , has revealed that the clinical picture of mcc deficiency is heterogeneous and often highly variable , even within the same family4,9,10 ) . some patients usually have no symptoms but do show symptoms such as vomiting , involuntary movements , seizures , coma and apnea associated with metabolic acidosis , hyperglycemia and mild hyperammonemia only during concurrent infections or illnesses10,11,12 ) . the majority of children diagnosed by the neonatal screening test have been reported to have remained asymptomatic so far6,13,14 ) . therefore , the importance of screening for the defect in the asymptomatic siblings of affected patients has been established15 ) however , several asymptomatic 3mcc - deficient mothers have been identified only by abnormal results in the neonatal screening test from their unaffected babies4,13 ) , which was observed in our case . the abnormal metabolites found in the healthy infants originated from the mothers , who are unrecognized 3mcc - deficient patients , via placental transfer4 ) . therefore , metabolic analysis of the mother in addition to screening positive infants is recommended . the mother should have a urine organic acid analysis and a plasma acylcarnitine profile15 ) . most affected mothers identified through their infant 's abnormal screening results were asymptomatic despite having consumed an unrestricted diet throughout their life . however , one of 4 affected mothers reported significant emesis with minor illness or after high protein meals3 ) . an additional 2 of 4 affected mothers reported by gibson et al.4 ) had mild symptoms such as fatigue , myopathy , weakness and elevated liver enzymes . according to the report by grunert et al.9 ) , 1 of 8 maternal 3mcc - deficient patients had symptoms such as several metabolic crises with hypoglycemia during febrile illnesses , metabolic stroke , cardiomyopathy , and paresthesias . in a korean case report7 ) , the affected mother was asymptomatic , which is the same as our case . supplementation with oral l - carnitine and a leucine - restricted diet is the treatment for 3mcc deficiency , but the efficacy of these approaches is unproven15 ) . moreover , there is consensus that leucine - restricted diets are not indicated for asymptomatic mothers and that the decision regarding restricted diets in symptomatic mothers should be individualized15 ) . because the mother of our case was asymptomatic although , confirming the diagnosis based on the enzyme assay whenever possible is preferable , there is consensus that 3mcc deficiency can sometimes be diagnosed based on metabolite levels alone without the enzyme analysis , depending on the specific metabolites and degree of elevation15 ) . moreover , the genotype does not appear to be predictive of the phenotype or metabolic risk13 ) . thus , dna analysis is not yet helpful in the management of affected patients , but it can assist with the confirmation of questionable cases15 ) . we identified asymptomatic 3mcc deficiency in an adult detected via an abnormal neonatal screening test result of her unaffected baby . although maternal 3mcc deficiency is uncommon and the investigation of asymptomatic mothers is difficult , we can confirm that investigating neonatal screening - positive infants and their mothers simultaneously is important .

3-methylcrotonyl - coenzyme a carboxylase ( 3mcc ) deficiency is an autosomal recessive disorder in which leucine catabolism is hampered , leading to increased urinary excretion of 3-methylcrotonylglycine . in addition , 3-hydroxyisovalerylcarnitine levels increase in the blood , and the elevated levels form the basis of neonatal screening . 3mcc deficiency symptoms are variable , ranging from neonatal onset with severe neurological abnormality to a normal , asymptomatic phenotype . although 3mcc deficiency was previously considered to be rare , it has been found to be one of the most common metabolic disorders in newborns after the neonatal screening test using tandem mass spectrometry was introduced . additionally , asymptomatic 3mcc deficient mothers have been identified due to abnormal results of unaffected baby 's neonatal screening test . some of the 3mcc - deficient mothers show symptoms such as fatigue , myopathy , or metabolic crisis with febrile illnesses . in the current study , we identified an asymptomatic 3mcc deficient mother when she showed abnormal results during a neonatal screening test of a healthy infant .

posttransplant lymphoproliferative disorder ( ptld ) is one of the most serious complications after solid organ transplantation and hematopoietic stem cell transplantation ( hsct ) . the incidence has been reported to be about 1 percent of all transplantations ( 1 , 2 ) . ptlds , including polyclonal lymphoproliferation of b lymphocytes , polymorphic ptld and monomorphic b - cell lymphoma , are extremely heterogeneous . the risk factors for ptld include the epstein - barr virus ( ebv ) serostatus , primary ebv infection , type of organ transplant , intensity of immunosuppression , presence of cytomegalovirus disease , and age ( 3 - 6 ) . ebv infection is thought to play the most important role in the pathogenesis of ptld ( 7 ) . during primary ebv infection , ebv infects , transforms and immortalizes host b lymphocytes , and the individual becomes a permanent carrier . ebv - infected b lymphocytes commonly remain in the latent state , protected from viral proteins by preventing death by apoptosis and from causing proliferation . in immunocompetent hosts , the proliferation of b lymphocytes is inhibited by cytotoxic t cells . however , in organ transplant recipients , t - cell function is inhibited through the use of immunosuppressants . therefore , ebv induces uncontrolled b - cell expansion , resulting in ptld . in other words , deficiencies of ebv - specific t - cell - mediated immunity may cause ptld ( 7 - 12 ) . other treatment methods such as chemotherapy , radiation therapy , antiviral therapy , anti - b - cell monoclonal antibody , and cytotoxic t cells are currently being investigated . a 16-yr - old korean girl who was previously healthy developed jaundice in march 2005 . a diagnosis of wilson disease was made on the basis of increased copper in 24-hr urine and a kayser - fleischer ring on cornea examination . in april 2005 , she received cadaveric liver transplantation . before transfusion , igg antibody against viral capsid antigen ( vca ) and igg antibody against epstein - barr nuclear antigen ( ebna ) were positive , and early antigen ( ea ) was negative . after liver transplantation , igg antibody against ea converted to being positive . before liver transplantation absolute neutrophil counts were below 200/l , which was compatible with severe aplastic anemia . in september 2005 , immunotherapy with antilymphocyte globulin ( alg ) , methylprednisolone and cyclosporine was performed to treat aplastic anemia , but it produced little therapeutic effect . in january 2006 , she received a bone marrow transplant from an unrelated 39-yr - old korean man who had 4 hla ag mismatch ( cd34 : 1.6910/kg ) . the conditioning regimen consisted of fludarabine , antithymocyte globulin ( atg ) and cyclophosphamide . we performed computed tomography ( ct ) of the abdomen and colonoscopy in order to find the cause of hematochezia . colon biopsy showed monoclonal b - cell proliferation , which was compatible with polymorphic ptld ( fig . in addition , ebv dna was detected by the polymerase chain reaction ( pcr ) ( 130.1copies per reaction ) . cyclosporine was stopped , and prednisolone ( 10 mg per day ) was started . however , 12 months after liver transplantation , colon biopsy still showed monomorphic ptld and a positive result for ebv in situ hybridization in succession . fourteen months after liver transplantation ( june 2006 ) , she received peripheral blood stem cell transplantation again from a 41-yr - old taiwanese man who had 1 hla ag mismatch ( cd34 : 3.8010/kg , cd3 : 9.22410/kg ) . the donor had positive results for ebv and cmv serologic tests . a combination of cyclophosphamide , atg and tli served as the conditioning regimen . one month after the second hsct , complete dna chimerism was achieved , and the result of xx / xy fish was 0.3%/99.7% . in addition , abdomen ct revealed that the size of intra - abdominal lymph nodes markedly decreased ( fig . twenty months after hsct , she is still alive under immunosuppression with cyclosporine , and there were no lymph node enlargement on abdomen ct scans . to treat ptld , various treatment strategies including chemotherapy , radiation therapy , antiviral therapy , anti - b - cell monoclonal antibody therapy and modalities for the restoration of ebv - specific cellular immunity , have been employed . reduction of immunosuppression remains the first - line treatment , and many cases of polyclonal ptld resolved completely in this manner . thus , many other therapeutic trials have been attempted . in this case , the patient underwent liver transplantation due to fulminant hepatitis and also underwent hsct due to aplastic anemia . recently several studies have supported the role of rituximab as a second - line therapy for ptld ( 13 - 15 ) . however , rituximab was not administered to the patient because she had severe pancytopenia due to graft failure . we hypothesized that hsct of an unrelated donor , which contains cytotoxic t lymphocytes presensitized to ebv , might be an effective treatment method . the patient underwent a second hsct from an unrelated donor , and the lesion of ptld disappeared . as mentioned earlier , deficiencies of ebv - specific t - cell - mediated immunity may cause ptld . recent reports have documented the benefit of cellular therapy with ebv - specific cytotoxic t lymphocytes ( 16 - 20 ) . cytotoxic t lymphocytes from the blood of a donor are transfused into a recipient with ptld . in this manner , remission of ptld has been achieved in as many as 90 percent of patients . in this case , peripheral stem cells , which the patient received at the second hsct , contain t lymphocytes ( cd3 : 9.22410/kg ) . the amount of t lymphocytes is larger than that of donor leukocyte infusion from a previous study ( 16 ) . a second hsct may serve as cellular therapy with cytotoxic t lymphocytes for ptld . in this case , we have shown that hsct can treat ptld and long - term survival is possible . the mechanism for this is unclear , but it is thought that hsct serves as cellular therapy with cytotoxic t lymphocytes . further investigations are needed to identify whether hsct is an available cellular therapy for refractory ptld .

a 16-yr - old girl received liver transplantation for fulminant hepatitis . aplastic anemia developed , and she received hematopoietic stem cell transplantation ( hsct ) . eleven months after liver transplantation , abdominal lymph node enlargement and colon ulcers were observed , and colon biopsy showed posttransplant lymphoproliferative disorder ( ptld ) . immunosuppression reduction was attempted , but it produced no therapeutic effect . fourteen months after liver transplantation , she received a second hsct due to engraftment failure , and ptld resolved completely . the second hsct can serve as cellular therapy for ptld .

protein losing enteropathy ( ple ) is a rare condition characterized by increased excretion of protein in feces leading to hypoproteinemia and generalized edema with ascites and plural and pericardial effusions.1 ple is a diagnosis of exclusion ( after ruling out proteinuria , malnutrition , and impaired protein synthesis due to hepatic cirrhosis ) . after exclusion of other causes , the most reliable method to determine enteric protein loss is to assess the clearance of 1-antitrypsin from plasma.1 several causes have been described for this condition such as cardiac conditions,2 lymphatic obstruction due to malignancy ( lymphoma ) , and gastrointestinal causes.1 gastrointestinal causes of ple are either erosive or nonerosive . the most common etiology of nonerosive ple is menetrier disease , which is rare in pediatric age group and is characterized by hypertrophic gastric folds.3 other nonerosive gastrointestinal conditions that may be complicated by ple include eosinophilic gastroenteritis , small intestinal bacterial overgrowth , celiac disease , microscopic colitis , and helicobacter pylori infection.1 ulcerative colitis and crohn disease are among erosive gastrointestinal diseases leading to ple.4 in pediatric age group , primary lymphangiectasis is seen rarely , which is characterized by the presence of dilated lymphatic channels in tips of small intestinal villi.5 secondary lymphangiectasis is seen mainly due to lymphatic obstructions.1 a recently published article denoted an infant with rotavirus infection who presented with ple.6 congenital malformations of lymphatics and retroperitoneal fibrosis are stated briefly as causes of ple.1 hereby we intend to report a case of unusual ple due to meso - intestinal fibrosis that led to secondary lymphangiectasis which we believe is yet an unreported entity . a 2.5-year - old girl referred with features of partial intestinal obstruction and underwent laparotomy . she had history of ple since 16 months of age with generalized edema and received albumin every other week . workup of ple was inconclusive and only a histologic report from duodenal biopsy taken during upper endoscopy noted an increase in eosinophils in lamina propria of small intestine . she also had a history of intermittent vomiting since 5 months of age treated with motilin and ranitidine with diagnosis of gastroesophageal reflux disease . vomiting increased in frequency from once a month to twice a week in recent months and each episode ended in bile vomiting . spiral abdominal computed tomography scan revealed an increased circumferential wall thickness of segments of jejunum with obstruction of loops proximal to it , suggesting infiltrative lesions . laparotomy revealed no visible obstruction but lace - like white areas in meso of small intestine . after laparotomy , the vomiting episodes are stopped , but she receives albumin to control hypoproteinemia as before . however , with institution of caprilon ( nutricia ltd . , wiltshire , uk ) ( having medium chain fatty acids ) , the need for albumin infusion is reduced . ( a ) small intestinal mucosa with rather tall villi and no significant inflammatory infiltrate ; hematoxylin and eosin stain ( 40 ) . ( b ) small intestinal submucosal with the presence of several dilated lymphatic channels ; hematoxylin and eosin stain ( 40 ) . ( c ) small intestinal wall with severe fibrosis of meso overlying muscularis propria ( blue colored area overlying muscularis propria ) ; trichrome stain ( 40 ) . there is no inflammatory infiltrate in fibrotic areas and other sites as well ; trichrome stain ( 40 ) . gastrointestinal causes are divided into nonerosive and erosive conditions.1 we investigated rather all the above - mentioned causes in our case and no stated hallmarks of these disorders were found . because of partial obstruction symptoms , laparotomy was performed and unusual findings such as severe fibrosis of meso overlying muscularis propria of the small intestine were observed . no such case was encountered in a thorough research of literature using the keyword of intestinal fibrosis . articles found with the keyword of intestinal fibrosis or meso - intestinal fibrosis were mostly dedicated to localized fibromatosis of intestine and patients were not referred with picture of ple.7 8 the most relevant condition is sclerosing mesenteritis , which is rarely seen in pediatric age group . in a case report concerning a 6-year - old girl , the aforementioned case also shows evidences of inflammatory process in the intestinal wall , which is not observed in our case . another complication of fibrosis of the intestinal wall appears to be impaired motility with signs and symptoms of partial intestinal obstruction in this case . parents are close relatives ( cousins ) and she is the only child of the family . although family history is negative for an identical case , the possibility of genetic disorders should be kept in mind . in conclusion , our case appears to be a newly encountered cause of ple and the prognosis and treatment options are not known for this patient .

introduction protein losing enteropathy is a symptom characterized by loss of protein in intestines resulting in low protein levels in serum and generalized edema . several causes are reported for this condition . hereby we report an as yet unreported cause of protein losing enteropathy that we named meso - intestinal fibrosis . case report a 2.5-year - old girl referred with features of partial intestinal obstruction and underwent laparotomy . she had history of protein losing enteropathy since 16 months of age with generalized edema and received albumin every other week . workup of protein losing enteropathy was inconclusive and only a histology report denoted increase in eosinophils in lamina propria of small intestine and hypoallergenic diet was started for her , but no significant response was noted . laparotomy revealed lace - like white areas in meso of small intestine and intestinal wall was firm in palpation in some areas . biopsy was taken from these sites and histology revealed severe fibrosis of meso overlying muscularis propria and also patchy fibrosis of intestinal meso led to severe lymphangiectasis in submucosa of small intestine . discussion secondary lymphangiectasis due to obstruction of lymphatic flow is mentioned as cause of protein losing enteropathy . meso - intestinal fibrosis seen in this case that led to secondary lymphangiectasis and also motility disorder has not been reported as yet .

triple - negative breast cancer ( tnbc ) is defined by a lack of expression of estrogen and progesterone receptors and her-2 as evaluated by immunohistochemistry methods . this subgroup accounts for about 15% of all types of breast cancers . additional biological characteristics of this subtype are epidermal growth factor receptor ( egfr ) and c - kit overexpression in 57% and 31% of cases , respectively . genomic expression profiling of this disease subtype has associated it with basal cells of the mammary epithelium ( basal - like subtype ) . the basal - like breast cancer subtype expresses a highly angiogenic phenotype , includes many brca1-mutated tumors and has a poor prognosis . furthermore , an earlier age of onset , a high rate of local relapse , a higher incidence of visceral metastases , and a high rate of cerebral metastases have been reported in patients with basal - like breast cancer . the basal - like subtype is assigned by gene expression profiling whereas the definition of tnbc is based on immunohistochemical characteristics . moreover , it is crucial to note that although most basal - like cancers are triple negative , there is a moderate discordance between tnbc and basal - like breast cancer . although most basal - like cancers do not express estrogen and progesterone receptors and her-2 , a small number do and , therefore , the overlap between basal - like breast cancer and tnbc is not complete and the terms are not completely synonymous . because of this discordance and potential misclassification , in this review we refer to basal - like breast cancer when a gene expression array was used for characterization and to the tnbc subtype when the analysis was limited to immunohistochemistry . preclinical studies on brca1-related breast cancers have shown high sensitivity to alkylating agents , mitomycin - c , and platinum compounds as well as sensitivity to agents inducing dna double - strand breaks such as etoposide and bleomycin , but resistance to mitotic - spindle poisons such as taxanes and vinca alkaloids has been recorded . multiple data have consistently identified a poorer clinical outcome for women with basal - like breast cancer , although modern regimens of chemotherapy can alter the history of the disease . the risk of recurrence is higher in the first 3 - 5 years , suggesting that a substantial number of women are cured if they remain disease - free for several years after diagnosis . a retrospective analysis of the cancer and leukemia group b ( calgb ) 9344 trial found that patients with either tnbc or her-2-positive breast cancer achieved the greatest benefit from the addition of paclitaxel to doxorubicin and cyclophosphamide . similarly , dose - dense therapy seems to have the greatest incremental benefit in women with estrogen receptor - positive tumors . pathological and molecular determinants of the chemosensitivity of breast cancers have been extensively explored through neoadjuvant trials . estrogen receptor negativity and high expression of ki67 , features inherent to basal - like cancers , have been consistently shown to be associated with clinical and pathological responsiveness to neoadjuvant chemotherapy . in the neoadjuvant setting , basal - like breast cancer has been associated with a significantly higher rate of pathological complete response ; however , relapse - free and overall survival were very short [ 14 - 16 ] . on the basis of limited clinical data , the tnbc subtype is probably the most chemosensitive subtype of breast cancer , although it is unclear which agents induce the best response rate . from a biological stand point , dna - damaging agents , such as platinating agents , are very high priority candidate agents based on the brca1 and dna repair dysfunction described in tnbc . two studies of neoadjuvant single agent cisplatin in women with tnbc and women with both brca1 mutations and tnbc have reported pathological complete response in 23% and 72% of cases , respectively . several new drugs , including anti - angiogenic agents , egfr inhibitors , poly(adp - ribose ) polymerase ( parp ) inhibitors and src kinase inhibitors , are currently under investigation for use in metastatic tnbc . based on egfr expression in gene profiling studies and the dependence of basal - like breast cancer cell lines on egfr for growth and proliferation , the tbcrc ( translational breast cancer research consortium ) 001 trial was a randomized trial of carboplatin in combination with cetuximab versus cetuximab alone in patients with metastatic tnbc . the response rate to the combination was 17% , with a clinical benefit seen in 29% of patients . a similar study of irinotecan plus carboplatin with or without cetuximab in metastatic breast cancer suggested , on subset analysis , a modest higher response rate ( 30% versus 40% ) for the patients with tnbc receiving cetuximab . the role of anti - angiogenic therapy in tnbc has been evaluated retrospectively on a subset analysis in the ecog ( eastern cooperative oncology group ) 2100 trial . the trial randomized patients with metastatic disease to receive palitaxel plus bevacizumab or paclitaxel alone as the first line of treatment . there was a significant improvement of progression - free survival with the addition of bevacizumab , including in the subgroup of patients with largely tnbc . a prospective trial of neoajuvant cisplatin plus bevacizumab in tnbc showed a pathological response ( miller - payne grade 4 - 5 ) of 36% . . additional benefits from combining carboplatin and paclitaxel and the addition of bevacizumab to paclitaxel in tnbc will be directly studied in the neoadjuvant trial calgb 40603 , which has a 22 randomized bi - factorial design . other novel agents of interest include the multitarget src kinase inhibitor dasatinib . a preclinical in vitro model of sensitivity of dasatinib applied to expression profiles from human tumors overlapped significantly with tnbc tumors , suggesting promising activity . however , data from a phase ii trial showed it had modest activity as a single agent . parps are molecules integrally involved in nonhomologous dna repair that become the primary means of double - strand dna repair when the preferred homologous recombinant mechanism is lost , as occurs when the brca1 pathway is defective . dysfunction of brca1 pathways is present in hereditary breast cancer and in some tnbc cases . recently , data from two phase ii clinical trials of parp inhibitors have been presented . olaparib is an oral parp inhibitor and , as a single agent , showed substantial activity in heavily pretreated brca1/brca2 carriers with advanced breast cancer : the overall response rate was 41% and the median progression - free survival was 5.7 months . presented data from a phase ii randomized trial of carboplatin plus gemcitabine with or without bsi-201 , a small - molecule parp inhibitor , in patients with metastatic tnbc . the experimental regimen including bsi-201 showed a significantly improved response rate ( 48% versus 16% ) , clinical benefit rate ( 62% versus 21% ) , median progression - free survival ( 6.9 versus 3.3 months ) and median overall survival ( 9.2 versus 5.7 months ) . in the adjuvant and curative setting , tnbc should be treated with conventional therapies at this time . despite promising data from preclinical models and early phase clinical trials , incorporation of platinum compounds or other novel therapies retrospective correlative strategies focusing on the tnbc subgroup may help to identify which patients will benefit most from standard drugs . however , patients with tnbc should be offered clinical trials looking at the efficacy and safety of new drugs . results from ongoing clinical trials will soon provide information to enable us to change therapeutic approaches to tnbc .

triple - negative breast cancer ( tnbc ) has been recently recognized as an important subgroup of breast cancer with a distinct outcome and therapeutic approach compared with other breast cancer subgroups . because tnbc is defined by the absence of a target ( either hormone receptors or her-2 ) , conventional cytotoxic therapy is still the mainstay of treatment . this report focuses on the current state and recent advances in managing tnbc .

most persons with stroke place more weight on their non - affected leg and therefore have an asymmetrical posture . transferring their body weight to the affected leg is a more difficult task than transferring it to the non - affected leg2,3,4,5 . difficulty in transferring body weight is also seen in both high and low stepping6 . one study reported an approximate 95.0% ability of subjects to transfer their body weight to each leg . in contrast , persons with stroke were only able to transfer 65.5% of their body weight to the affected leg . furthermore , they had an 85.0% ability to transfer their body weight onto the non - affected leg4 . diskstein and avulaffio studied differences in postural sway and found that persons with stroke have larger mediolateral postural sway than healthy people . stroke causes more significant sway on the affected side than on the non - affected side7 . persons with stroke who have impaired balance are at an increased risk of falls . those at most risk of falling tend to have more significant mediolateral sway than the non - fallers8 , 9 . the risk of falling is also associated with mediolateral balance in community - dwelling elder people . stroke patients with a history of falling also have larger mediolateral sway than non - falling stroke patients and healthy subjects while performing standing and sitting maneuvers10 . many studies have reported successful training for increased weight shifting , producing increased physical performance . weight - shifting training in the sitting position improved the trunk position error ( tre ) and trunk impairment scale ( tis ) and timed up and go ( tug ) scores in chronic strokes patients11 . after an intervention , one study reported increased berg balance scale ( bbs ) scores and forward reaching at the shoulder level with the non - affected arm1 . mccombe and prettyman studied a regime involving five arm exercises that improved the bbs score while standing12 . it is important that treatment for weight bearing and shifting during standing is associated with maintaining balance , good posture , and activities of daily living ( adl ) . in addition , fall risk increases with decreased functional performance in the stroke population . the purpose of this study was to show that the maximal lateral reaching distance on the affected is correlated with other reaching distances and functional performance using the multi - directional reach test ( mdrt ) for weight shifting . we also aimed to assess whether maximal lateral reaching distance on the affected side is a predictor of other variables . table 1table 1.common characteristics and functional performance in the participants ( n=51)variablesvaluegender ( male / female)30/21affected side ( rt / lt)26/25age ( yrs)57.411.9height ( cm ) 165.89.2body weight ( kg ) 63.412.1poststroke duration ( months ) 13.510.4bbs 36.17.7tug 33.517.1tis 11.73.3mbi 59.815.4maximal reaching distance ( cm)forward 13.26.9backward 7.74.8non - affected side 10.25.4affected side 9.25.5numbers , meansd shows their general characteristics . the inclusion criteria were a brunnstrom recovery stages of 35 , ability to stand for 30 seconds without assistive devices , no other neurologic and orthopedic diseases , and acute stage completion . the exclusion criteria were pain , musculoskeletal problems , and a mini mental state examination - korean version score < 24 . all tasks were measured by two physical therapists with over 7 years of work experience . weight shifting ability was examined for each direction of maximal reaching by the mdrt13 , 14 . however , reaching on the affected side was performed with the non - affected arm because it was difficult for patients to maintain the affected arm above shoulder level . during the examination , the subjects stood in a comfortable upright posture without assistive devices and raised their non - affected arm to the height of the acromion process . while pushing a yardstick , they kept their feet planted on the floor and pushed in each direction as far as possible . maximal backward weight shifting was measured by leaning back while pushing on the yardstick . maximal lateral reaching was measured by pushing the yardstick using the acromion of the affected side . trunk performance was measured using the tis and adl were assessed using the mbi . pearson s correlation coefficient was used to compare variables , and a stepwise multiple regression model was used to analyze maximal lateral reaching distance on the affected side to identify any causal relationships among variables including general characteristics , the bbs , tug , tis , and mbi scores ; and other maximal reaching distances . the subjects functional abilities are shown in table 1 , including their bbs ( 36.17.7 ) , tug ( 33.517.1 ) , tis ( 11.73.3 ) , and mbi scores ( 59.815.4 ) . the maximal lateral reaching distance on the affected side ( 9.25.5 ) was shorter than the maximal forward reaching distance ( 13.26.9 ) and maximal non - affected side reaching distance ( 10.25.4 ) , but not the backward reaching distance ( 7.74.8 ) . the maximal lateral reaching distance on the affected side was correlated with all variables except general characteristics . the maximal affected side reaching distance was correlated with the bbs ( r=0.571 ) , tug ( r=0.478 ) , tis ( r=0.561 ) , and mbi scores ( r=0.499 ) , maximal forward reaching distance ( r=0.673 ) , maximal backward reaching distance ( r=0.723 ) , and maximal non - affected side reaching distance ( r=0.785 ) . the final step of our stepwise multiple regression analysis demonstrated that the reaching distance on the non - affected side , backward weight shifting , and mbi score explained 69.5% of the variation in maximal lateral reaching distance on the affected side ( r=0.834 ) . the maximal lateral reaching distance on the affected side was the shortest , excluding the backward direction . it may be that the backward direction does not mirror much visual information to the direction . most persons with stroke have difficulty shifting their weight toward the affected side compared with the non - affected side . all functional performances and maximal reaching distances in each direction correlated with the maximal lateral reaching distance on the affected side . in particular , the bbs and tis scores showed strong correlation with the maximal lateral reaching distance on the affected side . the correlation of mdrt scores in all directions with bbs and tug scores have previously been studied in elderly adults13 . but frt has only a forward direction , while the mdrt has four directions : forward , backward , right , and left . stroke patients have unilateral impairment , which is why they have asymmetry of posture and less weight bearing and shifting on the affected side leg . regarding use of the frt for stroke patients , a multidirectional approach is better than unidirectional approach for elucidating the situation clearly . the lateral affected side reaching distance can especially predict not only balance but also trunk impairment and adl . the maximal lateral reaching distance on the affected side is related to the maximal reaching distance on the non - affected side , in addition to backward for weight shifting and mbi score . stroke patients were previously shown to have difficulty in successfully performing weight transfer and holding a single - limb stance on the affected side during gait5 . if a stroke patient has a serious impairment or deficiency on the affected side , therapists are unable to train in weight bearing and sifting on the affected side to improve functional performance . in this situation , a good method that can be tried is to get the stroke patients to attempt to perform adl when moving in different directions , such as moving toward the non - affected side and backward . this study used the mdrt to show that persons with stroke have different maximal reaching distances in all directions . healthy people rarely perform backward walking and arm activities without trunk rotation during adl . therefore , this study concentrated on the maximal lateral reaching distance on the affected side rather than backward leaning . the maximal lateral reaching distance on the affected side was related to balance and trunk impairment and was influenced by the maximal lateral reaching distance on the non - affected side , maximal backward reaching distance , and mbi score .

[ purpose ] this study aimed to examine the relationship between maximal lateral reaching distance on the affected side and weight shifting using the multi - directional reach test in persons with stoke . [ subjects ] fifty - one chronic stroke participants were recruited from two rehabilitation hospitals . this study administered the berg balance scale , timed up - and - go , trunk impairment scale , modified barthel index and measured different maximal reaching distances . [ results ] the maximal lateral reaching distance on the affected side was correlated with the bbs ( r=0.571 ) , tug ( r=0.478 ) , tis ( r=0.561 ) , and mbi scores ( r=0.499 ) , the lateral reaching distance in all directions on the non - affected side ( r=0.785 ) , the maximal backward reaching distance ( r=0.723 ) , and the maximal forward reaching distance ( r=0.673 ) . the maximal reaching distance on the affected side was also affected by that on the non - affected side , in addition to the maximal backward reaching distance and mbi score . the final step model of stepwise multiple regression was explained 69.5% . [ conclusion ] maximal lateral reaching distance on the affected side as determined by the multi - directional reach test is a good method of assessing functional performance in stroke patients . data regarding maximal reaching distance on the non - affected side can be used to measure functional impairment on the affected side in clinical settings .

lichen sclerosus ( ls ) is a chronic inflammatory skin disease of unknown etiology . at present , the typical first line of treatment for ls includes various topical steroids to control inflammation . its epidemiology is probably underestimated , but it has been calculated to have a prevalence of 0.10.3% among all patients referred to a community - based dermatology department . although the underlying cause is unknown , researchers have linked the disease to autoimmune mechanisms . a recent study analyzed serum autoantibody profiles in patients with ls versus healthy controls . this study found the presence of circulating autoantibodies to a specific skin protein , extracellular matrix protein 1 ( ecm1 ) , in most patients with ls . they concluded that ecm1 is a plausible target antigen for autoimmune mechanisms observed in ls pathology . this is the main rationale for the off - label use of ketamine infusions for the treatment of neuropathic pain . however , ketamine exhibits extensive polypharmacological effects , which has led it to be regarded as it also exhibits robust immunoinhibitory effects that have been studied mainly in the context of developing a novel antidepressant . entourage effect that could be uniquely beneficial for the treatment of painful inflammatory conditions with a possible autoimmune component such as ls . a 66-year - old female patient presented to the florida spine institute ( fsi ) as a referral from her dermatologist for the treatment of chronic pain in her bilateral lower limbs . she had begun having pain in her lower limbs approximately 8 years prior to her first visit to the fsi . the patient had developed a rash that encompassed large portions of her lower limbs and anus . the patient had been diagnosed with ls et atrophicus at the department of dermatology and cutaneous surgery of the university of south florida ( tampa , fla . , there , the patient had been treated with steroids , with little improvement . over time , the patient had developed significant skin scarring , skin atrophy , and edema . her pain was treated with a common neuropathic pain agent ( gabapentin ) and an opiate ( hydrocodone ) . this pain regimen gave the patient mild relief , but her ability to perform physical activities was only minimally affected . the patient stated that pain , weakness , and edema in her lower limbs were her main complaints and the reason for her intolerance of physical activity . the pain was described as constant burning with deep aching pain and sporadic sharp pains . on a visual analog scale ( vas ) , she stated that if her pain were controlled , she would be able to increase her physical activity and performance . on physical exam , the patient 's skin revealed skin atrophy , scarring , and plaques consistent with ls et atrophicus located in both legs , thighs , buttocks , and the anus ( fig . her lower limbs also demonstrated edema , color changes , and temperature changes in the distal parts of the legs ( when compared to the hands and upper thighs ) . the major muscle groups in her lower limbs were considerably weak , but she had a manual muscle strength grade of at least 4 out of 5 . thus , the patient was treated as a case of possible neuropathic pain , which was likely a complication of the patient 's ls . the patient 's pain started after months of having her rash and escalated to a severity at which her ambulation and ability to perform her activities of daily living were significantly affected . in addition , the patient 's sensory , vasomotor , and motor dysfunction as well as edema started months after the rash had started . at the time of her first visit , methadone was chosen because , in addition to being an opioid analgesic , it acts as a mild nmda receptor antagonist , a novel target for neuropathic pain . the patient 's pain improved over the next month ( to vas 5/10 ) . despite the improvement in the patient 's pain , the main goal for the patient and treating physician was ultimately to discontinue opiate medications while maintaining adequate pain control it has the ability to provide conscious sedation , but , more importantly , it is a potent nmda receptor antagonist . in may 2014 , the patient was started on the ketamine infusion protocol set forth by the fsi . on day 1 , the patient was infused for approximately 4 h with 200 mg ketamine , 200 mg lidocaine , and 6 mg midazolam in a 100-ml bag of saline . the ketamine dosage was increased by 200 mg each day until 800 mg was reached . the overall clinical course of the patient in this case study is plotted in fig . 2 . four days following the last ketamine infusion during a follow - up visit , the patient reported improvement in her pain levels ( to vas 4/10 ) . one month after the ketamine infusions , the patient was seen for another follow - up . areas that had previously been causing much discomfort due to sclerotic plaques and lesions showed drastic improvement . in addition , the patient reported decreased allodynia , hyperpathia , and hypersensitivity in her lower limbs . the patient volunteered to undergo 2 ketamine booster infusions over the course of 2 days . in july 2014 , her pain had significantly reduced ( to vas 1/10 ) from her pre - ketamine infusion state , and her ls rash and edema continued to be significantly reduced ( fig . the patient 's ability to perform activities of daily living and ambulation were greatly improved . over the course of 8 months , she received ketamine booster infusions every 23 months . her pain continues to be controlled without the use of opiates ( vas 1/10 ) . the patient 's rashes , edema , allodynia , and hypersensitivity continue to be significantly improved compared to the pre - ketamine infusion state . she has undergone physical therapy with significant improvement in ambulation ability and exercise / physical activity tolerance . the patient claims to be at a level of pain control and physical activity similar to her premorbid state . a 66-year - old female patient presented to the florida spine institute ( fsi ) as a referral from her dermatologist for the treatment of chronic pain in her bilateral lower limbs . she had begun having pain in her lower limbs approximately 8 years prior to her first visit to the fsi . the patient had developed a rash that encompassed large portions of her lower limbs and anus . the patient had been diagnosed with ls et atrophicus at the department of dermatology and cutaneous surgery of the university of south florida ( tampa , fla . , there , the patient had been treated with steroids , with little improvement . over time , the patient had developed significant skin scarring , skin atrophy , and edema . her pain was treated with a common neuropathic pain agent ( gabapentin ) and an opiate ( hydrocodone ) . this pain regimen gave the patient mild relief , but her ability to perform physical activities was only minimally affected . the patient stated that pain , weakness , and edema in her lower limbs were her main complaints and the reason for her intolerance of physical activity . the pain was described as constant burning with deep aching pain and sporadic sharp pains . on a visual analog scale ( vas ) , she stated that if her pain were controlled , she would be able to increase her physical activity and performance . on physical exam , the patient 's skin revealed skin atrophy , scarring , and plaques consistent with ls et atrophicus located in both legs , thighs , buttocks , and the anus ( fig . her lower limbs also demonstrated edema , color changes , and temperature changes in the distal parts of the legs ( when compared to the hands and upper thighs ) . the major muscle groups in her lower limbs were considerably weak , but she had a manual muscle strength grade of at least 4 out of 5 . thus , the patient was treated as a case of possible neuropathic pain , which was likely a complication of the patient 's ls . the patient 's pain started after months of having her rash and escalated to a severity at which her ambulation and ability to perform her activities of daily living were significantly affected . in addition , the patient 's sensory , vasomotor , and motor dysfunction as well as edema started months after the rash had started . at the time of her first visit , methadone was chosen because , in addition to being an opioid analgesic , it acts as a mild nmda receptor antagonist , a novel target for neuropathic pain . the patient 's pain improved over the next month ( to vas 5/10 ) . despite the improvement in the patient 's pain , the main goal for the patient and treating physician was ultimately to discontinue opiate medications while maintaining adequate pain control it has the ability to provide conscious sedation , but , more importantly , it is a potent nmda receptor antagonist . in may 2014 , the patient was started on the ketamine infusion protocol set forth by the fsi . on day 1 , the patient was infused for approximately 4 h with 200 mg ketamine , 200 mg lidocaine , and 6 mg midazolam in a 100-ml bag of saline . the ketamine dosage was increased by 200 mg each day until 800 mg was reached . the overall clinical course of the patient in this case study is plotted in fig . 2 . four days following the last ketamine infusion during a follow - up visit , the patient reported improvement in her pain levels ( to vas 4/10 ) . one month after the ketamine infusions , the patient was seen for another follow - up . areas that had previously been causing much discomfort due to sclerotic plaques and lesions showed drastic improvement . in addition , the patient reported decreased allodynia , hyperpathia , and hypersensitivity in her lower limbs . the patient volunteered to undergo 2 ketamine booster infusions over the course of 2 days . in july 2014 , her pain had significantly reduced ( to vas 1/10 ) from her pre - ketamine infusion state , and her ls rash and edema continued to be significantly reduced ( fig . the patient 's ability to perform activities of daily living and ambulation were greatly improved . over the course of 8 months , she received ketamine booster infusions every 23 months . her pain continues to be controlled without the use of opiates ( vas 1/10 ) . the patient 's rashes , edema , allodynia , and hypersensitivity continue to be significantly improved compared to the pre - ketamine infusion state . she has undergone physical therapy with significant improvement in ambulation ability and exercise / physical activity tolerance . the patient claims to be at a level of pain control and physical activity similar to her premorbid state . a recent case - control study suggested that ls is characterized by aberrant autoimmune function . that study compared a total of 190 women with adult - onset ls with healthy controls . the authors found that patients with ls more frequently had autoimmune disorders ( 28 vs. 9% ; p < 0.001 ) , supporting an autoimmune association with ls . thus , pharmacotherapies that address inflammation and autoimmune responses should be particularly useful for the treatment of ls . to our knowledge , there have been no other reports on the effects of ketamine in patients with ls until now . in our case study , we report that the pain and dermatological pathology associated with ls in one patient were significantly reduced following ketamine infusion therapy that was employed for neuropathic pain . even though this is an extremely rare case , we felt that these serendipitous observations related to the effects of ketamine in ls might spark further research to better understand its etiology . moreover , this case study provides evidence that supports intravenous ketamine as an alternative treatment option for patients who can not manage their ls with topical steroids . that intravenous ketamine infusions drastically improved symptoms of ls in one patient is scientifically interesting , in part due to its debatable etiology . ketamine is known to exert analgesic , anesthetic , bronchodilatory , immunomodulatory , neuroprotective , and antidepressant effects , probably via multiple pharmacological modalities . although extensive efforts are already underway to repurpose ketamine for medical use beyond anesthesia , no other studies have looked at ls . as described in this case study , intravenous ketamine infusion not only provided rapid and sufficient analgesia but it also produced drastic and unexpected improvements in lesions associated with severe ls . we believe that these therapeutic effects could be due to not yet fully understood immunomodulatory properties of ketamine . nonetheless , the results achieved for this patient merit further investigation . moreover , we hope that future studies reveal the importance of ketamine 's polypharmacological effects in the context of various disease states , rather than fearing the drug 's nonspecificity .

a patient reported to the florida spine institute ( clearwater , fla . , usa ) with severe lichen sclerosus of the anogenital region and legs . the patient 's pain presentation was neuropathic with hypersensitivity , allodynia , swelling , and weakness . the patient had failed multiple pain management modalities including opioid therapy , anticonvulsants , and antidepressants . the patient completed a standard intravenous ketamine infusion regimen developed at the florida spine institute and reported complete abolishment of her pain syndrome . for the first time , we report that ketamine infusions also dramatically improved a patient 's lichen sclerosus . that ketamine is known to have immunomodulatory properties , and given the clinical observations described in this case report , suggests that ketamine should be explored as a possible new therapeutic option for managing lichen sclerosus , especially in cases that are refractory to conventional therapies .

the irrevocable aim of endodontics is a three - dimensional unblemished seal of the root canal system which is achieved by perfect designing of the canal diameter and canal form . the biomechanical preparation is one of the major steps for removal of bacteria and debris in the root canal so as to achieve a successful endodontic treatment . during root canal instrumentation there are complications such as perforations , ledge formation , transportation of canal , and formation of cracks in the root dentin . at times , in the zeal of biomechanical preparation of the canal we inevitably end up damaging the root dentin , which becomes a gateway to dentinal cracks and minute intricate fractures ; thereby , causing failure of treatment . as a result of craze lines or microcracks , there might be occurrence of root fracture that propagates due to repeated application of stress by the occlusal forces . shemesh et al . , observed more dentinal defects in teeth which were obturated with spreader than teeth obturated without spreader . in different degrees , dentinal damage can occur due to procedures like biomechanical preparation , obturation , and retreatment . complexities in the preparation of root canal may be attributed to variation in the design of the cutting instrument , taper , or composition of the material from which it is made . hand instrumentation the milestone of endodontic practice in the past though have lost popularity , still remain the integral part of canal preparation . rotary instrument by its innate behavior in the canal may result in more friction , which may increase dentinal defects and microcracks formation in comparison to hand instruments . possible relationship between the design of niti rotary instruments and the incidence of the vertical root fractures was found by kim et al . , and it was concluded that the design of the file affects strain concentration and the apical stress during instrumentation of root canal . recently , the protaper next ( ptn , dentsply , maillefer ) files were introduced in the family of niti rotary instruments with a completely new design comprising of unique swaggering movement , greater flexibility , the m - wire technology , the 5 generation of continuous improvement , and its offset design . whether it is rotary or hand files ( hfs ) , they are assumed to cause limited frictional forces within the canal , hence creating dentinal defects . so there is need to study the behavior of different niti rotary instruments and the newly developed rotary system , ptn , on root dentin . teeth with curved roots , calcified canals , extracanals , and teeth with developmental anomaly or resorption were excluded from the study . the teeth were decoronated at coronal portions by using a diamond disc , leaving roots approximately of 10 mm in length . all the roots were inspected with transmitted light for detecting any preexisting cracks or any craze - lines by using a stereomicroscope under 12 , to exclude teeth with such findings from this study . patency of the canal was established using a # 10 k - file ( mani , japan ) in the canal . the specimens were then divided into four groups ; each group containing 15 specimens each . hfs upto file # 40 were used for canal preparation . in the pt ( dentsply , maillefer ) , hs ( micro - mega , besancon , france ) , and ptn ( dentsply , maillefer ) groups ; preparation of the canals was done using speed and torque controlled motor ( x - smart ; dentsply , maillefer ) . in the hand files group , step - back technique was used upto file # 40 . in the pt group , the following sequence of pt rotary niti files were used for preparation of canals at 300 rpm : the shaping file x for coronal enlargement , and s1 , s2 , f1 , f2 , and f3 files , corresponding to apical size 30 , used at the working length . in the hs group , the hs niti files were used upto file # 30 at 300 rpm in crown - down sequence . in ptn group , the ptn rotary system files were used at 300 rpm in the following sequence : x1 , x2 and x3 , corresponding to apical size # 30 . the ptn rotary files were used in a constant rotation at a speed of 300 rpm with light apical pressure ( recommended torque is 2.0 ncm , adjustable up to 5.2 ncm according to practitioner experience ) . flutes of the instruments were cleaned frequently to check any signs of distortion or wear . the ptn instruments are recommended to be used mechanically ( manually in very severe curvatures ) in a clockwise continuous motion with a brushing motion , away from external root concavities , to facilitate flute unloading and apical file progression . in all the experimental groups , sectioning of all the roots was done perpendicular to the long axis at 9 , 6 , and 3 mm using a diamond disc under water cooling . digital images of each sectioned root was captured using a 40 stereomicroscope by using a digital camera ( olympus , tokyo , japan ) . roots were classified as no defect , fracture , and other defects as described in table 1 . classification for identification of defects in the specimens the results were expressed as the number and percentage of defects in each group . chi - square test was used for the statistical analysis of the groups . the level of significance was set at p = 0.05 using statistical package for social sciences ( spss ) 20.0 . sectioning of all the roots was done perpendicular to the long axis at 9 , 6 , and 3 mm using a diamond disc under water cooling . digital images of each sectioned root was captured using a 40 stereomicroscope by using a digital camera ( olympus , tokyo , japan ) . roots were classified as no defect , fracture , and other defects as described in table 1 . classification for identification of defects in the specimens the level of significance was set at p = 0.05 using statistical package for social sciences ( spss ) 20.0 . figure 1 is a bar chart representing the number of root defects in each group . hfs group showed lowest defect ( 1/15 ) followed by pt ( 6/15 ) , hs ( 10/15 ) , and ptn ( 4/15 ) . statistical significant difference was seen between hfs and hs group and between hs and ptn groups ( p < 0.05 ) . no significant difference was found between the pt and hs ( p > 0.05 ) . bar chart representing number of root defects in each group the stereomicroscopic images of group i , ii , iii and iv are shown in figure 2 . stereomicroscopic images showing dentinal defects seen in groups i , ii , iii , and iv , showing craze lines seen in group i. fracture and other defects in group ii craze lines and partial crack in group iii and craze lines in group iv in the present study ; in hfs , pt , hs , and ptn , the number and incidence of defects observed in the root dentin was found to be 1/15 ( 6.67% ) , 6/15 ( 40% ) , 10/15 ( 66.67% ) , and 4/15 ( 26.7% ) , respectively . group i ( hfs ) showed the lowest incidence of defects ( 6.67% ) ; whereas , hs group showed the maximum incidence of defects ( 66.67% ) as compared to other groups . the results of our study are in accordance with imam , who reported lowest number of defects ( 1/20 ) by hfs ; and yold as et al . , observed highest incidence of defects ( 12/20 ) by hss rotary files . , in the present study the number and percentage of defects shown by the ptn rotary files were 4/15 , that is , 26.7% . the results of the present study are not in accordance with the results by bier et al . , where the hfs showed no defect and pt rotary files showed highest incidence of dentinal damage ( 16% ) . excess removal of root dentin during root canal preparation and obturation of the canal with spreader may create fracture in the teeth . the important goal in endodontics is resistance to tooth fracture because such fractures might cause decrease in the long - term survival rate . in the presents the number of rotations required for complete root canal preparation is more with niti rotary instruments than with the hfs . kim et al . , stated that taper of the files is the responsible for increase of stress on the walls of the root canal ; whereas , bier et al . , stated taper of the files as one of the contributing factor for crack formation in root dentin . pt have more taper ( 0.07 , 0.08 , and 0.09 , respectively ) than the hss ( 0.04 and 0.06 ) and the ptn ( x1 , x2 , and x3 ; 0.04 , 0.06 , and 0.07 , respectively ) . this explains that there can be formation of cracks in the pt group , as reported earlier by bier et al . , liu et al . , barreto et al . , and liu et al . furthermore , relatively low flexibility of the hs may have contributed to the maximum number of defects in hs group in the present study . rotational force is applied to the canals of the root by niti rotary instruments , thus creating craze line or microcracks in root dentin . formation of such defects may be associated with the design of tip , cross - sectional geometry , taper type ( constant or progressive ) , flute form , and pitch ( constant or variable ) . the pt files have a triangular cross - sectional geometry , hs having a triple helix cross - sectional geometry ; whereas , the ptn is rectangular . thus , it can be stated that design of the rotary files is not the only factor for defect formation in root dentin . lam et al . , stated that forces shaping the root dentin can be affected by the file design . risk of root fracture is increased due to the forces generated during the root canal preparation . ptn files have m - wire technology with off - centered rectangular cross - section , giving the file a snake - like swaggering movement as it moves along the root canal , thus reducing the screw effect , the unwanted taper lock , and torque on any of the given file ; thus decreasing the file - root dentin contact . m - wire alloy niti material with controlled memory niti wire are flexible than those made from conventional niti wire . thus , such flexibility of ptn rotary files may have contributed in less number of dentinal defects formation as compared to pt and hs . capar et al . , concluded that the swaggering motion and less taper of the ptn instruments could change the root canal volume to an extent as that of the higher tapered instruments . use of different speed and torque settings for each rotary system could be the limitation of our study . increase in the rotational speed is associated with increased cutting efficiency.simulation of periodontal ligament was not done in the present study . capar i d et al . stated that simulation of the periodontal ligament is necessary for investigating the influence of forces on formation of crack or fracture strength . it plays an important role in stress dissipation created by application of load to the teeth . use of different speed and torque settings for each rotary system could be the limitation of our study . capar i d et al . stated that simulation of the periodontal ligament is necessary for investigating the influence of forces on formation of crack or fracture strength . it plays an important role in stress dissipation created by application of load to the teeth . use of different speed and torque settings for each rotary system could be the limitation of our study . increase in the rotational speed is associated with increased cutting efficiency.simulation of periodontal ligament was not done in the present study . capar i d et al . stated that simulation of the periodontal ligament is necessary for investigating the influence of forces on formation of crack or fracture strength . it plays an important role in stress dissipation created by application of load to the teeth . use of different speed and torque settings for each rotary system could be the limitation of our study . capar i d et al . stated that simulation of the periodontal ligament is necessary for investigating the influence of forces on formation of crack or fracture strength . it plays an important role in stress dissipation created by application of load to the teeth . within the limitations of this in vitro study , ptn rotary system can induce less dentinal defects than pt and hs .

introduction : the objective of this study was to evaluate dentinal defects formed by new rotary system protaper next ( ptn).materials and methods : sixty single - rooted premolars were selected . all specimens were decoronated and divided into four groups , each group having 15 specimens . group i specimens were prepared by hand k - files ( mani ) , group ii with protaper universal ( pt ; dentsply maillefer ) , group iii with hero shaper ( hs ; micro - mega , besancon , france ) , and group iv with ptn ( dentsply maillefer ) . roots of each specimen were sectioned at 3 , 6 , and 9 mm from the apex and were then viewed under a stereomicroscope to evaluate presence or absence of dentinal defects.results:in roots prepared with hand files ( hfs ) showed lowest percentage of dentinal defects ( 6.7% ) ; whereas in roots prepared with pt , hs , and ptn it was 40 , 66.7 , and 26.7% , respectively . there was significant difference between the hs group and the ptn group ( p < 0.05).conclusion : all rotary files induced defects in root dentin , whereas the hand instruments induced minimal defects .

acute carbon monoxide ( co ) poisoning is an important clinical problem because of severe cardiovascular effects and a large proportion of fatal death . however , its severity and duration has not yet known.1 - 3 ) myocardial injury may occur as a consequence of moderate to severe co poisoning , mostly manifested as elevated cardiac biomarkers and the changes of regional wall motion abnormality in transthoracic echocardiography ( tte).4 ) however , there is a little data regarding the relationship between co poisoning and myocardial damage.3 ) left ventricular ( lv ) thrombus is not rare but well known complication of stress induced cardiomyopathy . however , its incidence and clinical significance in this stressful condition has not been well established . to the best of our knowledge , the present report is the first korean case of 66-year - old man with co poisoning induced cardiomyopathy accompanied by lv thrombus . a 66-year - old man was referred to the emergency room due to sudden onset of dyspnea with nyha iii - iv . physical examination revealed blood pressure 136/87 mmhg with a 1-year history of hypertension , body temperature 36.0 , heart rate 97/min , and respiratory rate 28/min . the initial electrocardiographic findings revealed sinus tachycardia with a heart rate of approximately 130/min , t wave inversion in ii , iii , avf and v3-v6 and diminished r waves in v1-v4 . laboratory findings on admission showed a marked elevation in the serum level of pro - brain natriuretic peptide of 18,699 pg / ml . also , cardiac enzymes were elevated to a troponin t of 0.88 ng / ml and ck - mb of 9.7 ng / ml , and arterial blood gas reveals ph 7.41 , paco2 26 mmhg , pao2 61 mmhg , hco3 16 mmol / l , sao2 92% , and the fraction of carboxyhemoglobin 20.2% ( reference range the tte done on the same day revealed akinesis at the apex of lv and lv ejection fraction of less than 30% ( fig . 1 ) . but the regional wall motion abnormalities extend beyond a single epicardial coronary distribution . coronary angiography recommended but the patient refused , so the 128-channel multidetector computed tomography ( mdct ) was conducted . he was transferred to the intensive care unit and provided oxygen for treatment of co poisoning . follow - up tte was done 7 days later , which showed a round thrombus ( 12 10 mm ) at the apex of lv ( fig . however , sufficient anti - thrombotic agents could not be administered because active gastric ulcer bleeding suddenly occurred on the next day . follow - up tte performed on the twenty - one day of admission revealed the full recovery of the regional wall motion of lv and complete resolution of thrombus at the apex of lv ( fig . the patient has been free of symptoms and there have been no clinical features of neurologic disorders or thromboembolic complications during the 6-months of clinical follow - up . the cardiovascular manifestations of co poisoning have been limited to case reports and presented variable type of myocardial dysfunction and injury . until recently , the various mechanisms have been proposed . myocardial injury from co poisoning results from tissue hypoxia as well as damage at the cellular level . the affinity of hemoglobin for co is 200 to 250 times greater than its affinity for oxygen . this results in competitive inhibition of oxygen release due to a shift in the oxygen - hemoglobin dissociation curve , reduced oxygen delivery , and subsequent tissue hypoxia.2)5 ) also , co may bind to heme proteins , including myoglobin and cytochrome c oxidase.6 ) and , it may bind to cytochrome c oxidase , which is an enzyme in the mitochondrial electron - transport system chain that produces adenosine triphosphate by catalyzing the reduction of oxygen to water.7 ) in a study by satran et al.,2 ) different clinical patterns of myocardial injury were found . the pattern seen in younger patients with few coronary risk factors but severe co poisoning was global lv dysfunction by tte , which improved or resolved . these patients had regional wall motion abnormalities suggesting that co poisoning unmasks underlying coronary artery disease by creating supply / demand mismatch.2)3 ) to our knowledge , this is the first korean case of acute co poisoning induced acute heart failure complicated with lv thrombus . however , stress induced cardiomyopathy associated with lv thrombus is not a rare but well known complication . de gregorio et al.8 ) reported that lv thrombus formation results in about 2.5% of all the patients with documented stress induced cardiomyopathy . in general , lv thrombus disappears together with or before lv functional recovery.8)9 ) we experienced a case of acute co poisoning induced transient lv dysfunction , which is apical ballooning form complicated with lv thrombus . the patient in this case has significant coronary artery disease , but he is fully recovered from segmental wall motion abnormality and lv thrombus within three weeks . in conclusion , although the optimal therapy for stress induced cardiomyopathy with lv thrombus is still unknown , the use of anticoagulant therapy in the acute phase and until complete resolution of wall motion abnormalities appears to be appropriate in patients with apical thrombus.8)9 ) because tte can evaluate rapid change in cardiac condition , frequent follow - up using this technique is recommended for patients with stress induced cardiomyopathy , especially when anticoagulant therapy is difficult .

the heart and the brain , most oxygen - dependent organs , may be severely affected after carbon monoxide ( co ) exposure . co induced cardiotoxicity may occur as a consequence of moderate to severe co poisoning , including angina attack , myocardial infarct , arrhythmias , and heart failure . we present a rare case of co poisoning induced cardiomyopathy with left ventricular ( lv ) thrombus . it is thought that lv thrombus may have been caused severely decreased lv function with dyskinesis . after short - term anticoagulant therapy , echocardiography findings revealed complete recovery of lv dyskinesis and resolution of lv thrombus .

the inferior vena cava ( ivc ) filter is an established therapeutic option for the prevention of pulmonary embolism in individuals with deep venous thromboembolism in whom conventional anticoagulation is contraindicated or deemed ineffective . the major complications associated with ivc filters include intravascular and extravascular migration , filter and venous thrombosis , recurrent pulmonary emboli and inferior vena caval obstruction . we report a case of transvenous migration of an ivc filter to the right atrium , which lead to a very unusual scenario of acute cardiogenic shock . a seventy - year old man with acute respiratory distress and fever was admitted to the intensive care unit ( icu ) coming from a rehabilitation center . the patient had suffered from a cerebrovascular accident ( hemorrhagic stroke ) subsequent to anticoagulation therapy for acute pulmonary embolism three months before . since hemorrhagic stroke is a well established contra - indication to oral anticoagulant therapy , the patient had undergone implantation of a vena cava filter to prevent new episodes of pulmonary embolism . on admission in the icu , the presence of hospital - acquired pneumonia with severe sepsis was strongly suspected , but patient s clinical conditions rapidly evolved into hemodynamic collapse with hypotension , cold sweating and hypoxia , in the absence of any evidence of lung infiltration at chest x - ray . a transthoracic echocardiography with both morphologic and functional evaluation was performed , showing massive tricuspid insufficiency with papillary muscle rupture and a suspected endocardial vegetation . immediately after , a transaesophageal echocardiography highlighted massive tricuspid insufficiency with leaflet rupture and lacked systolic closure due to reflective metallic structures trapping in valvular leaflets . a pericardial effusion without tamponade was also noticed ( figure 1 , figure 2 , and figure 3 ) . cardiogenic shock : bedside doppler echocardiographic assessment cardiogenic shock : bedside doppler echocardiographic assessment the suspected diagnosis of cava filter migration into cardiac cavity was confirmed by a chest - abdominal x - ray ( figure 4 ) which showed the presence of metallic elements in the right- heart and the concomitant absence of the cava filter in the cava district . following this evidence , the patient underwent open heart surgery . chest - abdominal x - ray confirming the appropriate diagnosis during surgery the tricuspid valve insufficiency with metallic fragments between leaflets was confirmed , along with the presence of 800 ml of blood in the pericardium due to the migration of the cava filter fragments through the interventricular septum and the right ventricular apex . the tricuspid valve and vena cava filter fragments were removed and a prosthetic tricuspid valve was implanted . we reported an insidious case of vena cava filter migration , clinically manifesting with signs and symptoms of cardiogenic shock . after dislocation , the filter was entrapped within the tricuspid valve and chordae tendineae , and surgical valve replacement became mandatory . intracardiac or intrapulmonary ivc filters migration is uncommon , and a total of nearly a hundred of episodes have been reported in literature . although unusual , vena cava filters migration is a potentially life - threatening event which requires a reliable and prompt diagnosis . for this reason , some instrumental tools are of crucial importance , starting from the hemodynamic monitoring . the type of hemodynamic monitoring performed in the icu depends on two elements : patient s clinical status and physician s experience . myocites stretching before systolic period , that s to say the ventricular volume after atrial contraction , in telediastolic phase . preload guides the treatment of hemodynamic impairment , the choice of fluids or inotropic drugs . other methods have been developed for preload evaluation . among these , the swan- ganz catheter ( pac ) is invasive , and requires a high learning curve . moreover , it lacks of a grade a evidence about reliability of the data and their impact on patient s outcome . other cardiac output monitoring systems have been developed during last years based on continuous and real - time analysis of systemic arterial pressure wave , stroke volume and stroke volume variation . in recent years , diagnosis - oriented treatment has supported the widespread use of echocardiography for the management of the hemodynamically unstable patients in the icu . current applications of echocardiography in critical care are represented by emergent diagnosis ( i.e. cardiac tamponade , papillary muscle rupture , massive pulmonary embolism ) and therapy , but it should not been underestimated also its role in the hemodynamic assessment [ 5 , 6 ] . indeed , bedside echocardiography is able to provide crucial information to decide on the following diagnostic steps and treatment . cholley and colleagues also suggested that every critical care physician should at least be able to perform a basic ultrasound examination of the heart when the aetiology of shock is not 100% clear , as echocardiography can be considered as a lifesaving tool . this case report showed how the echocardiographic assessment can be a life saving tool when an unusual cause of shock prompting quick and appropriate treatment is present . bedside echocardiography indeed allowed the intensivists to re - direct their diagnostic efforts toward the right cause of the shock sooner than the other monitoring strategies and with a valuable diagnostic accuracy .

dislocation and migration of the inferior vena cava filter to the right heart is an uncommon but serious complication , requiring prompt diagnosis and appropriate therapy . we report the case of a seventy - year old man , who had previously undergone vena cava filter implantation and who was admitted to the intensive care unit due to acute respiratory distress with the suspect of pneumonia - related sepsis . due to the worsening of hemodynamics and the development of cardiogenic shock , the patient underwent bedside echocardiography , which on the contrary revealed dislocation of the filter and the entrapment of the device within the tricuspid valve and chordae tendineae . this evidence was confirmed also by the chest - abdominal x - ray . the patient underwent tricuspid valve surgical replacement and successfully recovered . the transthoracic and transesophageal echocardiographies performed in the intensive care unit were able to first orient the diagnostic efforts toward the correct cause .

the smut fungus cintractia disciformis was originally described from a plant identified as carex hirtella ( sect . cintractia disciformis was first invalidly introduced without the mandatory latin description that was required from 1 january 1935 until 31 december 2011 ( liro 1935 ) . the species has only occasionally been reported in the literature , for instance in connection with a second finding on mt . sawi in indian kashmir on a new host , carex haematostoma ( ling 1949 ) , or in monographic studies on smut fungi ( zundel 1953 , zambettakis 1978 , piepenbring 2000 , vnky 2007a , 2012 , gandhe 2011 ) . ling ( 1949 ) and other authors have either repeated the description from the protologue ( zundel 1953 , gandhe 2011 ) , or not included one ( piepenbring 2000 , vnky 2007a , 2012 ) . in a monograph of anthracoidea , zambettakis ( 1978 ) proposed a new combination anthracoidea disciformis ( liro ) zambett . , but without giving any indication of the basionym or any reference to the place of its valid publication , rendering the combination invalid ( icn , art . vnky ( 2012 ) examined the type material of cintractia disciformis in h , and concluded that it was an anthracoidea . however , he did not accept the species or make any transfer to that genus as he noted that the host carex was not c. hirtella according to an annotation by i. kukkonen on the specimen . vnky commented that without the correct name of the host plant it can not be identified . aulocystis in the same geographical area of southern asia ( himalaya mts ) were described several decades later , anthracoidea nepalensis on carex nakaoana in nepal ( kakishima & ono 1988 ) and anthracoidea haematostomae on carex haematostoma in china ( guo 2006 ) . these two smuts were found to be conspecific by vnky & pitek ( in vnky 2007b ) and that treatment is followed in the monograph of vnky ( 2012 ) . this work aims to clarify the taxonomic status of cintractia disciformis and ascertain whether it is distinct from or conspecific with anthracoidea nepalensis ( incl . sori and spore characteristics were studied using dried herbarium material deposited in h , ibar and h.u.v . . the specimens were examined either by light microscopy ( lm ) and scanning electron microscopy ( sem ) or only by light microscopy ( lm ) . for light microscopy ( lm ) , small pieces of sori were mounted in lactic acid , heated to boiling point and cooled , and then examined under a nikon eclipse 80i light microscope . fifty spores were measured from each collection , using nis - elements br 3.0 imaging software . spore size ranges were assigned to one of the three groups distinguished by savile ( 1952 ) : ( 1 ) small - sized spores 1833 1328 m . unless otherwise stated , the spores were measured in plane view and measurements are adjusted to the nearest 0.5 m . for scanning electron microscopy ( sem ) , spores taken directly from dried herbarium samples were dusted onto carbon tabs and fixed to an aluminium stub with double - sided transparent tape . the stubs were sputter - coated with carbon using a cressington sputter - coater and viewed under a hitachi s-4700 scanning electron microscope , with a working distance of ca . sem micrographs were taken in the laboratory of field emission scanning electron microscopy and microanalysis at the institute of geological sciences of jagiellonian university ( krakw ) . sorus in one ovary of the inflorescence , black , ovoid , presumably around the achene , about 4 2.5 mm diam , composed of agglutinated spores , powdery on the surface , partly hidden by the perigynium and scales . spores small - sized , flattened , disc - shaped , chestnut - brown to reddish brown , regular in shape and size , in plane view globose , subglobose or broadly ellipsoidal , 16.518.5(19.0 ) ( 13.5)14.018.0 m [ av . sd , 17.6 0.6 15.7 1.2 m , n = 50 ] , in side view broadly ellipsoidal ( 8.5)10.012.0 m ( measurements without hyaline caps ) , usually enclosed by prominent mucilaginous sheath visible as hyaline caps on the flattened sides , up to 1.5 m wide ; wall even , 1.52.0 m , darker than the rest of spore ; surface finely papillate in lm , spore profile finely serrulate , surface sparsely papillate in sem , papillae up to 0.3 m high ( from sem micrographs ) , interspaces smooth . india : darma , nipchang , on carex plectobasis ( as c. hirtella ) , 31 aug . 3900 m , on carex haematostoma ( syn . c. nakaoana ) , 3 sept . 1986 , y. ono 86ne-223 ( ibar 0628 isotype of anthracoidea nepalensis ) ; elev . 3800 m , on carex haematostoma ( syn . c. nakaoana ) , 3 sept . 1986 , y. ono 86ne-214 ( ibar 0619 , paratype of anthracoidea nepalensis ) ; kyangjin , elev . 3800 m , on carex haematostoma ( syn . c. nakaoana ) , 4 sept . 1986 , y. ono 86ne-234 ( ibar 0639 paratype of anthracoidea nepalensis ) . hosts and distribution : on members of carex sect . aulocystis : carex digyna , c. haematostoma ( syn . c. nakaoana ) , and c. plectobasis ( syn . c. hirtella ) . known from china , india , and nepal . observations : while the host of cintractia disciformis is uncertain according to the annotation by ilkka kukkonen on the holotype ; re - identification of the specimen based on one inflorescence is difficult . however , the sedge definitely belongs to the section aulocystis , and the length of perigynia ( 5.06.5 mm ) indicates an affinity with carex plectobasis ( syn . c. hirtella ) according to the available keys and descriptions in the flora of pakistan and flora of china ( efloras , http://www.efloras.org ) . guo ( 1994 ) has also reported anthracoidea nepalensis on this host ( as carex hirtella ) . the host of anthracoidea nepalensis was reported as carex nakaoana , but this species is now considered synonymous with c. haematostoma ( chlebicki 2002 ) . yet another host of this smut is c. digyna listed in chinese reports of a. nepalensis ( guo 1994 , as digyne ) . vnky ( 2007b ) included the european sedge c. sempervirens in the list of hosts of a. nepalensis ; this was evidently a mistake , and the species was not cited as a host in his subsequent monograph ( vnky 2012 ) . carex sempervirens has to be excluded from the host range of a. disciformis . the internal structure of the sori is one of the main differentiating characteristics between anthracoidea and cintractia ( kukkonen 1963 , piepenbring 2000 ) . unfortunately this feature could not be examined in the holotype of cintractia disciformis without destroying the specimen . however , the hyaline caps on the spores preclude a placement in cintractia and support an affinity to anthracoidea . further , species of cintractia are not known to occur on carex , nor even members of the cariceae ( pitek & vnky 2007 ) . the internal sorus structure of anthracoidea nepalensis ( fig . 2 ) , regarded here as a synonym , is typical of anthracoidea species in that the spores are formed on the outer surface of the achene , and not within the u - shaped pockets embedded in the sterile stroma , a character of the genus cintractia ( kukkonen 1963 , piepenbring 2000 ) . this provides additional indirect evidence that cintractia disciformis is a member of the genus anthracoidea as indicated by zambettakis ( 1978 ) and vnky ( 2012 ) . the characteristics of the holotype of cintractia disciformis are included in the species description presented above and shown in the illustrations ( fig . the morphological details of specimens of anthracoidea nepalensis i examined were : sori globose or ovoid surrounding the achenes , about 1.53.0 long and 1.52.5 mm wide , spores disc - shaped , chestnut - brown to reddish brown , globose , subglobose , rarely broadly ellipsoidal or somewhat subangulate , ( 15.0)15.519.5(20.5 ) ( 12.5)14.018.0(19.0 ) m , the flattened sides of spores rarely enclosed by a hyaline mucilaginous sheath , spore wall even , 1.01.5(2.0 ) m , spore surface finely papillate , spore profile finely serrulate . the sem characteristics of spores of a. nepalensis ( kakishima & ono 1988 , chlebicki 2002 ) agree well with those of cintractia disciformis . the morphology of anthracoidea haematostomae was investigated by vnky & pitek ( in vnky 2007b ) to establish the synonymy between this species and a. nepalensis , although only the morphology of a. nepalensis was presented in the published results . however , the key morphological features of the material of a. haematostomae studied are : spores dark reddish brown , 17.522 1520 m ; spore wall even , 1.52.5 m thick , with hyaline caps , spore surface finely papillate , spore profile finely wavy . the spore ornamentation observed in sem ( guo 2006 ) also agrees well with that of cintractia disciformis . the morphology of cintractia disciformis , anthracoidea nepalensis and a. haematostomae is very similar , and the only differences concern the hyaline mucilaginous sheath . this sheath was less developed in the material of a. nepalensis , and the spores are somewhat larger and the spore wall slightly thicker in a. haematostomae compared to cintractia disciformis . however , these minor differences lie within the normal variability of a single anthracoidea species ( kukkonen 1963 , denchev 1991 , pitek & muenko 2010 , savchenko et al . in press ) . consequently , these three species names are considered as synonymous and the oldest available name , cintractia disciformis , is therefore taken up as a new combination , that proposed by zambettakis ( 1978 ) being invalid . the disc - shaped , papillate spores of anthracoidea disciformis are distinctive and rarely observed in other anthracoidea species that have verruculose or rarely smooth spores . this feature readily differentiates this smut from four other anthracoidea species infecting members of carex sect . a. altera , a. misandrae , a. sempervirentis , and a. stenocarpae ) . in the entire genus , only a few other anthracoidea species have disc - shaped and papillate spores , for example a. bistaminatae ( guo 2006 ) , a. lindebergiae ( vnky 1994 ) , a. mulenkoi ( pitek 2006 ) , a. pygmaea ( guo 2002 ) , a. royleanae ( guo 2006 ) , a. setschwanensis ( guo 2007 ) , a. smithii ( vnky 2007a ) , and a. xizangensis ( guo 2005 ) , all of which infect kobresia . an exception is a. lindebergiae , which is widely distributed in arctic and alpine ecosystems of the northern hemisphere . whether these anthracoidea species are closely related and have evolved from a common ancestor this study demonstrates that a critical evaluation of historical names could prevent an unnecessary proliferation of names proposed for the same organism . such taxonomical expertise appears even more urgent in the light of molecular initiatives , especially dna barcoding ( seifert 2008 , begerow et al . the molecular studies should be accompanied by a critical reassessment of as many historical names of fungal species as possible that can be linked to freshly collected specimens for use in molecular analyses ( lcking 2008 , hyde et al .

the identity of a neglected smut fungus , cintractia disciformis , described from carex hirtella in the western himalaya , india is reassessed . the species is excluded from cintractia and is confirmed as a distinct species of anthracoidea . two smuts , a. nepalensis on carex nakaoana in nepal , and a. haematostomae on carex haematostoma in china , are similar morphologically and considered to be later heterotypic synonyms of cintractia disciformis . the appropriate nomenclatural combination for this species , anthracoidea disciformis comb . nov . , is validated .

infertility is one of the crucial and critical events in sex life which engages 1015% of couples all over the world , and as one of the most distressful life experiences , exposes couples to social and psychological problems . couples , who are faced with this critical situation , are prone to depression , anxiety , loss of self - esteem and dissatisfaction with their sex life more than others . however , the intensity of psychological problems resulting from cultural - social circumstances varies in different societies , to the point that the frequency of anxiety in infertile couples has been reported in a wide range from 48% to 96% . although , the advances in assisted reproductive techniques have opened new doors for infertile couples , but studies have shown that these treatments are accompanied with stress , anxiety and depression . but the intensity of these disorders could be defined by the cause of the infertility . evaluating the related factors of depression and anxiety among iranian infertile couples showed that women who were infertile themselves showed higher levels of anxiety and depression than women with male factor infertility . however , in societies that define women as the main source of fertility , starting assisted reproductive treatments with limited successful outcomes could be harmful to these women 's mental health . utilization of assisted reproductive techniques requires processes such as daily injection to stimulate ovulation , vaginal ultrasound and painful processes such as oocyte aspiration which are all too expensive and alongside with the fear of failure could become a harmful condition . although , fertile women , who start assisted reproductive treatments due to their husband 's infertility have natural biological conditions to get pregnant , but they have to tolerate these critical processes due to male factor infertility . also , women are under more cultural and social pressures . these conditions could affect the vulnerability of fertile women during assisted reproductive treatment ; therefore the aim of this study was to evaluate the effect of assisted reproductive treatments on fertile women 's mental health . thus , the prospective study conducted on 70 fertile women who referred to receive assisted reproduction treatments ( in vitro fertilization / intracytoplasmic sperm injection ) due to male infertility . subjects had referred to the fertility and infertility center of esfahan from september 2013 to march 2014 . the number of samples was calculated based on 80% test power and 95% confidence level . inclusion criteria were primary infertility , not having any corporal and mental illnesses , not being a drug addict according to individual 's report , not having a history of mental illnesses , and not experiencing severe distress over 1-month prior to the treatment based on holmes - rahe scale . exclusion criteria included experiencing distressful conditions during the study , discontinuation of the treatment and the cancellation of egg harvesting . the study was approved by the medical ethics committee of the isfahan university of medical sciences . mental health evaluation tool was the valid 28-questioned general health questionnaire that measures mental health on likert scale ( 03 ) in hypochondriasis , anxiety , social impairment , and depression dimensions . in this method gaining the score of 5 in each subscale and 23 in all dimensions together was defined as having a mental disorder . sampling was conducted through simple sampling ; that is , all persons , who referred to fertility and infertility center of esfahan for treatment and to start the process protocol due to male factor infertility were interviewed . then by referring to their medical records and conducting holmes - rahe scale , their eligibility for the study was assessed . after being considered eligible for entering the study , their demographical features including age , educational level of couples , economic condition , and the duration of their infertility were recorded . ovulation was stimulated through the long protocol in all the participants . during the treatment period , ovarian reaction conditions and number of injections employed for ovarian stimulation were followed - up . 3 h after the pickup process , and under appropriate circumstances , the questionnaire for general health was completed again . if the circumstances were inappropriate filling of the questionnaire was delayed for 2 h. research data were analyzed using spss software version 16 [ spss inc . : chicago , il , usa ] , statistical paired t - tests and multi - variable linear regression tests . seven qualified subjects quit the study because of the unwillingness to continue ( three persons ) and ovarian hyper stimulation ( four persons ) . demographic and clinical data results showed no significant difference in the mean score of different dimension of mental health before ovulation induction and after oocyte harvesting [ table 2 ] . also , the rate of psychological disorder in the anxiety dimension showed no significant different before the induction ( 71.4% ) and after the pickup ( 66.7% ) ( p = 0.19 ) . but the level of depression after pickup ( 31.7% ) was significantly lower than before the induction ( 39.7% ) ( p = 0.007 ) . comparison of mental health dimensions b and a results showed no significant difference in the dimension of hypochondriasis before the induction ( 61.9% ) and after the harvesting ( 66.7% ) ( p = 0.07 ) . also , the level of social impairment showed no significant difference before the induction ( 84.1% ) and after the pickup ( 87.3% ) ( p = 0.08 ) . the results of multi - variable linear regression to evaluate the relation between underlying variables and mental health condition before starting the process with the level of depression and anxiety after the harvesting are shown in table 3 . the relation between mental health dimensions and background variables after ovulation stimulation the level of depression after egg harvesting was related to physical condition , depression and social impairment , independent from underlying variables . also , the level of depression after egg harvesting was related to the economic condition , it also showed a significant relation with social impairment and hypochondriasis [ table 3 ] . the present study aimed to assess the level of mental health in fertile women undergoing assisted reproductive treatments as a result of male factor infertility , at the beginning of ovulation stimulation process , and the effect of this process on their mental health . results showed that these women do not start assisted reproduction treatment under appropriate mental health conditions . but the level of depression and anxiety disorders at the beginning of ovulation stimulation was higher in the present research than other reports . this would indicate that the process of treatment in fertile women is also a critical one and might affect their mental health . in a pursuit , to achieve a conceptual model for the effect of ovulation induction on women 's health , its negative effects on women 's functioning and health have been shown . a qualitative study showed that iranian infertile couples show emotional reactions such as fear , concern , anxiety and depression as a result of fear of the failure of treatment during fertility treatment . however , these mental disorders may be harmful even for women with appropriate fertility potentials . also being angry with their husbands due to their infertility could be another explanation for women 's mental reactions . positive correlation between the level of depression and anxiety and other dimensions of experiences during infertility treatment might be accompanied with social impairment , thus affecting the levels of depression and anxiety . efforts to conceal infertility and efforts to get treatment as a result of concerns about being labeled as infertile , are common among iranian couples . this , by itself , could increase the level of anxiety among women when treatment starts . another reason for the high level of depression and anxiety among women at the beginning of the ovulation stimulation might be the negative impact of gonadotropin - releasing hormone ( gnrh ) agonists on the mental health . although , this research did not evaluate mental health before and after the beginning of gnrh agonists , but this might explain women 's psychological disorders before ovulation stimulation regarding high frequency of mental disorders at the time of ovulation stimulation . with regards to the negative impact of anxiety and depression during the treatment on the result of assisted reproduction treatment , it is necessary that this group of women would be examined before the treatment process , since they are exposed to risks of mental health disorders , and be treated in case of high levels of depression and anxiety . following the assessment of the main hypothesis of the research , that is the effect of ovulation stimulation on women 's mental health , study results showed that ovulation stimulation does not affect mental health ; the level of depression and anxiety , and the measure of psychological disorders in these two - dimensions did not show a significant difference before the ovulation and after the harvesting process . on the contrary , the depression level was decreased after the harvesting process . the negative impact of distress of infertility treatment on the level of depression has already been reported . the cessation of treatment distress with the conclusion of ovulation stimulation and harvesting processes might be a reason for the decrease of depression level in subjects under study . furthermore , results showed that fertile women 's level of depression and anxiety does not depend on the reaction of the ovary to the ovulation stimulation , and as these women have no problem in ovarian response to ovulation stimulation , their mental health depends more on other factors . in addition , all subjects , who sustained the research were those who reached the stage of the harvesting process ; the potential for ovum production was proven for these women . this would enhance the self - esteem of subjects and decrease their concern over ovarian nonresponsiveness . but direct correlation between the level of anxiety and depression in the stage after harvesting process with social impairment and hypochondriasis indicates that in this stage also the awareness of social dysfunction , independent from financial status , will have its own effect on mental health . factors other than ovulation stimulation process which might influence the individuals levels of depression and anxiety have not been assessed in the present research . depression and anxiety might result from a variety of factors , which require more extensive research . another result of this research was that financial status , independent from the quantity of follicle obtained from ovulation stimulation , showed a reverse correlation with anxiety level after harvesting process . in ozken 's research , also financial status was a factor determining the anxiety in infertile couples . regarding financial pressures resulting from high costs of assisted reproduction treatments , which lead to the success of only 35% for each cycle , women 's concerns over the success of results in fertilization as an outcome of infertility of the partner detected after harvesting process while insemination in laboratory are not far from expectation . nevertheless , although women are healthy in terms of fertility in couples undergoing male factor infertility treatment , effort to have babies not by normal methods and facing difficult , costly treatment protocols might threaten their evaluation of their feminine role , thus reducing their self - esteem . another finding of this research was the existence of correlation between depression level after treatment process and anxiety level at the first stage , while this correlation was observed between depression level after treatment process and anxiety level at the second stage . this finding indicates that women , who enter the process of treatment with a higher anxiety level are prone to a higher level of depression ; therefore necessary measures should be taken to prevent it . one of this study 's limitations was that mental health assessment was conducted after starting the primary stages of the treatment therefore , the stress of this stage could affect the mental health during the whole process . this study showed that fertile women who undergo assisted reproduction treatments do not start the treatment process in an appropriate mental health condition , and this condition would continue during the whole process until egg harvesting . therefore , it is suggested that before starting the treatment the mental health of these women should be evaluated using screening tools and counseling sessions would be applied for vulnerable women .

introduction : the process of assisted reproductive treatment is a stressful situation in the treatment of infertile couples and it would harm the mental health of women . fertile women who started infertility treatment due to male factor infertility have reported to experience less stress and depression than other women before the assisted reproductive process but considering the cultural and social factors and also the etiology of the assisted reproductive process , it could affect the metal health of these women . therefore , this study was conducted to evaluate the mental health of fertile women who undergo assisted reproductive treatment due to male factor infertility.materials and methods : this study was a prospective study on 70 fertile women who underwent assisted reproductive treatment due to male factor infertility . the exclusion criterion was to stop super ovulation induction . to assess mental health , anxiety and depression dimensions of the general health questionnaire were used . before starting ovulation induction and after oocyte harvesting , the general health questionnaire was filled by women who were under treatment . data were analyzed using multi - variable linear regression , paired t - test , and chi-square.results:the results showed that the mean score of depression and anxiety before ovulation induction and after oocyte harvesting were not significantly different ; but the rate of mental health disorder in the depression dimension was significantly decreased after oocytes harvesting ( 31.7% vs. 39.7% ) . also , there was a significant relation between the level of anxiety and depression before ovulation induction and after oocyte harvesting ( p < 0.05 ) . the anxiety level after oocyte harvesting had a positive and significant correlation with the economic situation ( p < 0.05).conclusion : this study revealed that the process of assisted reproductive treatment does not affect the mental health in fertile women independently , but these women start assisted reproductive process with high levels of depression and anxiety . therefore , prior to the assisted reproductive treatment mental health consultation is needed .

cholera case - patients were identified from updated lists from juba county s 5 cholera treatment centers ( ctcs ) , 2 of which were located in camps for internally displaced persons ( idps ; i.e. , persons who have left their homes but stayed within their country s borders ) . preventive oral cholera vaccination was conducted in the 2 idp camps before the outbreak began in juba . a case - patient was defined as a juba county resident > 2 years of age who 1 ) had an acute illness characterized by > 3 loose , watery stools within 24 hours or 2 ) was confirmed to be positive for v. cholerae infection by rapid diagnostic testing or culture during the cholera outbreak that began in juba county on april 23 , 2014 . for cholera case - patients enrolled in the study , a control matched by neighborhood , sex , and age was identified and invited to participate in the study . the study team traveled to the case - patient s village and worked with the local village leader or a social mobilization volunteer to identify a matching control from a household within a 100-m radius of the case - patient . a control was a juba county resident > 2 years of age with no history of clinical illness or no laboratory evidence of v. cholerae infection during this cholera outbreak . to match case - patients and controls by age , age groups of 35 years ( e.g. , 24 , 59 , and 6569 years of age ) were used . a team of 19 trained research assistants administered a pretested , semistructured questionnaire and conducted environmental assessments to evaluate the use of safe drinking water , improved sanitation facilities , personal and food hygiene , and oral cholera vaccination . using epi info ( centers for disease control and prevention , atlanta , ga , usa ) , we calculated matched unadjusted and adjusted odds ratios by using bivariate and multivariate models , respectively , to identify risk factors for cholera . a total of 134 matched pairs of case - patients and controls were enrolled in the study during june 26july 29 in 2014 ( figure ) . of the 134 case - patients enrolled , 9 were confirmed by culture and 104 by a cholera rapid diagnostic test ( onsite rapid test ; ctk biotech , san diego , ca , usa ) ; the remaining 21 were identified by epidemiologic linkage ( i.e. , a resident of juba > 2 years of age with > 3 loose stools in 24 hours after the beginning of the cholera outbreak ) . mean delay between admission to the ctc and interview after enrollment in the study was 21 days ( range 055 days ) ; most case - patients who were interviewed were admitted during the peak transmission phase of the outbreak ( figure ) . the distribution of age , sex , residence of origin , education level , and occupation were comparable among case - patients and controls ( table 1 ) . most ( 118 [ 88% ] ) case - patients enrolled in the study visited the ctc within 1 day of onset of cholera symptoms . all 134 patients had diarrhea ; 112 ( 84% ) had vomiting ; 45 ( 34% ) had abdominal cramps ; 37 ( 28% ) had some dehydration ( i.e. , any 2 signs of dehydration , including 1 major sign ) ; and 31 ( 23% ) had severe dehydration ( 23% ) . timeline showing number of cholera cases ( total cases = 2,260 ) , deaths from cholera ( total deaths = 43 ; case fatality rate 2.0% ) , and dates of study for cholera outbreak in juba county , south sudan , epidemiologic weeks 1743 ( april 23october 20 ) , 2014 . bivariate and multivariate analyses showed that persons who ate food outside their home before illness onset and those who traveled outside their home village ( even within the county ) before illness onset were significantly more likely to develop cholera ( table 2 ) . conversely , treating drinking water at home and receiving > 2 doses of oral cholera vaccine ( self - reported ) were protective against cholera ( table 2 ) . eating outside the home as a risk factor in this cholera outbreak popular eating places in juba county included roadside food vendors and restaurants in markets that did not meet minimum food hygiene standards yet remained open during the outbreak because public health inspection of eating establishments and a ban on roadside food vending were not uniformly enforced . our study identified recent travel to cholera outbreak areas as a risk factor , also a finding consistently associated with cholera spread to new locations during previous cholera outbreaks ( 10 ) . * the first 2 factors increased risk for cholera , whereas the other 2 factors decreased risk . or , odds ratio . travel from home to any area affected by cholera during the 2014 outbreak in south sudan . self - reported . also , as reported in previous cholera outbreaks in south sudan , uganda , haiti , and zimbabwe , household chlorination of drinking water was associated with significantly lower risk for developing cholera in our study ( 7,8,9,11 ) . in our study , water samples from case - patient households that did not chlorinate their drinking water showed evidence of contamination with fecal coliforms ( > 10 counts/100 ml ) . similarly , water samples from water storage vessels in 2 case - patient households that did not treat their drinking water were contaminated with fecal coliforms ( > 10 counts/100 ml ) . we found that oral cholera vaccination was associated with a significantly reduced risk of cholera infection and a vaccine effectiveness of 90% ( table 2 ) . these limitations include underreporting of high - risk behaviors , recall bias , potential misclassification of asymptomatic case - patients , narrow age ranges that caused difficulty in identifying matching controls , shared environmental risk factors ( e.g. , shared water source ) for case - patients and controls , unmeasured variables ( i.e. , factors not measured in this study , such as being an idp ) , and loss of oral cholera vaccination cards ( i.e. , vaccinations were self reported ) . for this cholera outbreak in south sudan , we found that travel and eating outside the home were risk factors for becoming ill and that treating drinking water at home and getting oral cholera vaccination provided protection against illness . for cholera prevention and control in humanitarian crises , we recommend that global oral cholera vaccine stockpiles be enhanced so that preventive oral cholera vaccination can be used to augment traditional interventions , such as improved access to safe drinking water and public education about risk factors .

we conducted a case control study to identify risk factors for the 2014 cholera outbreak in juba county , south sudan . illness was associated with traveling or eating away from home ; treating drinking water and receiving oral cholera vaccination were protective . oral cholera vaccination should be used to complement cholera prevention efforts .

ectopia cordis is defined as complete or partial displacement of the heart outside the thoracic cavity . it is a rare congenital defect with failure of fusion of the sternum with extra thoracic location of the heart . we had a case of a 16-hour - old male neonate weighing 2.9 kg with externally visible , beating heart over the chest wall . initial treatment included covering the heart with sterile - saline soaked dressing , starting systemic antibiotics and supportive care . a staged surgical approach to this defect with the initial aim of replacement of the heart to the thoracic cavity was opted . the neonate died twenty minutes after the surgical intervention due to cardiogenic shock despite adequate resuscitative measures . this case report underscores the missed opportunity of antenatal ultra - sonographic diagnosis and the challenge of ectopia cordis treatment in ethiopia . ectopia cordis ( ec ) is one of the rare congenital anomalies characterized by complete or partial displacement of the heart outside the thoracic cavity . the estimated prevalence of ec is 5.5 to 7.9 per million live births ( 1 ) . prenatal diagnosis is established by ultrasonography by visualizing the heart outside the thoracic cavity ( 25 ) . pentalogy of cantrell is considered when a combination of thoracoabdominal ec , anterior diaphragmatic hernia , lower sternal defect and midline supraumblical defect occurs . although surgical techniques have evolved , the prognosis and survival are limited ; thoracic type has the worst prognosis while the thoracoabdominal ec has a better prognosis ( 68 ) . an ec case neonate was seen and intervened at hawassa university referral hospital , hawassa , ethiopia . a 16-hour - old , vaginally delivered full - term male neonate , born to a 29 years old para iv mother was referred from a primary hospital after exposed beating heart was found over the chest wall with the patient experiencing difficulty of breathing . there was no history of consanguinity , infection , radiation , drug or any known herbal exposure . physical examination showed a full - term neonate of 40 weeks with heart rate- 124/ min , respiratory rate- 60/min and spo2 - 77% . the upper sternum was deficient with the heart lying outside the thoracic cavity and without pericardial protection with cephalic orientation of its apex ( figure 1 , figure 2 ) . laboratory test revealed : hemoglobin- 19g / dl , total leukocyte count- 20.5 10/ml , differential count : l-25.5 % , p-64.3 % , platelets count- 17310/ml , blood group of o + ve and imaging studies were not done . lateral view of the ectopia cordis neonate frontal view of the ectopia cordis neonate the patient was kept in a temperature regulated room . initial prompt treatment included covering of the heart with sterile - saline soaked dressing , systematic treatment and supportive care . then , a staged surgical approach to this defect with the initial aim of replacement of the heart to the thoracic cavity was chosen . the neonate died twenty minutes after the surgical intervention due to cardiogenic shock despite adequate resuscitative measures . ec is a rare congenital abnormality with reported point prevalence of 5.5 to 7.9 per million live births ( 1 ) . the burden of the disease is inadequately known in africa due to limited reports ( 25 ) . it is classified into cervical , thoracic , thoracoabdominal and abdominal ( 6 ) . only few patients with thoracic type have survived and the thoracoabdominal ec has a better prognosis . thoracic ec was explained embryonically by the rupture of the chorion at 3 weeks of gestation with resultant compression of the thoracic cavity and failure of descent of the heart at this stage . ec may occur in isolation or in association with other ventral body wall defects ( 7 ) . antenatal ultrasound during the first trimester helps in the diagnosis of ec . in our case , ec was diagnosed postnatally after a home delivered neonate was brought to our hospital ( 2,3,9 ) . there was no history of consanguinity , similar history or any congenital heart disease in our case . although the genetic causes for ec are not exactly known , certain associations with chromosomal abnormalities have been reported ( 7 ) . survival of thoracic ec case is limited despite advances in care , and its management is challenging . aggressive surgical procedures are recommended to increase the survival ( 7,10 ) . in our case report , death occurred within twenty minutes of the initial surgical intervention . earlier studies showed a lethal course of the thoracic ec . in conclusion , this report underscores the missed opportunity of antenatal ultrasound diagnosis and the challenges in the management of ec in ethiopia .

backgroundectopia cordis is defined as complete or partial displacement of the heart outside the thoracic cavity . it is a rare congenital defect with failure of fusion of the sternum with extra thoracic location of the heart . the estimated prevalence of this case is 5.5 to 7.9 per million live births.case presentationwe had a case of a 16-hour - old male neonate weighing 2.9 kg with externally visible , beating heart over the chest wall . initial treatment included covering the heart with sterile - saline soaked dressing , starting systemic antibiotics and supportive care . a staged surgical approach to this defect with the initial aim of replacement of the heart to the thoracic cavity was opted . the neonate died twenty minutes after the surgical intervention due to cardiogenic shock despite adequate resuscitative measures.conclusionthis case report underscores the missed opportunity of antenatal ultra - sonographic diagnosis and the challenge of ectopia cordis treatment in ethiopia .

push - ups are used for many purposes , including strengthening the upper body , rehabilitating the shoulder , stabilization training of dynamic joints , and improving proprioceptive feedback mechanisms1 , 2 . among the various exercises that are generally used to strengthen the shoulder and upper extremity muscles , the push - up is classified as a closed chain exercise and is used to strengthen the pectoralis major , triceps brachii , and shoulder stabilizing muscles3 . recent studies have examined the effects of variation in the push - up position , including rotation of the hand / wrist , different distances between the palms , changing the height of the legs , and performing push - ups on an unstable surface4 . despite the many advantages of the exercise , push - ups also have negative consequences , such as low - back pain , because the push - up position places much resistance on the trunk muscles , which can place a huge load on the lumbar vertebrae5 . changing the push - up position can affect the abdominal and vertebral muscles and lumbar angle and load5 . therefore , the purpose of this study was to compare the activity of the shoulder and trunk muscles in two push - up positions : standard push - ups and push - ups with the trunk flexed . fifteen young adult males with no history of musculoskeletal disorders or pain associated with the upper or lower extremities in the past 6 months participated in the study . their average age , height , and weight were 21.2 2.4 years , 173.1 5.13 cm , and 62.27 5.26 kg , respectively . the study was approved by the inje university faculty of health science human ethics committee , and the subjects provided written informed consent before participating . electromyography ( emg ) data were collected using a biopac mp150wsw ( biopac systems , santa barbara , ca , usa ) . all emg signals were amplified , band - pass filtered ( 20450 hz ) , and sampled at 1,000 hz using acqknowledge ver . the root mean square values of the raw data were calculated for 250 samples , with the amplitude normalized to the maximum voluntary isometric contraction . we measured the clavicular and sternocostal portions of the pectoralis major , the serratus anterior , and the rectus abdominis on the right side during push - ups under two conditions : the standard position with the body forming a straight line ( condition 1 ) and the experimental position with the waist flexed at 30 ( condition 2 ) . subjects placed their feet horizontally on a wooden scaffold and assumed the push - up position by grabbing a push - up bar with their hands at shoulder width . each push - up consisted of lowering the body over a period of 2 seconds and returning to the start position over another 2 seconds . the mean value of muscle activity during the 2 seconds when returning to the start position was analyzed from the emg data . the paired t - test ( spss ver . 18.0 ; chicago , il , usa ) was used to analyze differences in the normalized emg muscle activity of the right clavicular and sternocostal portions of the pectoralis major and the triceps brachii , serratus anterior , erector spinae , and rectus abdominis muscles between conditions 1 and 2 . the activity of the sternocostal portion of the pectoralis major and that of the rectus abdominis were significantly greater under condition 1 than under condition 2 ( p < 0.05 ) . in contrast , the activity of the clavicular portion of the pectoralis major and that of the serratus anterior were significantly greater under condition 2 compared with condition 1 ( p < 0.05 ) ( table 1table 1 . comparison of emg data between the 2 conditionsmusclesmean sd ( % mvic)condition 1condition 2cpm79.118.084.317.4*spm64.518.3 * 55.223.4sa45.519.457.424.4*ra21.814.5 * 15.112.0 ) . we found that the activity of the clavicular portion of the pectoralis major and that of the serratus anterior was significantly greater when the push - up was performed with the trunk flexed . the serratus anterior plays an important role in the stability of the scapula , and several studies have examined various exercises for selectively strengthening this muscle6 , 7 . in the push - up with the trunk flexed , the weight of the upper extremity is directly loaded on the serratus anterior as the center of the upper body is moved forward . thus , performing a push - up with the trunk flexed significantly increases the activity of the clavicular portion of the pectoralis major , whereas in a traditional push - up , the activity of the sternocostal part of the pectoralis major is significantly greater . these results indicate that exercises can selectively activate muscle parts under different clinical situations . excessive hyperlordosis is said to be the main cause of positional pain , facet joint pain , and nerve root disease8 , and the abdomen and back muscles affect pelvic tilt and lordosis8 . because the abdominal muscles originate from the iliac crest and pubic symphysis and insert at the xiphoid process of the 5th to 7th rib cartilage , posterior pelvic tilt is possible , which alters the lumbar intervertebral curve9 . in a traditional push - up , the activity of the rectus abdominis is significantly greater than that in the push - up with the trunk flexed . we found that push - ups with the trunk flexed decreased the resistance of the abdominal muscle needed to maintain position compared with a traditional push - up by controlling excessive extension of the lower back . push - ups with the trunk flexed are required to improve shoulder flexion posture , so physical therapists should pay attention to this when treating shoulder pain patients .

[ purpose ] the purpose of this study was to compare the activity of the shoulder and trunk muscles in two push - up positions : standard push - ups and push - ups with the trunk flexed . [ subjects ] fifteen young adult males participated in the study . [ methods ] this study measured the clavicular and sternocostal portions of the pectoralis major , the serratus anterior , and the rectus abdominis during push - ups under the two conditions . [ results ] the activity of the sternocostal portion of the pectoralis major and that of the rectus abdominis were significantly greater under condition 1 than under condition 2 . the activity of the clavicular portion of the pectoralis major and that of the serratus anterior were significantly greater under condition 2 compared with condition 1 . [ conclusion ] these results indicate that exercises can selectively activate muscle parts under different clinical situations .

nowadays , context - specific changes in gene expression levels can be easily monitored on a genome - wide scale by using microarray analysis and serial analysis of gene expression , but the molecular mechanisms and the specific transcription factors ( tfs ) that drive those specific changes remain unknown in most cases . identification of the components and mechanisms of signaling pathways is a slow process that inevitably involves a strategy of trial - and - error . therefore , in silico prediction of the components before and during the identification process is highly desirable . in silico approaches estimate that there are about 2000 human tfs ( 3 ) , of which about 800 have been characterized to varying degrees . for many of them , information on dna - binding sites is available , allowing the modeling of binding characteristics to a reasonable extent . the most commonly used model for tf binding specificity is the position weight matrix ( pwm ) , although it does not account for potential position dependencies within a transcription factor binding site ( tfbs ) ( 4 ) . when a pwm or even a more advanced model such as a hidden markov model ( hmm ) is used to predict binding sites for a specific tf , the results include a very large proportion of false positives . the reason is that tfbss are very short , often between 6 and 15 nt , and tolerate relatively high degrees of degeneracy in the sequence . the use of orthologous sequences to find conserved and , therefore , potentially functional tfbss is called phylogenetic footprinting . this in silico technique is commonly and successfully used in combination with the pwm model to reduce its rate of false positive predictions . the main difficulties of this kind of approach lie in correct aligning regulatory elements in promoter sequences that might have diverged a lot during evolution ( 5 ) . comparison of predicted tfbss in one species with those of other species is not only used to reduce the number of false positive predictions , but also can be a goal in its own right . it is now widely accepted that many differences in animal morphology are due to specific changes in sequences that control gene expression , especially during development ( 6 ) . consequently , one expects to find important differences between species in the presence and position of tfbss . conservation of a tfbs among several species observed in a multiple alignment is not proof that it is functional . neither is the conservation of a tfbs required for functionality , because differences between species are at least as biologically important as the similarities furthermore , the apparent lack of conservation might not have biological reasons , but could result from incorrect alignment . thus , although systematic hard conclusions are extremely difficult to make , proper display of predicted sites in several possible alignments would certainly be of help to the biologist seeking to generate or support a hypothesis . despite the availability of a number of web tools that offer phylogenetic footprinting together with some visualization interface , the biologist at the bench still lacks a compact and user - friendly tool that suggests answers to a regularly recurring question . contra , the web tool presented in this article , offers interactive visualization of all predicted sites for selected tfs on aligned sequences of orthologous promoters . furthermore , a simple scoring analysis can be applied before visualization to identify the tfs that are most likely to bind the promoter(s ) of interest . contra enables easy and fast look - up of all known transcripts related to the human gene(s ) or transcript(s ) of interest , given by gene name , gene symbol , ensembl gene i d , entrez gene i d , refseq transcript i d or ensembl transcript i d . the results are fully linked to ncbi ( http://www.ncbi.nlm.nih.gov/ ) , ucsc ( http://genome.ucsc.edu/ ) and ensembl ( http://www.ensembl.org/ ) . transcripts are grouped according to transcription start site ( tss ) , and each group can be analyzed separately . this important feature of contra differentiates it from most other web tools that provide only one promoter per gene for analysis . the potential importance of alternative promoter regulation is exemplified by an alternative promoter of the dicer1 gene . the tss of the dicer1 transcript nm_030621 , predominantly expressed in breast tissue ( 7 ) , is positioned more than 16 kb upstream from the tss of the transcript nm_177438 , which has been reported to be predominantly expressed in several other tissues ( 8) . it is very likely that some important differences in the spectrum of tfbss between the two promoters are causing the observed transcript proportion differences in different tissues , and contra could help to start exploring these differences . the transcriptional regulation of the dicer1 transcripts is further discussed in the supplemental data document nr 1 . for every group of transcripts that has been selected , available qualitative pairwise and multiple alignments on man from ensembl or ucsc are offered to choose from , and they can be retrieved by simple selection . offered alignments include the multiz 17-way and 28-way multiple alignments from ucsc ( 9,10 ) . the 28-way alignment has been produced recently and has been proven powerful for exploring vertebrate and mammalian evolution ( 11 ) . other offered alignments are the pecan ( http://www.ebi.ac.uk/~bjp/pecan/ ) 7-mammals and 10-amniota - vertebrates multiple alignments from ensembl . the pecan algorithm has been shown to be one of the best algorithms in terms of specificity and sensitivity ( 12 ) . contra also offers most available pairwise blastz - net alignments on man from ucsc ( 13,14 ) . the premade alignments offered by contra always have the human promoter sequence as the reference sequence because in our experience these alignments are the most frequently asked for . however , users can upload in fasta format their own alignment files with any other reference species . we also plan to enable the upload of own pwms in order to expand the series of tfs for which predicted binding sites can be visualized . vertebrate pwms from the most recent versions of transfac ( 1 ) or jaspar ( 2 ) . we have chosen to visualize tfbss predicted by the simple , often used pwm system as is . restricting the predicted tfbss to only those that are phylogenetically conserved or taking into account extra features such as clustering tendency ( 15 ) or distance from tss ( 16 ) would produce less false positive predictions . however , these filters would also , respectively , create a bias of the true positive predictions towards conserved tfbss or towards tfbss that meet the theoretical assumptions of models developed with too little experimental data . prediction of tfbss must and can be improved a lot , but much more experimental data needs to be really available , not just dispersed throughout scientific literature . recently a few databases were designed that are suitable to contain complex regulatory data , namely oreganno and pazar ( 17,18 ) , and biologists are strongly encouraged to deposit their regulatory findings in these databases . the parameters that can be set are the length of upstream promoter sequences and the thresholds for pwms that correspond to the stringency to be used when predicting tfbss . the visualization of predicted tfbss in html allows javascript user interaction that is similar to the interaction provided by jalview , a freely downloadable java alignment editor ( 19 ) . it also facilitates observation of potential coincident binding of several tfs and hence possible coregulation . files needed for customized jalview visualization , which is suitable for publication purposes , are provided as well . contra provides links to experimentally defined binding sites in the selected promoter region when these are available in oreganno ( 17 ) . more contra visualizations of experimentally proven tfbss are linked from the contra doc page at http://bioit.dmbr.ugent.be/contra/contradoc.php#examples . figure 1.visualization of the predicted tfbss for tfs ap-2 , ccaat box , e - box and gc box in the multiz 28-way alignment of the promoter of the e - cadherin transcript nm_004360 . visualization of the predicted tfbss for tfs ap-2 , ccaat box , e - box and gc box in the multiz 28-way alignment of the promoter of the e - cadherin transcript nm_004360 . the other part of contra , the exploration part , predicts which tfs are most likely to bind to the given promoter sequence(s ) . this prediction is done by using a simple , intuitive but effective score that takes into account the number of predicted binding sites , the extent of phylogenetic conservation , the distance from the tss , the proportion of conserved predicted tfbss and the information content ( ic ) of the predicting pwm . this likelihood score for promoter regulation is calculated for each pwm from both transfac and jaspar ( core and phylofacts ) . for every promoter sequence , the top 100 best ranked pwms are given , a selection of which can be directly forwarded to the visualization part . predicting which tfs regulate the exploration part is mainly intended to give an idea of which tfs are more likely to bind to the promoter and thus to indicate the pwms for which visualization of predicted tfbss could be interesting . in the supplemental data document most experimentally defined tfbss described in the literature are ranked at the top of the full list delivered by the contra exploration . the second example uses the promoter of mx1 ( myxovirus resistance 1 ) , which has two interferon - stimulated response element ( isre ) sites known to be crucial for its expression . the pwms corresponding to tfs that bind to isre sites appear in the top of the resulting list . the third example considers the exploration of the promoter of the dicer1 gene , for which , as far as we know , no transcription regulation experiments have been described in the literature . those results are intriguing in that they might be correlated with recent findings showing that mirnas involved in cancer are regulated by tfs already known to play a role in cancerous processes ( 21 ) . several other web tools provide information about tfbss predicted by pwms ( or hmms ) in the context of ( multiple ) promoter alignments . the supplemental data document nr 2 lists those web tools with their features we think contra competes well with the other tools in this list as it is a compact and user - friendly web tool that provides the biologist at the bench with useful visualization of predicted tfbss in a cross - species alignment context . contra works per alternative promoter and is flexible with respect to promoter length , alignment type and pwm prediction stringency . also important are the up - to - date pwm libraries of transfac and jaspar . making input user - friendly was accomplished by the integration of resources from hgnc ( 22 ) , ucsc and ensembl . golden path of ucsc ( http://hgdownload.cse.ucsc.edu/goldenpath/hg18/ ) and the program axtandbed from the ucsc genome browser source code , or by perl scripts using the ensembl compara perl api . the pwm libraries used by contra contain 101 vertebrate matrices from the latest jaspar core database , 174 matrices from jaspar phylofacts database and a nonredundant selection of 214 matrices from one of the latest transfac database versions ( 11.4 ) . jalview ( 19 ) is used to create an overview picture of each promoter alignment , whereas the dynamic view of predicted tfbss in the html - embedded promoter alignments is accomplished by javascript changing css properties . the likelihood score for promoter regulation of each pwm in the exploration part is obtained by an accumulation of the weights of its predicted tfbss on the reference sequence . the weight of a predicted tfbs depends mainly on the extent of phylogenetic conservation , which is determined by the number of species with a predicted tfbs for the same pwm at about the same position and by the conservation extent of that position . this simply represents the basic concept behind phylogenetic footprinting , i.e. cross - species conserved tfbss are more likely to be functional compared to nonconserved ones . the score even rises if tfbss predicted by the same pwm are near each other , because of the frequently observed presence of homotypic clusters of functional sites and weak another factor influencing the weight of a predicted tfbs is the distance to the tss . ( 16 ) , which prove that functional tfbss are mainly situated in the first 200 nt upstream of the tss . continuous high ranking of pwms with a rather bad quality , i.e. predicting many false positives , is avoided by having the ic of the predicting pwm influence the weight of each predicted tfbs . for the same reason , the accumulated amount of weights is divided by a factor proportional to the number of nonconserved predicted tfbss .

transcription factors ( tfs ) are key components in signaling pathways , and the presence of their binding sites in the promoter regions of dna is essential for their regulation of the expression of the corresponding genes . orthologous promoter sequences are commonly used to increase the specificity with which potentially functional transcription factor binding sites ( tfbss ) are recognized and to detect possibly important similarities or differences between the different species . the contra ( conserved tfbss ) web server provides the biologist at the bench with a user - friendly tool to interactively visualize tfbss predicted using either transfac ( 1 ) or jaspar ( 2 ) position weight matrix libraries , on a promoter alignment of choice . the visualization can be preceded by a simple scoring analysis to explore which tfs are the most likely to bind to the promoter of interest . the contra web server is available at http://bioit.dmbr.ugent.be/contra/index.php .

as the development of virtual reality ( vr)-based treatment systems such as the interactive binocular treatment ( i - bit ) system presented by eastgate et al1 and the viston - vr system presented by qiu et al2 have demonstrated , the advent of vr technology has been introduced as a promising solution for the management of amblyopia . preliminary findings imply that vr - based treatment could be effective3 and does not involve many of the numerous problems confronted in the conventional approach of occlusion or penalization . conventional occlusion therapy , by patching the dominant eye to encourage stimulation of the amblyopic eye , is traditionally the mainstay treatment for amblyopia.4 although effective,57 this simple intervention produces variable and unsatisfactory outcomes , long durations of treatment , high costs , negative psychological and emotional impacts , and poor compliance , which may even render the treatment completely ineffective.8 atropine penalization of the dominant eye is a recently developed alternative with reportedly better compliance and lower costs,9 and of equal efficacy.6,7,9 however , atropine as a medication has its side effects , ranging from the common and benign experience of light sensitivity,7,10,11 to a large variety of less common but more serious symptoms.4 although rare,7,12 there have also been reports of reverse amblyopia,13,14 a complication in which the unaffected penalized eye becomes amblyopic due to inhibition . vr - based treatment is interactive and adjustable for age and therefore it is enjoyable for the patients and results in excellent patient compliance.1 it does not entail the stigmatization of patching or side effects of atropine , and has no risk of reverse amblyopia , since the healthy eye is not occluded or rendered inactive and is not deprived of stimuli . vr - based treatment is said to be successful in preliminary reports.3 in addition , while occlusion and penalization can potentially disrupt fusion , vr - based therapy encourages fusion and is expected to enhance binocular vision . on the other hand , . it would be costly to implement on a large scale , and it would not be accessible or convenient for most children . the current paper attempts to introduce a method that could encompass the advantages of vr - based treatment , at a much lower cost . the introduced system can produce an effect similar to the underlying concept of vr - based treatment , using simple technology and obviating the need for complex equipment . the software of this system could be installed on a personal computer at home , and conveniently operated along with a pair of special glasses . the essence of vr - based treatment consists of feeding the two eyes two different but related images . instead of having the two images differ slightly in perspective , as would be intended for three - dimensional ( 3-d ) viewing , the two images would overlap and create a single image , however some elements would be missing for each eye . in particular , there would necessarily be main active elements that would be presented to the amblyopic eye but not to the non - amblyopic eye . thus , the amblyopic eye would need to play an active role in binocular vision in order to see the complete image , whether it be a video or a game . vr , however , is not the only method that can be used to feed two different images to the two eyes . long before the very concept of feeding a different image to each eye was adopted for the treatment of amblyopia , it had been used to create 3-d images and movies . an older technique for creating 3-d experiences was the anaglyphic method . in this method , two images created from a slightly differing point of view were presented in two distinct colors . the viewer would wear a pair of 3-d glasses consisting of two color filters , each to filter one of the images . the system consists of a software package and a pair of glasses made of two color filters . the software is designed to be engaging and interactive , but in a manner that at least some of the main active moving components can only be seen by the amblyopic eye and are filtered out for the other eye . this is achieved by simply arranging these elements ( and the corresponding backgrounds they cover ) to appear in the same colors that the filters allow entry for . some components , especially the nonmobile or background elements , would be seen by both eyes to encourage fusion . the result is , the patient must use both eyes , and specifically the amblyopic eye , to play the games ( figure 1 ) . the glasses consisted of two blue ( wratten # 47 ) and orange ( wratten # 21 ) generic photographic filters . software of the prototype model consisted of simple modified open source flash ( adobe , san jose , ca ) games . the games used included the open source flash games of ping , xtreme climber , snake , and pacman . the backgrounds of all games were changed to white , and main elements were changed to the filtered colors . codes # 99ffff and # ccffff were filtered by the blue lens and # ffff33 and # ffff99 were filtered by the orange lens . this enabled us to create images with three shades ( two shades of color and white ) , which could be filtered out for one eye . a laboratory prototype of the proposed system , the abg insight ( v1.2 ) , was designed . the system was used on nine monitors , with different manufacturers and models , and complete filtering was confirmed by twelve people without a history of any ophthalmologic or neurological problems . a simple calibration module could be added to the software later to guarantee consistency in filtering elements , or for the time being the monitors could be adjusted by any person without color vision deficits , to ensure correct filtering . the glasses consisted of two generic photographic filters , which were for the purpose of this study , blue and orange , but other color pairs , such as the traditional 3-d red - cyan or amber - pure dark blue ( used in colorcode 3-d)15 would presumably be equally functional . the prototype system was capable of successfully filtering out elements of a certain color and therefore , was found to be a potential alternative to vr for amblyopia management . as mentioned , the computer - based anaglyphic system provides most of the advantages of the vr - based treatment , in addition to reduced cost and high availability . the open source initiative allows for the modification , and in most cases , distribution , of a variety of software packages , free of charge and licensing . this creates the opportunity for researchers to gain access to libraries of software , and from the many available programs , select and use those that may suit their purpose . in this case , applying a few simple changes in the code of a game , such as changing the color of the elements , could make it completely compatible with the proposed system . for this means , many of the available games can be used , taking into consideration only the appropriateness of the game for the target age group , and complexity of the graphic interface . the license of some open source games does not allow them to be modified for commercial use . this should be taken into consideration , the license respected , and no financial gain received from such games . one of the limitations for such a system would be the main limitation of all anaglyphic systems : the limited use of color . games that include color as a main theme or include color - based elements , as well as games and media with complex graphics , would be slightly restricted . although anaglyphs can reproduce color images and to a point , color distinction and clarity , the scope of options is limited . for example , the main moving elements , as well as other components which are selected for filtering , along with the corresponding backgrounds they cover , must be invariably monochrome . for this reason , the background and main elements can only consist of white and various shades of the filtered color . in most cases , between the darkest shade of the filtered color and white this limits the colors for use in the main elements and backgrounds to three colors ; white and the two shades of the filtered color . aside from this issue . a minor advantage for some vr - based systems would be that they can be made to adjust for angles of strabismus , which means they can be used for untreated strabismic amblyopes and adjusted as such to provide binocular vision and fusion without requiring satisfactory alignment . since the anaglyphic system uses a single display , its use is limited to amblyopic patients for whom the underlying condition , usually strabismus or anisometropia , has been resolved , at least to some extent , by corrective glasses or other means . a minor advantage of the anaglyphic system is that the fusion promoted for seeing the images in this system , is similar to the fusion required in the actual world , because both eyes are watching the same interface . vr - based systems may not represent the actual angles , distances , or proportions seen in the natural surroundings . this is why prolonged work with vr systems has been associated with vomiting , sweating , headaches , and drowsiness.16 the anaglyphic system has much potential to become a large - scale open source research project . various open source applications could be modified by volunteers to enrich the library of software used in the project , and researchers throughout the world could use standard filters to create the glasses , and download the software free of charge . a major concern is the actual effectiveness of the vr - based systems . although the anaglyphic system could potentially serve as an alternative to vr - based systems by accomplishing the same objectives , the evidence supporting vr - based systems as a therapeutic intervention is limited , and the only available studies including clinical data in this regard are two case series reporting the short - term outcomes in six and twelve patients , respectively.3,17 computer - based active vision therapy has received much attention for amblyopia and one of the recent publications by hess et al,18 demonstrating success for active vision therapy in three amblyopic patients . however , there is still not much evidence in the literature to support most modalities . nonetheless , introducing the anaglyphic system provides an excellent opportunity to investigate the role of computer - based therapy in the management of amblyopia , by enabling researchers worldwide to evaluate its effectiveness without the need for expensive or exclusive equipment , and therefore allowing interested researchers to continue from where the previous studies were left . the current lack of clinical data for the amblyopic system is a major drawback of this introductory paper . however , it has not been claimed that the anaglyphic method is an effective treatment for amblyopia , but rather that the system could logically be a suitable alternative to the vr systems . the cost of anaglyphic systems is much lower , therefore they may be a more viable option for research and maybe ultimately , treatment . the evidence for vr - based systems could be intriguing enough for researchers to test an anaglyphic system that functions similarly , with better availability and lower costs . future clinical trials performed on vr - based treatment systems can document the effectiveness of the underlying concept , on which the current system was designed . in addition , clinical trials and case series performed with the anaglyphic system itself will determine its true effectiveness and implications . in conclusion , the anaglyphic system maintains most advantages of the vr - based systems , but is less costly and more accessible . the system logically fulfills what the vr - based system was designed to achieve and therefore , warrants further investigation .

purposevirtual reality ( vr)-based treatment has been introduced as a potential option for amblyopia management , presumably without involving the problems of occlusion and penalization , including variable and unsatisfactory outcomes , long duration of treatment , poor compliance , psychological impact , and complications . however , vr - based treatment is costly and not accessible for most children . this paper introduces a method that encompasses the advantages of vr - based treatment at a lower cost.methodsthe presented system consists of a pair of glasses with two color filters and software for use on a personal computer . the software is designed such that some active graphic components can only be seen by the amblyopic eye and are filtered out for the other eye . some components would be seen by both to encourage fusion . the result is that the patient must use both eyes , and specifically the amblyopic eye , to play the games.resultsa prototype of the system , the abg insight , was found capable of successfully filtering out elements of a certain color and therefore , could prove to be a viable alternative to vr - based treatment for amblyopia.conclusionthe anaglyphic system maintains most of the advantages of vr - based systems , but is less costly and highly accessible . it fulfills the means that vr - based systems are designed to achieve , and warrants further investigation .

adult ( 12 months ) and aged ( 25 months ) c57bl/6 male mice were purchased from charles river and housed in the specific pathogen - free ( spf ) facility at the university of liverpool for at least 2 weeks before use . all experiments were performed in accordance with united kingdom home office guidelines under the united kingdom animals ( scientific procedures ) act 1986 . a gastrocnemius muscle from each mouse was placed immediately in a thiol blocking buffer containing ( 25 mm d(0 ) nem , 50 mm ammonium bicarbonate , ph 8) for redox proteomic analysis . briefly protein extracts for redox analysis were prepared in the presence of thiol blocking buffer containing d(0 ) nem under anaerobic conditions . homogenized protein lysates were cleared by centrifugation at 15,000 g for 10 min at 4 c and protein concentrations were calculated by bradford assay ( biorad ) using bsa as a standard . protein extracts for redox analysis were desalted using zeba spin desalting columns ( thermo ) and protein concentrations were re - calculated as before . 200 g in 160 l of 25 mm ammonium bicarbonate of the desalted protein extract was denatured by addition of 10 l of 1% w / v rapigest ( waters , manchester , uk ) in 25 mm ammonium bicarbonate followed by incubation at 80 c for 10 min . reversibly oxidized cys residues were reduced by the addition of 10 l of 100 mm tcep and incubated at 60 c for 10 min . newly reduced cys residues were subsequently alkylated with 10 l of 200 mm d(5 ) nem and incubated at room temperature for 30 min . trypsin ( sigma , poole , uk ) was reconstituted in 50 mm acetic acid and 2 g added to the samples followed by incubation overnight at 37 c . the digestion was terminated and rapigest removed by acidification ( 3 l of tfa and incubation at 37 c for 45 min ) and centrifugation ( 15,000 g for 15 min ) . the data - dependent label - free analysis was performed using an ultimate 3000 rslc nano system coupled to a qexactive mass spectrometer ( thermo scientific ) . the sample ( 5 l corresponding to 200 ng of protein ) was loaded onto the trapping column ( thermo scientific , pepmap100 , c18 , 75 m20 mm ) , using partial loop injection , for 7 min at a flow rate of 4 l / min with 0.1% ( v / v ) tfa . the sample was resolved on the analytical column ( easy - spray c18 75 m500 mm2 m column ) using a gradient of 97% a ( 0.1% formic acid ) 3% b ( 99.9% acn 0.1% formic acid ) to 60% a 40% b over 120 min at a flow rate of 300 nl / min . data dependent acquisition consisted of a 70,000 resolution full - scan ms scan ( agc set to 106 ions with a maximum fill time of 250 ms ) . the 10 most abundant peaks were selected for ms / ms using a 17,000 resolution scan ( agc set to 5104 ions with a maximum fill time of 250 ms ) with an ion selection window of 3 m / z and a normalized collision energy of 30 . to avoid repeated selection of peptides for ms / ms the program used a 30 s dynamic exclusion window . raw spectra were converted to mascot generated files ( mgf ) using proteome discoverer software ( thermo scientific ) . the resulting mgf files were searched against uniprot mouse database sequence database ( 12/05/2012 , 16376 sequences ) using an in - house mascot server ( matrix science , london , uk ) . search parameters used were : peptide mass tolerances , 10 ppm ; fragment mass tolerance , 0.01 da , 1 + , 2 + and 3 + ions ; missed cleavages , 1 ; instrument type , esi - trap . variable modifications included were : d(0 ) nem , d(5 ) nem , mono- , di- and tri - oxidation of cys residues and oxidation of methionine . label - free relative quantification software peaks7 was used to analyze raw data files against the same mouse protein database used for identifications with mascot . proteins were considered significantly changed between adult and aged samples using a -10logp score of 20 ( equivalent to a p value of 0.01 ) , a fold change 1.5 , using a quality value of 0.8 and fdr set to 1% . supplementary file 1 contains additional information on the search and result parameters used including a volcano plot for peptides , the distribution of feature vector ratio by quality , distribution of feature vector ratio by intensity , retention time shift distribution and m / z shift distribution . a volcano plot of the expression of proteomic data is provided in fig . 1 and a list of proteins identified and quantified is included in supplementary table 1 . an example of a peptide containing a redox sensitive cys residue ( cys385 from aconitase ) is presented in fig . analysis of redox peptides identified with both d(0 ) nem and d(5 ) nem was performed using skyline and the relative quantification of the reversible oxidation state of cys residues ( reduced : reversibly oxidized ) was calculated from the intensity of precursor ions and is included in supplementary table 2 . adult ( 12 months ) and aged ( 25 months ) c57bl/6 male mice were purchased from charles river and housed in the specific pathogen - free ( spf ) facility at the university of liverpool for at least 2 weeks before use . all experiments were performed in accordance with united kingdom home office guidelines under the united kingdom animals ( scientific procedures ) act 1986 . a gastrocnemius muscle from each mouse was placed immediately in a thiol blocking buffer containing ( 25 mm d(0 ) nem , 50 mm ammonium bicarbonate , ph 8) for redox proteomic analysis . briefly protein extracts for redox analysis were prepared in the presence of thiol blocking buffer containing d(0 ) nem under anaerobic conditions . homogenized protein lysates were cleared by centrifugation at 15,000 g for 10 min at 4 c and protein concentrations were calculated by bradford assay ( biorad ) using bsa as a standard . protein extracts for redox analysis were desalted using zeba spin desalting columns ( thermo ) and protein concentrations were re - calculated as before . 200 g in 160 l of 25 mm ammonium bicarbonate of the desalted protein extract was denatured by addition of 10 l of 1% w / v rapigest ( waters , manchester , uk ) in 25 mm ammonium bicarbonate followed by incubation at 80 c for 10 min . reversibly oxidized cys residues were reduced by the addition of 10 l of 100 mm tcep and incubated at 60 c for 10 min . newly reduced cys residues were subsequently alkylated with 10 l of 200 mm d(5 ) nem and incubated at room temperature for 30 min . trypsin ( sigma , poole , uk ) was reconstituted in 50 mm acetic acid and 2 g added to the samples followed by incubation overnight at 37 c . the digestion was terminated and rapigest removed by acidification ( 3 l of tfa and incubation at 37 c for 45 min ) and centrifugation ( 15,000 g for 15 min ) . the data - dependent label - free analysis was performed using an ultimate 3000 rslc nano system coupled to a qexactive mass spectrometer ( thermo scientific ) . the sample ( 5 l corresponding to 200 ng of protein ) was loaded onto the trapping column ( thermo scientific , pepmap100 , c18 , 75 m20 mm ) , using partial loop injection , for 7 min at a flow rate of 4 l / min with 0.1% ( v / v ) tfa . the sample was resolved on the analytical column ( easy - spray c18 75 m500 mm2 m column ) using a gradient of 97% a ( 0.1% formic acid ) 3% b ( 99.9% acn 0.1% formic acid ) to 60% a 40% b over 120 min at a flow rate of 300 nl / min . data dependent acquisition consisted of a 70,000 resolution full - scan ms scan ( agc set to 106 ions with a maximum fill time of 250 ms ) . the 10 most abundant peaks were selected for ms / ms using a 17,000 resolution scan ( agc set to 5104 ions with a maximum fill time of 250 ms ) with an ion selection window of 3 m / z and a normalized collision energy of 30 . to avoid repeated selection of peptides for ms / ms the program used a 30 s dynamic exclusion window . raw spectra were converted to mascot generated files ( mgf ) using proteome discoverer software ( thermo scientific ) . the resulting mgf files were searched against uniprot mouse database sequence database ( 12/05/2012 , 16376 sequences ) using an in - house mascot server ( matrix science , london , uk ) . search parameters used were : peptide mass tolerances , 10 ppm ; fragment mass tolerance , 0.01 da , 1 + , 2 + and 3 + ions ; missed cleavages , 1 ; instrument type , esi - trap . variable modifications included were : d(0 ) nem , d(5 ) nem , mono- , di- and tri - oxidation of cys residues and oxidation of methionine . label - free relative quantification software peaks7 was used to analyze raw data files against the same mouse protein database used for identifications with mascot . proteins were considered significantly changed between adult and aged samples using a -10logp score of 20 ( equivalent to a p value of 0.01 ) , a fold change 1.5 , using a quality value of 0.8 and fdr set to 1% . supplementary file 1 contains additional information on the search and result parameters used including a volcano plot for peptides , the distribution of feature vector ratio by quality , distribution of feature vector ratio by intensity , retention time shift distribution and m / z shift distribution . a volcano plot of the expression of proteomic data is provided in fig . 1 and a list of proteins identified and quantified is included in supplementary table 1 . an example of a peptide containing a redox sensitive cys residue ( cys385 from aconitase ) is presented in fig . 2 . analysis of redox peptides identified with both d(0 ) nem and d(5 ) nem was performed using skyline and the relative quantification of the reversible oxidation state of cys residues ( reduced : reversibly oxidized ) was calculated from the intensity of precursor ions and is included in supplementary table 2 .

the data provides information in support of the research article , differential cysteine labeling and global label - free proteomics reveals an altered metabolic state in skeletal muscle aging , journal of proteome research , 2014 , 13 ( 11 ) , 200821 [ 1 ] . raw data is available from proteomexchange [ 2 ] with identifier pdx001054 . the proteome of gastrocnemius muscle from adult and old mice was analyzed by global label - free proteomics and the relative quantification of specific reduced and reversibly oxidized cysteine ( cys ) residues was performed using skyline [ 3 ] . briefly , reduced cysteine ( cys ) containing peptides was alkylated using n - ethylmalemide ( d0-nem ) . samples were desalted and reversibly oxidized cys residues were reduced using tris(2-carboxyethyl)phosphine ( tcep ) and the newly formed reduced cys residues were labeled with heavy nem ( d5-nem ) . label - free analysis of the global proteome of adult ( n=5 ) and old ( n=4 ) gastrocnemius muscles was performed using peaks7 mass spectrometry data analysis software [ 4 ] . relative quantification of cys containing peptides that were identified as reduced ( d(0 ) nem labeled ) and reversibly oxidized d(5)nem labeled was performed using the intensity of their precursor ions in skyline . results indicate that muscles from old mice show reduced redox flexibility particularly in proteins involved in the generation of precursor metabolites and energy metabolism , indicating a loss in the flexibility of the redox energy response .

in medicine , the randomized controlled clinical trial ( rct ) is the gold standard in research design for assessing the level of evidence for new treatments.1 nevertheless , the clinical applicability of rct results has shortcomings . rcts often focus on short - term efficacy and safety in a controlled clinical environment among well - educated affluent patients.2 in addition , the scientific investigation per se may influence the subject and the results of an investigation , also called the hawthorne effect.3 important elements of study design are intensity of and methods for collection of follow - up data . these elements are likely to influence the completeness , validity , and number of events assessed , and may lead to biased estimates of the prognosis , because some study participants drop out over time . in a population - based health care database , this may reduce certain forms of bias , such as nonresponse bias , recall bias , and bias from loss to follow - up , which may influence prognostic estimates.4 also , there are considerable costs associated with conducting an rct . based on our experience with head - to - head stent comparisons,58 we present a novel research tool in interventional cardiology : event detection using population - based health care databases . when event detection relies on population - based databases , conduct of rcts does not influence everyday clinical practice . complete and lifelong follow - up is possible , and a large - scale rct may be performed at relatively low cost . event detection using population - based databases requires access to existing health care databases , permission to merge different databases at the patient level , and algorithms to ensure anonymity for individual patients . it is essential that the database cover the target population over the entire study period and that patient migration out of the catchment area is minimal.9 treatment with coronary stents is usually assessed using safety end points ( all - cause death , cardiac death , and myocardial infarction [ mi ] ) and efficacy end points ( targetlesion or vessel revascularization [ tlr or tvr ] following percutaneous coronary intervention [ pci ] or coronary bypass surgery).10 it is well known that study - related follow - up procedures may affect the number of end points detected . in interventional cardiology , the benestent study11 noted that tvr was found more often in patients undergoing systematic angiographic follow - up than in patients followed clinically . thus , mandated angiographic monitoring increases event rates significantly , as the presence of visually assessed coronary artery stenosis leads to new revascularization procedures . much effort has been made to avoid study - induced repeat revascularizations . in the nordic bifurcation studies,12 clinical and angiographic monitoring other investigators have established strict rules for revascularization following angiographic detection of a new coronary artery narrowing.13 clinical study - related monitoring by means of outpatient visits or telephone contacts also is likely to lead to changes in patient compliance , increased detection of events , and registration of events that would remain undetected in everyday clinical practice . the sort out ii v trials58 used existing national registries covering the entire population to detect events in the study cohorts . data on mortality ( cardiac and noncardiac ) were obtained from the danish civil registration system and the national registry of causes of death,14,15 hospital admission for myocardial infarction from the danish national registry of patients,16 and basic descriptive data , coronary angiography , repeat pci , and coronary bypass surgery from the western denmark heart registry.17 an important advantage of this study approach is the ability to describe baseline demographics and clinical outcomes in all patients treated with coronary stents during the study period , and not only those included in the rct . thus , important information is available regarding the general applicability , ie , the external validity , of study results . in denmark , all citizens have a personal civil registration number assigned at birth or upon immigration.14 this unique personal identifier allows linkage of individual - level information across registries and databases . the danish civil registration system is updated daily , and maintains records on date of birth , death , and current residence of all danish citizens . the danish national registry of patients contains information on all admissions and outpatient visits to the 52 danish hospitals . for each hospital admission , the registry records dates of admission and discharge , surgical procedures performed , and up to 20 diagnoses classified according to the international classification of diseases ( icd ) , eighth revision , until the end of 1993 , and tenth revision thereafter.16 the western denmark heart registry contains detailed patient- and procedure - specific information on all coronary angiographies , coronary interventions and coronary bypass surgery performed at the three interventional and eight noninterventional cardiac centers in western denmark.17 information from the western denmark heart registry and the danish national registry of patients has been validated in earlier studies , and the registries data completeness and validity are continuously monitored.16,18 the sort out trials58 used the danish civil registration system to assess all - cause mortality . the original death certificates were obtained from the national registry of causes of death to classify deaths by underlying cause . we defined new mis as rehospitalization for mi after the index pci , based on mi - related admissions and readmissions i ( icd-10 codes i21i21.9 ) identified from the danish national patient registry . information on new diagnostic angiograms and new revascularizations performed with coronary bypass surgery or pci was available from the western denmark heart registry . all possible end points were adjudicated by an independent end - point committee consisting of interventional and noninterventional cardiologists , who examined hospital files and reviewed diagnostic and therapeutic angiograms . the trial end points were all - cause death , cardiac death , noncardiac death , mi , tvr , tlr , and stent thrombosis , using academic research consortium definitions.10 the health care database - based event detection is shown schematically in figure 1 . in the ongoing swedish taste trial,19,20 the investigators have added a randomization module to their population - based pci database , taking the integration of clinical databases and rcts to a higher level . in taste , patients admitted with acute st - elevation mi for primary pci are randomized to thrombectomy or to conventional primary pci . when initial procedural data are entered in the database and prespecified inclusion and exclusion criteria this is an excellent example of a study design incorporating the essentials of an rct in interventional cardiology . the study has a large sample size ( > 5,000 patients ) , a high inclusion rate , and a focused primary end point ( 1-month all - cause mortality).19 combining event detection using population - based health care databases with a randomization module may be a very efficient and cost - effective option when designing large scale rcts with long term follow - up . event detection using population - based registries in rcts is a novel research tool that may be applied in a number of clinical settings , including coronary interventions.21 this approach allows large rcts to reflect daily clinical practice , to cover a broad range of patients , and to facilitate complete lifelong follow - up at low cost . drug - eluting stents were accepted for extensive clinical use based on randomized trials involving relatively few and selected patients , with angiographic follow - up data serving as the primary end point.2224 years later , detection of an increased risk of late stent thrombosis in patients treated with these stents raised questions about the scientific rigor of the device - approval process . subsequently , large rcts with few exclusion criteria and clinical end points were recommended to document acceptable safety and efficacy of new stents . event detection using population - based databases may provide additional clinical support for this type of study . this method may make it possible , at low cost , to use an rct design to study the safety and efficacy of medical devices in large cohorts of unselected patients , with a lifelong follow - up period and a clinical research setting identical to routine clinical practice . furthermore , combining different health care databases may allow assessment of variables not directly related to the rct for generation of hypotheses for new prospective studies.25,26 finally , combining event detection using population - based health care databases and a randomization module within the database20 may be a very efficient and cost - effective option for large - scale long - term follow - up rcts . we do not know the extent to which event rates differ between clinical studies using population database - based event detection and those using conventional angiographic or other follow - up for event detection . it is likely that registration of death will be the same . with symptom - driven event detection , incidence of spontaneous mi may be slightly reduced and procedure - related mi further reduced due to fewer revascularizations . because new revascularizations will be symptom - driven , it also is likely that rates of new revascularizations will be lower . however , the randomization process would balance possible under- or overreporting in the study groups . the generalizability , or external validity , of study findings is a common challenge in clinical research , since information about nonstudy patients remains unknown or associated with a high degree of uncertainty . in this context , trials using population - based health care databases for event detection provide a significant advantage.25,26 since all patients are registered in the existing databases , equally valid procedure and background information is available for both study patients and nonstudy patients . databases have important limitations , which are frequently ignored , because researchers do not control methods of data collection . therefore , a primary concern in health care database - based event detection is related to the quality of health care databases used . here , a prerequisite is reliable population - based databases , which register all relevant data in a timely manner in a well - defined population . additional requirements include the ability to identify all patients and link their data among different databases . further , it is important to review and validate the information recorded in the databases continuously.25 so far , our population - based health care database event detection has not been evaluated or approved by competent national health authorities . further , we have no comparison of traditional event detection using clinical follow - up by phone call or outpatient visits and data registration by clinical research forms versus our proposed health care database - based event detection . therefore , we may suggest a randomized comparison of the different forms of event detection to describe possible event - rate differences and a comparison of event rates and types of events detected by traditional event detection versus a health care database - based event detection in the same study cohort . there are specific ethical aspects to using population - based health care database event detection in rcts . first , the randomized patient should be informed how follow - up data will be obtained , and that , in principle , the event detection will be lifelong . second , randomized and nonrandomized patients should be informed that treatment and outcome data will be registered in national health care databases and used to describe general treatment results and to assess the external validity of ongoing rcts . databases have important limitations , which are frequently ignored , because researchers do not control methods of data collection . therefore , a primary concern in health care database - based event detection is related to the quality of health care databases used . here , a prerequisite is reliable population - based databases , which register all relevant data in a timely manner in a well - defined population . additional requirements include the ability to identify all patients and link their data among different databases . further , it is important to review and validate the information recorded in the databases continuously.25 so far , our population - based health care database event detection has not been evaluated or approved by competent national health authorities . further , we have no comparison of traditional event detection using clinical follow - up by phone call or outpatient visits and data registration by clinical research forms versus our proposed health care database - based event detection . therefore , we may suggest a randomized comparison of the different forms of event detection to describe possible event - rate differences and a comparison of event rates and types of events detected by traditional event detection versus a health care database - based event detection in the same study cohort . there are specific ethical aspects to using population - based health care database event detection in rcts . first , the randomized patient should be informed how follow - up data will be obtained , and that , in principle , the event detection will be lifelong . second , randomized and nonrandomized patients should be informed that treatment and outcome data will be registered in national health care databases and used to describe general treatment results and to assess the external validity of ongoing rcts . event detection using population - based health care databases is a new research tool in interventional cardiology that may allow large rcts to reflect daily clinical practice , to cover a broad range of patients , and to facilitate complete lifelong follow - up at low cost .

aimto describe a new research tool , designed to reflect routine clinical practice and relying on population - based health care databases to detect clinical events in randomized clinical trials.backgroundrandomized clinical trials often focus on short - term efficacy and safety in a controlled environment . trial follow - up may be linked with study - related investigations and differ from routine clinical practice . because treatment and control in randomized trials differ from daily practice , trial results may have reduced general applicability and may be of limited value in clinical decision - making . further , it is economically very costly to conduct randomized clinical trials.methods and resultspopulation - based health care databases collect data continuously and prospectively , and make it possible to monitor lifelong outcomes of cardiac interventions in large numbers of patients . this strengthens external validity by eliminating the effects of study - related monitoring or diagnostic tests . further , follow - up data can be obtained at low expense . importantly , data sources encompassing a complete population are likely to reflect clinical practice . because population - based health care databases collect data for quality - control and administrative purposes unrelated to scientific investigations , certain biases , such as nonresponse bias , recall bias , and bias from losses to follow - up , can be avoided.conclusionevent detection using population - based health care databases is a new research tool in interventional cardiology that may allow large , low - cost , randomized clinical trials to reflect daily clinical practice , covering a broad range of patients and end points with complete lifelong follow - up .

brain disorders such as dementia change a person s personality and behavior and cause a continuous loss of intellectual and emotional functions . since the risk of brain disorders are greater in older as compared with young adults , the chances of limitations in the former s daily life also increase1 , 2 . as elderly adults can not perform daily activities independently , they may be taken care of in an institution such as a nursing home when their cognitive ability declines beyond a certain level . advances in medical technology have increased the average life span and consequently the number of elderly adults worldwide3 . this in turn is causing a rise in the number of individuals with dementia . the number of care facilities for the elderly is increasing in countries with a large elderly population . the service at each care facility may be at a different level , but it is not surprising that these facilities pay more attention to caring services and safety than normal homes do because they serve institutionalized elderly adults who are incapable of living independently4 . however , the elderly s attitude towards the same living environment may vary according to individual cognitive level . this study investigated the correlation between the cognitive levels of the elderly and their attitude towards the living environment . this study was conducted with 80 elderly people who were institutionalized in a nursing home in k city . the selection criteria for the subjects were as follows : at least 65 years of age and having no disease that might affect the results of the test . those who had visual impairments , hearing damage , or nervous system or vestibular organ problems or were unable to understand the nature of the study were excluded . all subjects understood the purpose of this study and provided written informed consent prior to participation in the study in accordance with the ethical standards of the declaration of helsinki . the average age , height , and weight of the subjects were 79.9 8.5 years , 154.3 9.4 cm , and 56.3 15.1 kg , respectively . the mini mental state examination - korean version ( mmse - k ) was used to evaluate their cognitive ability . the measurement of quality of the environment ( mqe ) scale was administered to evaluate subjects attitude towards their surrounding environment . the mqe assesses whether environmental factors act as a facilitator or as an obstacle for a person s daily activities . characteristics of the environment are scored on a seven - point scale from facilitator ( 0 to + 3 ) to obstacle ( 0 to 3)5 . pearson correlation analysis was used to examine the correlation between the mmse - k and the mqe ( facilitator and obstacle ) . a positive and moderately strong correlation ( r = 0.462 ; p < 0.05 ) was found between the mmse and the mqe ( obstacle ) ( table 1table 1.correlation between the mmse and mqe ( obstacle and facilitator)mqeobstaclefacilitator5.15.922.29.9mmse17.35.30.462 * 0.223meansd , score , * p<0.05 ) . this study administered the mmse and the mqe to a sample of 80 elderly people in a nursing home and investigated the correlation between the mmse and the mqe ( facilitator and obstacle ) . a positive and moderately strong correlation was found between the mmse and the mqe ( barrier ) . in other words , previous studies have shown that the life satisfaction of the elderly changes when they experience cognitive decline , such as in dementia6 , 7 . clare et al . revealed that moderate to severe dementia caused feelings of uncertainty , loneliness , helplessness , or pain and decreased life satisfaction7 . however , the present study obtained contradictory results : the elderly who needed care in a nursing home were stressed , shocked , or worried about moving into a facility8 . in addition , according to onishi et al . , maladjustment to the new environment in newly hospitalized elderly people affected their life satisfaction6 . a possible explanation for this finding is that the sample of newly institutionalized patients may have had higher levels of consciousness because of the relatively low rate of conversion to dementia , whereas the present institutionalized sample had already progressed to dementia . therefore , in addition to their denial of reality , the fact that they were hospitalized and their inability to adapt to the new environment affected the results . in conclusion , in a nursing home , patients with relatively higher cognitive levels perceive more obstacles in the surrounding environment . therefore , nursing homes should implement measures to promote patients adjustment to the new environment . after the adjustment period , facilities should provide patients with leisure activities or pastimes to increase their life satisfaction rather than leaving them to merely rest9 . a limitation of this study is that correlations between the mqe scores and duration of hospitalization were not calculated .

[ purpose ] this study aimed to investigate the correlation between the cognitive level of the elderly and their attitude towards the living environment . [ subjects and methods ] a total of 80 elderly people hospitalized in a nursing home in k city , south korea , participated in this study . pearson correlation analysis was used to test the relationships between scores on the mini mental state examination - korean version and measurement of quality of the environment ( facilitators and obstacles ) . [ results ] a positive and moderately strong correlation ( r = 0.462 ) was found between scores on the mini mental state examination and the measurement of quality of the environment ( obstacle ) . [ conclusion ] in a nursing home , patients with relatively higher cognitive levels can perceive more obstacles in the surrounding environment .

a longitudinal , observational study was conducted in 2216 patients who reported to the department of oral medicine and radiology ( ksridsr , tamilnadu , india ) , to identify the frequency of supernumerary teeth occurrence . for each patient with supernumerary teeth , we recorded the demographic variable ( age and sex ) following clinical examination . in required situations , we took intraoral periapical radiograph ( iopa ) to confirm the condition and we documented the location of the tooth . the pathology associated with the supernumerary teeth was also recorded , such as displacement , delayed eruption , dental caries , and associated lesions ( presence of follicular cyst ) . all obtained data were statistically analyzed with spss-16.0 version ( spss , inc , chicago , il , usa ) software program for windows by using descriptive statistics , cross tabulations , and chi - square test . twenty - seven supernumerary teeth were detected from 2216 patients examined [ table 1 ] ; this yields a total prevalence of 1.2% , 1.49% in males , and 0.85% in females [ table 2 , figure 1 ] . in the total 27 supernumerary teeth observed , 18 ( 66.7% ) were located in the maxilla and 9 ( 33.3% ) in the mandible . in maxilla , the most common supernumerary teeth was mesiodens ( 44.44% , n = 12 ) followed by distomolar ( 14.81 , n = 4 ) and in premolar region was ( 7.4% , n = 2 ) [ tables 3 and 4 , figure 2 ] . in mandible , the most common location was premolar region ( 22.22% , n = 6 ) followed by distomolar ( 11.11 , n = 3 ) [ table 5 , figure 2 ] . the prevalence of supernumerary tooth was nil in the maxillary canine and mandibular incisors and canine region . the overall prevalence rate of supernumerary teeth was higher in the maxillary anterior region ( 51.85 , n = 14 ) in comparison to the other areas , followed by mandibular premolar region ( 22.22% , n = 6 ) . in comparison to the other areas ( 22.2% ) of maxilla , supernumerary teeth were found commonly in the anterior region ( 77.8% ) . in mandible , the most frequent location was premolar region ( 66.67% ) than the other locations ( 33.33% ) . the teeth most commonly manifested in the 3 decade of life ( 46.3% ) , followed by the 2 decade ( 29.2% ) . number of patients examined supernumerary teeth found frequency of supernumerary teeth occurrence among sexes distribution of supernumerary teeth distribution in maxilla distribution of supernumerary teeth according to location distribution in mandible based on the study findings , the prevalence of supernumerary teeth in 2216 patient was 1.2% , which coincides with the other studies , with a range of 0.13.8% . the mean age of the patients in our study was 24.6 years , i.e. , 3 decade of life . it coincides with the findings of other authors who report this decade to be the most common period for presence of supernumerary tooth . in terms of location , the present study is in agreement with this report , as 77.8% was found in the anterior maxilla . regarding gender distribution , most of the supernumeraries in this study showed that the prevalence was much higher among males ( 1.49% ) than females ( 0.85% ) , i.e. , the ratio coincides with that in other studies.[182023 ] considering the mechanical and pathological changes induced by supernumerary teeth , displacement of adjacent teeth is higher ( 40.7% ) , followed by dental caries , which coincides with the findings of leco - berrocal mi et al . the prevalence of supernumerary teeth in the patients who reported to the dental op was 1.2% and is comparable to that reported in previous studies .

aim : supernumerary teeth are considered as one of the most significant dental anomalies during the primary and early mixed dentition stage . the main objective of the study was to determine the prevalence rate of supernumerary teeth in the patients who reported to the department of oral medicine and radiology and to study the associated clinical complications.materials and methods : a longitudinal observational study was conducted of 2216 patients for a period of 4 months with the documentation of demographic data , the presence of supernumerary teeth , their location , and associated complications such as mechanical trauma , dental caries , and associated pathology.results:the study recorded 27 supernumerary teeth from the examined 2216 patients . this yields a prevalence of 1.2% , with greater frequency in males which was 1.49% and in females the frequency was 0.85% . the greatest proportion of supernumerary teeth was found in the maxillary anterior region ( 77.8% ) . out of this , 85.7% were classified as mesiodens based on their location . the displacement of adjacent teeth was the most common finding , followed by dental caries.conclusion:the prevalence of supernumerary teeth in this study was 1.2% which is in agreement with that reported in similar studies and the maxillary mesiodens was the most common location . displacement of adjacent teeth was the most common finding .

a wealth of evidence indicates that regular physical activities reduce the risk of cardiovascular diseases , diabetes , obesity , hypertension , skeletal and joints disorders , and some cancers ( colon and breast ) ( 1 - 5 ) . regular physical activities among women bring fitness , balance , and muscular strength ( 6 , 7 ) . also , physical activities have positive effects on the bone density ( 8 , 9 ) . moreover , regular physical activities are effective in reducing body mass index ( 10 , 11 ) . in addition to the mentioned advantages , these activities in women provide mental benefits , too ( 7 ) . despite the mentioned advantages , a lot of women exercise no regular physical activities in different countries ( 12 - 15 ) . different studies conducted in the provinces of iran showed that inactivity is prevalent , especially among women ( 15 , 16 ) . findings of a national survey among iranian adults have shown that more than 80% of the population are physically inactive ( 17 ) . a review of studies have shown that physical activity is low in iran ( 68.7% - 70.8% ) ( 18 ) . momenan study reported that the prevalence of physical inactivity was 69.8% and only 30.3% of women had adequate physical activity ( 19 ) . considering inadequate physical activities in women and their susceptibility to many diseases and other problems caused by the lack of regular physical activities , communities should give priority to solve this problem and education is one of the most effective ways to solve it . today , the education based on theory or models has priority over traditional interventions , since theories identify the main causes that affect the behavior and changing them can lead to behavior change . one of the most popular models for studying physical activity behavior is the transtheoretical model or the stages of change . the transtheoretical model has emphasized on describing how the attitude changes ( 20 ) . determining the time dimension of behavior change , this model can contribute to the classification of people and help them change and maintain their behavior by applying different strategies and processes suitable for each stage . the transtheoretical model has 4 constructs of stages of change , processes of change , self - efficacy , and decisional balance . stages of changes include ; 1 ) precontemplation : people in the this stage do not intend to take action in the foreseeable future , usually measured as the next 6 months , 2 ) contemplation : in this stage , people intend to change in the next 6 months , 3 ) preparation : people now intend to take action in the immediate future , usually measured as 6 months , 4 ) action : the stage in which people have made specific overt modifications in their lifestyles within the past 6 months , and 5 ) maintenance : in which people have made specific overt modifications in their lifestyles ( 21 ) . processes of change is the second construct that includes cognitive and behavioral processes ( 22 ) , self - efficacy ( this construct reflects the degree of confidence individuals have in maintaining their desired behavior change ) ( 23 ) and decision - making balance ( pros and cons ) . several experimental studies conducted on women using this model indicate the efficacy of this model in changing the physical activity behaviors . in a study on 150 white women , bock showed that intervention according to the model of stages of change increased physical activities in the intervention group , 6 months after the intervention ( 24 ) . dallow and anderson also showed that intervention according to the model of stages of change increased physical activities in obese women ( 25 ) . the study by opdenacker et al . also indicates that the application of processes in this model have positive effects on the physical activities ( 26 ) . in the study conducted by shirazi it is stated that the stages of change model increased physical activities in the intervention group ( 27 ) . various studies conducted on the basis of the transtheoretical model on women in different countries with various diseases such as obesity , diabetes , or osteoporosis have shown the effectiveness of the mentioned model . to our knowledge , no studies have been done by applying the transtheoretical model to promote physical activities among women . thus , we decided to conduct this study with the aim of determining the application of a transtheoretical model in promoting the physical activities behavior among women residing in isfahan . this was a quasi - experimental study conducted on the women from the health centers in esfahan , iran . sample was selected through two - stage cluster sampling . since , there are two district health centers in isfahan , 2 city health centers were randomly selected from each district and then the members of control group were randomly selected from one city health center and the members of case group from the other health center . the sample size ( participants ) comprised 71 people who were regrouped in the contemplation ( 28 women ) , preparation ( 23 ) , and action ( 20 ) stages . inclusion criteria were lack of medical prohibition for physical activities , ability to read and write , married , affected by metabolic syndrome , and take a place in the contemplation , preparation , or action stage for doing physical activities according to the stages of change . the exclusion criteria were unwillingness to participate and medical prohibition for physical activities . after becoming familiar with the objectives of the study , participants completed informed consent forms . the following questionnaires were also used to collect the data in 3 time points ( preintervention , 3 , and 6 months postintervention ) in health centers : international physical activities questionnaire ( ipaq - short form ) , which rated the individual s physical activity during the last 7 day as vigorous , moderate , and walking ( 28 ) . the 5-point scale questionnaire to determine the stages of change ( secq ) ( stages of exercise change questionnaire ) was prepared by marcus et al . it places the individuals in one of the stages of precontemplation , contemplation , preparation , action , and maintenance ( 29 ) . in this study , stable ones and the individuals with one or more returning back level were placed in the regressive group . processes of change questionnaire includes cognitive and behavioral items which is rated on a 5-point scale from 0 ( never ) to 4 ( always ) ( 30 ) . after translation into persian and then back translation , validity of the questionnaire was confirmed by an expert panel . the 4-point scale of decisional balance includes the benefits and hindrances of a physical activity and is rated from 0 to 3 ( 43 items ) ( 31 ) . also , the self - efficacy questionnaire was used with 16 items which is rated on a 4-point scale ( not quite sure to i am quite sure ) . after the questionnaire was completed in preintervension time , the participants were placed in one of the stages ( contemplation , preparation , and action ) . the processes of consciousness raising , dramatic relief , and environmental reevaluation were used in the contemplation stage , for the case group . also , the processes of self - reevaluation and self - liberation were used for the people in the preparation stage . after decision - making balance , the processes of counter conditioning , reinforcement management , stimulus control , and helping relationships were used for the stage of action . educational sessions for physical activities were held by expert trainers , as follows : first session was allocated to introduce physical activities pyramid ( with educational slides ) that included endurance and strength training , active and aerobic exercises , and daily activities ( walking ) , lasting 45 minutes . in the second session , the endurance exercises , strength training , balancing , and static contraction were taught in the gathering hall of the health center for 60 minutes . in the third session , the above exercises together with warming - up exercises were done in a park by a trainer and cooperation of the participants and the way of cooling down was instructed at the end for 60 minutes . the correct way of walking and respiration were instructed in the fourth session by the trainer . to develop self - efficacy , in addition to breaking the sporting behavior into different stages , the women were asked to do the activities step - by - step together with female trainers . three and 6 months after intervention , the questionnaires were completed again by the case and control groups . the repeated measures anova test was used to compare the variables of the stages of change in each group . to compare the other variables ( processes of change , self - efficacy , and decisional balance ) , in each group , the chi - square test showed no significant differences in the age distribution of the two groups . in the case group , 2 persons ( 2.8% ) were in the age group of 30 - 40 years ; 20 ( 28% ) were in the age group of 40 - 50 years and 49 ( 69% ) were in the age group 50 - 60 years . in the control group , 5 ( 7% ) , 22 ( 31% ) , and 44 ( 62% ) women were within the age groups of 30 - 40 , 40 - 50 , and 50 - 60 years , respectively . regarding the education , in case and control group , 53 ( 74% ) and 57 ( 80% ) persons were without a high school diploma , respectively and the rest had a high school diploma . chi - square test showed no significant differences between the two groups ( p = 0.422 ) . before the intervention , the people stages were as follows : 28 people in the contemplation stage , 23 people in the preparation stage , and 20 people in the action stage . the numbers of progressive , stable , and regressive participants are presented in this table too . table 2 shows the mean of constructs processes of change , self - efficacy , and pros and cons during 3 periods of preintervention , 3 months , and 6 months after intervention . repeated measure anova has shown that processes of change , self - efficacy , and the pros and cons have significant changes ( p < 0.001 ) . the t test showed that intense and intermediate activities and walking had no significant differences in both groups ( case and control ) before the intervention . however , a significant increase is seen after intervention in the case group , in the two categories of intense activities and walking . this study was conducted to evaluate the application of transtheoretical model in promoting the physical activities behavior . after 3 months from intervention , 89.29% and 65.21% of the case group had shown progress in the contemplation and preparation stages , respectively . these changes caused by interventions based on the transtheoretical model and using processes of change . the progress during the stages of change could also be seen in other studies such as titze et al . the progress in the stages of change is possible by using different processes of change . as it can be seen in the present study , the processes of change showed significant increase , 3 and 6 months after the intervention as compared to preintervention period ( p < 0.001 ) . have also shown that the processes of change have increased after a period of time ( 25 , 36 ) . on the other hand , one of the effective factors in doing physical activities is self - efficacy , which increased over time in the case group . manely and nishida have also emphasized the effectiveness of self - efficacy in the behavioral changes . their studies indicate that the people with higher self - efficacy do better and significantly in their physical activities ( 37 , 38 ) . these results agree with results of dallow study , in which the efficacy has increased in women after the intervention . likewise , in pan study , self - efficacy has increased in case group after intervention . increase in self - efficacy needs intervention , as the callaghan study , which was conducted prospectively showed a slight increase in self - efficacy ( 39 ) . because the study was conducted step - by - step with female trainers and encouragement , intervention was effective . in addition , the use of effective strategies to increase self - efficacy has been recommended in several studies ( 40 ) . after the intervention in the case group , the pros also had significant increase ( p < 0.001 ) . various studies have shown direct or indirect roles of pros on physical activities ( 38 , 40 , 41 ) . reducing the cons is another effective factor in the physical activities and progression in stages of change . this change has been observed for the case group , in the present research ( p < 0.001 ) . it is stated in gorely s study that reducing cons moves the people from the contemplation to the action stage ( 42 ) . according to kim , the cons had its effective role in self - efficacy ( 43 ) . in the study by pan on students and the study by taymouri on young adults , the cons had no direct effects on physical activities ( 44 , 45 ) . however , decisional balance is an important aspect and the balance between the pros and cons could make the individuals to have physical activities . the mean duration of intense physical activities has shown significant increase in this study . in the case group after 3 and 6 months of intervention , it reached to 69 minutes ( p < 0.001 ) . the mean duration of moderate physical activities has increased too , but its change was not significant ( p = 0.131 ) . after 3 months , walking time has reached from 16.41 minutes to 60.20 minutes and to 79.94 minutes after 6 months , in case group , showing a significant increase ( p < 0.001 ) . since the world health organization has announced that people should have a minimum of 75 minutes intense physical activities , or 150 minutes of moderate physical activities or a combination of both ( 46 ) , it seems that we could make the physical activities in the case group to the required minimum rate . increasing the physical activities has been approved by various studies by the use of the transtheoretical model ( 26 , 27 , 36 , 37 ) . first , given the level of female literacy , questionnaires were very time - consuming and beyond the scope of participants . physical activity questionnaires were self - administered that seemed to cause a bias in the results . finally , generalizability of our results to the whole women from the sample of women attending health centers is not possible . this study showed that in addition to having effects on the progress of individuals during the stages of change , education based on transtheoretical model has promoted the regular physical activity behavior among the women of isfahan using the processes of change , increasing the pros and self - efficacy and even decreasing the perceived cons .

background : physical activity is one of the most important indicators of health in communities but different studies conducted in the provinces of iran showed that inactivity is prevalent , especially among women.objectives:inadequate regular physical activities among women , the importance of education in promoting the physical activities , and lack of studies on the women using transtheoretical model , persuaded us to conduct this study with the aim of determining the application of transtheoretical model in promoting the physical activities among women of isfahan.materials and methods : this research was a quasi - experimental study which was conducted on 141 women residing in isfahan , iran . they were randomly divided into case and control groups . in addition to the demographic information , their physical activities and the constructs of the transtheoretical model ( stages of change , processes of change , decisional balance , and self - efficacy ) were measured at 3 time points ; preintervention , 3 months , and 6 months after intervention . finally , the obtained data were analyzed through t test and repeated measures anova test using spss version 16.results:the results showed that education based on the transtheoretical model significantly increased physical activities in 2 aspects of intensive physical activities and walking , in the case group over the time . also , a high percentage of people have shown progress during the stages of change , the mean of the constructs of processes of change , as well as pros and cons . on the whole , a significant difference was observed over the time in the case group ( p < 0.01).conclusions : this study showed that interventions based on the transtheoretical model can promote the physical activity behavior among women .

chinese postpartum care ( zuoyuezi ) has been regarded as a crucial rite - to - passage for the woman 's recovery and the transition to motherhood after childbirth . the use of sheng - hua - tang , a well - known traditional chinese medicine ( tcm ) compound prescription , during the postpartum has been popular in chinese communities over a long period . previous study has shown that sheng - hua - tang use during the first month of the postpartum period may have a positive effect on women 's health - related quality of life , especially in terms of role limitations due to physical health and emotional problems . wu - jia sheng - hua capsule ( comprising radix et caulis acanthopanacis senticosi , radix angelicae sinensis , rhizoma chuanxiong , semen persicae , radix glycyrrhizae , and rhizoma zingiberis preparata ) , derived from sheng - hua - tang , has been used widely in chinese women to promote blood flow , resolve blood stasis , ease postchildbirth pain , reduce bleeding volume and shorten bleeding duration after induced abortion in chinese women [ 3 , 4 ] . the material base , namely the bioactive components , of wu - jia sheng - hua ( wjsh ) capsule is still unclear , though the prostaglandin f2alpha ( pgf2 ) , prostaglandin e2 ( pge2 ) , endothelin ( et ) , and nitrogen monoxide ( no ) levels were found to be partially responsible for the curative effects and recovery benefits of wjsh capsule on induced abortion with vaginal haemorrhage . tcm serum pharmacochemistry , based on hypothesis that active compounds should appear in blood after administration of tcm , was proposed by homma et al . , it was proved to be helpful in recognizing the real active components in tcm and in gaining a better understanding of the mechanisms under the therapeutic effects of tcm [ 79 ] . in the present study , an ultraperformance liquid chromatography coupled with electrospray ionization mass spectrometry ( uplc / esi - ms ) method was developed and applied for investigating the serum pharmacochemistry of wjsh capsule . the identification of wjsh 's multiple absorbed bioactive components and metabolites might be helpful for better understanding the mechanisms under its therapeutic effects . syringin , protocatechuic acid , liguiritin , ferulic acid , isofraxidine , chlorogenic acid , and liqustilide ( standards ) were purchased from national institute of control of pharmaceutical and biological products ( beijing , china ) . acetonitrile , methanol , formic acid , and ammonium formate ( hplc grade ) were obtained from merck ( darmstadt , germany ) and sigma - aldrich ( st . louis , mo , usa ) , respectively . wu - jia - sheng - hua capsule and each single herb in the prescription of wu jia sheng hua capsule were gifts from duo duo pharmaceutical co. ltd . the chromatographic separation of the absorbed components and metabolites were performed on a waters acquity uplc system ( waters corp . , milford , ma , usa ) equipped with an uv detector , an autosampler , an acquity uplc beh c18 column ( 2.1 50 mm , 1.7 m ) , and an automatic thermostatic column oven . the mobile phase consisted of ( a ) water buffered with ammonium acetate ( 10 mm ) and formic acid ( 0.1% , v / v ) and ( b ) acetonitrile . the elution of the target compounds was conducted in a gradient mode with the volume percentage of b changed from 5% to 50% in the initial 10 minutes and from 50% to 80% in the next 6 minutes . the flow rate was 0.4 ml / min , and the injection volume was 8 l . to obtain the ms and ms / ms data of the investigated compounds , a waters quattro premiere xe triple - quadrupole mass spectrometer ( micromass ms technologies ) was coupled to the abovementioned uplc system . the mass range was set at m / z 1001000 da with the scan time being 0.5 s. the ionization parameters were as follows : interval time , 0.2 s ; capillary voltage , 3.5 kv ; cone voltage , 35 kv ; ionization resource temperature , 120c ; desolvation temperature , 380c , desolvation gas flow rate , 500 l / h ( n2 ) ; and cone gas flow rate , 50 l / h ( n2 ) . masslynx software ( version 4.1 ) and quanlynx software were used for system control and data processing , respectively . 5 ml methanol was added to 1 ml blank rat serum sample or wjsh capsule serum sample . the mixture was vortexed for 3 min . and centrifuged for 15 min . each residue was reconstituted in 1 ml methanol and centrifuged for 15 min . the extracts of wjsh capsule and raw medicinal materials of wjsh capsule were prepared separately . 10 ml methanol was added to 0.4 g wjsh or each raw medicinal material . centrifuged ( 3000 rpm ) for 15 min . , and filtered through 0.45 m micropore film ( millipore , usa ) . male sprague - dawley rats ( 230 g 10 g , experimental animal center of heilongjiang university of traditional chinese medicine ) were randomly divided into eight groups ( six for each ) : group a to group h. all care and handling of animals were performed with the approval of institutional authority for laboratory animal care of heilongjiang university of traditional chinese medicine . after 12 hours of fasting , normal saline ( blank control ) and extract of wjsh capsule were given intragastrically to rats in group a and group b , separately . extracts of raw medicinal materials were given intragastrically to rats of the other 6 groups ( one extract per group ) . the dosage was 1.5 ml/100 g body weight , and the administration frequency was once daily in three consecutive days in each group . at forty minutes after the last administration , 5 ml blood the blood samples were centrifugated for 10 min . at 5000 rpm at 4c to separate serum samples . to purify the serum sample , the protein precipitation , liquid - liquid extraction , and solid - phase extraction methods were tried . finally , the simple protein precipitation method with methanol was chosen , since most investigated compounds were found in the purified samples . as compared to methanol - water system , higher resolution , better peak shape , and faster elution of compounds were achieved using acetonitrile - water system buffered with ammonium acetate and formic acid . the chromatographic separation of the absorbed components and metabolites was conducted in gradient elution mode to overall reduce the retention time of these compounds characterized by different polarities . the timetable of gradient elution was listed in table 1 . for the esi - ms conditions , the stronger responses of all compounds were obtained in positive ionization mode than in negative mode . thus , positive mode was employed in the total ion current ( tic ) chromatograms of wjsh capsule serum samples in the m / z range of 100 to 1000 da . the multiple bioactive components in tcm could be simultaneously identified using the uplc - esi - ms technique . it is generally helpful in better understanding the mechanisms underlying tcm 's therapeutic effects . the serum pharmacochemistry study of wjsh capsule was conducted in rats orally administered with wjsh capsule . then , the absorbed bioactive components including their metabolites were identified by the established uplc - esi / ms method . the typical tic chromatograms of wjsh capsule extract , wjsh capsule serum sample , and blank serum sample were shown in figure 1 . twelve chemicals of which chromatographic peaks appeared in the tic chromatograms of wjsh capsule serum sample and wjsh capsule extract , but not in that of the blank serum sample , were presumed to be the absorbed components . similarly , four chemicals whose chromatographic peaks presented only in the tic chromatograms of wjsh capsule serum sample , but not in that of the wjsh capsule extract or the blank serum sample , were supposed to be metabolites . by comparing the ms / ms spectra , the chromatographic peaks in tic chromatogram of wjsh capsule serum sample versus the standards , respectively , seven absorbed components were identified unequivocally . for instance , the ms / ms spectrum of peak 5 was compared with that of the isofraxidine standard . these ms / ms spectra were shown in figure 2 . since the quasi - molecular ion at m / z 223 [ m + h ] , fragmentation ions at m / z 192 [ m + h - och3 ] , and at m / z 161 [ m + h - och3-och3 ] were found simultaneously in the ms / ms spectra of peak 5 and the standard of isofraxidine ; this absorbed component was confirmed to be isofraxidine . the other five absorbed components and the four metabolites were not identified and need further investigation . by comparing the tic chromatograms of serum samples , wjsh capsule , wjsh capsule without radix et caulis acanthopanacis senticosi , and radix et caulis acanthopanacis senticosi alone , similarly , the original plant(s ) of the other absorbed components and metabolites were confirmed . the retention times , ms / ms data , and original plants of the absorbed components and metabolites were listed in tables 2 and 3 , respectively . by revealing the bioactive components of tcm compound prescriptions , serum pharmacochemistry studies might be significantly helpful in better understanding the mechanisms under the therapeutic effects of these prescriptions . for instance , wjsh capsule and danggui - shaoyao - san have been used extensively in chinese women to enhance uterine involution after giving birth and alleviate dysmenorrhea , respectively [ 11 , 12 ] . in pharmacological experiments , the prostaglandins ( pg ) levels regulation was proved to be partially responsible for the myometrium contraction stimulation and inhibition effects of wjsh capsule and danggui - shaoyao - san , separately [ 4 , 12 ] . in previous and present serum pharmacochemistry investigations , identical ( ferulic acid and liqustilide ) and different ( syringin , protocatechuic acid , liguiritin , isofraxidine , and chlorogenic acid for wjsh capsule ; paeoniflorin sulfonate , albiflorin , paeoniflorin , butylidenephthalide , and senkyunolide i for danggui - shaoyao - san ) bioactive components in wjsh capsule and danggui - shaoyao - san were identified . by conducting comparative pharmacokinetic and pharmacological experiments , the major bioactive components in wjsh capsule and danggui - shaoyao - san related to the up- and downregulation effect on myometrium contraction might be confirmed , and the influence of other coexisting components on these effected might be revealed . thus , the mechanisms under wjsh capsule and danggui - shaoyao - san 's therapeutic effects might be elucidated . in this study , an uplc - esi - ms method was established for investigating the serum pharmacochemistry of wjsh capsule . in this way these results might be helpful for better understanding the mechanisms underlying the therapeutic effects of wjsh capsule .

to identify the compounds absorbed in rat serum after the oral administration of wu - jia sheng - hua ( wjsh ) capsule , a traditional chinese medicine ( tcm ) compound prescription , an ultraperformance liquid chromatography coupled with electrospray ionization mass spectrometry ( uplc / esi - ms ) method , was established . the chromatographic separation of the absorbed compounds and metabolites was achieved with an acquity uplc beh c18 column ( 2.1 mm 50 mm , 1.7 m ) under a gradient elution . the mobile phase was composed of acetonitrile and water buffered with ammonium acetate ( 10 mm ) and formic acid ( 0.1% , v / v ) . twelve absorbed compounds and four metabolites were found . seven of the absorbed compounds were identified by esi - ms . the identification of absorbed compounds might be helpful for the better understanding of the mechanisms underlying the pharmacological effects of wjsh capsule .

we identified rvh in a porcine intestinal sample ( rvh / pig - wt / usa / ar7.10 - 1/2012/gxp[x ] ) submitted from a farm in arkansas in 2012 . subsequently , we rescreened 204 available rva- , rvb- , and/or rvc - positive porcine samples collected during 20062009 from 16 us states for rvh . the samples were from 5 different age groups of pigs : 13 days ( 21 samples ) , 47 days ( 23 ) , 820 days ( 19 ) , 2155 days ( 110 ) , and > 55 days ( 9 ) ; 22 samples were from pigs of unknown age . sample selection , histologic examination , extraction of genomic material , reverse transcription pcr ( rt - pcr ) amplification , sequencing of viral protein ( vp ) 6 gene , and statistical and sequence analysis are described in the online technical appendix ( http://wwwnc.cdc.gov/eid/article/20/7/14-0034-techapp1.pdf ) . we identified rvh in 30 ( 15% ) of the 204 samples , including sample ar7.10 - 1 ( online technical appendix table ) . rvh strains were identified in samples from 10 us states ( figure 1 , panel a ) . the first us sample was identified on november 7 , 2006 . of samples from age groups in which we detected positive results , most ( 20/111 , 18% ) were from 2155-day - old pigs ; rvh was not detected in 13-day - old piglets . we also detected rvh - positive samples in 420-day - old ( 5/42 , 12% ) and > 55-day - old ( 5/9 , 56% ) pigs . the number of positive and negative samples differed significantly between age groups ( p = 0.036 , fisher exact test ) . the odds of 2155 day - old pigs being rvh positive was not significant ( odds ratio [ or ] 1.63 , p = 0.36 ) ; however , in the > 55-day group , the odds of being rvh positive was significant ( or 5.92 , p = 0.031 ) , compared with odds for the 420-day group . the trend for increased rvh positivity by age group was not significant ( p = 0.94 , wald test ) . epidemiologic and molecular distribution of porcine rotavirus h ( rvh ) strains , united states , 20062009 . a ) geographic distribution of rvh - positive porcine samples / total number of samples tested . pink indicates states containing positive samples ; green indicates states negative samples ; white indicates states from which samples were not submitted . b ) distribution of rvh - positive samples and age group in pigs co - infected with rva , rvb , and/or rvc . blue indicates samples from the 420-day age group ; pink indicates samples from the 2155-day age group ; green indicates samples from the > 55-day age group . although we identified only 5 samples with rvh in pigs co - infected with rva and rvb , co - infections with rvh and rva , rvb , both rva and rvc , or both rvb and rvc ( 1 sample each ) also were identified but did not differ significantly ( p>0.05 , fisher exact test ) ( figure 1 , panel b ) . most rvh samples ( 21 [ 70% ] ) were identified from pigs co - infected with rva , rvb , and rvc , which was significantly higher from any other rvh co - infections with rva , rvb , rvc , rvab , rvac , or rvbc ( p<0.001 , fisher exact test ) . of these 21 rva , rvb , rvc , and rvh co - infected samples , 15 were from 2155-day - old pigs ( figure 1 , panel b ) . kf757260kf757289 ) exhibited 91%100% nt identity with each other and shared 89%92% nt identity with japan porcine strain ska-1 and 85%87% nt identity with brazil porcine strains br63 , br60 , and br59 ( table 1 ) . the us porcine rvh vp6 sequences were 97%100% aa identical with each other and 97%98% and 96%98% aa identical with the japan and the brazil porcine strains , respectively . the us porcine and human rvh vp6 sequences were 75.3%76.8% aa identical ( table 1 ) . the nucleotide and amino acid pairwise identity charts ( figure 1 , panels c and d ) and phylogenetic trees ( figure 2 , panel a ) suggest the existence of at least 2 distinct rvh vp6 ( i ) clusters / genotypes containing human and porcine strains , respectively . * rvh , rotavirus h ; na , not applicable a ) nucleotide neighbor - joining phylogenetic tree of rotavirus ( rv ) a d and f h viral protein ( vp ) 6 sequences . blue strains are from the united states ; green strains are from brazil ; and the red strain is from japan . b ) time - scaled phylogeny of swine rvh vp6 sequences using a bayesian markov chain monte carlo approach . blue shaded region indicates the time from the most recent common ancestor range ( tmrca ) of the us strain ; red shaded region indicates the us and japan rvh tmcra range ; green shaded region indicates the tmrca range for all swine rvh vp6 sequences . compared with other rv species , the us rvh vp6 sequences shared the highest nucleotide and amino acid identities with rvg ( 51%53% and 39%41% , respectively ) and rvb ( 47%52% and 34%39% , respectively ) ( table 2 ) . in the rv vp6 phylogenetic tree , the rvh , rvg , and rvb vp6 sequences clustered in 1 large branch , whereas the rva , rvc , rvf , and rvd sequences clustered separately in another large branch ( figure 2 , panel a ) . the rvh evolutionary rate ( substitution / site / year ) from beast ( http://tree.bio.ed.ac.uk/ ) was estimated at 2.6 10 ( 95% ci 5.83 10 to 4.46 10 ) . on the basis of the estimate of the time from the most recent common ancestor for the vp6 gene segment , we believe that us rvh strains circulated in us swine for at least a decade and possibly much longer ( the time from the most recent common ancestor 19632002 , 95% highest posterior density [ hpd ] ) ( figure 2 , panel b ) . the us and japan rvh vp6 sequences diverged during 19551993 , 95% hpd , and the estimated divergence of the brazil rvh vp6 sequences from the us and japan rvh vp6 sequences was 18321991 , 95% hpd . * rv , rotavirus ; na , not applicable . although the samples analyzed already were known to be positive for rv species a , b , and/or c , our identification of rvh in 15% of samples is remarkable . in the united states , piglets are weaned at 21 days of age and then mixed with other piglets from different production sites , which may explain the higher rate of rv co - infections in 2155-day - old pigs ( 10,11 ) . these findings suggest that rvh is underdiagnosed in us swine herds and requires further surveillance . our phylogenetic analysis indicates that the rvh strains circulating in us swine is evolutionarily distinct from that found in humans , as well as from swine in brazil and japan . although our low sample number and sequencing of a single gene ( vp6 ) makes the genetic diversity of rvh in us swine herds difficult to fully assess , the lack of spatial structure in the tree indicates extensive gene flow of rvh between swine herds in different us regions . inferring the circulation of rvh in us swine herds is difficult because of the small sample size , although our time - structured phylogenetic analysis indicates at least 1 decade of circulation . although us swine are routinely transported to south america , the phylogeny indicates that the vp6 gene of us swine rvh viruses is more closely related to that of japan strain ska-1 than to those of the 3 brazil strains included in this analysis . in conclusion , we identified rvh in 30 samples from pigs co - infected with rva , rvb , and/or rvc in the united states , which indicates that rvh has been circulating in us swine for at least 1 decade and perhaps for longer . the human and porcine rvh vp6 sequences clustered into separate branches in the phylogenetic tree , but the presence of rvh in swine clearly raises the possibility of interspecies transmission . because the swine samples were co - infected with rva , rvb , and/or rvc , the role of rvh in pathogenesis remains unknown but this circumstance illustrates the need for molecular epidemiologic studies . sample selection , histologic examination , extraction of genomic material , reverse transcription pcr amplification , sequencing of viral protein 6 gene , and statistical and sequence analysis of rotavirus h , united states , 20062009 .

we investigated the presence in us pigs of rotavirus h ( rvh ) , identified in pigs in japan and brazil . from 204 samples collected during 20062009 , we identified rvh in 15% of fecal samples from 10 us states , suggesting that rvh has circulated in the united states since 2002 , but probably longer .

a 67-year - old post - menopausal woman visited the clinic due to vaginal bleeding . levels of serum tumor markers , including carbohydrate antigen 125 and carbohydrate antigen 19 - 9 , were normal . curettage of the endometrial lesion showed endometrioid adenocarcinoma , the international federation of gynecology and obstetrics ( figo ) g1 . there was an ill - demarcated grayish mass , measuring 43.73.5 cm , on the anterior wall of the endometrium considered to be endometrial origin . there was another well - demarcated heterogeneous white to yellowish partially hemorrhagic and fibrotic mass , measuring 654.4 cm , on the posterior wall of the myometrium . the cut surface of the mass showed an ill - demarcated yellowish necrotic lesion , enclosed by a whitish fibrotic area . 1 ) . the endometrial lesion had the histologic appearance of endometrioid carcinoma , the same as the previous curettage ( fig . the histologic findings of the myometrial mass were characterized by infiltration of spindle to ovoid cells into the surrounding leiomyoma . frequent mitotic activity was encountered in up to 14/50 high - power fields ( hpf ) . immunohistochemical staining was performed on the myometrial lesion for cd10 , caldesmon , desmin , -smooth muscle actin ( sma ) , human melanoma black 45 ( hmb-45 ) , melan - a , transcription factor e3 ( tfe3 ) , and ki-67 . the infiltrating tumor cells were positive for sma , hmb-45 , and tfe3 with a low ki-67 index of about 5% , but they were negative for cd10 , caldesmon , and desmin ( fig . pecomas , which have no known normal tissue counterpart , are unique in that they react immunohistochemically for both melanocytic and myoid markers . reviewed 26 cases of pecomas of soft tissue and gynecologic origin . according to that report , all cases demonstrated expression of at least one of the melanocytic markers ( hmb-45 , melan - a , and microphthalmia transcription factor ) , and hmb-45 showed the highest rate of positivity at 92% . they also showed positivity for myoid markers with sma ( 80% ) and desmin ( 36% ) . our case demonstrated positivity for both hmb-45 and melan - a , and melanin pigments were observed in some cells . among the myoid markers , our case was positive for sma and negative for desmin and caldesmon . the existing leiomyoma was positive for desmin and caldesmon , so the pecoma was clearly defined from the large preexisting leiomyoma at the peripheral portion of the bulky mass . we reviewed all case series published in english available in pubmed that included more than three cases of pecoma in the female genital tract , for a total of 63 cases . the results ( table 1 ) [ 6 - 8 ] show that all ( 100% ) of the tested cases showed positivity for hmb-45 , and 52.8% were positive for melan - a . myoid markers including sma , caldesmon , and desmin were positive in 74.5% , 66.0% , and 94.4% of tested cases , respectively . cd10 immunostaining was performed in 23 cases and showed positivity in six cases ( 26.1% ) . these results confirm the diagnostic value of immunohistochemistry profiling in uterine pecoma , especially the use of melanocytic and myoid markers , due to their high rates of positivity . the differential diagnosis of uterine pecoma includes uterine smooth muscle tumor , endometrial stromal tumor , gastrointestinal stromal tumor ( gist ) with secondary involvement of the uterus , and other sarcomas such as alveolar soft part sarcoma ( asps ) . paraganglioma , metastatic melanoma / clear cell sarcoma of soft part , and rarely , carcinoma should also be considered in the differential diagnosis due to their epithelioid cytomorphology . positivity enables a differential diagnosis of pecoma from uterine smooth muscle tumor , endometrial stromal sarcoma , and asps . there was a report of late pulmonary and renal metastatic pecomas with initial misdiagnosis as uterine leiomyosarcomas . cd10 , which usually shows diffuse and strong immunoreactivity in endometrial stromal tumors , may be helpful in the differential diagnosis because 25% of uterine pecomas are reported to be positive for cd10 . the exclusion of gist from pecoma may be possible on the basis of cd34 staining , as well as c - kit positivity and melanocytic marker negativity in gists . metastatic melanoma and/or clear cell sarcoma can be distinguished from pecoma by the strong s-100 protein immunoreactivity of the former and their muscle marker negativity . tfe3 is a member of the mit family of transcription factors , and tfe3 gene fusions have been found in some neoplasms such as asps and a subset group of renal cell carcinoma . the group harboring tfe3 gene fusion is reported to be more common in young patients , to be unrelated to tuberous sclerosis , to show alveolar architecture , and to have more epithelioid than spindle cell cytology and minimal immunoreactivity for myocytic markers . because of the small number of cases , however , it is difficult to define these cases as a single distinct group showing specific clinical characteristics compared with conventional pecomas . there was a report of a concomitant pecoma and an endometrioid carcinoma with synchronous / metastatic bilateral ovary carcinomas and uterine leiomyoma . the case had a finding common to ours in that there was a well differentiated endometrial carcinoma involving a depth of more than half of the myometrium with a synchronous separate pecoma . in that case , however , the pathologic examination revealed benign features of pecoma and it presented as a subserosal mass , unlike our case , which presented as a protruding endometrial mass and showed malignant features . criteria for malignancy of pecoma of the female genital tract are currently not clearly defined due to insufficient case studies . according to criteria that are currently accepted , pecomas are classified into three categories : benign , uncertain malignant potential , and malignant . benign is defined to exhibit the following gross or histologic features : gross size < 5 cm , non - infiltrative growth , non - high - grade nuclear features , no necrosis or vascular invasion , and a mitotic rate < 1/50 hpf . tumors of uncertain malignant potential are defined as corresponding to one or more of the following features : nuclear pleomorphism or multinucleated giant cells , or gross size > 5 cm regardless of cellular features . satisfying the malignant category refers to cases which show two or more of the following features : gross size > 5 cm , infiltrative growth , high - grade nuclear features , necrosis , vascular invasion , or a mitotic index 1/50 hpf . according to the largest single series of pecomas of gynecologic origin , the current classification system was very specific and sensitive for the diagnosis of malignant pecoma in the gynecologic tract .

perivascular epithelioid cell tumors ( pecomas ) refers to a family of mesenchymal neoplasms composed of angiomyolipomas , clear cell sugar tumors of the lung , and lymphangioleiomyomatoses . these tumors have a distinctive and common component of perivascular epithelioid cells that show an association with blood vessel walls and immunohistochemically display myomelanocytic differentiation . the unique neoplasms have been shown to have an expanded range through a variety of case reports , including visceral , intra - abdominal , soft tissue , and bone tumors . the retroperitoneum , abdominopelvic region , and uterus have been reported to be the most common sites . most pecomas follow a benign course . however , reports of malignant pecomas are increasing . many papers have described uterine pecomas , but to our knowledge , there have not yet been any reports of a malignant pecoma arising concomitant with another epithelial tumor and mesenchymal tumor . we report herein the case of a 67-year - old woman who experienced a malignant uterine pecoma infiltrating a preexisting intramural leiomyoma with synchronous well differentiated endometrial carcinoma and multiple liver and lung metastases .

in healthy subjects , euglycemic hyperinsulinemia and carbohydrate - rich meals increase skeletal muscle blood flow through insulin receptor signaling and activation of endothelial nitric - oxide synthase . this response leads to an increase in capillary blood volume ( cbv ) and a higher functional capillary surface area , which in - turn facilitates insulin - mediated glucose uptake . insulin resistance ( ir ) and obesity limit the insulin - mediated expansion of cbv , which is thought to contribute to reduced glucose uptake . furthermore , we have demonstrated that inactivity , in the absence of obesity , reduces the cbv response to a glucose challenge and strongly correlates with the degree of ir . vasoactive compounds other than nitric - oxide are thought to participate in the metabolic regulation of cbv . metabolism of arachadonic acid through cytochrome p-450 enzymes produce epoxyeicosatrienoic acids ( eets ) , a family of endothelial - derived vasodilators that can influence skeletal muscle blood flow . these vasodilatory eets are converted by soluble epoxide hydrolase ( seh ) enzymes to less biologically active dihydroxyeicosatrienoic acids ( dhets ) . inhibitors of seh have been shown to increase skeletal muscle blood flow and cbv and to improve insulin sensitivity . alternative metabolism of arachadonic acid through separate cytochrome p-450 enzymes produce the vasoconstrictors 18 , 19 , and 20-hydroxyeicosatetraenoic acids ( hetes ) that are associated with hypertension . while we have previously shown that the concentration of 14,15-eet may be suppressed in inactive and ir primates , little is known about hetes and measures of seh activity in regulating skeletal muscle blood flow and their contribution to ir in a non - human primates . we hypothesized that an imbalance in vasoactive arachadonic acid metabolites toward a more vasoconstrictive pattern in activity - restricted ir primates would correlate with abnormal cbv response to glucose and measures of ir . this study was approved by the animal care and use committee of the oregon national primate research center and conform to the guidelines for the care and use of laboratory animals published by the national institutes of health . sixteen adult male rhesus macaques ( macaca mulatta ) 912 yrs of age were studied . ten animals were activity - restricted for a mean of 6 years in single - cage housing and the remaining six animals that formed the normal - activity cohort were group - housed in 1-acre corrals . all animals were fed standard chow diet ( fiber - balanced monkey diet ) and underwent the following procedures as previously described : ( 1 ) intravenous glucose tolerance test ( ivgtt ) for calculation of insulin area - under - the - curve ( auc ) concentration and the homeostatic - model of ir ( homa - ir ) , ( 2 ) dual x - ray absorptiometry for assessment of lean muscle mass and truncal fat percentage , ( 3 ) flow - mediated vasodilation for nitric - oxide bioavailability , ( 4 ) contrast - enhanced ultrasound of the skeletal muscle for resting and glucose - stimulated peak skeletal muscle blood flow and cbv , and ( 5 ) calculation of the microvascular ir index as the change in insulin concentration divided by the peak cbv ( insulin / cbv ) achieved during the ivgtt . plasma samples were analyzed by liquid - chromatography / mass spectrometry for freely circulating eets cis - regioisomers ( 14,15-eet , 11,12-eet , 8,9-eet ) , their corresponding seh metabolites ( 14,15-dhet , 11,12-dhet , 8,9-dhet ) , and for hetes the ratio of vasodilatory eets to their less biologically active dhets ( dhet / eet ) was assessed as indirect measure of seh activity . data were analyzed by prism ( v5.0 , graphpad software , inc . ) and are expressed as se . parametric data were analyzed with unpaired student s t - test and pearson s product test for correlations . non - parametric data were analyzed with mann - whitney - u test and spearman s rho values for correlations . data were analyzed by prism ( v5.0 , graphpad software , inc . ) and are expressed as se . parametric data were analyzed with unpaired student s t - test and pearson s product test for correlations . non - parametric data were analyzed with mann - whitney - u test and spearman s rho values for correlations . compared to the normal - activity cohort , activity - restricted primates were similar in age , weight , lean muscle mass , and truncal fat % ( table 1 ) . although basal insulin and homa - ir were not significantly different between groups , the activity - restricted group was ir as indicated by elevated insulin auc concentration ( table 1 ) . on contrast - enhanced ultrasound imaging under basal / fasting conditions there was a trend for lower skeletal muscle microvascular blood flow and a significantly lower cbv in the activity - restricted versus normal - activity primates ( table 1 ) . during the ivgtt , there was a reduction in the microvascular response to the glucose bolus in the activity - restricted group manifest by a lower peak microvascular blood flow that was attributable to a lower peak cbv ( table 1 ) . the endothelial - derived eicosanoid vasodilators ( 8,9-eet , 11,12-eet , and 14 , 15-eet ) as well as the mean concentration of these vasodilators tended to be higher in the normal - activity primates but was not different between the two cohorts ( table 1 ) . conversely , each of the dhets regio - isomers was elevated in the activity - restricted cohort and the combined average of the dhets metabolites were significantly elevated compared to the normal - activity primates ( table 1 ) . the overall production of vasodilatory eicosanoids , assessed as the sum of all eets and dhets regio - isomers , was not different between the normal - activity ( 845 79 pg / ml ) and the activity - restricted primates ( 1026 141 pg / ml ) p=0.25 , suggesting that the increase in dhets concentrations were not due to an increased production of vasodilatory eicosanoids . as such , the dhet / ett ratio was assessed as an indirect measure of seh activity . each of the dhet / eet ratios was elevated in the activity - restricted cohort and the average dhet / eet ratio was significantly elevated ( table 1 ) suggesting an up - regulation of seh activity . the eicosanoid vasoconstrictor concentrations of 18-hete,19-hete , and 20-hete were elevated in the activity - restricted primates , though significant elevations were noted in 18 and 19-hete ( table 1 ) . the eicosanoid vasoconstrictors 18 , 19 , and 20-hete and the dhet / eet ratio all correlated inversely with the peak cbv during ivgtt ( figure 1 ) . conversely , both 18-hete and 19-hete correlated linearly with the microvascular ir index ( figure 1 ) . although brachial artery fmd was significantly reduced in the activity - restricted cohort ( table 1 ) , suggesting reduced nitric - oxide bioavailability , no correlations were noted with microvascular blood flow or measures of ir . eicosanoids are endothelial - derived vasoactive substances that can influence skeletal muscle blood flow and functional capillary recruitment . dynamic changes in cbv are thought to be important for facilitating skeletal muscle glucose uptake . our hypothesis that eicosanoid - mediated changes in cbv influence glucose handling are based on findings that seh inhibitors improve blood glucose concentrations , modulate cbv , and ameliorate ir in small animal models of disease . the purpose of this study was to examine the arachadonic acid derived vasodilator and vasoconstrictor pathways in concert with skeletal muscle blood flow in a primate model of ir produced by inactivity . our data indicate that elevated eicosanoid vasoconstrictors ( 18,19 , & 20-hete ) and the indirect measurement of seh activity ( elevated dhet / eet ratio ) are contributors in the pathophysiology of impaired capillary recruitment and microvascular ir in lean activity - restricted primates . furthermore , this study supports the notion of a reflexive shift between reduced physical activity and alterations in vascular tone as a potential pathophysiologic link between reduced activity , impaired microvascular capillary function , and ir . we studied a subset of ten activity - restricted primates that were part of a larger cohort of activity - restricted animals in which we first demonstrated that inactivity , in the absence of obesity , limits the cbv response to a glucose challenge and correlates with the degree of ir . in this original report it was the initial finding of a lower concentration of 14,15 eet that lead us to a more complete evaluation of eets , dhets , and hetes and their relationship to cbv and microvascular ir . thus , a full evaluation of arachadonic acid vasoactive metabolites was performed in ten out of the original thirteen primates previously described in which there was a sufficient amount of plasma available to complete testing . however , it should be noted that these vasoactive metabolites can be esterified and reincorporated into membrane phospholipid pools with future release into the circulation through phospholipase activity . thus , circulating concentrations of these metabolites do not reflect the complete vasoactive eicosanoid pool . an important limitation of the study is that we have not provided mechanistic proof that hetes or an altered dhet / eet ratio are responsible for abnormal cbv responses or contribute to ir . instead , we have provided compelling evidence for a relationship between elevated vasoconstrictors to a reduced cbv and elevated degree of microvascular ir . additionally , we have provided evidence for relationship between an elevated dhet / ett ratio as an indirect marker of seh activity with reduced cbv . these relationships support the notion that a shift in vasoactive arachadonic acid metabolites towards a more vasoconstrictive profile limit functional capillary recruitment and contribute to vascular ir . further long - term studies will be needed to understand the pathophysiologic consequences that may arise in the mediators of microvascular tone and the impact they have on skeletal muscle capillary function during the development of obesity . in summary , we have found that ir with inactivity shifts the plasma eicosanoids to a more vasoconstrictive profile and these findings may lead to new therapeutic vascular targets for the treatment of ir .

the inability to augment capillary blood volume ( cbv ) in response to insulin or glucose is thought to contribute to insulin resistance ( ir ) by limiting glucose uptake in key storage sites . understanding the mechanisms that contribute to impaired cbv augmentation early in the onset of ir may lead to new future therapies . we hypothesized that inactivity alters the balance of vasoactive eicosanoids and contributes to microvascular ir . in ten activity - restricted ( ar ) and six normal - activity ( na ) adult male rhesus macaques , contrast - enhanced ultrasound of skeletal muscle blood flow and cbv was performed at baseline and during intravenous glucose tolerance test ( ivgtt ) . plasma was analyzed for vasoconstrictor hydroxyeicosatetraenoic acids ( hetes ) and the ratio of vasodilatory epoxyeicosatrienoic acids ( eets ) to their less biologically active dihydroxyeicosatrienoic acids ( dhets ) as an indirect measure of soluble epoxide - hydrolase ( seh ) activity . ar primates were ir during ivgtt and had a 45% lower glucose - stimulated cbv response . vasoconstrictor 18-hete and 19-hete and the dhet / eet ratio were markedly elevated in the ar group and correlated inversely with the cbv response . additionally , levels of 18-hete and 19-hete correlated directly with microvascular ir . we conclude that a shift towards increased eicosanoid vasoconstrictor tone correlates with abnormal skeletal muscle vascular recruitment and may contribute to ir .

the human thumb is opposable and prehensile , making it the most unique digit of the hand , responsible for hand functions , grasp , manual dexterity , and fine motor skills . the thenar eminence constitutes the intrinsic muscles of the hand that are responsible for complex movements of the thumb . congenital anomaly of the thumb and/or of the thenar muscles can be quite a disabling condition . in 1979 , arminio was the first to report congenital absence of the flexor pollicis longus ( fpl ) tendon . since then , many cases have been published with congenital absence of the fpl tendon with or without associated anomalies of the thumb and thenar muscles . most of the reports have documented unilateral absence of fpl tendon ; bilateral absence is extremely rare . only three cases of bilateral congenital absence of fpl tendon have been reported so far ; no thenar atrophy was seen in these cases . we present a case of a 9-year - old female child with bilateral congenital absence of fpl tendon and associated thumb hypoplasia and thenar eminence atrophy . a 9 year old female child presented to our hospital with difficulty in performing tasks like writing or holding an object . there was absence of flexion movement at interphalangeal ( ip ) joints of bilateral thumbs . local examination revealed minor hypoplasia of the thumbs and absence of dorsal wrinkles [ figure 1a ] and flexion creases [ figure 1b ] at the ip joints of both the thumbs . minor hypoplasia of both the thumbs and absence of dorsal wrinkles are seen ( arrows ) . ( b ) palmar surface of the hands show absent flexion creases ( arrows ) of bilateral thumbs . ( c ) functional limitation in holding a pen ; note the absence of active flexion of the interphalangeal joints of both the thumbs radiograph of hands showed mild skeletal and soft tissue hypoplasia of bilateral thumbs [ figure 2 ] . radiograph of both hands shows mild skeletal and soft tissue hypoplasia of bilateral thumbs magnetic resonance imaging ( mri ) of hands showed absence of bilateral fpl muscles . in addition , there was absence of flexor pollicis brevis ( fpb ) and abductor pollicis brevis ( abpb ) muscles and hypoplasia / atrophy of bilateral opponens pollicis ( op ) muscles . bilateral adductor pollicis brevis ( adpb ) muscles appeared normal in morphology [ figure 3 ] . t1w coronal image of both the hands shows absence of bilateral flexor pollicis longus ( fpl ) tendons . normally , fpl tendon is seen between the lateral head of flexor pollicis brevis ( fpb ) and the oblique head of adductor pollicis brevis ( adpb ) muscles , and is inserted into the base of the distal phalanx of thumb ( see inset images ) . bilateral flexor pollicis brevis ( fpb ) and abductor pollicis brevis ( abpb ) muscles were also absent . bilateral adpb muscles appeared normal in morphology after pre - anesthetic checkup , the patient was planned for fpl reconstruction in bilateral thumbs . two - staged surgery was planned ; in the first stage , flexor pulley was reconstructed , and 2 months later , fpl reconstruction was done using flexor digitorum superficialis ( fds ) tendon to the ring finger . postoperative physiotherapy was done to increase the range of motion ( rom ) of the ip joints of both thumbs . at this moment , the patient has achieved ~20 of flexion at the ip joints bilaterally . congenital inability to flex the ip joint of the thumb may be due to several causes , including congenital absence of fpl , anomalous insertion of fpl , congenital tenovaginitis of the flexor tendon sheath , partial anterior interosseous nerve paralysis , traumatic rupture of the fpl , and anomalous connection between the tendons . among these , congenital absence of the fpl is extremely rare . absence of fpl may occur with or without associated anomalies of the thumb and thenar muscles . thumb hypoplasia with congenital absence of the fpl tendon , but without hypoplasia of the thenar muscles is the rarest variation . congenital absence of thenar muscles ( e.g. fpb and abpb ) without absence of fpl has also been reported in literature . most cases are reported in the pediatric age group and only a few are described in adults . clinically , the affected thumb shows absent or less evident dorsal wrinkles and flexion creases . skeletal and soft tissue hypoplasia of thumb may be present . according to blauth et al . , thumb hypoplasia may be classified as isolated minor hypoplasia ( type 1 ) , associated with thenar hypoplasia and metacarpophalangeal ( mcp ) joint instability ( type 2 ) , musculotendinous / osseous deficiency with absent active motion at mcp or ip joint ( type 3 ) , floating thumb ( type 4 ) , and complete absence of the thumb ( type 5 ) . imaging may show absence ( agenesis ) , hypoplasia , or atrophy of the muscles and tendons . ultrasonography ( usg ) is a low - cost , safe , non - invasive , and rapid method of evaluating musculoskeletal system . it is indicated in patients with cardiac pacemakers and metal implants where mri is contraindicated . computed tomography ( ct ) and mri may be used to confirm and support the usg findings . surgical reconstruction followed by rigorous rehabilitation the preferred surgical technique is one- or two - staged tendon transfer using the fds tendon of the ring finger . the range of flexion achieved at ip joint after the surgery varies between 20 and 35. following surgery , planned physiotherapy is a must to obtain satisfactory results . this case is unique as it demonstrates bilateral congenital absence of fpl tendon in association with thumb hypoplasia and thenar atrophy in a child . thenar atrophy was due to selective absence of bilateral fpb and abpb , and hypoplasia / atrophy of op .

congenital absence of flexor pollicis longus with or without associated anomalies of thenar muscles and thumb is of rare occurrence . inability to flex the interphalangeal joint of the thumb and absent dorsal wrinkles and flexion creases of the thumb are important clues to the diagnosis . routine radiography and cross - sectional imaging help to confirm and document the condition . this article presents an extremely rare case of bilateral congenital absence of flexor pollicis longus tendon with thumb hypoplasia and thenar atrophy .

allergic conjunctivitis is the most common type i ige - mediated hypersensitivity reaction to environmental allergens involving the ocular surface , affecting approximately 25% of the general population and 30% of allergy - predisposed children.1 symptoms of allergic conjunctivitis include ocular pruritus , tearing , conjunctival edema , hyperemia , watery discharge , burning , and photophobia.2 treatment of allergic conjunctivitis involves topical and sometimes oral therapy as well as allergen avoidance . the current literature is limited in terms of the association between sinus disease and chronic allergic conjunctivitis.3,4 while in other ophthalmic symptomatology ( proptosis , epiphora , deep orbital pain , double vision),58 physicians often look to the adjacent sinus for the etiology , such an analysis is often overlooked in the patient with severe , unremitting allergic conjunctivitis refractory to traditional medical management . in particular , paranasal sinus mucocele has not been well documented as a possible cause of conjunctivitis , particularly in children . to our knowledge , there is only one case reported of a mucocele leading to chronic blepharoconjunctivitis and this was in an adult patient ( the adult population is more likely to have mucoceles than the pediatric population).8 more common ophthalmic symptoms of these benign , epithelial - lined , mucus filled sacs include proptosis , visual disturbances , motility defects , and pain due to mass effect.38 mucoceles have been documented in association with systemic diseases , such as cystic fibrosis ( cf ) , with a prevalence of 16% in cases of cf with symptoms of chronic upper airway disease . in addition , patients with cf generally have a large number of bacteria in their sputum and nasal secretions9 and therefore have a higher risk of infection ( mucopyocele).10 in cases of infection , drainage of the mucopyocele is indicated to ensure eradication of the organism that can have significant pulmonary consequences . identification and diagnosis of the mucocele is critical in helping maintain the pulmonary health of such patients , which can be difficult in atypical cases without symptoms of nasal obstruction . we present herein a case of a 3-year - old cf patient misdiagnosed for 2 years with chronic allergic conjunctivitis whose symptoms were caused by an ethmoidal mucopyocele infected with escherichia coli . a 3-year - old boy under pediatric pulmonary care for cf presented to the bascom palmer eye institute , university of miami , with a 2-year history of chronic bilateral conjunctival inflammation , mild epiphora , and irritation . despite bilateral disease , the patient was evaluated in multiple subspecialty ophthalmology clinics both in the united states and internationally and in each , he was diagnosed with allergic conjunctivitis . his parents denied symptoms of nasal obstruction , other than snoring , which had been present prior to the onset of the eye symptoms . treatment regimens , including emergency room treatment , involved the use of topical anti - allergy drops such as olopatadine ( patanol ) which improved the swelling only temporarily . he was referred to us for further evaluation . clinical examination disclosed erythema in the medial aspect of the orbit , lower lid greater than upper eyelid , a palpable prominence under the medial canthal tendon and in the region of the nasolacrimal sac , and telecanthus on the right ( figure 1 ) . he had a normal tear lake and no mucopurulent reflex with compression of the nasolacrimal sac . past medical history was notable for cf ; pancreatic insufficiency had been appropriately managed with pancreatic enzymes . additionally , he was noted to have chronic airway ( deep throat culture based ) colonization with e. coli , an organism seen infrequently in young children with cf . despite multiple attempts to eradicate it with nebulized tobramycin and oral antibiotics , the organism persisted . a decision was made against long - term antibiotics , as e. coli is not considered to be a gram - negative organism that predicts an adverse pulmonary outcome in patients with cf . magnetic resonance imaging ( mri ) of the brain was obtained to further evaluate the medial canthal prominence . in the orbits , an area of mass effect was seen in the canthal region of the right orbit . this area extended inferiorly to the level of the inferior turbinate and involved a large area of the ethmoid sinus on the right side . the mass had high signal intensity on t1 and low signal on t2 weighted images , and there was ring - like enhancement ( figure 2a c ) , most consistent with an ethmoidal mucocele . the patient underwent functional endoscopic sinus surgery at the university of miami with marsupialization of the right ethmoidal mucocele ( figure 3a and b ) , which was later confirmed by culture to be infected with e. coli . after post - operative follow - up and continuous pulmonary care , the patient showed no symptoms of allergic conjunctivitis , the telecanthus and medial canthal mass resolved , and the upper airway has remained free of e. coli . the association between chronic conjunctivitis and mucocele in cf patients has not been well established in the literature but is an important consideration for the ophthalmologist , otolaryngologist , and pulmonologist managing these patients . disease of the nose and paranasal sinuses occurs in almost all cf patients ; most patients develop chronic sinusitis , and often bacterial infection thereof early in the course of their disease . while there is little recognition in the cf community of the presence of mucoceles , paranasal mucocele have in fact been documented to have a prevalence as high as 16% in patients with cf with symptoms of chronic upper airway disease who underwent otolaryngology evaluation.10 interestingly , ocular or orbital findings are relatively rare in this population . only one patient in this series presented with hyperemic conjunctiva , and this patient also had nasal symptoms including persistent purulent rhinorrhea and nasal obstruction.10 other case reports document mucoceles in the pediatric cf patients with the more typical findings of nasal obstruction.11 thus , in the common cf practice , conjunctival disease is not viewed as part of the presentation of a mucocele , and its presence would not alert the cf expert to a potential underlying contiguous infectious focus . more specifically , sinus disease is often not considered in a patient who presents with symptoms of periorbital or ocular allergic disease . our patient developed chronic , refractory , and asymmetric allergic conjunctivitis as well as recurrent e. coli colonization of the respiratory tract , both of which were manifestations of an ethmoidal mucopyocele . both the recurrent airway e. coli colonization and symptoms of allergic conjunctivitis resolved post - functional endoscopic sinus surgery and he has remained stable . we hypothesize that the chronic low grade exposure to e. coli created an atypical allergic conjunctivitis . this hypothesis is supported by previous documentation of allergic conjunctivitis secondary to stimulus of the nasal mucosa , thought to be potentially related to various neuropeptides , cytokines , chemokines , chemotactic , and other factors.12 it is also possible that he in fact had a low - grade bacterial conjunctivitis given the significantly worse symptoms and signs on the eye ipsilateral to the mucocele , but this can not be confirmed as cultures of the ocular surface were not performed . e. coli is a rare cause of ophthalmic infection , most commonly in the neonate causing infectious conjunctivitis or in immunosuppressed adults and is rarely found in the normal conjunctival flora.13 the important clinical factor is that his symptoms and exam , which were most consistent with allergic conjunctivitis , resolved completely after eradication of the mucocele . it is always important to consider the adjacent sinuses when managing a patient with chronic periocular symptomatology , particularly allergic disease , even in pediatric cases . of further important note is that in the specific condition of cf , mucoceles are more common and are more likely to be infected ( ie , mucopyoceles ) , while in otherwise normal patients they are almost uniformly sterile . this is an important distinction for the patient with cf , since a chronic source of bacterial infection in the upper airway can become the source of infection spread to the lower airway , the latter infections being the major determinant of long - term outcome in such patients . our case report highlights that chronic conjunctivitis in cf patients that is refractory to standard management should lead to a thorough evaluation including bacterial cultures and in some cases neuroimaging to determine and properly treat a putative underlying cause .

this case report details an association of chronic allergic conjunctivitis and respiratory tract colonization in a cystic fibrosis ( cf ) patient due to an ethmoidal mucocele infected with escherichia coli . a 3-year - old cf patient presented for evaluation with complaints of chronic periocular erythema , conjunctival injection , and irritation for 2 years . he was treated for presumed allergic conjunctivitis with no improvement and continued to have overall worsening of symptoms on the right greater than the left eye in a waxing and waning pattern . on presentation to the bascom palmer eye institute , he was noted to have telecanthus and prominent erythema in the region of the medial canthus . orbital imaging disclosed a mucocele in the right ethmoid sinus . the patient underwent functional endoscopic sinus surgery , with successful marsupialization of the ethmoidal mucocele , which was found on culture to be infected with e. coli . post - operatively with continuous pulmonary care , the patient remains free of allergic conjunctivitis and e. coli colonization of the upper airway . this case highlights the importance of analyzing the adjacent sinus in patients with chronic , relapsing allergic conjunctivitis refractory to medical management , particularly in patients with underlying systemic diseases such as cf .

over the years , various surgical techniques have been used in patients with coarctation of the aorta . the choice of procedure has been influenced , on one hand , by the trend at the time of presentation and on the other hand , by the presence of associated cardiac anomalies . in this article , we review the common techniques before dwelling on the one mostly used in recent years . in most cases , the surgical approach is through a left thoracotomy performed usually in the fourth intercostal space . the patient is placed in a lateral position with the left side up ( fig . a curved incision is made , starting at the anterior axillary line and extending posteriorly just below the tip of the scapula where it curves upward to end midway between the vertebral column and scapula over the anteroinferior margin of the trapezius muscle ( fig . the serratus anterior is mostly preserved while the fourth intercostal space is identified and opened . the rib spreader is inserted and opened in stages to avoid rib fractures ( fig . the lung is retracted anteriorly and the mediastinal pleura opened over the aorta downward for about 3 cm below the coarctation site and then upward across the entire left subclavian artery . the proximal left subclavian artery , the distal transverse arch and the aortic isthmus are dissected and tapes may be placed around them . to minimize the possibility of damage to the thoracic duct , all dissection is done close to the aorta . when present , abbott 's artery which arises from the medial aspect of the isthmus , should be ligated and divided . patient position ( left lateral approach ) a curved incision is made on the left thorax left lateral thoracotomy mobilization of the aorta and other structures a. a view of the site of coarctation after mobilization of key structures . b : in the extended resection technique , the transverse arch is also dissected to enable wider mobility and resection with the patient 's nasopharyngeal temperature at about 33c , aortic clamps are placed above and below the site of coarctation . the position of the vascular clamp , proximal to the site of coarctation , will depend on the site of coarctation and the type of procedure chosen ( fig . position of the aortic clamps and resection of the coarctation site resection and end - to - end anastomosis first developed by gross et al,3 this technique is still widely used especially in older children and adults . after sufficient mobilisation of the aortic arch and placement of the vascular clamps , the aorta is transected proximal to the coarctation at a level that ensures removal of any narrowed portion of the isthmus as well as the coarctation . a similar transection is made below the site of coarctation . with the aortic clamps held by the second assistant , dotted lines indicate the points of resection . ia inominate artery , lcc left common carotis ls left subclavian artery da ductus arteriosus subclavian flap angioplasty also known as the waldhausen4 procedure after its author , it involves transection of the subclavian artery and its subsequent use as a flap to enlarge the site of coarctation . the subclavian flap technique . the left subclavian artery is transected ( b ) and used as a flap to enlarge the site of coarctation ( c ) prosthetic patch aortoplasty this technique was first used by vosschulte5 in 1957 and entails the use of a prosthetic patch to enlarge the site of coarctation . the prosthetic patch aortoplasty . the ducuts is ligated and transected extended resection and end - to - end anastomosis . unlike in the first procedure described above , the proximal incision in this case is extended to the under - surface of the aortic arch ( fig . a. resection of the coarctation lesion b. further resection of the distal end may be necessary . c. the proximal incision is extended to the under - surface of the transverse arch ( extended resection ) state after resection the aortic clamps are approximated and sutures placed beginning from the deep angle . the clamps are released - first , the distal and then the proximal clamp ; haemostasis is secured a line drawing of the extended resection and end - to - end anastomosis technique the choice of a particular surgical technique for the treatment of aortic coarctation is determined not only by the type of coarctation lesion but also by factors such as the presence of associated anomalies , the age at presentation and not the least , the surgeon 's preference . however , objective comparisons can be made based on such determinants as the rate of recoarctation and freedom from re - intervention . we conducted a study of 201 patients undergoing surgery for coarctation of the aorta over a period of ten years . 139 of these patients had simple or isolated coarctation , 35 had coarctation with ventricular septal defects ( vsd ) , while 27 patients had coarctation with complex intra - cardiac anomalies including hypoplastic left heart syndrome , transposition of the great arteries ( tga ) and shone syndrome . on the whole , our results showed that patients who underwent resection and end - to - end anastomosis were at a greater risk of recoarctation than were those who underwent other surgical procedures ( p = 0.01 ) . of the 19 cases of recoarctation , 15 ( 79% ) were patients who underwent resection and end - to - end anastomosis , 2 had extended resection and end - to - end anastomosis while the remaining 2 patients underwent subclavian flap angioplasty and total arch reconstruction respectively . . a further look at the cases of recoarctation showed that 12 of the 19 patients were neonates . 10 of these neonates were treated using resection and end - to - end anastomosis , 1 by extended end - to - end anastomosis , while 1 underwent total arch reconstruction . hence , the use of resection and end - to - end anastomosis in neonates is associated with a higher risk of recoarctation ( p>0,0001 ) than the use of extended resection and end - to - end anastomosis . these include : postoperative bleeding in 4 ( 2% ) patients , phrenic nerve injury in 3 ( 1.5% ) , horner 's syndrome in 1(0,5% ) and chylothorax in 4 ( 2% ) . we did not record any case of paraplegia or cns damage due to aortic cross - clamping . protective measures such as cooling the body temperature to about 33 c and maintaining a distal blood pressure of over 45mmhg during cross - clamping were employed in all patients . the duration of aortic cross clamp in most of our cases was less than 20 minutes .

coarctation of the aorta accounts for about 8% of all congenital heart diseases . since the first successful case of surgical treatment in 1944 by crafoord and nylin1 in sweden , several surgical techniques have been employed in the treatment of this anomaly . here , we review by illustration the various surgical options in coarctation of the aorta with emphasis on our preferred technique the extended resection and end - to - end anastomosis . why the extended resection technique ? our experience - and that of other institutions - has shown that this is a better option in childhood as it is associated with a lesser degree of recoarctation and subsequent need for re - intervention.2

a 33-year - old woman was admitted to our hospital with a two - month history of abdominal distension and edema . the patient had no prior history of drug usage , including oral contraceptives , and no relevant family medical history . upon admission , the patient underwent a physical examination , which revealed diffuse hepatomegaly , pitting edema in both legs , however no abnormal cardiac murmur . the laboratory findings indicated abnormalities including a hemoglobin level of 7.5 g / dl , a platelet count of 18,000/mm , as well as a slightly elevated serum alanine aminotransferase ( 50 u / i ) and aspartate aminotransferase ( 56 u / i ) . moreover , the hepatitis b virus antigen was negative , and the titer of the hepatitis b virus antibody and alpha - fetoprotein were normal . the clinical and radiological evaluation showed no evidence of rendu - osler - weber disease or hemangiomas in the extrahepatic region . an ultrasonography revealed a diffuse heterogeneous echoic infiltrative mass containing numerous and various - sized hypoechoic nodules involving the entire liver ( fig . 1a ) . a doppler ultrasonography revealed no remarkable tumor vascularities except for the underlying hepatic parenchymal vascular flow ( fig . a hepatic dynamic ct was performed and demonstrated the multifocal enhancing hepatic nodules on both the arterial and portal phases , as well as an increased area of contrast enhancement with a centripetal filling pattern of nearly the entire hepatic tumor on a delayed phase ct ( fig . however , there was no remarkable tumor calcification or intervening normal hepatic parenchyma in either of the hepatic lobes . subsequently , a 99mtc - labeled red blood cell scan was performed and the blood pool images were taken at five hours after inhomogeneous diffuse activity in the entire hepatic mass ( fig . 1 g ) . however , no extrahepatic mass with abnormally increased radioactivity was observed on this 99mtc - labeled red blood cell scan . our differential diagnoses included a diffuse hemangiomatosis , epithelioid hemangioendothelioma , and angiosarcoma . to rule out a hepatic angiosarcoma , an ultrasound - guided automated gun biopsy , using an 18-gauge core needle was performed in the right hepatic lobe . before the biopsy , the patient 's platelet count was 170,000/mm after infusion of fresh frozen plasma . the patient 's histology revealed prominent cavernous vascular proliferation and fibrosis without angiosarcomatous components ( fig . further , the patient showed no hemangiomas in other regions of the body , including the skin . the patient continued to complain about continuous abdominal distension , which rapidly progressed to the deterioration of hepatic function . it occurs in all age groups , although hepatic hemangiomatosis occurs predominantly in infants and may cause life threatening conditions ( 1 ) . however , diffuse hepatic hemangiomatosis in adults is very rarely encountered and moreso when observed without any other organ involvement ( 2 - 4 ) . although several cases of long - term adult survival of diffuse neonatal hemangiomatosis have been reported ( 5 , 6 ) , the etiology and natural history of diffuse hepatic hemangiomatosis remains unclear . the histological characteristics of hemangiomatosis includes the presence of large vascular channels in both the normal - appearing hepatic parenchyma and the cavernous tumor region ( 2 ) . the histological findings of our ultrasound - guided biopsy specimen revealed prominently increased vascular proliferation and fibrosis with no sarcomatous change on staining ( fig . 1h ) , as well as vascular endothelial cells showing positive staining on immunochemical stains , which included masson 's trichrome stain and the gomori reticulin stain . as no reliable clinical or radiological findings have been reported for the differential diagnosis of hepatic hemangiomatosis from rare primary vascular hepatic tumors such as hepatic hemangioendothelioma or angiosarcoma , the diagnosis relies solely on the histological findings ( 7 ) . also , because it is so rare , only a few reports document the imaging findings of diffuse hepatic hemangiomatosis . however , these imaging findings are similar to those of other common hepatic hemangiomas , including variable echoic lesions on the ultrasound , vascular pooling of contrast material within the tumor on angiography , a centripetal enhancement pattern on dynamic enhancement studies , and bright tumor signal intensities on t2-weighted mr images ( 2 , 3 , 8) . in our patient , the ultrasonography findings included a heterogeneous echoic infiltrative hepatic mass containing numerous hypoechoic nodules . compared to the histological findings our case showed a delayed centripetal contrast - enhancement pattern of the tumor on a dynamic ct and diffuse uptake on vascular pooling images from a 99mtc - labeled red blood cell scan . because our case revealed imaging findings similar to hepatic hemangiomas , epithelioid hemangioendotheliomas , and angiosarcomas , diffuse hepatic hemangiomatosis although previous reports have cited the role of steroid medications in the development of hepatic cavernous hemangiomas ( 10 ) and the administration of metoclopramide medications in a patient with diffuse hepatic hemangiomatosis ( 8) , no history of steroid or estrogen use was documented in the reported cases of diffuse hepatic hemangiomatosis , including our patient . the prognosis of diffuse hepatic hemangiomatosis without extrahepatic involvement is still unclear because it occurs so rarely and has variable clinical courses in affected patients . in the literature , various prognoses have been reported for diffuse hepatic hemangiomatosis without extrahepatic lesion in adults ( 2 , 3 , 8 , 11 ) . in our patient , the possibility exists that a minimal amount of the remaining normal hepatic parenchyma with extensive hepatic hemangiomatosis involving the entire liver may have caused hepatic failure and subsequent patient death . more cases of diffuse hepatic hemangiomatosis are needed to establish their natural course and prognosis . despite its rarity , we concluded that the diagnosis of diffuse hepatic hemangiomatosis in adults can be suggested in patients with a diffusely involved hepatic tumor showing radiologic findings of hepatic hemangioma .

we report an extremely rare case of a diffuse hepatic hemangiomatosis without extrahepatic involvement in an adult . the imaging findings of this tumor were similar to those of a hepatic hemangioma and included contrast enhancement with a centripetal filling pattern of the entire hepatic tumor on the delayed phase of a dynamic ct and inhomogeneous diffuse uptake of the entire tumor on blood - pool images obtained five hours later on a 99mtc - labeled red blood cell scan . despite its rarity , diffuse hepatic hemangiomatosis can be suggested in adult patients with diffusely involved hepatic tumors showing the radiological findings of a hepatic hemangioma .

odontomas are hamartomas of aborted tooth formation , which account for 22% of the odontogenic tumors . compound odontomas manifest as a regularly shaped , solitary or multiple small tooth - like denticles , where all dental tissues are represented in a structural and more orderly pattern . a complex odontoma presents as an amorphous conglomeration of dental tissues consisting of enamel , dentin , cementum , pulp , and enamel organ . peripheral compound odontomas are rare , arise extraosseously , and have the tendency to exfoliate . the majority of compound odontoma cases ( 74.3% ) , are diagnosed before the age of 20 years , during routine radiographic examination , occurring commonly in the anterior maxillary region , without any gender bias . a 15-year - old , apparently healthy female patient reported to the department of orthodontics , with the chief complaint of forwardly placed front teeth . , it was found that 47 was missing and in place of that a small tooth - like structure was present [ figure 1 ] . the lesion was asymptomatic , with no signs of infection or ulceration of the surrounding mucosa . erupted odontoma in the region of 47 orthophantomogram revealed a missing 47 and a single small tooth - like radiopaque structure with a single root above the alveolar bone level in place of the missing second molar . a radiolucent zone was seen around the root - like structure [ figure 2 , figure 3 ] . orthophantomogram showing the odontome erupted position of the odontoma seen after 18 months this structure was extracted and it showed no morphological resemblance to any tooth of the normal series . after extraction the specimen was sent for histopathological examination , which confirmed it as a compound odontoma having enamel , dentin , pulp chamber , and cementum in the same order of arrangement as that of a normal tooth [ figure 5 ] . they are the most common odontogenic tumors constituting 22% of all odontogenic tumors of the jaws . the world health organization defines odontomas as being of two types : complex odontomas , a malformation in which all dental tissues are present , but arranged in a more or less disorderly pattern ; and compound odontomas , a malformation in which all the dental tissues are represented in a pattern that is more orderly than that of the complex type . enamel , dentin cementum , and pulp are arranged as they would be in a normal tooth . the intraosseous odontomas occur inside the bone and may erupt into the oral cavity ( erupted odontoma ) . the extraosseous or peripheral odontomas are odontomas occurring in the soft tissue covering the tooth bearing portions of the jaws , having a tendency to exfoliate . the review of literature reveals that 16 cases of erupted odontomas have been reported in which eight were compound odontomas . the etiology of odontomas has been attributed to various pathological conditions like local trauma , inflammatory and/or infectious process , hereditary anomalies ( gardners syndrome , hermanns syndrome ) , odontoblastic hyperactivity , and alterations in the genetic component responsible for controlling dental development . the persistence of a portion of lamina may be an important factor in the etiology of a compound or complex odontoma and either of this may occur instead of a tooth . peripheral odontogenic hamartoma 's ( poh ) histogenetic source may arise from soft tissue remnants of dental lamina . gingival rests of serres , seem to retain the ability to pursue epithelial - mesenchymal interactions that could lead to odontoma formation . since odontomas are seen in hereditary anomalies like gardners syndrome and hermanns syndrome , alteration of the genetic components might be responsible for odontoma formation . hitchin suggested that the odontomas are inherited through a mutant gene or interference , possibly postnatal , with genetic control of tooth development . stated that the differentiation of normal and tumor odontogenic cells is accompanied by the expression of some common molecules . the gene products present in some mesenchymal cells were also seen in the odontogenic tumor epithelium . the data may be related to a tumor - specific overexpression of the corresponding genes transcribed at an undetectable level during normal development and / or to an epithelial - mesenchymal transition proposed to occur during normal root formation . a plausible explanation for the result is that odontogenic tumor epithelial cells are recapitulating genetic programs expressed during normal odontogenesis , but the tumor cells demonstrate abnormal expression patterns for these genes . in 70% of odontomas , pathological anomalies are observed in relation to the neighboring teeth such as devitalization , malformation , aplasia , malposition , and impacted teeth ( unerupted teeth ) , where , as in the present case , the odontoma was associated with aplasia of 47 . radiographically , odontomas present as well - defined , radio - opacities situated in the bone , but with a density that is greater than bone and equal to or greater than that of a tooth . a radiolucent halo , typically surrounded by a thin sclerotic line , surrounds the radio - opacity . the radiolucent zone is the connective tissue capsule similar to that of the normal tooth follicle . in this case it was seen radiographically as a dense radiopaque structure outside the jaw bone , with clear external margins , presenting normal organization of dental tissues ( like enamel , dentin , pulp , and cementum ) . histopathological examination showed the presence of enamel , dentin , cementum , as well as pulp chamber in the normal order . commonly compound odontoma ( intraosseous ) is located between the apex of a primary tooth and the crown of a permanent tooth preventing the eruption of the latter . however , in the present case , the odontoma was located outside the jaw bone , in the soft tissue covering the tooth bearing portion of the jaw . it presented an area of bone resorption from the periosteal surface , which looked like a concave radiolucent zone . this odontome had the tendency to exfoliate as it had erupted into the oral cavity and was also mobile and about to be exfoliated . although microscopic and radiographic examinations confirm the diagnosis of compound odontoma , this case needs to be differentiated from supplemental and supernumerary teeth . supplemental tooth is the one , which resembles a normal tooth both morphologically and histologically and is located adjacent to the normal tooth , whereas , a supernumerary tooth is a tooth - like structure of variable size and shape . however , histologically it represents the normal organization of the tooth structure , like enamel , dentin , pulp , and cementum , including the periodontal ligament . in this case odontoma was associated with aplasia of 47 , whereas , the supplemental tooth and the supernumerary tooth were seen along with the normal series of teeth . the odontoma may arise from the remnants of dental lamina , gingival rest of serres . immunocytochemical investigations have indicated that a pattern of cellular activity involving reduced dental epithelium is associated with tooth eruption . this epithelial signaling could explain the remarkable consistency of eruption times , as it is likely that the dental epithelium is programmed as a part of its functional life cycle . however in the case of odontomas erupting into the oral cavity the mechanism behind the eruption times remains uncertain , as some odontomas erupt at a very young age and others at an older age . in the present case , after examining the two radiographs taken at an interval of 18 months [ figure 2 , figure 3 ] , it can be said that the erupting third molar beneath the odontoma might have been the cause of eruption and mobility of this odontoma . in the present case , since it was an erupted odontoma attached only to the soft tissue and being mobile on palpation , it was extracted . since these odontomas are not adherent to the bone they can be easily enucleated and curetted . in cases of larger odontomas where there are multiple components , it is necessary to take intraoperative radiographs to ensure that all the calcified masses have been removed . if any portion of the lesion is left unexcised such residual odontomas may remain unchanged throughout . very rarely the wound may get infected after an incomplete removal , since the avascular odontoma portion acts like foreign body . a rare case of erupted compound odontoma that was about to be exfoliated has been reported . the presence of a single tooth - like structure in the region of 47 , associated with a congenitally missing 47 is reported . the important feature found in this case was that the eruption time of this odontoma was approximately the same as that of the mandibular right second molar , which could be related to the aborted tooth formation .

odontomas are considered to be hamartomas rather than a true neoplasm . they consist chiefly of enamel and dentin , with variable amount of pulp and cementum when fully developed . they are generally asymptomatic and are included under the benign calcified odontogenic tumors . they are usually discovered on routine radiographic examination . eruption of an odontoma in the oral cavity is rare . peripheral compound odontomas arise extraosseously and have a tendency to exfoliate . in this article we are reporting a case of a 15-year - old girl with peripheral compound odontoma , with a single rudimentary tooth - like structure in the mandibular right second molar region , which is about to be exfoliated . its eruption in the oral cavity and location in the mandibular posterior region is associated with aplasia of the mandibular right second molar , making it an interesting case for reporting .

it has been postulated that the consumption of a high protein diet may cause harmful effects , particularly in the kidneys . approximately a century ago , investigators found at least some or very severe renal damage in a small group of rats on a high protein diet in which one kidney had been removed . other work on rodents found no evidence of renal damage ; however , they did find that rats receiving a high protein diet experienced renal hypertrophy . notwithstanding , a more recent rat study reported that 30 days of very high whey protein supplemented diet ( i.e. , 6 human - equivalent 20 g doses per day ) did not adversely affect blood and/or histological markers of liver or kidney health and instead may improve liver health when compared to rats not receiving protein . the challenge with determining the effects of high protein diets on measures of health is the lack of agreement with what constitutes a at least in athletic populations , the international society of sports nutrition's position stand on protein states that protein intakes of 1.42.0 g / kg / day for physically active individuals is not only safe , but may improve the training adaptations to exercise training . for instance , protein intakes greater than 15 - 16% of total energy , as high as 35% of total calories , or intakes that exceed the rda have been postulated as reaching the threshold of what constitutes a that is , if one were to consume a hypoenergetic diet of 1000 kcal in which 35% of the calories were derived from protein , then that would amount to a paltry 87.5 grams of protein . instead , high protein diets should always be defined as the amount of protein consumed per unit body weight . it is our contention that high protein diets should necessarily exceed 2.0 g / kg / d . previous work from our laboratory discovered that an eight - week period of heavy resistance training coupled with high protein consumption ( > 3.0 g / kg / d ) results in improvements in body composition . furthermore , at least in the short term , high protein intakes had no harmful side effects [ 6 , 7 ] . however , long - term longitudinal data are lacking in terms of the effects of high protein diets . thus , the purpose of this investigation was to examine the effects of high protein consumption in a group of resistance - trained young males over a 1-year period . fourteen resistance - trained male subjects volunteered for this investigation ( racial / ethnic background : 10 white males , 3 black males , and 1 pacific islander ) . subjects took part in a randomized crossover trial in which they consumed their habitual ( i.e. , normal protein ) or high protein diet for two months and four months , respectively . subjects followed their normal and high protein intake phases for a total of 6 months , respectively . they were tested at baseline and then subsequently after two 2-month periods and two 4-month periods of following the respective diet . the extra protein consumed by each subject was obtained primarily from whey protein powder , which was provided to each subject at no cost ( dymatize iso-100 with 25 grams of protein , 1 gram of carbohydrate , and zero grams of fat per serving of one scoop ) . however , subjects did not have to consume the extra protein as powder ; instead , they could consume whatever extra protein source they preferred . nova southeastern university 's human subjects institutional review board in accordance with the helsinki declaration approved this study and written informed consent was obtained prior to participation . subjects kept a diary ( i.e. , three days per week for one year ) of their food intake via a smartphone app ( myfitnesspal ) equaling ~150 daily food logs over the treatment period . the use of mobile apps for dietary self - reporting has been previously used [ 69 ] . the myfitnesspal app is a database comprised of over 5 million foods that have been provided by users via entering data manually or by scanning the bar code on packaged goods . thus , the data themselves are primarily derived from food labels ( i.e. , nutrition facts panel ) derived from the usda national nutrient database . height was measured using standard anthropometry and total body weight was measured using a calibrated scale . body composition was assessed by whole body densitometry using air displacement via the bod pod ( cosmed usa , concord , ca ) . subjects were instructed to come into the lab after a 3-hour fast and no exercise 24 hours prior to assessment . subjects were tested while wearing only tight fitting clothing ( swimsuit or undergarments ) and an acrylic swim cap . thoracic gas volume was estimated for all subjects using a predictive equation integral to the bod pod software . data from the bod pod include body weight , percent body fat , fat - free mass , and fat mass . all testing was done with each subject at approximately the same time of day for each of the five testing sessions . although hydration status was not assessed , each subject was tested in an identical manner throughout the investigation . the bod pod was calibrated the morning of the testing session as well as between each subject . subjects presented in a fasted state at a local quest diagnostics facility on five separate occasions . a blood lipid and comprehensive metabolic panel was done . this includes the following measures : glucose , blood urea nitrogen ( bun ) , creatinine , glomerular filtration rate , bun / creatinine ratio , sodium , potassium , chloride , carbon dioxide , calcium , total protein , albumin , globulin , albumin / globulin ratio , total bilirubin , alkaline phosphatase , alanine transaminase , aspartate transaminase , total cholesterol , high - density lipoprotein cholesterol , triglycerides , low - density lipoprotein cholesterol , and the total cholesterol to high - density lipoprotein cholesterol ratio . the investigators were in regular contact with each subject to ensure that each subject completed a training log . the volume load ( i.e. , total weight lifted per week ) was determined for each treatment period . a 2-way analysis of variance ( anova ) was used to analyze the data with p < 0.05 considered as significant . the data that were compared were baseline and the mean of the normal treatment period [ combined 2-month and 4-month treatment ] as well as the mean of the high protein treatment period [ combined 2-month and 4-month treatment ] . the statistical analysis was completed using prism 6 graphpad software ( la jolla , california ) . subjects consumed more absolute and relative calories and protein during the high protein phase ( p < 0.05 ) . there were no significant differences between the normal and high groups in any measure of health or body composition ( tables 3 and 4 ) . it should be noted that one subject completed 6 months on the high protein phase and only 2 months on the normal protein phase . he did not complete the final 4 months of the normal protein phase due to geographic relocation . thus , for this particular subject , we compared the mean of his normal ( 2 months of data ) and high protein phases ( 6 months of data ) . this is the first randomized controlled trial that has examined the effects of a high protein diet in resistance - trained subjects over a 1-year treatment period . in brief , we found no deleterious effects of a high protein diet ( 2.513.32 g / kg / d ) over a 1-year period . prior work from our lab has shown that consuming a high protein diet in the short term has no harmful effects on any clinical measure ( i.e. , blood lipids and comprehensive metabolic panel ) [ 6 , 7 ] . the subjects in the current investigation alternated between their normal or habitual protein intake and a high protein intake . it should be noted however that even their normal protein intake would be considered high by other investigators [ 5 , 11 , 12 ] . thus , our study does not support the notion that protein intakes 3 - 4 times greater than the current rda cause any harmful effects . moreover , the amount of dietary fiber consumed by our subjects was ~30 grams per day . this is in contrast with the average fiber intake in the united states of ~16 grams per day . thus , it is a falsehood to promote the idea that high protein diets are mutually exclusive with a diet that is also high in fiber . our subjects showed no harmful effects of a hyperenergetic , high protein diet and this ( i.e. , blood lipids , renal and hepatic function , etc . ) it is known that higher fiber intakes are associated with a lower risk of cardiovascular disease , cancer , and all - cause mortality [ 1416 ] . on the other hand , the cholesterol intake of our subjects was twice as high as the typical recommendation of 300 mg per day . the notion that high cholesterol intakes have a deleterious effect on blood lipid markers of cardiovascular disease is not supported by our data . prior work from our laboratory has shown that consuming protein ( 2.33.4 g / kg / d ) in amounts that are 3 - 4 times greater than the rda results in a similar ffm increase for both the normal and high protein groups ; however , the high protein group lost more fat mass compared to the normal protein group in spite of the fact that they consumed on average ~400 kcals more per day over the treatment period . this is in contrast with the current study that showed no change in body composition . the primary difference between the current study and the aforementioned one is that subjects in the current study did not purposely alter their training program . on the other hand , subjects in our previous study were subjected to a different training stimulus ( i.e. , periodized resistance - training program ) than they had been accustomed to . inasmuch as the focus on our current work was on the markers of health , subjects in the current study were instructed to not alter their training regimen . an examination of their volume load shows indeed that they did not make any significant alterations in training volume . thus , one would speculate that , without significant changes in the training stimulus , the mere provision of extra protein would likely not lead to changes in body composition . conversely , the mere addition of extra protein calories also will not lead to gains in fat mass . one might speculate that a limitation of this investigation is that the subjects were young males who had several years of resistance - training experience and were regularly consuming a high protein diet at baseline . however , the fact that they increased their protein intake by ~32% and still had no deleterious side effects is further evidence that a high protein diet in exercise - trained individuals is indeed safe . the small sample size may also preclude one from applying the results from this study to other populations ( i.e. , sedentary men or women ) . nonetheless , we would posit that the only populations that would consume a high protein diet are athletes ( e.g. , highly trained endurance and strength - power athletes ) . thus , the need to apply our data to other populations may be a moot point . in male subjects with several years of experience with resistance training , chronic consumption of a diet high in protein had no harmful effects on any measures of health . furthermore , there was no change in body weight , fat mass , or lean body mass despite eating more total calories and protein . contrary to popular belief , the consumption of a high protein diet is not mutually exclusive with a diet high in fiber nor does the consumption of cholesterol above the standard recommendations result in any untoward effects on blood lipids . this is the first 1-year longitudinal investigation in resistance - trained males that demonstrates the lack of harm caused by a high protein diet .

the purpose of this investigation was to determine the effects of a high protein diet over a one - year period . fourteen healthy resistance - trained men completed the study ( mean sd ; age 26.3 3.9 yr ; height 178.5 8.4 cm ; and average years of training 8.9 3.4 yr ) . in a randomized crossover design , subjects consumed their habitual or normal diet for 2 months and 4 months and alternated that with a higher protein diet ( > 3 g / kg / d ) for 2 months and 4 months . thus , on average , each subject was on their normal diet for 6 months and a higher protein diet for 6 months . body composition was assessed via the bod pod. each subject provided approximately 100168 daily dietary self - reports . during the subjects ' normal eating phase , they consumed ( mean sd ) 29.94 5.65 kcals / kg / day and 2.51 0.69 g / kg / day of protein . this significantly increased ( p < 0.05 ) during the high protein phase to 34.37 5.88 kcals / kg / day and 3.32 0.87 g / kg / day of protein . our investigation discovered that , in resistance - trained men that consumed a high protein diet ( ~2.513.32 g / kg / d ) for one year , there were no harmful effects on measures of blood lipids as well as liver and kidney function . in addition , despite the total increase in energy intake during the high protein phase , subjects did not experience an increase in fat mass .

neural tube defects ( ntds ) are common congenital malformations ( second most common major congenital malformations after cardiac anomalies and the most common malformation of the central nervous system ) . craniorachischisis is a rare and severe form of ntd that results when the neural tube fails to close normally in the primary neurulation / dorsal induction stage of the central nervous system development , during the 34 week of gestation , leading to fetal loss and stillbirth . the failure of closure of cranial pore and parts of neural tube produces the two severe forms of ntds , namely , the anencephaly and spinal rachischisis totalis . ultrasound has established itself as a sensitive and accepted modality of choice for the prenatal detection of all congenital anomalies , including the ntds . recent studies have shown the complementary role of fetal magnetic resonance imaging ( mri ) for the confirmation of such anomalies . maternal folic acid supplementation significantly reduces the number of ntds including lethal defects such as acrania , exencephaly , anencephaly , and rachischisis , with various studies showing 35%75% reduction in ntds by maternal folic acid ingestion . we present two cases of 22 and 25 weeks of gestation who came for routine obstetric scan and subsequently underwent fetal mri for anencephaly and craniorachischisis that was confirmed after termination . a 21-year - old primigravida presented at 25 weeks of gestation for her routine evaluation . this pregnancy was a spontaneous conception , confirmed by urine pregnancy test at 2 months of amenorrhea . she had previous two antenatal visits and started taking oral iron - folic acid tablets only from the 4 month of pregnancy . there was no history of epilepsy , diabetes mellitus , thyroid disorders , hypertension , psychiatric disorders , or chronic intake of medications . there is no family or history of diabetes , hypertension , multiple pregnancies , or congenital anomalies . b - mode ultrasonography ( usg ) ( mylab50 , esoate ) evaluation revealed a single live fetus in unstable lie . fetal calvarium was not clearly visualized , the brain tissue appeared deformed , and the orbits were prominent . the fetal spine showed the absence of vertebral posterior elements with splaying of the lamina at all levels and exposing the spinal cord to amniotic cavity . sagittal and coronal views of the spine showed loss of the normal thoracic kyphotic curvature . fetal mri ( 1.5 tesla avanto , siemens ) revealed the absence of calvarium with deformed brain tissue directly exposed to amniotic cavity suggestive of exencephaly . the spine also showed open spinal dysraphism with the absence of posterior elements and splaying of the spinal laminae at all levels , leading to exposure of spinal cord to the amniotic cavity noted , suggestive of rachischisis . the prognosis was explained to the patient , and she opted to undergo medical termination of pregnancy . she delivered a fetus with exencephaly and spinal rachischisis confirming the in utero imaging findings [ figure 3 ] . transabdominal ultrasonography images showing absent calvaria with deformed brain tissue ( upper ) , absence of posterior elements with splaying of lamina and exposure of spinal cord to the amniotic fluid ( arrows in middle ) , and spinal kyphotic deformity ( lower ) t2-weighted coronal magnetic resonance image ( left ) showing absent calvarium with deformed brain tissue exposed to amniotic fluid with spinal kyphotic deformity . axial magnetic resonance images ( on right ) showing absence of posterior elements and splaying of laminae with neural tissue exposed to amniotic fluid ( arrows ) posttermination of pregnancy fetus showing craniospinal rachischisis totalis a 23-year - old consanguineously married woman with 5 months amenorrhea was referred for routine obstetric usg . antenatal usg revealed a single live fetus in cephalic presentation at 22 weeks of gestation . important findings include severe polyhydramnios , bulging eyes , protruded tongue , absent cranial vault , contiguous bony defect of the spine and overlying soft tissue / skin , exposure of neural tissue . on the basis of the grayscale findings spine showed open canal and exposed neural tissue to the amniotic fluid , confirming the diagnosis of craniospinal rachischisis totalis [ figures 4 and 5 ] . t2-weighed images from second patient showing sagittal view of the fetus with exposed cord / neural tissue ( arrows ) due to complete rachischisis magnetic resonance imaging coronal and axial t2-weighted images showing the spinal defect ( left ) and the exposed neural tissue ( arrows in right ) a 21-year - old primigravida presented at 25 weeks of gestation for her routine evaluation . this pregnancy was a spontaneous conception , confirmed by urine pregnancy test at 2 months of amenorrhea . she had previous two antenatal visits and started taking oral iron - folic acid tablets only from the 4 month of pregnancy . there was no history of epilepsy , diabetes mellitus , thyroid disorders , hypertension , psychiatric disorders , or chronic intake of medications . there is no family or history of diabetes , hypertension , multiple pregnancies , or congenital anomalies . b - mode ultrasonography ( usg ) ( mylab50 , esoate ) evaluation revealed a single live fetus in unstable lie . fetal calvarium was not clearly visualized , the brain tissue appeared deformed , and the orbits were prominent . the fetal spine showed the absence of vertebral posterior elements with splaying of the lamina at all levels and exposing the spinal cord to amniotic cavity . sagittal and coronal views of the spine showed loss of the normal thoracic kyphotic curvature . fetal mri ( 1.5 tesla avanto , siemens ) revealed the absence of calvarium with deformed brain tissue directly exposed to amniotic cavity suggestive of exencephaly . the spine also showed open spinal dysraphism with the absence of posterior elements and splaying of the spinal laminae at all levels , leading to exposure of spinal cord to the amniotic cavity noted , suggestive of rachischisis . the prognosis was explained to the patient , and she opted to undergo medical termination of pregnancy . she delivered a fetus with exencephaly and spinal rachischisis confirming the in utero imaging findings [ figure 3 ] . transabdominal ultrasonography images showing absent calvaria with deformed brain tissue ( upper ) , absence of posterior elements with splaying of lamina and exposure of spinal cord to the amniotic fluid ( arrows in middle ) , and spinal kyphotic deformity ( lower ) t2-weighted coronal magnetic resonance image ( left ) showing absent calvarium with deformed brain tissue exposed to amniotic fluid with spinal kyphotic deformity . axial magnetic resonance images ( on right ) showing absence of posterior elements and splaying of laminae with neural tissue exposed to amniotic fluid ( arrows ) posttermination of pregnancy fetus showing craniospinal rachischisis totalis a 23-year - old consanguineously married woman with 5 months amenorrhea was referred for routine obstetric usg . her first child was healthy female baby of 3 years of age . antenatal usg revealed a single live fetus in cephalic presentation at 22 weeks of gestation . important findings include severe polyhydramnios , bulging eyes , protruded tongue , absent cranial vault , contiguous bony defect of the spine and overlying soft tissue / skin , exposure of neural tissue . on the basis of the grayscale findings spine showed open canal and exposed neural tissue to the amniotic fluid , confirming the diagnosis of craniospinal rachischisis totalis [ figures 4 and 5 ] . magnetic resonance imaging sagittal t2-weighed images from second patient showing sagittal view of the fetus with exposed cord / neural tissue ( arrows ) due to complete rachischisis magnetic resonance imaging coronal and axial t2-weighted images showing the spinal defect ( left ) and the exposed neural tissue ( arrows in right ) ntds are common , congenital malformations resulting from complete or partial failure of the neural tube to close in the developing embryo , preventing muscle and bone from growing around the gap . clinically , neural tube disorders are classified into open and closed types . among these , closed ntds affect mainly the spinal cord without significant cranial involvement . however , open ntds often have cranial involvement . depending on the location and severity , open ntds can be classified as myelomeningocele , myeloschisis , or rachischisis . a thorough search of literature for similar cases in pubmed did not reveal any reported case of craniorachischisis with both usg and confirmatory fetal mri evaluation . after the advent of mri , its use was being considered to confirm the usg abnormalities . some studies have questioned this indication and demonstrated no added advantage in using mri for detecting fetal anomalies . in addition , there is a risk of recurrence of ntds in the subsequent pregnancies . in india , the incidence of ntds is considered higher than the average in rest of the world . a few studies from india that have analyzed the genetic component are also related to folate pathway only . . the proportion of ntds that can be prevented by periconceptional folic acid has not been established , but the general assumption is that it is probably in the area of 50%60% . however , even the recommendation of periconceptional folate supplementation in women of child - bearing age in vogue for the past three decades , there was no apparent effect on the number of pregnancies with ntds , possibly due to poor compliance apart from the unplanned pregnancies . to overcome this , folate fortification has been made mandatory in many countries and is being used in india also in a limited way . there is perceptible decrease in the incidence of ntds all over the world in recent years partly due to folate fortification programs . however , in india , this may have to be done with caution due to associated vitamin b12 deficiency getting aggravated after the correction of folate deficiency . in this regard , the role of naturally - occurring folate may be considered as an option if it is widely used in the food mainly in our country . this study showed high content of folate in coriander , a widely used green in indian food , and it needs further exploration .

craniospinal rachischisis is a rare and severe form of neural tube defects ( ntds ) , which is always fatal . it is characterized by anencephaly accompanied by a bony defect of the spine and exposure of neural tissue . we describe the two patients with ultrasonographic and magnetic resonance imaging appearance of craniospinal rachischisis totalis , detected antenatally at 22 and 25 weeks of gestation , and confirmed after termination of pregnancy . the multifactorial etiology of ntds , with specific reference to folate deficiency , is discussed with possible role of folate fortification in the indian context .

the patients typically present after an insidious onset with rapidly progressive cognitive decline , frequently with a fluctuating course and inflammatory cerebrospinal fluid findings . these patients often have autoantibody markers , including anti - cation channel complex antibodies , and respond to immunosuppression . however , autoimmune phenomena are common in the normal adult population , particularly if defined as the presence of antibodies against cellular components . up to 92% of the population harbour brain - reactive autoantibodies anti - thyroid peroxidase antibodies ( tpo - ab ) are associated with thyroid disease and are found in patients diagnosed with steroid responsive encephalopathy and thyroiditis ( sreat ) , and the presence of thyroid autoantibodies forms part of the diagnostic criteria . anti - nuclear antibodies ( ana ) are associated with systemic lupus erythematosus ( sle ) , a well - recognised cause of neurological and psychiatric disorder , but the diagnosis of sle relies on both clinical features and autoantibody findings and can be further confirmed through characteristic histological findings in tissues that can be readily biopsied . more recently , a number of well - characterised syndromes associated with specific but rare anti - neuronal autoantibodies , including potassium channel blocking antibodies and n - methyl - d - aspartate receptor antibodies , have been described . the presence of such rare autoantibodies in the context of a characteristic clinical presentation has aided in the recognition of these rare but clinically important syndromes . this paper takes a population approach to address the question of whether the presence of common autoantibodies such as tpo - ab and ana is useful in the diagnostic assessment of cognitive decline . the hunter community study ( hcs ) is a cohort of 3,253 subjects aged between 55 and 85 years and drawn at random from the australian electoral roll . the specifics of their recruitment and their characteristics have been described previously . a large subset of these participants had blood stored at baseline in 2004 - 2007 and had a concurrent cognitive screen . depression was assessed using the centre for epidemiological studies depression ( cesd ) scale , and psychological distress was assessed with the k10 kessler scale . a history of cardiovascular disease ( cvd ) and thyroid disease was sought by a general health questionnaire as well as a list of medications . the research was approved by the human research ethics committees of the hunter new england local health district and the university of newcastle . ana was assessed using hep-2 ana slides ( bio - rad laboratories , hercules , calif . , usa ) ; anas at a titre of 1/80 were defined as borderline , whereas those with an ana titre of > 1/160 were defined as positive . extractable nuclear antigens ( enas ) were assessed on those testing ana positive ( titre > 1/160 ) using elisa screening for the six antigens sm , rnp , ssa , ssb , scl-70 and jo-1 ( immuno concepts inc . , enas that tested positive in the screen assay in this test were classed as borderline if no defined antigen specificity was identified and as positive if one of the six antibody specificities was identified . thyrotropin levels were measured using sandwich chemiluminescent immunoassay on the dimension vista system ( siemens healthcare diagnostics ltd . , the arcs is a novel instrument , which uses an audio device to deliver neuropsychological tests to unsupervised participants who write their responses to the questions in a special booklet for later scoring . the arcs has been previously shown to be a sensitive and comprehensive method of assessment of cognitive impairment . five cognitive domains are assessed by the arcs , and a global , overall score can be obtained . the global and cognitive domain scores are adjusted for age , gender and education level and normalised to a mean of 100 with a standard deviation of 15 . the cross - sectional association between autoimmune thyroid markers and cognitive scores was examined using linear regression , with arcs as the outcome . the results were adjusted for known risk factors for cognitive decline including age , gender , self - reported mood disorder and depression , self - reported cvd and self - reported thyroid problems . given the non - normal distribution of the tpo - ab titres , this was log - transformed . the hunter community study ( hcs ) is a cohort of 3,253 subjects aged between 55 and 85 years and drawn at random from the australian electoral roll . the specifics of their recruitment and their characteristics have been described previously . a large subset of these participants had blood stored at baseline in 2004 - 2007 and had a concurrent cognitive screen . depression was assessed using the centre for epidemiological studies depression ( cesd ) scale , and psychological distress was assessed with the k10 kessler scale . a history of cardiovascular disease ( cvd ) and thyroid disease was sought by a general health questionnaire as well as a list of medications . the research was approved by the human research ethics committees of the hunter new england local health district and the university of newcastle . ana was assessed using hep-2 ana slides ( bio - rad laboratories , hercules , calif . , usa ) ; anas at a titre of 1/80 were defined as borderline , whereas those with an ana titre of > 1/160 were defined as positive . extractable nuclear antigens ( enas ) were assessed on those testing ana positive ( titre > 1/160 ) using elisa screening for the six antigens sm , rnp , ssa , ssb , scl-70 and jo-1 ( immuno concepts inc . , enas that tested positive in the screen assay in this test were classed as borderline if no defined antigen specificity was identified and as positive if one of the six antibody specificities was identified . thyrotropin levels were measured using sandwich chemiluminescent immunoassay on the dimension vista system ( siemens healthcare diagnostics ltd . , the arcs is a novel instrument , which uses an audio device to deliver neuropsychological tests to unsupervised participants who write their responses to the questions in a special booklet for later scoring . the arcs has been previously shown to be a sensitive and comprehensive method of assessment of cognitive impairment . five cognitive domains are assessed by the arcs , and a global , overall score can be obtained . the global and cognitive domain scores are adjusted for age , gender and education level and normalised to a mean of 100 with a standard deviation of 15 . the cross - sectional association between autoimmune thyroid markers and cognitive scores was examined using linear regression , with arcs as the outcome . the results were adjusted for known risk factors for cognitive decline including age , gender , self - reported mood disorder and depression , self - reported cvd and self - reported thyroid problems . given the non - normal distribution of the tpo - ab titres , this was log - transformed . a summary of the data , presented in relation to the global arcs score , is given in table 1 . in the primary analysis , log tpo - ab levels were used as a predictor for the arcs score in linear regression , adjusting for the confounding variables . adjustment for the self - reported history of autoimmune disease was attempted , but there was extensive co - linearity with cvd and , as a result , it was not included in the analysis . for this cohort ( n = 1,705 with non - missing covariates ) , there was no evidence that tpo - ab had a linear effect on arcs [ coefficient = exp ( 0.133 ) = 1.143 , p = 0.616 ] after adjusting for cvd status , age , depression and gender ( table 2 ) . there was a marginal effect on the arcs score due to self - reported thyroid problems ( coefficient = 2.064 , p = 0.09 ) and a statistically significant effect of self - reported cvd ( coefficient = 2.689 , p = 0.009 ) . subsequent to this analysis , investigations were undertaken to determine the association between tpo - ab and the global arcs score among patients with and without self - reported thyroid problems . we investigated the effect of tpo - ab on arcs in subjects with and without thyroid problems and included a term for the thyrotropin stimulatory hormone ( tsh ) category and other confounders . we found no evidence of an independent effect of the tpo - ab status ( coefficient = 0.67 , p = 0.831 , 95% ci 0.68 , 0.55 ) . this study also investigated the relationship between cognitive impairment , as measured by arcs , and the presence of two other common autoantibodies , ana and ena . the above analysis was repeated separately for the following outcomes : ena ( defined as positive , negative and borderline ) , ana ( positive , negative and borderline ) and a composite antibody score , which was defined as the number of positive findings against ana , ena and tpo - ab ( 0 , 1 , 2 or 3 ) . none of these variables showed evidence of an association with arcs after adjusting for known confounders ( see score in table 3 ) . ena positivity did show marginal evidence of an effect relative to ena negativity ( adjusted coefficient = 5.15 , 95% ci 0.50 , 10.80 ) , although this was likely due to the multiple comparisons made . we also found no evidence of an effect for any of the antibody measures on arcs for the subgroup without thyroid problems . the above analysis was repeated using the attentional task subscore of the arcs as an alternative proxy for a mild confusional state , but the outcome and results were consistent with those for global arcs . our results indicate that there is no statistically significant relationship between tpo - ab and arcs for patients either with or without self - reported thyroid problems , irrespective of the tsh level . we also looked at this relationship adjusting for other autoimmune markers and the relationship was still absent . in this situation , it is important to ensure that it is not a lack of power that leads to a false - negative result . given our sample size , the number of participants with an abnormal tpo - ab titre , a power of 80% and a p value of 0.05 , we had sufficient power to detect a difference of 2.9 points ( out of 100 ) between the tpo - positive and negative groups . alternatively , if there is an association between tpo - ab and cognition , it is very small in magnitude and clinically immaterial . the presence of tpo - ab alone does not increase the risk , at a population level , for cognitive impairment . sreat is an important diagnosis as it is a potentially reversible cause of cognitive impairment . however , the diagnosis is largely a clinical one , and the role of thyroid autoimmunity in this syndrome 's pathogenesis remains unclear . fluctuations in the tpo - ab titre have not been associated with clinical changes in the encephalopathy , and a reliable association between the response to immune - based therapy and tpo - ab has not been found . the clinical context is key in making a diagnosis of sreat , though the presentation can be variable and patients with sreat are frequently misdiagnosed at presentation with alternative diagnoses including viral encephalitis and degenerative dementia . . a second element of this study was to assess whether the presence of autoreactivity , as defined by the presence of tpo - ab , ana , or ena , increases the risk of cognitive decline . neither tpo - ab nor ana nor ena was associated with an impaired arcs score either alone or as a composite assessment of an autoimmune score . the result implies that like tpo - ab , ana is common in the population and not predictive of cognitive decline . it also suggests that the presence of multiple common autoantibodies is not a risk factor for dementia . sreat is an unusual diagnosis , so despite the large sample size , we could fail to find an association between tpo - ab and cognitive decline . however , this would not detract from the central finding of the study , namely that the detection of an autoantibody that is common in the community , such as ana or tpo - ab , does not increase the risk for cognitive decline and should be interpreted in the clinical context . in cerebral sle , the diagnosis of systemic disease can be strengthened by a biopsy of an easily accessible and potentially involved tissue such as kidney , muscle or skin , so one can be confident that the diagnosis of sle at least is secure . however , our results suggest that the finding of a positive ana in isolation would have limited independent diagnostic utility for the diagnosis of cerebral lupus in an aging cohort . the same point can be made in the diagnosis of sreat , where the clinical presentation is key to the diagnosis , and the presence of tpo - ab forms part of the syndrome diagnosis . another potential weakness in the analysis is that serial cognitive analysis was not performed to assess for serial changes in cognition over time . however , if there were a significant effect on the speed of cognitive decline due to the presence of autoimmunity , this should have been evident in the age cohort analyses , unless the effect size was small . the finding of associations between cvd , age and the arcs score is consistent with previous findings and reflects the validity of arcs as a tool for the measurement of cognition . age , as expected , was associated with a low arcs score , particularly when the age was > 75 . interestingly , co - linearity between self - reported cvd and self - reported autoimmune disease was also noted , consistent with the reported increased incidence of cvd in patients with autoimmune disorders including sle . this finding suggests that any association between autoimmunity and cognition would need to carefully consider the role of cvd in that association . in conclusion , the data demonstrate that autoantibody findings are common in an aging cohort and do not increase the risk of cognitive decline , as measured by arcs .

backgroundautoimmunity is considered an uncommon but under - recognised cause of cognitive decline.methodsserum samples from 3,253 randomly selected subjects enrolled in the hunter community study , aged 55 - 85 years , were assayed for thyrotropin stimulatory hormone , anti - thyroid peroxidase antibodies ( tpo - ab ) , anti - nuclear antibodies ( ana ) and extractable nuclear antigens ( ena ) . cognitive function was assessed using the audio recorded cognitive screen ( arcs ) tool.resultstpo-ab were found in 8.4% and ana in 27.9% of the study population , of whom 3% had positive ena findings . no relationship was found between the arcs score and either tpo - ab ( coefficient = 0.133 ; 95% ci 0.20 , 0.82 , p = 0.616 ) , ana at a low ( coefficient = 1.01 ; 95% ci 2.58 , 0.55 , p = 0.203 ) or a high titre ( coefficient = 0.65 ; 95% ci 2.59 , 1.28 , p = 0.508 ) , or ena antibodies ( coefficient = 5.12 ; 95% ci 0.53 , 10.77 ; p = 0.076).conclusionsautoantibody findings are common in an aging population and are not associated with cognitive decline .

a 42-year - old man , who had complained of seizure and headache , was admitted to another hospital , where angiography and ct revealed an avm in the left occipital lobe , with hematoma ( fig . preembolic cerebral angiography revealed a left - sided occipital avm fed by the left posterior parietal artery and branches of the left posterior cerebral artery ( fig . after local anesthesia , a 6-fr guiding catheter was positioned in the high cervical internal carotid artery using the femoral approach and the seldinger method . to prevent systemic coagulation , 5000 units of heparin was used , and to ensure that the anticoagulative effect was adequate , an activated clotting time of greater than 300 seconds was employed . throughout the procedure , all catheters were continuously flushed with saline . using a flow - directed 1.8-fr magic catheter ( balt , montmorency , france ) and a hydrophilic terumo 0.010 wire ( terumo , tokyo , japan ) , selective catheterization was performed . the tip of the magic catheter was j - shaped , with steaming , and initial embolization was attempted via the left posterior parietal artery ; for assessment of this vessel , a 1.8-fr magic catheter combined with a terumo 0.010 wire was employed . using a mixture of 1 ml of histoacryl and 3 ml of lipiodol , embolization was successfully performed . guided by a terumo 0.010 wire , a 1.8-fr magic microcatheter was advanced by flow control through the left vertebral artery into a branch of the posterior cerebral artery . the wire did not extend beyond the tip of the catheter , as commonly occurs in the standard microcatheter / wire system , and the microcatheter was subsequently advanced into a turn approximately 1.5 cm from the nidus , at which point it failed to progress . at this juncture , a lateral injection demonstrated no evidence of extravasation , but an anteroposterior injection revealed the extravasation of contrast medium at the point at which the parieto - occipital branch changed direction , at the a site of the microcatheter tip , approximately 1.5 cm from the nidus ( fig . the position of the magic microcatheter was not changed and angiography was again performed ; this time neither occlusion of the parieto - occipital branch nor contrast medium extravasation at the rupture site was seen . we believe that arterial rupture had occurred at the point at which the parieto - occipital branch turned sharply , approximately 1.5 cm from the nidus . because no changes had been made to the microcatheter or position of the wire , the reason for perforation was thought to be over - injection rather than catheter wedging . the tip of the magic catheter was located extravascularly , so in order to occlude the site of arterial rupture , the distal portion of the microcatheter was positioned at the perforation site . the extravascular compartment were sealed with a small amount of a 40% mixture of histoacryl and lipiodol , injected through the same magic catheter ( fig . control vertebral angiography revealed occlusion of the perforation site , with subtle narrowing at the point at which the parieto - occipital branch changed direction . this vessel was reselected and the feeder , including the sealed perforation site , was occluded . the remaining feeders of the posterior cerebral artery were occluded with a 25% mixture of histoacryl and lipiodol . control angiography of the vertebral artery after embolization revealed complete anatomic cure of the avm . after embolization and surgery , two days later , the patient no longer complained of neurologic symptoms or headache . although several reports have dealt with the vascular perforation that can occur during neurointerventional procedures , none has -to our knowledge- described vessel perforation by a flow - directed microcatheter itself and management of the perforation using this same microcatheter . the outcome of vascular perforation has ranged from asymptomatic to massive hemorrhage and death ( 2 , 3 ) . rupture of a vessel is usually related to guidewire manipulation and the use of steerable microcatheters such as the tracker catheter ( 2 , 3 ) . for the embolization of brain avms , the variable , stiff , guidewire - guided microcatheter has thus been gradually replaced by the very floppy , flow - directed catheter ( 4 ) . since january 1996 , we have used the hydrophilic terumo 0.010 wire in conjunction with the 1.8-fr magic microcatheter for superselective catheterization of the nidus of avms . the wire does not extend beyond the catheter tip , as is commonly seen in standard microcatheter / wire systems . endovascular embolization using flow - directed microcatheters has undergone considerable technical evolution in recent years , and during avm - related procedures , periembolic complications are now less frequent than before . even so , during endovascular embolization using flow - directed microcatheters , perforation of a vessel may occur at vessel angulations or in associated aneurysms -whether congenital , flow - related feeder , or intranidal -due to the fact that the wire is stiffer than the microcatheter ( 5 ) . the mechanisms involved in arterial perforation during neurointerventional procedures have been described in several reports ( 2 , 6 ) and fall into three groups : mechanical perforation of a normal vessel , mechanical disruption of a dysplastic vessel or aneurysm , and fluid overinjection ( 2 ) . we consider that in our case , perforation occurred due to the overinjection of contrast medium at a sharp angulation . the management of arterial rupture occurring during embolization has included surgical closure of the perforation , closure with various embolic materials , or conservative management(2 ) . we believe that the most expeditious treatment is occlusion of the perforation by embolization via the offending catheter . despite new developments in the field of flow - directed microcatheters and associated techniques , prompt recognition and closure of the perforation site by embolization via the offending catheter are essential .

we present a case in which an arterial rupture occurring during embolization of an arteriovenous malformation of the left occipital lobe with a flow - directed microcatheter , was successfully sealed with a small amount of glue . we navigated a 1.8-fr magic catheter through the posterior cerebral artery , and during superselective test injection , extravasation was observed at the parieto - occipital branch . the catheter was not removed and the perforation site was successfully sealed with a small amount of glue injected through the same catheter . prompt recognition and closure of the perforation site is essential for good prognosis .

seborrheic dermatitis ( sd ) is a common chronic erythematous scaly eruption usually seen in areas rich in sebaceous glands . two main factors are the presence of a generous amount of epidermal lipids and colonization by malassezia species ( lipophilic , usually non pathogenic yeast forms , a part of normal human cutaneous flora ; however , under the influence of certain predisposing factors , they become pathogenic ) . erythematous reddish yellow , poorly circumscribed patches with fine scale , which are mildly pruritic , are seen . common sites are scalp ( dandruff ) , eye brows , perinasal areas , ears , retroauricular areas , neck , and anterior and posterior trunk ( annular or petaloid forms are seen ) . secretion in sebum is a major route by which the drug reaches the stratum corneum . the aim of the study was to determine the efficacy and safety of oral itraconazole capsule 100 mg given twice daily for 7 days and consecutive usage in the treatment of the severe sd . written consent was obtained from each patient before entering the study . the patients were clinically evaluated according to the following items : itching , burning erythema , scaling , and seborrhea . this study was carried out in the winter and early spring seasons , in which sd is normally exacerbated . the clinical efficacy parameter was the proportion of patients who achieved complete or nearly complete disappearance of clinical features . patients who had used systemic antibiotics , systemic antifungals , topical steroids , topical antifungals , selenium sulfide or zinc pyrithione within 15 days prior to the study were excluded . in all the patients , complete blood count , liver function test ( lft ) , serum urea , serum creatinine , and mycological examination were done before starting the therapy . in the treatment protocol , itraconazole capsule 100 mg twice a day was given for 1 week ; then after a 3-week interval 100 mg capsule was given twice a day for 2 days of following months for two consecutive months . the evaluation of results was performed on day 15 , day 30 , day 60 , and day 90 . thirty patients were enrolled in the study . out of these 30 patients , 21 were male and 9 were female . in all of these patients , response to conventional therapy was very unsatisfactory . the evaluation of clinical improvement showed at the end of 90 days was that a markedly effective result was seen in 18 patients ( 60% ) . a moderate response was seen in 7 patients ( 23.3% ) and in 5 patients ( 16.6% ) no improvement was seen . sd is an inflammatory disorder of the skin characterized by erythema and scaling over the areas rich in sebaceous glands , the scalp , face , chest , back , and flexural areas . probably the organism pityrosporum ovale , pityrosporum lipase activity , skin surface lipids , and lastly immune dysfunction may play a role . malassezia restricta / globosa , which plays an important role in the pathogenesis of sd , stimulates cytokine production by keratinocytes . many studies showed that antimycotics are effective in clearing lesions with a reduction in the number of malassezia yeasts . the efficacy of azole and imidazole antimycotics may be due to their anti - inflammatory action . they inhibit the cell wall lipid synthesis of the organisms ( antifungal activity of the azoles is via inhibition of lanosterol 14 demethylase ) and may have some effects on the skin surface lipids . itraconazole is anti - inflammatory primarily because of its inhibitory effect on the synthesis of 5-hypoxygenase metabolites , which are involved in several inflammatory diseases such as sd . in one study , mastaro treated 30 patients with sd of head and face , who used 150 or 200 mg once per week for 2 - 3 months . if this dosage was well tolerated , the dose was increased to 100 mg per day for another 4 weeks . five patients were cured . in our study , patients were given itraconazole 200 mg per day for 7 days and then 200 mg per day for 2 days in the following 2 months . by the end of 90 days , the treatment was found to be markedly effective in 60% cases , moderately effective in 23.3% , and no improvement was noticed in 16.6% . the use of oral itraconazole capsule clearly diminished the symptoms ( especially erythema and desquamation ) of the disease . the anti - inflammatory activity of oral itraconazole and its efficacy on malassezia yeast suggest that itraconazole may be one of the safe and effective treatments of sd although it is evident that future research is needed about the efficacy and safety of this drug in a comparative or placebo - controlled clinical trial .

background : seborrheic dermatitis ( sd ) is an inflammatory skin disorder in which colonies of malassezia furfur have been found in affected areas.aim:the aim of this study was to evaluate the efficacy of itraconazole in the treatment of severe sd.materials and methods : itraconazole was given to 30 patients of sd in a dose of 100 mg twice daily for 1 week followed by 200 mg / day for first 2 days of the following 2 months . the response was noted on day 15 , 30 , 60 , and 90 . the clinical response was graded as markedly effective , effective , or ineffective.results:clinical improvement ( evaluated as markedly effective or effective ) was observed in 83.3% cases.conclusion:the anti - inflammatory activity of oral itraconazole suggests that it should be the first - line therapy in severe sd .

hemophagocytic lymphohistiocytosis ( hlh ) 1 is a rare and lifethreatening hyperinflammatory syndrome caused by genetic mutations ( primary hlh ) or systemic acquired conditions ( secondary hlh ) which in adults is most commonly associated with hematological malignancies 2 , 3 . although primary and secondary hlh have usually been considered distinct entities , recent evidence has pointed to an increase in the frequency of heterozygous mutations in prf1 , unc13d , and stxbp2 genes , suggesting an increased overlap between the two forms of the disease 4 . the central nervous system ( cns ) is commonly affected in children with hlh where white matter abnormalities are characteristic 5 . in adults , neurological manifestations have been reported in up to 25% of cases 1 , 2 , although hlh is not usually considered in the differential diagnosis of white matter abnormalities in this age group . we report an adult hemophagocytic syndrome presenting like a primary hlh with a good response to therapy that evolved subsequently to a unique form of diffuse large bcell lymphoma with fulminant cns involvement and concomitant intravascular lymphoma ( ivl ) . a 47yearold healthy woman , with no significant family history , was admitted with a 4month history of fever , anorexia , and loss of 10% of body weight . blood tests showed normocytic anemia and thrombocytopenia ( 35,000 platelets/l ) , elevated creactive protein ( 23.6 mg / dl ) and erythrocyte sedimentation rate ( 110 mm ) , hypertriglyceridemia ( 546 mg / dl ) , and hyperferritinemia ( fig . . additional evaluation , including extensive cultural , serological and molecular microbiologic tests , full autoantibody serologic profile , cardiac ultrasound , upper endoscopy , colonoscopy , and bronchoscopy , were normal . bone marrow biopsy showed a normocellular bone marrow tissue with normal counts of plasma cells and lymphocytes with no morphological changes . liver and lung transbronchial biopsies showed a reactive inflammatory response , prompting a spleen biopsy which revealed an extensive histiocytosis with erythrophagocytosis . clinical course and management during 5 months ( a ) and brain axial t2flair mri images evolution ( b ) . ( a ) clinical course and treatmentinduced remission with ivig ( 400 mg / kg / day ) plus iv methylprednisolone ( 1 g / day ) and hlh94 chemotherapy protocol ( dexametasone 10 mg / m , daily , during 2 weeks and then tapering plus etoposide 150 mg / m , iv , twiceweekly for the first 2 weeks and weekly dosing thereafter during the following 6 weeks ) . ( b ) ( left ) : after seizure : right temporal subcortical lesion hyperintense on t2 flair , with no restriction on diffusion and without gadolinium enhancement ( not shown ) , with little mass effect , small supratentorial bilateral lesions hyperintense on t2 flair . b ( middle ) : after ivig plus methylprednisolone : decrease in volume and mass effect and resolution of gadolinium enhancement ( not shown ) . b ( right ) : during acute confusional state : multiple edematous lesions in basal ganglia and supratentorial white matter , with gadolinium enhancement ( not shown ) , restriction on diffusion ( not shown ) and mass effect . hemophagocytic lymphohistiocytosis was assumed and , accordingly , an increased level of soluble cd25 ( 7460 u / ml ) was detected , fulfilling 7/8 of hlh diagnostic criteria 1 . four weeks after admission a complex partial seizure occurred with conjugate right eye deviation and leftsided hemiparesis . the patient refused a brain biopsy and was treated with levetiracetam 500 mg twice daily plus a 5day course of intravenous methylprednisolone and ivig ( fig . after a week a substantially improvement of her brain mri lesions was attained ( fig . 1b , middle ) , but due to worsening of cytopenias and persistence of hlh markers , there was a substantial response to treatment with ferritin levels lowering past 2000 ng / ml ( fig . two months after hlh94 induction , she was readmitted because of acute confusional state and visual hallucinations . , the patient suffered sudden clinical deterioration into coma and death , caused by diffuse brain edema with central transtentorial herniation . postmortem brain pathology was consistent with a primary diffuse large bcell lymphoma of the cns with an angiocentric distribution associated with hemophagocytosis ( fig . the presence of an intravascular restricted infiltration by monoclonal cd20 + lymphocytes in all other tissues ( fig . 2c and d ) led to the concomitant diagnosis of ivl . there were no known hlhrelated mutations on prf1 , unc13d , stxbp2 , and stx11 genes . postmortem pathological diagnosis of primary bcell lymphoma of the cns ( a and b ) and intravascular lymphoma ( c and d ) . ( a ) numerous macrophages with ingested lymphocytic cells ( hemophagocytosis ) ( h&e 1000 ) . accumulation of tumor cells within the perivascular space , sparing vessel lumina ( h&e 400 ) . ( c and d ) intravascular lymphoma cells are present in the sinuses of the lung ( c , h&e 100 ) and they fill the lumen of small vessels in the kidney ( d , h&e 200 ) . the tumor cells are highlighted by staining for cd20 ( red ) and the endothelium is staining for cd34 ( brown ) ( inserts ) . hemophagocytic lymphohistiocytosis truly remains a clinical challenge , particularly in adults who comprise around 40% of cases 1 . hemophagocytic lymphohistiocytosis is usually suspected in a patient with fever , cytopenias , increased acute phase reactants , and altered liver tests . soluble cd25 is used as a marker for the hyperinflammatory state , although other markers such as nse have been reported in pediatric hlh 6 . interestingly , nse was found increased in our patient , suggesting that nse could possibly be also used in adults with hlh . the cns involvement in hlh is heterogeneous ranging from altered mental status to seizures and coma typically with csf abnormalities 1 . even though adult hlh has been better characterized in the last years , cns involvement and mri changes in adults are still poorly documented . in children , white matter abnormalities the lesions are usually multiple , asymmetrical and fuzzy , hyperintense on t2 with contrast enhancement , and a periventricular or juxtacortical distribution 5 , 7 . these abnormalities are not usually considered a feature of adult hlh , although this case , like others 8 , suggests that this may be a wrong assumption . compared to other published cases of adult hlh 2 , 8 , our case has a detailed documentation of hlh neurological involvement and resembles a children primary hlh . moreover , it has the particularity of remission of hlh markers after treatment with an almost complete resolution of cns lesions , and the resurgence of cns lesions without reappearance of hlh blood markers leading to death and the postmortem diagnosis of ivl . this case resembled a primary hlh clinical picture as no cause could be identified after extensive investigation . the remission of hlh markers after treatment with an almost complete resolution of cns lesions would argue in favor of this possibility , but the subsequent emergence of an aggressive bcell lymphoma during hlh remission questioned this initial interpretation . in this case , it is difficult to define whether the lymphoma was already evolving during initial months of hlh , or whether it developed after secondary immunodeficiency caused by hlh and its treatment , but the duration and type of immunosuppression does not favor this second possibility . although , there was no evidence of lymphoma at presentation even after an extensive investigation ( favoring the diagnosis of primary hlh ) , the exclusion of known hlhrelated mutations clearly favors the diagnosis of secondary hlh . thus , the possibility of a subclinical evolving lymphoma since the beginning of the clinical course seems to be the most plausible interpretation . it is well known that some hematological conditions , like autoimmune hemolytic anemia , can precede the emergence of nonhodgkin and hodgkin lymphomas , especially after immunosuppression for the presenting condition . it is possible that a hlh presenting as a primarylike form represents a similar phenomena . tcell lymphoma and epsteinbarr virus infection are the most common causes of adult hlh 1 , 2 , 3 . bcell lymphoma presenting with hlh is less common and it is mostly seen in the asianvariant of ivl 9 , but not in western countries 9 , 10 . besides the unusual association of hlh with ivl in european patients , there are other features that do not favor a classical ivl in this case . in fact , brain pathology resembled primary diffuse large bcell lymphoma of the cns and while some cases of ivl have brain masslike lesions 11 , ivl with secondary cns involvement usually have brain vessel and leptomeningeal infiltration 9 not seen in this case . it is thus plausible to assume a primary diffuse large bcell lymphoma of the cns with synchronous ivl . in conclusion , we report a rare case of an adult hemophagocytic syndrome presenting as a primarylike hlh with a good response to therapy and a subsequent emergence of a unique form of diffuse large bcell lymphoma with fulminant cns involvement and concomitant ivl . this case highlights that cns involvement can occur at early stage of hlh even in adults and that lymphoma can emerge even after remission of a hlh resembling a children primary hlh . although in this case a brain biopsy could not be obtained , this should always be considered as it may prove crucial in diagnosis the underlying hematological disorder . a written informed consent for patient information and images was provided by the patient 's husband as this case reports on a deceased patient .

key clinical messagehemophagocytic lymphohistiocytosis ( hlh ) should be considered in the differential diagnosis of adult patients with white matter disease . brain involvement can be lifethreatening and should prompt aggressive therapy . even after hlh remission , the possibility of subsequent deterioration due to emergence of an aggressive intravascular lymphoma is highlighted here .

congenital choanal atresia ( ca ) is a failure in the development of communication between the nasal cavity and nasopharynx causing complete obstruction of the choana.1 although its incidence is rare ( 1 in 7000 births),2 it represents the most common congenital abnormality of the nose.3 congenital ca showed abnormally thickened third portion of the vomer.3 paranasal computed tomography ( ct ) scan and nasal fiberoptic endoscopy are the gold standard of diagnostic tools,4 since they set the diagnosis and enable the examiner to identify the type and thickness of atresia.4 congenital ca can be associated with other congenital anomalies in 50% of cases5 6 and studies have reported accumulated tenacious mucous secretion with ca.7 at birth , the entire midline of the face may be composed of a radiolucent stripe of cartilage that lies between paired ossifications in the lateral masses of the ethmoids . on ct , this radiolucent fibrocartilage can simulate midline defect.8 9 the cribriform plate begins to ossify between 2 and 8 months . the metso ethmoidal center forms the perpendicular plate of the ethmoid and begins to ossify between the ages of 4 and 11 months . at age 6 years , the lateral masses and the perpendicular plate of the ethmoid unite across the nasal cavity by ossification of cribriform plate.8 the skull develops from three major ossification centers : the basioccipital , the basisphenoid , and the pre - sphenoid . the midline septal cartilage is continuous with the cartilaginous skull base and is not ossified at birth.8 the aim of this study was to describe and bring attention to false ct findings suggesting unilateral encephalocele in neonates with bilateral ca . this study was conducted in the department of otorhinolaryngology head and neck surgery department on neonates with bilateral congenital ca in the period from october 2011 to january 2015 . we reviewed the full history of all patients , which underwent a physical examination by attempt to pass six - french catheter through the nasal cavity to the nasopharynx . before surgical repair , patients underwent axial and coronal non - contrast ct scanning with 23 mm sections . then , we evaluated coronal ct to study the skull base area in the neonates . this study included 14 neonates that had bilateral ca ; 10 ( 71.4% ) girls and 4 ( 28.6% ) boys . the mean age of the patients was 7 3.5 days , ranging from 3 to 15 days . we detected mixed atretic plates in 12 ( 85.7% ) cases while two patients ( 14.3% ) had pure bony atresia . isolated ca was found in 9 cases ( 64.3% ) while 5 ( 35.7% ) cases had associated anomalies ; one case had charge syndrome with coloboma , ventricular septal defect , bilateral ca , retardation of growth and development , undescended small testis , and bilateral sensorineural hearing loss . while four cases had cardiac anomalies . coronal ct showed soft tissue density in the nasal cavity appeared to extend through an apparent defect in the nasal roof ( cribriform plate ) . the radiologists falsely diagnosed this soft tissue density as associated encephalocele ( figs . 1 , 2 ) . coronal ct of a neonate with bilateral choanal atresia with soft tissue density in nasal cavity appeared continuous with brain parenchyma due to lack of ossification along the floor of the anterior cranial fossa , falsely appearing as a bony defect . another case , a ; coronal ct showed soft tissue density in the nasal cavity appeared continuous with the brain parenchyma due to lack of ossification of the floor of the anterior cranial fossa . b ; axial ct showed bilateral choanal atresia appeared thick due to accumulated secretion in front . at the time of surgical repair , all patients showed thick tenacious mucous secretions in both nasal cavities and endoscopic assessment confirmed the diagnosis of bilateral ca , revealing no encephalocele with intact nasal roof in all cases . bilateral ca causes complete bilateral nasal obstruction leading to immediate respiratory distress and even potential death due to asphyxia . this is because the newborn is obligated to nose breathe until 46 weeks of life when he learns mouth breathing . therefore , bilateral ca is a life threating condition making early diagnosis and treatment is imperative.10 encephaloceles occur as result of herniation of meninges , with or without brain tissue , through a congenital skull base defect . all encephaloceles involve a midline skull defect , which corresponds to the site of neural tube closure in the midline . in the nasal region they may result in nasal obstruction , snoring , or respiratory distress.11 ct scanning is the radiology of choice in the evaluation of ca12 and it is useful for visualization of the skull base defect.11 in 14% of infants less than one year old , there is no midline ossification of the anterior cranial fossa or septum . thus , the entire midline of the face may be a radiolucent stripe of cartilage situated between the paired ossifications in the lateral masses of the ethmoids . this radiolucent line can simulate a midline cleft on imaging studies.8 13 accumulated tenacious mucous secretion in nasal cavity is one of the features found in ca.7 in axial ct , this secretion gives false appearance of thickened atretic segment.12 however , in the current study , ct also gave a false encephalocele appearance in the very young neonates with bilateral ca . the lack of midline facial ossification is not problematic in imaging in neonates with patent choanal because air in the nasal cavity abuts the cribriform plate.14 in ca , however , accumulated thick fluid in the nasal cavities with fluid attenuation approximates that of adjacent brain parenchyma , as described here . thus , midline encephalocele may be impossible to exclude on the basis of ct examination alone . after an extensive literature review using pubmed database , we found that only three neonates presented with bilateral ca associated with encephalocele . they were published as case reports14 15 with no consistent association between fronto ethmoidal encephalocele and ca.11 12 our case series increases surgeon and radiologist awareness of the developmental anatomy of the nasal cavity during interpretation of ct of ca . moreover , we highly recommend performing proper and complete suction of the nasal cavity of the suspected cases in the ct center after the neonate is sedated and just before ct scanning . it is highly recommendable to perform proper suction of the nasal cavity of the suspected cases just before ct scanning .

introduction choanal atresia ( ca ) is a challenging surgical problem defined as a failure in the development of communication between the nasal cavity and nasopharynx . objective the objective of this study is to describe computed tomography ( ct ) findings in cases with bilateral choanal atresia . methods the study involved performing axial and coronal non - contrast ct scanning with 23 mm sections on14 neonates that had bilateral ca . we used fiberoptic nasal endoscopy to confirm the diagnosis . we evaluated coronal ct to study the skull base area in such neonates . results this study included 14 neonates with bilateral ca ; with mean age of 7 3.5 days . mixed atretic plates were found in 12 ( 85.7% ) cases while two ( 14.3% ) had pure bony atresia . isolated ca was detected in 9 cases ( 64.3% ) and 5 ( 35.7% ) cases had associated anomalies . coronal ct showed soft tissue density in the nasal cavity that appeared to extend through an apparent defect in the nasal roof ( cribriform plate ) , falsely diagnosed by radiologists as associated encephalocele . at the time of surgical repair , all patients showed thick tenacious mucous secretions in both nasal cavities and revealed no encephalocele . nasal roof remained intact in all cases . conclusion the thick secretion of bilateral ca could give a false encephalocele appearance on the ct . it is highly recommended to perform proper suction of the nasal cavity of suspected ca cases just before ct scanning .

the international pilot study of schizophrenia estimated that 70% of schizophrenia patients suffered from hallucinations . 25 - 30% of the auditory hallucinations in schizophrenia are refractory to traditional antipsychotic drug treatment . even with the advent of newer antipsychotics , a significant minority of patients continue to experience persistent hallucinations . apart from pharmacological treatments , other therapies such as transcranial magnetic stimulation , cognitive behavior therapy , and hallucination - focused integrative treatment tiapride , is a substituted benzamide antipsychotic drug and has a selective d2 and d3 dopamine receptor antagonist activity in limbic brain areas and the locus ceruleus . the usual indications of tiapride use are the presence of extrapyramidal symptoms or other dyskinesias , hyperkinesias , patients with huntington 's chorea and also geriatric agitation and restlessness . the common side - effects with tiapride are drowsiness , extrapyramidal symptoms , dizziness , and orthostatic hypotension . here , we report two cases of schizophrenia with persistent auditory hallucinations that responded favorably to tiapride as an add on drug to their already existing drug treatments . a 37-year - old right handed female christian graduate was brought to the out - patient department by family members with chief complains of hearing voices inaudible to others , suspiciousness toward others as though they are talking about her and plotting against her since the past 5 years . she would hear voices of known and unknown people saying sometimes good things and majority of times saying bad things to her . she would get commanding hallucinations telling her to tear her books , bible , certificates , etc . , she also complained of occasional anger outbursts , decreased sleep , and stopped doing household activities . she was diagnosed as having paranoid schizophrenia as per diagnostic and statistical manual for the classification of psychiatric disorders 4 edition text revised ( dsm - iv tr ) ( dsm - iv tr ) criteria and was started on olanzapine 10 mg / day , haloperidol 10 mg / day and trihexyphenidyl 4 mg / day all in oral formulations . gradually , the doses were increased weekly to olanzapine 20 mg / day , haloperidol 20 mg / day , and trihexyphenidyl 6 mg / day . clozapine 25 mg at night was added , which was gradually increased to 100 mg at night . her hallucinations persisted , but there was some improvement in that the number of people whose voices she used to get reduced . the patient and relatives were not willing for electroconvulsive therapy ( ect ) as a treatment option . hence , tiapride 50 mg / day was added after 6 months of addition of clozapine 100 mg . after 2 weeks of tiapride therapy , the dose was increased to 100 mg / day in divided doses . olanzapine was reduced as she complained of excessive sedation with it . currently , the patient is on haloperidol 20 mg / day , olanzapine 10 mg / day , trihexyphenidyl 6 mg / day , clozapine 100 mg at night and tiapride 100 mg / day . she was assessed for hallucinations using the hallucinations subscale of the psychopathology rating scale ( psyrats ) . her score on the hallucination subscale improved from 28 to 11 after the addition of tiapride . a 32-year - old married 10 standard educated female was brought to the out - patient department by her sister with complaints of suspiciousness toward the neighbors that they are talking about her and that they would kill her and her family members since the past 6 months . she would feel that they are keeping a watch on her by cameras fitted in her house by them . she would also hear voices inaudible to others commenting on her actions and sometimes giving running commentary also . she was diagnosed as having paranoid schizophrenia as per dsm - iv tr criteria and was started on risperidone 4 mg / day and trihexyphenidyl 4 mg / day . gradually risperidone was increased to 8 mg / day in weekly increments and trihexyphenidyl to 6 mg / day . her symptoms showed no improvements after 1 month and olanzapine 10 mg / day was added , which was increased gradually to 20 mg / day . she and her family members were not consenting for ect and tiapride 50 mg / day in divided doses was added to her medication . she started feeling better , her voices began to reduce and the intensity and frequency of hallucinations decreased . the patient claimed 80% improvement in auditory hallucinations after 2 months of addition of tiapride to her medication . her total score on the psyrats - hallucination subscale improved from 41 to 25 after addition of tiapride . a 37-year - old right handed female christian graduate was brought to the out - patient department by family members with chief complains of hearing voices inaudible to others , suspiciousness toward others as though they are talking about her and plotting against her since the past 5 years . she would hear voices of known and unknown people saying sometimes good things and majority of times saying bad things to her . she would get commanding hallucinations telling her to tear her books , bible , certificates , etc . , she also complained of occasional anger outbursts , decreased sleep , and stopped doing household activities . she was diagnosed as having paranoid schizophrenia as per diagnostic and statistical manual for the classification of psychiatric disorders 4 edition text revised ( dsm - iv tr ) ( dsm - iv tr ) criteria and was started on olanzapine 10 mg / day , haloperidol 10 mg / day and trihexyphenidyl 4 mg / day all in oral formulations . gradually , the doses were increased weekly to olanzapine 20 mg / day , haloperidol 20 mg / day , and trihexyphenidyl 6 mg / day . clozapine 25 mg at night was added , which was gradually increased to 100 mg at night . her hallucinations persisted , but there was some improvement in that the number of people whose voices she used to get reduced . the patient and relatives were not willing for electroconvulsive therapy ( ect ) as a treatment option . hence , tiapride 50 mg / day was added after 6 months of addition of clozapine 100 mg . after 2 weeks of tiapride therapy , the dose was increased to 100 mg / day in divided doses . olanzapine was reduced as she complained of excessive sedation with it . currently , the patient is on haloperidol 20 mg / day , olanzapine 10 mg / day , trihexyphenidyl 6 mg / day , clozapine 100 mg at night and tiapride 100 mg / day . she was assessed for hallucinations using the hallucinations subscale of the psychopathology rating scale ( psyrats ) . her score on the hallucination subscale improved from 28 to 11 after the addition of tiapride . a 32-year - old married 10 standard educated female was brought to the out - patient department by her sister with complaints of suspiciousness toward the neighbors that they are talking about her and that they would kill her and her family members since the past 6 months . she would feel that they are keeping a watch on her by cameras fitted in her house by them . she would also hear voices inaudible to others commenting on her actions and sometimes giving running commentary also . she was diagnosed as having paranoid schizophrenia as per dsm - iv tr criteria and was started on risperidone 4 mg / day and trihexyphenidyl 4 mg / day . gradually risperidone was increased to 8 mg / day in weekly increments and trihexyphenidyl to 6 mg / day . her symptoms showed no improvements after 1 month and olanzapine 10 mg / day was added , which was increased gradually to 20 mg / day . she and her family members were not consenting for ect and tiapride 50 mg / day in divided doses was added to her medication . she started feeling better , her voices began to reduce and the intensity and frequency of hallucinations decreased . the patient claimed 80% improvement in auditory hallucinations after 2 months of addition of tiapride to her medication . her total score on the psyrats - hallucination subscale improved from 41 to 25 after addition of tiapride . tiapride offers good results in patients whose main complains are auditory hallucinations , which have not responded to other antipsychotics . tiapride does not cause sedation ; hence , it can be added easily with other antispychotics and no worries of cumulative sedation effects . to best of our knowledge , there are no literature on use of tiapride for auditory hallucinations , but there is one report on the treatment of visual release hallucinations with tiapride .

hallucinations are considered as core symptoms of psychosis by both international classification of diseases10 ( icd-10 ) and diagnostic and statistical manual for the classification of psychiatric disorders 4th edition text revised ( dsm - iv tr ) . the most common types of hallucinations in patients with schizophrenia are auditory in nature followed by visual hallucinations . few patients with schizophrenia have persisting auditory hallucinations despite all other features of schizophrenia having being improved . here , we report two cases where tiapride was useful as an add - on drug for treating persistent auditory hallucinations .

scoliosis is a deformity of the spine resulting in a lateral curvature of the spine , which is associated with rotation of the vertebrae and deformity of the rib cage . its prevalence in the general population varies from 0.3% to 15.3% with a female preponderance of 3:1 . scoliosis is associated with restrictive lung disease and hypoxemia , which can lead to cardiovascular compromise . if untreated severe idiopathic scoliosis is fatal by the fifth decade as a result of pulmonary hypertension and respiratory failure . a 142 cm , 54 kg , 22-year - old 39-weeks pregnant woman , who was diagnosed as a case of cephalo - pelvic disproportion ( cpd ) , was posted for emergency cesarean section . she gave a past history of surgery on her spine at 9 years of age for correction of scoliosis for which luque rods were placed from t4t12 vertebrae . anesthetic airway assessment revealed a mallampatti score of one , with intact dentition , adequate mouth opening , and a full range of neck movements . a full stomach status was present as the patient had taken a meal 3 h before surgery ; metoclopromide 10 mg and ranitidine 50 mg were administered intravenously 30 min prior to the surgery . examination of the spine revealed a lateral curvature along with an incision scar extending from t3l2 vertebrae . the lower lumbar vertebrae were clearly visible and the intervertebral spaces could be easily identified . chest x - ray and pulmonary function tests , done a year ago , revealed a severe restrictive pattern with a forced expiratory volume 1 ( fev1 ) 38% and functional vital capacity ( fvc ) 40% . chest x - ray pa view done 1 year prior to this admission revealed a lateral curvature of the dorsal spine with rotation of the heart , luque rods present in situ , and a cobb 's angle curvature of 60 [ figure 1].the thorax was asymmetric with dorsolumbar kyphoscoliosis with a scar over the thoracolumbar spines extending from t3 to l2 and a scar over the right hip . on admission , she had a pulse rate of 88/min , bp 110/80 mmhg , and spo2 99% . chest x - raypa view : lateral curvature of the dorsal spine with rotation of the heart , luque rods in situ , cobb 's angle curvature the patient was shifted to the operating room where peripheral venous access was secured with an 18 g cannula . the various anesthetic options were discussed with the patient , and it was decided to administer spinal anesthesia due to the severe restrictive lung disease as well as the full stomach of our patient.the patient was then placed in the lateral position and a 26 g quinke needle was introduced into the l4l5 interspace until clear csf was obtained . the patient was then placed in the supine position and the sensory blockade was confirmed by loss of sensation to pinprick below the t7dermatome.oxygen supplementation was administered to the patient.the e patient delivered of a baby girl with an apgar score of 9/10 in the first minute and 9/10 in the fifth minute . postoperatively she did not complain of back pain or headache and was discharged after 4 days . an important focus in obstetric surgery is the safe and skilled anesthetic management to minimize risk to the mother and the fetus . foran emergency cesarean section in a patient with severe restrictive lung disease , who had undergone spinal deformity correction with luque rods , with a full stomach status , the feasibility and choice of anesthesia for delivery is important . the physiological changes in pregnancy can worsen the respiratory function in a scoliosis patient with restrictive lung disorder . the maternal mortality and morbidity correlates well with the degree of functional impairment before pregnancy . increased mucosal vascularity of the respiratory tract during pregnancy may lead to difficulty in endotracheal intubation . edema of the airway results in increased potential for bleeding and smaller sized endotracheal tubes should be used for general anesthesia . crooked. patients with scoliosis suffer from restrictive lung diseasewhich decreased vital capacity , functional residual capacity , tidal volume , and increased respiratory rate . the severity of pulmonary impairment depends on the degree of the cobb 's angle , the number of vertebrae involved , and the cephalad location of the curvature . after surgical correction , the cardiorespiratory problems are usually arrested and slight improvements may be noticed . even if the lungs are healthy , the distortion of the thoracic cage makes the respiratory system much less compliant , and increases the work of breathing . in severe cases , displacement with rotation of the trachea and main stem bronchi may also be noted , which could cause problems during intubation for general anesthesia . the severity of scoliosis depends primarily on the type , duration of scoliosis , as well as on the cobb 's angle of curvature . idiopathic scoliosis is the most common and mostly occurs in the infantile , juvenile , and adolescent forms . the number of alveoli increases from approximately 20 million at birth to 200 hundred and 40 million at 4 years of age . thoracic scoliosis causes a significant reduction in the number of alveoli predisposing these patients to impairment in gas exchange and pulmonary hypertension . the cobb 's angle is a radiological measurement made on an ap view x - ray of the spine to evaluate the severity of scoliosis . an angle more than 60 results in a restrictive type of pulmonary impairment with a decrease in fev1 , fvc , and chest wall compliance . in this patient the cobb 's angle was 60. surgical correction of scoliosis is indicated when the cobb 's angle exceeds 50 in the thoracic spine and 40 in the lumbar spine . general anesthesia is indicated in scoliosis because of maternal preference ; when there is maternal cardiopulmonary disease ; and when there is difficulty in performing regional block . severe scoliosis is associated with altered anatomy of the airway causing difficulty in laryngoscopy and intubation . it is also associated with pulmonary hypertension and patients run the risk of increase in pulmonary artery pressures during laryngoscopy and difficult intubation . care should be taken to avoid hypoxia , hypercapnea , acidosis , and anesthetic gases such as nitrous oxide as they increase the pulmonary vascular resistance . in scoliosis with neuromuscular etiology , laryngeal incompetence and impaired swallowing may be present , which could increase the chances of intra and postoperative pulmonary aspiration of gastric contents . scoliosis patients with severe restrictive lung disease could present problems during extubation , may require postoperative ventilation , with difficulty in weaning off the ventilator . regional epidural anesthesia in a patient who had undergone correction of a spinal deformity for scoliosis with luque rods is a technical challenge to the anesthetist , as after spinal fixation the screws from the spinal implant can pass through the ligamentum flavum and the scarring from the applied bone graft can distort the anatomy and prevent the location of the epidural space . the rate of successful epidural placement varies depending on the level of fusion of the vertebrae distortion of the epidural space after surgical corrective surgery for scoliosis can prevent the normal spread of the local anesthetic in the epidural space , resulting in a high degree of patchy blockade . the cerebrospinal fluid ( csf ) provides a clear indication of successful needle placement and is a medium through which the local anesthetic solution usually spreads readily . spinal anesthesia was considered the best anesthetic choice because the intrathecal space is not directly affected by the previous spine surgery and the spread of local anesthetic is more reliable than by the epidural route . the other advantage is that the appearance of the csf eliminates the difficulty in identifying a distorted epidural space and the complication of dural puncture . the increased intraabdominal pressure in pregnancy and the presence of engorged veins in the epidural space causes a decrease in the subarachnoid space . in such cases , the normal dose of the local anesthetic can lead to higher levels of block leading to hypotension . this is more so in cases of severe scoliosis , which can be associated with decreased volumes of csf . there are reports of anesthetic management of the kyphoscoliotic parturient using a combined spinal epidural , continuous spinal anesthesia , and local infiltration anesthesia when there is a failure in spinal or epidural anesthesia . in conclusion , the etiology of scoliosis may be varied . based on the clinical assessment as well as the chest x - ray , pulmonary function tests , and full stomach status of this patient .

anesthesia for emergency cesarean section for the pregnant patient with surgically corrected scoliosis is associated with potential risks for both mother and the fetus due to alterations in maternal physiology and the pathological changes seen in scoliosis . the anesthetic management must address the well being of both mother and fetus . the need for anesthesia for obstetric delivery in pregnant women with scoliosis is much more than in the normal parturient . we report the successful use of spinal anesthesia in a patient with surgically corrected scoliosis for emergency cesarean section .

spinal artery aneurysms are most commonly associated with high - flow states secondary to either arteriovenous shunting or occlusive disease of larger arteries causing increased flow through spinal arteries recruited as collateral circulation.1)2)4 ) an aneurysm is considered " isolated " when it occurs in the absence of such a high flow state . aneurysms of the spinal vasculature are more common along the anterior axis than the posterior axis , and isolated aneurysms account for only a small fraction of these . histologically , isolated spinal artery aneurysms have features shared with cerebral artery aneurysms,7 ) suggesting that at least some may be the product of a congenital predisposition to aneurysm formation . however , isolated anterior spinal artery and cerebral artery aneurysms have been associated with both central nervous system - specific and systemic vasculitis.5)13)17)20 ) here , we present the first case to our knowledge documenting a posterior spinal artery ( psa ) aneurysm in the context of a hypersensitivity vasculitis ( leukocytoclastic vasculitis ) . a 53-year - old male with a history of hepatitis c , hepatitis b , and poly - substance abuse presented to an outside hospital for bilateral lower - extremity recurrent cellulitis , hypoalbuminemia and acute kidney injury . on the ninth day of admission , the patient developed acute paraplegia associated with a t5/6 sensory level deficit . a thoracic spine magnetic resonance imaging ( mri ) obtained on the day of presentation was read as negative for evidence of compressive cord lesion and the patient was medically managed with broad - spectrum antibiotics and steroids . the patient 's neurological symptoms did not improve with medical management and 15 days later a second thoracic spine mri was obtained . 1a ) with compressive effects at the level of c7-t1 with associated increase in t2 signal intensity in the cord extending from c7-t5 , suggesting edema . thoracic spinal angiography revealed a 1.5 mm ectasia of the right t9 segmental artery 's radiculopial branch , consistent with an aneurysm of the posterior spinal artery ( fig . in addition to the right t9 aneurysm , a segment of the left t5 radiculopial artery revealed vascular pathology along the posterior aspect of the spinal cord suggestive of either an inflammatory process or post - hemorrhagic reactive changes ( fig . vascular bleeding and lumen irregularities consistent with an acute inflammatory process were noted throughout the cervical and thoracic spine , and the angiogram also revealed a 3 mm right middle cerebral artery ( mca ) aneurysm . a coil was placed in the segmental artery supplying the t9 aneurysm for subsequent intra - operative localization during the open resection . the patient underwent a multilevel laminectomy ( c7-t2 and t8 - 10 ) for hematoma evacuation and microsurgical aneurysm resection . the histology was consistent with a dissecting aneurysm with localized regions of lymphocytic infiltration of the intima , and fibrosis and necrotic changes in regions of the tunica media ( fig . samples of the hematoma from the t2-level had histological features consistent with an organizing intradural hematoma . multiple medical issues complicated the postoperative course . neurologically , the patient 's pre - operative deficits remained unchanged for the duration of his hospitalization . renal biopsy demonstrated membranoproliferative glomerulonephritis secondary to hepatitis c virus - related cryoglobulinemic vasculitis and he underwent treatment with rituximab , plasmapheresis and prednisone with improvement in his renal function . the patient subsequently developed a urinary tract infection with multiple - drug resistant klebsiella and was started on imipenem . a 53-year - old male with a history of hepatitis c , hepatitis b , and poly - substance abuse presented to an outside hospital for bilateral lower - extremity recurrent cellulitis , hypoalbuminemia and acute kidney injury . on the ninth day of admission , the patient developed acute paraplegia associated with a t5/6 sensory level deficit . a thoracic spine magnetic resonance imaging ( mri ) obtained on the day of presentation was read as negative for evidence of compressive cord lesion and the patient was medically managed with broad - spectrum antibiotics and steroids . the patient 's neurological symptoms did not improve with medical management and 15 days later a second thoracic spine mri was obtained . 1a ) with compressive effects at the level of c7-t1 with associated increase in t2 signal intensity in the cord extending from c7-t5 , suggesting edema . thoracic spinal angiography revealed a 1.5 mm ectasia of the right t9 segmental artery 's radiculopial branch , consistent with an aneurysm of the posterior spinal artery ( fig . in addition to the right t9 aneurysm , a segment of the left t5 radiculopial artery revealed vascular pathology along the posterior aspect of the spinal cord suggestive of either an inflammatory process or post - hemorrhagic reactive changes ( fig . vascular bleeding and lumen irregularities consistent with an acute inflammatory process were noted throughout the cervical and thoracic spine , and the angiogram also revealed a 3 mm right middle cerebral artery ( mca ) aneurysm . a coil was placed in the segmental artery supplying the t9 aneurysm for subsequent intra - operative localization during the open resection . the patient underwent a multilevel laminectomy ( c7-t2 and t8 - 10 ) for hematoma evacuation and microsurgical aneurysm resection . the histology was consistent with a dissecting aneurysm with localized regions of lymphocytic infiltration of the intima , and fibrosis and necrotic changes in regions of the tunica media ( fig . samples of the hematoma from the t2-level had histological features consistent with an organizing intradural hematoma . . neurologically , the patient 's pre - operative deficits remained unchanged for the duration of his hospitalization . medically , the patient deteriorated over the next 60 days . renal biopsy demonstrated membranoproliferative glomerulonephritis secondary to hepatitis c virus - related cryoglobulinemic vasculitis and he underwent treatment with rituximab , plasmapheresis and prednisone with improvement in his renal function . the patient subsequently developed a urinary tract infection with multiple - drug resistant klebsiella and was started on imipenem . very little is known about the pathophysiology of isolated psa aneurysms . here , we present the case of a ruptured psa aneurysm in the context of a leukocytoclastic vasculitis . spinal angiography demonstrated evidence of diffuse inflammatory process affecting multiple levels , histology confirmed the presence of a leukocytic infiltrate at the site of the resected aneurysm and subsequent skin biopsy confirmed the diagnosis of leukocytoclastic vasculitis . leukocytoclastic vasculitis is a small - vessel hypersensitivity vasculitis resulting from immune complex deposition in the vessel wall , leading to lymphocytic infiltration . this inflammatory process may have predisposed our patient to aneurysm formation , or it may have compromised the wall integrity of a pre - existing psa aneurysm , precipitating rupture . we identified 14 cases of isolated psa aneurysms , which are summarized in table 1 . none occurred in the context of a confirmed vasculitis but it is not clear that vasculitis was ruled out . for the current case , an important question remains whether diagnosis and treatment of the vasculitis could have prevented aneurysm rupture . the natural history of spinal aneurysms likely mirrors that of intracranial aneurysms , although published natural history data of spinal aneurysms is sparse . most presented after an initial rupture and rehemorrhage occurred in 2 of 15 cases ( 13% ) . the average age at presentation was 48.6 ( 95% confidence interval : 37.8 - 59.5 ) years . when cervical and thoracolumbar lesions were considered separately , cervical lesions tended to present at a younger age ( fig . three of 15 patients ( 20% ) exhibited multiple aneurysms ; 2 of the 14 reported cases harbored other spinal artery aneurysms,14 ) while our patient had an additional mca artery aneurysm . this rate is similar to the rate of multiple aneurysms observed in patients with cerebrovascular aneurysms , where 20 - 30% of patients with at least one cerebrovascular aneurysm will have multiple aneurysms.19 ) our analysis of the limited data available is consistent with the assumption that psa aneurysms and cerebral aneurysms share similar epidemiology , natural history and re - hemorrhage risk . eighty - three percent of cervical - level psa aneurysms present with signs and symptoms of intracranial sah , including severe headache , nuchal rigidity , and nausea and vomiting in the absence of myelopathy . for infra - cervical psa aneurysms , the presentation is more suggestive of spinal sah ( myelopathy , localized back pain , and radicular pain ) . cervical lesions are more likely to present suddenly than infra - cervical lesions ( 66% vs. 33% , respectively ) . in summary , ruptured cervical psa aneurysms are more likely to present in younger patients with symptoms of intracranial sah ( including blood in the basal cisterns ) without any recent history of progressive symptom . in contrast , ruptured infra - cervical psa aneurysms presented in older patients with symptoms of spinal sah and a one - week history of lower back or abdominal pain . once identified , psa aneurysms are amenable to resection , endovascular intervention , or watchful waiting . for ruptured psa aneurysms , our literature analysis suggests that more aggressive management should be considered for cervical psa aneurysms , as the only reported deaths have followed re - hemorrhage in these lesions prior to intervention . indeed , the mortality rate of cervical lesions is higher than that of thoracolumbar lesions ( 33% vs. 0% mortality ; fig . while newer microcatheters have made it possible to embolize these lesions , surgeons have historically chosen resection because the operation is curative and the superficial nature of the psa aneurysm facilitates an open surgical approach . in addition , surgical decompression with a laminectomy can relieve compression caused by a hematoma . however , outcome is independent of approach ( endovascular vs. open ) . of patients who underwent intervention , those presenting with pain or meningitic symptoms were significantly more likely to have a positive outcome than those who presented with symptoms of cord compression ( 100% vs. 40% improvement ; fig . thus , outcome now appears more dependent on symptoms at presentation , leaving the physican to choose intervention based on case - specific factors and personal preference . for the present case , endovascular intervention was not pursued because occlusion of the proximal segmental vessel of the t9 aneurysm would not provide definitive cure , and there was concern that direct liquid embolic injection could result in additional spinal cord infarction . since the patient required an evacuation of his hematoma to decompress his spinal cord , we felt that the aneurysm could be resected surgically at the same time and would provide a tissue sample to help establish a diagnosis for his suspected systemic vasculitis . however , the patient 's postoperative course was complicated by medical factors that resulted in the death of the patient after a protracted hospital course . in general , isolated psa aneurysms are difficult to diagnose but are amenable to surgical intervention with good results . cervical lesions have a higher mortality than thoracolumbar lesions , providing justification for more aggressive management . patients who present with pain or meningitic symptoms are more likely to recover than those who present with symptoms of cord compression , a trend consistent with the results of the presented case . once diagnosed , both open and endovascular approaches have been used successfully with high cure rates and low morbidity . consequently , the choice of management strategy will ultimately depend on the specific anatomic pathology , the medical status of the patient , the patient 's personal preference and the surgeon .

rupture of isolated posterior spinal artery ( psa ) aneurysms is a rare cause of subarachnoid hemorrhage ( sah ) that presents unique diagnostic challenges owing to a nuanced clinical presentation . here , we report on the diagnosis and management of the first known case of an isolated psa aneurysm in the context of leukocytoclastic vasculitis . a 53-year - old male presented to an outside institution with acute bilateral lower extremity paralysis 9 days after admission for recurrent cellulitis . early magnetic resonance imaging was read as negative and repeat imaging 15 days after presentation revealed sah and a compressive spinal subdural hematoma . angiography identified a psa aneurysm at t9 , as well as other areas suspicious for inflammatory or post - hemorrhagic reactive changes . the patient underwent a multilevel laminectomy for clot evacuation and aneurysm resection to prevent future hemorrhage and to establish a diagnosis . the postoperative course was complicated by medical issues and led to the diagnosis of leukocytoclastic vasculitis that may have predisposed the patient to aneurysm development . literature review reveals greater mortality for cervical lesions than thoracolumbar lesions and that the presence of meningitic symptoms portents better functional outcome than symptoms of cord compression . the outcome obtained in this case is consistent with outcomes reported in the literature .

periapical periodontitis is an infectious and inflammatory disease of the periapical tissues caused by oral bacteria invading the root canal , and thus resulting in the formation of endodontic lesions . the microbiota in infected root canals has been reported to consist of anaerobic bacteria , by the adoption of various improved anaerobic culturing techniques , such as an anaerobic glove box [ 13 ] . however , identification of bacterial species by utilizing only these techniques is time consuming and labor intensive . in recent years , molecular biological methods such as random cloning and 16s rrna sequence analysis have been introduced in order to profile the microbiota [ 4 , 5 ] . however , live and dead bacterial cells in the microbiota could not be differentiated by utilizing only the molecular biological methods , and in consequence , the pathogenicity of live bacterial cells in the endodontic lesions remains to be fully determined . therefore , in the present study , we applied molecular biological techniques , that is , restriction fragment length polymorphism analysis of pcr - amplified 16s ribosomal rna genes ( pcr - rflp ) and sequencing , to bacterial colonies after anaerobic culture , for bacterial identification , in order to clarify the composition of live bacterial cells of the microbiota in infected root canals . subjects with periapical periodontitis ( five females and two males ; age , 3471 years ) , who were attending the clinical division of endodontology , tohoku university hospital , sendai , japan , were randomly selected for this study . periapical periodontitis was diagnosed based on clinical features , that is , putrefactive smell , spontaneous pain , sensitivity ( tenderness ) to percussion / occlusion , pus discharge , swellings and fistula , and radiographical findings . selected teeth had clinically no obvious margin leakages , had enough coronal structure for adequate isolation with a rubber dam , and were free of periodontal pockets deeper than 4 mm . based on history , all subjects were medically healthy and received no antibiotics for the 3 months before sampling . informed consent was obtained from all subjects , and this study was approved by the research ethics committee of tohoku university graduate school of dentistry , sendai , japan . each tooth was isolated with a rubber dam , and the operative field was disinfected with both iodine glycerin dental disinfectants showa ( showa yakuhin kako , tokyo , japan ) and 70% ethanol . coronal access cavity was prepared with a sterilized high - speed bur under irrigation with sterile saline solution . when the pulp chamber was exposed , a sterile no . 15 k - file ( gc , tokyo , japan ) was introduced and the canal length was determined using an apex locator ( root zx , morita , japan ) . the dentin sample was collected from an apical canal by filing intensively with a sterile k - file of the canal size . after the sampling , cleaning and shaping of the root canal was carried out with sterile k - files ( from # 15 to # 55 , gc , tokyo , japan ) . an intracanal medicament , that is , calcium hydroxide paste ( ultracal xs , ultradent products inc . , south jordan , ut , usa ) was applied , and the coronal access cavity was sealed with a temporary cement ( lumicon ; heraeus kulzer japan , tokyo , japan ) . each file cut off by a sterilized wire cutter was immediately transferred to an anaerobic glove box ( hirasawa , tokyo , japan ) containing 80% n2 , 10% h2 , and 10% co2 . while in the box , each sample was suspended in 1.0 ml of sterilized 40 mm potassium phosphate buffer ( ph 7.0 ) , and , after vortexing , the suspension was dispersed with a teflon homogenizer . serial 10-fold dilutions ( 0.1 ml each ) were spread onto the surface of cdc anaerobe 5% sheep blood agar ( bd , franklin lakes , nj , usa ) plates ( duplicate ) and incubated in the anaerobic glove box at 37c for 7 days . after the incubation , colony - forming units ( cfus ) were counted , and all colonies from suitably diluted plates having < 100 colonies ( mean 13.1 ; range 831 colonies ) were subcultured . genomic dna was extracted from each single colony with the instagene matrix kit ( bio - rad laboratories , richmond , ca , usa ) according to the manufacturer 's instructions . the 16s rrna gene sequences were amplified by pcr using universal primers 27f and 1492r and taq dna polymerase ( hot star taq master mix , qiagen gmbh , hilden , germany ) according to the manufacturer 's instructions . primer sequences were : 27f ; 5-aga gtt tga tcm tgg ctc ag-3 and 1492r , 5-tac ggy tac ctt gtt acg act t-3 [ 6 , 7 ] . amplification proceeded using a pcr thermal cycler mp ( takara biomedicals , ohtsu , shiga , japan ) programmed as follow : 15 min at 95c for initial heat activation and 30 cycles of 1 min at 94c for denaturation , 1 min at 55c for annealing , 1.5 min at 72c for extension , and 10 min at 72c for final extension . pcr products were separated on 1% agarose gels ( high strength analytical grade agarose , bio - rad laboratories ) in tris - borate edta buffer ( 100 mm tris , 90 mm borate , 1 mm edta , ph 8.4 ) , stained with ethidium bromide and photographed under uv light , and their sizes ( ca 1466 bp ) were confirmed comparing with the molecular size marker ( a 100 bp dna ladder , invitrogen , carlsbad , ca , usa ) . the 16s rrna genes were individually digested with hpaii ( fastdigest , fermentas , cosmo bio , tokyo , japan ) according to the manufacturer 's instructions . isolates were identified tentatively according to rflp analysis [ 813 ] as well as morphological data , that is , colony appearances and gram staining . then , representative isolates were conclusively identified by sequence analysis as described below , and there were no exceptions among the same rflp groups . the pcr products were purified with illustra gfx pcr dna and gel band purification kit ( ge healthcare , buckinghamshire , uk ) and then sequenced at fasmac ( atsugi , kanagawa , japan ) using the bigdye terminator cycle sequencing kit and an automated dna sequencer ( prism-3100 , applied biosystem japan , tokyo , japan ) . primer 1492r was used to sequence ( at least 900 bp ) , and the partial 16s rrna gene sequences were then compared with those from the genbank database using the blast search program through the website of the national center for biotechnology information . the mean bacterial count ( cfu ) in root canals was ( 0.5 1.1 ) 10 ( range 8.0 103.1 10 ) ( table 1 ) . the predominant gerera were olsenella ( 25.4% ) , mogibacterium ( 17.7% ) , pseudoramibacter ( 17.7% ) , propionibacterium ( 11.9% ) , and parvimonas ( 5.9% ) , thus indicating that anaerobic bacteria were totally predominant in infected root canals ( 89.8% ) ( table 2 ) . at the species level , mogibacterium timidum ( 17.7% ) , pseudoramibacter alactolyticus ( 17.7% ) , olsenella profusa ( 14.4% ) and parvimonas micra ( 5.9% ) were predominant ( table 2 ) . in the present study , the vast majority of the isolates from infected root canal dentin were found to be anaerobic bacteria ( table 2 ) . the result suggests that the environment of infected root canals is anaerobic and therefore supports the growth of anaerobic bacteria . the finding is in accordance with the previous studies on samples taken from oral cavities , when similar anaerobic incubation procedures were used [ 2 , 3 , 1417 ] . the anaerobic strains , belonging to olsenella , mogibacterium , pseudoramibacter , propionibacterium , and parvimonas consisted of the majority of isolates from infected root canals in the present study ( table 2 ) , in agreement with the previous studies [ 1 , 2 ] . in addition to pseudoramibacter and parvimonas , in those studies [ 1 , 2 ] , fusobacterium was also found among the predominant genera of isolates . these findings suggest that some anaerobic bacteria are common in infected root canals , and that these bacteria may contribute to play some etiological roles for endodontic infections . in the present study , molecular biological techniques , that is , pcr - rflp and sequencing , were applied to bacterial colonies after anaerobic culture , for bacterial identification . the combination of anaerobic culture and molecular biological techniques , utilized also in previous studies [ 14 , 15 ] , seems not only comparatively rapid and low cost but also accurate for the identification of oral microbiota , rather than the mere use of anaerobic culture . however , the number of samples for the analysis in the present study was restricted rather than by only molecular biological technique , for example , pcr or real - time pcr analysis , and the methods did not target noncultivable bacteria such as treponema . in addition , further studies , including examination of biological characteristics of each isolate , are necessary , as the role or complex nature of bacteria in endodontic lesions remains uncertain by the methods in the present study although its characteristics might be speculated based on the general characteristics of reference type strains . as a recently developed technique , pyrosequencing has been applied to analyze the composition of the microbiota of infected root canals [ 18 , 19 ] , showing that the microbiota was highly diverse as suggested previously although the technique is high cost for the present . since the technique is a culture - independent method as well as the real - time pcr amplification and random cloning analysis , it may include not only live but also dead bacterial cells of the microbiota in infected root canals . in the preliminary ( additional ) study , no bacteria were detected in the samples collected just before root canal obturation , that is , on second or third visits during root canal therapy ( data not shown ) , suggesting that adequate treatment may change both the microbiota and the environment of root canals drastically . in summary , the microbiota in infected root canals could be rapidly analyzed by the combination of anaerobic culture and molecular biological techniques . the overwhelming majority of the isolates from infected root canals were found to be anaerobic bacteria , suggesting that the environment in root canals is anaerobic and therefore supports the growth of anaerobes .

objective . periapical periodontitis is an infectious and inflammatory disease of the periapical tissues caused by oral bacteria invading the root canal . in the present study , profiling of the microbiota in infected root canals was performed using anaerobic culture and molecular biological techniques for bacterial identification . methods . informed consent was obtained from all subjects ( age ranges , 3471 years ) . nine infected root canals with periapical lesions from 7 subjects were included . samples from infected root canals were collected , followed by anaerobic culture on cdc blood agar plates . after 7 days , colony forming units ( cfu ) were counted and isolated bacteria were identified by 16s rrna gene sequencing . results . the mean bacterial count ( cfu ) in root canals was ( 0.5 1.1 ) 106 ( range 8.0 1013.1 106 ) , and anaerobic bacteria were predominant ( 89.8% ) . the predominant isolates were olsenella ( 25.4% ) , mogibacterium ( 17.7% ) , pseudoramibacter ( 17.7% ) , propionibacterium ( 11.9% ) and parvimonas ( 5.9% ) . conclusion . the combination of anaerobic culture and molecular biological techniques makes it possible to analyze rapidly the microbiota in infected root canals . the overwhelming majority of the isolates from infected root canals were found to be anaerobic bacteria , suggesting that the environment in root canals is anaerobic and therefore support the growth of anaerobes .

hemoglobin oxygen saturation in superior vena cava ( scvo2 ) is a commonly used parameter for hemodynamic monitoring in intensive care units ( icu ) and operating rooms . even if scvo2 can not be considered a completely reliable surrogate for svo2 , it is nevertheless a useful tool for the evaluation of the balance between oxygen delivery and consumption in major surgery and critical illness . a modified central venous catheter with a built - in infrared spectrophotometric probe for real - time hemoglobin oxygen saturation measurement is currently available from the market ( presep central venous oxymetry catheter , edwards lifesciences , irvine , ca , usa ) . this device , when coupled with either an edwards vigileo or an edwards vigilance monitor ( both edwards lifesciences , irvine , ca , usa ) gives continuous scvo2 reading after an initial calibration . we report here on a patient equipped with a presep catheter who apparently developed profound scvo2 desaturation during an erythrocytes transfusion through the catheter s main lumen . a 57-years - old otherwise healthy male patient was admitted to the icu with a diagnosis of septic shock . he underwent intestinal resection one year before for rectal cancer and was reoperated one month before current admission because of intestinal occlusion due to visceral adherences . he subsequently developed fever , abdominal pain and hypotension and explorative laparotomy revealed gut perforation and peritonitis . in the icu he was treated with broad spectrum antibiotics , intravenous immunoglobulin and noradrenaline infusion because of persistent hypotension despite massive fluids administration . for hemodynamic monitoring the patient was equipped with a flow - track sensor ( edwards lifesciences , irvine , ca , usa ) on a radial arterial line and with a presep central venous catheter inserted in his left internal jugular vein , the tip of which was confirmed to be correctly positioned in superior vena cava by chest radiography . both devices were connected to a vigileo monitor revealing a cardiac index of 2,4 l / min / m and an scvo2 of 78% . one hour later , because of plasma volume expansion with cristalloid and colloid solutions , hemoglobin concentration dropped below 7 g / dl and the physician in charge ordered a 2 units red blood cells transfusion . after the transfusion was started through the main lumen ( 14 gauge ) of the presep catheter , and without any other evident modification in physiologic conditions or therapeutic intervention , an scvo2 value of 35% was displayed on the vigileo monitor . since no other overt hemodynamic changes potentially responsible for this phenomenon was detectable , a causal association between the starting of the red cells transfusion and the scvo2 drop was hypothesized by the attending nurse . the transfusion was then stopped by clamping the infusion line and immediately scvo2 raised and reached the stable value of 78% . transfusion was then started again and scvo2 dropped immediately and reached 35% after 20 - 30 seconds ( figure 1 ) . left : vigileo monitor trend lines showing rapid increase in scvo2 after clamping red cells transfusion line without any perturbation in cardiac index . right : scvo2 drops to 35% immediately after restarting transfusion , with a 2 points signal quality index . of note , displayed signal quality index ( sqi ) at this point was 2 , indicating an acceptably good signal . we ascribed therefore the scvo2 drop to the passage close to the catheter s spectrophotometric probe of highly concentrated stored red cells rich in desaturated hemoglobin . we believe physicians caring for critically ill and surgical patients should be aware of this possible artifact since scvo2 misinterpretation could potentially lead to inappropriate therapeutic decisions unfavourably affecting patientsoutcome .

hemoglobin oxygen saturation in superior vena cava ( scvo2 ) is used as a parameter to guide hemodynamic management in shock patients and it can be continuously read through a central venous catheter equipped with a fiberoptic spectrophotometric probe ( edwards presep catheter ) connected to a specific monitor ( edwards vigileo ) . we report of an episode of erroneous scvo2 reading by this technology in a patient with septic shock who was receiving an erythrocytes transfusion through the presep catheter main lumen . we think this artifact should be known by intensivists since it can lead to scvo2 misinterpretation and subsequent erroneous therapeutic decisions .

central neurocytomas ( cns ) are slow - growing neuroectodermal tumors , which account for approximately 0.1 - 0.5% of all brain neoplasms . these typically affect young adults in the third decade of life , and have a predilection for the lateral ventricles at the foramen of monro . most of the available literature on cns is based on histopathological diagnosis , with only few case reports elaborating on the cytological features seen on intra - operative squash preparation . in the present report , we describe the cytomorphology of cn , along with its differential diagnoses and , finally , the approach to a definitive confirmation . a 22-year - old right - handed woman presented with global headache of 4 months duration , which was insidious in onset and gradually progressive , along with gradually deteriorating vision of both eyes . clinical examination of the central nervous system ( cns ) revealed normal higher mental functions and speech , with reduced visual acuity of both eyes . examination of other cranial nerves , sensory - motor system and cerebellum were within normal limits . magnetic resonance imaging ( mri ) scan showed a lobulated heterogeneously t2-hyperintense right - sided intra - ventricular mass measuring 3 cm , which was extending up to the foramen of monro . intra - operatively , the mass was found to be arising from the right third ventricle with extension into the foramen of monro . it was soft , moderately vascular and was suggestive of a high - grade glioma . total resection was performed and the mass was submitted initially for intra - operative evaluation , followed by histopathological examination . ( a ) mri skull ( t1-weighted image ) : right intra - ventricular mass with heterogenous hypointensity . ( b ) photomicrograph of squash preparation of tumor bits showing round monomorphic uniform - sized cells with finely stippled granular chromatin ( mgg , 200 ) . ( c ) histopathology of tumor tissue showing isomorphous cells , with round to oval nucleus , fine speckled chromatin and inconspicuous nucleoli ; few of the cells showed a perinuclear halo ( h and e , 100 ) , with ( d ) synaptophysin - immunoreactivity ( ihc , 100 ) the squash preparation showed a cellular tumor composed of round monomorphic uniform - sized cells set in a background of fibrillary matrix of neuropils . tumor cells displayed finely stippled granular chromatin , prominent micronucleoli and ill - defined cytoplasm . a diagnosis of low - grade tumor with differential of neurocytoma and oligodendroglioma were offered . all the tumor bits were processed and 5-m - thick sections were cut from routine formalin - fixed , paraffin - embedded tissue , and stained with hematoxylin and eosin ( h and e ) stain . immunohistochemistry ( ihc ) was done using streptavidin - biotin immunoperoxidase technique ( envision kit , m / s dakopatts , denmark ) using monoclonal antibodies to glial fibrillary acidic protein ( gfap ) , synaptophysin and mib-1 ( all antibodies were prediluted and obtained from m / s dakopatts , denmark ) . sections from the resected mass showed a tumor composed of monomorphic cells , with clear cytoplasm , round to oval nucleus , finely speckled chromatin and inconspicuous nucleoli . no evidence of calcification , anisonucleosis , increased mitosis , necrosis or microvascular proliferation was seen [ figure 1c ] . immunohistochemistry , however , displayed synaptophysin positivity in the tumor cells and neuropils , with gfap expression restricted to the entrapped astrocytes only . she was followed up for a period of 3 months , during which she remained symptom - free . the squash preparation showed a cellular tumor composed of round monomorphic uniform - sized cells set in a background of fibrillary matrix of neuropils . tumor cells displayed finely stippled granular chromatin , prominent micronucleoli and ill - defined cytoplasm . a diagnosis of low - grade tumor with differential of neurocytoma and oligodendroglioma were offered . all the tumor bits were processed and 5-m - thick sections were cut from routine formalin - fixed , paraffin - embedded tissue , and stained with hematoxylin and eosin ( h and e ) stain . immunohistochemistry ( ihc ) was done using streptavidin - biotin immunoperoxidase technique ( envision kit , m / s dakopatts , denmark ) using monoclonal antibodies to glial fibrillary acidic protein ( gfap ) , synaptophysin and mib-1 ( all antibodies were prediluted and obtained from m / s dakopatts , denmark ) . sections from the resected mass showed a tumor composed of monomorphic cells , with clear cytoplasm , round to oval nucleus , finely speckled chromatin and inconspicuous nucleoli . no evidence of calcification , anisonucleosis , increased mitosis , necrosis or microvascular proliferation was seen [ figure 1c ] . immunohistochemistry , however , displayed synaptophysin positivity in the tumor cells and neuropils , with gfap expression restricted to the entrapped astrocytes only . she was followed up for a period of 3 months , during which she remained symptom - free . in 1982 , hassoun et al . reported a tumor with round cells having a central round nuclei and perinuclear halo , which on immunohistochemistry and electron microscopy revealed to be neuroectodermal in nature . have extrapolated this hypothesis to include the third ventricle and the subependymal plate of the lateral ventricles , as well . cn is an intra - ventricular neoplasm , typically located in the foramen of monro , with a predilection for young to middle - aged adults , similar to the index case . a majority of the patients present with features of raised intracranial tension , while visual and mental disturbances with hormonal dysfunction may also be observed . a classical cn is either isodense or mildly hyperdense , with strong , uniform contrast enhancement on computed tomography ( ct ) scan , while mri shows a high signal on both t1- and t2-weighted images , with moderate to strong gadolinium enhancement . intra - operative cytological evaluation of brain tumors is generally practiced either to render a preliminary interpretation , or more often as a complement to frozen - section examination . since the latter has a drawback of freezing artifacts of nuclear and cytoplasmic details , a combination of the two procedures is considered ideal . considering the rarity of the neoplasm , and paucity of published literature , intra - operative analysis of cns is a diagnostic challenge to all cytopathologists . imprint cytological preparations of cns typically display sheets or clusters of uniform round cells without appreciable pleomorphism , which are set against a background of neuropils and admixed short straight capillaries . ng et al . detected calcospherites , neuropil islands and rosette - like structures as well further , kobayashi et al . noted typical perinuclear halo in the tumor cells , as observed in the present case , which simulated an oligodendroglioma . an isolated report by kiehl et al . documented pigmented neurocytoma resembling a melanocytic lesion . oligodendroglial cells , with monomorphic vesicular nuclei and ill - defined scant , wispy cytoplasm may resemble cn . further , oligodendrogliomas contain a population of fibrillary astrocytes or minigemistocytes , and display a loose aggregation and arrangement of cells around empty spaces , forming a ring - like pattern , contrary to cn . ependymomas , in contrast to cn , have perivascular rosettes and poorly formed acini , cords and fibrillary processes tumor cells . the typical histopathology of neurocytoma shows uniform , small to medium - sized cells with rounded nuclei , finely stippled chromatin and inconspicuous nucleoli , along with scant cytoplasm . cells are usually closely apposed but may also contain a background of finely filamentous stroma having a neuropil - like quality . h and e stained sections often reveal fixation artifacts in the form of cytoplasmic vacuolations . vascularity is represented by long , thin - walled , capillary - sized vessels , which are arranged in a linear arborising pattern , imparting an endocrine appearance . supplementing these cytological and histological features with confirmatory immunostaining for synaptophysin is imperative for cn . typically , synaptophysin immunoreactivity is noted in the neuropil , especially in the fibrillary zones and perivascular cell - free areas . false cytoplasmic immunopositivity may be attributed to pre - existent neuropil or neuronal structures , or faulty antigen - retrieval techniques and/or the use of polyclonal anti - synaptophysin antibody . cn ultrastructure shows cell processes containing parallel arrays of microtubules , with both clear vesicles and dense core granules in their terminations , thus confirming its neuronal origin . surgical resection is presently considered the ideal therapeutic option , with the best prognosis in terms of local control and survival . the role of adjuvant radiotherapy apparently seems to benefit patients with incomplete resection and in atypical neurocytoma . most cns are world health organization ( who ) grade ii tumors associated with a favorable prognosis . however , occasional cases may display histologic features of anaplasia or malignancy without clinical evidence of poor outcome , which have been termed as proliferating neurocytoma. to conclude , cns possess distinct cytomorphological features that aid in distinguishing them from other intra - ventricular tumors . however , definitive confirmation warrants an immunohistochemical workup , and correlation with the clinical - radiological and histomorphological profile of the case .

central neurocytomas ( cns ) are uncommon tumors of the central nervous system . these tumors have a predilection for the lateral ventricles of young adults and are known to display characteristic neuroimaging and histomorphologic features . typically , cns are associated with a favorable outcome , although cases with more aggressive clinical course with recurrences are not unknown . most descriptions of this tumor are available in the form of isolated histopathology - based case reports and small series . cytology - based publications of cn are rare . here , we report a case of cn in a 22-year - old girl . intra - operative squash cytology and subsequent histopathology of the tumor simulated an oligodendroglioma and a clear cell ependydoma . final confirmation was obtained on immunohistochemistry . this paper discusses the salient cytological , histomorphological and immunohistochemical features of cn that are useful in distinguishing from its mimickers .

a total of 12 mouse lemurs of both sexes ( center for breeding and experimental conditioning of animal models , university montpellier 2 , montpellier , france ) were maintained in animal biosafety level 3 facilities , according to requirements of the french ethics committee ( authorization ce - lr-0810 ) . young and adult lemurs were fed ( 8 animals ) or ic inoculated ( 4 animals ) with 5 or 50 mg of l - bse infected brain tissue ( 10% homogenate in 5% glucose ) ( table ) . the isolate for the l - bse agent ( 022528 ) was derived from cattle in france ( 11 ) . when progression of prion disease was evident , the lemurs were euthanized and their brains were isolated . brains were processed for western blot analysis with sha31 monoclonal antibody against prp for prp detection , as described in mice ( 11 ) ; for histologic examination by using hematoxylin and eosin staining ; and for disease - associated prion protein ( prpd ) immunochemical detection by using the paraffin - embedded tissue blot method or immunohistochemical analysis with monoclonal antibody 3f4 against prp . * l - bse , l - type bovine spongiform encephalopathy source ; prpd , disease - associated prion protein . results obtained by western blot analysis and/or paraffin - embedded tissue - blot analysis and/or immunohistochemical analysis . beginning 3 months before the terminal stage of the disease ( 1922 months after inoculation ) , neurologic symptoms developed in the 4 mouse lemurs that received ic inoculations ( table ) . in all 4 animals , initial clinical signs and symptoms were blindness , thigmotaxic behavior , and poor appearance of the fur . next , locomotion became slower , followed by incoordination and loss of balance in the last month of life . one orally inoculated lemur , which was fed 5 mg of infected brain and euthanized 27 months later , had signs and symptoms of disease similar to those in ic - inoculated animals , except for the ipsilateral circling behavior . in 2 lemurs fed 50 mg and 2 others fed 5 mg of l - bse infected brain , clinical signs and symptoms of prion disease developed just a few weeks before the animals were euthanized ( 18 and 32 months and 33 and 34 months after inoculation , respectively ) . disease was characterized by progressive prostration , loss of appetite , and poor appearance of the fur , without incoordination or disequilibrium . the 3 remaining lemurs were orally inoculated at 2 years of age and were still alive and healthy 28 months after inoculation ( table ) . prp was readily detected by western blot analysis in brain extracts ( thalamus / hypothalamus region ) from 8 of the 9 animals examined ( table ) , although at lower levels in the lemur that was euthanized earlier ( i.e. , 18 months after inoculation ) . western blot analyses showed uniform prp molecular profiles , irrespective of the route or dose of inoculation , with a low apparent molecular mass ( 19 kda , similar to the prp in the original cattle brain ) ( figure 1 ) . however , the prp profile in mouse lemurs was characterized by a higher proportion of di- and monoglycosylated species ( > 95% of the total signal ) than in the inoculum of the agent of bovine l - bse ( 80% ) . in addition , prp was detected by western blot in the spleens of 3 ( 1 ic inoculated and 2 fed with 5 mg of cattle brain ) of the 9 animals examined ( figure 1 ) . western blot analysis of protease - resistant prion protein in the brain ( thalamus / hypothalamus ) and spleen of mouse lemurs inoculated with a cattle - derived l - type bovine spongiform encephalopathy ( bse ) isolate by oral and intracerebral routes by using sha31 monoclonal antibody against prion protein . lanes 1 , 7 : cattle l - type bse isolate ( 02 - 2528 ) ; lanes 2 , 3 : brain sample from intracerebral inoculation at 5 mg ; lane 4 : brain sample from oral inoculation at 50 mg ; lanes 5 , 6 : brain sample from oral inoculation at 5 mg ; lanes 8 , 9 : spleen samples from oral inoculation at 5 mg , positive and negative , respectively . histopathologic analysis showed severe spongiform changes in the brains of the 4 ic - inoculated mouse lemurs ( figure 2 , panel a ) . the brains displayed a pattern of vacuolation characterized by intense spongiosis with many confluent vacuoles in the basal telencephalon ( septum , striatum , caudate putamen nuclei ) , midbrain ( thalamus , hypothalamus ) , mesencephalon ( colliculi ) , and in some parts of the brainstem ( tegmental ventral area , raphe nuclei ) . cerebellum showed occasional small - size vacuoles . among the 5 orally inoculated animals , 2 ( 1 fed 5 mg , the other fed 50 mg ) showed histopathologic features similar to those observed in ic - inoculated animals . in the other 3 orally inoculated animals , spongiosis was characterized by fewer vacuoles and was restricted to the striatum ( figure 2 , panel b ) , thalamus , colliculi , and brainstem . histopathologic and disease - associated prion protein ( prpd ) immunodetection in the brain of 2 mouse lemurs after intracerebral ( 5 mg ) or oral ( 50 mg ) inoculation with a cattle - derived l - type bovine spongiform encephalopathy isolate . a , b ) spongiosis in the striatum ; scale bars = 30 m . c , d ) paraffin - embedded tissue blot analysis of sagittal brain section ; scale bars = 500 m . analyses in c f were performed by using the 3f4 monoclonal antibody against prp . distribution of prpd in the brain was assessed by paraffin - embedded tissue blot ( figure 2 , panels c and d ) or immunohistochemical analysis with 3f4 antibody ( figure 2 , panels e and f ) . results for ic - inoculated animals showed that prpd strongly accumulated in a dense synaptic pattern associated with nonamyloid plaques in the striatum , several thalamic nuclei ( figure 2 , panel e ) , the external cortex of the colliculi , and the tegmental area . other areas that were slightly less affected ( e.g. , neocortex and hippocampus ) showed few coarse granules and synaptic deposits . the cortical molecular layer and the corpus callosum were devoid of prpd ( figure 2 , panel c ) . in orally inoculated animals , prpd was strongly accumulated in the striatum and thalamus ( figure 2 , panel d ) but weakly accumulated in the cortex . immunohistochemical analysis showed synaptic deposits ( figure 2 , panel f ) , and some focal deposits were evident in animals that survived longer . we demonstrated that the agent of l - bse can be transmitted by the oral route from cattle to mouse lemurs . as expected , orally inoculated animals survived longer than ic - inoculated animals . orally inoculated lemurs had less severe clinical signs and symptoms , with no evidence of motor dysfunction . it was previously suggested that the agent of l - bse might be involved in the foodborne transmission of a prion disease in mink ( 11,12 ) , a species in which several outbreaks of transmissible mink encephalopathy had been identified , notably in the united states ( 13 ) . our study clearly confirms , experimentally , the potential risk for interspecies oral transmission of the agent of l - bse . in our model , this risk appears higher than that for the agent of classical bse , which could only be transmitted to mouse lemurs after a first passage in macaques ( 14 ) . we report oral transmission of the l - bse agent in young and adult primates . transmission by the ic route has also been reported in young macaques ( 6,7 ) . a previous study of l - bse in transgenic mice expressing human prp suggested an absence of any transmission barrier between cattle and humans for this particular strain of the agent of bse , in contrast to findings for the agent of classical bse ( 9 ) . thus , it is imperative to maintain measures that prevent the entry of tissues from cattle possibly infected with the agent of l - bse into the food chain .

we report transmission of atypical l - type bovine spongiform encephalopathy to mouse lemurs after oral or intracerebral inoculation with infected bovine brain tissue . after neurologic symptoms appeared , transmissibility of the disease by both inoculation routes was confirmed by detection of disease - associated prion protein in samples of brain tissue .

arrayexpress is an international public repository for microarray data established at the european bioinformatics institute ( ebi ) in 2002 ( 1 ) . arrayexpress supports standards and recommendations developed by the microarray gene expression data ( mged ) society ( www.mged.org ) , including the minimum information about a microarray experiment ( miame ) ( 2 ) and microarray gene expression mark up language ( mage - ml ) ( 3 ) . along with gene expression omnibus ( 4 ) and cibex ( 5 ) , it is one of the three repositories recommended by the mged society ( 6 ) for storing data related to publications . the arrayexpress suite of databases and applications comprises : ( i ) miamexpress , a web - based miame supportive data - submission tool ; ( ii ) the arrayexpress repository that provides public and password - protected access to the submitted data ; ( iii ) a query optimized data warehouse containing a curated subset of normalized data ; and ( iv ) expression profiler , an integrated online visu - alization and analysis tool . we will focus on describing miamexpress , the repository and the data warehouse ; expression profiler has been reviewed recently ( 7 ) . as the number of journals requiring submission to public repositories is growing , the cost of microarray experiments is falling and as data submission tools are improving , the volume of data in arrayexpress is growing rapidly . during the last 12 months the arrayexpress content has grown more than 10-fold ( figure 1a ) , and as of november 2004 , the repository contains 12 000 hybridizations comprising more than 300 studies from 35 species ( figure 1b ) . the majority of studies concern samples from homo sapiens or mus musculus . although the majority of experiments study gene expression , there is a growing volume of chip on chip and comparative genome hybridization data in arrayexpress . there are two major submission routes to arrayexpress : ( i ) online via the miamexpress data submission tool , and ( ii ) via a mage - ml - based pipeline set - up with an external application or database . miamexpress is primarily aimed at users with no substantial local bioinformatics support and with no access to a local database providing direct deposition . no prior knowledge of the miame guidelines is required , as contextual help on the information required and help on the use of miamexpress is provided via links from the web interface . submitters progress through a series of simple web forms to describe their experiment and upload the data files . miamexpress is an open source software that can be customized for use by a single laboratory , or for particular application domains . examples of customization hosted at the ebi include the toxicology ( 8) and plant - specific miamexpress versions . source code and installation information can be found at http://sourceforge.net / projects / miamexpress/. the arrayexpress curation team processes each submission before it is loaded into the repository . submissions are checked for miame compliance , accuracy and completeness of biological information provided , as well as for data consistency ( e.g. it is checked if submitted data files match the specified array designs ) . during the curation process , the curation team may contact the submitter if inconsistencies in the data are found . once the data are successfully loaded into arrayexpress repository , the experiment is issued an accession number and a password is provided to the submitter if requested . the data in the repository are owned by the submitter , released on the date specified or upon publication in a journal and no changes are made without the submitter 's consent . where array designs are commercially available these information on custom - made arrays is submitted as a tab - delimited file containing position information and annotation information . the arrayexpress curators work with external databases when setting up a direct data - submission pipeline to ensure that data are miame compliant and well formatted . once a pipeline is established , the submissions are curated at the source database and monitored by arrayexpress curators . mage - ml - based pipelines have been established from 15 external databases , manufacturers or tools , including the stanford microarray database ( smd ) ( 9 ) , midas at tigr ( 10 ) , from externally installed miamexpress systems at cambridge university and the european molecular biology laboratory at heidelberg , as well as the array manufacturers , affymetrix and agilent . the curators select data based on their miame compliance , presence of normalized data and the quality of the biological annotation . array designs are additionally annotated to the current version of the sequence databases at the ebi and up - to - date gene annotation , such as interpro ( 11 ) gene ontology ( go ) terms ( 12 ) and gene names are added , while the original array annotation supporting the publication is maintained in the repository . the highest level of organization in the arrayexpress repository is the experiment , which consists of one or more hybridizations , usually linked to a publication . the arrayexpress query interface provides the ability to query for experiments , protocols and array designs by their various attributes , such as species , authors or array platforms . once an experiment has been selected the users can examine the description of the samples and protocols by navigating through the experiment , or they can download the data for analysis locally . password - protected access to pre - publication data is provided for submitters and reviewers . the arrayexpress data warehouse [ which is based on the biomart technology ( 11 ) ] supports queries on gene attributes , such as gene names , gene function ( go annotations ) or information on which family a gene belongs to or the motifs and domains it contains ( interpro terms ) , and on sample properties . leukemia retrieves all the experiments that contain data for a gene annotated with this name and that have been studied in experiments described using the term these can be visualized using line plots and data can be selected for further analysis . links are provided back to the repository where users can access the full annotation and supporting raw data . experimental data and corresponding array designs selected by the curators on the basis of miame compliance , annotation quality and comparability are loaded periodically into the warehouse . a schematic diagram of the software architecture is shown in figure 2 . the online submission tool miamexpress is being extended to allow a spreadsheet based data batch uploading to facilitate large - scale experiment submissions . the gene - based query facility in the warehouse will be used as the basis for integrating arrayexpress into all ebi services more closely , for instance expression data will be accessible from uniprot and ensembl databases via a distributed annotation system ( das ) ( http://www.biodas.org ) server . as the volume of submissions continues to grow , we expect that the curation phase at the point of submission to the repository will be fully automated and curation efforts will focus on adding value to submitted data made available through the data warehouse . we would like to acknowledge the work of patrick kemmeren , catherine leroy , pierre marguerite , bhuwan tiwari , jaak vilo , cath brooksbank , peteri jokkinen and the ebi systems group . the embl , the european commission ( temblor , cage ) , international life sciences institute ( ilsi ) and the national institutes of health ( nih ) support arrayexpress development .

arrayexpress is a public repository for microarray data that supports the miame ( minimum informa - tion about a microarray experiment ) requirements and stores well - annotated raw and normalized data . as of november 2004 , arrayexpress contains data from 12 000 hybridizations covering 35 species . data can be submitted online or directly from local databases or lims in a standard format , and password - protected access to prepublication data is provided for reviewers and authors . the data can be retrieved by accession number or queried by vari - ous parameters such as species , author and array platform . a facility to query experiments by gene and sample properties is provided for a growing subset of curated data that is loaded in to the arrayexpress data warehouse . data can be visualized and analysed using expression profiler , the integrated data analysis tool . arrayexpress is available at http://www.ebi.ac.uk/arrayexpress .

early - onset dementia ( at age < 65 years ) is an uncommon but important group of disorders . it has devastating impact on the lives of patients and families and deserves attention of the clinicians . dementia in younger people usually has some demonstrable secondary etiology ( psychiatric illness , alcohol or drugs or metabolic disturbance , familial alzheimer 's disease , wilson 's disease , etc ) . cognitive deficits secondary to brain tumors rarely occur , and there is little description in the available literature where it has been described in association with low grade gliomas , gliomatosis cerebri ( gc ) , and primary brain lymphoma . it is most commonly present as a diffusely infiltrating glial tumor of the cerebral cortex involving more than two lobes and occasionally infiltrating infratentorial structures and the spinal cord . we describe a young woman with gc confined to a single lobe ( right frontal ) and presented primarily as a dementia . before the advent of magnetic resonance imaging ( mri ) , diagnosis was generally not established until autopsy was done . even with mri , however , diagnosis is difficult . management of gc is also difficult by virtue of their diffuse nature , surgery is not suitable and large field radiotherapy carries the risk of severe toxicity . as per our knowledge , only few cases have been reported that had involvement of single hemisphere and presented only with memory loss . a 31-year - old woman was admitted to our hospital with a 3-year history of progressive memory loss and headache . the patient mainly complained of difficulties doing her usual daily routine activity job for about 1 year and misplacing personal objects , she was having difficulties doing simple calculations and drawing simple paper patterns , resulting in erroneous calculations and wrong measurements along with decreasing ability to perform complex tasks such as arranging a meeting with her old friend , pay bills , and marketing . childhood and prior developments were apparently normal . her past medical history was uneventful and was negative for stroke , transient ischemic attack , chronic infection , or other chronic illness . except for incontinence and a slight slurring of speech , the physical examination revealed no further neurological deficits , especially no speech impairment , seizures or myoclonia were observed . the mini mental state examination score was suggestive of dementia ( 21 of 30 ) and very low on the cognitive efficiency profile . nevertheless , she experienced no changes in personality , appetite , or sleeping pattern noted , nor was she observed to be a snorer or have spells of apnoea , and there was no history of auditory or visual hallucinations . blood count , biochemical profile , sedimentation rate , coagulation profile , and the results of radiography of the chest were normal . results of venereal disease research laboratories testing were negative , and no malignant cells were identified by cytological examination . serum vitamin b12 , folic acid , and thyroid - stimulating hormone levels were within normal limits . mr imaging and proton mr spectroscopy were performed on a clinical whole body 1.5-t imaging unit . t2-weighted and fluid attenuated inversion recovery flair images revealed an ill defined area of signal intensity alteration in the left frontal region with involvement of rostrum of corpus callosum with minimal postcontrast enhancement . the magnetic resonance spectroscopic imaging results showed an increased choline peak , a decreased n - acetyl aspartate ( naa ) peak with an increased ch / cr ratio at the site of lesion . the patient was given supportive care for a period of 15 days following that she improved a little bit and the patient was given supportive care for a period of 15days following that she improved a little bit and discharged , and at discharge , her mmse was 22/30 and she was also referred to higher centre . ( a ) axial view t2 flair image demonstrating tumor - related infi ltration involving left frontal lobe involvement of rostrum of corpus callosum . ( b ) axial view t2 flair image shows extensive hyper intensity involving the left frontal lobe and rostrum of corpus callosum , with a mild mass effect . ( c ) the mr spectroscopic imaging results showed an increased choline peak , a decreased naa peak with an increased ch / cr ratio at the site of lesion . ( d ) the mr spectroscopic imaging results showed an increased choline peak , a decreased naa peak with an increased ch / cr ratio at the site of lesion the differential diagnosis of young - onset dementia is extensive , including sporadic hereditary etiologies , neurodegenerative diseases , adult presentations of inborn errors of metabolism , other metabolic or storage diseases , and other syndromic diagnoses . although investigations of the etiologies and prevalence of early - onset dementia have been performed , in some individuals , the etiology remains indeterminate even after brain biopsy . in young adults ( up to 40 years of age ) , it is very rare to develop dementia without other features of neurological disease , or without features of disease elsewhere in the body . most cases of progressive cognitive disturbance in this age group are caused by psychiatric illness , alcohol , or other drugs or metabolic disturbance . these include familial alzheimer 's disease , spinocerebellar ataxia 17 ( dominant inheritance ) , adrenoleukodystrophy ( x - linked ) , gaucher 's disease type 3 , metachromatic leukodystrophy , niemann - pick disease type c , pantothenate kinase - associated neurodegeneration , tay - sachs disease , and wilson 's disease ( all recessive ) . dementia secondary to intracranial infections deserves a special attention especially in tropical and developing countries . syphilis , hiv infection , lyme neuroborreliosis , herpes virus , toxoplasmosis , cryptococcus , cytomegalovirus , or more rarely , whipple diseases are few of the infectious causes of behavioral changes including dementia . besides few isolated reports of neurocysticercosis presenting with dementia , a recent controlled study reported dementia in 12.5% of the patients with active neurocysticercosis . brain tumors can cause dementia by mass effect on structures such as the hypothalamus or pituitary gland , which control hormone secretion and can also press directly on brain cells , damaging them . treating the tumor , either medically or surgically , can reverse the symptoms in some cases . as in our case , the clinical course of gc is usually slow and long , especially when the neoplastic infiltrate is of low histological grade . the clinical course of gc is variable and includes pyramidal deficit , dementia , headache , cranial nerve changes , intracranial hypertension , seizures , and others . however , the present patient had a rare and atypical presentation in the form of dementia only . before the inception of mri , gc was diagnosed strictly in autopsy studies . however , mr imaging findings may be nonspecific , leading to a differential diagnosis that includes neoplastic , inflammatory , and vascular lesions . mr spectroscopy may further help in narrowing the differential diagnosis in favor of a neoplastic lesion by revealing increased cho / cr and cho / na and variably decreased na / cr.[9101214 ] some non - neoplastic lesions such as encephalitis , demyelinating disease , and organizing hemorrhage , may mimic these spectral changes in rare instances . if cho / cr or cho / na is not elevated , mr 5 spectroscopy may still help narrow the differential diagnosis in favor of gc . specifically , m - ins / cr and m - ins / na should be measured because they can be elevated even when cho / cr is normal . as a diffuse tumor , surgical treatment is usually not recommended , and radiology over extensive areas may cause serious toxicity . this case highlights two atypical findings : ( 1 ) dementia in the young patient caused due to gc and ( 2 ) involvement of single lobe of brain which may be initial stage of growing gc , later on bilateral lobes may be involved .

dementia with the onset before the age of 65 years is classified as early - onset dementia . although uncommon , it has considerable impact on the lives of patients and care givers , alike . a substantial subset of patients may have underlying reversible causes . yet , many , especially those of the very young may be initially misdiagnosed . a case of young woman with rapid mental decay is described here . she was finally diagnosed with gliomatosis cerebri ( gc ) involving only right frontal lobe . this atypical radiological feature of gc with primary presentation as memory loss needs special attention and clinicians should be aware of such conditions .

the possible presence of infection in cervical smear tests is usually reported by the cytologists based on cytological criteria . therefore , non - specific cervicitis or inflammatory changes in a smear report are common . these findings are usually unclear for clinical approaches and there is not an appropriate guideline for management of such patients . it is not known if these women should be recalled for cultures and treatment or inflammatory change should be considered as minor . changes in balance of normal vaginal flora can cause an overgrowth of pathogens that lead to discharge . although it is a common complain among sexually active women , there are still gaps in our knowledge about it . bacterial vaginosis ( bv ) , vaginal candidiasis ( vc ) and trichomoniasis are the three infections most commonly associated with vaginal discharge ( 1 ) . a number of studies have indicated the association of bv with postoperative complications after gynecologic surgery as well as pregnancy complications ( 25 ) . trichomonas vaginalis ( tv ) is also another common cause of vaginal discharge , but some studies have not found its association with pregnancy complications ( 3 ) or some other indicated that tv during pregnancy was a predisposing factor for preterm delivery and delivering low - birth weight infants ( 6 ) . the pap smear test for detection of bv has showed a sensitivity of 88.2% , a specificity of 98.6% , and a positive predictive value ( ppv ) of 96.8% ( 7 ) . the sensitivity , specificity , and ppv of pap test for tv diagnosis has been reported 98% , 96% , and 88% , respectively ( 8) . also , some recent studies have demonstrated the co - infection of vaginal pathogenic organisms in pap tests ( 2 , 9 , 10 ) . this study aimed to investigate the prevalence of pathogenic vaginal microorganisms and the presence of inflammation in pap smear among an iranian women sample and to evaluate the possible co - infection of these organisms . this cross - sectional study was carried out on pap smear samples of women referred to gynecological clinic of taleghani hospital in tehran , iran , between october 2008 and march 2009 . exclusion criteria were pregnancy , smoking , use of oral contraception and/or corticosteroids , regular use of vaginal douche , and women with chronic systemic diseases or systemic immunosuppression . prior to data collection , the objectives of the study were explained in community meetings . all women received their laboratory results in written form , and results were explained during a consultation . the study protocol was also approved by the institutional review boards of department of gynecology and obstetrics . data were obtained in privacy using an information form applied by one investigator , followed by gynecological examination and specimen collection all done by one gynecologist . cervical smear samples , based on the conventional method , were prepared with a spatula and fixed on glass slides and were stained with the papanicolaou technique . tv was defined as the presence of trophozoites in pap smears ; vc was diagnosed if fungal hyphae or budding yeasts were present in pap smears . the presence of inflammation in the smears was divided into mild , moderate , and severe categories . mild inflammation was defined as less than 30 inflammatory cells / high - power field ; moderate inflammation was defined as 30 to 100 inflammatory cells / high - power field ; and severe inflammation was defined as more than 100 inflammatory cells / high - power field . the frequency of pathogenic microorganism included bv , tv , and vc were determined in specimens . statistical significance was analyzed using statistical package for social sciences ( spss software version 17 ) . the comparison between data was performed with the pearson 's chi square or fisher 's exact test . mild inflammation was noted in 136 ( 26.1% ) , moderate in 155 ( 29.4% ) and severe in 117 ( 22.2% ) of them ( table 1 ) . the frequency of pathogenic vaginal microorganisms and inflammation among pap smear samples among all samples , bv ( the presence of clue cells ) was the most common pathogenic microorganism which was seen in 91 samples ( 17.2% ) , followed by vc ( n = 56 ; 10.6% ) . tv ( n = 2 ; 0.4% ) was shown to have a low prevalence among our patients ( table 1 ) . the overall prevalence of pathogenic microorganisms was greater among reproductive age participants , meanwhile the prevalence of bv as well as vc was significantly different ( p = 0.042 and p = 0.006 , respectively ) between non- and post- menopausal women . inflammation was detected in 76% ( n = 402 ) of pap smears , in which 80.1% ( n = 322 ) were reported among reproductive age women . however , the severity of inflammation was not significantly different between non- and post- menopausal women . overall , the presence of inflammation was significantly associated with vc ( p = 0.002 ) , but its severity was not correlated to the infection . although , there was no significant relation between the presence of inflammation and bv , the severity of inflammation in specimen was significantly increased in association with bv ( p < 0.001 ) . in our study , the prevalence of bv among pap smear specimens of women living in tehran was 17% which is similar to azargoon 's study ( 16% ) on a population in semnan ( another city in center of iran ) ( 3 ) , but it had a higher rate in hamadan ( a western city of iran ) and has been reported 28.5% ( 11 ) . in comparison with other asian countries , in india , but it was 38% in an african study in botswana on 703 pregnant women ( 13 ) . some predisposing factors for bv include having sexual relationship with more than one partner , early onset of sexual activity , orogenital sexual contacts , coitus during menstruation , use of iud , and smoking ( 2 , 14 ) . differences in sexual behavior and risk factors in different societies can justify the differences in bv prevalence of mentioned studies . reproductive age women indicated that the prevalence of bv in muslim women was lower than non - muslims . although the prevalence of tv in pap samples of our study was much less than several studies , similar reports demonstrated by depuydt et al in flanders detected by real - time pcr ( 0.37% ) ( 15 ) . however , this rate was 18% in the study in hamedan ( 11 ) , 8.5% among indian women ( 16 ) , and 19% in the african study ( 13 ) . a probable reason for these variations could be differences in pap sampling quality and cytologists skill . several studies show an increased vaginal ph ( 5 ) in both bv and tv infection ( 3 , 5 , 17 ) . demirezen et al in turkey on 600 pap tests detected tv in 6% of women and bv in 44% of tv cases . they also found a significant relationship between tv and bv infection , which might be due to this hypothesis that tv by phagocytosis the vaginal lactobacilli increases the vaginal ph and generates an anaerobic environment , providing an appropriate condition for the growth of anaerobic microorganisms ( 18 , 19 ) . also , it was confirmed by heller 's study on 400 pap samples which concluded that bv diagnosis should be considered at the presence of tv in pap smears ( 2 ) . in our study , we found no significant association between bv and tv in conventional pap smear sampling , which might be because of low prevalence of tv in our samples . the effect of habits and behaviors on vaginal flora among different population can be evaluated in further assessments . in our study , only the presence of candida in pap smear samples was associated with the report of inflammation . therefore , reporting inflammation in pap smear test might be considered for candidiasis evaluation and treatment . several studies investigated the association between infection and existence of inflammation in cervical smears ( 2023 ) . some of them found that inflammation on pap smear had a relatively low predictive value for the presence of infection ( 21 ) . they stated that the inflammation was not exactly a consequence of infection and other causes might be responsible for this appearance ( 20 ) . in contrast , others indicated a significant association between inflammatory smear and reproductive tract infections ( 22 , 24 ) . as burke et al ( 22 ) in their study on 256 women found an evidence of inflammation in 9.7% of smears and genital tract infection in 29.2% of their participants overall . they found infection in 48% of women having inflammatory changes on smear test vs. 27.3% of women whose smear tests showed no evidence of inflammation . they discovered that the prevalence of infection with chlamydia trachomatis , candida , bacteroides and gardnerella vaginalis was higher in the inflammatory smear group . they concluded that women with an inflammatory smear were more likely to mask the infection than women whose smear shows no evidence of inflammation ( 22 ) . prevalence of bv infection ( 17% ) in this study was similar to most other studies , which was not true for tv ( < 1% ) . the use of other diagnostic methods may be probably more valuable than conventional pap smear for evaluation of tv among iranian women and it needs further investigations . as the report of inflammation in our samples was very high , use the newer pap smear techniques such as thinprep ( liquid base preparation ) in the further studies is recommended . based on our results , inflammation reported in the pap smears demands the evaluation for vc and its proper treatment .

objectivenon - specific cervicitis or inflammatory changes in a smear report are common which are usually unclear for clinical approaches . to investigate the frequency of inflammation and pathogenic vaginal microorganisms in cervical smears among an iranian population sample.materials and methodsthis cross - sectional study was carried out on pap smear samples of women referred to gynecological clinic of taleghani hospital in tehran , iran , between october 2008 and march 2009 . this study was conducted on 528 conventional papanicolaou cervical smears . the frequency and severity of inflammation and prevalence of bacterial vaginosis ( bv ) , trichomonas vaginalis ( tv ) , and vaginal candidiasis ( vc ) was determined in the samples . also co - infection of the microorganisms in pap samples was evaluated . percentage , meanstandard deviation of the outcome parameters were calculated . the comparison between data was performed with the pearson 's chi square or fisher 's exact test.resultsthe prevalence of bv , vc , and tv in pap samples was 17% , 11% , and 0.4% respectively . overall , the prevalence of these microorganisms in women of reproductive age was higher than menopausal women . there was a significant association between vc and the presence of inflammation in our samples.conclusionbased on our results , inflammation in the pap smears can suggest an infection of vc and the patients should be considered for proper vc treatment .

esophageal carcinoma is one of the most common gastrointestinal cancers , which is considered as the sixth leading causes of morbidity and mortality worldwide . the preferred treatment for esophageal cancer or its related benign disease is esophagectomy with gastric conduit reconstruction . delayed gastric emptying is one of the most important problems after resection and reconstruction of the esophagus . it is reported that the problem is occurred in approximately 1050% of patients undergoing the procedure . it is associated with some other complications including increased aspiration and subsequent pneumonias , decreased patient satisfaction , and prolonged hospital stay . different pyloric drainage methods have been introduced and are currently used for preventing the problem such as pyloroplasty , pyloromyotomy , and buginage . though the techniques are used frequently , there are still controversies regarding the usefulness of them . some evidence demonstrated beneficial effects of the procedures in reducing gastric emptying times as well as earlier tolerance of solid diet in patients undergone gastric pull - up surgery , whereas others did not support the use of pyloric drainage procedures in this field . the findings of a systematic review study regarding the effectiveness of different pyloric drainage methods indicated that they are not significantly associated with the risk of developing delayed gastric emptying after esophagectomy , and regardless of using a pyloric drainage procedure , the gastric function would be improved with time . other reported that gastric conduit reconstruction without any drainage procedure is considered as an appropriate surgical option to restore digestive continuity after esophagectomy . in addition , it is well established that occurrence of some complications such as stricture , leak , bile reflux , esophagitis , and dumping syndrome are associated with pyloromyotomy and buginage . moreover , the methods could impair gastric mobilization due to shortening or anchoring the gastric outlet . considering the disparities regarding the usefulness of the methods as well as differences among various pyloric drainage techniques , this study compared the outcome of pyloromyotomy , pylorus buginage , and no intervention methods on gastric emptying among patients undergone esophagectomy . in this randomized clinical trial , patients with diagnosed esophageal cancer or any other benign lesions that diagnosed by pathology in a unique center referred to al - zahra hospital , affiliated to isfahan university of medical sciences , for esophagectomy were enrolled from the year 2012 to 2013 . the protocol of study was approved by the regional ethics committee of isfahan university of medical sciences ( research project number ; 389025 ) . patients with perioperative mortality due to medical or surgical complications or those with gastric ischemia or necrosis were excluded from the study . written informed consent all selected patients randomized in three groups with three different approaches for gastric pull - up esophageal surgery as follows [ figure 1 ] ; group 1 : esophagectomy with pyloromyotomy , group 2 : esophagectomy without intervention , and group 3 : esophagectomy with pylorus buginage by a bougie . consort diagram of the study in all studied patients , the method of gastric pull - up esophageal surgery was similar ( end to side esophagogastrostomy ) . all patients undergone esophagectomy and after the surgery , they were managed with nasogastric tubes postoperatively for 3 days with a cervical anastomosis and for 5 days with a thoracic anastomosis . all patients underwent a barium contrast agent swallow study on the 7 postoperative day to access gastric emptying in relation to the conduit and the pylorus and anastomotic integrity . the results of barium swallow test were evaluated by a radiologist blinded to the method of surgery . based on gastric emptying time , patients in three interventional groups were classified as normal and delayed gastric emptying or drainage . gastric emptying time 7 min considered as normal and more than 7 min as delayed . demographic characteristics , medical history , and surgical outcome of each patients were recorded by a trained nurse using a questionnaire . data analyzed using spss version 18 software ( spss , inc . , chicago , il , usa ) and studied variables in three studied groups compared using chi - square test . data analyzed using spss version 18 software ( spss , inc . , chicago , il , usa ) and studied variables in three studied groups compared using chi - square test . in this study , thirty patients who were candidate for esophagectomy were studied and randomly allocated in three different gastric pullup surgery . the characteristics of studied population group 1 ( esophagectomy + pyloromyotomy ) , group 2 ( esophagectomy + pyloric buginage ) , and group 3 ( no intervention ) mean ( standard deviation ) of gastric emptying time , the frequency of normal and delayed gastric drainage , and barium leakage in three studied groups are presented in table 2 . mean ( standard deviation ) of gastric emptying time , the frequency of normal and delayed gastric drainage , and barium leakage in three studied groups in this study , we compared the outcome of two methods of gastric drainage , pyloromyotomy , and pyloric buginage , with no intervention group on gastric emptying after esophagectomy . the findings indicated that there were not any significant differences between studied groups , and the gastric drainage methods had not significant superiority regarding gastric emptying than no intervention group . as mentioned , there are controversies regarding using of various methods of gastric pull - up surgeries as well as its different techniques . however , using of pyloric drainage during esophagectomy is a challenging issue . results of two meta - analysis studies suggest that the procedures could reduce gastric emptying time and rate of postoperative gastric outlet obstruction . the results of a more recent meta - analysis which reviewed studies within the last decades indicated that pyloric drainage was unnecessary and could be omitted , whereas another recent review study concluded that using of pyloric drainage strategies may be obsolete with the use of modern gastric tubes . there were some similar regional and worldwide studies that compared some methods of pyloric drainage . in this study , we compared the two most common procedures used in our department , i.e. , pyloromyotomy and pyloric buginage with esophagectomy without pyloric drainage method . though the results of our study showed that there were not any significant differences between studied methods , it seems that cases with delayed gastric emptying were more common in cases with no pyloric intervention . it is suggested that the results would be more accurate with larger sample size . in a similar study in mashhad - iran , jangjoo et al . have compared the results of gastric emptying test between finger bougie of pylorus and pyloromyotomy or pyloroplasty in gastric pull - up surgery . they concluded that the outcome of finger bougie of pylorus is the preferred and suggested method in this field . mahmodlou have investigated the utility of pyloromyotomy in improving gastric emptying in patients underwent transhiatal esophagectomy . in india have compared the patterns of gastric emptying using three different pylorus drainage procedures . in a recent study , antonoff et al . retrospective study compared the effectiveness of different pyloric drainage techniques among 293 patients . they found that using of pyloric drainage techniques could reduce the risk of aspiration and need for pyloric dilation before discharging from hospital and different drainage methods were similarly effective . in the current study , though we have few tubular gastric cases , the outcomes were not different in different statues of stomach . similarly , the results were not different in benign and malignant lesions . there are growing bodies of evidence that the drainage is more favorable in tubular gastric conduit than the whole stomach . in addition , it is recommended to evaluate other pyloric drainage methods including botulinum toxin injection as well as balloon dilatation in this regard for obtaining more conclusive result . however , some studies have reported the advantages of botulinum toxin injection than other methods . a recent study has reported an approximately 95% success rate for balloon dilation . gastric emptying time and delayed gastric emptying were not different between common pyloric drainage methods after esophagectomy and esophagectomy without drainage . using esophagectomy without pyloric drainage methods could also reduce the duration of surgery and related complication . further larger prospective studies with larger sample size and comparing other options of pyloric drainage are recommended . all authors contributed in the study design , conducting the systematic review , and drafting the manuscript . all authors approved the final version for submission and took the responsibility for the manuscript content .

background : there are controversies regarding the usefulness of the pyloric drainage methods after esophagectomy as well as differences among various pyloric drainage techniques . therefore , we compared the outcome of pyloromyotomy , pylorus buginage , and no intervention methods on gastric emptying among patients undergone esophagectomy.materials and methods : in this randomized clinical trial , patients with diagnosed esophageal cancer or any other benign lesions candidate for esophagectomy were selected . they randomized in three groups with three different approaches for gastric pull - up esophageal surgery including esophagectomy with pyloromyotomy , esophagectomy without intervention , and esophagectomy with pylorus buginage . the outcomes of procedures regarding gastric emptying time and delayed gastric emptying were compared.results:thirty patients were allocated in three groups . gastric emptying time was not significantly different in the three groups ( p > 0.05 ) . frequency of delayed gastric emptying , complications and barium leakage were not different in three studied groups ( p > 0.05).conclusion : gastric emptying time and delayed gastric emptying were not different between common pyloric drainage methods after esophagectomy and esophagectomy without drainage .

interstitial cystitis ( ic ) or bladder pain syndrome ( bps ) is a clinical condition that manifests as a sensory hypersensitivity of unknown cause , characterized by urinary frequency , bladder discomfort , and pelvic pain . the diagnosis of this condition was originally based on these symptoms bladder pain , urinary urgency , and evidence of supportive bladder pathology on cystoscopy under anesthesia ( inflammatory infiltrate , granulation tissue , detrusor mastocytosis , intrafascicular fibrosis , and hunner s ulcers ) , and exclusion of other possible diagnoses . ic was primarily described by hanash and pool as a condition characterized by urinary symptoms , markedly reduced bladder capacity , and cystoscopic findings of large irregular ( so called hunner s ulcers ) , i.e. , patches of reddened mucosa exhibiting small vessels radiating from a central pale scar . messing and stamey described nonulcer ic , characterized by multiple strawberry - like petechial hemorrhages referred to as glomerulations , and submucosal hemorrhages on cystoscopy and hydrodistension under anesthesia . in 1987 , the national institute of health - national institutes of diabetes , digestive , and kidney disease ( niddk ) in the united states of america established clinical and cystoscopic diagnostic criteria that included symptoms of bladder pain , urinary urgency , and evidence of bladder pathology , with the exclusion of other possible diagnosis . these strict criteria may exclude more than 60% of patients who actually have ic / bps , because they do not meet the criteria . in addition , there was neither any correlation between the histological severity of inflammation and the symptoms , nor with the niddk definition . in 2002 , bps was defined as the complaint of suprapubic pain related to bladder filling , accompanied by other symptoms such as increased daytime and nighttime frequency without evidence of proven urinary infection or other obvious pathology . more recently , the european society for the study of ic / bps ( essic ) suggested a new nomenclature and classification system . since pain is the fundamental character of the condition , it was proposed that the name be changed to bps . bps is diagnosed based on the presence of chronic pelvic pain lasting more than 6 months , pressure / discomfort perceived to be related to the urinary bladder , and one or more urinary symptoms such as urinary urgency or frequency . the american urological association defined ic / bps as follows : an unpleasant sensation ( pain , pressure , or discomfort ) perceived to be related to the urinary bladder , and associated with lower urinary tract symptoms of more than six weeks duration in the absence of infection or other identifiable cause . the essic suggests an optimal modality for diagnosing ic / bps using the 3-step - process described below . it was agreed that bps would be diagnosed based on chronic ( > 6 months ) pelvic pain , pressure , or discomfort perceived to be related to the urinary bladder . the second step is exclusion of similar diseases through medical history , physical examination , urinalysis , urine cultures , prostate - specific antigen in males > 40 years , uroflowmetry , postvoid residual urine volume by ultrasound scanning , cystoscopy , and biopsy . the diseases to be excluded include carcinoma , various infection , diverticulum , urogenic prolapse , endometriosis , vaginal candidiasis , gynecologic cancers , prostate cancer , benign prostatic obstruction , chronic bacterial / nonbacterial prostatitis , pudendal nerve entrapment , incomplete bladder emptying ( retention ) , and pelvic floor muscle related pain . the sources of the urinary infection include common intestinal bacteria , chlamydia trachomatis , mycoplasma , corynebacteria , herpes simplex virus , and human papillomavirus . the positive cystoscopic findings of bps are grade 23 glomerulations , hunner s lesions , or both . the positive histologic evidence of bps includes inflammatory infiltrate and/or granulation tissue and/or detrusor mastocytosis and/or intrafascicular fibrosis . each type is composed of 2 symbol - groups : symbols 1 , 2 , and 3 represent cystoscopic findings ( x , not done ; 1 , normal ; 2 , glomerulation ; and 3 , hunner s lesion ) , while symbols a , b , and c indicate biopsy findings ( x , not done ; a , normal ; b , inconclusive ; and c , positive ) . for example , bps type 1a means patients with normal finding at cystoscopy with hydrodistension and normal histology on biopsy . the most common indication is a search for urothelial carcinoma / carcinoma in situ of the bladder , which may be confused with ic . one group of authors suggest that the histopathologic findings are nonspecific , and of limited value to rule out carcinoma in situ . others contend that the histopathologic findings are useful to confirm the diagnosis . a significant number of patients with ulcerative ic show ulceration , severe inflammation , and granulation tissue . the surrounding tissue of the ulcer may show many lympho - plasmacytic infiltrates , frequently forming germinal centers . additionally , mast cells are significantly increased in the lamina propria and in the detrusor muscle . mucosal sloughing is more common in ulcer type ic than in nonulcer ic , but is rare in patients without cystitis . this phenomenon of denudation may result from instrumentation , but the urothelium in ic is particularly fragile , probably related to a type iv collagen defect in the urothelial basement membrane . about one - third of cases show abundant neutrophils in the venules with margination and involvement of the wall of the vein . hemorrhage of the lamina propria is more common in patients with ulcers than those without ulcers . about 80% patients have perineural inflammation ; however , this is finding is frequently also seen in those with bladder cancer and is not specific for ic . in these patients , significant fibrosis of the detrusor muscle was present in only 10% of patients , and this is exclusively noted in patients with ulcer . one group of authors described intrafascicular fibrosis as a unique histopathologic finding of ic , but this finding has not been firmly supported by subsequent studies . hemorrhage is present in 90% of cases with glomerulations , and while generally localized , the hemorrhage may extend into the urothelium . in 83% of cases , rupture may be related to suburothelial hemorrhage , likely secondary to a defect in the urothelial lining . most patients with nonulcerative ic have little or no inflammation , but edema and vascular congestion are frequently seen . some researchers consider that mast cells are strong histologic markers for ic , while others disagree . one study team suggested that up to 28 mast cells per square millimeter in the detrusor muscle was diagnostic of ic . the latter group of authors who disagree found that control patients without ic had higher numbers of infiltrating mast cells . some investigators contend that isosmotic formaldehyde / acetic acid is a better fixative to identify all mast cells rather than the conventional toluidine blue stains and giemsa stains . this fixative might prevent initial aldehyde blocking , and subsequent staining with toluidine blue discloses well a second population of mast cells uroplakin immunohistochemical staining revealed discontinuously reactive superficial / umbrella cells of the urothelium , suggesting a diagnostic value that awaits confirmation . uroplakin iii-4 , a splicing variant of uroplakin iii with significant upregulation has been reported in ic , suggesting a potential marker for identifying nonulcerative ic . the deposition of tamm - horsfall protein in the epithelium and submucosa has been seen in patients with ic , indicating a barrier defect in this disease . recently , a group of pathologic investigators suggested that patients with ic had prominent plasma cell infiltration and fibrosis in the affected bladder tissue , raising the suspicion that ic could be part of a systemic igg4-related disease . their cohort showed 60% igg4 positivity in both serum igg4 level and igg4-to - igg ratio . they proposed that a subset of ic may actually be an igg4-related disease , potentially providing a better understanding of the pathogenesis of ic . a new clinico - pathologic analysis for hunner / classic ic ( hic ) is suggested based on ( 1 ) light chain restriction of infiltrating b / plasma cells , and ( 2 ) fair correlation between the degree of lymphoplasmacytic infiltration and severity of urothelial denudation . the researchers suggest that non - hic and hic are distinct pathologic entities , and the latter is characterized by pancystitis , frequent clonal b - cell expansion , and epithelial denudation . an abnormality of the b - cell population ( significantly increased lymphoplasma cells , and light chain restricted b cells ) may be involved in the pathogenesis of hic . one investigator performed an extensive search of the literature for urinary markers of ic / bps , grouping findings according to their molecular structure and function . the inflammatory mediators were mast cells , histamine , methylhistamine , il-6 , crp , cxcl10 , cxcr3 , tnfsf14 , th chemokine , hip , pap , tyramine , 2-oxoglutarate , aibg , and orm1 . proteoglycans ( gp-51 , cd44 , and tamm - horsfall protein ) were shown to be a vital component of the bladder s defenses . various elevated proliferative factors ( pd - ecgf , vegf , ngf , egf , hb - egf , and antiproliferative factor [ apf ] ) have been found in ic . among them , apf was the most promising urinary biomarker . apf is a heat - stable sialogycopeptide that is a homolog of the human frizzled 8 glycopeptide . its role is mainly in the inhibition of urothelial proliferation , cooperated with other proliferative factors . apf has been detected in the urine of 95% ic patients compared to 9% in a negative control group . , apf activity and heparin - binding egf - like growth factor ( hb - egf ) levels seemed to respond to hydrodistension . apf and hb - egf levels were taken at baseline , was followed - up , and analyzed to assess for response assessment . nitric oxide gas production can be increased in tissue affected by inflammatory process and decreased during treatment with cyclosporine a. recently , gene analysis of urothelial proinflammatory markers has been actively tried as mentioned above , regulated by apf , the proinflammatory genes promote inflammatory cellular responses within the bladder . independent of essic recommendations , the first line of diagnosis is patient selection based on symptoms and an exclusion of other diseases with similar presentation . in addition , finally , updated pathophysiologic knowledge including numerous urinary biomarkers has led to changes in the diagnostic criteria .

interstitial cystitis / bladder pain syndrome ( ic / bps ) is characterized by bladder discomfort , urinary frequency , urgency , and pelvic pain . the etiology and pathogenesis of this condition is still unknown and remains diagnosed by exclusion . the histologic findings are also neither specific for diagnosis nor correlated with symptoms . however , the definition and diagnostic criteria for the condition was established in the last decade . in this paper , we review the changes in the definition , terminology , and diagnostic scheme of ic / bps , and summarize the histologic findings . we also briefly discuss some new pathologic suggestions and new urinary markers , focusing on the most promising ones .

denture stability is believed widely to be related to resistance against other forces like oblique and anterior - posterior forces . the patient s satisfaction is directly influenced by the amount of denture retention as it has been shown through several studies [ 24 ] . the need for correcting the patient s problems with faulty denture is an inevitable consequence of retention failure and residual ridge resorption . several different strategies have been introduced to overcome the problem , one of which is the use of dental implants . three distinct methods of prosthetic treatments based on implants in the lower jaw are : implant supported fixed prosthesis ( fp-1 , fp-2 , fp-3)removable implant supported overdentures ( rp-4)combined implant - tissue supported over - dentures ( rp-5 ) . implant supported fixed prosthesis ( fp-1 , fp-2 , fp-3 ) removable implant supported overdentures ( rp-4 ) combined implant - tissue supported over - dentures ( rp-5 ) . the third of the above mentioned methods has the advantage of reducing the number of implants with a more simplified prosthetic approach . intra - osseous implants are considered as acceptable abutments in conjunction to attachments for efficient retention of the overdentures . factors involved in choosing the type of attachment include available space , maintenance necessity , spare part availability and ease of change , force distribution to the soft tissue or implant and the level of retention . another important fact is the level of wear seen in attachments following the use of overdenture . the aim of this research was to compare the effects of three different attachments ; nobel biocare ball ( nbb ) , nobel biocare bar and clip ( nbbc ) and sterngold era red ( erar ) on the retention and resistance of implant - supported overdentures . this in vitro investigation was performed on a total of 15 samples divided into three groups of five . each group was designed to include the attachments with erar ( 0 degree era micro np abutment only , 1 mm cuff and micro era male - red overdenture 5 , sterngold , usa ) , the attachments with nbbc ( gold adapt & gold abutment bar and clip attachment , nobel biocare , sweden ) and attachments with nbb ( ball abutment titanium , branemark system , rp 1 mm and plastic cap , nobel biocare , sweden ) . all samples were tested for the retention and resistance of overdenture on vertical , oblique and anterior - posterior tensile force load . recordings were made after the first insertion of the overdenture ( sit . 1 ) and also following 100 times of insertion / removal process ( sit . a pair of implants , 3.7510 mm , ( mk iii , branemark system , nobel biocare , sweden ) was inserted at both sides of the midline at the symphysis region in a parallel position . a milling machine ( paraskop m , bremen , germany ) was employed to avoid any fault in the angulation of insertion ( fig 1-a ) . a framework of cobalt chromium alloy ( wiironit , bego , bremen , germany ) was fabricated to fit on the two implants and the model . metallic structure was used for its durability and stability in all stages of the experiment . four stainless steel bands were soldered to the framework , which was positioned at the anterior part of the overdenture close to the implants . the others were established on the midline in the buccal and lingual side of the ridge . the overdenture was attached to the testing machine through the hooks ( fig 1-b ) . a prototype of overdenture housing was then constructed over the metallic overdenture by use of a light cure acrylic resin ( vlmc , vita , badsackingen , germany ) ( fig 1-c ) . all overdenture housings were duplicated from the prototype and fabricated by use of a self cure acrylic resin ( orthocryl , dentaurum , ispringen , germany ) ( fig 1-d ) . therefore , an acrylic overdenture housing was made for each sample ( totally 15 ) . one part of the attachment was attached into the overdenture housing and the other part , the abutment , was screwed on the implant ( fig 1-e ) . after the confirmation of appropriate sitting of the overdenture and adaptation of attachments , a series of measurements were started for each sample . recordings were made at 51 mm / min speed similar to that of denture move at bite and mastication . vertical force was measured to assess the retention while oblique and anterior - posterior forces were evaluated for resistance testing . maximum dislodging force ( mdf ) was recorded at the point of complete detachment of the overdenture from the model . data were finally subjected to an analysis using one - way anova test as well as tukey s test . based on the results derived from the collected data , the clinical behavior of three different attachments tested were not similar during application of different forces . as the data was normally distributed , one - way anova test was performed to compare the differences among three attachments for their force tolerance . at the beginning ( sit . 1 ) , tukey s test revealed that there was significant differences between erar / nbb , erar / nbbc and nbbc / nbb for vertical and oblique tensile strengths ( p<0.001 ) . this result was reemphasized by one - way anova test ( p<0.001 ) . therefore , erar had the highest retention and oblique resistance and nbb had the least . for anterior posterior tensile strength , tukey s test showed significant differences between erar / nbbc and erar / nbb ( p<0.001 ) , while there was no significant difference between nbbc and nbb ( p=0.528 ) . so erar had the highest anterior - posterior resistance but nbbc and nbb had the same . figs 24 show mdf measured for these attachments under vertical , oblique and anterior - posterior tensile forces in both situations ( sit . 1 and 2 ) . 2 , these data were statistically significant in their differences among different attachments for vertical and oblique tensile strengths , using one - way anova test ( p<0.001 ) . however , tukey s test on nbbc / nbb showed no statistically significant difference for vertical ( p=0.198 ) and oblique tensile strengths ( p=0.462 ) . erar had the highest retention and oblique resistance , while nbbc and nbb had the same . a further kruskal - wallis test performed on three groups in anterior - posterior tensile strength showed significant differences ( p<0.01 ) . the paired t - test performed to evaluate the condition of the three attachments in two different situations ( sit . 1 and sit . this indicated that the insertion / removal of overdenture for 100 times caused the differences between sit . 1 and sit . 2 in all three groups ( erar , nbbc and nbb ) . over the past three decades the use of implant - tissue supported overdenture has raised considerably among dentists . it is mainly related to the rise in patient awareness and availability of attachments to the dentist . several force directions are considered as applied in the mouth during function of the overdenture with retention being the most critical issue . two important points of view are considered on the retention of prosthesis , including the patient s feeling and the dentist s assessment . the latter which is measured during maximum load force application was surveyed in this research . 1 , erar has the highest resistance against vertical , oblique and anterior - posterior tensile forces . this means that overdenture has a higher retention and resistance potential with a significant difference from the other two attachments . this difference could be due to the design of erar as being intra - radicular . this is explained further by a female segment on the abutment of the attachment in addition to high and parallel abutment walls ( 5 mm length ) . the nbb showed the least mdf against vertical , oblique and anterior - posterior tensile forces . this is concluded to be due to the extra - radicular design in addition to free movement of the male component inside the female component . retention and resistance of nbb was in the least level while erar was at the most with significant differences ( p<0.001 ) . anterior - posterior resistance of erar was also at the highest level as mentioned before , while no differences were established between nbbc and nbb ( p=0.528 ) . petropoulos has reported a roughly similar result on nbb and nbbc characteristics while results reported on erar were different from the result achieved in this research . this could be due to the use of sterngold era of intra - radicular type which was not the case in the earlier mentioned study . 2 ) showed a considerable reduction in retention and resistance of overdenture on attachments possibly due to constant wear ( p<0.01 ) . this difference was statistically significant even in several insertion/ removal tests which the level of mdf against vertical , oblique and anterior - posterior forces was higher in erar than the others ( p<0.001 ) . in sit . 2 , there were no differences in retention and oblique resistance of nbb and nbbc ( p=0.198 , p=0.462 ) , but the anterior - posterior resistance of nbb was more than nbbc ( p<0.01 ) . it could also be explained by the material the attachments were made of , resulting in a higher resistance to wear in nbb compared to nbbc . based on the results of this research , clinical behaviors of these attachments ( erar , nbbc , nbb ) have been well identified . therefore , the dentist can choose an appropriate attachment in implant - tissue supported overdentures according to the clinical situation . it is recommended to use erar attachment when a high amount of retention and resistance is necessary . for example , for a patient who has severe residual ridge resorption or used to remove and insert the denture frequently , erar attachment should be applied . nbb and nbbc attachments would be the choice when there is low demand of retention and resistance for overdenture . insertion and removal of overdenture gradually causes loss of retention and resistance due to the attachment s wear .

objective : retention and resistance of the implant - tissue supported overdenture may be affected by the type of attachment . the aim of this research was to compare the retention and resistance of nobel biocare ball ( nbb ) , nobel biocare bar and clip ( nbbc ) and sterngold era red ( erar ) attachments on an implant - tissue supported overdenture model.materials and methods : the attachment samples were divided into 3 groups of nbb , nbbc , and erar ( 5 samples in each group ) . two parallel nobel biocare branemark implants were placed symmetrically at the symphysis region of a mandibular test model . a metallic overdenture was fabricated precisely adapted to the model and attached to a zwick testing machine ( crosshead speed of 51 mm / min ) . dislodging tensile forces were applied in three vertical , oblique , anterior - posterior directions and two situations , at the beginning and after 100 times of insertion / removal of the overdenture , for each sample . the maximum dislodging force was measured . a one - way anova test was employed followed by tukey s test.results:erar was the most retentive and resistant in both situations . nbb and nbbc showed the same anterior - posterior resistance at the beginning . all test groups represented a large amount of retention and resistance loss after the insertion / removal of the overdenture , while nbbc showed a higher loss of anterior - posterior resistance than nb.conclusion:a highest level of retention and resistance was seen in erar . the retention and resistance were affected by the wear of attachments .

in january 2002 , a 74-year - old man sought medical care , reporting malaise , anorexia , and fever . past medical history included ischemic bowel disease , vascular disease , partial gastrectomy for peptic ulcers , and left upper lobectomy for squamous cell carcinoma ( december 1999 ) . on february 1 , he was hospitalized with persistent fever and nonproductive cough ; results of a chest radiograph were consistent with necrotizing pneumonia . a tuberculosis ( tb ) skin test ( tst ) result was negative , and a sputum smear was negative for acid - fast baccilli ( afb ) . after 5 days , the patient had not improved clinically ; chest radiograph showed increasing infiltrate on the left side . the condition of the patient deteriorated clinically over the next 10 days ; he died on day 16 of his hospitalization . laboratory confirmation for tb , speciation , and antimicrobial drug susceptibility testing were pending at the time of his death . genotyping analysis showed that the m. bovis isolated from this patient matched the circulating deer / cattle strain ( table 2 ) . * miru , mycobacterial interspersed repeat units ( 6 ) . international spoligotype database , available from www.mbovis.org ( 7 ) . patient 1 lived on a farm geographically distant from the current bovine tb endemic area . his first wife had a reported diagnosis of tb after their divorce > 40 years before , and his second wife reports he drank unpasteurized milk as a youth . he moved to the edge of deer management unit ( dmu ) 452 in 1994 , which is the focal area for the bovine tb outbreak in deer . there , he ran a business with a buck pole where hunters displayed killed deer . additional potential exposures included hunting white - tailed deer and consuming venison ( > 10 years before his death ) , handling a deer carcass from the dmu 452 vicinity in 2000 , and recreational feeding of deer . this patient was in poor health at the time of death , having acute and chronic illness . his poor health would have rendered him more susceptible to infection with m. bovis and would have made the progression from latent infection to clinical disease more likely . the pathology results from his lung resection in december 1999 provided no evidence of tb ; therefore , infection was likely acquired subsequently . the genotyping results from patient 1 matched those of the circulating deer / cattle strain , which suggested exposure to infected cattle or deer . the lack of recent exposure to cattle suggests that deer are the more likely source of infection . on october 1 , 2004 , he shot a white - tailed deer just outside dmu 452 . while field dressing the animal , he punctured his left index finger with a hunting knife . approximately 18 days after the injury , his finger became inflamed and painful , so he sought medical treatment . based on his history of exposure to a deer with lesions , a tst was administered ; the result was negative . an orthopedic specialist diagnosed infectious tenosynovitis of the flexor tendon of the left index finger . a wound culture was sent to michigan department of community health , bureau of laboratories . the patient was discharged and then readmitted to the hospital 12 days later with subcutaneous infection at the puncture site , which was again incised and drained . genetic probe results confirmed m. tuberculosis complex . by december 7 , 2004 , the culture was reported as resistant to pyrazinamide , suggesting m. bovis , which was later confirmed on the basis of susceptibility to thiopene-2-carboxylic acid hydrazide and biochemical testing for pyrazinamidase . the result of a second skin test , 14 weeks postexposure , was positive ( 6-mm induration ) . he continued to receive antimicrobial drug therapy for 9 months without further complications as an experienced hunter , patient 2 recognized the tan nodules in the deer s chest cavity as m. bovis and promptly buried the carcass . in december , he led michigan department of natural resources staff back to the carcass , which was retrieved ; the chest cavity was filled with lesions ( figure ) . although the carcass was buried for > 9 weeks , chest cavity samples were submitted for culture . genotyping results of the carcass isolate were identical to that recovered from patient 2 and the circulating deer / cattle strain ( table 2 ) . the investigation of the infection in patient 2 provided strong evidence of transmission of m. bovis infection from deer to human through percutaneous injection with a contaminated hunting knife . the patient s history of hunting exposure was essential to diagnosis and treatment of this rare form of tb . photo of the chest cavity of a deer shot by patient 2 ; the deer was retrieved after being buried for 9 weeks . in january 2002 , a 74-year - old man sought medical care , reporting malaise , anorexia , and fever . past medical history included ischemic bowel disease , vascular disease , partial gastrectomy for peptic ulcers , and left upper lobectomy for squamous cell carcinoma ( december 1999 ) . on february 1 , he was hospitalized with persistent fever and nonproductive cough ; results of a chest radiograph were consistent with necrotizing pneumonia . a tuberculosis ( tb ) skin test ( tst ) result was negative , and a sputum smear was negative for acid - fast baccilli ( afb ) . after 5 days , the patient had not improved clinically ; chest radiograph showed increasing infiltrate on the left side . the condition of the patient deteriorated clinically over the next 10 days ; he died on day 16 of his hospitalization . laboratory confirmation for tb , speciation , and antimicrobial drug susceptibility testing were pending at the time of his death . genotyping analysis showed that the m. bovis isolated from this patient matched the circulating deer / cattle strain ( table 2 ) . * miru , mycobacterial interspersed repeat units ( 6 ) . international spoligotype database , available from www.mbovis.org ( 7 ) . patient 1 lived on a farm geographically distant from the current bovine tb endemic area . his first wife had a reported diagnosis of tb after their divorce > 40 years before , and his second wife reports he drank unpasteurized milk as a youth . he moved to the edge of deer management unit ( dmu ) 452 in 1994 , which is the focal area for the bovine tb outbreak in deer . there , he ran a business with a buck pole where hunters displayed killed deer . additional potential exposures included hunting white - tailed deer and consuming venison ( > 10 years before his death ) , handling a deer carcass from the dmu 452 vicinity in 2000 , and recreational feeding of deer . this patient was in poor health at the time of death , having acute and chronic illness . his poor health would have rendered him more susceptible to infection with m. bovis and would have made the progression from latent infection to clinical disease more likely . the pathology results from his lung resection in december 1999 provided no evidence of tb ; therefore , infection was likely acquired subsequently . the genotyping results from patient 1 matched those of the circulating deer / cattle strain , which suggested exposure to infected cattle or deer . the lack of recent exposure to cattle suggests that deer are the more likely source of infection . on october 1 , 2004 , he shot a white - tailed deer just outside dmu 452 . while field dressing the animal , he punctured his left index finger with a hunting knife . approximately 18 days after the injury , his finger became inflamed and painful , so he sought medical treatment . based on his history of exposure to a deer with lesions , an orthopedic specialist diagnosed infectious tenosynovitis of the flexor tendon of the left index finger . a wound culture was sent to michigan department of community health , bureau of laboratories . the patient was discharged and then readmitted to the hospital 12 days later with subcutaneous infection at the puncture site , which was again incised and drained . the culture was reported as resistant to pyrazinamide , suggesting m. bovis , which was later confirmed on the basis of susceptibility to thiopene-2-carboxylic acid hydrazide and biochemical testing for pyrazinamidase . the result of a second skin test , 14 weeks postexposure , was positive ( 6-mm induration ) . he continued to receive antimicrobial drug therapy for 9 months without further complications as an experienced hunter , patient 2 recognized the tan nodules in the deer s chest cavity as m. bovis and promptly buried the carcass . in december , he led michigan department of natural resources staff back to the carcass , which was retrieved ; the chest cavity was filled with lesions ( figure ) . although the carcass was buried for > 9 weeks , chest cavity samples were submitted for culture . genotyping results of the carcass isolate were identical to that recovered from patient 2 and the circulating deer / cattle strain ( table 2 ) . the investigation of the infection in patient 2 provided strong evidence of transmission of m. bovis infection from deer to human through percutaneous injection with a contaminated hunting knife . the patient s history of hunting exposure was essential to diagnosis and treatment of this rare form of tb . photo of the chest cavity of a deer shot by patient 2 ; the deer was retrieved after being buried for 9 weeks . although epidemiologic evidence presented for patient 1 is not irrefutable , we conclude that both cases are part of a cluster that is epidemiologically and genotypically confirmed ( 11 ) . the initial tst result was negative in both of these cases , likely due to cutaneous anergy ( patient 1 ) and administration too soon after exposure ( patient 2 ) . the confirmation of a hunter s acquiring cutaneous m. bovis from an infected deer supports the need for public health precautions . second , hunter education was important in the second case because the hunter recognized the deer as infected and specifically mentioned his exposure each time he sought medical treatment . third , efforts to raise the index of suspicion of the medical community regarding cutaneous and other occupational or recreational exposures to tb continues to be important , so that appropriate diagnoses can be made . finally , in both cases , the initially negative tst result complicated the diagnostic efforts . it is an ongoing challenge to ensure that providers appropriately apply and interpret the tst .

mycobacterium bovis is endemic in michigan s white - tailed deer and has been circulating since 1994 . the strain circulating in deer has remained genotypically consistent and was recently detected in 2 humans . we summarize the investigation of these cases and confirm that recreational exposure to deer is a risk for infection in humans .

carcinoid tumors are rare tumors that display neuroendocrine properties . about 90% of carcinoid tumors arise in the gastrointestinal tract ( git ) . carcinoid tumor is the most frequent primary malignant tumor of the small intestine beyond the ligament of treitz and most frequently arises in the terminal ileum . secondary mesenteric involvement of small bowel carcinoid tumors is common , reported as occurring in 40% to 80% of cases . however , primary mesenteric carcinoid tumors are very rare and most solid tumors arising in the mesentery are usually metastatic tumors . distant metastasis rates from carcinoid tumors increases up to 80% to 90% when the size of the tumor is larger than 2 cm [ 3 - 5 ] . we present a very rare case of a primary mesenteric carcinoid tumor with 8.2 7.3 cm sized that demonstrated a benign character . a 73-year - old woman presented with a palpable abdominal mass which had been increased in size for 1 year . physical examination revealed an 8 cm sized round and movable mass without tenderness in the periumbilical area . computed tomography ( ct ) scan demonstrated an 8.2 7.3 cm sized well - defined mass with complex density located in the mesentery or adjacent proximal jejunum ( fig . , a well - encapsulated mass was found to be arising from the small bowel mesentery near the ligament of treitz ( fig . there were no abnormal findings in the other organs including the small bowel and colon . histological examination showed tumor cells composed of homogenous small cells arranged in a trabecular pattern with the nucleus showing a round to oval shape , indistinct nucleoli , and coarsely granular chromatin pattern . immunohistochemistry showed the tumor to be positive for multiple neuroendocrine markers including synaptophysin ( fig . histopathologic examination confirmed the mass as a carcinoid tumor with a benign nature . at 11 months of follow - up , the patient was asymptomatic and recurrence free . carcinoid tumor is a rare , slow - growing , neuroendocrine tumor with about 90% of the lesions arising in the git . git carcinoid tumors are classified by the embryologic origin as foregut , midgut and hindgut . 46% to 64% of git carcinoid tumors arise in the midgut and most midgut carcinoid tumors originate in the terminal ileum . however , primary carcinoid tumors of the mesentery are very rare . and carcinoid tumors arising in the mesentery are usually metastatic . midgut carcinoid tumors commonly spread to the mesentery , reported as occurring in 40% to 80% of cases in various series . on ct scan , mesenteric carcinoid tumors exhibit varying degrees of fibrosis , calcification , focal or diffuse neurovascular bundle invasion by the tumor or both mechanisms . generally , for tumors smaller than 2 cm without lymph node involvement , local segmental resection is adequate . and tumors larger than 2 cm with regional mesentery metastasis and lymph node involvement , wide excision of the bowel and mesentery with lymph node dissection is needed because tumors larger than 2 cm are associated with 80% to 90% incidence of metastasis [ 3 - 5 ] . also , surgical debulking of local or distant metastatic carcinoid tumors is recommended , both for relief of symptoms and prolonged survival , despite randomized evaluation not being done [ 3 - 5 ] . microscopically , typical carcinoid tumors have one of five growth patterns : insular , trabecular , glandular , undifferentiated , or mixed . , the tumor originated from the mesentery near the ligament of treitz and well encapsulated , free from the small intestine ( fig . 2 ) . at the time of surgery , the entire small bowel was meticulously inspected and no evidence of tumor mass or enlarged lymph node was found . in addition , there was no evidence of tumor anywhere else in the abdomen including the liver , ovary and other solid organs . so , it may be a primary mesenteric carcinoid tumor or metastasis from an occult primary site . carcinoid tumors often have advanced malignant potential depending on location , size , nature . but this case shows a rare large primary mesenteric carcinoid tumor with characteristics of uncommon position and benign nature .

primary mesenteric carcinoid tumor is very rare , although secondary mesenteric involvement is common , reported as 40% to 80% . and distant metastasis rate reported as 80% to 90% , when the size is larger than 2 cm . we present a case of very rare primary mesenteric carcinoid tumor showing benign character though large size . the patient visited st . vincent 's hospital , the catholic university of korea with increasing palpable abdominal mass . at laparotomy , a well encapsulated mass arising from the mesentery near the ligament of treitz was found without any adjacent organ invasion or distant metastasis . the mass was measured as 8.2 7.3 cm and histopathologically benign character . at 11 months of follow up , the patient was recurrence free .

the mobile phone camera can be used to perform indirect ophthalmoscopy when used in conjunction with a + 20d condensing lens . however , the flash in most phones is not continuously on in the still photography mode , flash firing only during the exposure . in the video mode , the flash can be programmed to be always on when in the recording mode and this would allow illuminating the fundus and obtaining a video of the same . hence the mobile phone in video mode can be used as a video indirect ophthalmoscope and we used this technique for fundus imaging . haddock et al . have described the technique of using an iphone ( apple inc , cupertino , usa ) in conjunction with software that allows manipulation of the camera parameters to obtain good quality images . the phone is set to video mode with the flash always on ( as described above ) . the condensing lens is held in the other hand as one would perform indirect ophthalmoscopy and starting the recording will turn the flash on and allow visualization of the fundus once the camera , light and the condensing lens are in line with the patient 's pupil . although , the condensing lens is held at the usual distance from the eye as one would during indirect ophthalmoscopy , the mobile phone need not be held at arm 's length , but much closer to the lens [ fig 1 ] . as in routine indirect ophthalmoscopy , tilting the condensing lens will avoid reflexes from the lens surface and moving both to different quadrants allows examination of the fundus periphery . the phone is held much closer to the condensing lens in contrast to routine indirect ophthalmoscopy the direct ophthalmoscope directs a focused beam of light into the eye , the reflected light being captured by the observer 's eye . by placing a led light source ( powered by an external battery source ) close to the camera , the mobile phone can effectively be transformed into a direct ophthalmoscope [ fig 2 ] . modification of the mobile phone camera by affixing a light emitting diode light with external power supply , allows it to be converted in to a direct ophthalmoscope the led light is turned on and taking the phone close to the eye of a patient with pharmacologically dilated pupil will allow imaging the fundus . still photography and video recording is possible with this technique as it does not depend on the in - built flash for illuminating the fundus . the mobile phone camera can be used to perform indirect ophthalmoscopy when used in conjunction with a + 20d condensing lens . however , the flash in most phones is not continuously on in the still photography mode , flash firing only during the exposure . in the video mode , the flash can be programmed to be always on when in the recording mode and this would allow illuminating the fundus and obtaining a video of the same . hence the mobile phone in video mode can be used as a video indirect ophthalmoscope and we used this technique for fundus imaging . haddock et al . have described the technique of using an iphone ( apple inc , cupertino , usa ) in conjunction with software that allows manipulation of the camera parameters to obtain good quality images . the phone is set to video mode with the flash always on ( as described above ) . the condensing lens is held in the other hand as one would perform indirect ophthalmoscopy and starting the recording will turn the flash on and allow visualization of the fundus once the camera , light and the condensing lens are in line with the patient 's pupil . although , the condensing lens is held at the usual distance from the eye as one would during indirect ophthalmoscopy , the mobile phone need not be held at arm 's length , but much closer to the lens [ fig 1 ] . as in routine indirect ophthalmoscopy , tilting the condensing lens will avoid reflexes from the lens surface and moving both to different quadrants allows examination of the fundus periphery . the phone is held much closer to the condensing lens in contrast to routine indirect ophthalmoscopy the direct ophthalmoscope directs a focused beam of light into the eye , the reflected light being captured by the observer 's eye . by placing a led light source ( powered by an external battery source ) close to the camera , the mobile phone can effectively be transformed into a direct ophthalmoscope [ fig 2 ] . modification of the mobile phone camera by affixing a light emitting diode light with external power supply , allows it to be converted in to a direct ophthalmoscope the led light is turned on and taking the phone close to the eye of a patient with pharmacologically dilated pupil will allow imaging the fundus . still photography and video recording is possible with this technique as it does not depend on the in - built flash for illuminating the fundus . video recording of fundus findings could be obtained by employing a mobile phone as a video indirect ophthalmoscope [ fig 3 ] . direct ophthalmoscopy was possible after pupillary dilation , particularly in patients with a clear lens [ fig 4 ] . the field of view is limited when using the mobile phone as a direct ophthalmoscope . mobile phone indirect ophthalmoscopic fundus images : ( a ) nonproliferative diabetic retinopathy ; ( b ) post pan retinal photocoagulation , ( c ) branch retinal artery occlusion with retinal whitening , ( d ) melanocytoma of the optic disc with peripapillary choroidal neovascular membrane mobile phone direct ophthalmoscopic images obtained in infants under general anesthesia : ( a ) active retinoblastoma ; ( b ) normal posterior pole , ( c ) partly regressed retinoblastoma post chemoreduction , ( d ) coats disease with subretinal exudates temporal to fovea mobile phones are ubiquitous with high - resolution cameras being de rigueur . using a mobile phone to image , it offers the facility to image and document the fundus even if a fundus camera is not available as in a primarily anterior segment clinic or in rural camp screening . all one would need is a condensing lens if performing indirect ophthalmoscopy or an easily affixed light source to perform direct ophthalmoscopy . mobile phones allow magnification and storing of the images , the data connectivity allowing sharing of the images for cross consultation . using a mobile phone as a direct ophthalmoscope avoids the discomfiting proximity of the examiner to the patient . there are limitations to using a mobile phone as a fundus camera , the primary one being the learning curve to perform indirect ophthalmoscopy . the inability to turn the flashlight on prior to capture in still photography forces us to use the video mode to perform ophthalmoscopy . the quality of images obtained is compromised to some extent as the flash of the mobile phone camera is not a focused beam as in an ophthalmoscope . direct ophthalmoscopy needs close proximity of the light source to the camera which can be achieved by affixing an additional light as described by us . we did try to move the light from the in - built flash close to the camera by re - routing it with fiber optic cable , but this provided either sub - optimal illumination or the protruding fiber prevented direct ophthalmoscopy that requires the ophthalmoscope to be rather close to the eye . optimized positioning of the light in relation to the camera should allow the mobile phone to be used as a direct ophthalmoscope . we have been using a mobile phone camera as a video indirect ophthalmoscope and a direct ophthalmoscope particularly to document the fundus findings of infants undergoing examination under anesthesia and also as a tool for fundus screening in camps . similar devices such as the peek ( peekvision.org , uk ) and cellscope ( cellscope , inc . san francisco , usa ) with hardware adapters and custom built software are being used by other investigators across the world for screening purposes in underdeveloped countries . being custom built devices they offer the ability of a wider field of view , ancillary testing such as vision and cataract testing , which are not possible with our techniques described above . the mobile phone camera has recently been used to perform fluorescein angiography , despite which it is unlikely that it will completely replace the fundus camera . however , the capability to image the fundus practically anywhere with a device that is always with us offers a freedom that is beyond the reach of a fundus camera .

fundus imaging with a fundus camera is an essential part of ophthalmic practice . a mobile phone with its in - built camera and flash can be used to obtain fundus images of reasonable quality . the mobile phone can be used as an indirect ophthalmoscope when coupled with a condensing lens . it can be used as a direct ophthalmoscope after minimal modification , wherein the fundus can be viewed without an intervening lens in young patients with dilated pupils . employing the ubiquitous mobile phone to obtain fundus images has the potential for mass screening , enables ophthalmologists without a fundus camera to document and share findings , is a tool for telemedicine and is rather inexpensive .

splenic tumors are rare and can be caused by a wide range of benign and malignant conditions including cysts and abscesses , granulomatous processes , castleman s disease , angiosarcoma , teratoma , lymphoma , and metastatic carcinoma . inflammatory pseudotumors ( ipt ) are uncommon , yet important lesions to consider in the differential diagnosis of splenic masses . these tumor - like masses of inflammatory cells , occur in a number of different organ systems , with the most common being the lung and orbit ; however they have also been reported in the meninges , testis , gastrointestinal tract , heart , liver , bladder , thyroid , nasal cavity and soft tissue . primary splenic ipt is rare ; and the precise number of cases is uncertain , with variable numbers reported in the literature since its first description in 1984 by cotelingam and jaffe . the number of cases reported varies between 80 reported in 2008 , to 114 in the most recent studies ; however , the available data is incomplete , and it remains unclear whether all of these cases are primary solitary splenic ipt or whether some of these are cases of secondary splenic involvement , or misdiagnoses of other histologically similar lesions . inflammatory pseudotumors may present with a wide range of clinical symptoms , non - specific imaging findings , and often , features of an underlying systemic inflammatory response , making the diagnosis challenging . the chronic inflammatory response is characterized biochemically by raised inflammatory markers , and often , polyclonal hypergammaglobulinemia , resulting from a diffuse activation of plasma cells . polyclonal hypergammaglobulinemia is seen in chronic infections and inflammatory conditions , connective tissue diseases , cases of liver disease , and ultimately , a myriad of other conditions leading to chronic stimulation of the immune response . we present a case of a young woman with non - specific , chronically elevated inflammatory markers , including raised c - reactive protein ( crp ) , erythrocyte sedimentation rate ( esr ) and polyclonal hypergammaglobulinemia , together with an isolated splenic lesion , who was found to have a rare inflammatory pseudotumor of the spleen . a 19-year - old woman was referred to our clinic for investigation of a 15-month history of fatigue , raised inflammatory markers , anemia and a polyclonal gammopathy of uncertain etiology . the patient originally presented to her general practitioner for a routine check - up prior to an extended overseas trip ; she was well with no significant medical history , and asymptomatic of her anemia . screening blood tests were suggestive of an iron deficiency anemia [ hemoglobin ( hb ) 105 g / l , mean corpuscle volume ( mcv ) 77 fl , ferritin ( fe ) 2 umol / l , transferrin saturation 3% ] associated with elevated inflammatory markers esr 73 mm / hr , crp 45 mg / l and a low vitamin d level . numerous investigations and specialist consultations followed to identify the cause of this non - specific inflammatory response . repeat blood tests including spep and hematinics were essentially unchanged ; blood cultures , autoantibodies , and hemoglobin electrophoresis were unremarkable . further investigations including a transthoracic echocardiogram , chest x - ray , magnetic resonance imaging ( mri ) small bowel series , colonoscopy and gastroscopy were non - contributory . she had two follow - up blood tests while overseas , which again remained unchanged . on return to australia , and in the setting of ongoing investigation for these persisting abnormalities , our patient developed anxiety and began to report a variety of non - specific symptoms , such as fatigue and muscle pains , which she attributed to her abnormal results . she was subsequently referred for a hematology opinion . once again , her hematology , electrolytes , hematinics , autoantibodies and spep were checked , and remained unchanged . viral testing for human herpesvirus-8 ( hhv-8 ) and epstein - barr virus ( ebv ) were negative . the patient was referred for a positive emission tomography - computed tomography ( pet - ct ) scan for further investigation , and hopefully exclusion , of malignancy . unexpectedly , the pet scan identified an area of mild fludeoxyglucose-18 ( fdg ) uptake in the superior pole of the spleen ; this was verified on ct where a heterogeneous lesion with a small area of calcification was noted ( figure 1 ) . on review of her prior mri , conducted 13 months previously , a similar sized lesion was retrospectively identified ( figure 2 ) . examination of the bone marrow demonstrated reactive trilineage hematopoiesis with no evidence of lymphoma or plasma cell proliferation . in view of the pet - avid splenic lesion , an uncomplicated , elective , the spleen was partially morcelated , weighting 178 grams with no discrete lesion identified on serial sectioning . microscopically , some sections showed replacement of splenic parenchyma by a lesion with abundant calcification and iron deposition , which was composed of interlacing fascicles of haphazardly arranged spindled myofibroblasts with extensive hemorrhage , and a polymorphic inflammatory infiltrate comprising plasma cells , eosinophils , small mature lymphocytes , and hemosiderin - laden macrophages ( figure 3a ) . the myofibroblastic cells were strongly positive for sma ( figure 3b ) and negative for desmin , cd34 , cd21 , cd8 , and alk1 . additional stains show that the majority of spindled cells are negative for s100 protein , and no acid fast bacilli were seen with ziehl - neelsen and wade fite stains . in - situ hybridization for epstein - barr virus encoded - small rna s ( eber ) and hhv8 were negative . she had an uncomplicated post - operative course and pleasingly , all hematological and biochemical abnormalities resolved within two months post splenectomy . inflammatory pseudotumors are rare masses of inflammatory cells that can be found in various anatomical areas of the body . the name inflammatory pseudotumor was first coined in 1954 by umiker and iverson , and encompasses a spectrum of inflammatory lesions including plasma cell granuloma , plasma cell pseudotumor and myofibroblastic tumor , which are all thought to arise from a similar underlying inflammatory disease process , eventually resulting in a tumor like mass of inflammatory cells . the pathogenesis and etiology of inflammatory pseudotumors is largely unknown and attracts varied theories according to the organ system involved , however , the two most widely accepted theories describe ipt as either primary reactive and inflammatory processes or low - grade neoplastic processes with secondary inflammation . splenic ipts have not been reported to possess malignant properties , and have commonly been associated with both ebv and hhv-8 viruses , and a review of all splenic ipt cases presented by rajabi et al . confirmed 41.2% of all published cases of splenic ipts tested positive ebv rna . other etiologies including trauma with secondary focal parenchymal necrosis , chronic infection , low - grade neoplastic processes , vascular causes and immunological derangement have been suggested . many splenic ipts are found incidentally , although presentations with left upper quadrant pain or epigastric pain , fever , weight loss and splenomegaly have been described . many patients have no detectable laboratory abnormalities ; however , anemia , thrombocytosis , hypercalcemia , both monoclonal and polyclonal hypergammaglobulinemia , and elevated inflammatory markers have been described . based on case studies , splenic ipts have been found in adults as young as 19 , but are more common in those of middle to advanced age ; there does not seem to be a gender association . ultrasound , ct scan , mri and pet scan are all commonly employed , but to date do not demonstrate many defining diagnostic characteristics allowing differentiation from other lesions . ct imaging commonly demonstrates a low - density mass in both non - enhanced and enhanced modes , while mri shows low to isointensity on t1- weighted imaging , and high intensity with surrounding low intensity on t2- weighted images . mri may be able to differentiate cavernous hemangioma , lymphangioma , hamartoma from ipt , based on the high intensity seen on t2-weighted images ; however ipt mirrors malignant neoplasms and lymphoma in appearance on mri . pet scan demonstrates fdg uptake within the ipt at a lower standardized uptake value ( suv ) than malignant tumors , however variations in fibrosis and inflammation , and thus suv , between ipts mean this is of minimal use . unfortunately , imaging alone is of limited value in differentiating ipt from other splenic lesions including benign inflammatory lesions , angiosarcoma , lymphoma and metastatic disease . histological examination is required for diagnosis , and thus , splenectomy is the management of choice . fine needle aspiration and core biopsy have been reported but are not recommended due to poor specificity , bleeding potential and risk of seeding if the tumor is malignant . in most cases of splenic ipt surgical management is deemed curative , and to the best of our knowledge there have been no reports of local invasion , recurrence or metastasis . pathologically , ipts resemble a benign tumor , comprising inflammatory cells and lymphoid cells with a well - circumscribed fibroblastic stroma . histologically , the cellular composition can be extremely heterogeneous , with cells associated with both acute and chronic inflammation . they are characterized by proliferation of epitheloid cells , myofibroblastic spindle cells and collagen , mixed with morphologically normal lymphocytes , plasma cells , eosinophils and histiocytes . splenic ipts often share similarities to neoplasms and other inflammatory diseases , and need to be differentiated histologically with the addition of immunohistochemistry . foremost , it is vital to distinguish ipt from ipt - like follicular dendritic cell sarcoma ( ipt - like fdc sarcoma ) , an extremely rare lesion which has a similar histologic appearance to ipt , but can be more aggressive . recognized as a variant of follicular dendritic cell sarcoma ( fdc sarcoma ) , ipt - like fdc sarcoma has a female predilection , is almost always localized to the liver or spleen , and is associated with a prominent lymphoplasmacytic infiltrate . we acknowledge the difficulty in differentiating these lesions based on histopathology alone . from the limited available literature , ipt - like fdc sarcoma is classically cd21 , cd23 , cd35 , cna 42 , and clusterin positive on immunostaining , and ebv is almost always clonally expanded in the tumor cells . ipt - like fdc sarcomas show variable staining for sma , hhf-35 , s100 protein , and cd68 , and they are usually alk negative.1 the other major mesenchymal lesions in the spleen that should be excluded include splenic harmatoma , sclerosing angiomatoid nodular transformation ( sant ) , and age - related ebv - associated lymphoproliferative disorder ; in these cases , the application of various fdc markers is also essential . based on the cd21 , alk1 and eber negativity together with the diffusely positive sma we are confident in our diagnosis of ipt ; however , additional immunostaining for cd 35 and cd23 would have been beneficial . this case highlights the need for consideration of a wide range of diagnoses during initial investigation , and also the need for rigorous histopathologic study of the specimen to ensure the diagnosis is made conclusively . given the difficultly in differentiation between ipt and ipt - like sarcoma , it is possible that a proportion of the previously reported 114 cases of splenic ipt were incorrectly diagnosed due to the lack of required immunohistochemical staining to sufficiently exclude ipt - like sarcoma . splenic ipts are rare , usually benign , inflammatory lesions with varied clinical presentations that pose a diagnostic challenge to clinicians due to their similarity in appearance to neoplasms . this case serves as a reminder to consider this rare diagnosis when evaluating patients with a splenic mass of unknown etiology , and highlights the need to be meticulous in order to differentiate ipt histologically from other similar lesions , particularly ipt - like fdc sarcoma , through engagement of experienced morphologists and the use of immunohistochemistry .

isolated splenic inflammatory pseudotumors ( ipt ) are extremely rare , typically benign , inflammatory lesions with varied clinical presentations that pose a diagnostic challenge to clinicians due to their similarity in appearance to neoplasms . we present the case of a young woman diagnosed with a splenic ipt following investigation for persistent anemia , raised inflammatory markers , and polyclonal hypergammaglobulinemia , whose symptoms resolved completely following splenectomy . this case highlights the need to consider this diagnosis when evaluating patients with a splenic mass of unknown etiology .

a 22-year - old male was admitted because of discomfort due to repeated upper respiratory tract infection symptoms , chronic cough , and sputum for several years . there were no abnormal findings reported in the initial laboratory results and electrocardiogram . chest x - ray and enhanced chest computed tomography ( ct ) scans were taken ; these revealed bilateral cystic lesions on both the lower lobes . like the chest x - ray , the chest ct also revealed bilateral cystic lesions . in particular , pneumonic consolidations were found on the lesions of the right lower lobe ( rll ) ( fig . 1 ) , and both the lesions were fed directly from the thoracic aorta and drained into the pulmonary vein ( fig . the patient was diagnosed as having bilateral intralobar pulmonary sequestration on the rll and left lower lobe ( lll ) . we planned staged bilateral lobectomy for both lungs and prophylactic embolization of the feeding vessels for preventing unexpected hemorrhage during the operation . on hospital day ( hd ) 1 , angiography was done for embolization of feeding vessels of the pulmonary sequestration . right lower lobectomy of lung with video - assisted thoracic surgery was done because of the pneumonic consolidations . the patient was discharged on postoperative day 10 without surgery of the lll because of personal schedules and recovery . in the serial outpatient department follow - up , the patient did not feel any respiratory discomfort and was satisfied with the result of angiographic embolization ; he refused additional surgery of the lll . of all congenital pulmonary malformations , pulmonary sequestration is the second most common congenital anomaly , having an incidence of 0.15% to 1.8% . however , bilateral pulmonary sequestration is extremely rare , and its exact incidence has not yet been determined . most authors believe that bronchopulmonary sequestration should be treated with ligation of the afferent artery and resection of the sequestered pulmonary parenchyma because of the propensity for recurrent infections . as compared to surgical resection with angiographic embolization in newborns , surgical resection of pulmonary sequestration is believed to be the safest and most effective method of treatment . in the case of non - symptomatic pulmonary sequestration , further , there is a case report of successfully treated bilateral pulmonary sequestration with a horseshoe lung in a young patent with lobectomy of the lll and ligation of a feeding vessel to the rll . however , there are very few studies that compare the result of embolization with that of surgical resection and report which treatment is better in the cases of symptomatic and non - symptomatic lung problems in adult patients . in our case , the initial plan included staged bilateral lobectomy for both lungs , but we treated the patient first with angiographic embolization for asymptomatic pulmonary sequestration of the lll and then with surgical resection for symptomatic pulmonary sequestration of the rll . although the two - year follow - up showed that the patient did not suffer from any complications , serial studies and follow - up are required for the left pulmonary sequestration of the lll .

in this article , we report a rare case of a 22-year - old male with bilateral pulmonary sequestration , treated with embolization and surgical resection . the initial plan involved staged bilateral lobectomy for both lungs and prophylactic embolization of feeding vessels for preventing unexpected hemorrhage during operation . symptomatic right lower lobe was resected with video - assisted thoracic surgery after embolization , and the patient refused surgery of left lower lobe upon symptomatic relief . the two - year follow - up examination revealed that the patient was healthy and had no relevant discomfort .

we initially studied 90 patients ( age 21 years ) who had newly diagnosed all and were enrolled on the st . , we subsequently studied an additional 170 patients with all enrolled on the same treatment protocol , using publicly available snp data we had previously reported . jude children s research hospital , and informed consent was obtained from patients , their guardians , or both before enrollment . leukemia cells were isolated by applying a ficoll - hypaque gradient to bone marrow aspirates obtained at diagnosis ( median , 97% blast cells ) . normal leukocytes were isolated from peripheral blood samples obtained after the successful completion of remission induction therapy ( on days 4548 after the start of treatment ) . to assess gene copy number loss in msh2-l leukemia cells , dna was extracted from leukemia cells and normal peripheral blood leukocytes ( obtained when patients were in complete remission ) and genotyped for 600k snps using the affymetrix genechip human mapping 50k - hind-240 , 50k - xba-240 , 250k - sty and 250k nsp snp arrays . dna was restriction enzyme digested , pcr - amplified , purified , labeled , fragmented and hybridized to the arrays according to the manufacturer s instructions . snp array data were analyzed using dchip for chromosomal abnormalities . to improve the accuracy of copy number inference using dchip , we applied a normalization procedure that uses snps exclusively from regions shown to be diploid in the normal leukocytes and maps signals from those snps to a common target probability distribution . the snps with an estimated copy number lower than 1.40 were considered as evidence of deletions . we initially performed snp analysis on prkcz , because it is known to regulate msh2 stability . this led us to subsequently perform a broader pathway analysis , to interrogate additional genes upstream of prkcz ( figure 1c ) . for each snp , we evaluated the over - representation of deletions in msh2-l leukemia cells compared to msh - h leukemias , using fisher s exact test . the significance of each snp was then adjusted for multiple testing using 100,000 permutations . at each permutation , we recorded the smallest p - value among all the 122 snps based on randomly assigned msh2 status . the adjusted p - values were computed as the proportion of permutations whose smallest p - values were lower than or equal to the observed . the human t - lineage leukemia cell line ccrf - cem was obtained from the american type culture collection . the human pre - b leukemia cell lines 697 and nalm-6 were obtained from the german collection of microorganisms and cell cultures . cells were cultured in rpmi-1640 medium containing 2 mm glutamine and 10% fetal bovine serum at 37 c with 5% co2 . ccrf - cem cells were infected with mission lentiviral transduction particles ( sigma - aldrich ) produced from a library of sequence - verified shrnas targeting human pik3c2b , frap1/mtor , herc1 or prkcz transcripts . non - target shrna control particles ( shc002v ) were also purchased from sigma - aldrich . fisher s exact test was used to test the overrepresentation of losses among msh2 low patients versus msh2 positive patients . a linear regression model was used to test the correlation between the levels of msh2 mrna and protein . the expression levels of the probe sets were analyzed by applying a general linear model in which the effect of msh2 status ( positive vs. negative ) was adjusted for the all genetic subtypes . the cox proportional hazards model was used to identify independent prognostic effect of msh2 status . for patients who achieved complete remission , cumulative incidence of hematological relapse were constructed by the method of kalbfleisch and prentice , and compared with gray s test . we initially studied 90 patients ( age 21 years ) who had newly diagnosed all and were enrolled on the st . , we subsequently studied an additional 170 patients with all enrolled on the same treatment protocol , using publicly available snp data we had previously reported . jude children s research hospital , and informed consent was obtained from patients , their guardians , or both before enrollment . leukemia cells were isolated by applying a ficoll - hypaque gradient to bone marrow aspirates obtained at diagnosis ( median , 97% blast cells ) . normal leukocytes were isolated from peripheral blood samples obtained after the successful completion of remission induction therapy ( on days 4548 after the start of treatment ) . to assess gene copy number loss in msh2-l leukemia cells , dna was extracted from leukemia cells and normal peripheral blood leukocytes ( obtained when patients were in complete remission ) and genotyped for 600k snps using the affymetrix genechip human mapping 50k - hind-240 , 50k - xba-240 , 250k - sty and 250k nsp snp arrays . dna was restriction enzyme digested , pcr - amplified , purified , labeled , fragmented and hybridized to the arrays according to the manufacturer s instructions . snp array data were analyzed using dchip for chromosomal abnormalities . to improve the accuracy of copy number inference using dchip , we applied a normalization procedure that uses snps exclusively from regions shown to be diploid in the normal leukocytes and maps signals from those snps to a common target probability distribution . the snps with an estimated copy number lower than 1.40 were considered as evidence of deletions . we initially performed snp analysis on prkcz , because it is known to regulate msh2 stability . this led us to subsequently perform a broader pathway analysis , to interrogate additional genes upstream of prkcz ( figure 1c ) . , we evaluated the over - representation of deletions in msh2-l leukemia cells compared to msh - h leukemias , using fisher s exact test . the significance of each snp was then adjusted for multiple testing using 100,000 permutations . at each permutation , we recorded the smallest p - value among all the 122 snps based on randomly assigned msh2 status . the adjusted p - values were computed as the proportion of permutations whose smallest p - values were lower than or equal to the observed . the human t - lineage leukemia cell line ccrf - cem was obtained from the american type culture collection . the human pre - b leukemia cell lines cells were cultured in rpmi-1640 medium containing 2 mm glutamine and 10% fetal bovine serum at 37 c with 5% co2 . ccrf - cem cells were infected with mission lentiviral transduction particles ( sigma - aldrich ) produced from a library of sequence - verified shrnas targeting human pik3c2b , frap1/mtor , herc1 or prkcz transcripts . non - target shrna control particles ( shc002v ) were also purchased from sigma - aldrich . fisher s exact test was used to test the overrepresentation of losses among msh2 low patients versus msh2 positive patients . a linear regression model was used to test the correlation between the levels of msh2 mrna and protein . the expression levels of the probe sets were analyzed by applying a general linear model in which the effect of msh2 status ( positive vs. negative ) was adjusted for the all genetic subtypes . the cox proportional hazards model was used to identify independent prognostic effect of msh2 status . for patients who achieved complete remission , cumulative incidence of hematological relapse were constructed by the method of kalbfleisch and prentice , and compared with gray s test .

dna mismatch repair enzymes ( e.g. , msh2 ) maintain genomic integrity , and their deficiency predisposes to several human cancers and to drug resistance . we found that leukemia cells from a substantial proportion of patients ( ~11% ) with newly diagnosed acute lymphoblastic leukemia ( all ) have low or undetectable msh2 protein levels ( msh2-l ) , despite abundant wild - type msh2 mrna . msh2-l leukemia cells contained partial or complete somatic deletions of 14 genes that regulate msh2 degradation ( frap1 , herc1 , prkcz , pik3c2b ) ; these deletions were also found in adult all ( 16% ) and sporadic colorectal cancer ( 13.5% ) . knockdown of these genes in human leukemia cells recapitulated the msh2 protein deficiency by enhancing msh2-degradation , leading to significant reduction in dna mismatch repair ( mmr ) and increased resistance to thiopurines . these findings reveal a previously unrecognized mechanism whereby somatic deletions of genes regulating msh2 degradation result in undetectable levels of msh2 protein in leukemia cells , mmr deficiency and drug resistance .

neurocysticercosis is the most common parasitic infection of central nervous system and result from infection with the intermediate stage of taenia solium . in india , cysticercosis is highly prevalent and cns involvement is seen in 60%90% of infested patient . cerebrum and cerebellum are common sites but may involve brainstem , basal ganglion , thalamus , and lateral sinus . seizures are the commonest presenting feature in majority but can present with headache , focal deficits , hydrocephalus , and raised intracranial pressure . we report a case of pontomedullary neurocysticercosis presenting with left vi and vii cranial nerve palsy of lower motor neuron type and contralateral hemiplegia , i.e. , millard gubler syndrome , which is not reported till date . a 7 year girl presented in outpatient department with history of vomiting and deviation of angle of mouth to right side for 3 days . there was no history of fever , headache , seizures , altered sensorium , diplopia , nasal regurgitation of feeds , trauma , ear discharge , rash , recent vaccination , and history of contact with an open or treated case of tuberculosis . examination of patient revealed palsy of vi and vii cranial nerve of left side with right - sided grade iii / v weakness , upper motor neuron type , of upper and lower limbs . her right - sided babiniski 's sign was positive with exaggerated deep tendon reflexes on same side . his complete blood count cbc , x - ray chest , blood glucose , electrolytes , liver and renal function tests were normal . mantoux test was negative at 72 h. cerebrospinal fluid study showed cells 8/mm protein ; 48 mg / dl , and glucose was 68 mg / dl . contrast - enhanced computed tomograph ( cect ) of cranium revealed single - ring enhancing lesion , with eccentric dot and perilesional edema at pontomedullary area of brain stem suggestive of inflammatory granuloma with possibility of neurocysticercosis [ figure 1 ] . magnetic resonance imaging ( mri ) of brain showed a well - defined ring enhancing lesion with thick rim noted in pontomedullary area of brain stem [ figure 2 ] , which appeared hypointense on t1-weighted and hyperintense on t2-weighted images . flair images showed suppression of internal signal with mild perilesional edema ; further suggestive of neurocysticercosis in its colloidal - vesicular stage . coronal cect image showing solitary ring enhancing lesion , with eccentric scolex , in pontomedullary area mri of cranium showing thick cyst wall enhancement with mild perilesional edema , depicting colloidal vesicular stage of cysticercosis in pontomedullary area patient was administered 20% mannitol ( 1 gm / kg / dose i.v . 8 hourly for 48 h ) , dexamethasone ( 0.5 mg / kg / day for 2 days ) , and then prednisolone 2 mg / kg / day along with acetazolamide at 75 mg / kg / day . on 3 day of steroid , oral albendazole at 15 mg / kg / day steroid was stopped after 7 days and patient was discharged on oral albendazole which was to continue for 28 days and advice of physiotherapy . at discharge , there was no vomiting but deviation of angle of mouth and right - sided weakness persisted . she was called for follow - up after 15 days and found to have no deviation of angle of mouth and weakness . patient is doing well at 1 and 3 months of follow - up with no clinical evidence of cranial nerve palsy and hemiparesis . unusual manifestations are stroke , visual loss , ataxia , dystonia , dementia , and hydrocephalus . intraventricular ( 5%10% ) and meningeal cysticerosis are associated with hydrocephalus , signs of meningeal irritation , and raised intracranial pressure . we here report a case of neurocysticercosis presenting as left vi and vii cranial nerve palsy of lower motor neuron type and contralateral hemiplegia , i.e. , millard gubler syndrome , which is unreported in literature . ct scan and mri are useful in anatomical localization of cysts , but mri cranium is more sensitive in picking up active lesions . our case fulfilled the imaging absolute diagnostic criteria ( histologic demonstration of the parasite from biopsy of a brain or spinal cord lesion , cystic lesions showing the scolex on ct or mri , and direct visualization of subretinal parasites by funduscopic examination ) . therefore , all patients with multiple cysts should receive treatment with steroid to reduce intracranial pressure and edema ; thereafter cysticidal drug , i.e. , albendazole . our patient improved and became asymptomatic with steroid treatment and albendazole . recognizing this clinical entity would avoid unnecessary antituberculous treatment and surgical intervention . cysticercosis is common in tropical countries including india but neurocysticercosis of brain stem is rare .

neurocysticercosis is a common childhood neurological illness in india . a variety of presentations have been reported in the literature , including weber syndrome . neurocysticercosis , manifesting as millard gubler syndrome , have not been reported in literature . therefore , we report a child presented to us with millard gubler syndrome due to pontomedullary neurocysticercosis and was treated successfully .

trichilemmal carcinoma ( tlc ) is a rare , cutaneous adnexal neoplasm that occurs on the sun - exposed areas of elderly people [ 1 , 2 ] . this neoplasm has been shown to exhibit outer root sheath differentiation and to be a malignant form of trichilemmoma . cases with erythematous , tan , or flesh - colored plaques and nodules that may be keratotic or have superficial ulceration have been described . the lesions had usually been present for less than 1 year before the diagnosis and had a recent rapid growth phase . though spontaneous regression of cutaneous tumors has been documented previously , that of tlc is extremely rare . in the present report , we describe a case of tlc with spontaneous regression and evaluate the profiles of the tumor - infiltrating lymphocytes ( tils ) . a 69-year - old japanese woman visited our outpatient clinic with a 3-year history of a tumor on her forehead . on her initial visit , physical examination revealed a papillomatous , dome - shaped , easy - to - bleed nodule on her forehead ( fig . a biopsy specimen revealed cytologically atypical clear cells with abundant glycogen in the pas staining . the tumor masses infiltrated the dermis with lobular growth patterns with keratinization , and partially with a horny cyst - like component ( fig . surprisingly , the tumor mass began decreasing 4 weeks after performing the skin biopsy ( fig . interestingly , the specimen from the widely excised area mainly consisted of dense infiltration of lymphocytes with collagen degeneration in the dermis , even around the hair follicles ( fig . epitheloidal cells with atrophic changes were observed in the superficial dermis . according to the above findings , the patient was diagnosed with tlc with spontaneous regression . to further investigate the possible mechanisms of the spontaneous regression , we employed immunohistochemical staining , especially focusing on the cytotoxic t cells and immunosuppressive lymphocytes as we have reported previously [ 4 , 5 ] . 3b , d , f ) of the tlc for cd4 , cd8 , granulysin ( fig . numerous foxp3 cells were also scattered in the dermis of both the tumoral and regressing areas . we calculated the numbers of these tils at the tumor - regressing and tumor - remaining areas . concerning the effector cells , the numbers of cd8 cells ( 91.0 27.5 vs. 151.4 35.2% ) and granulysin - bearing cells ( 25.4 13.5 vs. 56.4 16.6% ) were significantly increased in the tumor - regressing area compared to the tumor - remaining area . in contrast , there was no statistically significant difference between the numbers of immunosuppressive cells ( foxp3 regulatory t cells : 28.4 8.0 vs. 46.8 15.6% , cd163 m2 macrophages 54.0 7.7 vs. 102.0 41.0% ) . the numbers of immunoreactive cells were counted using an ocular grid of 1 cm at a magnification of 400 , and are summarized in fig . 4 . staining of infiltrated lymphocytes was examined in more than five random , representative fields from each section . for a single comparison of two groups , tlc is a rare , cutaneous adnexal neoplasm that occurs on the sun - exposed areas of elderly people [ 1 , 2 ] . in a rare case , garrett et al . interestingly , in our case , histological findings revealed spontaneous regression of the tumor with dense infiltration of lymphocytes around the tumor , which might suggest the induction of an anti - tumor immune response against tlc . specific activation of the immune system to control cancer growth has been a long - standing goal in cancer immunology and medical oncology . we have previously reported possible therapies for melanoma in which an anti - tumor immune response is induced by intratumoral administration of polyinosinic - polycytidylic acid / cationic liposome , which suggested the possibility of intra - tumoral administration of immunomodulating reagents for the treatment of skin cancers . more recently , we have also described the immunomodulating effects of peritumoral injection of interferon beta , which might suggest a relationship between the tumor regression and the profiles of the tils . therefore , in the present case , we examined the profiles of tumor - infiltrating cells in tlc to investigate the possible mechanisms of the spontaneous regression of the cutaneous tumor . concerning cutaneous tumors , particularly melanoma , there is evidence suggesting that the immune system plays a central role in mediating tumor regression . we have previously described a case of basal cell carcinoma with spontaneous regression and assessed the profiles of tils , which revealed an increase in effector t cells and a decrease in immunosuppressive cells , including regulatory t cells and cd163 m2 macrophages in the tumor - regressing area . however , to our knowledge , there is no report on tlc with spontaneous regression or on mechanisms underlying the spontaneous regression of tlc . in our present case , although increased numbers of cd163 m2 macrophages and foxp3 tregs were observed in both tumor - remaining and tumor - regressing areas , the numbers of effector cytotoxic t cells were significantly increased in the tumor - regressing area . as previous reports suggested , the expression of granulysin correlated with the prognosis of cancer patients [ 9 , 10 ] . altogether , the spontaneous regression of tlc might be related to the increased numbers of granulysin - bearing cells and cd8 cells . in summary our present study sheds light on the immunological mechanisms of tumor rejection in human skin cancer and might suggest a possible therapy for such skin tumors by modifying the tumor microenvironment .

we describe the case of a 69-year - old japanese patient with spontaneous regression of trichilemmal carcinoma . we investigated the immunohistochemical profiles of tumor - infiltrating lymphocytes , focusing on cytotoxic granules , granulysin - bearing cells and immunosuppressive cells , such as regulatory t cells and tumor - associated macrophages . our present study describes some of the possible mechanisms of the self - regression of cutaneous malignant tumors and potential therapies for trichilemmal carcinoma by modifying the tumor microenvironment .

early interaction with a marginally inappropriate extra - uterine environment in preterm infants could play a crucial role in short- and long - term sequelae . results from previous studies confirm the presence of high rates of neurodevelopmental impairment among preschool children with preterm birth history that span neuromotor functioning , cognition , language , and emotional / behavioral adjustment ( 1 ) . the average rate of preterm birth is 9.6% worldwide ( 2 ) . in the last two decades , the rate of survival after preterm birth , especially in socio - economically developed countries , studies investigating brain structural development in prematurely born group consistently show structural alterations in both cortical and sub - cortical structures at birth and , considerably , throughout childhood and adolescence ( 4 ) . vestibular evoked myogenic potential ( vemp ) is a short - latency response of the sternocleidomastoid muscle following high level of acoustic stimulation . it is a manifestation of the vestibulocollic reex , originated in the saccular macula , which moves through the vestibular nerve and nucleus , the vestibulospinal tract , on to the motor neurons of the sternocleidomastoid muscle ( 5 ) . vemps are used for diagnoses ranging from otologic disorders to neuropathies and brainstem lesions ( 6 ) . if there is no conductive hearing loss , the lesions of the end - organs , primary afferents , and the nerve root entry zone lead to absence of response ( 5 ) . although studies on vemps in preterm groups are rare in the literature , the available results of studies on preterm infants consistently have shown that they are at risk of disability related to maturation of the vestibulocollic reflex ( 7 - 9 ) . the vestibular system is important to motor development ; vestibular dysfunction may lead to delayed postural control and locomotor development at later ages ( 10 ) . children with histories of preterm birth are at greater risk for motor disabilities and poor postural control than those with normal deliveries ( 11 , 12 ) . this group should be followed closely for vestibular deficiency - related complications . the present study investigated the long term effects of preterm birth on the vestibulocollic reflex pathway . this comparative - analytic study was performed on 31 children with histories of preterm birth ( 18 males , 13 females ) and 20 with term births as controls ( 9 males , 11 females ) . the subjects were 5.5 to 6.5 yr of age and enrolled in the audiology clinic at school of rehabilitation between february and july of 2013 . children with preterm history were divided into very preterm ( vp ; less than 32 wk ) and mildly preterm ( mp ; 32 to 37 wk ) groups . the vp group comprised 10 children ( 6 males , 4 females ) and the mp group 21 children ( 12 males , 9 females ) . the mean gestational age for the vp , mp , and control groups were 30.6 0.94 ( 28 - 31 wk ) , 34.9 1.28 ( 33 - 37 wk ) , and 39.6 0.74 ( 38 - 41 wk ) , respectively . the exclusion criteria for all groups were a history of congenital abnormalities , ototoxic drug use , recurrent ear infections , previous ear surgery , high fever , head trauma , mental retardation , and psychological problems ( based on parental report ) . parental approval , good general health of the child , absence of abnormalities of the external and middle ear , normal peripheral hearing ( tested by conventional pure - tone audiometry and normal results for tympanometry ) were considered as inclusion criteria for all children . the subjects were selected through a review of their medical records for the past 5.5 to 6.5 yr . an ics charter ep device was used to record surface electromyographic activity of the scm muscle . the active electrodes were attached to the upper half of the bilateral scm muscles ; a reference electrode was attached to the suprasternal notch and a ground electrode to the forehead . to elicit the desired response from each ear , the child was trained to rotate his or her head toward the contralateral side and keep his or her head in this position for several seconds ( 13 ) . short tone bursts ( 95 db nhl , 500 hz each , rise - and - fall time = 2 ms , plateau time = 0 ms ) were delivered monaurally using an er-3a insert receiver . the 150 responses to stimuli were then averaged , and their band - pass filtered ( 10 - 1500 hz ) and amplified ( 5000 ) ( 14 ) . the one - way anova post - hoc lsd ctest was used to compare the results . for statistical analysis , the data were presented as a mean ( standard deviation ( sd ) ) . this study was approved by the ethics committee of tehran university of medical sciences . no statistically significant differences were observed between results of the both ears ( p 0.215 ) . the mean latencies of the p13 and n23 waves for all groups are compared in fig . 1 . comparison of the mean p13 and n23 latency between three groups . according to the one - way anova statistical test the difference between three groups was significant in p13 latency ( f=5.68 , p=0.005 ) , but not significant for n23 latency ( f=2.33 , p=0.10 ) , p13-n23 amplitude ( f=0.12 , p=0.88 ) and inter - aural amplitude difference ratios ( f=0.49 , p=0.60 ) . results from precise analysis by anova post - hoc lsd test are shown in table 1 . significant differences were observed in the latency of the p13 ( p= 0.002 ) and n23 ( p= 0.041 ) waves between the vp group and control group . 2 shows sample responses recorded from the right ear in one vp and one normal child . a significantly prolonged p13 latency moreover there was no significant difference between the mp and control groups for all test parameters ( p 0.773 ) . vemps result of very preterm child ( a ) verses normal child ( b ) . there was no significant difference between the three groups in p13-n23 amplitude ( p 0.627 ) and interaural amplitude difference ratios ( p 0.348 ) . no significant differences were observed between the left and right ears for each group . although , no similar study has been published on preschool aged children with preterm birth history , previous studies on term children reported non - significant differences between the right and left ears ( 15 - 17 ) . this reflective response generates from the lower brainstem and laterality has little effect on this potential . ecevit et al . ( 7 ) studied 17 late preterm infants ( mean gestational age : 35.11 wk 0.78 ) at 8 wk postnatal and found that the latencies of p13 and n23 in preterm infants were significantly longer than for term infants . ( 8) studied 50 newborns with a mean gestational age of 31.7 2.7 wk ( range= 26 - 36 wk ) . the results showed a significant difference between abnormal vemps rates for preterm and full term infants . ( 9 ) studied 27 low - risk preterm neonates and found that mean latency of peaks p13 and n23 in the preterm group were significantly longer than those in the full - term group . it has been reported that conditions affecting the vestibulospinal tract result vemps delay and that vestibule disorders frequently led to lack of response ( 18).imaging studies confirmed structural alterations in cortical and sub - cortical structures at birth , and in childhood and adolescence in the preterm group ( 4 ) . in other hand , previous studies have shown that the auditory brainstem response ( abr ) was affected by preterm birth in infancy and at preschool age . ( 19 ) studied 30 children with histories of preterm birth with 4 - 6 yr of age . significant differences in the abr test results were observed for the inter - peak intervals of the i - iii and iii - v waves and the absolute latency of the iii wave . overall , prolonged vemps in vp children may reflect incomplete maturation ( especially myelination ) and deficits in their vestibulospinal tract . in the present study , no significant difference was found between the mp and control groups for wave latency of vemps . in contrast , ecevit et al . ( 7 ) reported that wave latency for vemps in late preterm infants ( 34 - 36 wk ) was significantly longer than those with full term . this condition may relate to the delay in maturation of the sacculocollic pathways in the mp group in infancy . in other hand , the vp was significantly different from the mp group for p13 latency . previous studies have shown that the risk of mortality , morbidity , and neurodevelopmental impairment was tightly linked to gestational age and reached the highest rate for infants born at less than 32 wk ( very preterm ) ( 2 , 20 ) . consequently , increased gestational age ( ga ) in children born at ga > 32 wk gestation showed less long - term sequelae than children with ga < 32 wk . the p13-n23 amplitude did not differ between the three groups of children in this study . ( 9 ) on preterm and term infants ; these groups showed no significant differences in the raw and corrected p13-n23 amplitudes . vemps amplitude is dependent upon sound intensity and constriction of the scm muscle ( 21 ) . accordingly , since there are large variability in response amplitude , especially for the very young , fewer studies have considered it . the interaural amplitude difference ratio is the more informative parameter for investigating unilateral vestibular disorders ( 14 ) . in the present study , these findings support the possibility of a symmetrical function of the vestibular system for both ears . previous studies have also reported no effect for gender on vemps responses ( 15 , 22 , 23 ) . these findings could be a consequence of the elicitation of these reflecting responses from the lower brainstem ( 24 ) . findings of the present study revealed the positive effect of augmented in age on the improvement of vemps results . ( 9 ) study which vemps was not appeared in 74% of preterm neonates , in the present study , vemps was obtained in all children of the studied groups . although , in the present study , abnormal vemps results were still observed , especially in the vp group.the early exposure to an extra - uterine environment for the vp group could exposed the neurodevelopmental process of these infants to physiological , psychological , and environmental hazards ( 25 ) . it can be concluded that deficits in the central vestibular pathway could be related to incomplete myelinization of the neural pathways and the consequent delay in nerve conduction can leads to abnormalities such as delayed p13 and n23 waves in vemps . improvements in hygiene and reductions in the birth rate have decreased the incidence of preterm birth in iran and , consequently , decreased the pool of these children with a history of preterm birth ( especially very preterm ) . future studies should expand access to the population sample of preterm children in different regions so that longitudinal studies can be designed to obtain more precise information about the effect of preterm birth on vestibular evoked myogenic potentials and the neurodevelopmental process on improvements in this response . moreover , behavioral assessments of the vestibular system , especially on static balance skills , and electrophysiological tests can clarify the role of structural disabilities in balance and provide subtle information for counseling and planning useful treatment programs . the significant finding of the current study is the prolonged latency of p13 and n23 waves in the vemps in children with very preterm birth histories compared with those with histories of mildly preterm and full term births . possibly , the delay in and deficit of the neural pathway of the vestibulocollic reflex and inadequate neural synchronization were the main causes for the difference . the results of this study provide information about effects of preterm birth for both specialists and parents . since the vemps test evaluates the function of a part of the vestibular system , the probable effects of preterm birth on other aspects of the vestibular and balance systems should be studied . other area of future research should explore the usage of vemps testing on performance of vestibulocollic reflex among children with preterm birth at the preschool age . this study was approved by the tehran university of medical sciences , grant number 91/d/260/4955 . we are grateful to the mofid , akbarabadishaheedand comprehensive women hospitals for their assistance in the implementation of this project . we also extend our appreciation to the parents of our subjects for their help in this research .

background : preterm birth is a significant global health problem with serious short- and long - term consequences . this study examined the long term effects of preterm birth on vestibular evoked myogenic potentials ( vemps ) among preschool - aged children . methods : thirty - one children with preterm and 20 children with term birth histories aged 5.5 to 6.5 years were studied . each child underwent vemps testing using a 500 hz tone - burst stimulus with a 95 db nhl ( normal hearing level ) intensity level . results : the mean peak latencies of the p13 and n23 waves in the very preterm group were significantly longer than for the full - term group ( p 0.041 ) . there was a significant difference between very and mildly preterm children in the latency of peak p13 ( p= 0.003 ) . no significant differences existed between groups for p13-n23 amplitude and the interaural amplitude difference ratio . the tested ear and gender did not affect the results of the test . conclusion : prolonged vemps in very preterm children may reflect neurodevelopmental impairment and incomplete maturity of the vestibulospinal tract ( sacculocollic reflex pathway ) , especially myelination . vemps is a non - invasive technique for investigating the vestibular function in young children , and considered to be an appropriate tool for evaluating vestibular impairments at the low brainstem level . it can be used in follow - ups of the long - term effects of preterm birth on the vestibular system .

desmoid tumours are rare , locally aggressive tumours with no known potential for metastasis or differentiation , accounting for only 0.03% of all neoplasms ( 1,2 ) . there are three main types ( 3 ) : spontaneous tumours rare and occur mainly in the extremities and abdominal walltumours associated with familial adenomatosis syndrome ( gardner 's syndrome ) risk is 10 - 30 % in these patients , which is further increased in mutations between exon 1310 and 2011familial infiltrative fibromatosis ( hereditary desmoid disease ) extremely rare and also associated with adenomatous polyposis coli gene mutations spontaneous tumours rare and occur mainly in the extremities and abdominal wall tumours associated with familial adenomatosis syndrome ( gardner 's syndrome ) risk is 10 - 30 % in these patients , which is further increased in mutations between exon 1310 and 2011 familial infiltrative fibromatosis ( hereditary desmoid disease ) extremely rare and also associated with adenomatous polyposis coli gene mutations we present a case of spontaneous intra - abdominal desmoid tumour in an otherwise well male with a focus on management approach . a 46-year - old male presented with 10 day history of abdominal pain , nausea and vomiting . he denied change in bowel habit , anorexia or weight loss and had no significant past medical history . clinical examination revealed a gentleman of lean body mass but with apparently good nutritional status . a large , non - tender , firm smooth - surfaced abdominal mass was palpable in the lower midline . coronal contrast enhanced ct scan of the abdomen and pelvis demonstrating an homogenous 14.6 x 11 x 14.3 cm intra - abdominal mass closely associated with the small bowel computed tomography ( ct ) ( figure 1 ) showed a large well - defined tumour measuring 14.6 x 11 x 14.3 cm arising from the mid - small bowel mesentery and closely associated with , or involving , the small bowel lumen . subsequent magnetic resonance imaging ( mri ) proved involvement of a jejunal segment and encasement of left - sided branches of the superior mesenteric artery . at laparotomy there was no evidence of synchronous disease . the tumour and associated jejunum with its vascular pedicle was resected in - toto ( figures 2,3 ) . small bowel continuity was re - established with stapled side - to - side primary anastomosis . intra - operative photograph showing tumour arising from small bowel mesentery with local involvement of jejunum post - operative photograph showing resected specimen with associated jejunum and its mesenteric pedicle in the foreground on histological assessment the specimen showed bland spindled cells arranged in intersecting fascicles . involvement included the small bowel mesentery and jejunal muscularis propria with focal extension into submucosa ( figure 4 ) . the microscopic margin of the tumour was ill defined but appeared clear of the resection limit . immunohistochemistry showed strong nuclear expression for beta - catenin but was negative for c - kit , cd34 and dog1 consistent with a diagnosis of desmoid tumour ( 3,4,5 ) . h&e stained section , magnification x 40 , demonstrating a bland spindled cell lesion arranged in intersecting ill - defined fascicles , with some intervening collagen fibres and relatively limited infiltration at the lesion margin ( arrow ) the rarity of intra - abdominal desmoid tumour precludes the use of randomised controlled trials to compare treatment options . natural history of the disease is also variable : tumours may regress spontaneously , show long - term stability or behave aggressively . this further complicates the development of standardised treatment regimens and it remains unclear whether any intervention improves survival . current therapeutic modalities mirror those for most other neoplasms and include surgery , radiotherapy and systemic therapy . in the case of isolated intra - abdominal desmoid tumour surgical resection provides the most successful primary treatment , however a number of patient and disease factors require consideration . the importance of excision margin is unclear because although positive margins after surgery reflect higher risk , recurrence rates even after complete resection are 16 - 39 percent ( 1,3 ) . for isolated intra - abdominal disease the goal of surgery thus becomes complete resection but with maximal preservation of function to minimise morbidity ( 3 ) . surgery may also be indicated in the setting of multifocal disease where immediate threat to life or function exists . attempted curative resection for intra - abdominal desmoid associated with gardner s syndrome is contraindicated because disease is always diffuse and poorly defined ( 6 ) . in cases where there is no immediate threat to life or vital organ function , or surgery is not technically feasible and/or contraindicated due to co - morbidity or multifocal disease , ionising radiation and systemic therapy should be considered . such treatments may be employed in combination and can also provide adjunctive benefit before or after surgery . current guidelines from the national comprehensive cancer network suggest that post - operative radiotherapy be considered for large tumours and those with positive margins ( 3,7 ) . systemic therapy should be considered for localised disease not otherwise amenable to potentially curative resection or radiotherapy , as neo- or adjuvant treatment for localised intra - abdominal tumours , and in the setting of multifocal disease . the goal of pharmacotherapy may be to induce remission , prevent complications , and/or reduce morbidity ( 8) . the choice of agent depends on the urgency of the situation . cytotoxic agents generally provide the most rapid clinical response at the expense of increased systemic side - effects and are thus indicated where imminent ( but not immediate ) threat to life or function exists . retrospective data from two separate studies regarding single versus combination therapy is contradictory ( 3,9 ) . different combinations of doxorubicin , ifosfamide and methotrexate have resulted in disease stabilisation rates 50 - 80% after six months ( 1 ) . hormone modulators and non - steroidal anti - inflammatory drugs ( nsaid s ) have lower adverse risk profiles and should be considered for all other presentations where surgery is precluded . response rates of 50% have been reported , with regression rates of 10 - 15% and disease stabilisation or shrinkage in 25% ( 1,3 ) . the selective oestrogen receptor modulator tamoxifen is thought to act via er - beta expressed on tumour cells , however the exact mechanism by which regression occurs remains unclear ( 6 ) . the use of nsaids is based on a single case report where incidental total regression of tumour occurred in a patient taking indomethacin for radiation induced pericarditis ( 3 ) . success rates of between 37 - 57% have been reported with indomethacin and sulindac ( 3,8 ) . other proven therapeutic targets include immunomodulation with interferon alpha , and disruption of cellular signal transduction with selective tyrosine kinase inhibitors . interferon alpha provides an alternative to cytotoxic agents where tumour is refractory to nsaids and/or hormone therapy . the selective tyrosine kinase inhibitor imatinib has been shown to achieve disease stabilisation rates at least comparable to established cytotoxic chemotherapeutic regimens ( 3 ) . post - treatment surveillance for local recurrence involves clinical assessment and imaging of the tumour site every three to six months for the first two to three years , followed by annual follow - up thereafter ( 1,3 ) . in the event of recurrence all treatment modalities should be reconsidered , preferably in a multi - disciplinary conference . our patient was discussed by such a multi - disciplinary team consisting of surgeons , medical and radiation oncologists , and a histopathologist . surgery alone was recommended and the patient remains disease free six months following operative resection .

desmoid tumours are benign monoclonal myofibroblastic neoplasms arising from musculoaponeurotic stromal tissue . they infiltrate local tissue but have no known metastatic potential . the management of desmoid tumours is complicated by their unpredictable nature and rarity , which makes study into their behaviour , and therefore treatment , a challenge . we present a case of intra - abdominal desmoid tumour and discuss the recommended approach to management .

lupus vulgaris is the most common type of cutaneous tuberculosis , with most varied manifestations . it is a chronic and progressive form occurring in individuals with high degree of tuberculin sensitivity and moderate immunity . a characteristic feature of lupus vulgaris is its extremely chronic course with slow but steady growth of the lesions over a period of many years , even decades . we report a case of lupus vulgaris with very large sized , multiple plaques occurring at less common sites . a 40-year - old man presented with large plaques of 30 years duration over right upper limb , right side of the chest and back , and right lower limb . the lesion started as a small papule over right upper limb near the elbow when he was 10 years old . since then it steadily grew in size to involve whole of the limb and also the right side of the chest and back . he developed similar lesions , one over the right thigh after about 2 years of the first lesion that gradually enlarged to involve most of the thigh circumferentially and one more lesion over the left side of the back since one year [ figure 1 ] . there was no history of trauma prior to the onset of the lesions or the past history suggestive of tuberculosis of any part of the body . clinical photograph showing a large plaque over right upper limb and right side of the chest before treatment on examination , there were three plaques , two large and one small , with well - defined borders and irregular margins : plaque no . 1 : involving right upper limb , right side of the chest and back measuring about 60 45 cm.plaque no . 2 : about 6 3 cm over the left side of the back.plaque no . 3 : over right thigh , involving circumferentially , measuring about 40 cm longitudinally and 50 cm circumferentially . plaque no . 1 : involving right upper limb , right side of the chest and back measuring about 60 45 cm . plaque no . 3 : over right thigh , involving circumferentially , measuring about 40 cm longitudinally and 50 cm circumferentially . within the plaque , there were areas of thick hyperkeratosis and large , thick adherent crusts on an erythematous base . ulceration at some places and areas of scarring and atrophy in between the areas of hyperkeratosis were present . hematological investigations revealed anemia ( hb : 10.1 g% ) , raised erythrocyte sedimentation rate ( 67 mm / first hour ) . the mantoux test was strongly positive with a reading of 22 20 mm at 72 h. chest x - ray was normal . histopathologic examination of the biopsy specimen revealed hyperplastic epidermis , upper and mid - dermis showing numerous noncaseating epitheloid granulomas with langhan 's type of giant cells [ figure 2 ] . skin biopsy showing hyperplastic epidermis , upper and mid dermis showing noncaseating epitheloid granulomas with langhan 's type of giant cells based on clinical features and investigations , a diagnosis of lupus vulgaris was made and the patient was started on antitubercular treatment cat - i . there was dramatic improvement in skin lesions within 3 weeks and after 6 weeks the lesions showed 7080% of improvement . after 12 weeks , there was almost total healing of the lesions [ figure 3 ] . it usually occurs through contiguous extension of the disease from underlying affected tissue or hematogenous or lymphatic spread . lupus vulgaris is the most common type of cutaneous tuberculosis in india and commonly seen in the lower half of the body involving legs , thighs , buttocks , and feet . it is attributed to the habit of children playing without clothing or shoes and defecating in the open . pyogenic infection of the gluteal region is also common in india and the breach in the integrity of the skin can serve as a portal of entry for the afb . the initial lesion is a small , reddish - brown papule or nodule which later forms larger plaques by peripheral enlargement and coalescence that show evidence of healing and scarring in one area and activity in another . atrophic scarring , with or without ulceration , is a prominent feature of lupus vulgaris . the common variants are : plaque form , ulcerative and mutilating form , vegetative form , papular and nodular form and tumor - like ( hypertrophic ) form . the plaque form is the common type that presents as flat plaques with irregular or serpigenous edges , surface may be smooth or covered with psoriasiform scale . large plaques may show irregular areas of scarring with islands of active lupus tissue , the edge may be thickened and hyperkeratotic . histopathology shows tuberculoid granulomas composed of lymphocytes , plasma cells , epitheloid cells and giant cells , scant or absent central caseation , in the superficial dermis . after a thorough search of the literature , the largest size of lupus vulgaris lesion we could find was 30 25 cm . ours may be the first case showing largest lesions measuring 60 45 cm and 40 50 cm . other special features in our case were multiplicity ( lv commonly presents as a single lesion ) and extreme chronicity of the lesions , and occurrence at less common sites such as upper limb , chest , and back . this case also shows the level of ignorance among patients and consequent failure to take proper anti - tuberculous treatment despite extensive campaign in print and audiovisual media .

cutaneous tuberculosis continues to be an important public health problem even with the availability of highly effective anti - tuberculous drugs . it constitutes 0.1% of all cases of extrapulmonary tuberculosis . lupus vulgaris is the most common form of cutaneous tuberculosis that occurs in previously sensitized individuals with a moderate degree of immunity against tubercle bacilli . the different types of lupus vulgaris include plaque , ulcerative , vegetative , papular and nodular , and tumor forms . a 40-year - old man presented with large multiple plaques over right upper limb , right side of chest and back , and right lower limb for the past 30 years . histopathology showed numerous noncaseating granulomas with langhan 's type of giant cells . the mantoux test showed strong positivity and there was excellent response to anti - tuberculous treatment . this case is being reported because of its extreme chronicity of 30 years duration , unusually large size and multiplicity of lesions .

angiosarcoma is a rare malignant neoplasm representing less than 2% of all soft tissue sarcomas . the spleen and liver are the most commonly involved sites , and only a few reports of gastrointestinal tract involvement have been published . definitive diagnosis of angiosarcoma has only been possible by exploratory laparotomy and splenectomy because biopsy is contraindicated because of a high risk of rupture . moreover , no standard therapeutic method exists for angiosarcoma , and its prognosis is poor . most patients have a fulminant clinical course and a short mean survival time . here , we report a rare case of angiosarcoma who presented with life - threatening bleeding and involvement of the gastrointestinal tract ( stomach , duodenum , jejunum and ileum ) , liver , spleen , pancreas , kidney , lung and vertebrae , as well as bulky dissemination in the pleuroperitoneal membranes . a 72-year - old man with a chief complaint of dizziness and black stools arrived at a hospital by ambulance . the patient was a retired architect and builder who had spent 50 years in the construction industry , and he had neither a medical history nor a family history of malignant cancer . upper gastrointestinal endoscopy detected several elevated bright - red lesions in the stomach ( fig . 1b ) , but biopsy pathology findings were normal . since anemia and black stools persisted , the patient was transferred to our hospital 10 days after the initial examination at the first hospital . upper gastrointestinal endoscopy with biopsy was performed twice , but again biopsy findings were normal . computed tomography and fluorodeoxyglucose positron emission tomography , which were performed to search for the development of lesions in other organs , revealed multiple masses in the spleen , liver and thoracolumbar spine . endoscopic ultrasound - guided fine needle aspiration biopsy ( eus - fnab ) was performed via the stomach to obtain splenic mass specimens . hematoxylin - eosin staining revealed clusters of tumor cells ( fig . 2a ; 20 magnification ) , and immunohistochemical staining identified them as positive for cd31 ( fig . 2c ; 10 magnification ) and factor viii ( fig . 2d ; 10 magnification ) . a fourth upper gastrointestinal endoscopic biopsy was performed to make a definitive diagnosis , and immunostaining showed similar tumor cell clusters , leading to a diagnosis of gastric angiosarcoma . anemia and black stools persisted , suggesting the presence of lesions in other gastrointestinal tract organs . indeed , capsule endoscopy detected elevated bright - red lesions in the jejunum and ileum ( fig . a high risk of splenic rupture was indicated , so endoscopic splenectomy was performed as a preventive measure on hospital day 58 . a double balloon technique was used for endoscopic hemostasis , and multiple bleeding lesions were confirmed in the small intestine ( fig . surgical hemostasis was performed by partial enterectomy to remove the lesions with severe bleeding on hospital day 86 . since the effects of this surgical treatment on anemia and on the production of black stools were negligible , transcatheter arterial embolization was performed via the superior mesenteric artery . despite all efforts , gastrointestinal bleeding and the accompanying anemia persisted . the patient could not undergo chemotherapy and needed daily blood transfusions during his hospital stay , but despite receiving 92 units of red cell concentrate during his hospital stay , he eventually expired due to hemorrhagic shock on hospital day 103 . the subsequent autopsy revealed angiosarcoma in the stomach , duodenum , jejunum , ileum , liver ( fig . 3b ) , pancreas , kidney , lung and vertebrae , as well as bulky dissemination in the pleuroperitoneal membranes ( fig . the cause of death was determined to be rupture and bleeding due to disseminated involvement of the small intestine . angiosarcoma is a rare disease : only 2% of all sarcomas constitute the angiosarcoma subtype . exposure to thorium dioxide considering the long - term involvement of our patient in the construction industry , he might have been exposed to these chemicals for a considerable time . the first recorded angiosarcoma , found in the spleen , was reported by langhans et al . in 1879 . since then , only a limited number of cases of gastrointestinal angiosarcoma have been reported , and the present case is the first to show angiosarcoma lesions in the stomach , duodenum , jejunum , ileum , liver , spleen , pancreas , kidney , lung and vertebral body . although upper left abdominal pain has been reported in 80% of splenic angiosarcoma cases , typical symptoms of gastrointestinal angiosarcoma remain unclear . the present patient had painless splenic lesions , and it was the production of black stools that prompted a series of tests , which led to angiosarcoma being diagnosed . diagnosis of angiosarcoma in such organs is considered to be possible only via exploratory laparotomy and splenectomy . however , in the present case , diagnosis was made by eus - fnab and frequent endoscopic biopsies , indicating the utility of these techniques in the diagnosis of angiosarcoma . no serious complications of these biopsy procedures , such as bleeding or perforation , were observed in our case . eus - fnab has become widely established as an effective means for diagnosing tumors , suggesting that it can replace open biopsy as the standard diagnostic modality . in the present case , we performed several procedures such as splenectomy , enterectomy and transcatheter arterial embolization in an attempt to control bleeding attributed to angiosarcoma , but none were successful . the patient consequently died only 2 months after diagnosis , probably due to sudden severe bleeding . the prognosis of angiosarcoma is poor ; the median survival of splenic angiosarcoma is 5 months . when angiosarcoma is suspected in multiple organs , it is desirable to monitor the patient closely for bleeding and to provide hemostatic therapy at an early stage .

we report a rare case of angiosarcoma involving the gastrointestinal tract , liver , spleen , pancreas , kidney , lung and vertebrae , as well as bulky dissemination in the pleuroperitoneal membranes . a 72-year - old man with no history of illness became aware of melena . laboratory findings revealed anemia , and upper gastrointestinal endoscopy revealed multiple reddish nodules in the stomach and duodenum . however , biopsy specimens showed no evidence of histological features . computed tomography and fluorodeoxyglucose positron emission tomography showed space - occupying lesions in the spleen , liver and vertebrae . angiosarcoma was diagnosed by endoscopic ultrasound and fine needle aspiration biopsy of the spleen and repeated endoscopic biopsy of the stomach . we performed laparoscopic splenectomy to avoid rupture of the involved spleen . due to continuous gastrointestinal bleeding , double balloon endoscopy was performed and multiple bleeding lesions were detected throughout the small intestine . surgical hemostasis was performed by partial enterectomy , but anemia continued to worsen . therefore , we conducted transcatheter arterial embolization . despite attempting several modalities and frequent daily blood transfusion , the anemia did not improve , and the patient expired due to hemorrhagic shock . subsequent autopsy revealed the cause of death as rupture and bleeding due to disseminated involvement of the small intestine .

in 1963 lloyd and dennis described a patient named rachel cowden who died of bilateral breast cancer in her thirties . cowden syndrome is now recognized as an autosomal dominant syndrome characterized by multiple hamartomas originating from all three germ - cell layers . there is increased risk of early breast cancer from 14 years of age , and lifetime risk is estimated to 25 - 50% [ 3 - 5 ] . goitre and thyroid adenomas are frequently seen and the estimated prevalence of thyroid cancer is 3 - 7% . we have previously reported endometrial cancer in one norwegian family with cowden syndrome . in 1995 the international cowden syndrome consortium was formed and a set of clinical diagnostic criteria were suggested ; see table 1 . in 1997 the susceptibility gene for cowden syndrome was identified on chromosome 10q23.3 and was found to be pten . germline mutations are found throughout the pten gene , the majority in exons 5 , 7 and 8 . the frequency of germline pten mutations , including mutations in the promoter region , in cowden syndrome have been reported to approach 85 - 90% . genotype / phenotype correlations have been suggested , but have not been confirmed [ 15 - 17 ] . international cowden syndrome consortium operational criteria ( version 2000 ) as given by charis eng nelen has estimated the incidence to be between 1 per 200,000 and 1 per 250,000 in the dutch population . as for all inherited cancer syndromes , the penetrance of the underlying genetic defects and the full clinical spectrum of their expressions have been difficult to assess without access to genetic testing . fifty to sixty percent of patients with bannayan - riley - ruvalcaba syndrome ( brrs , mim 153480 ) have been shown to have germline mutations in the pten gene . an association between germline pten mutations and proteus syndrome ( mim 176920 ) has been disputed [ 19 - 22 ] . our aim was to validate strategies to identify families with pten mutations and to estimate prevalences and penetrances of pten mutations . the computerized medical files at the section for inherited cancer , rikshospitalet - radiumhospitalet medical centre , include more than 40,000 patients belonging to more than 3,000 families . these files were analyzed and all families with a diagnosis of cowden syndrome , all families suspected to have cowden syndrome , and all families with a combination of breast and thyroid cancers were identified . we had no families with suspected bannayan - riley - ruvalcaba syndrome , proteus syndrome or proteus - like syndrome . our two patients with lhermitte - duclos disease were also classified as having cowden syndrome and included above . all families were extended and offered genetic testing according to our genetic health care standards . because all activity was provided as health service , all information was kept in the medical files and no research registry was created . all diagnoses were confirmed in the medical files after written informed consent from each patient if alive or from their relatives if dead . we sequenced all nine exons , their flanking areas and 1500 basepairs upstream of atg ( the promoter region ) in the pten gene in all patients examined . the data were stored in oracle , pedigrees were displayed in cyrillicand the application to run the database as an electronic patient file system was programmed in db+ . we identified six families ( family a , b , c , d , e and f ) which fulfilled the international cowden syndrome consortium criteria ; for details see table 2 . four of them had been identified prior to the present study ( b , c , d , f ) . two families ( g and h ) had been clinically assumed to have cowden syndrome earlier on , but did not fulfil the diagnostic criteria . clinical signs in all demonstrated and assumed mutation carriers in the six cowden syndrome families with pten mutation . reference sequence nm_000314.1 ; * pid - patient identification number within the family ; all affected carried both mutations ; age at first detected polyp and total number of polyps up until last date of data collection are given . if the exact number is not given in the medical charts , polyps are interpreted as meaning a few . mutations in the coding sequence of pten were identified in all living affected members of the six families fulfilling the international cowden syndrome consortium criteria . all together 56 persons were subjected to genetic testing , out of whom 19 were identified as mutation carriers . in the two families clinically assumed to have cowden syndrome , but not fulfilling the clinical criteria , no pten mutation was identified ; for details see table 3 . in the eight families selected by a combination of breast and thyroid cancer no pten mutation was identified . number of patients with benign neoplasms and different cancer types , and the age range * two patients had bilateral disease , scored for age at first cancer ; two patients had a gangliocytoma ( lhermitte - duclos disease ) , one had a tumour of the pineal gland ; * * same patient . of the tested families , five families had a frameshift or nonsense mutation and one family had two missense mutations located in exon 9 located on the same chromosome . the detected mutations were located in exon 1 ( c.50delaa and c.68t > a ) , exon 5 ( c.328c > t ) , exon 6 ( c.565a > t ) , exon 8 ( c.1008c > g ) and exon 9 ( c.1028t > a and c.1039t > no mutations were found in regulatory regions . except for one family ( f ) , one family had a demonstrated de novo mutation ( d ) and two families most likely had de novo mutations ( c and e ) . the mothers of three of our probands had had breast cancer at age 45 ( bilateral breast cancer ) , 46 and 56 ( bilateral breast cancer ) years old . since they all were deceased and our attempts to perform mutation analysis from paraffin embedded tissue from these patients were unsuccessful , they were considered to be mutation carriers by state . the youngest mutation carrier was born with a demonstrated clinical sign ( macrocephaly , d-18 ) . twelve ( 63.2% ) patients had goitre and/or adenoma of the thyroid gland , ten ( 52.6% ) patients had polyps of the gastrointestinal tract , seven ( 36.8% ) patients had benign tumours of the breast , seven ( 36.8% ) patients had endometrial polyps and/or hyperplasia ; for details see table 3 . 1 shows age - related distribution of first clinical sign , as estimated by the kaplan - meier algorithm . age at onset of first clinical sign estimated by kaplan - meier algorithm for demonstrated mutation carriers . see table 2 for details of clinical signs one patient ( a-1 ) had multiple small colonic polyps interpreted as not having any dysplasia at age 33 . two years later she still had multiple small polyps less than 5 millimetres in diameter , now histologically described as lymphoid infiltrations and interpreted as an inflammatory condition . mutation analysis of the apc gene showed apc 7542 g > a , g2502s and apc 1496 c > t , y486y , interpreted as normal variation . we used centile charts for norwegian boys and girls aged 0 - 17 and for all patients above 17 years of age we used the centile for age 17 . macrocephaly was confirmed by exact measurement in 15 patients and judged to be clinically present in the remaining four . three ( 15.8% ) patients had thyroid cancer , age range 11 - 45 years . three ( 15.8% ) patients had tumours of the brain ( two had a gangliocytoma at age 24 and 51 and one had a tumour of the pineal gland at age 42 ) . two ( 10.5% ) patients had endometrial cancer at 31 and 47 years of age . one ( 5.3% ) patient had kidney cancer at 52 years of age . for details , see table 3 . results of kaplan - meier analysis for age of onset of cancer are given in fig . 2 . age at onset of first cancer estimated by kaplan - meier algorithm for demonstrated mutation carriers . cowden syndrome is rarely found in families attending our cancer genetics clinic . in the national survey presented here , pten mutations were found in all families fully meeting the cowden syndrome criteria , but in no cowden syndrome - like families not meeting the criteria . penetrance of pten mutations was high and expressions were cowden syndrome stigmata in early infancy or childhood and cancer in adolescence or early adulthood . in addition , the families were small with demonstrated de novo mutations , indicating low fitness before modern treatment and low population burden of mutation carriers . ten years ago we reported the well defined cowden syndrome families we knew at the time at rikshospitalet - radiumhospitalet medical centre . the national survey presented here revealed just two additional families , both fulfilling the clinical criteria for cowden syndrome . obviously , the numbers are too small to arrive at conclusions with respect to clinical manifestations in the mutation carriers . on the other hand , we had a large sample of cancer families initially not ascertained through cowden criteria - the families may be representative for families selected this way . on the other hand we described that in familial cancer all mutation carrying families had additional cowden syndrome stigmata . we have not examined whether or not cowden syndrome - like families without cancer may have pten mutations . we have previously reported on frequent cancer syndromes in norway ; we have a large number of cancer kindreds in our computerized database , and we found no additional families when searching for cowden syndrome associated cancers . we consider the low prevalence and the expressions found representative for cowden families with cancer . all families ( 100% , 95% ci 37 - 100% ) which fulfilled the cowden syndrome criteria carried pten mutations , which is in keeping with the previously reported estimate of 85 - 90% . our observed number of mutation carriers gives an observed prevalence of 1 per 242,063 , which is within nelen 's estimate of between 1 per 200,000 and 1 per 250,000 . we found only six families with mutations , which were considered too few for meaningful considerations with respect to where in the gene the mutations were located . twelve ( 63.2% ) patients had benign thyroid manifestations , which is a little less than three quarters reported by merg . the youngest age of onset for thyroid cancer was 11 years , which indicates that pten mutation carriers contract thyroid cancer both more frequently and at a younger age than the general population . seven ( 36.8% ) patients had benign breast lesions , compared to earlier reports of 50 - 60% . five out of 19 ( 26.3% ) had breast cancer at 24 - 45 years , which is within 20 - 30% and age range as previously reported . ten ( 52.6% ) patients had gastrointestinal polyps , which is close to earlier reports . none of our mutation carriers had colon cancer . according to lynch and de la chapelle a firm association between cowden syndrome and colorectal cancer has yet to be identified , and according to eng colorectal cancers are not components of cowden syndrome . one ( 5.3% ) of our mutation carriers had renal cell carcinoma , supporting the notion that renal cell carcinoma should be added to the operational criteria for cowden syndrome . thus , our findings add empirical support to established conclusions which have been questioned because of low numbers reported . if so , the uneven distribution of mutation carriers in families was a finding and possibly not a statistical problem reflecting random variation in low numbers . in sum , our results were that cowden syndrome families had pten mutations , while cowden - like families and breast and thyroid cancer kindreds did not . the number of cowden syndrome - like families was not more than what might be expected by chance alone . all examined mutation carriers had clinical signs , and cancer started to occur before the age of 16 . in cowden syndrome families , genetic testing to identify individuals at risk of contracting cancer can not wait until the kindreds are old enough to give informed consent . mutation carriers may be offered thyroid screening from childhood , and breast cancer screening may be considered from adolescence ( with mri , to avoid radiation exposure by mammography in puberty ) . our material is not large enough to conclude on which age to start breast cancer screening , but the youngest patient with breast cancer described internationally was 14 years old . we feel that we should try to do our best when it comes to screening , and therefore we recommend that one may consider breast cancer screening from adolescence . non - mutation carriers and members of cowden syndrome - like families may not be at risk for cancer in early age , and may need no special health care in infancy or adolescence . thorough clinical genetic work - up of families and access to genetic testing will discriminate between those who need health service from childhood , and those who do not .

cowden syndrome ( multiple hamartoma syndrome , mim 158350 ) is an early onset syndrome characterized by multiple hamartomas in the skin , mucous membranes , breast , thyroid and endometrium . patients with cowden syndrome have increased risk of breast cancer , thyroid cancer and endometrial cancer . in 1997 germline mutations in pten were demonstrated to cause cowden syndrome . we report the results of diagnostic and predictive testing in all families with cowden syndrome or suspected cowden syndrome registered at the norwegian cancer family clinics . pten mutations were found in all six families meeting the clinical criteria for cowden syndrome , in none of the two families assumed to have cowden syndrome but not fulfilling the criteria , and in none of the eight families selected in our computerized medical files to have a combination of breast and thyroid cancers . age - related penetrances for the various neoplasms are given . all families but one were small and de novo mutations were found .

bilateral locked facets are relatively common traumatic injuries of the cervical spine , but they are extremely rare in the lumbar spine . this is attributable to lumbar vertebrae having larger vertebral bodies and firm paraspinal muscle supporting them . in locked facet syndrome of lumbar vertebrae , in contrary to cervical lesion , a tremendous external force is needed to occur and fracture of facet is a common finding . this article contains a case of l4 - 5 locked facet . discussing the clinical features and injury mechanisms of the lumbar locked facet through reviewing several relevant literatures . a 37-year - old male welder with lower back pain and weakness in both lower extremities after being held down by aniron plate weighing 2,000 kg . neurologic examination revealed numbness in his right posterolateral thigh dorsiflexion and strength of both ankles and bigtoes was decreased ( grade iv ) . radiograph of the lumbar spine revealed anterior slippage of the 4 lumbar vertebra ( fig . 1 ) . a computed tomography ( ct ) scan found a bilateral l4 - 5 facet dislocation in which the l4 inferior articular process was located to the anterior of the l5 superior articular process ( fig . 2 , 3 ) . on t2-weighted magnetic resonance ( mr ) imaging , a high signal epidural hematoma was found at the l2 to l5 level and l4-l5 disc was disrupted ( fig . we proceeded open reduction and stabilization in which during surgery , we found that the interspinous ligaments and ligament flavum were partially torn and the l4 - 5 facets were locked bilaterally at the same time . the dislocation was reduced by resecting the superior facet of l5 and laminectomy of l4 was carried out . we then performed a posterior interbody fusion with cages , reinforced by a bilateral posterior rod and pedicle screw fixation . fracture - dislocations of the lumbosacral spine are rare . bilaterally locked facet injuries without fracture are even less common with only 11 cases of literature1 ) . the majority of dislocations involving the lumbar spine occur at the thoracolumbar junction , with decreasing frequency at the lower lumbar levels2,14 ) . anatomically , lumbar facet joints are arranged in the sagittal plane weak for hyperflexion yet strong for rotation . in 1940 , watson - jones described one patient with a lumbosacral fracture - dislocation and considered the mechanism of injury to be forcible hyperextension10 ) . however , hyperflexion with varying degrees of distraction is the most frequent mechanism of facet dislocation in the lumbar spine4,5,7,8,10,15 ) . hyperflexion alone is incapable of producing either pure dislocation or fracture - dislocation in the lumbar spine10 ) . therefore , in this case , we consider the mechanism of injury was a combination of hyperflexion , distraction , and rotation . radiologic diagnosis of this injury is dependent on initial good quality radiographs , which will demonstrate the altered associated of lumbar facet joints14,16 ) . but careful assessment of the ct and mri studies demonstrated facet dislocation and disruption of soft tissues . the mri allows assessment of the ligamentous and muscular structures , as well as the contents of the central canal and intervertebral neural foramen14 ) . a complete disruption of both joints in conjunction with avulsion of the interspinous ligaments and disc injury the non - articular convex sides of the articular facets were shown to be in contact . reconstruction in the sagittal plane can elegantly demonstrate the alignment of the vertebral bodies and facet joints and assess foraminal stenosis . in the coronal plane , lumbar spine alignment and asymmetry of the disc space can be assessed14 ) . a previous study showed the lumbar facet orientation in a normal lumbar spine , and noted that the facet joint and laminae are more sagittally oriented at the l4 - 5 level , while at l5-s1 they are more frontally oriented8,17 ) . in addition , a normal lumbar spine has the greatest flexion at l4 - 5 level8,10 ) . taking these findings into consideration , facet dislocation may occur more easily at l4 - 5 than l5- s1 , though the sacrum has good stability , it is fixed tightly to the pelvis by a sacro - iliac ligament . few authors have reported cases of bilateral dislocation successfully reduced with external reduction maneuvers3,6,9,19 ) . the selection of anterior or posterior fusion may be chosen based upon the proficiency and experience of the surgeon as well as the instability of the injury13 ) . the presence of an anterior slip , even if moderate , indicates a severe disc injury . disc assessment is mandatory in all cases because severe disc injuries requiring fusion may be found even in the absence of an anterior slip18 ) .

bilateral locked facets at l4 - 5 without facet fracture is a rarely known disease . we present a case of a 37-year - old male patient diagnosed as traumatic l4 - 5 bilateral facets dislocation without facet fracture . we carried out open reduction , epidural hematoma removal , posterior interbody fusion . after surgery , we attained rapid improvement of the neurologic deficits and competent stabilization .

ideally , the acetabular component should be placed at the natural hip center as close as possible . however , bone defect in those patients with development dysplasia of hip , acetabular migration superiorly followed by cup loosening , or severe periacetabular osteolysis , may prevent surgeon from placing the cup in a true anatomic hip center for achieving a sufficient contact with the host bone . bulk grafting with either femoral head autograft or allograft and cement has been reported to be filled in the location with deficient bone stock and furthermore to be helpful for rebuilding the native hip center with a successful early follow - up . but long - term follow - up studies have proven a high incidence of aseptic loosening . most clinical studies demonstrated that using a high hip center ( hhc ) could obtain good clinical results , especially in those patients with better acetabular bone stock superior to the anatomic hip center . obviously , the hhc could offer a chance to achieve better cup coverage with a cementless cup , which ensures initial stability , bony ingrowth , and long - term success in revision acetabular reconstruction . however , the elevated heights of the rotation center and prosthesis survival rate vary from each study . previous studies claimed that a 1% increase in hip load will occur for displacement 10 mm proximal of the rotation center , proper superior migration of the rotation center will not increase hip load dramatically , since the most common reason for surgery failure with the hhc was insufficient coverage of the cup . antoniades and pellegrini studied cross - sectional anatomy of the ilium from 16 cadaveric hips , claimed that there are substantial anatomic limitations to high hip reconstructions 2 cm above the acetabular dome , however , there were many limitations , and there is also some concern whether the calculations made in people of caucasian descent can be generalized to chinese people given that chinese people generally have a smaller physique than white people . we therefore , determined the thickness and width of the human ilium by measuring every section in mimics , and we also calculated cup coverage related to every specie thickness and width by a mathematical equation . a total of 120 normal iliums in 60 adult chinese patients ( 34 men , 26 women ) were chosen from those who received computer tomographic ( ct ) angiography for diagnosing vascular diseases in digital imaging and communications in medicine ( dicom ) database for this study . the average age was 55.2 years ( range , 3066 years ) , the average height was 161.5 cm ( range , 149187 cm ) , and the average weight was 62.7 kg ( range , 4790 kg ) . patients were included if they did not have severe osteoarthritis changes in hip and any deformities in the pelvis . the ct scans were performed previously with a toshiba brand aquilion ct scanner ( 120 kvp ; 320 ma ; 512 * 512 matrix ; slice thickness , 0.5 mm ) at the china - japan union hospital of jilin university . all patients were placed supine on the scanner with both knees taped to the scanner platform in an extended position with their patellar facing towards the ceiling . the scanning procedure was performed to acquire 0.5 mm ct slices from pelvis to the ankle joint . the dicom data were imported into mimics 16.0 ( materialise , leuven , belgium ) software . the rotational centers of the hips were obtained by drawing spheres to fit the femoral heads [ figure 1 ] . every 5-mm increments section of the ilium according the body sagittal axis in coronal plane from the rotational center of the hip to the cephalic [ figure 1a ] was marked , then measured the thickness ( ab ) and width ( cd ) of the pelvis in each slice [ figure 2 ] . the first slice was chosen at 25 mm above the rotation center , as the acetabular dome was located the place 25 mm above the rotation center for almost all the patients . ( a - h ) demonstrated the cross - sections from 25 to 60 mm above the rotation center respectively , and the measuring method was also shown on each slice . figure 2a is cephalic of the ilium and figure 2h is caudal of the ilium . to calculate the acetabular cup coverage rate at different levels above the rotation center , an equation improved from antoniades and pellegrini two - dimensional ( 2d ) linear acetabular cup coverage equation was used to estimate the three - dimensional ( 3d ) bony coverage rate of 40- , 50- , and 60-mm acetabular shells [ figure 3 ] . r = the prosthesis radius ; r = 1/2 of line ab or cd ; h = the depth of the covered part of the cup . a total of 120 normal iliums in 60 adult chinese patients ( 34 men , 26 women ) were chosen from those who received computer tomographic ( ct ) angiography for diagnosing vascular diseases in digital imaging and communications in medicine ( dicom ) database for this study . the average age was 55.2 years ( range , 3066 years ) , the average height was 161.5 cm ( range , 149187 cm ) , and the average weight was 62.7 kg ( range , 4790 kg ) . patients were included if they did not have severe osteoarthritis changes in hip and any deformities in the pelvis . the ct scans were performed previously with a toshiba brand aquilion ct scanner ( 120 kvp ; 320 ma ; 512 * 512 matrix ; slice thickness , 0.5 mm ) at the china - japan union hospital of jilin university . all patients were placed supine on the scanner with both knees taped to the scanner platform in an extended position with their patellar facing towards the ceiling . the scanning procedure was performed to acquire 0.5 mm ct slices from pelvis to the ankle joint . the dicom data were imported into mimics 16.0 ( materialise , leuven , belgium ) software . the rotational centers of the hips were obtained by drawing spheres to fit the femoral heads [ figure 1 ] . every 5-mm increments section of the ilium according the body sagittal axis in coronal plane from the rotational center of the hip to the cephalic [ figure 1a ] was marked , then measured the thickness ( ab ) and width ( cd ) of the pelvis in each slice [ figure 2 ] . the first slice was chosen at 25 mm above the rotation center , as the acetabular dome was located the place 25 mm above the rotation center for almost all the patients . ( a - h ) demonstrated the cross - sections from 25 to 60 mm above the rotation center respectively , and the measuring method was also shown on each slice . figure 2a is cephalic of the ilium and figure 2h is caudal of the ilium . thickness = ab ; width = cd . to calculate the acetabular cup coverage rate at different levels above the rotation center , an equation improved from antoniades and pellegrini two - dimensional ( 2d ) linear acetabular cup coverage equation was used to estimate the three - dimensional ( 3d ) bony coverage rate of 40- , 50- , and 60-mm acetabular shells [ figure 3 ] . the covered part of the acetabular component . r = the prosthesis radius ; r = 1/2 of line ab or cd ; h = the depth of the covered part of the cup . the results of measured thickness and the width of the ilium are shown in details in table 1 . the width was larger than the thickness in each cross - section , with the maximum difference of at the point 25 mm above the rotation center , which close to the acetabular dome [ figure 2a ] . at the acetabular dome , the average thickness and width of the ilium were 49.71 4.88 mm and 38.92 3.67 mm , respectively . whereas at 1 cm above the dome ( 35 mm above the rotation center ) , the average thickness and width were decreased to 41.35 5.13 mm and 31.13 3.37 mm , and at 2 cm ( 45 mm above the rotation center ) above the dome , the average thickness and width were decreased to 31.25 4.04 mm ) and 26.65 3.43 mm . with the slices went up above the rotation center , the thicknesses and the width of the pelvis were decreased sharply . considering the cups were placed at 45 inclination , the restricted boundaries of cup coverage were not in accordance to the values of ab but rather the values of cd , since the values of were bigger than those of cd [ table 1 ] . the mathematical model [ figure 3 ] was applied to calculate acetabular cup coverage for 40- , 50- , and 60-mm hemispheric shells , and the average results were 100% , 89% , and 44% at the acetabular dome , 100% , 43.7% , and 27.5% at 1 cm above the dome , 37.5% , 21.9% , and 14.2% at 2 cm above the dome , and 14.9% , 9.0% , and 6.1% at 3 cm above the dome [ table 2 ] . summary of value of ab and cd every 5-mm increments section of the ilium from 25 to 55 mm above rotational center ( mm ) ab presents the iliac thickness and cd presents the iliac width . coverage rates of the different diameter cups 40- , 50- , 60-mm at the level of 5-mm increments section of the ilium from 25 to 55 mm above rotational center ( % ) in the present study , we determined that the acetabular cup coverage rate varies across each section and individuals , within 1 cm above the acetabular dome being acceptable . our 3d measurement method may have solved some measurement limitations of the cadaveric approach used previously . the ilium thickness and width reached its peak 25 mm above the rotation center , approximately at the acetabular dome , and decreased quickly to approximately , especially 2 cm above the doom . at that height above the dome , a 50-mm cup would have only 21.9% coverage by our equation calculation . according to our result , hhc was applied to perform reconstruction of the acetabulum in those patients with peri - acetabular bone defect or osteolysis with good clinical results . however , there were also studies claimed that the risk of loosening was greater if the hip center was raised 30 mm above the teardrop . for now , none of the studies had reported the correlation between the loosening rate and the elevated height of the hip center . in addition , superior - only hip center relocation did not significantly affect the total joint force . although some surgeons claimed beneficial biomechanical effects of hip center medialization , our results do not recommend the empiric suggestion in hhc , the cup should be moved as medial as possible to improve acetabular component coverage , because our data provided no anatomic basis to ensure that increased medialization of the cup resulted in better bony coverage , moreover , medialization would increase the risk of breakthrough into the inner wall of the acetabulum and the difficult of rebuild the arm of gluteal muscle . therefore , we conducted this measurement to evaluate the elevated height of hhc , attempting to afford anatomical basis . antoniades and pellegrini measured the thickness of the ilium using cadaveric ilium and calculated the linear coverage of the cup , suggested that there were substantial anatomic limitations to high hip reconstructions 2 cm above the acetabular dome . but , there were limitations in his study , including small sample size and the linear cup coverage rate estimated in 2d . we conducted this measurement by obtaining the data from 60 chinese patients ( 120 ilium ) , and obtained the thickness of the ilium , which was smaller than caucasians . to calculate the cup coverage in 3d however , the conclusion of our study recommended that the elevated height within 1 cm above the doom would obtain sufficient coverage for asian . first , we did not consider the affection of bony stock in the sagittal plane , and the main reason was that the sagittal stock bone would affect cup coverage seldom as for 45 inclination cup placement . second , the study speculated the cup survival rate was correlated with the initial cup coverage rate , with the lacking of supporting clinical random control trails . third , the version of the cup will affect the cup coverage slightly , but in this study , we did not take into count . finally , the soft tissue balance did not take into count , the following study we would analysis the mechanics and soft tissue balance of the hip joint after hhc technique by finite element analysis . we emphasized the asian human ilium anatomy in a clinically relevant hhc technique during total hip arthroplasty . furthermore , we estimated that place the hip rotation center within 1 cm of the intact acetabular dome would achieve perfect initial coverage and a prosthetic stability . larger cup prosthesis may increase the loosening rate as for lower coverage rate of the cup . moreover , in complicated acetabular reconstruction surgeries , ct scanning will be necessary in performing preoperative planning , since that will provide detailed iliac bony stock situation , quantify the level of the hip center elevated and the stress variation , furthermore achieve good prosthesis survival rate .

background : many clinical studies have been published involving the use of a high hip center ( hhc ) , achieved good follow - up . however , there is a little anatomic guidance in the literature regarding the amount of bone stock available for initial implant coverage in this area of the ilium . the purpose of this study was to evaluate the thickness and width of the human ilium and related acetabular cup coverage for guiding acetabular component placement in hhc.methods:a total of 120 normal hips in 60 cases of adult patients from lower extremities computer tomographic angiography digital imaging and communications in medicine data were chosen for the study . after importing the data to the mimics software , we chose the cross sections every 5-mm increments from the rotational center of the hip to the cephalic of the ilium according the body sagittal axis , then we measured the thickness and width of the ilium for each cross section in axial plane , calculated the cup coverage at each chosen section.results:at the acetabular dome , the mean thickness and width of the ilium were 49.71 4.88 mm and 38.92 3.67 mm , respectively , whereas at 1 cm above the dome , decreased to 41.35 5.13 and 31.13 3.37 respectively , and 2 cm above the dome , decreased to 31.25 4.04 and 26.65 3.43 , respectively . acetabular cup averaged coverage for 40- , 50- , and 60-mm hemispheric shells , was 100% , 89% , and 44% at the acetabular dome , 100% , 43.7% , and 27.5% for 1 cm above the dome , and 37.5% , 21.9% , and 14.2% for 2 cm above the dome.conclusions:hhc reconstructions within 1 cm above the acetabular dome will be an acceptable and smaller diameter prosthesis would be better .

a 60-year - old man presented with a medical history significant for biopsy proven pan ( on prednisone and cyclophosphamide with prior failure on cyclophosphamide alone ) , paroxysmal atrial fibrillation , hypertension ( not on calcium channels blocker ) , dyslipidemia , non - insulin dependent diabetes mellitus , with multiple prior admissions for pan flares in the past , and with a history of an admission for septic shock 2 years prior to the current admission without any identifiable sources of infection . the patient initially presented with a scrotal pain , a fever of 103f , and fatigue . the patient was also found to be tachycardic to 130 beats per minute , hypotensive to 103/40 mm hg . the patient was initially started on broad - spectrum antibiotics consisting of vancomycin and zosyn ( piperacillin / tazobactam ) in the emergency department followed by an admission under medicine service . during the hospital course the patient s kidney function worsened leading to a switch in antibiotics to meropenem . despite switching antibiotics the patient was on 40 mg of prednisone daily making a suspicion of acute interstitial nephritis less likely . meanwhile , he continued to spike fevers without a specific source of an infection found in any of the blood , urine , and sputum cultures . also , no focus was found on the ct chest , abdomen , and pelvis which led to stopping all antibiotics . after a time span of 12 weeks our patient started developing a previously present macular rash that progressed slowly to involve his axillary area , later including his chest , head , neck , and abdomen . accompanied with these symptoms , the patient suffered an incendiary mental status than what was previously noted during the orientation exam . this was followed by a worsening of skin lesions with an element of bullae and vesicles . the dermatology team was involved , and a biopsy was obtained with a recommendation of initiating local steroid cream for the diagnosis of agep because of the given skin distribution and biopsy result , along with kidney injury , neutrophilia , and cyclic fevers . nine days after the initial appearance of the rash , the rash became pustular , accompanied by high grade fever of 109f leading to a transfer to the intensive care unit with a protocol of cooling . given prior discussions with rheumatology , nephrology , and infectious disease , the patient was administered pulse steroids , given low suspicion of infection and his prior history of pan flares and the general probability of autoimmune process . after completion of the third day of pulse steroids , the patient s fever subsided and subsequent improvement of the initial rash was observed , along with a decreased progression of sloughing and complete resolution of acute kidney injury . generalized acute pustular psoriasis ( von zumbusch type)acute generalized exanthematous pustulosis ( agep)drug reaction with eosinophilia and systemic manifestation ( dress)steven johnson syndromeleukocytoclastic vasculitissubcorneal pustular dermatosis ( sneddon wilkinson disease)cutaneous candidiasis generalized acute pustular psoriasis ( von zumbusch type ) acute generalized exanthematous pustulosis ( agep ) drug reaction with eosinophilia and systemic manifestation ( dress ) steven johnson syndrome leukocytoclastic vasculitis subcorneal pustular dermatosis ( sneddon wilkinson disease ) cutaneous candidiasis agep is a rare condition with incidence of 15 cases per million cases per year . agep is described as an acute eruption , characterized by the development of numerous non - follicular sterile pustules on a background of edematous erythema ( 1 , 2 ) . the rash is usually associated with a high fever ( > 38c ) and high blood neutrophil counts ( > 7,000 cells / mm ) ( fig . the pathophysiology of agep is a t cell - mediated neutrophilic inflammation involving cd4 t cells , cytotoxic cd8 t cells , and inflammatory cytokines and chemokines , which produce large amounts of cxcl8 , gm - csf , and reduce neutrophil apoptosis ( 38 ) . this is reflected on histological features by superficial , interstitial , and mid - dermal infiltrate rich in neutrophils . pan s mechanism is still unknown , but it was described as an immune complex - mediated disease that leads to medium - sized arterial inflammation and yet spares arterioles , capillaries , and venules . agep is a condition which usually manifests as a rapid development of small sized pustules on a background of edematous erythema with flexural accentuation ( 1 , 2 ) . in a series of 97 cases of agep , the median time between drug exposure and development of agep was 1 day for antibiotics and 11 days for all other drugs ( 9 ) . the rash begins on the face , and extends to the trunk and limbs with a diffuse or patchy distribution . during the acute phase , the patient has a fever above 38c ( 100.4f ) , leukocytosis with a neutrophil count > 7,000 cells / mm , and usually mild eosinophilia . organs are not usually affected by agep , but can be , particularly in older or compromised patients . a mild and reversible reduction in the creatinine clearance has been reported in some patients ( 1 , 2 , 10 ) . in a retrospective study of 58 patients with agep done by hotz and his group , liver and/or kidney function tests were abnormal in seven patients , two developed acute respiratory distress , and one agranulocytosis ( 11 ) . our pan patient , who had a fever and leukocytosis , was started on vancomycin and zosyn , and developed acute kidney injury , which can often be associated with the use of zosyn . giving this factor , this was followed by a macular back rash and after 12 weeks progressed slowly to involve his axillary area and later his chest , head , neck , and abdomen , accompanied by a decline of his mental status , followed by a worsening of skin lesions and also an element of bullae and vesicles . around 9 days after the first day of noticing the rash , the rash became pustular , and the patient developed a high grade fever of 109f . three days following the pulse steroids , the patient s fever subsided with a drastic decline in the patient s rash and progression of sloughing , along with a complete resolution of acute kidney injury . 2 ) spongiform , with superficial , interstitial , mid - dermal infiltrate rich in neutrophils , and dermal edema . intra- and subcorneal spongiform , with superficial , interstitial , and mid - dermal infiltrate rich in neutrophils , dermal edema was also seen . the differential diagnosis in our patient included : agep syndrome , dress , gpp , a pan typical rash , steven johnson syndrome , leukocytoclastic vasculitis , subcorneal pustular dermatosis ( sneddon wilkinson disease ) , and cutaneous candidiasis . both agep and gpp could be accompanied by a fever , neutropenia , and systemic manifestations ( 11 ) . however , gpp is more commonly associated with cholestasis and hepatic involvement in around 90% of cases . also , in retrospect our patient did not have any family history of psoriasis , or psoriasis . skin manifestations of pan may include : tender erythematous nodules , purpura , livedo reticularis , ulcers , and bullous or vesicular eruption ( 1214 ) . these are different from our patient s rash . excluding this factor , the biopsy showed a better description of agep , giving the dermal edema , and multiple spongiosis . other rashes that potentially have such a degree of skin reactions could be dress , steven johnson syndrome , and leukocytoclastic vasculitis which were unlikely given the biopsy result . subcorneal pustular dermatosis ( sneddon wilkinson disease ) was also in our deferential diagnosis list ; however , on histology there was a subcorneal accumulation of neutrophils without spongiosis or keratinocyte damage and a perivascular infiltrate of neutrophils ( 1519 ) . however , given the negative blood cultures when the patient first was presented , and the clinical scenario , with significant improvement on pulse steroids , this diagnosis was unlikely . a vast majority of agep cases are secondary to antibiotics , and it usually start 12 days after starting the agents . however , there are some patients that do not have known etiology . given that our patient started with fevers and acute kidney injury prior to instating any antibiotics and also having a rash which started more than a week after initiating zosyn this also did not reoccur when the patient re - challenged with meropenem and vancomycin . our final thought about our patient with pan , being difficult to control with multiple admissions for pan flares , and having poor responses to cyclophosphamide , is that his agep skin rash , could have been a manifestation of his autoimmune process that led to his prior pan manifestations . after mentioning a rational of diagnosis management from the prospect of clinical manifestation for the agep in this case , would be weaning off the steroids as agep is a self - resolving disease . however , with a severity of fevers , we believe pulse steroids are the best treatment at this point . initiating other immunosuppressive would have been a premature decision and inaccurate given the nature of agep . however , because of the history of difficult to control pan , and the lack of explanation of agep syndrome , the patient would eventually benefit from immunosuppressive management guided toward his pan . yet , agep associates well with penicillin , which would make it prudent clinically to abstain from using penicillin antibiotics in such a patient . first , the association between agep and the patient s history of pan opens further questions about etiology of pan and possibilities of involvement of t cell proliferation inducing neutrophilic proliferation in the pathogenesis . management includes withdrawal of the offending drug , supportive care , and symptomatic treatment of pruritus and skin inflammation . in our case , agep was extensive , and the etiology was unknown , with unresponsiveness after switching the antibiotics . this opens the door for the use of systemic steroids , which was followed by dramatic improvement in the patient s rash and his kidney function . systemic corticosteroids have been used to treat agep , but evidence that they shorten the disease course is still unknown ( 2022 ) . finally , the severity of the case , agep usually resolves spontaneously . our patient presented with systemic manifestations that followed with an extensive rash . systemic manifestations involved a very high fever that required icu admission , and the functioning of the kidneys . clinician should be aware that pustular skin lesion could be autoimmune rather than infection.prior autoimmunity manifested as vasculitis can predispose to other process such as agep in this case.agep progression can start with other generalized manifestation then progress with skin lesions.autoimmune process such as agep can lead to severe fevers.consideration of immunosuppression should be thought as primary treatment when clinical suspicion is high , especially with negative cultures . prior autoimmunity manifested as vasculitis can predispose to other process such as agep in this case . agep progression can start with other generalized manifestation then progress with skin lesions . autoimmune process such as agep can lead to severe fevers . consideration of immunosuppression should be thought as primary treatment when clinical suspicion is high , especially with negative cultures . the authors have not received any funding or benefits from industry or elsewhere to conduct this study .

a patient with a known biopsy of polyarteritis nodosa diagnosis presented with cyclic fevers , acute kidney injury , and progression of rash from macular to pustular , worsening despite being on antibiotics , without evidence of infection on multiple cultures . the patient had a pathological diagnosis from a skin biopsy of acute generalized exanthematous pustulosis syndrome , with a total resolution of rash , fevers , and acute kidney injury on treatment with pulse steroids .

non - hodgkin lymphomas ( nhls ) account for approximately 60% of all lymphomas in children and adolescents . childhood nhls are subdivided into burkitt 's lymphoma , diffuse large b - cell lymphoma ( dlbcl ) , lymphoblastic lymphoma , and anaplastic large - cell lymphoma . dlbcl is characterized by relatively more frequent extranodal presentation , seen in upto 40% of the cases . primary involvement of the lymphoma of the middle ear is rare , with only about 18 cases being reported in literature so far . here , we report a case of dlbcl , presented with features of facial palsy and otitis , who received initial symptomatic treatment and later chemotherapy after diagnosing dlbcl . a 2 years 8 months old boy visited our tertiary care hospital with complaints of ear ache ( left side ) and left facial palsy of 4 weeks duration . after initial 2 weeks of these symptoms , there was whitish serous discharge from the left ear . before referral to our hospital , he was treated for otitis media with antibiotics , details of which were not available . his complete blood picture and biochemistry investigations done in our hospital were within normal limits . as the symptoms persisted for 4 weeks , computed tomography of head and neck was done which was suggestive of solid mass lesion of 2 cm 2 cm size in the left mastoid with destruction of mastoid bone [ figure 1 ] . the disease was in stage 1 ( as per murphy 's staging ) and was completely resected . histopathological examination showed large cells of lymphoid cell proliferation immune histochemistry was positive for cd20 , bcl-2 and negative for cd3 , with low mib-1 , which confirmed dlbcl . his positron emission tomography for staging , bone marrow and cerebrospinal fluid revealed no abnormality . computed tomography head and neck suggestive of solid mass lesion of 2 cm 2 cm size in the left mastoid with destruction of mastoid bone computed tomography head and neck of right side showing no abnormality his initial clinical symptoms of earache and facial nerve palsy followed by ear discharge resolved after starting chemotherapy as per b - cell lymphoma protocol for 6 months . currently , he is 37 months off treatment , and no disease recurrence is seen clinically as well as radiologically . it is an aggressive form of lymphoma , usually curable with appropriate treatment and has high survival rate . rapid disease progression of dlbcl calls for an early , accurate diagnosis and appropriate treatment . however , unusual presentation can mislead the physician resulting in wrong diagnosis , which delays the treatment , thus promoting disease progression . extranodal presentations of childhood dlbcl are relatively uncommon in clinical practice , and much rarer are those primarily involving middle ear and mastoid . involvement of middle ear and mastoid can resemble the features of otitis media and unusual facial palsy mimicking mastoiditis . although these initial symptoms were suggestive of middle ear infection , the distinguishing factor was unresponsiveness to antibiotics . there have been very few reports of nhl with facial nerve involvement ; ogawa et al . mccabe et al . , reported a case of 2-year - old , an immunocompetent boy with spontaneous regression of an epstein - barr - virus - associated monoclonal lymphoid proliferation who presented with acute otitis media and facial palsy . have described a case of dlbcl with features of otitis media , mastoiditis , and facial palsy . as symptoms persisted even after 4 weeks of treatment , the patient was started on chemotherapy , to which he promptly responded . extranodal nhls of middle ear which is not a common clinical presentation may present as facial palsy , and misdiagnosed as otomastoiditis . there should be a high index of suspicion for primary neoplasms of the middle ear in patients with chronic otomastoiditis refractory to appropriate initial antibiotic therapy ; early diagnosis and appropriate treatment results in good therapeutic outcome and minimizes further complications .

extra nodal presentation of non hodgkins lymphoma ( nhl ) is a rare entity , and data available about the nhl that primarily involves of middle ear and mastoid is limited . we report a case of diffuse large b cell lymphoma ( dlbcl ) , in a 2 year 8 month old boy , who developed otalgia and facial palsy . computed tomography revealed a mass in the left mastoid . mastoid exploration and histopathological examination revealed dlbcl . this case highlights the importance of considering malignant lymphoma as one of the differential diagnosis in persistent otitis media and / facial palsy .