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we analyzed passive surveillance data on hca cases reported to the national center for disease control and public health ( tbilisi , georgia ) during 20102012 . self - reported source of infection was ascertained from categorical responses that included butchering / slaughtering cattle , handling / preparing meat , performing field work / harvesting crops , processing hair / wool , receiving an insect bite , unknown , or other . we also obtained information about regional - level anthrax cases in livestock ( www.oie.int/wahis_2/public/wahid.php/diseaseinformation/statusdetail ) . hca cases and incidence per million persons were plotted over time with livestock cases . to estimate changes in hca risk over time , we compared data for the study period with data for 20072009 by using a cumulative incidence ratio ( total cases / median year population ) . we calculated incidence risk ratios for demographic characteristics by using a negative binomial regression ( technical appendix ) . data were anonymized and aggregated to each case - patient s community of residence and mapped in a geographic information system . we extrapolated current population from the 2002 census using the united nations medium variant population growth projections ( http://data.un.org/ ) . cumulative incidences per 10,000 population were calculated for each community ( total cases / median year population ) . we adjusted for community population heterogeneity using empirical bayes smoothing estimates of the cumulative incidence ( technical appendix ) . kernel density estimation was used to map the cumulative incidence risk / km ( technical appendix ) . to identify community - level hca spatial clustering , we used the poisson model in satscan ( 7 ) with a maximum cluster size of 25% of the population at risk . we compared the proportion of urban and rural communities inside and outside clusters using a analysis ( proc freq , sas institute , cary , nc , usa ) . during 20102012 , a total of 251 hca cases and 74 livestock cases ( 38 cattle , 1 pig , 4 sheep / goats , 1 horse ) were reported ( figure 1 ) . hca cases peaked in 2012 ( 142 cases ) , corresponding to a national incidence of 31.7 per million population ( 95% ci 28.436.1 ) . compared with 20072009 ( 133 cases ) , the period studied had a higher risk for hca ( cumulative incidence ratio 1.89 [ 95% ci 1.642.33 ] , p<0.01 ) . total number of human cutaneous anthrax cases ( light gray ) and livestock cases ( dark gray ) , georgia , 20102012 . incidence rates ( irs ) ( 95% cis ) of human cutaneous anthrax per million population are displayed above the bars . cases occurred predominantly in males ( 209 [ 84% ] ) ( table 1 ) . butchering / slaughtering cattle as a source of infection was more common among male patients ( 143 [ 68% ] ) ; processing / handling meat was more common among female patients ( 28 [ 68% ] ) . the adjusted incidence risk ratios from the negative binomial model showed a stronger association of risk in males ( 4.95 [ 95% ci 2.918.42 ] ) than in females ( table 2 ) . persons 5064 years of age were at greater risk than were persons in all other age groups . risk did not differ between case - patients who processed / handled meat and those who slaughtered / butchered cattle . * population estimates were obtained from the georgian state statistical office ( geostat , http://geostat.ge ) and are based on median year population totals for the study period . * goodness - of - fit test indicated the model fit the data ( df = 31 , = 40.71 , p = 0.11 ) . empirical bayes smoothed incidence per 10,000 population ranged from 0.11 ( 95% ci 0.030.37 ) to 213.8 ( 95% ci 72.8552.6 ) ( figure 2 , panel a ) . the kernel density analysis identified a higher risk per squared kilometer in the southeast and west ( figure 2 , panel b ) . we identified 3 spatial clusters of high risk ; the clusters comprised 58 communities with 197 cases ( figure 2 , panel c ) . cumulative incidence inside the clusters was 12.8/10,000 population compared with 0.96/10,000 population outside the clusters . the proportion ( = 0.65 , p = 0.4 ) of urban and rural communities ( 22 and 36 , respectively ) within clusters did not differ from the proportion outside clusters ( urban : 14 ; rural : 24 ) . clusters 1 and 2 in the southeast bordered the densely populated urban area of the capital ( tbilisi ) and were associated with grazing lands , whereas cluster 3 bordered the urban area of poti in the west and was associated with a higher percentage of croplands . a ) empirical bayes smoothing cumulative incidence ( per 10,000 population ) of human cutaneous anthrax at the community level , georgia , 20102012 . green star indicates the location of the capital , tbilisi ; gray star indicates the fourth most populous city , rustavi . c ) spatial clustering of human cutaneous anthrax cases as determined by using satscan ( 7 ) . rr , risk ratio . despite an apparent decline in hca cases worldwide ( 8) , incidence in georgia has increased and is now comparable with that in turkey , where the disease is hyperendemic ( 1,9,10 ) . our analysis identified clusters of communities that were of historical importance for hca risk and new communities that represent areas of ( re)emergence ( 6 ) . our findings indicate that hca cases were concentrated within specific areas associated with agriculture and in close proximity to urban centers ( figure 2 ) , consistent with research linking urban livestock trading centers and markets to outbreaks and higher rates of hca ( 5,911 ) . sick and dying animals are often slaughtered and brought to market quickly to mitigate economic losses , thereby exacerbating exposure risk while limiting livestock reporting ( 10,11 ) . hca is primarily associated with rural , agrarian areas ( 2,3,12 ) , but we found no difference in the proportion of urban and rural communities in high - risk clusters . this association with urban zones suggests reliance on these areas for commerce , coupled with increased agricultural employment from 25% of the population in 1990 to 55% in 2010 ( 5,13 ) . one hypothesis is that contaminated meat is brought into urban areas and sold at informal meat markets that because of fiscal constraints have little to no regulation . cases were predominantly linked to contact with infected livestock or meat , as observed elsewhere ( 2,3,9,11 ) . field work was a self - reported source of infection in 27 ( 10.7% ) cases . this risk factor is not well documented and might reflect recall bias or unwillingness to admit to slaughtering infected animals . our findings that males were at higher risk than females for hca , as reported elsewhere ( 2,14 ) might reflect occupational exposures or gender roles , with males slaughtering / butchering livestock and females more involved in preparing meat ( 14 ) . in contrast , no gender differences were reported in turkey or kazakhstan ( 3,9 ) . although age was not a risk factor in other regions ( 2,3 ) , persons 5064 years of age in this study were at higher risk for infection ( table 2 ) , reflecting changing sociocultural practices related to an agrarian lifestyle . although the true cause of the increase in hca cases is unknown , it is probably due to a combination of factors related to decreased public health funding and agricultural reform resulting in a shift from collectivization to private ownership ( 1,5,13 ) . these factors , coupled with limited veterinary control and the cessation of compulsory livestock vaccination , have played plausible roles in the increased incidence of hca . livestock cases were out of sync temporally and spatially with human cases , indicating anthropocentric reporting or high incidence from relatively few animals , although differences in the aggregation of livestock cases limit the inference of spatial synchrony . controlling hca requires controlling the disease in livestock ( 1,2,9 ) and highlights the need for a one health approach . our findings can be used to formulate public health interventions aimed at controlling anthrax in livestock and increasing awareness of the disease , particularly in urban areas . given the limited resources available , future efforts should focus on high - risk areas for livestock surveillance and control , such as targeted vaccination campaigns ( 15 ) .

we assessed the occurrence of human cutaneous anthrax in georgia during 2010-2012 by examining demographic and spatial characteristics of reported cases . reporting increased substantially , as did clustering of cases near urban centers . control efforts , including education about anthrax and livestock vaccination , can be directed at areas of high risk .

protein - losing enteropathy is not a disease , but rather it is the manifestation of a diverse group of disorders characterized by the excessive loss of plasma proteins into the lumen of the gastrointestinal tract , and this results in hypoproteinemia . the pathophysiology of protein - losing enteropathy can be summarized as increased mucosal permeability , mucosal erosions / ulcerations , and lymphatic obstruction . we experienced such a case of severe protein - losing enteropathy as the late complication of pelvic irradiation for the treatment of uterine cervical carcinoma . radiation - induced enterocolitis can manifest as a distressing protein - losing enteropathy , and it can result in a dreadful outcome . a 66-year - old woman was referred to us by the gynecology clinic because of her progressively aggravated pitting edema of the bilateral lower extremities ; in addition , she suffered from intermittent abdominal pain , persistent anemia with intermittent hematuria and hematochezia , and all of these symptoms had occurred during the previous 4 years . 26 years ago , she received a radical hysterectomy with pelvic lymphadenectomy and external irradiation at a dose of 6100 cgy for the treatment of her uterine cervical carcinoma ( stage ib ) . she had received intermittent transfusions of packed rbcs , about a total of 8 to 10 pints yearly , under the presumptive diagnosis of radiation colitis and cystitis . 20 years ago , she experienced an episode of liver abscess that was treated by liver surgery . 7 years ago , gross hematuria had developed and she was diagnosed as having bladder cancer ( stage i ) with a background of radiation cystitis , for which she had undergone a transurethral bladder resection . when we examined the patient , we observed severe anemia and a grade 3 pitting edema on the affected parts of her body , and cachexia was also noticed . the liver was not palpable and a previous operation wound scar was found on the right upper abdomen . the laboratory tests revealed microcytic , hypochromic anemia ( hemoglobin : 6.7 g / dl , normal : 12.018.0 g / dl ) with a serum iron level of 17 g / dl ( normal : 37170 g / dl ) , a total iron binding capacity of 123 g / dl ( normal : 250450 g / dl ) , and a ferritin level of 78 ng / ml ( normal : 20.0300.0 ng / ml ) . the levels of vitamin b12 and folate in the serum were normal and the stool occult blood test was positive . the serum protein level was 4.7 g / dl ( normal : 6.38.2 g / dl ) , the albumin level was 1.6 g / dl ( normal : 3.55.1 g / dl ) , the cholesterol was 87 mg / dl ( normal : 100200 mg / dl ) , and the serum total bilirubin , ast / alt , alkaline phosphatase and prothrombin time were all normal . the bun and creatinine levels were normal . the urinalysis results revealed microscopic hematuria ( rbc 59/hpf ) and pyuria ( > 30/hpf ) without proteinuria . urine cytology did nt reveal any malignant cells , and the urine culture was negative . the result of the alpha-1- antitrypsin ( 1-at ) clearance test using 24hr stool collection was 169 mg/24hr ( normal : 0.027.0 mg/24hr ) , which was markedly increased and diagnostic for a protein - losing enteropathy . the small bowel series showed multifocal thumb - printing lesions in the ileum with delayed passage ( figure 1 ) . on the barium enema , there was diffuse luminal narrowing with the loss of haustral markings in the rectum and sigmoid colon . the sigmoidoscope findings were diffuse mucosal friability and vascular ectasia , which were gross and microscopic findings compatible with radiation colitis ( figure 3 ) . chest x - ray , electrocardiogram , echocardiogram , lung function tests and upper endoscopic findings were unremarkable . abdominal ct scan showed liver cysts ( size : 22 cm and 0.80.8 cm ) in segments 4 and 6 , respectively . cystoscopic examination showed the mucosal thickening with edema and vascular ectasia , but there was no evidence of tumor recurrence . tc - human serum albumin scintigraphy showed localized radioactivity in upper abdomen ( figure 4a ) on the 24hr delay image , which meant there was a small amount of bowel leakage of radiolabeled albumin in the ascending colon . tc - labeled dextran lymphoscintigraphy showed a decreased inguinal uptake in the left ileac lymph nodes with delayed migration and collateral circulations ( figure 4b ) , suggesting lymphatic obstruction in that area . the patient s symptoms persisted and she required transfusion of 1 pints of packed rbcs due to the anemia , and she also received infusion of 25 grams of albumin in a month s time to reduce her edema and dyspnea . about 5 months later , she was re - admitted with symptoms of fever and severe dyspnea . the laboratory findings showed azotemia ( bun 89 mg / dl , serum creatinine 5.0 mg / dl ) , leukocytosis ( 14,500/mm , neutrophils 89% ) , hematuria and pyuria . on urine culture , her hemoglobin level was 9.6 g / dl , and the serum protein ( 4.8 g / dl ) and albumin ( 1.6 g / dl ) levels were very low . the patient s condition was severe ; she had a urinary tract infection associated with urinary flow stasis that was probably due to a neurogenic cause because there was no mechanical cause for the obstruction on the cystoscopic examination . the patient received prompt administration of broad spectrum antibiotics and percutaneous nephrostomy on the right kidney . the patient condition then gradually improved with recovery of the serum creatinine to 1.9 mg / dl . however , a generalized seizure suddenly developed on the 18 day of admission . the magnetic resonance image ( mri ) of the brain demonstrated diffuse brain atrophy and multiple small high signal intensity lesions in the bilateral hemispheres , and this was suspected of being small vessel disease or vasculitis . the level of complement 3 , complement 4 , fibrinogen and fibrinogen degradation product were within the normal limits . the seizure was not controlled with phenytoin and carbamazepin , and it became progressively aggravated in terms of frequency and duration . on the 32 day of admission , she finally expired after a severe attack of seizure . the diagnosis of protein - losing enteropathy can be made based on an increase in the alpha-1-antitrypsin ( 1-at ) clearance . however , the 1-at clearance may be invalidated by intestinal bleeding , because this condition falsely elevates the 1-at clearance ( 1-at clearance rises 5.5 ml / day for each 10 ml of intestinal bleeding ) . our patient suffered from chronic intestinal bleeding , so that her markedly increased 1-at clearance ( 169 ml / day ) might have been a false - positive result . we assumed that her bleeding rate might not exceed 20 ml / day , because she required about 2 pints of packed rbc for 2 months to maintain her hemoglobin level . therefore , her increased 1-at clearance was diagnostic for the protein - losing enteropathy , along with the other clinical and laboratory results . we used 24hr stool collection instead of 72hr stool collection because of her poor compliance . some studies have shown that the single - day stool collection provided as useful data as the does the 3-day stool collection did . tc - human serum albumin scintigraphy is also a useful test for the diagnosis and monitoring of enteric protein loss , although it is less sensitive than the 1-at clearance test . our patient showed diffuse , localized bowel activity in the right abdomen ( colonic retention ) on the 24hr delay scan , which was suggestive of bowel leakage , but the localization was not compatible with the radiological findings . tc - labeled dextran lymphoscintigraphy of our case showed lymphatic obstruction at the left ileac lymph nodes with collateral circulations that was probably due to the previous lymph node dissection and pelvic irradiation , and this might well have contributed to the development of the protein - losing enteropathy . mucosal injury causes increased permeability for the plasma proteins , and the mucosal erosions and ulcers result in the loss of an inflammatory , protein - rich exudate . moreover , the lymphatic obstruction results in the dilatation of intestinal lymphatic channels and the rupture of lacteals that are rich in plasma proteins . the intestinal mucosa of our case displayed diffuse destruction from the ileum to the rectum with intermittent partial intestinal obstruction and chronic bleeding ; these lesions were demonstrated by the barium studies and they were due to the previous irradiation . we thought the protein - losing enteropathy of our case was caused by mucosal injury and lymphatic obstruction that were the results of previous radiation and lymph node dissection . the acute changes noted after radiation exposure are damages to the mucosal epithelial cells and the vascular endothelial cells . in the late phase after increasing doses of radiation , the ulceration , severe fibrosis and vascular ischemia progresses to stricture , fistulization and perforation . exposure to ionizing radiations has been shown to cause increased protein leakages in the gastrointestinal tract of laboratory animals . after an acute exposure of radiation , the intestinal protein loss developed within 24 hours and maximal loss was observed in 4 or 5 day after radiation . the mechanism of protein loss in this acute phase was an increased vascular permeability and an abnormality of cellular membranes in the intestine . metabolic studies with i albumin in the patients with bladder cancer or renal cell carcinoma showed an increased albumin loss across the intestinal tract after radiation therapy . case reports of radiation enterocolitis also have described hypoalbuminemia as a manifestation of these complications . the occurrence of radiation injury is dose dependent , and 90% of the patients having gastrointestinal complications have received more than 3,000 cgy . our patient received a high dose of irradiation , 6,100 cgy , which resulted in severe , late complications . the development of chronic radiation enterocolitis is highly variable with a mean incidence of 5% to 15% . the management of chronic radiation enterocolitis remains a challenge because of the progressive evolution of the lesions , which are eventually observed mainly as obstructive endarteritis and fibrosis . the treatment should be as conservative as possible because of the diffuse nature of the lesions and the high morbidity associated with surgery . conservative therapy includes loperamide for diarrhea , antibiotics for bacterial overgrowth , nutritional support for malnutrition and endoscopic coagulation for the bleeding lesions . the use of corticosteroids or sulfasalazin is usually not consistently helpful because of the lack of inflammation in chronic radiation disease . our case was a severe protein - losing enteropathy due to radiation enterocolitis and lymphatic obstruction that was the result of treatment for uterine cervical carcinoma in the remote past . her clinical course showed nearly the whole spectrum of complication for pelvic irradiation such as enterocolitis that manifested as protein - losing enteropathy , continuous intestinal bleeding , partial obstruction of the intestine and also liver abscess that was probably related to the incompetent intestinal mucosal barrier ; all of this was in addition to the hemorrhagic cystitis with secondary neoplasm of the bladder cancer , urinary stasis and severe urinary tract infection . although she recovered from the uterine cervical carcinoma , her quality of life was miserable after the treatment for the cancer . the treatment of radiation enterocolitis is very limited , so that prevention is the best way to avoid these problems . to reduce these complications , better radiation technique and better patient selection for the use of radiotherapy is definitely warranted . new therapeutic trials with treatment methods such as hyperbaric oxygen therapy and the search for the effective radioprotective agents should be continued .

protein - losing enteropathy is the manifestation of a diverse set of disorders , and it is characterized by the excessive loss of plasma proteins into the affected portions of the gastrointestinal tract , and this results in hypoalbuminemia . we report here on a case of severe protein - losing enteropathy with the typical clinical features of hypoalbuminemia , dependent edema and increased alpha 1-antitrypsin ( 1-at ) clearance , as measured by using 24hr stool testing . the associated disorder with the protein - losing enteropathy of our case was radiation enterocolitis and lymphatic obstruction that was due to radiation treatment and lymph node dissection in the remote past for the treatment of uterine cervical carcinoma . our case suggests that chronic radiation enterocolitis can result in irreversible injury to the intestinal mucosa and a protein - losing enteropathy , which can bring about a very poor quality of life and even the loss of life .

accessory spleen ( as ) may develop during the sixth week of embryogenesis following the deposition of spleen cells along the path from the midline , usually occurring on the left side . an as is commonly located near the spleen s hilum and in the pancreas tail , and is generally asymptomatic and diagnosed incidentally during laparotomy or radiological examination performed for other reasons . adnexal masses typically originate from the genital tract ; however , extrapelvic organs are rarely found in this location . herein , we present the sonographic and histopathologic findings in the case of a woman with left lower quadrant pain whose final diagnosis was as in the pelvis . although extremely rare , this possibility must be considered in the differential diagnosis of pelvic masses . a 43-year - old woman was presented to our university hospital with recurrent left lower abdominal pain of 6 months duration . she had a history of subtotal hysterectomy and unilateral salphingo - oopherectomy for uterine myoma 9 years prior . she did not know the details of her operation and did not remember which ovary had been removed . a solid mass approximately 4 cm in diameter was palpable in the left adnexa . laboratory evaluation was normal , including erythrocyte sedimentation rate and c - reactive protein levels . transvaginal ultrasound examination was performed with a 7.0 mhz vaginal transducer ( voluson 730 , ge healthcare , usa ) . sonography revealed a left adnexial mass 46.1 31.9 mm in diameter showing a homogeneously isoechoic pattern . the mass was solid and well circumscribed , and pathologic blood flow was not detected in doppler ultrasonography . pelvic magnetic resonance imaging ( mri ) demonstrated a 4.5 4 4 cm solid mass in the left adnexa , but did not provide additional information ( fig . ca125 , ca15 - 3 , ca19 - 9 , cea , and afp values were within normal limits . a laparotomy was performed under general anesthesia , during which inspection of the pelvis revealed a solid , firm , oval , left - sided tumor with a smooth surface , approximately 4 cm in diameter . the tumor was located in the left pararectal space , adjacent to the obturator fossa . macroscopic analyses showed a pinkish , clear , 5.5 5 5 cm mass with a smooth surface ( fig . microscopic analyses showed normal splenic red and white pulp components in a 5:1 ratio , including lymphoid follicles with germinal center formation ( fig . an upper abdominal sonography was performed , confirming that the spleen had a normal localization and size . the patient s symptoms were completely relieved following surgery and the postoperative period was uneventful . the spleen is a large encapsulated mass of vascular and lymphoid tissue situated in the upper left quadrant of the abdominal cavity . various developmental anomalies of the spleen have been observed , including complete agenesis , multiple spleens or polysplenia , isolated small additional accessory spleens , and persistent lobulation . as may be formed during embryogenesis , developing from the left side of the dorsal mesogastrium as a result of imperfect fusion of separate splenic masses . the localization varies widely , but the most common locations are the splenic hilum ( 75% ) or the pancreas tail ( 20% ) , as well as the greater omentum , along the greater curvature of the stomach , and the small and large intestine mesentery [ 13 ] . the regions adjacent to the left ovary or left testis and the pouch of douglas are uncommon localizations . the case presented herein is one with a rare localization of as , of interest due to its proximity to the obturator fossa and retroperitoneal area . ectopic splenic tissue can be either congenital ( as or splenunculi ) or acquired ( splenosis ) . the patient discussed herein had no history of trauma or splenectomy ; therefore , this may have been a case of a previously undiagnosed as , missed during hysterectomy due to its deep localization . investigated 720 autopsy cases , and as was found in 6.7% cases , 2 of which were pelvic as ; thus , classifying the pelvis as an atypical localization . further , the common presentation is of a single as ( 85% ) , although two ( 14% ) , and rarely three or more ( 1% ) , can also be observed . the size of the as ranges from microscopic to 4 cm in diameter , as observed in the present case . as presents 13 times more frequently in females than males , and the mean age is reported between 20 and 40 years ; the present case agreeing with these statistics . a wandering spleen is a separate entity , resulting from incomplete development of the ligamentous splenic apparatus allowing the spleen to migrate within the abdomen . . reported on a wandering as attached to the greater omentum resected from a 26-year old female . . also reported on a pelvic wandering as in a 44-year - old female and emphasized on its differential diagnosis from adnexal masses . an as is an incidental finding of no clinical significance in most patients . as are generally determined during radiological investigations or during open or laparoscopic surgeries . they are usually asymptomatic and have rarely been reported to present clinically as an abdominal mass related to complications such as torsion , spontaneous rupture , hemorrhage , or cyst formation . torsion and ischemia of as can lead to acute abdomen as seen in the main spleen . . also reported on an acute abdomen due to spontaneous torsion of the as . the differential diagnosis of pelvic as could include adnexal mass features such as enlarged lymph nodes , subserosal fibroid , ovarian tumors , organized hematoma , and tubo - ovarian abscess . our initial diagnosis was also of an ovarian neoplasia . owing to fact that , pelvic mass was considered as malignancy before surgery and its deep localization , open surgery was prefered . despite pelvic as being a rare , usually asymptomatic , pelvic mass condition , it should be considered in the differential diagnosis of symptomatic pelvic masses . written informed consent was obtained from the patient for publication of this case report and and accompanying images . mine islimye taskin , ertan adali , banu gulec baser contributed to study design and writing , erdogan bulbul contributed to data collection and evaluation of mri .

highlightsectopic splenic tissue can be either congenital ( accessory spleen ) or acquired ( splenosis).accessory spleen ( as ) is commonly located near the spleen s hilum and in the pancreas tail.pelvic as is a very rare entity.as is generally determined incidentally during radiological investigation or surgery.pelvic as may be considered in differential diagnosis of adnexal masses .

acne vulgaris is the chronic inflammatory disease of the pilosebaceous units , which chiefly involves face and upper part of the trunk and is characterized by seborrhea , comedo , red papules , superficial pustules , deep or pseudocystic nodules , pustules , and sometimes scar . four main factors play roles in its pathogenesis : increase of sebum production , hyper cornification of the pilosebaceous duct , microbial flora , especially colonization of propionibacterium acne , and inflammation knowledge of relationship between skin diseases and mental health is increasing . there are some reports of existence of mental disorders such as anxiety , depression , aggression , low self esteem , suicidal thoughts and attempts in patients with acne vulgaris . in some studies , increase of prevalence of anxiety in patients with acne and positive relationship between severity of anxiety and severity of acne are reported.[357 ] however , in some other studies , no relationship between acne and anxiety is seen or the severity of anxiety and depression was not related to the severity of acne clinically . some studies reported that anxiety and depression are not correlated with age and sex , but some studies reported that these disorders are more prevalent in women . in one study , among 16 cases of reported suicide in skin disease , seven cases were due to acne . in kellet study on 34 patients with acne , using hospital anxiety and depression scale ( hads ) questionnaire , depression and anxiety score in these patients were more than in patients with psoriasis and cancer and mental disorders were more in women . considerable clinical depression and anxiety were present in 18 and 44% of the patients , respectively . yazici et al . performed a study on 61 patients with acne , using hospital anxiety and depression score ( hads ) , dermatology life quality index ( dlqi ) , acne quality of life ( aqol ) , global acne grading system ( gags ) , and it was found that amount of anxiety and depression in patients group were respectively 0 and 7.9% ( p=0.001 , p=0.011 respectively . because some confirmed psychological disorders in patients with acne , we decided to evaluate the prevalence of anxiety depression in comparison to healthy people . in this cross - sectional study , 82 patients with acne vulgaris and 82 healthy companions ( with no acne ) at the age of 1430 , who referred to razi hospital skin clinic and a specific office for skin disease in rasht , were enrolled into the study . inclusion criterion was the diagnosis of acne including presence of white head comedo and black head comedo , papule , pustule , pseudocyst and scar , and all individuals between 14 and 30 years old individuals accepted and signed our agreement based on helsinki contract . exclusion criteria were : ( 1 ) patients or healthy individuals with history of a known mental disorder ; ( 2 ) patients with somatic diseases such as heart , pulmonary and joint diseases , diabetes and epilepsy that affect their mental status ; ( 3 ) patients who used topical or systemic medicines disposing acne during one month before refer for acne ; these medicines included anabolic steroids , corticosteroids ( topical , oral , injection ) , corticotropin , phenytoin , phenobarbital , lithium , isoniazid , iodides , bromides , cyclosporin , and azathiopreine . hads questionnaire was completed by both groups and their anxiety score(had - a ) and depression score ( had - d ) were calculated . severity of acne was identified in patients and data were analyzed by spss ver 14.0 software . mean of anxiety and depression scores in two groups of being less and more than 20 years old , men and women , married and single patients and healthy individuals were compared between two groups by t - test and different levels of anxiety and depression frequency were compared by chi - square test . to adjust the confounding effect of age , sex , marital status , severity of acne , and scar of it on anxiety and depression scores , we used multivariate evaluated using analysis of covariance t -test . hads questionnaire includes 14 questions ( seven questions related to anxiety and seven questions related to depression ) [ figure 1 ] and each question scores 0 to 3 depending on the severity of the problem . summing anxiety score , had - a(anxiety subscale ) , and summing depression scores , had - d ( depression subscale ) were achieved . frequency distribution of anxiety and depression level in two groups of study hads interpretation : 0 - 7 scores : normal ; 8 - 10 scores : mild ; 11 - 14 score : moderate ; 15 - 21 scores : severe . internal consistency according to -chronbach for persian copy of hads questionnaire based on montazeri et al . study for had - d and had - a is 0.86 and 0.78 , respectively . gags is a simple , accurate , fast method for the determination of severity of acne , and it requires no special equipment and is relatively cost - effective . its personal and interpersonal differences is low and it was first used by doshi and his colleagues in 1997 in usa . patients group included 82 patients ( 26 men and 56 women ) with the age range of 20.46 - 21.97 years and mean age of 21.22 years and control group included 82 patients with the age range of 21.08 - 22.82 years and mean age of 21.95 years . there was no significant difference between two groups in sex , age , and marital status . among 82 patients with acne , 38 cases were with mild acne ( 46.3% ) , 37 cases were with moderate acne ( 45.2% ) , and seven cases were with severe acne ( 8.5% ) [ table 1 ] . demographic characteristics of two groups characteristics anxiety was seen in 68.3% of the patients and depression was seen in 25.6% of the patients . there was a significant difference in anxiety prevalence between patients group and control groups ( p < 0.001 ) . mean scores of anxiety and depression were 9.26 0.382 and 7.10 0.339 , respectively , and mean score of anxiety was more in patients group than control group ( p = 0.001 ) [ table 2 part 1 ] . frequency distribution of anxiety and depression scores in two group by demographic variables prevalence and mean scores of anxiety and depression had no relationship with severity of acne and sex , age , marital status , and scar of acne ( using analysis of covariance test ) [ table 1 ] . in patients group , there was no significant difference in incidence of anxiety and depression and mean of their scores between women and men , married people and single ones , and two groups of being 20 years old and > 20 years old . severity of anxiety and depression was not related to the severity of acne and its scar [ table 2 part 2 ] . in different studies , presence of some mental disorders in patients with acne was reported , including low self esteem , avoidance , hastiness and anxiety , depression , shame , suicidal thoughts and attempts , and difficulties in applying for a job . prevalence of anxiety and depression in patients with acne is different in some studies . in our patients , prevalence of anxiety was 68.3% in acne patients which show a significant difference with control group ( p<0.001 ) . considerable clinical anxiety ( moderate to severe had - a10 ) was 39% in patients group and 13.5% in control group with a significant difference ( p = 0.001 ) . this result was similar to those of yazici et al . study . in turkey in which hads was used to determine anxiety and depression.[24 ] in our study , depression was seen in 25.6% of the patients with no significant difference with control group . this result was similar to those of aktan , niemerir , and yazici study and is contrast to the results of some studies in which there was a positive relationship between severity of acne and severity of anxiety and depression . also , the severity of anxiety and depression was not related to age , sex , marital status , and scar of acne . these results were contrast to the results of some studies in which prevalence of anxiety and depression was more in women than men . psychosocial problems such as low self esteem , anxiety and depression , and decrease in social relationships in patients with acne are considered to be due to disorder of self body image . in self - body image , some parts of the body including face play an important role . existence of even a minor lesion in this part may be unpleasant for the patient and seems large . this image can cause mental disorders including depression and anxiety , low self esteem , and decrease in social relationships . improvement in mental disorders following treatment of acne , specially oral isotretinoin , has been reported in patients with acne along with the improvement of self body image . according to existence of some mental disorders in patients with acne , independent of age , sex , marital status , severity of acne and its scar , evaluation and screening of these disorders in all patients with acne who referred for treatment are suggested . this can be done by simple questionnaires such as hads with high sensitivity and specificity , which is not very time consuming . these questionnaires can be used as a tool to evaluate the effect of treatment besides clinical signs . studies in the field of evaluation of the effect of different treatments of acne using these questionnaires are suggested .

background : acne vulgaris is a chronic inflammatory disease of the pilosebaceous units , which chiefly involves face and upper part of the trunk . its prevalence is highest in adolescence , where the individual counters several psychosocial changes . depression , suicidal thoughts , and low self esteem are reported in the patients with this disease.aim:the goal of this study is to compare prevalence of anxiety and depression in the patients with acne vulgaris and normal population.materials and methods : in this cross - sectional study , 82 patients with acne vulgaris and 82 persons without acne who referred to a dermatology clinic and a specialized office for skin diseases in rasht were studied . anxiety and depression were evaluated by hospital anxiety and depression scale ( hads ) questionnaire and severity of acne was evaluated by global acne grading system ( gags ) . data were analyzed by spss ver . 14.0 software , independent t - test , multi variate analysis of covariance ( mancova ) and chi - square test for comparison the quantitative and ordinal data , respectively ; with =0.05.results : prevalence of anxiety and mean of anxiety scores were 68.3% and 9.17 3.52 , respectively , in patients group and 39.1% and 7.10 3.07 , respectively , in control group in which there was a significant difference ( p = 0.001 ) . prevalence of depression and mean of depression scores were 25.6% and 5.34 3.29 , respectively , in patients group and 28.1% and 5.01 3.32 , respectively , in control group in which there was no significant difference.conclusion:according to high prevalence of anxiety in patients with acne vulgaris , assessment of the screening mental status of the patients by simple questionnaire such as hads is suggested .

a 43 year - old female patient with american society of anesthesiologists ( asa ) physical status i was diagnosed with uterine myoma and was scheduled to undergo total laparoscopic hysterectomy . the patient was 160 cm tall and weighed 63 kg with no unusual medical history , and in the preoperative laboratory tests , her mean corpuscular hemoglobin concentration was 7.5 g / dl . premedication was not used , and upon arrival in the operating room , an electrocardiogram , pulse oximeter , and non - invasive blood pressure monitor were attached . before anesthesia , blood pressure was 150/90 mmhg ; heart rate was 90 beat / min , and peripheral oxygen saturation was 100% . glycopyrrolate ( 0.1 mg ) and propofol ( 120 mg ) were iv injected , and while conducting mask ventilation with o2 , rocuronium ( 5 l / min , 50 mg ) was iv injected . the patient was intubated and anesthesia was maintained with sevoflurane ( 1 - 2 vol% ) , o2 ( 2 l / min ) , and no2 ( 2 l / min ) . breathing was controlled to a tidal volume of 600ml and the breathing rate was 10 /min . co2 was inserted into the abdominal cavity until the intra - abdominal pressure became 13 mmhg and the hysterectomy was done . two units of concentrated red blood cells were transfused and there were no abnormalities with blood pressure at 120/80 mmhg , heart rate at 10 beats / min , and 99% peripheral oxygen saturation . two hours after inducing anesthesia , 5 ml of indigo carmine was slowly iv injected to identify the ureter . one minute later the etco2 fell from 33 mmhg to 12 mmhg ; blood pressure became 60/40 mmhg ; peripheral oxygen saturation fell to 89% , and patient displayed bradycardia and then asystole on the ecg . one milligram of epinephrine was iv injected ; chest compressions were given , and the right radial artery was punctured and a catheter inserted to continually monitor the arterial pressure . the pulse recovered , but the patient 's state did not improve so 1 mg of epinephrine was administered 3 more times over 20 minutes . a ph of 7.095 was measured by the arterial blood gas analysis so 60 ml of 8.4% sodium bicarbonate was iv injected ( table 1 ) . twenty minutes after cardiac arrest , blood pressure was 65/50 mmhg ; peripheral oxygen saturation was 72% ; etco2 was 18 mmhg , and dopamine was infused at 20 g / kg / min to maintain blood pressure . atropine ( 0.5 mg ) , epinephrine ( 1 mg ) was injected , and 20 ml of 8.4% sodium bicarbonate was injected because a ph of 7.204 was measured by the arterial blood gas analysis . forty minutes after cardiac arrest , the patient 's status improved with a blood pressure of 70/40 mmhg , peripheral oxygen saturation of 100% , and etco2 of 38 mmhg , and spontaneous breathing commenced . the patient 's vital signs normalized so the surgery was completed ; muscle relaxation was reversed with intravenous injection of glycopyrrolate ( 0.4 mg ) and pyridostigmine ( 10 mg ) , and the patient was transferred to the intensive care unit with intubation . in the icu , the blood pressure was 90/50 mmhg ; heart rate was 100 beats / min ; o2 ( 5 l / min ) was administered through the endotracheal tube , and mental status was not restored . there were no abnormalities in the brain ct , but in the brain mri taken on the second postoperative day , there were bilateral infarctions in the subcortical white matter in the parieto - occipital lobe ( fig . 1 ) . on the third postoperative day , the peripheral oxygen saturation did not rise more than 88% even though o2 was administered at 10 l / min so controlled mandatory ventilation was done . on the seventh postoperative day , mechanical ventilation was stopped . twenty days after surgery , the patient was extubated , and on the twenty - fifth postoperative day , the patient 's mental status recovered , but there was motor weakness in the left arm and visual disturbance with difficulty in the lateral gaze . three months after surgery , the patient recovered from motor weakness and visual disturbance . the patient is currently hospitalized for rehabilitation . indigo carmine has been used widely and safely for iv injection , but there are rare cases of complications reported . arterial pressure can rise from an increase in peripheral vascular resistance while bradycardia may be a reflex response from circulatory baroreceptors , and cardiac output can decrease . decreased cardiac output occurs due to increased afterload and reflex bradycardia . an increase in the mean arterial pressure and total peripheral resistance and a decrease in the cardiac output and cardiac rate with essentially no change in the stroke volume are a typical response to alpha receptor stimulation . the molecular structure of indigo carmine resembles two molecules of serotonin arranged as if one is a mirror image of the other ( fig . 2 and 3 ) . increase in blood pressure and tachycardia that arises from such similarity with the serotonin structure has been reported , but it is very rare to cause severe hypotension and cerebral infarction as in our case . there is a case report of severe hypotension after intravenous indigo carmine in a patient undergoing radical prostatectomy under epidural anesthesia . indigo carmine has both the effects of a stimulant and a depressant ; however , in that case , the commonly observed effect as a stimulant was prevented by the epidural anesthesia thus , leaving the depressant component of the drug unmasked and causing a decline in blood pressure . however , in our case , epidural anesthesia was not done so this hypothesis does not explain what happened . hypovolemia , which is commonly considered as a cause for hypotension , can also be excluded because there was no heavy blood loss , and the patient 's fluids were adequately replaced . reaction to transfused blood was also considered , but the accuracy of the cross - matching was verified , and the clinical signs of mismatched transfusion such as fever , increased heart rate , and renal failure were not evident . in addition , since the temporal relationship between the time of induction and the onset of hypotension did not correspond with each other , it suggests that the probability of this factor is low . other than these , neuromuscular blocking agents such as atracurium can cause the release of histamine and secondary vasodilation or hypotension in poorly controlled diabetes mellitus but does not apply in our case . in our case , it is assumed that the insertion of indigo carmine and hypotension are clearly related because there were no other factors to cause hypotension and because the blood pressure dropped abruptly within 1 minute of injection . in a case where severe hypotension , bronchospasm , and urticaria occurred from intravenous indigo carmine , an anaphylactic reaction with resultant hemodynamic collapse was seen to be the cause of hypotension but given her lack of prior allergies or atopy , or prior exposure to indigo carmine , it is unlikely that the patient had a true , immunoglobulin e - mediated anaphylactic reaction . therefore , it was assumed that the patient had an idiosyncratic reaction or anaphylactoid reaction to the dye ; in other words , a non - immunological reaction , possibly by means of histamine release or other mediators . a domestic case report also considered idiosyncratic anaphylactoid reaction as the cause for blood pressure decline where hypotension occurred without concurrent anaphylactic signs such as cutaneous erythema , rash , laryngeal edema , or bronchospasm . coronary vasospasm has previously been associated with allergic anaphylactoid reactions and may be a possible explanation for the reversible myocardial dysfunction that developed . the sodium bicarbonate administered for the correction of acidemia can temporarily increase the ph but can have an ill - effect on acid - base balance and the hemodynamic state by decreasing the supply of oxygen to tissues due to an increase in co2 in the body , an increase in hypocalcaemia and hyperosmolality , and the formation of lactate as well as left movement of the oxygen dissociation curve . therefore , the increase in etco2 and decrease in ionized calcium occurred from the administration of sodium bicarbonate when the ph was lower than 7.25 ; thus , suitable pulmonary ventilation and enhancement of the blood circulation using fluids and medication is thought to be more effective than sodium bicarbonate . it is inferred that cerebral ischemia is caused by an insufficient supply of oxygen , embolism , or thrombus from hypotension ; however , indigo carmine - induced hypertension has been reported to be a result of interference with the nitric oxide - mediated vasodilatory mechanism and direct vasoconstriction with spasm of the cerebral arteries . in addition , a gas embolism within the artery may have been formed from the absorption of co2 into the abdominal organs from the laparoscopy or absorption of gas bubbles created from the galvanocautery during the hysteroscopy . twenty to thirty percent of normal adults have patent foramen ovale , and through this foramen ovale , a right to left shunt can be formed to cause paradoxical embolism and this can cause embolisms in the cerebral or coronary artery . in our case , there were no ekg changes upon arrival in the icu , and the timing of the occurrence of hypotension was not in the early stages of the laparoscopy where gas embolisms frequently occur but near the end of the surgery directly after the injection of indigo carmine so the possibility is low . the visual disturbance was cortical blindness from cortical ischemia , which occurs when there are barriers in the geniculocalcarine visual pathway . this occurrence is very rare and can be critical , but the symptoms may improve . in conclusion , indigo carmine is used widely and safely as an intravenous dye , but severe hypotension can occur besides the relatively common complications of increased blood pressure and brachycardia . when complications occur , careful observation of manifestations of neurological abnormalities is necessary even after the surgery is complete .

indigo carmine ( sodium indigotindisulfonate ) is a safe , biologically inactive blue dye routinely administered intravascularly during urologic and gynecologic procedures to localize the ureteral orifices and to identify severed ureters and fistulous communications . we report a case of hypotension , cardiac arrest , and cerebral ischemia after the administration of indigo carmine in a patient under total laparoscopic hysterectomy .

xenopus laevis cdna corresponding to the following fragment of nup107 - 160 and -turc components were sub - cloned into bacterial expression vector pet28a+ for bacterial expression : nup160 ( aa 1100 - 1400 ) , nup133 ( aa 865 - 1138 ) , nup107 ( aa 216 - 516 ) , nup96 ( aa 679 - 924 ) , nup85 ( aa 352 - 653 ) , sec13 ( aa 1 - 320 ) , seh1 ( aa 195 - 360 ) , elys ( aa 2106 - 2408 ) , gcp2 ( aa 1 - 260 ) and nedd1 ( aa 351 - 651 ) . proteins were expressed in e. coli bl21 ( de3 ) cells . except for xnedd1 and xsec13 , insoluble proteins were purified from inclusion body and gel bands were used for immunizing rabbits . antibodies against human nup160 ( aa 994 - 1316 ) and human gcp2 ( aa 286 - 486 ) were also raised similarly . to affinity purify antibodies , the recombinant fragments were solubilized in urea and cross - linked to nhs - sepharose beads . in supplementary information , crest sera were a gift from i. ouspensky ( national institutes of health , bethesda , md ) . 500 g of control igg or indicated antibodies were immobilized on protein a sepharose beads and cross - linked with 5 mg ml of dimethyl pimelidate ( dmp ) in 0.2 m triethanolamine ( ph=8.3 ) . s2b , csf xees containing sperm chromatin were driven into interphase by addition of 0.6 mm cacl2 . after 60 minutes at room temperatures , csf arrest was reinstated through addition of 0.5 volumes of fresh csf extract , with simultaneous addition of 0.04 mg ml nocodazole . reactions were diluted 10-fold in dilution buffer 1 ( 0.8x csf - xb , 250 mm sucrose ) and fixed with an equal volume of fixation buffer ( 4% formaldehyde in dilution buffer 1 ) for 30 minutes . the chromatin was spun onto coverslips through 40% glycerol cushion ( in csf - xb and 0.1% triton x-100 ) and post - fixed in chilled methanol for 5 minutes . the coverslips were re - hydrated in 0.1% triton x-100 containing pbs and processed for immunofluorescence as described elsewhere29 . 25 g anti - xnup160 , anti - xgcp2 antibodies or non - specific rabbit igg controls were bound to 100 l magnetic beads , crosslinked , and incubated in csf xees for 90 minutes at 25c with rotation . the beads were separated from the extract , washed three times with cold csf - xb and once with brb80 . 15 l beads containing proteins precipitated from xees by anti - xnup160 , anti - xgcp2 antibodies or non - specific rabbit igg controls were incubated at 37c for 10 minutes in reactions containing 30 m unlabeled tubulin and 5 mm gtp . the samples were fixed with 1% glutaradehyde for 5 minutes , diluted 5-fold with 60% glycerol in brb80 29 and spun through 25% glycerol cushion in brb80 at 6,000 rpm for 6 minute at room temperature . the beads were once washed with brb80 , resuspended and spread onto coverslips and processed for immunofluorescence with anti--tubulin antibodies14 . in fig . 4c , beads were incubated in csf xees that contained buffer or 0.2 mg ml of ranq69l , rant24n or importin- , as indicated . 293 t and hela cells were maintained in dmem medium with 10% fetal calf serum ( dmem complete medium ) and 5% co2 at 37c . , cells were grown on coverslips and tranfected using lipofectamine sirna max or oligofectamine reagents ( invitrogen ) with oligonucleotides directed against nup160 ( aac gag gac agt tct gca ttt ) , gcp2 ( set of 3 sirna oligo s for gcp2 from invitrogen ) or control oligonucleotides ( aac tgt cag tca gtc gta gta ) . all oligonucleotides were obtained from qiagen , except gcp2 oligonucleotides were from invitrogen . in fig . s2a , hela cells were incubated in 0.1 g ml of nocodazole in dmem complete medium for 16hrs at 37c . for immunofluorescence , cells were permeabilized with phem buffer for 5 minutes , followed with fixation for 15 minutes with 4% formaldehyde in pbs . in fig . 3 , 0.1 g ml of nocodazole in dmem complete medium was added 56 hours after transfection , and incubation was continued for 16 hours at 37c . the nocodazole - containing medium was removed , and the cells were washed twice with cold complete dmem medium , with further incubation in dmem medium for 45 minutes on ice . the medium was replaced with fresh 37c complete dmem medium and incubation was continued at 37c for 2 minutes . cells were permeabilized with phem buffer for 5 minutes , followed with fixation for 5 minutes with 4% formaldehyde in brb80 and for 10 minutes with 4% formaldehyde in pbs . xenopus laevis cdna corresponding to the following fragment of nup107 - 160 and -turc components were sub - cloned into bacterial expression vector pet28a+ for bacterial expression : nup160 ( aa 1100 - 1400 ) , nup133 ( aa 865 - 1138 ) , nup107 ( aa 216 - 516 ) , nup96 ( aa 679 - 924 ) , nup85 ( aa 352 - 653 ) , sec13 ( aa 1 - 320 ) , seh1 ( aa 195 - 360 ) , elys ( aa 2106 - 2408 ) , gcp2 ( aa 1 - 260 ) and nedd1 ( aa 351 - 651 ) . proteins were expressed in e. coli bl21 ( de3 ) cells . except for xnedd1 and xsec13 , insoluble proteins were purified from inclusion body and gel bands were used for immunizing rabbits . antibodies against human nup160 ( aa 994 - 1316 ) and human gcp2 ( aa 286 - 486 ) were also raised similarly . to affinity purify antibodies , the recombinant fragments were solubilized in urea and cross - linked to nhs - sepharose beads . in supplementary information , crest sera were a gift from i. ouspensky ( national institutes of health , bethesda , md ) . 500 g of control igg or indicated antibodies were immobilized on protein a sepharose beads and cross - linked with 5 mg ml of dimethyl pimelidate ( dmp ) in 0.2 m triethanolamine ( ph=8.3 ) . s2b , csf xees containing sperm chromatin were driven into interphase by addition of 0.6 mm cacl2 . after 60 minutes at room temperatures , csf arrest was reinstated through addition of 0.5 volumes of fresh csf extract , with simultaneous addition of 0.04 mg ml nocodazole . reactions were diluted 10-fold in dilution buffer 1 ( 0.8x csf - xb , 250 mm sucrose ) and fixed with an equal volume of fixation buffer ( 4% formaldehyde in dilution buffer 1 ) for 30 minutes . the chromatin was spun onto coverslips through 40% glycerol cushion ( in csf - xb and 0.1% triton x-100 ) and post - fixed in chilled methanol for 5 minutes . the coverslips were re - hydrated in 0.1% triton x-100 containing pbs and processed for immunofluorescence as described elsewhere29 . 25 g anti - xnup160 , anti - xgcp2 antibodies or non - specific rabbit igg controls were bound to 100 l magnetic beads , crosslinked , and incubated in csf xees for 90 minutes at 25c with rotation . the beads were separated from the extract , washed three times with cold csf - xb and once with brb80 . 15 l beads containing proteins precipitated from xees by anti - xnup160 , anti - xgcp2 antibodies or non - specific rabbit igg controls were incubated at 37c for 10 minutes in reactions containing 30 m unlabeled tubulin and 5 mm gtp . the samples were fixed with 1% glutaradehyde for 5 minutes , diluted 5-fold with 60% glycerol in brb80 29 and spun through 25% glycerol cushion in brb80 at 6,000 rpm for 6 minute at room temperature . the beads were once washed with brb80 , resuspended and spread onto coverslips and processed for immunofluorescence with anti--tubulin antibodies14 . in fig . 4c , beads were incubated in csf xees that contained buffer or 0.2 mg ml of ranq69l , rant24n or importin- , as indicated . 293 t and hela cells were maintained in dmem medium with 10% fetal calf serum ( dmem complete medium ) and 5% co2 at 37c . , cells were grown on coverslips and tranfected using lipofectamine sirna max or oligofectamine reagents ( invitrogen ) with oligonucleotides directed against nup160 ( aac gag gac agt tct gca ttt ) , gcp2 ( set of 3 sirna oligo s for gcp2 from invitrogen ) or control oligonucleotides ( aac tgt cag tca gtc gta gta ) . all oligonucleotides were obtained from qiagen , except gcp2 oligonucleotides were from invitrogen . in fig . s2a , hela cells were incubated in 0.1 g ml of nocodazole in dmem complete medium for 16hrs at 37c . for immunofluorescence , cells were permeabilized with phem buffer for 5 minutes , followed with fixation for 15 minutes with 4% formaldehyde in pbs . in fig . 3 , 0.1 g ml of nocodazole in dmem complete medium was added 56 hours after transfection , and incubation was continued for 16 hours at 37c . the nocodazole - containing medium was removed , and the cells were washed twice with cold complete dmem medium , with further incubation in dmem medium for 45 minutes on ice . the medium was replaced with fresh 37c complete dmem medium and incubation was continued at 37c for 2 minutes . cells were permeabilized with phem buffer for 5 minutes , followed with fixation for 5 minutes with 4% formaldehyde in brb80 and for 10 minutes with 4% formaldehyde in pbs .

the metazoan nuclear pore complex ( npc ) disassembles during mitosis , and many of its constituents distribute onto spindles and kinetochores , including the nup107 - 160 sub - complex1,2 . we have found that nup107 - 160 interacts with the -tubulin ring complex ( -turc ) , an essential and conserved microtubule ( mt ) nucleator3,4 , and recruits -turc to unattached kinetochores . unattached kinetochores nucleate mts in a manner that is regulated by the ran gtpase5 ; such mts contribute to the formation of kinetochore fibers ( k - fibers)6 , mt bundles connecting kinetochores to spindle poles . our data indicate that nup107 - 160 and -turc act cooperatively to promote spindle assembly through mts nucleation at kinetochores : hela cells lacking nup107 - 160 or -turc were profoundly deficient in kinetochore - associated mt nucleation . moreover , co - precipitated nup107 - 160/-turc complexes nucleate mt formation in assays using purified tubulin . while ran did not regulate mts nucleation by -turc alone , nup107 - 160/-turc complexes required ran - gtp for mt nucleation . our observations collectively show that nup107 - 160 promotes spindle assembly through ran - gtp - regulated nucleation of mt by -turc at kinetochores , and reveal a novel relationship between nucleoporins and the mt cytoskeleton .

of 5,208 randomly selected participants aged 1875 years from the prevalence , prediction , and prevention of diabetes ( ppp)-botnia study ( 2 ) , representing the adult population residing in the botnia region of western finland , 206 individuals with previously diagnosed and 100 individuals with newly diagnosed diabetes were excluded , as were 36 individuals using antipsychotic medications and 5 using lithium . this resulted in a sample of 4,419 participants ( 2,095 men and 2,324 women ) with complete data . those with incomplete data ( n = 442 ) were older , were more likely to be retired , and consumed less alcohol compared with those with the complete data . the participants gave their written informed consent , and the study protocol was approved by the ethics committee of helsinki university central hospital , finland . during an oral glucose tolerance test ( ogtt ) ( 75 g of glucose after a 12-h overnight fast ) , venous samples for plasma glucose ( dehydrogenase method ; hemocue , ngelholm , sweden ) and insulin ( fluoroimmunoassay , delphia ; perkin - elmer finland , turku , finland ) were drawn at 0 , 30 , and 120 min ( [ means sd ] 5.3 0.6 , 8.3 1.5 , and 5.2 1.6 mmol / l and 6.6 5.6 , 59.7 37.9 , and 33.1 35.6 u / ml , respectively ) . the homeostasis model assessment of ir ( homa - ir ) ( 12 ) and corrected insulin response ( cir ) ( 13 ) were calculated . depressive symptoms were self - rated using the short - form 36/rand-36 ( 14 ) . we used the mental health index ( mhi ) , the vitality scale ( vs ) , and their sum ( 20.0 6.7 , 9.8 3.7 , and 10.2 3.7 , respectively ) to capture depressive symptoms . the rationale for calculating the sum was based on a finnish validation study concluding that the vs items also characterize aspects of depression in a finnish population ( 15 ) . in the current study , the mhi and vs were significantly correlated ( r = 0.70 , p < 0.001 ) . we considered self - reported current use of ssri / serotonin - norepinephrine reuptake inhibitor medication ( n = 98 ) , tricyclic medication ( n = 36 ) , tricyclic and ssri / serotonin - norepinephrine reuptake inhibitor medication ( n = 10 ) , and antidepressant medications not specified ( n = 3 ) as an indicator of the use of antidepressant medications ( n = 147 , 110 women and 37 men ) . logistic regression analyses , odds ratios ( ors ) , and 95% cis were computed to examine associations with homa - ir and cir as dichotomized ( top / bottom quartiles vs. the other three ) . associations were adjusted first for sex and age and then additionally for regular exercise ( yes : > 30 min intense physical activity three or more times per week resulting in breathlessness / sweating vs. no : less or no activity ) , alcohol consumption ( grams per week ) , current smoking status ( yes vs. no or former smoker ) , bmi ( kg / m ) , occupational status ( manual workers , junior clericals , senior clericals , students , and retirees ) , and family history of diabetes in at least one first - degree relative . modulation by antidepressant medication use was examined by entering the interaction term depressive symptoms antidepressant medication use into the regression equation followed by the main effects . because we found no significant sex - interaction terms ( all p values > 0.26 ; data not shown ) , we report the results in both sexes combined . during an oral glucose tolerance test ( ogtt ) ( 75 g of glucose after a 12-h overnight fast ) , venous samples for plasma glucose ( dehydrogenase method ; hemocue , ngelholm , sweden ) and insulin ( fluoroimmunoassay , delphia ; perkin - elmer finland , turku , finland ) were drawn at 0 , 30 , and 120 min ( [ means sd ] 5.3 0.6 , 8.3 1.5 , and 5.2 1.6 mmol / l and 6.6 5.6 , 59.7 37.9 , and 33.1 35.6 u / ml , respectively ) . the homeostasis model assessment of ir ( homa - ir ) ( 12 ) and corrected insulin response ( cir ) ( 13 ) were calculated . depressive symptoms were self - rated using the short - form 36/rand-36 ( 14 ) . we used the mental health index ( mhi ) , the vitality scale ( vs ) , and their sum ( 20.0 6.7 , 9.8 3.7 , and 10.2 3.7 , respectively ) to capture depressive symptoms . the rationale for calculating the sum was based on a finnish validation study concluding that the vs items also characterize aspects of depression in a finnish population ( 15 ) . in the current study , the mhi and vs were significantly correlated ( r = 0.70 , p < 0.001 ) . we considered self - reported current use of ssri / serotonin - norepinephrine reuptake inhibitor medication ( n = 98 ) , tricyclic medication ( n = 36 ) , tricyclic and ssri / serotonin - norepinephrine reuptake inhibitor medication ( n = 10 ) , and antidepressant medications not specified ( n = 3 ) as an indicator of the use of antidepressant medications ( n = 147 , 110 women and 37 men ) . logistic regression analyses , odds ratios ( ors ) , and 95% cis were computed to examine associations with homa - ir and cir as dichotomized ( top / bottom quartiles vs. the other three ) . associations were adjusted first for sex and age and then additionally for regular exercise ( yes : > 30 min intense physical activity three or more times per week resulting in breathlessness / sweating vs. no : less or no activity ) , alcohol consumption ( grams per week ) , current smoking status ( yes vs. no or former smoker ) , bmi ( kg / m ) , occupational status ( manual workers , junior clericals , senior clericals , students , and retirees ) , and family history of diabetes in at least one first - degree relative . modulation by antidepressant medication use was examined by entering the interaction term depressive symptoms antidepressant medication use into the regression equation followed by the main effects . because we found no significant sex - interaction terms ( all p values > 0.26 ; data not shown ) , we report the results in both sexes combined . the sample age averaged 48.5 15.4 years , 52.6% were women , and the average bmi was 26.3 4.3 kg / m . a total of 54.7% of subjects reported regular exercise ; 14.7% reported smoking ; 46.4 and 28.1% reported a weekly alcohol consumption of 1260 g and > 60 g , respectively ; and 28.6 reported having a family history of diabetes . in addition , 17.4% of subjects were of senior clerical , 30.2% were of junior clerical , and 26.1% were of manual worker occupational status , whereas 21.8% were retired and 4.6% were students . depressive symptoms were associated with increased odds for antidepressant medication use ( total score : or 2.64 [ 95% ci 2.223.13 ] ; mhi : 2.42 [ 2.052.85 ] ; and vs : 2.52 [ 2.103.02 ] per each sd unit increase in symptoms ) . antidepressant medication use was significantly associated with a higher odds for belonging to the top quartile of homa - ir but not with cir ( table 1 ) or with insulin and glucose values during an ogtt ( supplementary table a1 ) in models adjusted for confounding and mediating factors . associations between depressive symptoms , the use of antidepressant medications , and homa - ir and cir as indices of ir and secretion data are or ( 95% ci ) . * homa - ir was dichotomized contrasting the highest quartile ( referent ) with the other three quartiles , n = 1,105 vs. 3,314 . cir was dichotomized contrasting the lowest quartile ( referent ) with the other three quartiles , n = 1,104 vs. 3,315 . full model refers to adjustments for age , sex , regular exercise ( yes : > 30 min intense physical activity three or more times per week resulting in breathlessness / sweating vs. no : less or no activity ) , alcohol consumption ( grams per week ) , current smoking status ( yes vs. no or former smoker ) , bmi ( kg / m ) , occupational status ( manual workers , junior clericals , senior clericals , students , and retirees ) , and family history of diabetes in at least one first - degree relative . although depressive symptoms were significantly associated with higher odds for belonging to the top quartile of homa - ir ( table 1 ) , with higher fasting and 30-min insulin ( supplementary table a1 ) , they were not associated with cir ( table 1 ) in models adjusted for confounding and mediating factors . analyses addressing interactions between antidepressant medication use and depressive symptoms showed that depressive symptoms were associated with higher 120-min glucose in participants using antidepressants ( total score : 5.6% increase [ 95% ci 0.810.5 ] , p = 0.02 , and vs : 5.9% [ 0.0811.0 ] , p = 0.02 , per sd unit increase in symptoms ) . in contrast , the associations were not significant in those who were not using antidepressants ( p values > 0.24 ) ( p values < 0.05 for antidepressant medication use depressive symptoms interactions ) . the current study examined the associations between depressive symptoms and ir and insulin secretion in a large , population - based sample of adult men and women without previously or newly diagnosed diabetes . depressive symptoms were associated with higher odds for being insulin resistant but not with changes in insulin response when corrected for ir ( cir ) . these associations were not modulated by antidepressant medication use . taken together , our findings suggest that depressive symptoms are associated with ir , even in individuals without diabetes , and that the use of antidepressant medications may neither augment nor explain these effects . although our study was cross - sectional , constituting an obvious and major study limitation , the fact that the associations characterized participants without diagnosed diabetes suggests that depressive symptoms should be regarded as a clinically important risk factor for both metabolic syndrome and type 2 diabetes . thus , the detection and prevention of depressive symptoms are of importance in everyday clinical practice . additional study limitations include a lack of opportunity to address potential mechanisms underlying the reported associations , generalizability from our findings to non - whites , a lack of information regarding psychiatric disorders and/or the duration of antidepressant medication use , and the low prevalence of antidepressant medication use , which may have attenuated our ability to detect stronger associations , thereby limiting generalizability from the findings to less healthy populations . in conclusion , depressive symptoms are associated with ir but not with changes in insulin response when corrected for ir in individuals without diabetes . thus , the detection of individuals with higher depressive symptoms may benefit programs of early prevention of type 2 diabetes and related disorders .

objectivealthough insulin resistance ( ir ) may underlie associations between depressive symptoms and diabetes , previous findings have been contradictory . we examined whether depressive symptoms associate with ir and insulin secretion , and , additionally , whether antidepressant medication use may modulate such associations.research design and methodsa total of 4,419 individuals underwent an oral glucose tolerance test ( ogtt ) . participants with previously or newly diagnosed diabetes are excluded from this sample . the homeostasis model assessment of ir ( homa - ir ) and corrected insulin response ( cir ) were calculated . depressive symptoms and antidepressant medication use were self-reported.resultsafter controlling for confounding factors , depressive symptoms were associated with higher fasting and 30-min insulin during the ogtt and higher homa - ir but not cir . antidepressant medication use failed to modify these associations.conclusionsdepressive symptoms are associated with ir but not with changes in insulin response when corrected for ir in individuals without previously or newly diagnosed diabetes .

traditionally , most rna molecules were regarded as carriers conveying information from the gene to the translation machinery . the most prominent exceptions to this are transfer rna ( trna ) and ribosomal rna ( rrna ) , both of which are directly involved in the process of translation . however , since the late 1990s , it has been widely acknowledged that other types of non - protein - coding rna molecules are present in organisms ranging from bacteria to mammals , which affect a large variety of processes including plasmid replication , phage development , bacterial virulence , chromosome structure , dna transcription , rna processing and modification , development control and others ( 116 ) . these observations suggest that the traditional view of the structure of the genetic regulatory systems in organisms is far from complete . therefore , further research on non - protein - coding rna will give us a new framework for considering and understanding the genomic programming of biological complexity . however , the unsystematic naming of non - protein - coding rnas may be an impediment to effective research . the term small rnas ( srnas ) has been predominantly used for such rnas in bacteria , whereas the term non - coding rnas ( ncrnas ) has been the most common term for eukaryotic rnas of this kind ( 17,18 ) . to have a common term for all such rnas , we have opted to apply the term ncrna to all these functional rnas , irrespective of the realm of life in which they might appear . the understanding of the importance of ncrnas in basic cellular processes is ever increasing , and new members and classes of ncrnas are continuously being reported . thus , over the years , several databases have been established to collect , organize and classify ncrna sequences and information . some databases are intended to collect only certain category of ncrnas , such as srp rnas , tmrnas or rnase p rnas , whereas others , such as the small rna database , the non - coding rna database and the rfam database , have collected ncrnas of several categories ( 1924 ) . however , even in the latter kind of databases certain ncrna members or classes are missing . another problem with all the current databases is that the classification systems for ncrnas used nowadays are not uniform and only a few attempts have been made to integrate the various classification systems . in these classification systems , some ncrna groups are named according to cellular localizations , such as snrnas , snornas or scrnas , some are named according to functions , like prnas ( package rnas ) , grnas ( guide rnas ) or tmrnas ( transfer - messenger rnas ) , and others again are simply labeled according to their sedimentation coefficients ( 6s rna , 5.3s rna , etc . ) . furthermore , because of this lack of integration , one type of ncrna often appears under several names or in more than one category ( 7,12,2530 ) . noncode comprises almost all ncrnas now publicly available ( except trnas and rrnas ) that are either confirmed experimentally or predicted computationally . the first release of noncode ( v1.0 ) contains 5339 non - redundant sequences from 861 organisms , including eukaryotes , eubacteria , archaebacteria , virus and viroids . furthermore , to integrate existing classification systems , a new classification system labeled the process function class ( pfclass ) has been introduced , based on the cellular process and function in which a given ncrna is involved . pfclass provides a unified classification system and a concise functional annotation of ncrnas . according to the cellular process involved , the pfclass classification system is the first attempt of a unified classification system for ncrnas . it is our hope that this integrated system will help in clearing up the classification problem . in conclusion , the aim of the noncode database is to be a unified gateway to search , retrieve and update information about ncrnas in order to facilitate research on ncrnas , gene networks and functional genomics . through a user - friendly web interface at http://noncode.bioinfo.org.cn , genbank entries were the major source of data , and the pubmed database was used as the starting point for the data collection ( 31 ) . the publications that matched with these queries were then examined and the ncrna sequences were extracted from the obtained literature . by reading the filtered literature , a new set of ncrna keywords were gained and added into the keywords table . this new keywords table was used to filter the genbank bct , inv , mam , phg , pln , pri , rod , vrl and vrt divisions automatically , and the filtered result was then manually confirmed . all the data are integrated and organized in such a manner that users can efficiently query and browse information . one significant characteristic of noncode is its content of additional information on the ncrnas obtained from the related literature . ( i ) for each sequence filtered from genbank , we manually checked whether or not it represented an actual ncrna and assigned the confirmed sequence an accession number ( ncid , i.e. ncrna i d ) . ( ii ) basic information name , alias , length , organisms , references , etc.of confirmed sequences was collected from genbank . ( iii ) additional information concerning function , cellular role , cellular location , etc . each ncrna has also been annotated with one of the five specific mechanisms ( sequence base pairing , structural complementarity , spatial blocking , catalysis or epimodification ) , through which it exerts its function . ( iv ) according to our pfclass classification system , one or more of the 26 pfclasses were assigned to all ncrnas . moreover , a subset of 1114 ncrnas have been divided into nine additional categories according to whether they are specific to gender or tissue or associated with tumors and diseases , etc . ( v ) to visualize the location of an ncrna in the genome or in a specific dna fragment , along with regulatory elements in the flanking sequences , genbank annotations were used to create figures for all ncrnas . ( vi ) each ncrna sequence was checked for redundancies using perl scripts , and each cluster of redundant sequences was given a non - redundant accession number ( uniqid , i.e. unique ncrna i d ) . ( vii ) the secondary structures of non - redundant ncrna sequences were predicted using the vienna rna package ( 32 ) . ever since the beginning of ncrna research there has not been in place any integrated system for classification , and therefore , exists a considerable measure of confusion with respect to naming of ncrnas . therefore , when the noncode database was established it was carefully considered as how to establish classification criteria that might increase the usefulness of the database resource . the cellular process and function of an ncrna was chosen as the basic criterion for a unified classification system called pfclass in noncode . when labeled according to this system , each kind of ncrna is named after its cellular process and corresponding function . the actual category is given according to two or three levels of keywords connected by an underscore . the first keyword will be dna , rna or protein , representing a cellular process in which either of the three molecular types is a crucial component . the second keyword describes the actual process , and if the ncrna is involved in a complex process with several aspects , a third keyword may further indicate a more specific function of the ncrna . for example , the snrna u1 will be assigned to the pfclass rna_processing_splicing , and rnase p rnas to the pfclass rna_processing_cleavage ( for details see table 1 ) . the pfclass classification system represents the first attempt of a unified classification system for ncrnas . in the future , as our understanding of ncrnas deepen , and the content of noncode further expands , steps will be taken to further extend and perfect the pfclass system in order to increase its usefulness . to further harmonize the exchange of data between different systems , application of gene ontology ( go ) ( 33 ) annotation on our pfclass system will be considered . genbank entries were the major source of data , and the pubmed database was used as the starting point for the data collection ( 31 ) . the publications that matched with these queries were then examined and the ncrna sequences were extracted from the obtained literature . by reading the filtered literature , a new set of ncrna keywords were gained and added into the keywords table . this new keywords table was used to filter the genbank bct , inv , mam , phg , pln , pri , rod , vrl and vrt divisions automatically , and the filtered result was then manually confirmed . all the data are integrated and organized in such a manner that users can efficiently query and browse information . one significant characteristic of noncode is its content of additional information on the ncrnas obtained from the related literature . briefly , seven steps were carried out after the genbank screening . ( i ) for each sequence filtered from genbank , we manually checked whether or not it represented an actual ncrna and assigned the confirmed sequence an accession number ( ncid , i.e. ncrna i d ) . ( ii ) basic information name , alias , length , organisms , references , etc.of confirmed sequences was collected from genbank . ( iii ) additional information concerning function , cellular role , cellular location , etc . each ncrna has also been annotated with one of the five specific mechanisms ( sequence base pairing , structural complementarity , spatial blocking , catalysis or epimodification ) , through which it exerts its function . ( iv ) according to our pfclass classification system , one or more of the 26 pfclasses were assigned to all ncrnas . moreover , a subset of 1114 ncrnas have been divided into nine additional categories according to whether they are specific to gender or tissue or associated with tumors and diseases , etc . ( v ) to visualize the location of an ncrna in the genome or in a specific dna fragment , along with regulatory elements in the flanking sequences , genbank annotations were used to create figures for all ncrnas . ( vi ) each ncrna sequence was checked for redundancies using perl scripts , and each cluster of redundant sequences was given a non - redundant accession number ( uniqid , i.e. unique ncrna i d ) . ( vii ) the secondary structures of non - redundant ncrna sequences were predicted using the vienna rna package ( 32 ) . ever since the beginning of ncrna research there has not been in place any integrated system for classification , and therefore , exists a considerable measure of confusion with respect to naming of ncrnas . therefore , when the noncode database was established it was carefully considered as how to establish classification criteria that might increase the usefulness of the database resource . the cellular process and function of an ncrna was chosen as the basic criterion for a unified classification system called pfclass in noncode . when labeled according to this system , each kind of ncrna is named after its cellular process and corresponding function . the actual category is given according to two or three levels of keywords connected by an underscore . the first keyword will be dna , rna or protein , representing a cellular process in which either of the three molecular types is a crucial component . the second keyword describes the actual process , and if the ncrna is involved in a complex process with several aspects , a third keyword may further indicate a more specific function of the ncrna . for example , the snrna u1 will be assigned to the pfclass rna_processing_splicing , and rnase p rnas to the pfclass rna_processing_cleavage ( for details see table 1 ) . the pfclass classification system represents the first attempt of a unified classification system for ncrnas . in the future , as our understanding of ncrnas deepen , and the content of noncode further expands , steps will be taken to further extend and perfect the pfclass system in order to increase its usefulness . to further harmonize the exchange of data between different systems , application of gene ontology ( go ) ( 33 ) annotation on our pfclass system will be considered . till date , more than 10 000 sequences filtered from genbank by our in - house program have been manually examined . the current release ( v.1.0 ) of noncode contains a total of 6232 entries assigned to 26 pfclasses , and covers 109 traditional classes such as snrna , snorna , microrna and rnase p rna . basic information on each entry is provided , including accession number in genbank , traditional class , name , pfclass , organism , reference , uniqid ( accession number without redundancy in noncode ) and ncid ( accession number with redundancy in noncode ) , all of which can be used as keywords for data search . noncode also provides additional information on function and cellular role , cellular location , chromosomal information , alternative names , secondary structure and whether or not the ncrna has undergone splicing . each ncrna has also been annotated with one of the five specific mechanisms ( sequence base pairing , structural complementarity , spatial blocking , catalysis or epimodification ) , through which it exerts its function . figures showing genomic locations for all ncrnas and their regulatory elements have been included , and a subdivision into nine additional classes ( outside the pfclass system ) has also been applied to a number of ncrnas . noncode also offers an efficient search option , allowing recovery of sequence , related publications and other information . in the near future ( i ) for a number of ncrnas , information on function , location , etc . is still lacking , and this information will be completed as soon as it becomes available . ( ii ) as the information on ncrnas increases and the content of noncode further expands , the pfclass system will be further extended and perfected in order to increase its usefulness . go annotation on the pfclass system will also be considered seriously , with the aim of harmonized exchange of data between the different systems . ( iii ) additional services such as blast alignment , ncrnas prediction and possibilities for submission and registration of users ' sequences will be provided . in addition , two large - scale screens for novel ncrnas in caenorhabditis elegans and human tissues are being carried out in our laboratory ( y. wang , z.y . he , unpublished data ) , and the results will be added in the next version of noncode . noncode is thus designed to adapt and to reflect the most current information on ncrnas available . it will continue to grow in both content and functionality , and will be updated every six months to include any new data from literature and genbank . we are indebted to all of our colleagues who focus much of their research efforts on the analyses of ncrnas . kscx2 - 2 - 27 , national sciences foundation of china grant nos 39890070 and 60496320 , the national high technology development program of china under grant no . 2002aa231031 , national key basic research & development program 973 under grant nos 2002cb713805 and 2003cb715900 , and beijing science and technology commission grant no . h010210010113 .

noncode is an integrated knowledge database dedicated to non - coding rnas ( ncrnas ) , that is to say , rnas that function without being translated into proteins . all ncrnas in noncode were filtered automatically from literature and genbank , and were later manually curated . the distinctive features of noncode are as follows : ( i ) the ncrnas in noncode include almost all the types of ncrnas , except transfer rnas and ribosomal rnas . ( ii ) all ncrna sequences and their related information ( e.g. function , cellular role , cellular location , chromosomal information , etc . ) in noncode have been confirmed manually by consulting relevant literature : more than 80% of the entries are based on experimental data . ( iii ) based on the cellular process and function , which a given ncrna is involved in , we introduced a novel classification system , labeled process function class , to integrate existing classification systems . ( iv ) in addition , some 1100 ncrnas have been grouped into nine other classes according to whether they are specific to gender or tissue or associated with tumors and diseases , etc . ( v ) noncode provides a user - friendly interface , a visualization platform and a convenient search option , allowing efficient recovery of sequence , regulatory elements in the flanking sequences , secondary structure , related publications and other information . the first release of noncode ( v1.0 ) contains 5339 non - redundant sequences from 861 organisms , including eukaryotes , eubacteria , archaebacteria , virus and viroids . access is free for all users through a web interface at http://noncode.bioinfo.org.cn .

so far , only four case reports and one case series has been published . due to the paucity of data , not much is known about the biological and clinical behavior of ahl . both ahl and ah are considered to have a better prognosis and considerably less cardiac involvement when compared with its more frequent counterpart , al . a 12-lead electrocardiogram revealed complete heart block with a ventricular rate of 40 beats / minute . echocardiogram showed left ventricular hypertrophy with interventricular septal thickness of 26 mm ; ejection fraction 55% , normal aortic , mitral , tricuspid and pulmonary valves , mild mitral regurgitation , and normal right ventricular pressures . based on these findings , patient was diagnosed to have hypertrophic obstructive cardiomyopathy ( hocm ) with complete heart block . the patient received a dual chamber pacemaker following which he remained relatively asymptomatic ; his systolic blood pressures documented during follow - up visits were consistently around 100 mm hg . nine months later , he noticed mild pedal edema and progressive numbness of toes , for which he did not seek medical attention . he presented 18 months after the pacemaker implantation with worsening pedal edema shortness of breath and frequent episodes of syncope . on examination the serum cr was 2.2 mg / dl , serum protein levels were 7.4 g / dl with an albumin : globulin ratio of 2.9 . his 24 h urine protein excretion was 2208 mg / day , urinary sediment was inactive . a 12-lead electrocardiogram showed that the pacemaker initiated rhythm in the ventricular demand mode with a rate of 60 beats / minute with intermittent under - sensing and a qrs amplitude of 5 mm in the limb leads . serum electrophoresis revealed a monoclonal band in the region of gamma globulins and elevated free light chains ( free kappa 39.4 mg / l , free lambda 136 mg / l ) with a kappa / lambda ratio of 0.29 . light microscopy ( lm ) revealed 27 glomeruli , of which 15 glomeruli were completely sclerosed . viable glomeruli were enlarged in size and showed marked mesangial widening with prominent nodules composed of glassy , homogenous eosinophilic material , which was periodic acid - schiff ( pas)-positive and silver - negative [ figure 1a and 1b ] ; many blood vessels showed similar material causing luminal occlusion . interstitium showed moderate inflammatory infiltrate composed of lymphocytes and few plasma cells , and there was tubular atrophy amounting to 60% of the core . immunofluorescence ( if ) microscopy showed strong positive staining for heavy chain immunoglobulin ( ig ) g and light chain lambda in the mesangium , along the glomerular basement membrane , tubular basement membrane as well as along the vessels [ figure 1c and 1d ] . the glomerular deposits revealed apple green birefringence on polarized microscopy [ figure 2a and 2b ] . electron microscopy ( em ) revealed normocellular glomerulus with marked mesangial widening and numerous haphazardly arranged , nonbranching fibrils ranging from 7 nm to 10 nm in diameter [ figure 2c ] . a repeat echocardiogram revealed concentric left ventricular hypertrophy , mild mitral regurgitation , mild tricuspid regurgitation , right ventricular systolic pressure of 44 mm hg and a restrictive filling pattern [ figure 2d ] . ( a ) glomeruli with marked mesangial widening , prominent nodules composed of glassy , homogenous , and eosinophilic material . in addition , one small arteriole shows luminal occlusion by similar material ( h and e , 200 ) . ( b ) glomeruli show periodic acid - schiff ( pas ) positive mesangial widening and nodules ( pas , 400 ) . ( c and d ) immunofluorescence ( if ) shows strong positivity for both igg and lambda in the mesangiun , glomerular and tubular basement membrane ( if , 400 ) ( a and b ) congo red staining with apple green birefringence on polarized microscopy . ( c ) characteristic amyloid fibrils ranging from 8 nm to 10 nm in diameter . ( d ) echocardiogram showing left ventricular hypertrophy based on the above findings , the patient was diagnosed to have systemic amyloidosis ( heavy and light chain ) with multiple myeloma . patient was started on bortezomib - based chemotherapy . amyloidosis is characterized by extracellular deposition of insoluble 7 - 10 nm fibrils , having a beta - pleated ultrastructure . ig - derived amyloid deposits accounts for about 85% of cases of systemic amyloidosis . of this majority is al , characterized by ig light chain deposition . on the other hand , ah and ahl there have been case reports of ahl occurring in the setting of lymphoma as well . apart from case reports , there is only one systematic analysis of ah / ahl , which has compared the characteristics of this rare disease with the more common variant , al . even though ahl has a similar age of presentation , gender predisposition and vital organ involvement , nasr et al . reported three patients with ah / ahl to have concurrent cardiac and renal involvement , of which two had ah whereas one had ahl . there are no previous reports of ahl presenting with cardiac involvement with subsequent involvement of kidney . ahl is reported to have a considerably lesser diagnostic yield from abdominal fat pad and bone marrow biopsies . when compared to al , majority of the patients will have an intact circulating monoclonal ig as there is concomitant production of light as well as heavy chain . the monoclonal light and heavy chains are considered to be secreted by a single clone of b cells . a higher proportion of patients with ahl tend to have plasma cell dyscrasias when compared to al . certain unique challenges can stand in the way of making a conclusive histologic diagnosis of ahl . the hallmark of renal amyloidosis is the presence of homogenous , amorphous , faintly eosinophilic pas and silver - negative extracellular deposits on lm . this deposit exhibits a characteristic apple green birefringence on congo red staining when viewed under polarized microscope . the deposits are composed of 7 - 10 nm fibrils , which can be visualized under em . em will reveal the fibrillary nature of the deposits , but is not useful for subtyping the amyloid . these include pas and silver - positive deposits , prominent glomerular basement membrane involvement and mesangial hypercellularity . these lm features are likely to be mistaken for fibrillary glomerulonephritis . in resource - poor settings where em is not routinely employed , it is prudent to screen for congo red positivity in all suspected cases of fibrillary glomerulonephritis , especially when it is associated with restriction of a heavy chain and/or light chain . most of the centers rely on if microscopy for subtyping of renal amyloidosis . in ahl , if microscopy will demonstrate restriction of a single ig light chain and heavy chain , but can be negative in approximately 18% of cases . the antibodies used in if bind to the epitopes on constant domains of light and heavy chains . if these epitopes are deleted or significantly altered , the antibodies will not be able to bind . it is likely that a proportion of ahl amyloidosis may be missed if if alone is used for amyloid typing . the demonstration of light and heavy chains may require additional testing by use of laser microdissection with tandem mass spectrometry ( lmd / ms)-based proteomic analysis . employing lmd / ms as a tool for renal amyloid typing is likely to increase the diagnostic yield . another potential problem that may seriously affect the validity of if is the nonspecific ig and complement staining by amyloid deposits . this is encountered more frequently in aa amyloidosis than al ; this results from an in vitro phenomenon due to increased affinity to amyloid aa protein by the antibodies used or because of an in vivo stickiness of the amyloid to igs . if if methods alone are used , the diagnosis of ahl should be limited to cases that show intense equal staining for a single heavy chain and one light chain . cardiac involvement is common in al but considered to be less common in ah / ahl . the classic clinical finding of low - voltage qrs complexes ( limb leads < 5 mm in height ) with poor r wave progression in the anterior chest leads ( pseudo infarction pattern ) is described in 50% of patients in cardiac amyloidosis . complete heart block is an uncommon presentation of amyloidosis ; it has been described in < 3% of patients who have cardiac amyloidosis . typical echocardiographic findings include concentric ventricular thickening with right ventricular involvement , poor biventricular long - axis function with normal or near - normal ejection fractions . a speckled or granular myocardial appearance is considered to be characteristic , but seldom demonstrated and may depend on the machine gain settings . the classic restrictive pattern , biventricular thickening and valvular infiltration occurs late in the course of amyloidosis . in 5% patients , an echocardiographic appearance indistinguishable from hocm has been described . cardiac magnetic resonance imaging with gadolinium contrast is a useful noninvasive test , which could differentiate amyloidosis from other causes of left ventricular hypertrophy . to the best of our knowledge , this is the first report of ahl from india . we wanted to highlight the atypical presentation of complete heart block , which is a rare initial manifestation of ahl . the initial echocardiographic appearance was indistinguishable from hocm ; a restrictive pattern classical of amyloidosis was demonstrated fairly late in the course of the disease . amyloidosis , even though uncommon , needs to be considered strongly in elderly patients presenting with left ventricular hypertrophy in the absence of hypertension . the renal biopsy showed significant pas positivity , a finding , which is unusual in amyloidosis . considering the fact that a major proportion of ah / ahl exhibit atypical features on lm , congo red screening should be considered for amyloid - like deposits even if it is pas / silver - positive . in view of the intrinsic limitations of if in subtyping amyloid , it is possible that ahl might be underdiagnosed . incorporating a direct protein identification method like lmd / ms is likely to improve the diagnostic yield .

amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix , which results from abnormal protein folding . even though more than 25 precursor proteins are identified , majority of systemic amyloidosis results from deposition of abnormal immunoglobulin ( ig ) light chains . in heavy chain amyloidosis ( ah ) , deposits are derived from both heavy chain alone , whereas in heavy and light chain amyloidosis ( ahl ) , the deposits are derived from ig heavy chains and light chains . both ah and ahl are extremely rare diseases . here , we report an unusual presentation of igg ( lambda ) ahl amyloidosis in the background of multiple myeloma , where the initial clinical presentation was complete heart block , which preceded the definitive diagnosis by 18 months .

he narrated that when he was in second grade ( age 7 ) , he and a fellow student were irritating his neighbor in the classroom . the patient mentioned that the point broke off in his thigh and was never extracted . he complained that the site still hurt intermittently and after all this time , he wanted the lump and the reported pencil point to be removed . examination of the anterior left thigh skin revealed a palpable 0.5-cm subdermal / subcutaneous elliptical lump in the skin . there was a tinge of black to blue to it as if it had been tattooed . the patient was explained the indications , risks and benefits of the procedure and he provided consent . a time - out was performed . firm tan dermal - based soft tissue nodule with associated dark graphite precipitate was removed . in the midst of the removed tissue , a 4-mm cone - shaped pencil ( graphite ) two buried absorbable sutures were placed and three simple interrupted 4 - 0 vicryl sutures were used to close the wound . a triple antibiotic ointment was applied and the wound dressed in sterile fashion . the patient was put on cephalexin to prevent secondary infection . the surgical wound healed without complications or significant scarring . the literature reports on hyperpigmented nodules in the skin secondary to a retained pencil core . hatano et al . in 2000 reported on a pencil core granuloma from a pencil tip injury that had occurred about 30 years prior . fukunaga et al . in 2011 summarized 9 previously reported cases of pencil core granulomas , the oldest of which was 58 years old . our case is unique in that we were able to recover the cone - shaped pencil tip and still write with it ( fig . 1 ) . in previous examinations of pencil core granuloma , giant cells and epithelioid cells had been observed . histologic examination in our case similarly revealed foreign body reaction with abundant entrapped dark black pigment and chronic reparative changes , including dense sclerosis and focal granulation tissue formation ( fig . furthermore , one report suggested more rapid growth of lesions and greater degree of tissue injury by colored pencils when compared to non - colored graphite pencils . a number of authors have commented on temporal changes in the granuloma , going from a relatively unchanged appearance to a rapid growth phase , ultimately leading to excision . the decision to explore and excise a pencil core granuloma can be thus based on changes in the skin lesion and/or concern for possible malignancy .

a pencil core with an intact pencil tip was excised from the thigh of a 60-year - old male 53 years after a puncture wound . histologic examination of the excised pencil core and the surrounding tissue revealed a foreign body reaction with abundant entrapped dark black pigment and chronic reparative changes , including dense sclerosis and focal granulation tissue formation .

fibrosing cholestatic hepatitis ( fch ) characterized by cholestasis leading to rapidly progressive hepatic failure is an aggressive and usually fatal form of viral hepatitis in immunocompromised patients , the characteristic histopathological features of which include : periportal fibrosis , ballooning degeneration of hepatocytes , cholestasis , with minimal inflammation . liver injury in fch is mediated via the direct viral cytopathic effects of virus antigen over - expression in hepatocytes . fch has been reported almost exclusively in heavily immunosuppressed organ transplant recipients or subjects with human immunodeficiency virus ( hiv ) infection and to be usually associated with hepatitis b virus ( hbv ) and hepatitis c virus ( hcv ) and cytomegalovirus ( cmv ) infection . it has occurred mostly in patients after liver transplantation ; some cases are also described as an uncommon complication of renal transplantation or bone marrow transplant . these findings may be a direct effect of immunosuppressive agents on the virus as well as a reduced immune response to virus . without treatment allogeneic hematopoietic stem cell transplantation ( ahsct ) without ablative conditioning may control host autoimmunity and induce transplantation tolerance in the host to the graft to prevent rejection of donor cells . hematopoietic stem cells ( hscs ) may potentially aid tissue repair and contribute to restoration of damaged hepatocytes . this case report describes a successful treatment of a uremic patient with previously stable chronic hepatitis c who developed fch after kidney transplantation with ahsct . a 60-year - old male patient was admitted to the hospital with progressive deterioration , jaundice , and abdominal distension . he had suffered the chronic glomerulonephritis for 10 years and had to accept peritoneal dialysis for 1 year because of uremia prior to renal transplantation . during pre - transplant period and at the time of transplant his liver functions were normal and his serum was positive for anti - hcv antibody but negative for hepatitis b surface antigen ( hbsag ) , hepatitis b e antigen ( hbeag ) , hbv dna , hiv rna . immunosuppressive therapy after transplantation included tacrolimus ( 68 mg / day ) , mycophenolate mofetil ( 1 g / day ) , and meprednisone ( 16 mg / day ) . in december 2007 , he presented with yellowish discoloration of eyes and urine with decreased appetite for 3 weeks prior to admission . on examination he was afebrile , icteric , and had 2 cm nontender hepatomegaly with smooth surface and regular margins . his investigations revealed serum creatinine 105 mol / l ; total bilirubin 30 mol / l with direct bilirubin of 12.8 mol / l ; aspartate aminotransferase ( ast ) 418 iu ( n : up to 50 iu ) ; alanine aminotransferase ( alt ) 998 iu ( n : up to 50 iu ) ; gamma - glutamyl transferase ( ggt ) 698 u / l , albumin ( alb ) 48 g / l ; hbsag negative ; immunoglobulin m ( igm ) hepatitis a ( hav ) negative ; igm hepatitis e ( hev ) negative ; igm hepatitis b core antigen ( hbcag ) negative ; hbeag negative ; cmv - igm negative ; anti - hcv positive , polymerase chain reaction ( pcr ) hbv negative . the titer of hcv is 2.5 10 copies / ml . abdomen ultrasound sonography test ( usg ) showed hepatomegaly . mycophenolate mofetil was stopped at admission and he was continued on 3 mg / kg of tacrolimus and 8 mg of meprednisone . ursodeoxycholic acid ( losan pharma gmbh ) , compound glycyrrhizin ( minophagen pharmaceutical co. , ltd ) and transmetil ( abbott laboratories ) were administrated to protect the live . at day 42 , after stable disease condition for 6 weeks , the patient 's condition suddenly deteriorated . he presents the clinical manifestation of acute liver failure such as further deepened jaundice , nausea , vomiting , extreme fatigue . liver biopsy was performed and the result showed marked cholangiectasis , chronic inflammation and fibrosis with spotty necrosis . ck19 was highly expressed in portal areas and hepatic parenchyma , which showed significant fibroplasia of liver ( figure 1c ) . he was started on iv injection of antibiotics and fresh frozen plasma for bacterial peritonitis . in view of the stop of immunosuppressive agents , which may give rise to renal rejection the experimental protocol was approved by our institutional committee on human research . because renal allograft was from a dead body and the donors matching with the renal donor in human leukocyte antigen ( hla ) were not found in chinese hematopoietic stem cell donor databank , the stem cells had to be recruited from appropriate donor among his sons or brothers . genotyping of the hla in the renal donor were a203 , 203 ; b 60 , 55 ; dr9 , 16 and the abo blood group and rhd of renal donor are a and positive respectively . fortunately , one of his sons was found to have the same blood group as the renal donor and have the haploidentical hla typing . genotyping of the hla of his son were a 203 , 24 ; b60 , 61 ; dr9 , 11 . + peripheral blood cells were obtained by cd34 + positive selection ( isolex 300imagnetic cell separator ; baxter , deerfield , il ) from this son . the patient immediately received 5.8 10 cd34 + stem cells / kg by peripheral vein . at the same time , he continued to be treated with antibiotics and other adjunctive drug . before day 70 he had made a remarkable recovery with resolution of all symptoms , and before day 160 liver biochemistry and prothrombin time returned to normal ( figure 2 ) . a flow - cytometry analysis was used for detecting specific cd cell - surface epitopes on single fixed cells to assess chimerism after 4 months . the percentage of donor cells circulating in the recipient 's peripheral blood , including leukocytes , cd3 + and cd34 + cells were 4.7% , 3.3% , 36.8% . a dramatic decrease of serum hcv rna concentration was observed . serum hepatitis c viral load gradually decreased from 2.5 10 copies / ml at day 1 to 3.2 10 copies / ml at day 98 and became negative ( < 400 copies / ml ) at day 126 and remains negative at the last available assessment . at day 98 the patient has received continuous tacrolimus therapy ( 1 mg / d ) to prevent renal rejection . at day 160 he was discharged , and at 10 months he was able to return to work . he was requested to visit monthly for the first year , and bimonthly from the second to the third year . he was tested for liver function , kidney function , drug levels ( tacrolimus , cyclosporin a , or mycophenolate ) , lipid profile , whole blood cell count , routine urine test , hcv rna and anti - hcv at each visit . renal graft and liver ultrasound were performed every 3 months or as ordered by doctors . the test results included tacrolimus drug level of 4.10 ng / ml , white blood cell of 6.28 10/l , hemoglobin of 152 g / l , platelet 187 10/l , normal urine test , serum creatinine of 88 mol / l , albumin of 40 g / l , alt of 4 u / l , ast of 14 u / l , ggt of 15 u / l , tbil of 11.3 mol / l and normal ultrasound images of renal graft and liver . liver histology . ( a ) hepatocytes obviously displayed ballooning degeneration , necrosis with a ground glass aspect . ( b ) there was marked periportal and septal fibrosis with moderate pericellular fibrosis ( silver staining ) . ( c ) ck19 was highly expressed in portal areas and hepatic parenchyma ( 1200 ) . the alt and ast ( reflects the hepatocyte injury ) were high at first and decreased after treatment , while ggt ( reflects cholestasis ) were not high but gradually increased within 2 months . these two indicators reflect the liver synthetic function , their alterations were similar to those in figure c , which show the liver metabolic function . changes in plasma bilirubin . from day 42 to 98 , the patients showed severe cholestasis and the bil curve ascended sharply . fch is a rapidly progressive form of hepatitis that occurs in the organ transplant recipients or subjects with hiv infection in which there are the presence of significant immunosuppression . the diagnosis of fch was based on the typical histological picture with pericellular fibrosis , ductular proliferation , cholestasis , and intense positivity for hbs and hbc antigens in an immunocompromised setting . different from the common virus hepatitis in which liver injury result from immune clearance of hepatotropic virus , fch has been postulated to result from a direct cytopathic effect of hbv or hcv on hepatocytes associated with immunosuppression . treatment by liver transplantation carries a high risk of mortality . in the last 40 years , monaco 's research laboratory has worked with donor bone marrow derived cells infusion to augment tolerance , and this has remained the central theme of his research work . recently , different approaches have been successfully used in both experimental and clinical settings to increase the likelihood to induce chimerism and operational tolerance . promotion of permanent chimerism resulting in exhaustive clonal deletion was considered to be the most probable mechanism for this effect . in this case , based on fch , the patient developed spontaneous bacterial peritonitis and lung infection , a disease associated with high inpatient mortality . after renal transplantation , immunosuppressive therapy can result in an increased burden of hcv viremia . so all the immunosuppressive agents had to be stopped and antibiotics were administrated . in view of the possibility of renal rejection , we performed allogeneic hsc infusion to induce recipient hematopoietic chimerism and graft tolerance . in this successful case , there may be other mechanisms taking part in the liver repair such as infused hsc cell , transdifferentiation into functional hepatocytes and/or paracrine effects that promote liver regeneration and suppress local inflammation . at present , after renal transplantation , there is no current safe and efficient therapy for hcv infection . alpha - interferon ( alpha - ifn ) does not give a sustained virological response , and is associated with a high rate of renal failure . ribavirin and amantadine monotherapies are associated with a significant improvement in liver enzymes , but have no impact upon hcv viremia . in our patient described here , loss of serum hcv rna from such a high baseline level may be result from recovery of anti - viral immune responses after stop of immuno suppressive agents . in summary , this case suggests that hscs from the donor who has haploidentical hla typing with renal graft can induce the transplantation tolerance and may take part in the liver repair of the patient who suffers fch after renal transplantation . it is the first report of renal transplantation patient who survived fch with allogeneic hsc infusion .

abstractfibrosing cholestatic hepatitis ( fch ) is an uncommon complication of renal transplantation and usually associated with hepatitis b and c viral infection . without treatment , the prognosis is usually fatal within weeks of onset . there was rarely report with successful treatment intervention.this case report describes a uremic patient with hcv infection who developed a fatal form of fch after kidney transplantation . this is the first reported successful case with allogeneic hematopoietic stem cell transplantation ( ahsct ) without ablative conditioning.a dramatic virologic and clinical improvement was observed in this post - transplantation patient . but no adverse events related to ahsct were observed . the patient returned to work full - time at 10 months of hospitalization and is still in good health by now . serum hcv rna gradually decreased from 2.5 106 copies / ml at day 1 to 3.2 104 copies / ml at day 98 and became negative ( < 400 copies / ml ) at day 126 of hospitalization and remains negative at the last available assessment.our report suggests that allogeneic hsct may have a therapeutic role in fch .

neuralgic amyotrophy ( na)-also known as parsonage - turner syndrome or brachial plexus neuritis - is an under - recognized but distinct clinical syndrome , with a characteristic clinical presentation of an acute , severe neurogenic pain in the shoulder or arm lasting for several days or weeks , followed by muscle weakness , atrophy , and sensory loss as the pain diminishes.13171920212223 ) the pain is a hallmark of na and typically relentless and severe [ numerical rating scale ( nrs)>7].1721 ) there is no successful treatment of na yet and the initial pain at the onset of an attack is only partly relieved by traditional analgesics.1721 ) although spinal cord stimulation ( scs ) has been known as an accepted , effective therapy for patients with chronic neuropathic pain such as complex regional pain syndrome ( crps ) type i as well as in a variety of other neuropathic conditions,127121524 ) its effectiveness against the neuropathic pain of na was not reported . herein we describe a 35-year - old woman with intractable neuropathic pain from na who responded to scs.61524 ) a 35-year - old female presented with an eight - week history of a severe , unrelenting pain in the left palm and radial four fingers , medial forearm , and in the shoulder pain waking her from sleep . the pain was described as dull , crushing , and deep pressure - like and of an extreme severity ( 8 - 9/10 on nrs ) . the pain made the patient sit on the table constantly holding her arm close to her body , keeping it immobile . eight weeks ago , she woke up in the morning with a severe pain in her left shoulder and hand and this pain was unlikely any pain she experienced before . the pain worsened at this day and become constant and unrelenting since then and it was heavier at night . a weakness in her left hand progressively developed 2 weeks after the onset of pain . the electromyography study suggested an incomplete brachial plexopathy . on examination , a moderate tenderness in the left shoulder with a moderate weakness [ manual muscle testing ( mmt ) grade 3 ] of the left hand grasping and finger movement was observed . the sensory examination showed patch areas of hypesthesia , paresthesia , and mechanical allodynia to light touch and pressure in her left shoulder , medial forearm , thenar side of the palm and in four fingers which corresponded to the pain sites ( figure 1a ) . her nrs at examination was ( 8/10 , nrs ) and the pain was more severe at night ( 9/10 , nrs ) . the mri of the left brachial plexus showed a diffuse swelling , increased signal intensity , and an enhancement of whole trunks of the left brachial plexus and its divisions suggesting a brachial plexopathy ( figure 1b and c ) . there was a marked asymmetrical uptake in the blood pool phase of the three - phase bone scintigraphy ( figure 1d ) and skin temperature asymmetry on digital infrared thermal imaging ( figure 1e ) . after admission for pain control , the amount of daily medication was increased to gabapentin 2,400 mg , ir - codon 40 mg , oxycodone 40 mg , amitriptyline 20 mg , and 50 mcg / hr transdermal fentanyl . however , the pain relief was not satisfactory and the patient got an injection of fentanyl 10 mg five times a day as needed . considering the chronicity and severity of neuropathic pain , a temporary trial of scs was performed ( approximately 10 weeks after onset of pain ) with a cylindrical electrode ( octrode , plano , tx , usa ) at the level of c3 - 5 ( figure 2a ) . the severe dull , crushing and deep pressure - like spontaneous pain and the evoked pain ( mechanical allodynia ) in the arm and hand was alleviated for about 50% ( contact polarity 3 - 4 + , 100 usec , 100 hz , 1.5 ma ) . she assessed the effect of scs as fairly successful and expressed the pain intensity ( 4 - 5/10 , nrs ) . during the temporary stimulation period of 21 days , she was satisfied with the analgesic efficacy of scs and wanted to have a chronic stimulation . approximately 12 weeks after the onset of severe pain , a chronic scs system was implanted through a paddle lead scs ( penta and eon - mini rechargeable , st . after one week of adjustment of the stimulation parameters ( 1 - 4 + , 400 usec , 90 hz , 1.4 ma ) , she finally discontinued a nighttime injection of fentanyl and switched into ir - codon 10 mg as needed . the analgesic efficacy of scs was more effective in controlling pain and allodynia in the medial forearm , palm and 2nd , 3rd , 4th fingers ( more than 60% relief , subjective assessment ) . the effectiveness of chronic scs was fairly consistent during the follow - up of 12 months and she evaluated her pain as 4 ( daytime)-5 ( nighttime ) in on an 11 point nrs . at the last follow - up of 12 months after the onset of pain , the patient still suffered a serious , chronic pain ( fluctuating 3 - 6/10 , nrs ) and grade iv mmt weakness of left hand . her medication at the last follow - up was gabapentin 1,200 mg , oxycodone 20 mg , amitriptyline 10 mg , and ir - codon 20 mg per day . na , which was first described by dreschfeld4 ) in 1886 as a distinct clinical syndrome , is characterized by attacks of neuropathic pain and subsequent patch paresis in the upper extremities . the etiology of idiopathic na remains unknown and an immune - mediated process seems to garner the most support currently.111425 ) a hallmark of na is a sudden , severe painful onset and the patch distribution of motor , sensory and autonomic symptoms.1727 ) any part of the brachial plexus and the lumbosacral plexus can be involved , with any combination of motor and sensory impairment.1721 ) a bilateral involvement of the brachial plexus occurs in approximately 30% of patients ; clinical features are commonly asymmetric in presentation.21 ) the upper trunk of the brachial plexus is most usually involved , but any part of this plexus can be affected too . also painless attacks can occur.1721 ) in 96% of patients , na presents with acute , severe pain in the upper extremities , neck and/or trunk , which usually causes the individual to wake up early in the morning . the pain then increases to its maximum severity over the next few hours.21 ) typically is the pain relentless , worse at night and is unlikely anything the patient has ever experienced before , with pain scores of at least 7 being assigned on the numerical scale of 0 to 10.19 ) this initial pain lasts for 4 weeks on average , but disappears in 5% of cases within 24 hours and lasts for at least 2 months in 10% of individuals.21 ) subsequently , at least 75% of patients will go on to develop an additional type of pain , possibly because of hypersensitivity of the damaged nerves to mechanical stretch or maintained posture , shooting or radiating pains to the arms or trunk that dissipate over a period of weeks to months . additionally , two - thirds of individuals develop a musculoskeletal pain at the origin or insertion of the paretic or compensating muscles , especially in the periscapular and cervical - occipital regions.182021 ) the treatment of pain and residual sequele of a na is directed to a supportive management . adequate analgesia including the use of opiates in the acute painful phase and appropriate physical therapy and rehabilitation for shoulder paresis and glenohumeral instability in the chronic phase are the cornerstones of management.172123 ) the prognosis of na was traditionally thought to be positive , with full recovery occurring in 80% to 90% of patients 2 to 3 years following the onset of symptoms.316 ) however , subsequent studies showed that the overall recovery was less favorable than usually assumed.172123 ) persistent pain and paresis was experienced in approximately two - thirds of patients that were followed for 3 years or more , with a marked effect on their daily life and employment.5172123 ) scs is known to be a safe and effective treatment option for selected patients with medically refractory chronic pain syndrome such as failed back surgery syndrome or crps , and peripheral neuropathic pain.127121524 ) scs involves the placement of electrodes in the epidural space and production of an electrical current by means of a pulse generator . the analgesic mechanism produced by scs is believed to work by the gate control mechanism and modulation of excitatory and inhibitory neurotransmitter release in the dorsal horn.924 ) although scs has been reported to be effective in various kinds of neuropathic pain,127121524 ) the effectiveness of scs was not reported in the treatment of a typical neuropathic pain of na . the reason why we performed the trial scs in this patient is simple ; we wanted to relieve an extraordinary prolonged period of severe pain refractory to maximal medical treatment ( nrs>7/10 ) . therefore , we adopted a temporary scs as a salvage procedure within a desperate condition in our case . this kind of temporary scs treatment has already been reported in the acute and subacute phase of postherpetic neuralgia.1026 ) another reason for temporary scs was that the typical neuropathic pain nature of na . although a typical cutaneous manifestation of crps-1 , such as edema and sudomotor sign , was absent , the symptoms and signs and some ancillary investigations were comparable to those of typical crps-1.8 ) further controlled studies are needed to evaluate the efficacy of early scs in the severe neuropathic pain of na . temporary scs was effective in achieving an adequate analgesia in the acute phase of na and chronic scs was also useful to control the chronic pain . however , na has been known to spontaneously resolve and we think scs trial should be limited to selected patients with pain is notoriously refractory to conservative management .

the aim of this paper was to report the effect of temporary and chronic spinal cord stimulation for refractory neuropathic pain in neuralgic amyotrophy ( na ) . a 35-year - old female presented with two - months history of a severe , relentless neuropathic pain of the left shoulder , forearm , palm , and fingers . the neuropathic pain was refractory to various medical treatments , including nonsteroidal anti - inflammatory drugs , opiates , epidural and stellate ganglion blocks , and typically unrelenting . the diagnosis of na was made with the characteristic clinical history and magnetic resonance imaging . the patient underwent a temporary spinal cord stimulation to achieve an adequate pain relief because her pain was notoriously difficult to control and lasted longer than the average duration ( about 4 weeks on average ) of a painful phase of na . permanent stimulation was given with paddle lead . the neuropathic pain in her na persisted and she continued using the spinal cord stimulation with 12 months after development of na . the temporary spinal cord stimulation was effective in a patient with an extraordinary prolonged , acute painful phase of na attack , and the subsequent chronic stimulation was also useful in achieving an adequate analgesia during the chronic phase of na .

kawasaki disease ( kd ) is a self - limited , systemic vasculitis of unknown etiology that affects the small and medium - sized blood vessels of the body . occur in children less than 5 years of age , and the incidence is highly varied , ranging from 4 to 216 per 100,000 children less than 5 years of age worldwide . the most serious complication of the disease is coronary vasculitis , leading to abnormalities in the coronary arteries that affect 15% to 25% of untreated patients . in addition to the cardiac complications , other abnormalities such as ataxia , facial paralysis , behavior disorders , and ocular complications can also be present . sensorineural hearing loss ( snhl ) is seldom cited as a kd complication yet is known as an additional , potentially severe , and frequently irreversible sequel . however , the vestibular effects of kd have been underestimated , and these could also be an important complication combined with snhl in kd . here we describe the case of a 4-year - old boy who developed vestibular loss in addition to snhl and recovered successfully with a combined treatment . a 4-year - old boy with no relevant prenatal or neonatal background and no history of hearing impairment had adequate normal growth and normal development of vocabulary and language . he was admitted to our pediatrics department due to uncontrolled fever and sudden onset vertigo persisting for 4 days . on admission , he presented with bilateral non - exudative conjunctival injection , marked injected and fissured lips , polymorphous rash of the face and trunk , and cervical lymphadenopathy ( right multiple palpable lymph nodes > 2 cm ) , in addition to the fever ( fig . he had moved back and forth from severe nausea and vomiting to loss of balance ; however , visual acuity and brain mri was normal . laboratory workup revealed leukocytosis ( 19,000/l ) with neutrophilia ( 79.5% ) , and neither anemia nor thrombocytosis was detected . renal function tests and liver enzymes were within the normal range . upon performing a lumbar puncture an electrocardiogram was normal , and no echocardiogram abnormalities were observed , with results showing normal dimensions of the coronary arteries . a clinical diagnosis of kd was established according to the american heart association criteria . treatment with intravenous immunoglobulin was promptly initiated ( 1.5 g / kg in a single and continuous perfusion ) in association with acetylsalicylic acid ( asa ) ( 80 mg / kg / day ) . he became apyretic within 24 hours of treatment implementation , with progressive regression of the remaining clinical symptoms . he soon recovered from nausea and vertigo after the treatments and was discharged 5 days later , maintaining asa with low - dose prophylaxis ( 5 mg / kg / day ) . four days after discharge , his parents noticed a sudden absence of response to sound stimuli and brought him to the clinic of otorhinolaryngology . assessment of hearing function was obtained through impedance audiometry , play audiometry , and auditory brainstem response ( abr ) ( fig . his impedance audiometry showed a type a curve bilaterally with no response of stapedial reflex at a sound of 100 db hl . play pure tone audiometry confirmed severe bilateral snhl with right mixed hearing loss components ( right ear , 75 db with an air - bone gap of 20 db ; left ear , 45 db ) . a v wave in the abr test was present until 75 db stimuli on the right ear and 55 db on the left ear . after the exclusion of salicylate toxicity ( therapeutic drug monitoring level < 0.3 g / ml plasma ) , we thought that the hearing loss could possibly be due to the subacute phase after the acute phase of kd . blood tests confirmed thrombocytosis during the second week of disease ( 606,000/ml , compared with 416,000/ml at the initial admission ) as well as a progressive decrease of acute inflammatory response markers ( wbc=89,400/l ; neutrophil percentage=40.3% ) . there were no visualizations of either anterior inferior cerebellar artery ( aica ) , the feeding vessel of the cochlea , in 3d - magnetic resonance angiography ( mra ) ( fig . 3 ) . to stop the progression of kd we administered a corticosteroid for immunosuppression and added an anticoagulant drug to interrupt the vascular insufficiency of the cochlea . intravenous steroid pulse therapy ( methylprednisolone sodium succinate , started at 200 mg / day initially for 5 days and then tapered down ) was initiated with plavix ( clopidogrel bisulfate , 18 mg / kg ) , instead of asa . during follow - up , there was a significant improvement of auditory acuity in both ears ( 5 days after steroid therapy : right ear=50 db , left ear=45 db ; 3 weeks later : both=25 db ) ( fig . tonal audiometry , performed 2 months after the diagnosis of kd , confirmed a normal hearing threshold . we observed another kind of severe complication in this case : snhl and vestibular loss ; which is not frequently reported in the literature . the presence of hearing loss during the subacute phase of kd in children is very rare , especially when accompanied by canal paresis causing vestibular hypofunction . moreover , the successful combined treatment restored the functions of the cochlea completely . therefore , this report is important for assessing effective treatment in these patients . until now , the association of snhl with kd seems to be underestimated , as hearing dysfunction can be discreet and transient in this disease , detectable only by audiometry or bera in very young children who can not express themselves well linguistically . knott , et al . found that 19 of 62 patients experienced snhl with kd . similarly , in the most recent and largest study of 115 kd patients by alves , et al . , 33% had snhl during the acute and subacute phases of the disease . in the present case , the patient 's parents failed to identify the hearing problem early after discharge and brought him to our clinic 4 days later , when he failed to correctly recognize words , even when hearing his own speech . audiometry results then revealed that his right ear threshold was 75 db , and his left ear threshold was 40 db . the hearing loss may be associated with the aberrant inflammatory process , due to the intense immune activation observed in the acute phase . this systemic inflammatory process can affect the membranes of the labyrinth and the osmotic balance in the fluid inside the compartments of the inner ear or in the cochlear vessels , thus leading to hearing loss . secondary abnormalities of the vasa nervorum and perineural vessels resulting in damage of the acoustic nerve could be other possible causes of hearing loss . the inflammatory cells that infiltrate the vasa nervorum and epineural arteries lead to obstruction , axonal ischemia , and consequent nerve injury . the changed expression of metalloproteinases in the vessel walls can contribute to their subsequent destruction , which can participate directly in the injury caused by nerve ischemia . in addition to this pathophysiology of kd , thrombocytosis in this case indicated a possibility of ischemia injury owing to vascular insufficiency . the aica , the feeding vessel of the cochlea and vestibule , was not visible on the images from 3d - mra . however , we are uncertain as to whether the small vessels in both ears were obstructed or were too small to be visualized . the potential role of salicylate ototoxicity in the genesis of hearing loss in acute kd patients has been raised . higher doses tend to cause more severe hearing loss , although a precise dose - response relationship can not be demonstrated . it is unlikely , however , that the snhl experienced in this case was caused by asa ototoxicity alone . the therapeutic drug monitoring level was very low ( < 0.3 g / ml plasma ) , and the patterns of hearing impairment differed from the patterns characteristic of salicylate ototoxicity , in which binaural flat or high - frequency deficits predominate . at the initial audiometry , there was an air bone gap that recovered within a few days . although it might have been an error from the young child 's play audiometry , we think that acute cochlear injury caused a stiffness of the ossicular chains , especially the stapes , due to a lateralization of oval window caused by endolymphatic hydrops . kd can result in ataxia due to the involvement of the vestibular division of the acoustic nerve . other cranial nerves may also be affected , and facial paralysis secondary to involvement of the seventh nerve has also been described . although this patient had initial symptoms of a vestibular deficit with severe nausea , no one was able to determine when the hearing loss started . the results of the caloric test indicated no response from the right ear canal , showing that dizziness and ataxia might have originated from a complete loss of vestibular function . despite the fact that the symptoms of nausea and unbalance subsided due to a compensation of the contralateral side , the canal paresis still remained . the early treatment initiated during the first week of hearing loss , including the use of high - dose systemic steroids combined with anticoagulants , is thought to possibly prevent the progression of hearing deficit . complete remission within two months was obtained due to early awareness of the possibility of snhl associated with kd , which allowed for a timely intervention . children with kd may be referred to the otolaryngologist for a variety of signs and symptoms during their acute illness . referral for evaluation of dizziness as well as hearing loss may occur long after signs and symptoms of acute kd have disappeared . given that kd is a self - limited illness that resolves even in the absence of treatment , the diagnosis may be missed and the illness forgotten . therefore , pediatrics and otolaryngologists should refer symptomatic patients for audiologic and vestibular evaluations and for kd evaluations , such as an echocardiogram .

sensorineural hearing loss ( snhl ) that is seldom cited as a kawasaki disease ( kd ) complication is known as an additional , potentially severe , and frequently irreversible sequel . furthermore the vestibular functions of kd have been underestimated and it could be an important complication combined with snhl in kd . we described a case that a 4 year - old boy who developed vestibular loss with snhl has recovered successfully with a combined treatment .

an estimated 235,030 new breast cancer cases are expected to occur for the year in 2014 ( 3 ) . consequently , more women are living with the negative effects of cancer , either by the disease itself , or as a result of treatment ( radiation , chemotherapy , hormonal therapy etc . ) . some of the negative effects include cancer related fatigue ( crf ) , pain , irregular sleeping patterns , increased risk for osteoporosis and decreased cardiovascular and pulmonary function ( 6 , 13 ) . furthermore , survivors can experience emotional distress including lower quality of life ( qol ) and symptoms of anxiety and depression . an increasing number of studies have emerged promoting exercise and physical activity ( pa ) as a means to attenuate the negative side effects and improve cancer - related qol among survivors . several studies have hypothesized , with relative success , that exercise can be used to prevent , attenuate , treat and rehabilitate the physiological and psychosocial challenges faced by survivors both during and post - treatment ( 4 , 7 , 9 , 13 , 14 , 16 ) . exercise programs traditionally utilize a treadmill , elliptical , or stationary bike to provide cardiovascular training . recognizing the need for lower - impact exercises with survivors , particularly with their increased risk of falls and fractures following treatment ( 6 ) , researchers have examined the use of water - based exercise programs to unweight participants ( 4 , 7 ) . these studies provide important implications that lower impact exercises may be a feasible alternative to load - bearing activities for breast cancer rehabilitation . this study utilized an anti - gravity ( alter - g ) treadmill to build on studies with lower - impact pa programs . the antigravity treadmill ( alter - g ) is a relatively new piece of equipment used in a range of settings from physical therapy to sports performance . this treadmill uses a chamber attached to a pair of modified shorts at waist - level . after calibration , the treadmill can then increase air pressure inside the chamber to unweight the participant to as low as 20% of their body weight . the alter - g treadmill builds on the premise set forth by the aquaciser treadmill ( hudson aquatic , angola in ) by using pressure to unweight the participant ; the advantage of the alter - g is that it allows the technician to modify the air pressure in the chamber , providing a range from 20100% of the participants body weight . this range allows participants the ability to start at a relatively low weight on their bones and joints , with the option to gradually increase the load throughout the duration of the program to eventually reach 100% body weight . recent studies have supported its safety and efficacy in training lower body injuries and obese patients ( 14 ) . the purpose of this study was to determine the effectiveness a pa program , including an anti - gravity ( alter - g ) , treadmill in improving physiological and psychosocial measures in female breast cancer survivors . female breast cancer survivors [ n=6 , mean ( sd ) age : 51 ( 18 ) years , weight : 73.12(45.8 ) kg , height : 166.12(17.78 ) cm ] were recruited via word of mouth , fliers , and cancer support - group meetings to participate in the study ( table 1 ) . participants were included in the study if they had completed treatment ( radiation , chemotherapy , or hormonal therapy ) at least 6 months prior to the intervention , and had received physician s clearance . one participant dropped out of the program due to an extended vacation taken towards the end of the study . the program began with a screening session , where physician release forms were reviewed ; participants filled out informed consent forms and were given an overview of the study and the risks and benefits of participation . the design consisted of four phases over the course of 14 weeks : a baseline testing ( a ) phase to establish initial values for each variable ( 2 weeks ) , followed by an intervention phase ( b)(5 weeks ) , a return to baseline ( a)(2 weeks ) and a final replication phase ( b)(5 weeks ) . scrd is unique in that is allows for repeated measurement of a variable , with each participant serving as their own control . baseline phases ( 2 weeks apiece ) included flexibility and resistance training twice weekly , with testing ( cardiovascular endurance , quality of life ( qol ) , and weight ) on a third day . intervention phases were similar to the baseline phases , with the addition of the alter - g to administer cardiovascular training two days per week , with the same testing protocol as baseline on a third day . participants began at a percentage of their bodyweight they felt comfortable ( at least 50% of their body weight ) . percentage of bodyweight was increased ( ~5% per week ) as participants progressed throughout the program . flexibility via modified sit - and - reach ( s / r ) was measured each session . weight ( kg ) , cardiovascular endurance via time on a modified balke protocol , and qol using ferrans and powers quality of life index cancer version iii were measured once a week on the testing day . the primary investigator was a certified professional with an extensive background working with cancer survivors . general standards of the exercise intervention included : resting heart rate ( rhr ) and blood pressure ( bp ) were monitored prior to the beginning of each session . 60-minute sessions 2 days per week ( a minimum of 24 hours rest was required between training days ) . a third day each week warm - up , followed by bouts of aerobic , resistance , balance and flexibility training , followed with a cool down . rpe was used to monitor & adjust levels of intensity for both aerobic and resistance training . participants began with 12 sets of 1215 repetitions ; gradually increasing to 3 sets of 812 repetitions . visual inspection was used to analyse changes in magnitude ( mean and level ) and the rate of change ( trend and latency ) ( 10 ) . female breast cancer survivors [ n=6 , mean ( sd ) age : 51 ( 18 ) years , weight : 73.12(45.8 ) kg , height : 166.12(17.78 ) cm ] were recruited via word of mouth , fliers , and cancer support - group meetings to participate in the study ( table 1 ) . participants were included in the study if they had completed treatment ( radiation , chemotherapy , or hormonal therapy ) at least 6 months prior to the intervention , and had received physician s clearance . one participant dropped out of the program due to an extended vacation taken towards the end of the study . the program began with a screening session , where physician release forms were reviewed ; participants filled out informed consent forms and were given an overview of the study and the risks and benefits of participation . the design consisted of four phases over the course of 14 weeks : a baseline testing ( a ) phase to establish initial values for each variable ( 2 weeks ) , followed by an intervention phase ( b)(5 weeks ) , a return to baseline ( a)(2 weeks ) and a final replication phase ( b)(5 weeks ) . scrd is unique in that is allows for repeated measurement of a variable , with each participant serving as their own control . baseline phases ( 2 weeks apiece ) included flexibility and resistance training twice weekly , with testing ( cardiovascular endurance , quality of life ( qol ) , and weight ) on a third day . intervention phases were similar to the baseline phases , with the addition of the alter - g to administer cardiovascular training two days per week , with the same testing protocol as baseline on a third day . participants began at a percentage of their bodyweight they felt comfortable ( at least 50% of their body weight ) . percentage of bodyweight was increased ( ~5% per week ) as participants progressed throughout the program . flexibility via modified sit - and - reach ( s / r ) was measured each session . weight ( kg ) , cardiovascular endurance via time on a modified balke protocol , and qol using ferrans and powers quality of life index cancer version iii were measured once a week on the testing day . the primary investigator was a certified professional with an extensive background working with cancer survivors . general standards of the exercise intervention included : resting heart rate ( rhr ) and blood pressure ( bp ) were monitored prior to the beginning of each session . 60-minute sessions 2 days per week ( a minimum of 24 hours rest was required between training days ) . a third day each week warm - up , followed by bouts of aerobic , resistance , balance and flexibility training , followed with a cool down . rpe was used to monitor & adjust levels of intensity for both aerobic and resistance training . participants began with 12 sets of 1215 repetitions ; gradually increasing to 3 sets of 812 repetitions . visual inspection was used to analyse changes in magnitude ( mean and level ) and the rate of change ( trend and latency ) ( 10 ) . visual analyses showed improvements in mean treadmill time between both the baseline and intervention , and return to baseline and final replication phase for all participants ( figures 1a . 1e . ) . visual analyses also found improvements in flexibility observed from baseline to intervention among all participants . 2e . ) for participants 1 , 2 , and 5 between the baseline phase and intervention phase , and between the return to baseline phase and final intervention phase . participants 3 and 4 saw small increases in mean weight between the baseline and intervention phases , and a decrease in mean weight from the return to baseline and replication phase . 3e . ) from baseline to intervention phase , and return to baseline and final replication phase for participant 1 , 2 , and 3 . there was an improvement in mean qol for participant 4 from the baseline phase to the first intervention phase , with a decrease from the return to baseline phase and final replication phase . participant 5 showed a slight decrease in qol from the first baseline phase to intervention phase , with an improvement in mean qol throughout the subsequent phases . the purpose of this study was to determine if using a physical activity program , including an anti - gravity ( alter - g ) treadmill , would aid in improving physiological and psychosocial measures in female breast cancer survivors . it was hypothesized that using a pa program , including an anti - gravity treadmill , would improve physiological and psychological measures in participants . our analyses suggest that a 14-week exercise program utilizing an alter - g treadmill can at least maintain , and in some cases , improve physiological and psychosocial variables . this is consistent with previous literature exercise demonstrating significant improvements in cardiovascular function in female breast cancer patients following exercise programs of varying length ( 2 , 4 , 6 ) . this study is the first of its kind to examine the inclusion of an alter - g treadmill in a pa program directed at bcs . low - impact activity may also reduce the risk of falls and fractures that may occur during traditional treadmill training among bcs who are at an increased risk following treatment7 . while further research is needed to determine loading and progression protocols , our results suggest that the alter - g treadmill is a safe and well - tolerated alternative to regular treadmill training . participants improvements in flexibility are consistent with previous studies noting similar improvements in flexibility following exercise programs ( 11 , 12 ) improvements in flexibility may increase range of motion and improve physical functioning needed for activities of daily living ( 13 ) . our results showed that all participants at least maintained if not experienced a favourable weight change . it is likely that more pronounced improvements in weight would be achieved with the addition of a dietary intervention ( 5 ) . our results also suggest that qol can at least be maintained , if not improved in some cases . this is consistent with previous studies noting significant improvements in qol in bcs following pa programs ( 14 ) . cancer survivors often experience reduced bone mineral density following treatment , and are consequently at a greater risk for falls and injury ( 6 ) furthermore , researchers have utilized aqua aerobics with cancer survivors with the premise that the buoyancy of water will reduce axial loading and allow participants to perform exercises they may not be able to on land ( 4,7 ) . this study is the first of its kind to examine the inclusion of an alter - g treadmill in a pa program directed at breast cancer survivors . the treadmill is unique in its ability to modify the percentage of weight a participant works at , allowing for a progression from unloading exercise to loaded which may contribute to the gradual strengthening of bones , and bone ossification . although not measured in this study , this mode of exercise progressing from low - impact to bodyweight training on the treadmill may serve to strengthen bone mineral density in survivors . this low - impact activity may also reduce the risk of falls and fractures that may occur during traditional treadmill training among breast cancer survivors who are at an increased risk following treatment . while further research is needed to determine loading protocols and progression , the results of this study suggest that the alter - g treadmill is a safe , well - tolerated and feasible alternative to regular treadmill training . the nature of breast cancer rehabilitation is progressing to a more individualized method of exercise prescription . researchers have proposed individual surveillance models to assess survivors progress throughout the cancer continuum , and adjust exercise prescription accordingly ( 15,16 ) these models allow for physical limitations and impairments to be addressed consistently and exercise prescription to be modified accordingly . utilization of an scrd design , such as the one used in this study may be an effective way of monitoring patients . this is advantageous in a population where response to exercise may not represent that of an apparently healthy individual , and exercise prescription may vary accordingly . the simplicity of visual analysis provides practitioners a quick , straightforward method of analysing a participant s response to training . testing time was minimal with the exception for cardiovascular testing which was simultaneously used as an exercise session . the small sample size makes it difficult to generalize to a larger population of survivors . however , the benefit of this type of study design allows for each participant to be his or her own control . this gives the unique advantage of being able to analyse individual results rather than as a group . research of this nature highlights the individual response to exercise and supports the idea that variability in treatment received , duration of treatment , age , time since diagnosis , severity of disease , among others , may affect the response of breast cancer survivors to exercise . future studies may be strengthened by administering longer baseline phases between intervention phases to allow for a longer period of deconditioning . this in turn may make it easier to infer that it was the intervention that caused changes . this study took place in a small south eastern rural town and thus may not be generalizable to other geographical areas . the lack of laboratory tests may also be a limitation , particularly for methods of assessing cardiorespiratory fitness and body composition . future studies may be strengthened by more robust methods of assessment such as gas exchange analysis to determine vo2max and dual energy x - ray absorptiometry to evaluate changes in fat mass and lean body mass . inclusion of an anti - gravity treadmill in a pa program may provide practical and meaningful improvements in physiological and psychosocial variables in female bcs .

breast cancer survivors can experience a myriad of physical and psychological benefits as a result of regular exercise . this study aimed to build on previous research using lower impact exercise programs by using an antigravity ( alter - g ) treadmill to administer cardiovascular training . the purpose of this study was to determine the effectiveness a physical activity program , including an alter - g treadmill , for improving physiological and psychosocial measures in female breast cancer survivors . a 14-week intervention using an ab - ab study design was employed . six female breast cancer survivors were recruited to participate in the study . participants attended three 60-minute sessions per week , consisting of a combination of muscular strength / endurance , and cardiovascular endurance exercises . consistent with current literature and guidelines , exercise interventions were individualized and tailored to suit individuals . data was collected and analyzed in 2013 . visual inspection of results found improvements in cardiovascular endurance and measures of body composition . quality of life was maintained and in some cases , improved . finally , no adverse effects were reported from the participants , and adherence to the program for those who completed the study was 97% . the results of this study suggest that the use of a physical activity program in combination with an alter - g treadmill may provide practical and meaningful improvements in measures of cardiovascular endurance and body composition .

semiconducting metal oxide sensors are one of the most studied groups of the chemical sensors which have been designed to react with gases . different materials such as sno2 , wo3 , zno , moo3 , tio2 , inox , and mixed oxides have been studied and showed promising applications for detecting gases such as nox , o3 , nh3 , co , co2 , h2s , and sox [ 2 , 3 ] . therefore , improvement in the sensitivity , selectivity , rate of gas response , and reliability of oxide semiconductor gas sensors is important [ 46 ] . among various metal oxide semiconductors , tungsten oxide exhibits various special properties , which makes it very promising for applications in catalysis [ 7 , 8 ] and detection of the toxic gases . wo3 based mixed oxides such as wo3-ti , wo3-pd , pt , or au , wo3-in2o3 , and wo3-bi2o3 have also been investigated for their sensing characteristics . these mixed oxides have been especially used in fabricating selective and sensitive nox gas sensors . this is because the w ions have different oxidation state ( w , w ) enhancing the adsorption activity of nox molecule on the surface of wo3 structures [ 14 , 15 ] . recently , novel sensors based on tungsten oxide have been used for ozone monitoring [ 16 , 17 ] . tungsten oxide has attracted a lot of interests as an n - type oxide semiconductor . wo3 band gap has been measured by optical absorption in the range of 2.5 to 3.2 ev and is smaller than other semiconductors [ 19 , 20 ] . for wo3-based gas sensors , wo3 plays a role as a sensitive layer for detecting small quantities of nox and such nanoscale assemblies can achieve high sensitivity and fast response times . despite the considerable amount of works done on wo3 crystal structure so far , there are still important aspects of the electronic and structural properties of the wo3 nanoclusters and nox adsorption which are unclear , especially for the small clusters of wo3 . furthermore , the theoretical works which have been done so far are based on the standard dft methods which seriously underestimate the semiconductor band gap . this problem can be improved by using dft in combination with the hybrid functionals which provide a satisfactory option for the description of both the electronic and the structural properties of wo3 [ 22 , 23 ] . in this work a theoretical procedure was applied to study the nox ( x = 1,2 ) adsorption on the ( wo3)n ( n = 26 ) nanoclusters to evaluate the reactivity of wo3 nanoclusters from the quantum chemistry point of view . knowledge of the quantum reactivity indices and their role on the sensing properties of metal oxides is important to have an insight into the adsorption process and factors involved . in order to study the nox ( x = 1,2 ) adsorption on the cyclic ( wo3)n ( n = 26 ) nanoclusters , theoretically , dft method has been applied . lanl2dz and 6 - 311++g(d , p ) basis sets have been applied for w and other atoms , respectively [ 2527 ] . ( wo3)n ( n = 26 ) structures were generated in the vacuum and fully optimized using two kinds of hybrid functional of b3lyp and x3lyp . the adsorption of no and no2 molecules on the clusters was investigated to evaluate some aspects of nanoclusters and nox interactions . for geometry optimization , nox molecules were taken relaxed but the optimized structures of ( wo3)n ( n = 26 ) were kept frozen . the adsorption energies of nox molecule and five different substrates have been computed according to ( 1)e = enox @ wo3n ewo3nenox , where e[nox @ ( wo3)n ] is the total energy of the tungsten oxide cluster - nox complex and e(wo3)n and e(nox ) are the total energy of the isolated ( wo3)n and nox , respectively . [ 28 , 29 ] was carried out to explore the distribution of the electrons into atomic and molecular orbitals . based on these data , by homo - lumo analysis , the stabilization energies were calculated . chemical hardness , , and charge transfer , n , have been computed by koopmans theorem , using the following , respectively : ( 2)=lh , ( 3)n=bab+a , ( 4)e=l+h2 , where h and l correspond to the kohn and sham one - electron eigenvalues associated with the frontier molecular orbitals of homo and lumo , respectively . e is the electronic chemical potential . a and b subscripts stand for nox and ( wo3)n , respectively . densities of states ( dos ) were also calculated in order to analyze the band structures and fermi level changes of wo3 clusters , during the nox adsorption . figure 1 demonstrates all optimized cyclic structures of wo3 . in order to evaluate their abilities for using as the gas sensors since there are different adsorption sites on wo3 clusters for no adsorption , interfacial interactions between the clusters and no molecule will be different from the energy point of view . the most important parameters which affect the adsorption energy are the adsorption site and no conformation on the clusters . this means that for better analysis of the systems , it is necessary to investigate different orientations of no molecule on the different sites of the clusters . theoretical calculations confirmed that no adsorption through the n - head ( onwo3 ) is the most stable orientations through which the most adsorption energy is obtained ( table 1 ) . figure 3 shows the potential energy diagram for no adsorption on w2o6 clusters as an example . according to figure 3 , relaxed no molecule is close to wo3 clusters from a distance of 6 . considering table 1 , it can be concluded that x3lyp functional predicts stronger physical adsorption than b3lyp . correlation between the size of the cluster and adsorption energy is according to n : 2 > 3 4 > 5 > 6 at the x3lyp functional . the energy of adsorption for the most stable structures of on @ w2o6 and no @ w2o6 complexes is 0.685 and 0.340 ev , respectively . since on @ w2o6 complex is a better candidate than others from the energy viewpoint , in the next stage of our study , we concentrated on this type of interaction and it has been fully investigated through the quantum chemistry approach . table 2 shows the quantum chemistry reactivity indices for the stable structures . according to table 2 , charge transfer and chemical hardness have been increased from no to the surface with increase in the ( wo3)n clusters sizes . higher values of the charge transfer and chemical hardness mean that increase in the size of the system makes its electronic charges unstable and lowers its flexibility . natural population analysis confirms that there are considerable orbital overlap between w and n atoms of the clusters and no molecule , respectively . natural charges for n and w atoms of no @ w2o6 complex are + 0.08 , + 1.5e before adsorption and + 0.12 , + 1.38e after adsorption , respectively . this type of charge fluctuation indicates the charge flow from the adsorbate to the surface . the influence of no adsorption on the electronic properties of the tungsten oxide clusters was also investigated . as an example , figure 4 presents dos spectra of w2o6 cluster before and after adsorption . considering all systems , it was found that band gap ( e g ) changes are between 4.37 and 9.91% after the adsorption process . these results show that the adsorption of no molecule can not significantly affect the e g and conductivity of the nanostructures while the fermi level energy ( e fl ) is shifted by 0.385 ev towards the higher energies . due to this effect , metal oxide work function ( ) is decreased . finally , the dispersion corrected functional , x3lyp , shows that the theoretical results which have been computed by this method differ from the b3lyp in all cases . this means that the inclusion of an empirical dispersion correction to the density functional amplifies the calculated energies of physisorption . since , in the previous section , stronger adsorptions were obtained by x3lyp functional , this method is chosen for analysis of no2 @ ( wo3)n systems . figure 5 shows these adsorption models ( a)(d ) for no2 @ w2o6 complex as an example . adsorption energies for no2 @ ( wo3)2 systems have been calculated and reported in table 3 . according to table 3 , model d is the best configuration for no2 adsorption from the energy point of view , 2.0 ev . this extent of adsorption energy corresponds to no2 chemisorption on the w2o6 cluster . considering all possible models , it is confirmed that the reactivity order is according to the following : d > a > c > b. obtained correlation between the size of the cluster and adsorption energy is according to the following : n = 2 > 3 > 4 > 5 > 6 . different behavior of no2 adsorption on ( wo3)n ( n = 26 ) has been seen in the fermi level shifting character . as an example , w2o6 band gap is decreased from 10.10 to 9.97 ev after adsorption . due to no2 adsorption , fermi level is shifted by 0.26 ev towards high - energy region ( from 4.95 to 4.69 ev ) . charge transfer and chemical hardness changes during the no2 adsorption have been calculated and reported in table 4 . according to table 4 , there is a similarity between no2 and no adsorption behavior from the chemical hardness viewpoint . considering the electronic charge transfer , this means that increase in the size of the cluster promotes the chemical hardness while reducing the charge transfer between no2 and clusters . figures 6 and 7 show the obtained linear correlation of the adsorption energy - chemical hardness and adsorption energy - charge transfer , respectively . good correlation between the adsorption energy and chemical hardness is obtained while this correlation is weak in the case of the charge transfer . therefore , it can be concluded that the extent of chemical hardness fluctuation is one of the important parameters in sensing properties of the metal oxide clusters . natural population analysis confirms that w atom of w2o6 in the vicinity of no2 molecule has a positive character and carries a charge of + 1.6e . one o atom of no2 molecule which is closer to w atom of the nanocluster has obtained more negative charge than the other . due to this charge transfer from w , oxygen atomic charge is changed from 0.24 to 0.27e . comparing between the negative character of o atom and positive character of w atom , it can be concluded that w and o atoms do not exist as w and o as in the bulk of wo3 . therefore , we can conclude that there are considerable orbital overlaps between w and o atoms . back - donation of lone pair electrons of o atoms to the vacant d orbitals of w atoms is the source of this covalent character for w the adsorption of nox ( x = 1,2 ) molecules on the tungsten oxide clusters was investigated using density functional theory calculations by b3lyp and x3lyp functionals . during the adsorption of nox on the ( wo3)n ( n = 26 ) nanoclusters , energy is released with a significant charge transfer from the nox to the nanoclusters . the results showed that the adsorption energy depends on the size of the cluster . x3lyp w2o6 cluster is the best candidate for nox adsorption from the energy point of view . in order to have a meaningful understanding of molecular changes during the adsorption process , quantum chemistry reactivity indices such as chemical hardness and charge transfer parameters were evaluated . obtained results from the natural bond orbital and electronic density of states analysis confirmed the electronic charge transfer from the adsorbates to the wo3 clusters and fermi level shifting after adsorption , respectively .

today 's wo3-based gas sensors have received a lot of attention , because of important role as a sensitive layer for detection of the small quantities of nox . in this research , a theoretical study has been done on the sensing properties of different cyclic nanoclusters of ( wo3)n ( n = 26 ) for nox ( x = 1,2 ) gases . based on the calculated adsorption energies by b3lyp and x3lyp functionals , from the different orientations of nox molecule on the tungsten oxide clusters , o nw was preferred . different sizes of the mentioned clusters have been analyzed and w2o6 cluster was chosen as the best candidate for nox detection from the energy viewpoint . using the concepts of the chemical hardness and electronic charge transfer , some correlations between the energy of adsorption and interaction energy have been established . these analyses confirmed that the adsorption energy will be boosted with charge transfer enhancement . however , the chemical hardness relationship is reversed . finally , obtained results from the natural bond orbital and electronic density of states analysis confirmed the electronic charge transfer from the adsorbates to wo3 clusters and fermi level shifting after adsorption , respectively . the last parameter confirms that the cyclic clusters of tungsten oxide can be used as nox gas sensors .

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

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

however , simple open prostatectomy is a recommended method for extremely enlarged prostatic hyperplasia . here , we report a case with a 475 g adenoma that was enucleated by retropubic open prostatectomy . a 70-year - old man was admitted to our hospital with a complaint of asymptomatic macrohematuria . urinalysis showed 5099 red blood cells / high - power field and 01 white blood cell / high - power field . the result of his urinary cytology was class i. on digital rectal examination , the prostate was found to be grossly enlarged . the serum prostate - specific antigen ( psa ) level was 9.430 ng / ml ( normal range 04 ng / ml ) . a computed tomography scan of his abdomen and pelvis confirmed a considerably heterogeneous enlarged prostate measuring 580 ml . on t1- and t2-weighted magnetic resonance imaging ( mri ) , a heterogeneous prostate with sharply marginated nodules was found . drip - infusion pyelography showed a normal upper urinary tract with a huge shadow defect of the urinary bladder ( figure 2 ) . a prolonged and narrow prostatic urethra was observed by retrograde vesicourethrography ( figure 3 ) . total international prostate symptom score ( ipss ) was 14 points , and quality - of - life index was 4 . uroflowmetry ( ufm ) demonstrated maximum urinary flow rate and average urinary flow rate to be 12.6 ml / second and 4.8 ml / second , respectively , with 50 ml of residual urine volume . thus , he was diagnosed as having giant prostatic hyperplasia and underwent retropubic open prostatectomy through a lower abdominal midline incision . as expected , a markedly enlarged prostate with smooth surface could be seen in the pelvic cavity . the removed specimen was 13 11 6 cm in size and weighed 475 g ( figure 4 ) . the operation time was 70 minutes , and blood loss during surgery was 1758 ml including urine . vesicourethrography at postoperative day 7 showed that the prostatic urethra was obviously wider than before operation . at a month after surgery the results of the ufm were found to be maximum urinary flow rate of 29.2 ml / second , average urinary flow rate of 13.1 ml / second , and residual urine of 20 ml . etiology of prostatic growth demonstrates that prostate size increases slowly and steadily with aging.1 however , cause and effect links have not been established . the term giant prostatic hyperplasia was defined by fishman and merrill2 as exceeding 500 g. in this case , preoperative mri revealed a 580 ml prostate , and actual weight was 475 g. although we thought that the increment in the psa level was probably due to the enlarged prostate adenoma , we performed a biopsy ( ten specimens ) to rule out prostatic cancer . surgical treatment for men with bph is reserved for those who do not respond well to medical therapy or who have complications such as urinary retention . in this case , we considered that there was a surgical indication since macrohematuria continued and he was suffering from lower urinary tract symptoms . transurethral resection of the prostate , the gold - standard surgery , is usually applicable to a bph of up to moderate size ( < 5080 ml).3 on the other hand , the surgical treatment options for bph have dramatically changed over the past two decades with the development of minimally invasive therapies . they include holmium laser enucleation of the prostate , transurethral electrovaporization of the prostate , transurethral microwave thermotherapy , and others.3 however , these techniques are also performed for patients with slightly to moderately enlarged prostates . rocco et al stated that 100 g is regarded as the limit of weight for those minimally invasive procedures.4 european association of urology guidelines also show that open prostatectomy is the treatment of choice for large prostatic glands more than 80100 ml5 in size . mccullough et al published the data that laparoscopic simple prostatectomy for patients with bph was less invasive compared to open prostatectomy.6 they stated that men who underwent laparoscopic prostatectomy had less postoperative catheter time and a shorter hospital stay , although a longer operation time . as for the prostate size , the average preoperative prostatic volume was 111.3 35.3 cm in the laparoscopic group.6 it was thought that patients with severely enlarged adenoma were not treated with laparoscopic surgery . in 2008 , robotic simple prostatectomy was first reported by sotelo et al.7 furthermore , vora et al summarized the studies of robotic simple prostatectomy.8 in summary , robotic surgery provides all the merits of laparoscopy with a potentially shorter learning curve . urinary flow rate , postvoid residual urine , and ipss scores were also improved by robotic prostatectomy . operation time and estimated blood loss were similar to those seen in the laparoscopic group . however , sutherland and colleagues reported that they could not successfully perform robot - assisted simple prostatectomy for a man with severe prostatomegaly ( 260 g ) , although a maximal limit was not placed on prostatic adenoma size during the preoperative evaluation.9 these two papers indicated that both laparoscopic and robotic simple prostatectomy would not be feasible for severely enlarged prostate . thus , we considered that simple prostatectomy was the recommended treatment for men with enlarged prostate , including giant hyperplasia . in this case , as the estimated prostate volume based on mri was 580 ml , we performed retropubic open prostatectomy . operation time was short , and no major complication occurred . to the best of our knowledge , this is the 15th - heaviest adenoma ever reported in the english - language literature.10 simple open prostatectomy was performed in all 15 cases .

we report a rare case of giant prostatic hyperplasia treated by open surgery . a 70-year - old man was suffering from macrohematuria . computed tomography revealed a markedly enlarged prostate measuring 580 ml . the serum prostate - specific antigen level was 9.430 ng / ml . prostatic biopsy showed benign prostatic hyperplasia . we perfomed retropubic open prostatectomy , since macrohematuria continued and he was also suffering from lower urinary tract symptoms . the adenoma was completely enucleated in one piece . the removed specimen was 13 11 6 cm in size and weighed 475 g. histological examination also demonstrated prostatic fibromuscular hyperplasia . this is the 15th - heaviest adenoma ever reported in english - language journals . transurethral surgical techniques or other minimally invasive approaches are performed for patients with small to medium - sized prostates . however , open surgery is recommended for markedly enlarged prostatic hyperplasia .

hearing evaluation usually includes hearing threshold assessment , middle ear function , and word recognition tests that lead to an accurate result of peripheral and central auditory system [ 13 ] . however , they have some limitations because they can not fully encompass all aspects of hearing loss problems . communicative ability of patients with sensory - neural hearing loss heavily depends on important factors like acceptance or denial of hearing loss , general communication skills , emotional adaptation , friends and family condition . because of these nonauditory factors ; audiological tests could not evaluate individual ability for communication and participation . therefore , this group of test in the best conditions can only provide some information of communicative handicap indirectly . using self - assessment approach , via a questionnaire or telephone survey is one of the easiest methods to study hearing loss in population [ 57 ] . many of the self - assessment tools are designed for using in a particular population for instance hearing performance inventory ( hpi ) questionnaire is appropriate for evaluation of noise induced hearing loss cases , hearing handicap inventory ( hhie ) scale is suitable for elderly patients with hearing loss , and communication profile for hearing impaired ( cphi ) questionnaire is considered for military studies . these scales are helpful in order to identify the problems and issues related to hearing handicap , understand the communication difficulties , and determine special needs of patients but nhhi focused specifically only on nursing home elderly . in fact , they are not only an objective evaluation method to monitor the progress of rehabilitation process but also provide invaluable information about awareness and consultation for individuals and their families . nursing home staffs just ask a few questions about hearing problems during completing every case profile and obviously it is not enough to find hearing impaired persons [ 1214 ] . using hearing aids with environmental modification in nursing home might improve general situation and specially hearing condition for this group of people . therefore , hearing handicap self - assessment results , audiometric findings and patient 's tending to use hearing aids or any assistive listening devices reflect their aural rehabilitation needs more clearly . nursing home residents problems were focused in nhhi ( nursing home hearing handicap index ) questionnaire which developed by show and nerbonne in 1977 . the 20 items questionnaire divided into two versions : the self - version which was completed by residents ( 10 items ) and staff - version that should be fulfilled by the nursing home staff ( 10 items ) . 60 nursing home residents ( 27 females and 33 males ) ranging from 55 to 85 years with a mean age of 71 5.5 were selected . after case history and otoscopy examination , pure tone audiometry test was conducted via madsen ob822 audiometer to identify hearing loss , and tympanometry test was performed by interacoustics at235h tympanometer to rule out any middle ears disorders . then nhhi questionnaire was completed by the elderly cases ( nhhi self - version ) and the other one was filled by the nursing home personnel ( nhhi staff - version ) . kruskal - wallis statistical test and hearing loss level data is found in table 1 divided into severity of hearing loss and gender . the analysis of questionnaire results showed that the average score of self - version part was 33.80% 27.01 and the average score of staff - version was 34.54% 26.48 . the effects of the hearing loss level on the self- and staff - version scores indicated that there is a significant relationship between self- and staff - version with hearing loss levels ( p < 0.05 ) . in other words , the severity of hearing loss becomes greater as the questionnaire score goes up and followed by hearing handicap is also increasing in elderly . this relationship is not significant in male group ( p > 0.05 ) however it is significant in the female group ( p < 0.05 ) in the self - version . on the other hand , the relationship between the hearing loss levels and staff - version is significant in both men and women groups ( p < 0.05 ) as can be found in table 3 . in testing the relationship between nhhi results and audiological findings by using chi - square and pearson 's correlation coefficient , the results revealed significantly correlated with each other at a statistically significant level ( p value ) of < 0.05 as shown in table 4 . outcomes from a hearing handicap scale can give more information about the patient 's understanding of hearing loss effects on daily life . if the resident reports a considerable handicap , then auditory rehabilitation will be suggested . nursing home staffs that are close to resident can also complete a hearing handicap scale . results can provide essential information on how others distinguish the resident 's hearing loss and audiological rehabilitation necessitate . in the present study , we used nhhi questionnaire and compared its results with pta findings . moreover , we investigated the correlation of hearing impairment severity on nhhi ( two versions ) scores in nursing home elderly . because of significant pearson 's correlation coefficient results ( p < 0.05 ) between both versions with hearing loss levels and as other studies suggested [ 1719 ] it can be inferred in cases who were not able to respond scale , staff answers might be considered . in this study results indicated using self - report scale could be valuable in order to prepare rehabilitation needs of elderly before hearing handicap was grown up and its difficulties came out . results from this study demonstrate the usefulness of nhhi questionnaire for evaluating hearing handicap of aged people and it may be a useful adjunct in setting up treatment and determining proper care . limitation of studyin spite of searching for new resources in this field and no newer - revised version of the nhhi questionnaire , references might be somewhat old , but nevertheless they are reliable in this area . in spite of searching for new resources in this field and no newer - revised version of the nhhi questionnaire , references might be somewhat old , but nevertheless they are reliable in this area .

hearing evaluation usually includes hearing threshold assessment , middle ear function , and word recognition tests that lead to an accurate result of peripheral and central auditory system . however , they have some limitations because they can not fully encompass all aspects of hearing loss problems . using self - assessment approach , via a questionnaire or telephone survey , is one of the easiest methods to study hearing loss in population . in this research , 60 nursing home residents ( 27 females and 33 males ) ranging from 55 to 85 years with a mean age of 71 5.5 were studied via completing self - assessment questionnaire by the elderly cases ( nhhi self - version ) and the other one was filled by the nursing home personnel ( nhhi staff - version ) . the effects of the hearing loss level on the self- and staff - version scores indicated that there is a significant relationship between self- and staff - version with hearing loss levels ( p < 0.05 ) in male and female . results from this study demonstrate the usefulness of nhhi questionnaire for evaluating hearing handicap of aged people and it may be a useful adjunct in setting up treatment and determining proper care .

clinical history is not helpful , and only 50% of ingested toothpicks are radioopaque 2 . a 82yearold woman was admitted to our university hospital because of fever of unknown origin ( t 39c ) , leukocytosis ( wbc 16730 mmc , n 85% ) , and severe inflammatory markers ( pcr 20.90 mg / dl ) . for this reason , patient was first admitted to division of infectious diseases to make a diagnosis . ultrasonography revealed an 8cmdiameter hypoechoic hepatic mass in the left lobe with a linear hyperechoic foreign body inside . after execution of abdominal ultrasound , routinely performed to exclude abdominal causes of fever , the patient was referred to our division of surgery where an abdominal ct was performed to confirm and better describe the nature of the foreign body and hypoechoic mass in the liver . helical ct scan confirmed the presence of the lesion and the foreign body located mainly in segment 2 and extended to segment 3 , which was interpreted as a multilocular abscess with a wooden toothpick inside . the patient underwent laparoscopy , and a wooden toothpick tip was noted on the inferior surface of the left lobe without any sign of previous gastrointestinal perforation . a 3port laparoscopic left hepatic lobectomy was performed , and a 6cm wooden toothpick was extracted along with the resected liver . the histopathologic diagnosis was foreign body granuloma with sterile abscess ( probably due to broadspectrum antibiotic therapy ) . in case of fever of unknown origin , it is important to exclude surgical causes by ultrasonography and helical ct scan when indicated 3 . en bloc laparoscopic segmental liver resection in case of abscess secondary to foreign bodies the authors declare that there is no conflict of interest regarding the publication of this manuscript .

key clinical messageingestion of foreign bodies is a common clinical problem , but intrahepatic migration is an exceptional occurrence . clinical history is not helpful . abdominal ultrasonography and ct are fundamental to exclude surgical causes of fever of unknown origin . laparoscopic segmental liver resection is recommendable to avoid generalized peritonitis .

vitreous inflammation , or vitritis , may result from many causes , including both infectious and noninfectious . epidemiologic studies indicate that uveitis accounts for 210% of prevalent blindness in the european and north american population and is therefore an underrated and significant public health problem . infectious etiologies include bacterial lyme , syphilis , or bartonella ; viruses hsv , vzv , and cmv , and a variety of fungal and parasitic causes . noninfectious etiologies include rheumatologic and autoimmune processes , examples being sarcoidosis , systemic lupus erythematosus , multiple sclerosis , and behcet 's disease . however , idiopathic vitritis without associated systemic disease is most common . vitritis is sometimes visionthreatening , due to sequelae such as cystoid macular edema ( cme ) , vitreous opacities , and retinal detachment , ischemia / neovascularization , or pigment epithelium changes . glaucoma and cataracts may also form . with such serious sequelae , there are multiple methods of systemic treatment for vitritis . on the other hand , mild vitritis without vasculitis or cme the goal of all types of treatment is to rapidly alter and stop the course of intraocular inflammation but at the same time minimize any side effects from these systemic drugs . we reviewed these treatment categories last year , but , even over the course of just a year , many therapies have made progress , as we have learned more about their indications and efficacy . this group of drugs is used to suppress inflammation , either systemically or intraocular . the accepted algorithm for treatment begins with topical glucocorticoids , with frequency depending upon severity and not necessarily etiology . however , topical corticosteroids have been shown to have poor penetration into the posterior segment and are thus not used often for posterior segment disease ; they are more commonly used to reduce anterior chamber inflammation and have only a minor effect on vitreous inflammation . oral or intravitreal corticosteroids are therefore used to treat cases of posterior segment disease . oral prednisone ( 1 mg / kg / day with gradual tapering ) intravitreal delivery systems include injection or implantation of periocular or intravitreal steroid compounds ( triamcinolone acetonide ) . there are several different types of systems , either nonbiodegradable or biodegradable ; a more extensive review of drug delivery implants is reviewed in our other paper . although previous studies raised concern for recurrence of inflammation as intravitreal steroid concentration decreases , some recent trials elude that this may no longer be the case . it has however been reported that localized side effects may occur , such as cataract formation , increased intraocular pressure , and transient vitreous hemorrhage . on the other hand , those undergoing systemic corticosteroid therapy often encounter nonocular adverse events , such as arthralgia and hypertension . other common complications range from those affecting the musculoskeletal system ( osteoporosis , aseptic bone necrosis , and myopathy ) , gastrointestinal system ( ulcers and pancreatitis ) , endocrine ( hyperglycemia and cushinoid features ) , infectious , ( delayed wound healing , secondary infection , and reactivation of latent herpes simplex or tuberculosis ) , or even psychosis . if patients develop adverse effects , or are refractory to treatment with corticosteroid therapy , switching to an intravitreal delivery system or considering systemic immunosuppressive therapy is indicated . systemic immunosuppressive therapy can either supplement or completely replace corticosteroid therapy , for the reasons touched upon above . there are several conditions that have been found to be refractory to corticosteroid treatment but instead respond to immunosuppressives . examples of these conditions ran the gamut of several autoimmune diseases such as behcet 's , wegener 's , or juvenile idiopathic arthritis - associated uveitis . there are several categories of immunosuppressive agents : antimetabolites , alkylating agents , t - cell inhibitors / calcineurin inhibitors , and biologic agents . information about these categories is available in table 2 , while newer biologics and investigations are discussed below . table 3 addresses ocular diseases and which groups of immunosuppressive agents are used to treat them . in general , treatment with immunosuppressives starts after or with corticosteroid therapy , with local treatment attempted before systemic treatment , if the disease process is amenable . systemic treatment attempts to start with the least toxic medications in the case of mild - moderate disease ; methotrexate and cyclosporine are most commonly used after corticosteroids , followed by more antimetabolites . severe , vision - threatening disease may require the use of biologic or cytotoxic agents , although they are avoided whenever possible due to their severe adverse effects . leflunomide is a noncytotoxic drug that works on both the cellular and humoral immune response . it is most commonly used for systemic rheumatologic diseases , examples being severe rheumatoid or psoriatic arthritis . recently , leflunomide was proven as both safe and efficacious for long - term therapy treating chronic anterior uveitis associated with juvenile idiopathic arthritis . most patients maintained an ocular response to the drug and underwent only a few mild adverse effects . common adverse effects of leflunomide include hepatotoxicity with known fatalities , myelosuppression with resulting opportunistic infection and anemia , interstitial lung disease , alopecia , and skin reactions ( stevens johnson and toxic epidermal necrolysis ) . leflunomide is also a teratogen ( pregnancy class x ) , and patients need to be on contraception during treatment . overall , it is a promising form of treatment , as methotrexate is currently the first and was previously the only choice for patients with juvenile idiopathic arthritis . they were originally developed for preventing organ transplant rejection but were found to be useful for treating systemic inflammatory diseases as well . they are now used off label in treating uveitis , and have been used with some success for refractory cases . biologic agents ' major mechanisms of action all revolve around targeting specific inflammatory molecules , with the goal of inhibiting mediators or cytokines . examples of these inflammatory mediators include tumor necrosis factor alpha and interleukin-2 . due to their strong immunologic suppression , latent and opportunistic infections are especially important to monitor for and include those such as tuberculosis , histoplasmosis , coccidiomycosis and herpes viruses . monoclonal antibodies are further classified and suffixes named based on their regions ( either human , murine , or a combination of regions ) . fusion proteins are created by joined genes , and are a combination of a receptor and another protein fragment . adalimumab is a recombinant , full - length humanized immunoglobulin directed against tumor necrosis factor ( tnf ) . it is able to bind with both high affinity and specificity to soluble tnf or , thus neutralizing the biological function of tnf , as well as modulating biological responses that tnf is responsible for inducing or regulating . it is currently used with increasing frequency for treating several autoimmune diseases such as behcet 's , juvenile idiopathic arthritis - associated uveitis , vogt - koyanagi - harada ( vkh ) disease , and birdshot retinochoroidopathy [ 1216 ] . a recent multicenter trial found it to be a useful treatment for patients with refractory uveitis , with a 10-week success rate of 68% . a more recent retrospective analysis of 60 patients , the largest case series to date , showed a positive effect of adalimumab in 82% of these patients with different uveitis types , independent of additional systemic disease . this study found that those who had been treated with infliximab and etanercept with insufficient response were effectively treated with adalimumab in 92% of cases . another interesting finding was that patients pretreated with other tnf agents still had good results ; thus , it is reasonable to switch to another tnf agent if the first was ineffective . in this study , no major infections nor serious complications known to tnf inhibitors ( demyelinating disease , reactivation of tb ) occurred . this is a significant finding , as adalimumab may thus be a better option than infliximab , although follow - up was short and the study 's power would need to be increased in a further study . another prospective study evaluated the efficacy and outcomes of using adalimumab to treat uveitis associated with juvenile idiopathic arthritis . ocular symptom improvement was seen in 76% of cases , with anterior uveitis flare rate reduced after starting treatment . this study also confirmed a lack of serious sideeffects and infections and fewer hypersensitivity reactions than infliximab . overall , this study concluded that adalimumab was a reasonable adjuvant therapy for treating uveitis . most commonly used in hematologic and autoimmune disorders , it has been found to be effective as a sole treatment for wegener 's uveitis and retinal vasculitis [ 19 , 20 ] . the value of rituximab in behcet 's disease is yet to be determined , due to limited evidence . in addition , it has also been used with intravenous igg to treat ocular cicatricial pemphigoid . tocilizumab is a humanized antibody that binds both to il-6 receptors , originally used for treating rheumatoid arthritis and systemic juvenile idiopathic arthritis . il-6 has a role in proliferation and differentiation of t- and b - cells , with persistent production demonstrated in chronic inflammatory diseases . although ophthalmologic usage is currently limited , patients with active posterior uveitis have been found to have elevated il-6 levels in serum and intraocular , although levels were not specifically correlated with a clinical diagnosis . in one retrospective study , tocilizumab was found to be efficacious in treating uveitis patients with cystoid macular edema that was refractory to intraocular steroids or other immunosuppressive therapies . these patients were found to have complete resolution after six months of therapy and were also found to have no recurrence of inflammation at follow - up , suggesting that it is able to maintain disease remission . in another recent case study , a patient with severe refractory posterior uveitis improved , with decreasing levels of il-6 after treatment . it is a new therapy whose indications and efficacy are still being studied ; a recent pilot study for patients with refractory behcet 's disease showed promising results , with only two infusions needed to render patients attack - free for several months . treatment led to a rapid reduction in manifestations of intraocular inflammation , without the rebound attacks associated with discontinuation of corticosteroid use . this was thought to be in part due to accumulation of gevokizumab in ocular tissues , thus being able to sustain its therapeutic effect with an infrequent dosing interval . ifn- 2a , ifn- 2b , ifn- 1a , and ifn- 1b are the classes most commonly used in therapy . interferons are commonly used to treat conditions ranging from malignancy ( cutaneous melanoma ) , infection ( hepatitis c ) , and inflammatory ( multiple sclerosis ) [ 28 , 29 ] . as far as ophthalmologic uses , ifn- 2a has successfully treated behcet 's disease , and ifn- 1a reduced uveitis recurrences in multiple sclerosis patients [ 3033 ] . in behcet 's disease , interferon demonstrated significant benefit by decreases in aphthous ulceration and the number of lesions . several studies consistently reported that many patients had durable remissions of ocular inflammatory disease after discontinuation . anakinra is an interleukin-1 receptor antagonist , which competitively inhibits il-1 binding to its receptor . il-1 has been found to have significance in systemic autoinflammatory diseases , where excessive il-1 signaling will occur . it plays a key role in auto inflammatory diseases such as muckle - wells and neonatal onset multisystem inflammatory disease ( nomid ) , which are rare causes of uveitis in childhood . it may in the future be used to treat refractory juvenile idiopathic and behcet 's disease , for which it is currently in phase iii clinical trials . uveitis is a vision - threating group of diseases that encompasses a variety of etiologies , which are either infectious or noninfectious . uveitis resulting from infection , however , focuses on eradicating the source with antibiotics or antivirals . these antimetabolites , cytotoxic agents , biologics , and immunomodulators can be used either alone or together , to control inflammation of the vitreous . as with any medication , especially immunosuppressants , side effects must be balanced with therapeutic benefit a determination still in process for many drugs and indications . even with its difficulties , research on expanding indications for existing therapies and the discovery of new systemic agents continues to progress .

vitreous inflammation , or vitritis , may result from many causes , including both infectious and noninfectious , including rheumatologic and autoimmune processes . vitritis is commonly vision threatening and has serious sequelae . treatment is frequently challenging , but , today , there are multiple methods of systemic treatment for vitritis . these categories include corticosteroids , antimetabolites , alkylating agents , t - cell inhibitors / calcineurin inhibitors , and biologic agents . these treatment categories were reviewed last year , but , even over the course of just a year , many therapies have made progress , as we have learned more about their indications and efficacy . we discuss here discoveries made over the past year on both existing and new drugs , as well as reviewing mechanisms of action , clinical dosages , specific conditions that are treated , adverse effects , and usual course of treatment for each class of therapy .

xanthogranulomatous pyelonephritis ( xgpn ) is an uncommon condition that can present in multiple ways . the index of suspicion should be present , especially in the setting of obstructive urolithiasis . conservative treatment with antibiotics is an option in focal cases , but surgery is usually required in diffuse cases or when malignancy can not be ruled out . to the best of our knowledge , this is the first reported case of xgpn presenting with an anterior abdominal preperitoneal collection . a 47-year - old immunocompetent chinese lady , who had no medical history , was admitted to the hospital for investigation of increasing abdominal distension . computed tomography abdomen / pelvis showed significant right hydronephrosis with a 2 cm mid - ureteric calculus ( figs 13 ) . there was also associated soft tissue thickening in the lower pole of the right kidney . she underwent insertion of a right percutaneous nephrostomy drain , percutaneous drainage of the anterior abdominal collection , as well as a percutaneous biopsy of the right renal soft tissue lesion . magnetic resonance imaging ( mri ) of the abdomen was then performed to better evaluate the nature of the preperitoneal anterior abdominal collection ( fig . small non - dependent peritoneal nodules were noted , which raised the concern for the possibility of malignancy . after a period of antibiotic treatment , she underwent open right nephroureterectomy with exploration , drainage and washout of the preperitoneal collection . during surgery , 1 l of pus was drained from the preperitoneal space , and cultures grew p. mirabilis . the ureter was ligated below the level of the calculus and removed together with the kidney . final histopathology results showed xgpn with no evidence of malignancy in the kidney or peritoneal lining . post - operatively , she had small residual subhepatic collections , which were drained percutaneously , and she was discharged on the 11th post - operative day . a recently published case series of 12 xgpn cases showed that only one patient presented with fever . our patient had an atypical presentation with abdominal distension and presumed ascites , which was eventually revealed to be an anterior preperitoneal collection secondary to infection . although the initial suspicion was that of a malignant process complicated by ascites , subsequent cytology and histopathological results showed that it was likely benign . in view of the non - functioning renal unit and significant abdominal collection the most common urinary pathogen identified was escherichiacoli , and common areas of involvement were the retroperitoneum and psoas muscle . in our patient , the retroperitoneal space was surprisingly not greatly involved , but rather it was the anterior preperitoneal space that had significant adhesions and inflammation . the pathogen identified from both nephrostomy and preperitoneal collection was p. mirabilis , showing that both pathologies were linked . previous authors have described laparoscopic approaches for the treatment of xgpn , but this would unlikely have been suitable for our patient with a large anterior abdominal collection . conservative management with antibiotics , or partial nephrectomy , has been described for focal forms , but diffuse forms usually require total nephrectomy . none of the contributing authors have any conflict of interest , including specific financial interests or relationships and affiliations relevant to the subject matter or materials discussed in the manuscript .

xanthogranulomatous pyelonephritis ( xgpn ) is a rare form of chronic pyelonephritis with progressive loss of renal function . commonly , obstructing urinary calculi are seen . it is difficult to differentiate between xgpn and malignancy in many cases , and the diagnosis is usually only confirmed post - operatively upon histopathological examination of the specimen . surgical treatment is often the main treatment modality due to suspicion for malignancy . here , we present a case of xgpn that presented with abdominal distension , which was eventually discovered to be due to a preperitoneal abscess .

a 21-year - old woman visited our department complaining of a large painless swelling in the left submandibular region . on palpation , the swelling revealed a soft , painless , and fluid - containing mass . the patient had no traumatic or surgical history , and the swelling did not cause difficulty in swallowing or speaking . contrast - enhanced computed tomography ( ct ) scan demonstrated a large rim - enhanced fluid attenuation mass occupying both sublingual spaces with an anterior connection ( fig . the lesion extended into the left parapharyngeal space superiorly and compressed the left submandibular gland inferiorly ( fig . anteriorly , it extended to the right sublingual space in a horseshoe shape ( fig . at the lower level of the lesion , several linear septa were noted ( fig . 1c ) . a fluid - fluid level , which is the interaction between two fluids with different viscosities , was also noted ( fig . although the septation and fluid - fluid level within the lesion made the differential diagnosis from a cystic hygroma difficult , considering the location of the lesion in the sublingual space , it was diagnosed as a plunging ranula . under general anesthesia , an incision was made in the left lingual vestibule , and excision of the lesion along with extirpation of the left sublingual gland was performed . at surgery , the cystic lesion was found to be filled with a viscous and yellowish mucous fluid . after removal of the left sublingual gland , a cut - down tube was inserted into the middle portion of the left wharton 's duct . the histopathologic examination of the specimen from the sublingual gland revealed ruptured acinar cells ( fig . the cut - down tube inserted into the left wharton 's duct was removed after 2 weeks . the descriptive term ranula normally refers to a bluish , transparent , thin - walled swelling in the floor of the mouth . while simple ranulas are all confined to the sublingual space , plunging ranulas are centered on the submandibular space and tend to spill into one or more adjacent spaces.7 the nature of ranulas was unknown until 1956 , when bhaskar et al8 investigated the pathogenesis histopathologically and experimentally , and they concluded that ranula was produced by the extravasation of saliva from a damaged salivary sublingual gland and was not lined by epithelium . the occurrence of ranula is rare , and the reported male - to - female ratio is 1 : 1.3 , without significant side preference.9 the plunging ranula most frequently occurs in the second and third decades of life , with an age range from 3 to 61 years , and most commonly involves the right side.10,11 most giant plunging ranulas are located from the ipsilateral sublingual space to the parapharyngeal space . however , the present case of plunging ranula passed the midline and extended to the contralateral sublingual space . based on our review of the english literature , only two cases of huge plunging ranula which passed the midline have been reported.11,12 the previous cases which passed the midline showed an extension into the cervical space inferiorly , but the present case did not extend beyond the submandibular gland . a rare case of plunging ranula with subtle septa these septa might have been secondary to surgical procedures or a traumatic history . in those cases , wall thickening and minimal internal septa formation were noted.13,14 a trauma or a surgery might lead to the development of scar tissue , and it might be detected as a subtle septation within the plunging ranula . in the present case , although no previous trauma or surgery was found by history taking , it might be expected that the patient was unaware of the previous trauma considering the fluid - fluid level within the lesion . a fluid - fluid level has , in rare cases , been reported to occur in the plunging ranula and refers to the interaction between two fluids with different viscosities , commonly by hemorrhage.13 the blood vessels near the submandibular gland area are weak ; therefore , the fluid - fluid level might easily result from trauma to the area . cystic hygroma rarely presents in the sublingual space , but if present , it reveals very similar images on ct scan to those of a plunging ranula . for cystic hygromas , the mainstay of treatment is surgical excision . the surgical team should attempt to completely remove the lymphangioma or to remove as much as possible , sparing all vital neurovascular structures.15 treatment of a plunging ranula is also surgical excision , but the difference is the complete excision of the sublingual gland . there are several treatment options for ranula , which include excision of only the ranula and marsupialization . however , excision of the entire sublingual gland and ranula reported the lowest recurrence rate of 1.55% . as plunging ranula and cystic hygroma are managed with different surgical approaches , the differential diagnosis is critical.14 cystic hygroma arises from the abnormal development of fetal lymphatic tissue . it typically presents early in life , with 50% present at birth and 90% evident by 2 years of age . cystic hygroma is characteristically infiltrative in nature and typically involves contiguous anatomic regions in the neck . it appears as defined but poorly circumscribed , lobulated , septated , homogeneous , and with fluid attenuation on ct images . a previously infected lesion may show heterogeneous attenuation due to previous hemorrhage or high protein content . in case of hemorrhage therefore , the differential diagnosis between plunging ranula and cystic hygroma is often difficult on imaging . the characteristics of cystic hygroma for lobulation , strong septation , and rarity in the sublingual space should be helpful for diagnosis . in our case , the histopathologic examination demonstrated ruptured acinar cells of the sublingual gland , which confirmed the diagnosis of the plunging ranula . the recurrence rates of ranula were not related to the swelling patterns and surgical approaches , but intimately related to the methods of surgical procedure.16 effective treatment is removal of the involved sublingual gland or inducing sufficient fibrosis to seal the leak through which mucus extravasates.17 in the present case , the plunging ranula and ruptured sublingual gland were removed and the patient showed no recurrence 6 months postoperatively . in conclusion , as plunging ranula and cystic hygroma are managed with different surgical approaches , it would be important to differentiate them radiologically . although a submandibular cystic lesion with septa and a fluid - fluid level would be unusual for a ranula , a plunging ranula should be considered in the differential diagnosis along with a cystic hygroma .

a ranula is a bluish , transparent , and thin - walled swelling in the floor of the mouth . they originate from the extravasation and subsequent accumulation of saliva from the sublingual gland . ranulas are usually limited to the sublingual space but they sometimes extend to the submandibular space and parapharyngeal space , which is defined as a plunging ranula . a 21-year - old woman presented with a complaint of a large swelling in the left submandibular region . on contrast - enhanced ct images , it dissected across the midline , and extended to the parapharyngeal space posteriorly and to the submandibular space inferiorly . several septa and a fluid - fluid level within the lesion were also demonstrated . we diagnosed this lesion as a ranula rather than cystic hygroma due to the location of its center and its sublingual tail sign . as plunging ranula and cystic hygroma are managed with different surgical approaches , it is important to differentiate them radiologically .

although the exact pathogenesis is uncertain , it is known that functional over - immunosuppression and epstein - barr virus ( ebv ) infections are strong risk factors for the development of ptld . lung - transplant recipients have at least a twofold greater risk of developing ptld compared to other solid - organ transplants . the general therapy for ptld includes the restoration of cellular immunity by reducing the intensity of immunosuppression . conventional antiviral therapy with acyclovir , valganciclovir , or ganciclovir has proven ineffective , but yet remains the recommended first - line therapy for ebv infection in cases of ptld . herein , we present a case of ebv - associated ptld following lung transplantation showing clinical improvement of lymphadenopathy with reduction in immunosuppression intensity but having persistent ebv infection , requiring foscarnet for viral clearance . a 24-year - old woman underwent successful sequential bilateral living lobar lung transplantation for cystic fibrosis . four years following transplant , she experienced her first and only mild acute cellular rejection ( ishlt grade a2 ) that was successfully treated with a 3-day course of intravenous solumedrol ( 1000 mg ) followed by prednisone taper . her immunosuppressive regimen at the time included prednisone 5 mg daily , tacrolimus 2.5 mg twice daily with a therapeutic drug level of 12.4 ng / ml , and mycophenolate mofetil 250 mg twice daily . additionally , she developed chronic kidney disease with a gfr 40 cc / min/1.73 m. to preserve renal function , sirolimus was added for calcineurin - inhibitor - minimization immunosuppressive regimen . additionally , one unit of cmv negative / leucophoresed blood was transfused for a moderate degree of normocytic / normochromic anemia ( hct 22% ) . the workup for blood loss had been inconclusive , and no further events occurred when seen in subsequent visits in clinic . six months later , she was admitted for fatigue and b symptoms of fevers , night sweats , and chills of three days duration . all other reviews of systems were negative . aside from tachycardia at 110 beats / minute and febrile at 39.4 c , other vitals were normal . physical examination was only remarkable for a palpable 2 cm 2 cm right - sided firm and nonpainful cervical lymph node . complete blood count showed pancytopenia , leucocyte count 2.4 10 cells / ml with an absolute neutrophil count 1.6 10 cells / ml , hematocrit 28.7% , and platelets 104 10 cells / ml . the immunosuppression regimen included prednisone 10 mg daily , tacrolimus 0.5 mg twice daily , mycophenolate mofetil 500 mg twice daily , and rapamycin 2 mg daily . tacrolimus and rapamycin levels were 11.4 ng / dl and 12.4 ng / dl , respectively . polymerase chain reaction ( pcr ) did not reveal cmv - dna , but did demonstrate a significant number of ebv - dna genome copies ( 870,908 dna copies / ml blood ) . a combined approach of intravenous ganciclovir 5 mg / kg twice daily with immunoglobulin ( cmv ig ) administration and rapid reduction of baseline immunosuppression therapy was instituted . both prednisone and sirolimus were tapered to 5 mg daily and 1 mg every 72 hours , respectively , giving a therapeutic drug level of sirolimus at 6.9 ng / dl . ct of chest , abdomen , and pelvis revealed numerous lymph nodes in the mediastinum , cervical , and abdominal regions ( figure 1 ) . excisional lymph node biopsy of the right scalene lymph node was positive for polymorphic ptld ( figure 2 ) . intravenous ganciclovir was initiated for the control of the ebv . with the reduction in immunosuppression therapy , a desired effect of lymph node size reduction was seen on ct scan 22 days later ( figure 3 ) . however , while on intravenous ganciclovir , pcr analysis detected continued elevation in ebv dna levels for an additional 35 days . the peak value was 10,200,000 dna copies / ml . ganciclovir was changed to foscarnet 90 mg / kg . this prompted a significant reduction in ebv pcr values to undetectable levels as depicted in figure 4 . aside from a mild increase in serum creatinine ptld is a well - recognized complication of solid organ and hematopoietic stem cell transplantation . it is a part of a group of heterogenous lymphoproliferative disorders primarily related to the oncogenic epstein - barr virus ( ebv ) . it generally develops within a year of transplantation but in our patient it developed 5 years after lung transplant . cytotoxic t - cell response is pivotal in controlling the reactivation and proliferation of the virus . ebv - infected cd20 + b cells replicate and proliferate in an environment of t - cell over - immunosuppression . rather than undergoing lytic replication , ebv - infected cells within ptld lesions replicate through proliferation of the transformed b cells . a constant degree of excessive immunosuppression allows for proliferation of ptld b - cell lymphocytes to manifest in an aggressive monoclonal or polyclonal b - cell lymphoma . besides impaired t - cell immunity , other risk factors of developing ebv infection following lung transplant include donor or recipient ebv seropositivity , a natural primary transmission , and hla - a3 expression . this group has a 30-fold higher risk compared to the seronegative group ( d/r ) . molecular analysis , however , shows that ebv - associated ptld following lung transplant more commonly originates from the recipient . some reports have shown that ebv can be transmitted and induce infectious mononucleosis if the donors were viremic for ebv at the time of donation . however in a study by wagner et al . , the effects of transfusing 15 ebv - seropositive blood products in 15 ebv - seronegative patients were assessed , and the results did not indicate ebv transmission . nevertheless , it is prudent to avoid the risks of transfusing blood products that are known to be contaminated with ebv . due to its rare occurrence , it is challenging to make definitive therapeutic recommendations for ptld . the cornerstone of therapy is the reduction or complete withdrawal of immunosuppressive therapy for enhancement of cellular immunity . this allows the normalization of the t - cell immunity and reduces proliferation of the transformed b cells . of course , this is in concert with balancing the risk of allograft rejection . in the management of ebv - associated ptld , the control of the ebv infection may or may not play a pivotal role , but antiviral therapy has been advocated by some centers . european best practice guidelines recommend the use of antivirals for at least 1 month after the diagnosis of ptld . acyclovir , valganciclovir , or ganciclovir are first - line therapeutic recommendations . when monitoring the ebv pcr values in association with ptld , the dna levels generally fall within 2 weeks and become undetectable by reducing immunosuppression and initiating antiviral therapy [ 7 , 9 ] . patients have been reported to have peak plasma ebv dna pcr levels of 663,000 copies / ml . in our case , it was clearly evident that clinical response of ptld was effectively attained with reduction in the immunosuppression regimen , but dna copies of ebv by pcr were persistently detected at high levels weeks after . controlling ebv infection is generally successful with nucleoside analogues , but ebv viral loads can be exceedingly high despite the continuous administration of intravenous ganciclovir in patients with ptld . the mechanism of action of nucleoside analogues , such as ganciclovir is the inhibition of viral dna polymerase and affecting cells that undergo lytic cycle . their use in ebv - infected ptld cases is of limited value because as many as 90% of ebv - infected ptld lesions are transformed cells that do not undergo lytic replication . foscarnet is distinct from the nucleoside analogues such that it does not require viral enzyme activation . its use has been reported in another patient with ebv - associated ptld who received a heart and kidney transplant ( 10 ) . that patient had a successful and persistent 10-month remission of the disease with reduction in the level of immunosuppression and a 4-week foscarnet therapy . similar to our case , anti - cd 20 monoclonal antibodies or chemotherapeutic agents were not required for the resolution of the ptld and ebv infection . the resulting impairment of ebv - specific cytotoxic t lymphocytes ( ctls ) , donor and recipient seropositivity , and hla - a3 expression and primary transmission are the primary risk factors for developing ptld . it is challenging to standardize a comprehensive treatment strategy due to ptld rare occurrence . a rapid reduction or complete withdrawal of immunosuppression nucleoside analogues such as acyclovir , valganciclovir , or ganciclovir are of limited value in ebv - associated ptld due to the proliferation of the cells remaining in latent form and requiring viral enzyme activation . however , the ebv pcr values continued to escalate while receiving nucleoside analogue against persistent ebv infection following clinical remission of lymphadenopathy . the use of foscarnet in combination with immunoglobulins resulted in successful reduction in ebv pcr values . this is only the second case reported of a persistent and successful remission of ebv infection and ptld . further analysis is warranted to assess foscarnet 's role as a first - line agent for the control of ebv associated with ptld .

posttransplant lymphoproliferative disorder ( ptld ) is a serious complication following solid organ transplantation with an annual incidence rate of 35% in lung - transplant recipients . pathogenesis indicates a strong association with functional over - immunosuppression and ebv infection . clinical improvement is generally observed with reduction in immunosuppression intensity alone . we present a case of a 24-year - old woman with ebv - associated ptld following lung transplant where decreasing the immunosuppression improved ptld but was ineffective against controlling the ebv infection . foscarnet in combination with immunoglobulins was successfully administered to cause a remission of the ebv infection . this is the second case reported of a persistent ebv infection after reducing immunosuppression levels and evidence of ptld remission that required foscarnet for ebv infection control .

it is generally presumed that the presence of post - operative pain adversely influences the patient 's experience of the perioperative period and negatively impacts perioperative satisfaction . although various therapeutic options to minimise acute post - operative pain have been evaluated by researchers from india , not much data could be retrieved by the authors regarding the prevalence or factors influencing the other aspects of post - operative pain from the indian subcontinent , even after thorough literature search . therefore , this study aims to evaluate the prevalence and intensity of acute post - operative pain and examine if there exists any correlation between patient 's intensity of pain and level of satisfaction with his / her pain management , in patients of inpatient abdominal surgery in a government - run academic tertiary care centre . mc/233/2013/354 ) , a prospective , single - group , descriptive study was conducted after obtaining informed consent from the participants during january - may 2015 . the study population consisted of patients between 18 and 60 years of age , inclusive of all sexes , who underwent elective abdominal surgery of 13 h in duration and were able to communicate in hindi with the first author . those patients who were unable to understand the questions posed by the researcher , with chronic pain , receiving antipsychotic drugs , on chronic use of analgesics , pregnant patients , patients undergoing surgery for malignant disorder and trauma were excluded from the study . in all the cases who received spinal anaesthesia , 3.23.8 ml 0.5% hyperbaric bupivacaine with 60100 g buprenorphine was used . general anaesthetic management was similar as the drugs that were in government supply ( ondansetron hydrochloride , propofol , tramadol hydrochloride , atracurium besylate , ketorolac tromethamine , paracetamol hydrochloride infusion , halothane , isoflurane , neostigmine methylsulphate , midazolam hydrochloride and glycopyrrolate bromide ) were used . all patients received a combination of intramuscular pentazocine and promethazine along with diclofenac sodium and/or paracetamol hydrochloride infusion . acute post - operative pain at rest was evaluated at the fifth post - operative hour , second and third post - operative days by numeric rating scale ( nrs ) . for further analysis , pain was classified as mild ( nrs 13.5 ) , moderate ( nrs 46.5 ) and severe ( nrs > 6.5 ) . the three questions ( question numbers 11 , 12 and 18 ) that were put to patients to rate their satisfaction required them to report satisfaction on a six - point scale [ questionnaire available online ] . the treating physician and nursing staff were not aware of the study hypothesis or outcome measures . the first author collected the data and was not a part of the team that provided perioperative care to the patients . data obtained were exported to a microsoft excel 2007 ( v12.0 , microsoft ) spreadsheet . demography and surgery - related characteristics including age , gender , level of education , occupation and type of abdominal surgery are reported with frequency , percentage , median with interquartile range and mean with standard deviation as deemed necessary . scatter plots were generated using microsoft excel 2007 ( v12.0 , microsoft ) . proportions of patients at different categories of pain intensity ( mild , moderate and severe ) were compared with two - sample z - test [ table 1 ] . patients with nrs < 4 and 4 were compared with chi - square test with yates ' continuity correction [ table 1 ] . spearman correlation coefficient ( ) and its 95% confidence interval ( ci ) were calculated using an online calculator ( available from http://vassarstats.net/corr_rank.html accessed on april 16 , 2016 ) . receiver operating characteristic ( roc ) curve was built by plotting the sensitivity , or true positive rate , as a function of the false positive rate ( 1-specificity ) at different nrs points . for roc analysis , those entire patients who rated their satisfaction with overall pain management very satisfied and satisfied were regarded as satisfied and the rest as not satisfied. calculation of cronbach 's alpha and creation of the roc curve and calculation of the area under curve ( auc ) were carried out by the second author using microsoft excel 2007 ( v12.0 , microsoft ) . prevalence of acute post - operative pain as we could not gather data regarding the prevalence of acute post - operative pain following abdominal surgery from developing countries , considering the reported prevalence of 55% for day care surgeries , for a population of 1500 with a desired precision of 0.08 and confidence level of 0.95 , 136 samples were needed . with an error of 0.05 and power of 0.8 , considering a spearman rank correlation coefficient of 0.31 between pain intensity score and patient satisfaction with overall pain management , a sample size of 63 was required . the sample size was calculated using two online calculators ( available from http://epitools.ausvet.com.au/content.php?page = 1proportion and https://www.statstodo.com/ssizcorr_pgm.php ) . thus , considering a possible attrition rate of 10% , we decided to include 150 patients . in this study , among the 150 patients eligible to participate , complete data could be obtained from 120 post - operative patients ( 60 males and 60 females ) only ( 80% response rate ) . the demographic profile and the description of the surgical procedures demographic characteristics and surgery - related data spinal anaesthesia was used in 19.16% ( 23/120 ) patients and none have received regional or epidural anaesthesia / analgesia . the prevalence of pain at different study points in time is mentioned in table 1 . the median with an interquartile range of nrs at the fifth post - operative hour , second and third post - operative days the number of patients experiencing no pain was significantly low on the third post - operative day compared to the fifth hour . there was an increase in a number of patients experiencing moderate pain as the post - operative period progressed and it reached statistical significance [ table 1 ] . less number of patients ( statistically significant ) experienced severe pain on the third post - operative day compared to those at the fifth post - operative hour ( p = 0.00046 ) [ table 1 ] . the number of patients with pain intensity of nrs < 4 increased significantly over the studied points of time ( between the fifth post - operative hour and second post - operative day , p = 0.0317 ; the fifth post - operative hour and third post - operative day , p = 0.0001 ; the second and third post - operative days , p = 0.0282 ) . box - and - whisker plot of intensity of pain during the study cronbach 's alpha for the questionnaire ( question numbers 11 , 12 and 18 ) was 0.70 [ questionnaire ] . ninety - four ( 78% ) patients were either very satisfied or satisfied with nurse 's response whereas 95.8% ( 115/120 ) patients were either very satisfied or satisfied with doctor 's response to pain treatment . around 92% ( 110/120 , 91.7% ) of patients reported that they were either very satisfied or satisfied with overall pain management . spearman correlation coefficients between nrs and level of satisfaction , along with their 95% ci and two - tailed p values are mentioned in figure 2 . the roc curves for prediction of satisfaction with overall analgesic management and nrs values at the three study points of time are mentioned in figure 2 . auc ( 95% ci ) of the roc curves for nrs at the fifth post - operative hour , second and third post - operative days are 0.334 ( 0.1430.524 ) , 0.420 ( 0.2270.612 ) and 0.583 ( 0.4070.759 ) , respectively . on hypothesis analysis , the two - tailed p values for the auc mentioned above are 0.087 , 0.413 and 0.356 , respectively . responses regarding pain management and patient satisfaction spearman correlation coefficient and receiver operating characteristics curve of numeric rating scale and level of satisfaction acute post - operative pain is very much prevalent in patients undergoing elective abdominal surgeries at our institution . data regarding the prevalence and other aspects of acute post - operative pain from india are not available . reported worldwide prevalence varies from 14% to 70% depending on the intensity considered , type of surgery and anaesthesia , time of data collection , institutional protocol for pain management , etc . while comparing the prevalence of patients experiencing different intensities of pain , it should be noted that nrs has been found to be reliable to measure post - operative pain in a rural population from this subcontinent , irrespective of literacy status . the patients in our study underwent abdominal surgeries ( mainly open upper abdominal surgeries ) with increased risk of intense pain , whereas in many studies , the patients underwent surgeries of different level of invasiveness with the diverse propensity for severe acute post - operative pain . the interplay of a multitude of factors acts as barriers to an effective management of post - operative pain . among others , the lack of routine monitoring of pain , pre - existing pain , surgical fear , inadequate awareness about perioperative pain , attitude of the attending physician and nurse and use of an inadequate dose of analgesics are responsible for the inadequate address of post - operative pain . at present , our hospital does not have an acute pain treatment service and analgesics are commonly prescribed by the surgeons unless a continuous regional block technique is used . it is surprising that in a highly developed country of europe , even with an acute pain control program in place , up to 50% patients experienced moderate to severe pain after abdominal surgery . nonetheless , this high prevalence of acute post - operative pain clearly demonstrates that optimal management is definitely lacking . although access to limited resources , be it physical capital , consumable or human , should not be a limiting factor to optimal pain management , in our opinion , it might have played a role . however , we need to look into the other barriers that prevented the provision of adequate pain relief so as to device a comprehensive departmental pain management strategy . in the meantime , we have started more frequent use of some less costly interventions , for example , infiltration of the surgical site with local anaesthetic ( la ) , infiltration of the transversus abdominis plane with la by the surgeon , single - shot intercostal block , etc . indices based on patient satisfaction are increasingly recognised as an important quality outcome indicator of health care . we observed that although a large number of patients have experienced moderate or even severe pain , vast majority of patients were satisfied with their post - operative pain management . a weak correlation ( < 0.3 ) between pain intensity and level of satisfaction was also observed in our study . the auc of the roc curve suggests that nrs on the fifth post - operative hour , second and third post - operative days is of no value in predicting satisfaction with overall analgesic management . in contrast to hanna et al . , chung and lui and our findings , many authors have reported that a relationship exists between increasing pain relief and satisfaction . considering the overall high level of satisfaction in our study group , it appears that pain relief alone is not the only factor that affects patient satisfaction with pain management . the observed high level of satisfaction with pain management even with inadequate management of pain is very relevant . this observation further substantiates the fact that there exists a complex interplay of the intensity of the perceived pain and how other pain specific needs are met . various other factors , for example , attitude of the care giver , age , sex , pre - operative expectation and actual experience of pain relief , ethnicity and a variety of other complex variables determine the disparities in clinical pain , both in patient 's perception of pain and its treatment . patient 's response may also be modified to please the staff and vary with the social gap between the patient and health care provider . it is very crucial to note that in india , satisfaction level regarding health care is high in certain populations . it is noteworthy that the p values of the correlation coefficient and the auc of the roc measured in our study are rather large and not all the studies consulted by the authors report the p value . it is difficult to comment whether the observed high p value for and auc was due to small sample size or plain chance ; however , the 95% ci values suggest that there is a very weak relationship of post - operative pain intensity and overall satisfaction with analgesic management . thus , it may be argued that it is just an illusion that low pain intensity scores are epitome of positive patient satisfaction and high pain intensity scores are a symbol of negative patient satisfaction . the strength of this study could be limited by the fact that we employed a convenience sample and could not reach the targeted sample size . this is very important as patients with different socio - demographic background may have a different perspective towards pain . many may answer survey questions by reporting how they think the questions should be answered instead of how they actually feel as respondents frequently report the positive answers when answering questions on satisfaction . both government - run public and for profit private health - care facilities from middle- and low - income group countries have their strengths and weakness ; however , public sector hospitals are known to be less responsive to patients and have inadequate availability of supplies compared to private sector hospitals . thus , data from health - care facilities belonging to different organisational arrangement need to be reported . it is the need of the hour to report the prevalence of acute post - operative pain from different categories of health - care facilities across india . the factors behind the differences of prevalence , if observed , need to be studied . it is also needed to analyse the factors behind patient 's satisfaction with their analgesic treatment , keeping in mind the diversity of the country we live in . the present study demonstrates that a significant proportion of patients suffer moderate to severe intensity of pain in the immediate as well as early post - operative period after abdominal surgery in an academic tertiary care government - run hospital . despite this

background and aims : considering the paucity of regional data , this study was designed to investigate the prevalence of post - operative pain and determine if there exists any correlation between the intensity of post - operative pain and patient 's level of satisfaction with their pain management after inpatient abdominal surgery at an academic tertiary care government centre.methods:pain intensity was measured in 120 patients with numeric rating scale at the fifth post - operative hour , second and third post - operative day . a questionnaire was used to measure the level of satisfaction with nurse 's and doctor 's response to their pain and overall pain management.results:the prevalence of post - operative pain was 84.17% , 92.5% and 96.66% at the fifth post - operative hour , second and third post - operative day , respectively . less number of patients experienced severe intensity pain on the third post - operative day ( p = 0.00046 ) , whereas the number of patients experiencing mild pain increased ( p < 0.000 ) compared to the fifth post - operative hour . the number of patients with complete analgesia decreased on the third post - operative day ( p = 0.001 compared to fifth post - operative day ) . the spearman correlation coefficient between pain score on the third post - operative day and level of satisfaction with nurse 's response , doctor 's response to pain and the overall pain management was 0.0218 ( p = 0.8107 ) , 0.1307 ( p = 0.1553 ) and 0.0743 ( p = 0.4195 ) , respectively.conclusion:there is a high prevalence of acute post - operative pain in patients undergoing inpatient abdominal surgery at our institute . there is a weak correlation between the intensity of pain and level of satisfaction with pain management .

. this might be , eg , due to degenerative changes of the spine of the patient or due to a limited ability of the patient to flex his hips . it is usually performed after palpation of the tips of the spinous processes above and under the intended level of entry of the needle . several factors have been implicated to determine the difficulty of the intended puncture . both patient - related factors eg , age,1 body mass index,1 deformities of the spine,2,3 the ability of the patient to flex his back,3 palpability of bony landmarks2,3 and non - patient - related factors eg , equipment used , experience of the person performing the procedure,4 patient position chosen by the clinician1 it would be very useful to know , how to optimize factors that are under the influence of the clinician performing the procedure because repeated attempts increase the incidence of complications and patient discomfort.5- 7 one of these factors might be the optimal place to insert the needle . to the best of our knowledge , surprisingly few data exist on where between the tips of the spinous processes the needle should be introduced to approach the subarachnoid ( sas ) or epidural space ( es ) without bone contact ( for simplicity , in the subsequent text we mean both the sas and the es , where only the es is mentioned ) . data on this subject would be very useful , eg , to instruct a resident how to perform neuraxial anesthesia when using a midline approach . for example , pitknen8 gives no hint for an optimal point of insertion in cousins et al s textbook of regional anesthesia . the same textbook9 advises [ ] insertion closer to the superior spinous process and with a slight upward angulation [ ] for lumbar epidural anesthesia and [ ] extreme upward angulation [ ] for epidural anesthesia in the mid - thoracic region . no further details are provided here . for thoracic epidural anesthesia , brull et al10 point out that the distance travelled by the needle is modified by a more perpendicular angle . however , they do not suggest an optimal point of insertion at the different levels . according to fettes et al , the needle should be introduced [ ] precisely in the mid - line , mid - way between the posterior spines [ ] for lumbar puncture . this suggestion is not substantiated by clinical or experimental data.11 in one paper it is suggested that puncture at the lumbar region should involve insertion of the needle at the superior aspect of the spinous process that lies inferior to the space to be entered.12 here , too , the authors provide no further explanation for this approach . we hypothesize that the point of insertion of the needle determines the range of angles at which the es can be reached ( explained in figure 1 ) . it is assumed , that the larger this range is , the bigger the chance of successfully reaching this space in one attempt . we have tested this hypothesis in a simple geometrical model . two adjacent spinous processes of two vertebrae ( a ) are represented by two parallelograms ( [ b ] , shaded areas ) . the following variables were chosen in the model ( figure 1 ) : the angle ( ) of the spinous processes relative to the virtual skin ( sk).the distance between two adjacent spinous processes ( d).the length of the spinous processes ( l ) perpendicular to the sk . the angle ( ) of the spinous processes relative to the virtual skin ( sk ) . the range of angles at which the es can be reached by the tip of the needle is represented by ( figure 1 ) . calculation of , figure 2 : sk represents the patient s skin surface . points a , b , c , and d variables x and y were attributed to a , b , c , and d ; for point a xa and ya , and similarly for b , c , and d. the needle is inserted at point pi ( xpi , ypi ) . the range of angles at which the es can be reached is represented by : =;(1 ) tan=y1/l=tan1{y1/l},wherey1=ycypi;(2)and tan=y2/l=tan1(y2/l),wherey2=ybypi(3 ) the variables , d , and l were varied over a wide range , in order to be able to make solid statements of their effects on ; varied from 0 to 72. calculations were performed in excel spreadsheets ( microsoft office , 2007 ) . in all these various cases , ( y - axis ) was plotted as a function of the points of insertion ( x - axis , pi ) in diagrams . a total number of 196 spreadsheets were made . two adjacent spinous processes of two vertebrae ( a ) are represented by two parallelograms ( [ b ] , shaded areas ) . the following variables were chosen in the model ( figure 1 ) : the angle ( ) of the spinous processes relative to the virtual skin ( sk).the distance between two adjacent spinous processes ( d).the length of the spinous processes ( l ) perpendicular to the sk . the angle ( ) of the spinous processes relative to the virtual skin ( sk ) . the range of angles at which the es can be reached by the tip of the needle is represented by ( figure 1 ) . calculation of , figure 2 : sk represents the patient s skin surface . points a , b , c , and d variables x and y were attributed to a , b , c , and d ; for point a xa and ya , and similarly for b , c , and d. the needle is inserted at point pi ( xpi , ypi ) . the range of angles at which the es can be reached is represented by : =;(1 ) tan=y1/l=tan1{y1/l},wherey1=ycypi;(2)and tan=y2/l=tan1(y2/l),wherey2=ybypi(3 ) the variables , d , and l were varied over a wide range , in order to be able to make solid statements of their effects on ; varied from 0 to 72. calculations were performed in excel spreadsheets ( microsoft office , 2007 ) . in all these various cases , ( y - axis ) was plotted as a function of the points of insertion ( x - axis , pi ) in diagrams . a total number of 196 spreadsheets were made . in figure 3a , c , e , g ( left part ) the angle ( explained in figure 1 ) is varied , resulting in a horizontal ( figure 3a ) to steep ( figure 3 g ) position of the spinous processes relative to the sk . in all these cases , is maximal when pi is chosen at the point that is the projection of the point halfway between points b and c on the skin ( explained more extensively in the figure ) . this optimal point of insertion is represented by pi , opt in figure 3c , e and g. the corresponding plots , which vary in shape , are shown in figure 3b , d , f , h ( right part ) . when the spinous processes run horizontally , is maximal when the point of insertion is chosen halfway between points a and d ( figure 3b ) . when increases , the point of insertion where is maximal gradually shifts cranially , ie , pi , opt approaches point d. in figure 3e the point of insertion where is maximal corresponds with point d. this means that when steeper angles are chosen than in this particular situation , pi , opt is consistently at point d , ie , the most cranial point between two adjacent spinous processes ( figure 3 g ) . according to this model , the chosen point of insertion between the spinous processes determines the value of . this dependency is most pronounced when the spinous processes run steeply . in the situation of figure 3h , the absolute increase of when it is compared to the least favorable point of insertion , ie , point a ( compare figure 3e ) is 9 ( from 18 to 27 ) , which is a relative increase of 50% . for the situations of figure 3b , d , and f , these numbers are 1 and 4% , 4 and 17% , and 6 and 27% , respectively . our geometrical model clearly demonstrated , that the range of angles at which the es can be reached , is dependent on the point of insertion between the tips of the spinous processes when using a midline approach . many anesthesiologists perform both lumbar and thoracic neuraxial blockade by using a midline approach.13 therefore , this finding is relevant for daily anesthetic practice . especially in patients where neuraxial anesthesia turns out to be technically difficult eg , due to degenerative changes of the spine choosing the optimal point of insertion may enhance the chance of successfully reaching the es . although we studied the median approach in neuraxial anesthesia , some anesthesiologists advocate a paramedian approach . comparative studies in the literature , we found , usually focused on the lumbar region of the spine . indeed , some studies found an advantage for the paramedian approach eg , in terms of a higher success rate at the first puncture attempt,14 or time needed to reach the es.15 other studies , however , could not confirm that the paramedian approach is superior to the median approach . these studies were for example looking at predictors for success during the first puncture attempt7 or the incidence of post - dural puncture headache.16 apparently , more and larger studies are needed to answer the question which approach under what conditions should be preferred. according to our results , the optimal point of insertion of the needle shifts cranially when the spinous processes run steeper . choosing a more cranial point of insertion of the needle will not only increase the range of angles at which the sas and es can be reached , but will also shorten the puncture route . the borders of spinous processes are not smooth , straight lines in vivo and adjacent spinous processes do not run perfectly parallel to each other as in our model . however , these simplifications enabled us to make calculations and eventually enabled us to test our hypothesis that the point of insertion of the needle is an important determinant for the chance of reaching the es . however , many if not the majority of anesthesiologists still use the landmark - guided technique , probably since it is relatively effective and the use of ultrasound requires additional skills.17 it would be of interest to investigate if ultrasound can be helpful to find the optimal point of insertion of the needle . previously , it has been shown that a change in flexion of the hips changes the curvature of the spine.18 consequently , a change in the curvature of the spine , will probably also change the width between adjacent spinous processes . indeed , several papers describe the influence of patient positioning on the interspinous space width in the lumbar region of the spine.19 - 22 we are not aware of studies of the thoracic region of the spine . for example , in the study by fisher et al , the absolute increase in width between lumbar interspaces was 1 mm or less in 60% ( 21 of 35 measurements ) of the studied cases and 1 to 2 mm in 31% . the corresponding relative increases varied from 5% to 14% ( cases with an absolute increase of 1 mm or less ) and from 12% to 33% ( cases with an absolute increase of 1 to 2 mm).19 in the study by sanodoval et al ( when comparing the sitting position with unsupported feet to sitting with supported feet ) , the absolute increase in width between spinous processes was 1 mm or less in nine of 16 cases , 1 to 2 mm in four of 16 cases , and more than 2 mm in three cases ( being 2.1 , 2.4 , and 3.6 mm respectively).20 since our model did not take the role of patient positioning into account , our results should be interpreted with caution . on the other hand , as we discussed above , the changes in interspinous space width when changing from a position with no or limited hip flexion to more hip flexion seem to be limited , both in absolute and in relative numbers . furthermore , the influence of changing patient positioning on the ease of performing a neuraxial blockade seems also to be limited.23 - 25 from the available data , it is difficult to predict how changes in the spinal curvature and forthcoming changes in the angulations of the spinous processes will affect the optimal point of needle insertion . therefore , it is worthwhile to test the findings in our model in patients , both with and without flexion of their hips . results from these future studies may further substantiate a scientific rationale , how to perform neuraxial anesthesia when using a midline approach .

performance of neuraxial blockade using a midline approach can be technically difficult . it is therefore important to optimize factors that are under the influence of the clinician performing the procedure . one of these factors might be the chosen point of insertion of the needle . surprisingly few data exist on where between the tips of two adjacent spinous processes the needle should be introduced . a geometrical model was adopted to gain more insight into this issue . spinous processes were represented by parallelograms . the length , the steepness relative to the skin , and the distance between the parallelograms were varied . the influence of the chosen point of insertion of the needle on the range of angles at which the epidural and subarachnoid space could be reached was studied . the optimal point of insertion was defined as the point where this range is the widest . the geometrical model clearly demonstrated , that the range of angles at which the epidural or subarachnoid space can be reached , is dependent on the point of insertion between the tips of the adjacent spinous processes . the steeper the spinous processes run , the more cranial the point of insertion should be . assuming that the model is representative for patients , the performance of neuraxial blockade using a midline approach might be improved by choosing the optimal point of insertion .

the lifetime prevalence of urinary stones is estimated to be 1% to 15% , with the probability of having a stone varying according to age , gender , race , and body mass index ( bmi ) . acute colic due to a ureteral stone is the most common situation encountered by urologists in an emergency setting . ureteral stones have been treated by different modalities depending on location , size , and urgency of clearance . besides watchful waiting , management of ureteral stones is undertaken with extracorporeal shock wave lithotripsy ( eswl ) or ureteroscopic lithotripsy . eswl has advantages such as low morbidity , no need for hospitalization or anesthesia , and avoidance of initial stone manipulation . currently , eswl has been recommended as the first - line treatment for ureteral stones with a success rate of 80% to 90% [ 4 - 6 ] . however , a recent meta - analysis showed that , compared with ureteroscopic lithotripsy , stone - free rates were lower and re - treatment rates were higher in patients who underwent eswl . thus , interest has increased in adjunctive treatment to enhance the passage of stone fragments after eswl . we aimed to evaluate the efficacy of tamsulosin as an adjunctive treatment on stone clearance after eswl in patients with a single proximal ureteral stone . since march 2011 , an open - label , prospective randomized controlled trial was performed to evaluate the efficacy of tamsulosin on stone clearance after eswl in patients with a single proximal ureteral stone in an outpatient setting . the study protocol was approved by the institutional review board of seoul national university hospital , and written informed consent was obtained from eligible patients . patients in the age range of 18 to 70 years with symptomatic , unilateral , and single proximal ureteral stones ranging from 6 to 20 mm in the longest axis proved on plain abdominal kidney , ureter , and bladder ( kub ) radiography and nonenhanced kidney computed tomography ( ct ) were included in this trial . exclusion criteria were as follows : active urinary tract infection ; severe hydronephrosis ; pregnancy ; inadequate renal function ( serum creatinine , > 2.0 mg / dl ) ; concomitant treatment with alpha - blockers , calcium channel blockers , or steroids ; hypotension ; multiple urinary stones ; morbid obesity ( bmi , > 30 kg / m ) ; stone on nonfunctioning kidney ; history of previous failed eswl ; history of urinary tract surgery ; or uncorrected urinary tract obstruction . after consenting , patients were allocated to the treatment ( tamsulosin 0.2 mg once a day ) or control ( no medication ) group by computer - generated randomization concealed in a sealed envelope until the day of eswl . patients in the treatment group received tamsulosin 0.2 mg once a day just before the session of eswl until the clearance of the ureter stone . all lithotripsy sessions were performed by using the sonolith praktis electroconductive lithotripter ( edap tms s.a . , lyons , france ) with a shock wave frequency of 2 hz by the same team of radiographers under the supervision of a urologist . the power was gradually increased during the initial minute of treatment with steps from 25% to 70% . all patients were allowed to use aceclofenac 100 mg on demand and were asked to drink 1.5 to 2.0 l of water per day . the primary outcome of this study was the stone - free rate , and the secondary outcomes were the time until stone clearance , pain intensity , analgesic requirement , and incidence of complications . stone - free state was defined as the complete absence of any stone or the presence of residual fragments smaller than 3 mm in diameter . patients were assessed at 1 , 2 , and 3 weeks for these outcomes by means of kub and/or kidney ultrasonography when it was required , urinalysis , serum level of creatinine , and visual analogue scale . all demographics and follow - up data were analyzed by using the ibm spss ver . comparisons of all available variables were performed by student t - test , mann - whitney u test for continuous or ordinal scales , and chi - square test for categorical scale . all p - values were 2-sided , and data were considered statistically significant at p<0.05 . ninety - six patients with a mean age of 46.7 years ( range , 22 to 67 years ) were randomly assigned to the treatment ( n=48 ) and control ( n=48 ) groups . of the 96 patients , 88 patients completed the study . four patients in the treatment group and 4 in the control group dropped out of the trial owing to withdrawal of consent ( n=3 ) or loss of follow - up for an unknown reason ( n=5 ) . there were no significant differences between the two groups in terms of age , gender , bmi , affected side , or stone diameter . the mean stone diameter before eswl was 9.2 and 9.6 mm in the treatment and control groups , respectively . a stone - free state was reported in 37 of 44 patients ( 84.1% ) in the treatment group and 29 of 44 ( 65.9% ) in the control group ( p=0.049 ) . the mean expulsion period of the stone fragments was 10.0 days in the treatment group and 13.2 days in the control groups ( p=0.012 ) . there were no statistically significant differences between the two groups in aceclofenac requirement or pain score ( table 2 ) . steinstrasse developed in 4 patients in the treatment group and in 5 patients in the control group , without statistical significance . four patients passed stone fragments by conservative management , whereas 5 patients required auxiliary ureteroscopic lithotripsy . only one patient in the treatment group experienced transient dizziness associated with medical expulsive therapy . patients who were not stone - free after 3 weeks of follow - up ( 7 in the treatment group and 15 in the control group ) were successfully treated with watchful waiting ( n=9 ) , repeated eswl ( n=8 ) , or ureteroscopic lithotripsy ( n=5 ) . eswl is now accepted as the gold standard for ureteral stones because it is minimally invasive . it should be noted that eswl for ureteral stones often achieves excellent results after repeated treatments and secondary procedures such as ureteral stenting . in a recent cochrane library review , compared with the rates after ureteroscopic lithotripsy , stone - free rates were lower ( risk ratio [ rr ] , 0.84 ; 95% confidence interval [ ci ] , 0.73 to 0.96 ) and re - treatment rates were higher ( rr , 6.18 ; 95% ci , 3.68 to 10.38 ) in patients who underwent eswl . as a result , a study to evaluate the treatment modalities that enhance the clearance of stones would be of particular interest . evidence that ureteral stone clearance may be enhanced with medical expulsive therapy has been accumulating for several years . furosemide , calcium channel blockers , -blockers , and corticosteroids have been widely investigated as effective therapies to promote stone clearance . among these medications , -blockers are a particularly promising class of medical expulsive therapy , including tamsulosin , alfuzosin , doxazosin , terazosin , and naftopidil [ 8 - 11 ] . with the identification of large populations of 1a and 1d adrenoreceptors in the human ureter [ 12 - 14 ] , medical expulsive therapy with tamsulosin , a selective 1a and 1d adrenoreceptor antagonist , has been widely investigated as a potential treatment strategy that may lead to ureteral relaxation and enhance the passage of stone fragments after eswl . the present study was designed to prospectively investigate the role of tamsulosin as an adjunctive therapy after eswl of proximal ureter stones . the study results showed that tamsulosin helps in the earlier clearance of stone fragments and reduces the expulsion duration of stone fragments after eswl . numerous clinical trials have been performed to investigate the efficacy of tamsulosin . also , several systematic reviews and meta - analyses have already reported the clinical effectiveness of tamsulosin in stone clearance after eswl . zhu et al . reported that the pooled absolute risk difference of the stone clearance rate was 16% ( 95% ci , 5% to 27% ) and the pooled mean difference of the expulsion time was 8 days ( 95% ci , -3 to 20 days ) in favor of the tamsulosin medication . in another meta - analysis by zheng et al . , tamsulosin had an overall benefit for stone clearance ( rr , 1.24 ; 95% ci , 1.12 to 1.37 ) and expulsion time ( mean difference , -0.34 ; 95% ci , -0.56 to 0.11 ) compared with the control group . in addition , lower analgesic requirements and fewer colic episodes and adverse effects were demonstrated . however , information on the efficacy of tamsulosin in stone clearance after eswl in korean populations is sparse . in the korean population , reported a higher expulsion rate ( 90.9 vs. 65.2% , p=0.038 ) and lower analgesic requirement ( 0.23 injections vs. 0.78 injections , p=0.042 ) with tamsulosin treatment compared with the control . choi et al . evaluated the effect of tamsulosin and nifedipine in stone clearance after eswl and reported that the total stone expulsion rate was significantly higher in the tamsulosin group ( 84.4% ) than in the nifedipine ( 67.7% ) and control ( 60.6% ) groups ( p=0.032 ) . however , another multicenter , prospective , randomized trial by kang et al . demonstrated that there were no significant differences in expulsion rate ( 50.4% vs. 39.1% , p>0.05 ) and mean distance of stone migration ( 7.1 cm vs. 5.5 cm , p>0.05 ) between the tamsulosin and control groups . kim et al . also reported similar negative results for the complete stone expulsion rate between the tamsulosin and control groups . on the basis of these studies , lee et al . performed a meta - analysis and demonstrated that tamsulosin had an overall benefit for ureteral stone clearance over the control after eswl ( rr , 1.38 ; 95% ci , 1.14 to 1.68 ) . however , several limitations of their meta - analysis , such as poor quality of included studies and publication bias , could have affected the pooled analysis . in that respect , well - designed randomized controlled trials are needed to confirm these findings . the results of this prospective randomized controlled trial concerning the efficacy of tamsulosin after eswl for a single proximal ureteral stone suggest that tamsulosin helps in the earlier clearance of stone fragments and reduces the expulsion period of the stone fragments after eswl .

purposethe objective of this study was to evaluate the efficacy of tamsulosin on stone clearance after extracorporeal shock wave lithotripsy ( eswl ) in patients with a single proximal ureteral stone.materials and methodsthis prospective randomized controlled trial was performed on 88 patients with a single proximal ureteral stone . after consenting with a doctor , the patients were allocated to the treatment ( tamsulosin 0.2 mg once a day ) or control ( no medication ) group , and the efficacy of tamsulosin was evaluated . the primary outcome of this study was the stone - free rate , and the secondary outcomes were the period until clearance , pain intensity , analgesic requirement , and incidence of complications.resultsa stone - free state was reported in 37 patients ( 84.1% ) in the treatment group and 29 ( 65.9% ) in the control group ( p=0.049 ) . the mean expulsion period of the stone fragments was 10.0 days in the treatment group and 13.2 days in the control group ( p=0.012 ) . there were no statistically significant differences in aceclofenac requirement or pain score between the two groups . only one patient in the treatment group experienced transient dizziness associated with medical expulsive therapy , and this adverse event disappeared spontaneously.conclusionsthe results of this prospective randomized controlled trial of the efficacy of tamsulosin after eswl for a single proximal ureteral stone suggest that tamsulosin helps in the earlier clearance of stone fragments and reduces the expulsion period of stone fragments after eswl .

sometimes , pathogens may reach the bone directly during a neurosurgical operation , e.g. lumbar discectomy . rarely , vertebral discitis is reported as a complication of laparoscopic operations with fixating sutures on the promontory . three weeks later , she presented with increasing back pain without neurological signs and symptoms or fever . due to elevated c - reactive protein ( crp ) , a deep - seated surgical site infection was suspected . computed tomography ( ct ) scan and magnetic resonance imaging ( mri ) of the pelvis were normal besides presacral seroma . however , one of four blood culture bottles was positive with pseudomonas aeruginosa and the patient was treated with piperacillin / tazobactam for 14 days . three months after the initial operation , the patient presented with severe back pain radiating to both legs . the lower lumbar spine was highly tender on percussion , but the neurologic examination revealed only a slight loss of muscle strength in the big right toe . the mri of the spine now revealed vertebral discitis without epidural abscess formation ( fig . 1 ) . culture of ct - guided needle biopsy was positive with p. aeruginosa and antibiotic therapy with 6 1 g ceftazidime i.v . per day the loss of muscle strength in the big right toe persisted and was interpreted as stenosis of right s5 foramina due to infective destruction which did not require neurosurgical decompression . it is also possible that after the operation the presacral seroma was not the primary infectious site but got infected during the pseudomonas sepsis . spinal tuberculosis and brucellosis mainly occur in endemic areas , but should also be suspected in migrants . most patients present with back pain , but motor weakness and sensory changes are only found in a minority . a high level of suspicion is required in patients with opioid - dependent back pain and an unexplained inflammatory response . leucocyte counts may be elevated or normal , whereas crp levels are increased in 58 to 82% of patients . if a vertebral discitis is suspected , an mri of the affected area should be performed . this is the gold standard with sensitivity , specificity and accuracy of 96 , 92 and 94% , respectively . typically , mri shows decreased signal intensity of vertebral bodies in t1-weighted images and increased disc signal intensity in t2-weighted images . however , mri may be negative early in the disease course and should be repeated after 714 days if the diagnosis is still likely . in the absence of positive blood cultures with a typical microorganism ct - guided biopsy for microbiology and histology if microbiological culture of a representative biopsy remains negative for > 5 days , broad spectrum bacterial dna amplification may help to identify a causative microorganism , particularly if antibiotics had been administered before biopsy . if empirical therapy is needed before the availability of first microbiologic results , the choice of antimicrobials is dependent on likely pathogens , individual patient history and local resistance patterns . however , intravenous therapy with high doses of antimicrobials sufficiently covering staphylococci and other gram - positive bacteria are the first priority to rapidly reach bactericidal drug levels in bone , disc and epidural space . in regions and/or situations with a low pre - test probability for mrsa empirical treatment for gram - negative bacteria including pseudomonas is usually reserved for patients with additional risk factors . the switch to oral therapy depends on oral bioavailability , drug susceptibility , individual patient parameters and on a good clinical response . blood counts , liver and kidney function tests should be used to guide optimal dosage and monitor adverse events of prolonged and high - dose antimicrobial therapy . routine follow - up imaging is not recommended unless disease progression or treatment failure is suspected based on clinical and laboratory assessment . surgical debridement is usually needed in the case of epidural abscess formation or disease progression despite adequate antimicrobial therapy . a review of the literature in medline revealed only a few case reports of vertebral discitis after fixation on the promontory . a fixation on the promontory can be a trauma of the spine leading to a locus of minor resistance to subsequent infection . only straight forward diagnostic followed by a consequent therapy can avoid unnecessary postoperative morbidity by persistent neurological deficits because of this rare complication .

vertebral discitis usually arises from haematogenous spread of pathogens to the discs and bones . vertebral discitis can rarely occur as a complication after laparoscopic operations with fixating sutures on the promontory . we report the case of an 81-year - old woman who underwent a laparoscopic resection rectopexy because of rectal prolapse . weeks after the operation , the patient developed lower back pain with radiation to both legs not responding to symptomatic therapy . two months later , a magnetic resonance imaging of the lumbar spine showed vertebral osteomyelitis and discitis . a fixation on the promontory may be sufficiently traumatic to the spine to pave the way for subsequent infection . a high index of suspicion should be raised in patients with persistent , severe back pain . anamnesis , imageing and an adequate specimen from the affected area for microbiological analysis are crucial for timely diagnosis and appropriate management involving targeted and prolonged antimicrobial therapy .

the new generation oral anticoagulants include the direct thrombin inhibitor , dabigatran and factor xa inhibitors rivaroxaban and apixaban . factor xa inhibitors are now widely used for stroke prevention in atrial fibrillation ( af ) and in the treatment and prevention of venous thromboembolism ( vte ) . a major benefit of these agents , over the vitamin k antagonist , warfarin , is that they do not require serial monitoring . a recent meta - analysis has shown rivaroxaban to be a safe alternative to warfarin with significantly lower rates of intracranial bleeding and fatal haemorrhage risk , while also achieving improved efficacy in stroke prevention . the main disadvantage of these drugs is lack of a direct reversing agent which can cause significant problems in the setting of trauma and emergency surgery . although dabigatran can be reversed by haemodialysis , this method is ineffective for the factor xa inhibitors . vitamin k and freshly frozen plasma ( ffp ) have limited efficacy in reversing the anticoagulant effect and although the use of octaplex and factor viii inhibiting agents has been advocated in major bleeding , these are expensive and may be potentially difficult to obtain in emergency situations . however , ~60% are managed conservatively , with a 10% failure rate of this approach . management of splenic injury in the elderly population may be further complicated by co - morbidity and frailty ; despite this there is literature that describes high rates of success when non - operative management was adopted in patients > 55 years of age . cullen 's sign , first described by thomas stephen cullen in 1916 , describes peri - umbilical bruising . initially reported as a clinical sign in relation to a ruptured ectopic pregnancy , it may be present in many other conditions causing intrabdominal haemorrhage including haemorrhagic pancreatitis , splenic injury and aortic aneurysm rupture . turner 's sign of bruising in the flanks , indicating retroperitoneal bleeding , may also accompany cullen 's sign . an 80-year - old female was admitted to the acute elderly care team with acute confusion and syncope resulting in a fall . her past medical history consisted of atrial fibrillation ( af ) , mitral regurgitation and osteoporosis ; and she was anti - coagulated on rivaroxaban . prior to the fall , she experienced re - syncopal symptoms of dizziness and vertigo . her regular medications included digoxin , bumetanide and nebivolol . on initial presentation , she was stable from a cardiovascular perspective and there were no signs of peritonitis . however , there was tenderness in the left upper abdomen and thorax . g / l , a platelet count of 230 000/l and an elevated prothrombin time of 22 s in keeping with her anticoagulation . on day 4 , her haemoglobin had decreased to 64 g / dl . her blood pressure and heart rate remained within normal parameters but a repeat clinical examination revealed a large peri - umbilical ecchymosis ( cullen 's sign ) ( figs 1 and 2 ) . at this point , she was referred to the surgical team and a computed tomography ( ct ) scan confirmed a grade v splenic injury with overlying rib fractures , free fluid within the pelvis , but no active bleeding ( figs 3 and 4 ) . the patient responded well to fluid and blood - product resuscitation , and since discussion with the radiology team excluded active haemorrhage on the ct non - operative treatment was opted . concurrent treatment was given for pneumonia and the patient was discharged on the 14th day . rivaroxaban was re - commenced in the community on discharge following advice from the hospital haematology team . a 24-h ecg and cardiology follow - up was arranged as an outpatient . up to the current time of publication figure 1:clinical photography of peri - umbilical ecchymosis . figure 2:clinical photography of peri - umbilical ecchymosis . figure 3:coronal image from ct with iv contrast . figure 4:axial image from ct with iv contrast . admissions secondary to falls in the elderly are incredibly common and these patients may not always be considered as classical trauma patients . as a significant proportion of elderly patients will be anti - coagulated , they are at increased risk of haemorrhagic complications of injuries sustained . it should also be borne in mind that many of those anti - coagulated for af may also be on rate - controlling medications , such as beta - adrenoceptor - blocking agents , which may mask the early clinical signs of haemorrhage . for these reasons , these patients with a history of a low - impact fall and falsely reassuring clinical parameters may lead to a late radiographic diagnosis of an acute intra - abdominal injury . there should be a high index of suspicion when assessing patients such as this , in particular , where a decision regarding anticoagulation needs to be made . early imaging will identify significant injuries and allows optimization of medical treatment , which will improve survival in these high - risk patients . although ultrasound and focused assessment with sonography for trauma ( fast ) scanning in the emergency department may be effective at detecting free intra - peritoneal fluid keeping with likely solid organ injury , ct radiography with intravenous contrast serves as a more sensitive and specific modality for confirming and identifying the grade of splenic injury , as well as helping to diagnose active haemorrhage . given the choice in an unstable patient , ct scanning may well be a more timely and useful option for diagnosis before possibly proceeding to a laparotomy . regarding the novel anticoagulants in use today , research into reversal strategies is ongoing and as such we would recommend early involvement of a haematologist to assist with these patients ; whether they need surgery or not .

new anticoagulants such as rivaroxaban have become a popular choice for patients needing anticoagulation for atrial fibrillation or venous thromboembolism , chiefly because anticoagulation is maintained without the need for monitoring . this can be problematic in cases of trauma , and in this article , we discuss the management and outcome of managing an elderly patient with a shattered spleen while on rivaroxaban .

plants have been used for therapeutic applications ever since man has been concerned about his health . for centuries , the world has depended on the useful possessions of plants as a source of medicines . ethnobotanical investigations done in the last few decades had discovered the analgesic properties of plants mentioned in the traditional information . the exploration for new analgesic compounds from the enormous arrays of medicinal plant resources is growing . this is because such information may hold guarantee for the finding of new therapeutic agents capable of inhibiting , decreasing , or relieving pain . plants characterize a huge natural supply of valuable compounds that might achieve as lead for the expansion of novel drugs . the exploration of the effectiveness of plant - based drugs used in the traditional medicine has been given great considerations because they are cheap and have little side effects , and , according to world health association ( who ) , about 80% of the world population still relies chiefly on plant - based drugs . one of these medicinal plant species that has dramatic pharmaceutical values is leonurus cardiaca l. . leonurus cardiaca , commonly known as motherwort , is a member of the lamiaceae family that has been consumed in asian countries as a traditional remedy against nervous and functional cardiac disorders [ 6 , 7 ] . it is a perennial herb prevalent in europe , usually found in country areas throughout the plains and hills , as well as in east asia to the himalayas and eastern siberia , northern africa , and north america . motherwort consists of the aerial portions of leonurus cardiaca collected through the flowering time and dried at 35c and , according to european pharmacopoeia 7th edition , must encompass a minimum of 0.2% flavonoids expressed as hyperoside . in the aerial parts of leonurus cardiaca , there are ingredients belonging to the group of terpenes , including monoterpenes such as iridoids , diterpenes of clerodane , furanolabdane , and labdane types , triterpenes including ursolic and oleanolic acids [ 11 , 12 ] , nitrogen - containing compounds such as leonurine and stachydrine , and phenylpropanoids such as lavandulifolioside , as well as flavonoids , phenolic acids , volatile oils , sterols , and tannins . pharmacological reports have established antimicrobial [ 10 , 19 ] , antioxidant [ 15 , 16 ] , and anti - inflammatory effects , as well as the effects of the herb on the heart and circulatory system . sedative and hypotensive properties since pharmacological studies are limited , the use of motherwort is mainly based on traditional suggestions . analgesic drugs are one of the most products that are used in numerous diseases for alleviating the pain . most analgesic drugs , accessible in the market , exhibit an extensive range of adverse effects including gastrointestinal disorders , kidney problems , and other unwanted effects . this situation highlights the need for advent of safe , novel , and effective analgesic compounds . the aim of the present study was to investigate the analgesic activities of aerial part of leonurus cardiaca using three analgesic tests in mice . the animals were handled in accordance with the criteria outlined in the guide for the care and use of laboratory animals ( nih us publication 86 - 23 revised 1985 ) . 68 weeks of age , were kept in a controlled environment ( 22 2c , 50 5% humidity ) under a 12-hour light / dark cycle ( light on 08:0020:00 ) and had free access to a standard pellet chow and tap water throughout the study . all experiments were conducted at tehran university of medical sciences according to the recommendations of the ethics committee for animal welfare and have been approved by institutional animal care and utilization committee . one hundred grams of aerial parts was placed into a flask ; one liter of 96% ethanol was then added . after 24 hours , when the solution had become clear , this was transferred into another flask . one liter of 70% ethanol was then added to the solid residue and after 12 hours the supernatant was again decanted into another flask . both solutions were then combined and concentrated by vacuum distillation at a temperature of 50c and 70 rpm rotation speed , until the volume decreased to 1/3 of the initial volume . the solution was then poured into a petri dish and dried in the autoclave at temperatures below 50c in sterile conditions . the formalin test is an acceptable and reliable model of nociception that generates two separate phases of increased licking activity that can be recognized to different nociceptive mechanisms . the initial licking stage lasts for the first five minutes and a late phase takes from 15 to 45 minutes after the injection of formalin . as previously defined , formalin ( 20 l of a 2.5% solution ) was injected subcutaneously into the dorsal surface of the right hind paw . the animals were then placed under a glass funnel on a glass surface ; a mirror was angled at 45 degrees . the pain response time ( licking time ) was calculated in two periods : 0 to 5 min , the first phase ( caused by direct motivation of the nociceptors ) , and 15 to 45 min , the second phase ( inflammatory pain produced by release of inflammatory mediators ) . morphine ( 10 mg / kg , temad co. , iran ) was injected to animals in the positive control group . the other groups received different doses of leonurus cardiaca extract ( 125 , 250 , and 500 mg / kg ) . the tail flick examination was used to calculate analgesic activity by the method defined by d'amour and smith 1941 , with minor alterations in the procedure . basal reaction time of animals to radiant heat was recorded by locating the tip ( last 1 - 2 cm ) of the tail on radiant heat source . the tail removal from the radiant warmth mice were treated with morphine ( 10 mg / kg ) , normal saline , and leonurus cardiaca ( 125 , 250 , and 500 mg / kg ) . the latent period of the tail - flick response was determined at 30 , 45 , 60 , 75 , and 90 minutes after the administration of drugs . the hot plate test was used to calculate analgesic activity by the method explained by eddy and leimbach with minor modifications . mice were retained on a hot plate having a stable temperature of 55 1c . the time taken for either paw licking or jumping each mouse was individually placed on the hot plate in order to find the animal 's reaction to electrical heat - induced pain ( licking of the forepaws and eventually jumping ) . the latency until mice showed first signs of discomfort ( hind paw lifting , hind paw licking , or jumping ) was recorded , before ( baseline ) , and response was determined at 30 , 45 , 60,75 , and 90 min after the administration of normal saline , leonurus cardiaca ( 125 , 250 , and 500 mg / kg ) , and morphine ( 10 mg / kg ) . one - way analysis of variance ( anova ) test was used to ascertain the significance of variations between the times of licking in formalin test . two - way repeated measure anova test used to assay the differences in reaction time in tail flick and hot plate tests . the treatment of mice with leonurus cardiaca resulted in an inhibition of the formalin - induced licking in the early phase and inflammatory pain ( late phase ) of the formalin test . in the early phase , the maximum analgesia was observed at dose of 500 mg / kg of leonurus cardiaca extract ( p < 0.01 compared to control group ) and was equal to morphine in dose of 10 mg / kg . in the late phase , the dose of 250 mg / kg of leonurus cardiaca extract showed the most analgesic effects ( p < 0.05 compared to control group ) and it was comparable to morphine in dose of 10 mg / kg . pretreatment with leonurus cardiaca ( 250 or 500 mg / kg ) demonstrated a significant and dose - dependent antinociceptive activity in the tail flick test ( figure 2 ) . the 500 mg / kg of leonurus cardiaca increased an antinociceptive activity in 30 ( p < 0.01 ) , 45 , 60 , and 75 ( p < 0.01 ) minutes after injection that were comparable to the normal saline . this effect was significant in time 45 and 60 minutes after injection for doses 125 and 250 mg / kg of leonurus cardiaca . under similar conditions , treatment with morphine significantly increased latency to thermal stimulation 30 min after administration and the antinociceptive effect was maintained during the entire period of evaluation . the results in figure 3 show that the treatment of mice with morphine ( 10 mg / kg i.p . ) increased the latency response in the hot plate test from 30 to 120 minutes after treatment . on the other hand , leonurus cardiaca significantly influence the reaction time of the animals to the hot plate at doses of 500 mg / kg in 45 and 60 minutes ( p < 0.05 ) and 75 and 90 minutes ( p < 0.01 ) after treatment . in this study , we pointed to investigate the potential antinociceptive effect of aerial part ethanol extract from leonurus cardiaca by chemical and thermal models of nociception . the first test to assess the antinociceptive property leonurus cardiaca was the formalin test . the formalin test initially described by dubuisson and dennis and categorized by the first phase , which is induced by direct formalin stimulation of the sensorial c - fibers followed by substance p release , and the second phase ( inflammatory ) principally due to a following inflammation reaction in the peripheral tissue mediated by the release of various inflammatory mediators has been related with the augmented level of pg , stimulation of cox , and release of nitric oxide ( no ) [ 25 , 26 ] . the biphasic nature of pain response in this test , which presents diverse pathological procedures , can be used to clarify the probable mechanism involved in analgesia . centrally acting drugs , such as opioids , prevent both phases of pain , whereas peripheral - acting drugs such as acetylsalicylic acid , which inhibit cox activity , only inhibit the second phase [ 24 , 28 ] . our results showed that the leonurus cardiaca extract at dose of 500 mg / kg and 250 mg / kg was more effective in the first and second phases , respectively , as well as morphine 10 mg / kg , suggesting possible peripheral and central antinociceptive mechanism . this extract was possibly able to inhibit this inflammation , so it can be deduced that peripheral mechanisms might also be involved in antinociceptive effects . it is generally believed that centrally acting analgesics possess effects on both phases , while peripherally acting analgesics affect only the first phase . this is because the injected formalin into the paw results in release of several neurotransmitters including glutamate and aspartate in dorsal horn of spinal cord . so the early phase of the formalin test represents the transmission of nociceptive impulses , while late phase is associated with the development of a delayed inflammatory response . opioid analgesics suppress both of early and late phases of formalin test , while none steroidal anti - inflammatory drugs ( nsaids ) mainly act on the late phase . as shown in figure 1 , morphine could alleviate both of phases , whereas leonurus cardiaca at dose of 250 mg / kg diminished only the formalin - induced pain of the late phase . this effect maybe contributed to presence of some anti - inflammatory compounds which may act like nsaids . demonstrating in figure 1 , leonurus cardiaca extract only at the maximum administrated dose ( 500 mg / kg ) was capable of reducing the formalin - induced pain in the early phase , and other doses ( 125 and 250 mg / kg ) did not show such effect . a pharmacokinetic involvement may partly clarify this finding that describes that leonurus cardiaca extract at the maximum dose ( 500 mg / kg ) could pass through blood - brain barrier and show its analgesic properties in early phase , which is mainly central , while lower doses did not display such effect perhaps due to poor passing via this barrier . aiming to study the spinal antinociceptive action , we performed the tail flick test . this model , like the hot plate test [ 22 , 29 ] , measures animal nociceptive response latencies to thermal stimulus but tail flick is principally a spinal response and hot plate is predominantly supraspinal [ 3032 ] . treating the animals with leonurus cardiaca , at dose 500 mg / kg , alters mouse latency to painful thermal stimulus in tail flick and hot plate tests . these findings suggest that central and peripheral mechanisms are involved in the antinociceptive activity of the extract . demonstrating in figure 2 , leonurus cardiaca extract only at the maximum dose ( 500 mg / kg ) could alleviate the pain in all times of tail flick test , whereas the lower doses ( 125 and 250 mg / kg ) reduced only late pain ( times 60 and 75 minutes ) . this finding is similar to results of formalin test ; in both of them , leonurus cardiaca extract only at dose of 500 mg / kg was capable of diminishing the early pain , which is mainly central , and , as aforementioned , this event can be contributed to pharmacokinetics . in this study , it was shown that the administration of ethanolic aerial part extract of leonurus cardiaca possesses antinociceptive effects in tail flick , hot plate , and both phases of formalin test . the results obtained in this study indicate that the extract possesses analgesic properties , which are mediated through peripheral and central inhibitory mechanisms . this could provide a rationale for the use of this plant in pain and inflammatory disorders in folk medicine . further studies should be performed for the isolation of new chemical constituents of the plant as well as for a better understanding of the mechanism of antinociceptive activity presented by the extract .

leonurus cardiaca , commonly known as motherwort , is a member of the lamiaceae family . it has a number of interesting biological activities , for example , sedative and hypotensive , antioxidant , anti - inflammatory , and antimicrobial activities . the aim of the present study was to investigate the effect of alcoholic extract of aerial part of leonurus cardiaca on nociceptive response using formalin , tail flick , and hot plate tests in mice . the acute treatment of mice with an ethanolic extract at doses of 500 and 250 mg / kg by intraperitoneal administration produced a significant antinociceptive in the first and second phases of formalin test , respectively . the hot plate and tail flick tests showed an increase in the antinociceptive effect at dose 500 mg / kg . these results suggest that leonurus cardiaca possesses central and peripheral antinociceptive actions .

critically ill patients often need blood transfusion or any other blood product when they are facing a life threatening situation . however , some patients , such as jehovah s witnesses ( jw ) , may refuse their administration due to religious beliefs . based on those believes , humans must not sustain life with other creatures blood , ( genesis 9:3 - 4 , leviticus 17:10 - 11 ) . if these directives are not followed , members face the risk of being ostracized or excommunicated . so physicians have to solve the difficult problem of treating patients , who are jw without offending their religious beliefs . it is clear that refusal of blood transfusion is associated with increased morbidity and mortality and health care system is charged with higher expenses . studies have showed that a nadir hemoglobin ( hb ) concentration is a poor predictor of mortality of jw patients with anemia due to early ( age 45 years old , weight 90 kg , hypertension , cardiac arrhythmia , angina , previous myocardial infarction , valvular heart disease , heart failure , being on hemodialysis , acute admission and hb 80 g / l on admission to hospital ) and late ( shock , acute gastro - intestinal bleeding , pneumonia , nadir hb concentration 70 g / l , septicemia , worsened congestive heart failure and neurologic complications ) mortality risk factors . since recombinant human erythropoietin ( rhuepo ) became available , several cases have been reported in which rhuepo was successfully administered to critically ill jw . administration of rhuepo in combination with other blood conservation techniques has been shown to increase hemoglobin levels and survival in patients who experienced trauma , surgery , gastrointestinal bleeding or potential fatal hematological malignancies like lymphoma . even though jw patients do not accept blood transfusion , it is possible to overlap this obstacle especially in critically ill patients by giving alternative a nd effective treatment like recombinant human erythropoietin . this case report describes the successful treatment of a jw severe anemia , due to newly diagnosed non - hodgkin lymphoma a 57-year - old patient was admitted to our clinic due to high fever and lymphadenopathy . he complained for fever , up to 39c , for five days despite the fact he received intravenous antibiotic treatment , piperacillin - tazobactam ( i.v . ) and doxycycline ( per os ) , for 5 days in a peripheral hospital . from his past medical record , he had known hbv hepatitis treated with tenofovir disoproxil for four months . from his clinical examination during his admission , he had hepatosplenomegaly , and palpable tracheal , axillary , inguinal lymph nodes on both sides . the computed tomography ( ct ) scan confirmed the generalized lymphadenopathy with no other signs of infection . the examinations for any bacterial or viral infection was negative except for the hbv infection ( hbsag , anti - hbe , anti - hbc : positive ) . the antibiotic treatment with ciprofloxacin which started during admission was discontinued after 10 days , as there was no evidence of infection . laboratory data disclosed pancytopenia with severe anemia ( ht : 20.5% , ht : 7.4 gr / dl ) neutropenia ( wbc : 1.610 l , neutrophils : 36% , lymphocytes : 52% ) and thrombocytopenia ( platelets : 7410/l ) . the bone marrow aspiration and bone marrow biopsy had no signs of infiltration from any kind of malignancy while the lymph node biopsy revealed histological picture compatible with non - hodgkin lymphoma diffuse large b cell lymphoma type , high grade , ( cd 20 , cd79 : positive , cd3 , cd5 , cd10 , cd23 , cyclin d1 : negative ) . investigation concerning the cause of his anemia was done , including measurement of vitamin b12 and folic acid which were among normal levels but ferritin was increased ( 2286 g / dl ) probably acting as acute phase protein . fever was considered more as a b - symptom due to its pattern of appearance ( mainly afternoon time ) and his diagnosed underlying lymphoma . patient had 4% auckland anemia mortality risk score ( amrs ) and 4% hamilton amrs . the patient was informed about the seriousness of his condition and that he should start chemotherapy and blood transfusions . although recent data suggest that critically ill patients in general can tolerate anemia to an hb level of 7 g / dl , concerns have been raised that this level of anemia may not be well tolerated by certain critically ill patients as the patient herein who had to undergo chemotherapy for an aggressive hematologic malignancy . he did nt oppose to the chemotherapy but he strongly refused , in a written form , blood transfusion as this was against his believes . the health care professionals were obliged to respect patient s preferences , and seek alternatives to blood transfusion . the patient was monitored primarily by hematologists but he had consultations with gastroenterologists as well , due to his hbv infection without having any kind of intervention beside his hbv treatment . he started darbepoetin alfa 300 mg once every week immediately ( hb : 7.5 g / dl ) . he also started chemotherapy ( r - chop ) after one week from his admission . he continued chemotherapy without any side effects and on the third cycle of r - chop , hemoglobin levels was 11.5 g / dl . he finished 6 cycles of r - chop after six months without receiving blood transfusion and with hemoglobin levels being 13.5 g / dl at his final chemotherapy cycle . this clinical case highlights some of the therapeutic challenges that can be met in the treatment of severe anemia in a patient who does not wish to receive blood transfusion . evaluation of religious beliefs that affect treatment , such as transfusion preferences , should be made initially , and the patient and/or family provided with information and thereby the ability to make an informed choice . when a patient refuses a treatment option and could die in a potentially treatable situation creates an ethical dilemma for the health care professional , as well as being a frustrating experience . whole blood as well as its components , erythrocytes , white blood cells , platelets and plasma are considered prohibited . however , there is some variation within the religious group , with some members accepting components such as albumin , recombinant human erythropoietin and immunoglobulin . this must be discussed with each individual patient in order to apply his / her personal choice . without the possibility of transfusion as the standard treatment of severe acute anemia , clinicians must use supportive techniques to improve the patient s own circulation and oxygen - carrying capacity . epo is an endogenous hormone produced primarily by the kidneys that stimulates the bone marrow to produce red blood cells in response to hypoxemia . using recombinant dna technology , exogenous epo is now commercially available and is routinely used to treat anemia in pre - dialysis patients , patients with end - stage renal failure , and patients infected with hiv with anemia related to zidovudine therapy . in jw patients , epo has been proposed as an alternative to administering blood products to replace lost blood or to increase their vascular volume before elective surgery . epo has been useful in the jw reported in the literature in whom it has been used instead of blood or blood products . the watchtower society s bible information services has stated that the use of epo should not be objectionable in jw who receive treatment with epo because this synthetic hormone is a product of recent technology . there might , however , be some individual jw who would find it unacceptable to use a solution that contains albumin . the case reported here shows that it is possible to survive with hemoglobin lower than 7.5 g / dl and receiving in the meantime chemotherapy for an aggressive hematological malignancy . early initiation of rhuepo therapy may be required to achieve optimal response in jehovah s witnesses , who are a group of patients with different attitude towards blood transfusion and must be treated with respect to their beliefs .

blood transfusion many times works in a life - saving way when a patient is facing a critical situation . however , some patients , such as jehovah s witnesses , may refuse their administration because it opposes to their religion beliefs . thus , clinicians are forced to respect patients preferences and seek other treatments in order to overcome the obstacle of the transfusion . in 1989 , recombinant human erythropoietin ( rhuepo ) was approved by the united states food and drug administration ( fda ) for the treatment of anemia associated with chronic renal failure . this is an amino acid glycol - protein that stimulates red blood cell production in the same manner as endogenous erythropoietin . other treatment indications approved by the fda include anemia due to chronic kidney disease , anemia secondary to zidovudine therapy in patients with human immunodeficiency virus infection , and anemia secondary to cancer chemotherapy . the drug also has been used for many off - label indications . many jehovah s witnesses have accepted rhuepo as a treatment option to maintain and enhance erythropoiesis . this paper reports the case of a 57-year - old jehovah s witness man , who was diagnosed with severe anemia due to aggressive non hodgkin lymphoma and refused transfusion of blood ; thanks to the treatment with rhuepo he has managed to complete chemotherapy and has survived a life threatening situation .

in february october 2002 , as part of a broader study , we captured , banded , and marked 156 american crows ( c. brachyrhynchos ) in champaign and urbana , illinois ( yaremych sa . many of the study crows died in the summer ; all recovered crows were tested for wnv . dead crows were retrieved by tracking the radio signal to the carcasses , by chance encounter , or by notification from the public . dead study crows with transmitters were typically recovered < 36 hours after death , as this period was the maximum amount of time elapsed between the last live observation of a crow during radio tracking and recovery of the carcass upon death . we estimated that other marked study crows without transmitters were retrieved up to 72 hours after death . the abundance of dead crows allowed for a simple comparative study involving the use of vectest , rt - pcr , and ihc tests to detect wnv in crow fecal , saliva , and tissue samples . for each dead crow , we diluted fecal scrapings from the cloaca and salivary scrapings from the mouth in vectest buffer solution in the vials provided in the kit . a metal spatula was used to obtain samples , and instruments were sanitized with a wash of soap and water and 70% ethanol before and after use . in some cases , maggots were in such abundance in the mouth and cloaca that they could not be removed from the sample ; they were added to the vials with the feces and saliva . for carcasses with no moist fecal or saliva sample , small metal scissors were used to clip any available dried internal tissues around the mouth and cloaca . samples were shaken by hand for approximately 60 seconds for homogenization . from this point , we followed manufacturer s directions , having replaced mosquitoes with fecal , saliva , and tissue samples . indicator strips were inserted into the solution and interpreted in the field after 15 minutes . samples were stored at 80c after we performed the test . to confirm the results , we used rt - pcr taqman to detect the presence or absence of wnv - rna in these samples by a method similar to that used by lanciotti et al . alternatively , vectest results were confirmed by ihc testing of the brain , heart , kidney , and spleen of the crow carcass from which the samples were derived . the ihc testing was conducted by the university of illinois veterinary diagnostic laboratory , according to the method outlined by heinz - taheny et al ( 7 ) . we used vectest to test all 20 crow samples ; all indicator strips developed control lines , which indicated that the test had performed according to instructions . nineteen samples were positive for wnv with a faint - to - bold wnv line ; one sample was negative for wnv . ihc testing was performed on the crow carcasses from which five of these positive samples were derived , and ihc labeling for wnv antigen was present in all five of these samples , indicating 100% confirmation of the vectest results . the remaining 15 vials containing the vectest crow sample , composed of 14 positives and 1 negative , were assayed by rt - pcr taqman . results from taqman showed 11 positives and 4 negatives ( table ) . in total , 17 ( 85% ) of 20 of the vectest results were confirmed with either ihc or rt - pcr taqman , and 3 ( 15% ) of 20 involved conflicting results between the two testing methods for the samples . no significant difference existed between the positive and negative rates of vectest and rt - pcr in a chi - square analysis of a 2x2 contingency table ( chi square = 2.16 , df=1 , p=0.14 ) . using rt - pcr as the standard criterion , we found that vectest results included three false positives , yielding a false - positive rate of 75% . vectest west nile virus / saint louis encephalitis virus antigen panel assay ( medical analysis systems inc . reverse transcriptase polymerase chain reaction ; taqman ( applied biosystems , foster city , ca ) . although the rates of positives and negatives did not differ between vectest and rt - pcr in this study , this result may be an artifact of small sample size . the false - positive vectest results on american crow fecal , saliva , and tissue samples suggest a low specificity ; therefore , we recommend that vectest be considered experimental in its application to dead american crows until more extensive investigations are conducted . vectest may be useful in early season screening , when rates of positives are typically low , or in nonpeak areas . we conducted this study in mid- to late summer in east - central illinois , during a time when death rates of free - ranging american crows were high . rt - pcr detects genomic sequences of wnv , whereas vectest detects the viral capsid . because of the abundance of environmental rnaase and the possibility of the wnv capsid s persisting longer than the rna , the three false positives detected by vectest may indeed contain wnv capsid . alternately , the conjugate in vectest may react with a nonspecific protein in the fecal , saliva , or tissue samples of the dead crows to create a false positive . this preliminary investigation establishes the basis for more comprehensive research on the full capabilities of this test for wnv detection in birds , including the sensitivity of the test , the postmortem period for which the test is viable , and the effectiveness across a range of species . we suggest that vectest may be a cost - effective , rapid field technique for wnv detection in dead american crows in the early transmission season or in areas with low transmission rates , although confirmation of positives is suggested at this time . this assay may be a useful tool for epidemiologic studies of wnv transmission cycles involving american crows and will help to provide an epidemiologic basis for vector control efforts , although further study is warranted .

a dipstick immunochromatographic assay used for west nile virus ( wnv ) detection in mosquitoes was investigated for application to testing of fecal , saliva , and tissue samples from dead american crows ( corvus brachyrhynchos ) . results suggest that vectest may be an efficient method for wnv detection in field - collected , dead american crows , although confirmation of results and further investigation are warranted .

takayasu arteritis ( ta ) is a chronic vasculitis that causes inflammation and stenosis of medium- and large - sized arteries . its incidence is low , estimated to be 1.2 to 2.6 cases per 1,000,000 annually ; however , it is more common in asian populations . ulcerative colitis ( uc ) is a chronic inflammatory bowel disease characterized by diarrhea , rectal bleeding , and abdominal pain . its incidence varies geographically ; the highest is in the northern hemisphere and in caucasians . in north america , coexistence of ta and uc is reported in japan occasionally , but this is the first case reported in korea . a 38-year - old female was admitted with a 14-day history of dizziness , headache , and neck pain . she had a history of visual disturbance and was diagnosed with optic neuritis 4 years prior to admission . five months later , she developed diarrhea , intermittent hematochezia , and iron deficiency anemia . her body temperature was 36.7 , and her pulse was regular at a rate of 80 per minute . however , her radial and brachial pulses were not detectable on either arm , and bruits were heard over the cervical region on the medial side of the sternocleidomastoid muscle . her femoral artery , popliteal artery , and dorsalis pedis pulses were easily palpable . laboratory findings were as follows : white blood cell count , 6,170/mm ; hemoglobin , 8.0 g / dl ; and platelet count , 532,000/mm . her erythrocyte sedimentation rate ( esr ) was 120 mm / hr , and her c - reactive protein ( crp ) level was 45.93 mg / l . other laboratory findings were within normal limits , including liver function , renal function , and urine analysis . antineutrophil antibodies , anticardiolipin immunoglobulin m ( igm ) , anticardiolipin igg , anti--2-glycoprotein1 igg , anti--2-glycoprotein1 igm , and antimyeloperoxidase ( anti - mpo ) antibodies were all negative ; however , antiproteinase-3 antibodies were positive . ultrasonography of the neck showed severe stenosis of both common carotid arteries and total occlusion of the left subclavian artery ( fig . the left common carotid artery showed 90% luminal narrowing by dimension , whereas the right common carotid artery showed 78% luminal narrowing by dimension . the results of computed tomography scans and brain - neck magnetic resonance imaging showed diffuse wall thickening of the mid - descending thoracic aorta and aortic arch branches , diffuse stenosis of both common carotid arteries and the proximal right subclavian artery , and complete occlusion of the proximal left subclavian artery ( fig . positron emission tomography scans also showed fdg uptake along the thoracic aorta and arch branches , which was consistent with ta ( fig . an echocardiogram showed gi - ii / iv mitral valve regurgitation due to aortic root effacement . for uc assessment , we performed sigmoidoscopy , which showed erythema , edema , exudates , and spontaneous bleeding of the bowel , which were consistent with uc ( fig . 4 ) . for treatment , we started high - dose prednisolone ( 1 mg / kg , 50 mg ) and added 50 mg of azathioprine . after this treatment , the patient 's dizziness improved , her neck pain subsided from a visual analogue scale score of 7 to 1 , and her esr decreased from 120 to 38 mm / hr . in addition , the bruits in the cervical region became weaker , which implied that the inflammation had improved with the medication . ta and uc are both chronic inflammatory diseases of uncertain etiology , and both diseases are thought to be mediated by an immune reaction . nk cell and t lymphocyte infiltration is found in the aortic tissue of patients with ta , and levels of various cytokines , such as tumor necrosis factor ( tnf)- , interleukin ( il)-6 , and il-18 , are significantly higher in patients with ta than in healthy controls . the production of proinflammatory cytokines , such as il-1 , il-6 , and tnf- , is increased in patients with uc , indicating that an immune reaction is also associated with the pathogenesis of uc . an extensive literature review revealed that the coexistence of these two diseases was occasionally reported in japan , but this is the first report of such coexistence in korea . our patient was diagnosed with ta based on age , diminished brachial artery pulses , bruits over the common carotid arteries , and images showing stenosis of both common carotid arteries and the left subclavian artery . 4 ) . coincidence of ta and uc is rare , but has been reported in japan occasionally . to date , 39 japanese patients and three non - asian patients have been reported to have both diseases . interestingly , the present report is the first case of a patient with both diseases in korea , although koreans and japanese are both asians and have similar biological traits . patients with ta accompanied by uc have a tendency to be positive for specific types of hla , such as a24 or b52 . analyzed reports of 12 patients with ta with uc and discovered that 10 were positive for hla - b52 . however , it is well known that the presence of hla - b52 is closely associated with ta in both korea and japan , so more patients with both ta and uc may exist in korea . we should keep in mind that patients with ta or uc may have other autoinflammatory diseases . in this case , the patient was positive for anti - pr3 antibodies ( pr3-antineutrophil cytoplasmic autoantibody [ anca ] ) . although antiphospholipid antibodies can be detected in patients with ta , no report has suggested the presence of positive pr3-anca in patients with ta . in one study conducted in mexico , none of the 39 patients with ta were anca - positive , even during the active phase . pr3-anca is not common in patients with uc , but there are reports that pr3-anca can be detected in these patients . a study conducted in china reported that five of 58 patients with uc were pr3-anca - positive , while mpo - anca demonstrated higher positivity . an interesting feature of this case of ta is that the patient had suffered from optic neuritis in addition to uc . five months before the diagnosis of uc , she had a concentric visual disturbance of left eye and was diagnosed with optic neuritis in the us . like most other cases of optic neuritis , her symptoms fully recovered spontaneously without recurrence . the cause of optic neuritis in our patient was unclear , but we assumed that it could have been associated with uc . both uc and optic neuritis are immune - mediated , and specific mechanisms or target antigens of these diseases are not known . one study demonstrated that patients with uc were 75% more likely than community controls to have been diagnosed with optic neuritis , multiple sclerosis , or another demyelinating condition . in addition , a few case reports have shown that optic neuritis is associated with crohn disease . our patient was diagnosed with ta , uc , and optic neuritis , which supports the emerging concept that a patient with one immune - mediated condition is likely to have another autoinflammatory disease . therefore , when we meet a patient with an autoinflammatory disease , we must look at the patient from a systemic viewpoint and keep the possibility of other autoinflammatory diseases in mind . in conclusion , we reported the first korean case of a patient with both ta and uc . because there are few cases in japan , more might occur in korea . therefore , when physicians in korea see patients with ta , they should consider the possibility of other coexisting autoimmune diseases , such as uc . the significance of this case is that there may be more patients with coexistence of ta and uc in korea , so we patients with ta should be evaluated more thoroughly .

takayasu arteritis ( ta ) is a chronic vasculitis that affects the aortic arch and its primary branches . ulcerative colitis ( uc ) is an inflammatory bowel disease of unknown etiology . patients diagnosed with both ta and uc have rarely been reported . the pathogenesis of ta and uc is uncertain , but cell - mediated mechanisms play an important role in both diseases , and a genetic factor is thought to have an effect on the coincidence of these two diseases . we herein report a 38-year - old female with ta who had a history of uc with optic neuritis . we believe that this is the first case of the coexistence of ta and uc in korea .

the increasing use of motorcycles in commercial transportation in developing countries has led to explosion of their number in many countries [ 13 ] . in nigeria , travelled , motorcycle riders have a 34-fold higher risk of death in a crash than people driving other vehicles and are 8 times more likely to be injured . we studied motorcycle - related traumatic brain injury patients in our center over a three - and - half - year period . it was a prospective , descriptive , and cross - sectional study involving motorcycle - related traumatic brain injury patients managed in our center from august 2010 to january 2014 . patients were managed in accident and emergency using advanced trauma life support ( atls ) protocols ( primary and secondary surveys ) . in primary surveys , we gave adequate analgesia , antiepileptic drugs in posttraumatic seizures , and calm aggressive patients with chlorpromazine . quick checks for other organ injuries that could be life threatening to patients were made . in secondary survey patients with severe traumatic brain injuries were admitted to intensive care unit while those with mild and moderate traumatic brain injuries were admitted to the wards . patients with ct scan lesions not requiring surgery and those who could not afford ct scan were managed nonoperatively . patients with lesions requiring surgery such as extradural , subdural , and intracerebral hematomas / contusions and depressed skull fractures had surgical care . surgical procedures included craniotomy for acute extradural , acute subdural , and intracerebral hematomas / contusions , burr hole for subacute and chronic subdural hematomas , and craniectomy with primary bone fragment replacement or depressed bone elevation for depressed skull fractures . we gave broad spectrum antibiotics ( to those who had open tissue injuries ) , multivitamins , high energy and high protein diet . the diet was constituted thus : 500 ml pap , two tablespoonsful of powdered milk , one tablespoonful of red oil , two tablespoonsful of soya bean powder , and one tablespoonful of crayfish powder . their daily fluid requirements were calculated and factored into the fluid content of the diet . we used locally prepared diet because most of our patients could not afford complan or casilan and there was no functional dietetic unit in our hospital . on discharge , patients were followed up in the outpatient clinic and by phone calls when they failed to attend the clinic . data were collected using structured proforma which was part of our prospective data bank that was approved by our hospital 's ethics and research committee . the biodata , position of patient at the time of crash ( driver , passenger , or pedestrian ) , helmeted or not helmeted at the time of crash , severity of injury ( using glasgow coma score after resuscitation ) , and other clinical signs were collected in accident and emergency ( a&e ) unit . radiological findings were documented either in a&e or in the wards depending on the time the radiological imaging was done . it classifies patients into 1 dead , 2 vegetative state , 3 severe disability , 4 moderate disability , and 5 good recovery . the functional outcome was determined in outpatient clinic or by phone discussion ( those who failed to attend the clinic ) at three months after injury . the functional outcome three months after injury had been found to be the best predictor in the long term . motorcycle drivers , their passengers , and pedestrian hit by motorcycles were included in the study . data were analyzed using environmental performance index ( epi ) info 7 software ( center for disease control and prevention , atlanta , georgia , usa : http://wwwn.cdc.gov/epiinfo/7/index.htm ) . the frequency gadget was used to analyze gender , helmet use , severity of injury , and mode of treatment . we used the mean gadget to determine the mean age of the patients . the ages were recoded in groups of tens and their frequency was determined also . mxn/2x2 table was used in analyzing two variables such as effect of severity of injury on outcome , while its advanced part was used in three variables such as position of patient , severity of injury , and outcome . with 95% confidence interval , their ages ranged from three years to 69 years with mean age of 31.89 years . of the 87 drivers / passengers 98.85% ( 86 ) did not wear helmet at the time of crash while 1.15% ( one patient ) wore helmet . fifty - three patients had mild injuries , 29 had moderate injuries , and 23 had severe head injuries . thirty - eight of them ( 86.36% ) had intracranial lesions while six patients had no intracranial lesion . three patients had burr holes for subacute / chronic subdural hematomas , six had craniotomy for acute subdural / epidural hematoma , three had craniectomy with bone fragments replacement for depressed skull fractures , and three had repair of scalp avulsions . severity of the injury significantly affected the outcome , p = 0.0002 ( table 3 ) . they were young men in their prime trying to make ends meet through commercial motorcycle driving since collar jobs were hard to come by in our country . with long traffic holdups in our city , the patronage encourages many young ones to join commercial motorcycle driving as source of living . low percentage of patients who could afford ct scan led credence to the level of income among the patients . nwadiaro et al . in their study in north - central nigeria found 100% not using helmet . arosanyin et al . in zaria , nigeria , found 16% helmet use in their study . in ilorin , nigeria , arosanyin found 13.5% helmet use . in iribhogbe and odai study , they found that many motorcyclists complain of cost of helmet while many had helmets but refused to wear them due to inconveniencies . in spite of overwhelming evidence that helmet use prevented head trauma [ 7 , 21 ] , there had been hostilities towards helmet use mainly due to cost , ignorance , drug use , and discomfort . in united states of america ( usa ) the congress mandated us department of transportation to withhold federal funds from states without mandatory helmet laws . in 1975 organization such as abate ( a brotherhood against totality enactment ) lobbied usa congress to repeal the mandatory helmet laws . . in usa showed that the use of helmets decreased the overall death rate of motorcycle crashes when comparing helmeted with nonhelmeted patients ; helmet decreased the incidence of lethal head injury in crashes compared to nonhelmeted ones ; helmet decreased the severity of nonlethal head injury compared to nonhelmeted ones ; helmet laws reduced mortality and head injuries in areas with the law compared with those without the law . the protective effect of helmet use was also found in the study across three cities in europe ( hannover , munich , and glasgow ) by richter et al . . in italy , latorre et al . studied 736 injured riders and found 12% helmet use but the protective effect of helmet was significant . in jamaica , opponents of helmet law said that crashes in developed countries were due to high speedways and well maintained roads unlike windy poor surfaced and congested local highways in their country where the speed was low . study carried out by crandon et al . in university of west indies showed otherwise . in many developing countries these showed that low level of helmet use was not peculiar to our center but a global disease . the fact that the only helmeted patient in our study had severe head injury was of note . head injury had been found to be the leading cause of death even in helmeted riders . it had also been deduced that helmet and the other safety equipment showed efficacy in reducing deaths or serious injuries , but they had not been sufficient for safe lives [ 29 , 30 ] . it should be noted that obedience to traffic laws is complimentary to helmet use . the failure of drivers to comply with basic road safety legislation was the main cause of serious crashes in many series [ 16 , 17 , 3133 ] . in nigeria , arosanyin et al . found that , of the 344 commercial motorcyclists studied , 64% had driving license , 16% used helmet , 58.2% were aware of highway code , and 45% obeyed legal permissible passengers . siviroj et al . found that , among 18,998 riders studied during songkran festival , 44.2% had not been using helmet and 72.5% of passengers had not been using helmet . they also found that 75% agreed with the danger of nonhelmet use and 47.2% had been caught with the nonuse of a helmet before . they found that 83.7% had heard about road safety awareness campaign . inasmuch as helmet use and safety laws are good , motorcycle rider education is also essential as this has been found to have positive effect on changing risky behavior of riders and motorcycle - related injuries in rural thailand . in malaysia it was found that provision of exclusive lane for motorcycles reduced deaths by 60% . among our patients , in the study of 344 patients with traumatic brain injury in nepal , agrawal et al . found good recovery in 87.7% and mortality of 4.5% . in zaria , nigeria , found mortality of 13.2% among traumatic brain injury patients in their study . among patients with mild head injuries in our study , jacobs et al . studied 2784 patients with mild traumatic brain injuries and found favorable outcome in 87% and mortality was 2% . in our study , patients with moderate head injury had 95% favorable outcome and 5% mortality . in hitimana et al . the favorable outcome in moderate head injury was 75% , while , in mild head injury , it was 100% . andriessen et al . found that , in 169 moderate head injury patients in their study , the mortality was 17.68% . among patients with severe head injuries in our study , andriessen et al . found mortality of 41.79% among 335 severe head injury patients in their study . . found that , in 895 patients with severe head injury they studied , the mortality was 46.8% . wang et al . in taiwan found 86.6% mortality among severe head injury patients . from above studies , rudehill et al . studied 1,500 patients and found that intracranial lesions did not affect the outcome significantly . however , chastain et al . studied both ct scan and mri ( t2 and flair ) findings of their patients and found that ct scan findings did not predict the outcome but mri findings predicted the outcome . that was because our patients did ct scan only as there was no mri in our center and in our city . studied found that extradural hematoma positively predicted outcome . in our study , patients with extradural hematoma had 100% favorable outcome . in contrast , patients with subdural hematoma had 63.64% favorable outcome and mortality of 27.72% . in subdural hematoma , the impact is severe compared to extradural hematoma , and parenchymal injuries associated with subdural hematoma play major role in outcome determination . while we are heading towards zero mortality in acute extradural hematoma as predicted by bricolo and pasut et al . found that , in 101 patients with acute subdural hematoma studied , the mortality was 66% and favorable outcome was 19% . lobato et al . found that , in 64 patients with extradural hematoma they studied , the favorable outcome was 68.8% , while the mortality was 28.1% . ayub et al . in 108 patients with acute extradural hematoma they studied found that the favorable outcome was 69% and mortality was 8% . in 107 patients with extradural hematoma studied by bricolo and pasut , the favorable outcome was 89% and mortality was 5% . in combined study of acute extradural and acute subdural hematoma by taussky et al . , mortality among patients with acute subdural hematoma was 41% , while those with acute extradural hematoma had 3% mortality . these studies with our study showed marked improvement in outcome in extradural hematoma when compared with acute subdural hematoma . we also found that the outcome was significantly related to severity of injury at presentation . we believe that reasons advocated by opponents of helmet use were not strong enough to outweigh the protective effects of helmet . we thus recommend that the federal road safety corps ( frsc ) in our country should broaden riders ' education and enforce road safety regulations and helmet use laws .

summary . with increasing use of motorcycle as means of transport in developing countries , traumatic brain injuries from motorcycle crashes have been increasing . the only single gadget that protects riders from traumatic brain injury is crash helmet . objective . the objectives were to determine the treatment outcome among traumatic brain injury patients from motorcycle crashes and the rate of helmet use among them . methods . it was a prospective , cross - sectional study of motorcycle - related traumatic brain injury patients managed in our center from 2010 to 2014 . patients were managed using our unit protocol for traumatic brain injuries . data for the study were collected in accident and emergency , intensive care unit , wards , and outpatient clinic . the data were analyzed using environmental performance index ( epi ) info 7 software . results . ninety - six patients were studied . there were 87 males . drivers were 65 . only one patient wore helmet . majority of them were between 20 and 40 years . fifty - three patients had mild head injuries . favorable outcome among them was 84.35% while mortality was 12.5% . severity of the injury affected the outcome significantly . conclusion . our study showed that the helmet use by motorcycle riders was close to zero despite the existing laws making its use compulsory in nigeria . the outcome was related to severity of injuries .

jaundice presenting after cholecystectomy may be the initial manifestation of a serious surgical misadventure and requires rigorous diagnostic pursuit and therapeutic intervention . a 23-year - old female underwent laparoscopic cholecystectomy for symptomatic gallstones and three weeks postoperatively developed painless jaundice . radiographic and endoscopic studies revealed a subhepatic biloma causing extrinsic compression and obstruction of the common hepatic duct . percutaneous catheter drainage of the biloma combined with endoscopic sphincterotomy successfully relieved the extrahepatic biliary obstruction and resolved the intrahepatic ductal leak responsible for the biloma . although heretofore undescribed , post - cholecystectomy jaundice due to extrahepatic bile duct obstruction caused by biloma may occur and can be successfully treated by means of standard radiologic and endoscopic interventions . extrahepatic biliary obstruction following cholecystectomy is a worrisome occurrence that mandates immediate investigation to determine its cause . when choledocholithiasis is found not to be responsible , the etiology is usually a serious iatrogenic injury to the common bile duct , common hepatic duct , or both . less frequently , the obstruction is due to an obscure and self - limited process , such as inflammatory swelling of the duct . bilomas occurring after cholecystectomy are due to major or minor biliary leaks and virtually always imply an operative technical error . most patients with bilomas present with right upper abdominal pain and/or fever , and only rarely do they suffer gastrointestinal obstructive symptoms , such as nausea and emesis . although bilomas have frequently accompanied biliary ductal injuries , to our knowledge biloma has not been previously reported to cause biliary obstruction by extrinsic compression of the adjacent bile duct . a 23-year - old hispanic female underwent an apparently uneventful laparoscopic cholecystectomy for symptomatic cholelithiasis . no anatomic abnormalities of the common hepatic duct , common bile duct or cystic duct were noted at operation . she had no nausea or emesis , but her stools were light in color , and her urine was dark . liver function tests revealed marked elevations of the total and conjugated bilirubin and alkaline phosphatase suggestive of biliary obstruction . an abdominal computed tomography ( ct ) scan demonstrated a subhepatic fluid collection in the gallbladder fossa ( figure 1 ) . also noted was mild dilatation of the intrahepatic but not the extrahepatic biliary ductal system . a ct - guided needle aspiration of the subhepatic collection produced bilious fluid , and a percutaneous pigtail drainage catheter placement yielded 200 ml of bile . two days later , a diagnostic endoscopic retrograde cholangiopancreatography ( ercp ) study revealed a tapered narrowing of the common duct with posterior displacement consistent with residual extrinsic mass effect and associated inflammatory changes ( figure 2 , 3 ) . multiple air bubbles were noted to be present within the bile duct that were felt by the endoscopist to have been introduced during the procedure . the metal clips placed at surgery were seen not to be in unusually close proximity to the common hepatic duct . an endoscopic sphincterotomy was performed , and no stones were retrieved from the common duct . nevertheless , the procedure was complicated by acute pancreatitis of moderate severity that subsided spontaneously over two weeks . the biliary drainage from the percutaneous catheter initially decreased and then remained steady at about 60 ml per day . a catheter fistulagram demonstrated a small right hepatic duct branch in the area of the gallbladder fossa ( figure 4 ) . after four weeks of drainage , there was complete resolution of the subhepatic biloma , and a repeat ercp demonstrated a normal common duct with absence of the narrowing seen on the initial study ( figure 5 ) . the bile drainage gradually decreased to nil over six weeks , and the percutaneous catheter was removed . ercp cholangiogram demonstrating a residual tapered stenosis of the common duct due to compression by the biloma and associated inflammation . lateral oblique view of ercp cholangiogram showing posterior displacement of the common duct consistent with an extrinsic mass effect exerted by the biloma . fistulagram through the percutaneous drainage catheter demonstrating a communication between the decompressed biloma cavity and a small branch of the right hepatic duct in the area of the gallbladder fossa . repeat ercp cholangiogram showing resolution of the stenosis of the common duct following closure of the biliary fistula and collapse of the biloma cavity . bilomas typically present as right upper quadrant abdominal pain and may be accompanied by nausea , emesis and fever . they most often are located in the subhepatic space but may occur intrahepatically or , rarely , in the retroperitoneal space . the frequency of biloma as a complication of cholecystectomy has been reported to range from 0.14% to 2.65% . the etiology is most often bile leakage from either an accessory bile duct , a duct of luschka in the gallbladder fossa of the liver , or an inadequately secured cystic duct stump . the diagnosis is supported by an abdominal ct , ultrasound ( us ) or magnetic resonance imaging ( mri ) scan showing a homogenous density fluid collection in the right upper abdomen and can be confirmed by a radionuclide ( hida ) scan demonstrating continuity of the collection with the biliary ductal system . ercp and transhepatic cholangiography are the most accurate techniques for delineating the exact anatomy of the biliary leak . initial management options include percutaneous catheter drainage , ercp with sphincterotomy and/or biliary stent placement , or a combination of these techniques . if initial percutaneous aspiration of the biloma yields a large volume or infected fluid , a drainage catheter should be placed . some authors recommend an algorithmic approach with percutaneous drainage followed by endoscopic stent placement only for persistent leakage . relaparoscopy has also been advocated based on its ability to cleanse the peritoneal cavity , replace cystic duct clips , electrocoagulate the gallbladder fossa and accurately place drainage catheters . surgical control of the biliary leak is reserved for cases of failed conservative management or major bile duct injury requiring biliary reconstruction . biliary obstruction manifesting after laparoscopic cholecystectomy most often is due to either a retained common duct stone or an unrecognized surgical misadventure , such as transection or clipping of the common hepatic or common bile duct . retained stones may cause postoperative cholangitis or pancreatitis but frequently manifest only as uncomplicated jaundice or elevated liver function tests . as iatrogenic injuries to the biliary tree have similar symptoms , signs and laboratory abnormalities , imaging of the ducts is essential . abdominal us , ct , mri and hida scans all have the ability to detect biliary obstruction , but differentiation between obstructing calculi and bile duct injury may be problematic . therefore , ercp and/or transhepatic cholangiography are usually required for accurate diagnosis of postoperative biliary obstruction . while common duct stones are typically successfully extracted by endoscopic or interventional radiologic means , biliary ductal injuries may or may not be amenable to nonsurgical techniques . early ductal strictures , partial transections and nonocclusive clips may sometimes be definitively treated by biliary dilatation and stenting , but complete transections or occlusions invariably require surgical reconstruction , usually by means of biliary - enteric anastomosis . on occasion , partial biliary obstruction appears to be temporary and self - limited , with spontaneous resolution over a period of days to weeks . this may be attributed to localized inflammation or even ductal spasm , although the etiology usually remains speculative . in the case presented , the specific cause for the partial biliary obstruction was the extrinsic pressure and inflammatory changes imparted by the adjacent biloma . this was manifested on ercp by the long , smoothly tapered stricture and displacement of the common duct . decompression of the biloma by percutaneous catheter drainage and treatment of the small intrahepatic ductal leak by sphincterotomy successfully relieved the extrinsic pressure and resulted in resolution of the biliary obstruction . although biloma has previously been reported to cause gastric outlet obstruction , this to our knowledge , is the first documented instance of extrahepatic biliary obstruction due to a biloma . ironically , the pressure exerted on the extrahepatic bile duct by the biloma served to increase the pressure within the more proximal biliary system , thus exacerbating the leakage of bile from the intrahepatic ductal branch and further contributing to the size of the biloma . the process thus became a self - perpetuating vicious cycle of ductal compression leading to higher biliary pressure leading to increased bile leakage and even greater ductal compression . decompression of the biloma was probably critical to relieving not only the biliary obstruction per se but also the pressure - head contributing to the perpetuation of the biloma itself . though obviously rare , extrahepatic biliary ductal obstruction caused by biloma may follow laparoscopic cholecystectomy and should be recognized as a possible etiology of postoperative jaundice .

background : jaundice presenting after cholecystectomy may be the initial manifestation of a serious surgical misadventure and requires rigorous diagnostic pursuit and therapeutic intervention . biloma is a well recognized postcholecystectomy complication that often accompanies biliary ductal injury.case report : a 23-year - old female underwent laparoscopic cholecystectomy for symptomatic gallstones and three weeks postoperatively developed painless jaundice . radiographic and endoscopic studies revealed a subhepatic biloma causing extrinsic compression and obstruction of the common hepatic duct.results:percutaneous catheter drainage of the biloma combined with endoscopic sphincterotomy successfully relieved the extrahepatic biliary obstruction and resolved the intrahepatic ductal leak responsible for the biloma.conclusion:although heretofore undescribed , post - cholecystectomy jaundice due to extrahepatic bile duct obstruction caused by biloma may occur and can be successfully treated by means of standard radiologic and endoscopic interventions .

cerebral venous and sinus thrombosis is a rare condition accounting for < 1% of all strokes.7 ) its annual incidence is estimated at three to four cases per one million members of the population , most often affecting young adults and children.19 ) in adults , the peak incidence is in their third decade , and approximately 75% of adult patients are female.5)7 ) thrombotic risk factors or direct causes are identified in approximately 85% of patients with cerebral sinus thrombosis.19 ) superior sagittal sinus thrombosis ( ssst ) is associated with a variety of hypercoagulable , states including crohn 's disease , diabetes insipidus , direct injury to the sinus , iatrogenic causes , malignancy , nephrotic syndrome , oral contraceptives , paroxysmal nocturnal hemoglobinuria , polycythemia , pregnancy , puerperium , systemic lupus erythematosus , and ulcerative colitis.1)19 ) coagulation abnormalities are commonly seen in patients with hyperthyroidism.6)9)18 ) however , the association between hyperthyroidism and cerebral venous thrombosis is poorly understood . to investigate the possible association between these two clinical conditions , we report on a case of a 31-year - old male patient with a six - year history of hyperthyroidism who developed ssst . a 31-year - old male patient was admitted to our institute with seizure , headache , and mental deterioration . during the recent six years he did not undergo a regular follow - up and had poor compliance to the medication . one day before visiting our institution , the patient was admitted at a local hospital for transient weakness of both lower extremities . the patient underwent treatment for thyrotoxic periodic paralysis or thyroid crisis , but became progressively stuporous and experienced seizure attacks several times . findings on immediate brain computerized tomography ( ct ) showed multiple hemorrhages in the subcortical area of both middle frontal gyrus ( fig . after two hours , the patient was transferred to our institute and still exhibited a stuporous mentality with no motor weakness . findings on brain ct showed a slight increase of hemorrhage and ct angiography showed no abnormalities of the major cerebral artery system ( fig . laboratory results showed hyperthyroidism with the following values : 176.2 ng / dl of t3 ( normal range , 80 - 200 ng / dl ) , 3.84 ng / dl of high free t4 ( normal range , 0.89 - 1.76 ng / dl ) , and less than 0.01 iu / ml of thyroid - stimulating hormone ( normal range , 0.35 - 5.5 iu / ml ) . hematologic and coagulation parameters , including platelet count , prothrombin time , activated partial thromboplastin time , fibrinogen , anti - thrombin ill , fibrin degradation products , d - dimer , lupus anticoagulant , protein c activity , and protein s activity were all normal . two days after the initial visit , the patient became nearly alert and fully oriented . cerebral digital subtraction angiography ( dsa ) was performed in order to determine the causes of the non - traumatic cerebral hemorrhage . cross - sectional echocardiography showed a normal left ventricular size and function with no evidence of intra - cardiac thrombus . following the diagnosis of ssst , the patient received anticoagulation therapy with warfarin 5 mg qd and avoided systemic heparinization on account of the aggravating hemorrhage . four weeks after treatment , follow - up cerebral dsa showed a recanalization of the superior sagittal sinus ( fig . 4a , b ) , and laboratory findings indicated a normal free t4 level of 0.81 ng / dl . the patient had no recurrence of neurological symptoms and maintained a euthyroid state for the next nine months . ssst is an uncommon cerebrovascular accident ; due to a broad spectrum of symptoms and clinical courses , a diagnosis is still frequently overlooked or delayed.7 ) the average delay from the onset of symptoms to the diagnosis is seven days.8 ) in addition , approximately 15% of cases of ssst are considered to be idiopathic.19 ) although coagulation disturbances are reported in hyperthyroidism , an association between hyperthyroidism and cerebral venous thrombosis has not been well established . schutta et al.16 ) reported on a case of a 34-year - old male patient with hyperthyroidism and inherited plasminogen deficiency . siegert et al.17 ) documented on two patients ( a 24-year - old male and a 32-year - old female ) with ssst during the thyrotoxic phase of grave 's disease . dai et al.4 ) demonstrated on a 39-year - old male patient with undiagnosed hyperthyroidism who developed ssst . the patient had a high free t4 level , hot thyroid up - take , and rapid atrial fibrillation . in our patient , along with previous reports , it can be hypothesized that hyperthyroidism is an independent risk factor for cerebral venous thrombosis . thrombotic events in thyrotoxic patients are in danger of systemic and cerebral arterial infarctions and have been directly attributed to atrial fibrillation , suggesting emboli as the causative agent.2)11)13 ) in our case , however , normal sinus rhythm was observed on the electrocardiography . in addition , findings on echocardiography showed normal left ventricular size and function with no evidence of intra - cardiac thrombus . development of ssst occurs due to multi - factorial causes , commonly including three factors : stasis of the blood stream , abnormalities of the vessel wall , and hypercoagulability . these three factors are involved in promoting venous thrombosis.17 ) large thyrotoxic goiters may cause stasis of venous blood flow from the cerebral circulation through local obstruction by itself or large blood flow of the thyroid gland.3)10 ) however , our patient did not present with a goiter . and no other causes of vessel wall abnormality , such as vascular inflammation and direct injury to veins , were detected . therefore , we suppose that hypercoagulability was the main cause of ssst in our patient with hyperthyroidism . to date , numerous studies have indicated an association of coagulation disturbances with hyperthyroidism . several authors have reported that the intrinsic clotting system , particularly factor viii , was markedly affected by hyperthyroidism.6)9)15)18 ) high adrenergic tone and hyper - metabolic state of hyperthyroidism resulted in factor viii hyperactivity , thus increasing the likelihood of hypercoagulation.6)14)18 ) although our patient exhibited a normal range of factor viii activity ( 135% , normal range , 60 to 140% ) , he showed high activity of factors ix and xi ( > 160% for both ) . these results are consistent with hypercoagulation through activation of the intrinsic clotting pathway , factor xi in particular.12)20 ) in this regard , based on our case report , it is probable that activation of intrinsic clotting factors by hyperthyroidism might be the factor responsible for the occurrence of ssst . abnormal activity of the clotting factor is recovered to normal after reaching the euthyroid state ; therefore , anti - thyroid therapy constitutes an important part of the treatment.6)9)15)18 ) we suggest that , because of the hypercoagulability , patients with hyperthyroidism may be predisposed to development of ssst . consideration of the possibility of development of cerebral venous thrombosis in patients with hyperthyroidism who present with neurological symptoms is mandatory . conversely , hyperthyroidism as the thrombotic factor in a patient with cerebral venous thrombosis who is not at risk of developing cerebrovascular events must also be considered .

superior sagittal sinus thrombosis ( ssst ) is an uncommon cause of stroke , whose symptoms and clinical course are highly variable . it is frequently associated with a variety of hypercoagulable states . coagulation abnormalities are commonly seen in patients with hyperthyroidism . to the best of our knowledge , there are few reports on the association between hyperthyroidism and cerebral venous thrombosis . we report on a 31-year - old male patient with a six - year history of hyperthyroidism who developed seizure and mental deterioration . findings on brain computed tomography ( ct ) showed multiple hemorrhages in the subcortical area of both middle frontal gyrus and cerebral digital subtraction angiography ( dsa ) showed irregular intra - luminal filling defects of the superior sagittal sinus . these findings were consistent with hemorrhagic transformation of ssst . findings on clinical laboratory tests were consistent with hyperthyroidism . in addition , our patient also showed high activity of factors ix and xi . the patient received treatment with oral anticoagulant and prophylthiouracil . his symptoms showed complete improvement . a follow - up cerebral angiography four weeks after treatment showed a recanalization of the sss . in conclusion , findings of our case indicate that hypercoagulability may contribute to development of ssst in a patient with hyperthyroidism .

the plantation convention of the international labour organisation ( ilo ) defines plantations as any agricultural undertaking regularly employing hired workers which is situated in the tropical or sub tropical regions and which is mainly concerned with the cultivation or production for commercial purposes of coffee , tea , sugarcane , rubber , bananas , cocoa , coconuts , groundnuts , cotton , tobacco , fibers ( sisal , jute , and hemp ) , citrus , palm oil , cinchona or pineapple . plantation industries in india employ over 1 million people and are among the largest private employers in india . coffee is grown mainly in the three south indian states , namely karnataka , tamil nadu , and kerala , and tea is grown predominantly in the northeastern part of india and south india . studies have shown that people with good work ability and capacity have a lower risk for early retirement and a higher quality of life . work capacity can be assessed by aerobic capacity , endurance , energetic efficiency , voluntary activity , and work productivity . endurance is defined as the maximum length of time an individual can sustain a given workload ( without rest ) . work ability is of high relevance for each worker and for his or her organization . how good the worker is at present , in the near future , and how able he / she to do his / her work with respect to the work demands and health and mental resources . work ability is a result of the interaction of the worker and his or her work . work ability may also be described as the balance of the workers resources and the work demands . very few studies have been published regarding work capacity and work ability among indian plantation workers . studies of this nature helps in developing appropriate strategies to improve work capacity and ability . this study would also help us understand the factors associated with work capacity and ability . to assess the work capacity of workers at a tea plantation in south indiato assess the work ability of the workers at a tea plantation in south indiato study the factors associated with work capacity and work ability among the plantation workers . to assess the work capacity of workers at a tea plantation in south india to assess the work ability of the workers at a tea plantation in south india to study the factors associated with work capacity and work ability among the plantation workers to assess the work capacity of workers at a tea plantation in south indiato assess the work ability of the workers at a tea plantation in south indiato study the factors associated with work capacity and work ability among the plantation workers . to assess the work capacity of workers at a tea plantation in south india to assess the work ability of the workers at a tea plantation in south india to study the factors associated with work capacity and work ability among the plantation workers a cross - sectional study was conducted at a tea plantation company with six estates located in annamalai , south india , from march to may 2015 , after obtaining necessary permission . after obtaining institutional ethical committee ( iec ) approval , the study subjects were selected based on the inclusion criterion , that is , all tea pluckers of the plantation aged above 18 years and exclusion criterion , that is , workers with history of ischemic heart diseases and serious illness . a sample size of 164 was calculated using prevalence of 70% , with 5% level of significance and 95% confidence interval with 7% of true estimate . however , we could cover 199 subjects in this study and convenience sampling was followed . data were collected using standard questionnaire and predesigned and structured interview schedule comprising of three parts as follows : sociodemographic data , assessment of work capacity , and a work ability questionnaire . the questionnaire used was translated into local language , that is , tamil , following which it was back translated to ensure that the meaning of the questions were conveyed appropriately . work capacity was assessed by aerobic capacity , endurance , energetic efficiency , voluntary activity , and work productivity . the harvard step test was used in this research , which is a test of aerobic capacity ( physical fitness ) developed by brouha et al . physical fitness index ( pfi ) is calculated by = ( 100 test duration in seconds ) divided by ( 2 sum of heart beats in the recovery period ) . heart rate was calculated at the end of 1 min , 2 min , and 3 min . endurance was calculated as the maximum length of time an individual can sustain a given workload ( without rest ) . work productivity and energetic efficiency in our study was assessed by average number of tea leaves plucked . voluntary activities like time spent for sleep , childcare , social activities , leisure , and household chores were also assessed . the wai is a validated instrument to assess the individual work ability of an employee . the score categories are 727 points : bad , 2836 points : moderate , and 3743 points : good . the data were entered and coded in microsoft excel and were analyzed using statistical package for the social sciences ( spss ) version 16 ( spss - inc . , other tests used in this study were correlation , kruskal - wallis , one - way analysis of variance ( anova ) , and independent t - test . a total of 199 workers participated in this study and were representative of all the six estates . majority [ 90 ( 45.3% ) ] were in the age group of 4655 years , females 128 ( 64.3% ) , belonging to class i 105 ( 52.8% ) socioeconomic status , permanent workers 186 ( 93.55% ) . among the workers majority 78 ( 39.2% ) had work experience of 2130 years , married 190 ( 95.5% ) , belonging to hindu religion 177 ( 88.9% ) , completed primary education 158 ( 79.4% ) , had normal body mass index ( bmi ) of 118 ( 59.4% ) , with majority having no habits 101 ( 50.8% ) . work capacity among plantation workers most of the workers had endurance of more than 1 hour that is the maximum length of time an individual can sustain a given workload ( without rest ) . majority [ 141 ( 70.9% ) ] of workers had the work productivity ( weight of tea leaves plucked ) of 101150 kg . apart from sleep , majority of workers spend maximum of their time for household chores as voluntary activity . only 9.6% of the workers had good work ability , whereas majority [ 179 ( 89.9% ) ] of workers had moderate work ability [ table 3 ] . while assessing work ability , majority [ 133 ( 66.8% ) ] were found to have moderate grade in relation to physical demands and also in relation to mental demands majority [ 146 ( 73.4% ) ] were found to have moderate grade . when assessing work ability in the next 2 years majority [ 104 ( 52.3% ) ] were relatively certain of their work ability . in majority [ 168 ( 84.4% ) ] of workers work ability among plantation workers when assessed about the sick leave majority [ 100 ( 50.3% ) ] were found to have taken 19 days of sick leave in the last 1 year . work ability was found to be significantly associated with work capacity ( p < 0.05 ) . workers with moderate work ability were also found to have average work capacity on objective assessment . statistically significant association was found between work ability and work experience , that is , those with less work experience were found to have good work ability on subjective assessment . association of work ability with various factors similarly , work ability is significantly associated with motivation , sleep , musculoskeletal problems , average weight of leaves plucked and mental capacity that is with increased motivation , better sleep , less musculoskeletal disorders , and better mental capacity work ability has also increased . work capacity did not have associations with the following : gender , job category , marital status , habits , endurance , motivation , sleep , fatigue , sickness absenteeism , and bmi . there is negative correlation between work ability and bmi that is as the bmi increases work ability decreases with correlation coefficient of -0.74 . pfi ( work capacity ) has no significant association with sex , marital status ( independent t - test ) . there is significant association between pfi and work ability ( one - way anova ) . those who were found to have better work ability on subjective assessment were also found to have better work capacity on objective assessment . majority , 70.9% , of workers were able to pluck > 100 kg per day . work ability assessed by wai found that 89.9% workers have moderate work ability and 9.5% have good work ability . it is also found that 11.6% of workers take more than 25 days of sick leave in 1 year . most of the plantation workers had musculoskeletal problems followed by gastritis , endocrine problems such as diabetes , thyroid disorders followed by cardiovascular problems such as hypertension . very few workers were also found to have dermatological , respiratory , genitourinary and neurological disorders , anemia , and autoimmune diseases such as systemic lupus erythematosis ( sle ) and scleroderma . work ability was found to be significantly associated with work capacity , work experience , marital status , endurance , motivation , sleep , musculoskeletal problems , average weight of leaves plucked , and mental capacity . in a study conducted in norway on work ability among female employees , 8.9% reported an extremely or very reduced ability to work , 24% reported poor physical health , and 21.9% reported mental distress . work ability in that study was found to be significantly associated with age and unskilled occupation . association of work ability with poor physical health , such as musculoskeletal problems , was similar to our study results . in a study conducted in finland among 818 employees working in different occupations where workers were followed up for a period of 11 years they were assessed for their work ability according to an index on work ability , physical and mental work demands , diagnosed diseases , work impairment from disease , sickness absence , work ability prognosis , and psychological resources , similar to our study . while our study could not find any association of work ability with age , we did find a significant association with work capacity . kruskal - wallis test proved that there is no significant association between bmi and work ability . independent t - test proved that work capacity has no significant association with sex and marital status . one - way anova proved a significant association between work capacity and work ability . in a study conducted in the palm oil plantation in sarawak , malaysia , work capacity has significant association with iron deficiency anemia , mental capacity , and socioeconomic status , whereas in our study work capacity did not have associations with gender , socioeconomic status , job category , marital status , habits , endurance , motivation , sleep , fatigue , sick absenteeism , and bmi . in another study to find association between functional capacity and work ability among elderly municipal employees , they found a significant association between work capacity and work ability that is similar to our study results . recall bias , undiagnosed medical conditions that may interfere with the results , and observer variability were some limitations of the study . of the 199 workers assessed 12.5% has poor work capacity ; endurance capacity was poor among 4% of workers . of all , 70.9% of workers can able to pluck > 100 kg of leaves per day . work ability assessed by wai found 89.9% of workers with moderate work ability and 9.5% with good work ability . it is also found that 11.6% of workers take > 25 days of sick leave in 1 year . work ability also has significant association with experience , endurance , motivation , musculoskeletal problems , mental capacity , and productivity . active measures are necessary for in the long run maintaining and promoting work ability . several finnish studies have shown that work ability can be sustainably promoted , even among older workers . periodic health examinations ( to alleviate musculoskeletal problems and to regulate bmi ) or other screening procedures , constant motivation , measures to improve mental capacity will help to improve work ability and thereby capacity and productivity .

background : work capacity is the ability to perform real physical work , and work ability is a result of interaction of worker to his or her work that is how good a worker is at present , in near future , and how able is he or she to do his or her work with respect to work demands and health and mental resources.objective:to assess the work capacity and work ability and to study the factors associated with work capacity and work ability of workers at a tea plantation in south india.materials and methods : a cross - sectional study was conducted at a tea plantation in annamalai , south india , from march to may 2015 . data were collected using a structured interview schedule comprising of three parts as follows : sociodemographic data , work ability questionnaire , and work capacity assessment.results:of the 199 subjects participated in the study , majority [ 90 ( 45.3% ) ] were in the age group of 4655 years , and 128 ( 64.3% ) were females . of the 199 workers , 12.6% had poor aerobic capacity ( by harvard step test ) , 88.4% had an endurance of more than 1 h , 70.9% had better work productivity and energetic efficiency , and the voluntary activity workers spent most time on household chores . of the 199 workers assessed , only 9.6% had good work ability . there is negative correlation between work ability and body mass index ( bmi).conclusion : our study found 12.6% workers with poor aerobic capacity and 9.6% of workers with good work ability . periodic health examinations and other screening procedures should be made as routine in workplace to improve work ability and capacity .

kimura 's disease ( kd ) is a rare benign disorder of unknown etiology , and is observed primarily in young asian men . kd may the result of an allergic or chronic inflammatory response , preferentially occurring in the head and neck . the clinical symptoms are usually manifest either as painless unilateral lymphadenopathy , predominantly in the head or neck region , or elevated serum immunoglobulin ( ig ) e and eosinophilia1,2 ) . kd lesions usually precede or coincide with the development of renal disease2,8 ) . early diagnosis and recognition of kd may spare both patient and doctor from the need for unnecessary invasive diagnostic procedures . in the present case , the patient exhibited an unusual case of kd , occurring during hemodialysis , involving the thoracic and abdominal lymph nodes , which resolved itself spontaneously , and nearly completely , after two months . a 45-year - old man was admitted for evaluation of a series of painless , firm , movable neck masses . he had received maintenance hemodialysis for 3 years , for end - stage renal disease resulting from chronic glomerulonephritis . hemodialysis was performed 3 times weekly for 4 hours per session , using polysulfone dialysis columns . in the preceding 4 months the patient had no history of fever , cold sweating , or weight loss . during the physical examination , firm and movable masses , measuring up to 332 cm ( the largest one ) were found . these masses were palpable with no tenderness , and were located primarily in the right anterior triangle of the neck . although there were also several palpable masses in both the axillary and inguinal areas , no hepatosplenomegaly was detected . laboratory findings included a hemoglobin level of 7.3 g / dl , platelet count of 20010/l , and a white blood cell ( wbc ) count of 6.2 10/l : the differential wbc count revealed 68.9% segmented neutrophils , 10.2% lymphocytes , 8.4% monocytes , 12.1% eosinophils , and 0.4% basophils . serum total ige level was 261.0 iu / ml . the blood urea nitrogen and serum creatinine level were 56 mg / dl and 4.8 mg / dl . fine needle aspiration cytology of the neck mass revealed findings of nonspecific reactive lymphadenitis . a computed tomography ( ct ) scan of the neck and chest revealed masses adjacent to both sternocleidomastoid muscles , numerous lymph nodes of varying size in both axillary areas , and over lymph nodes of over 1 cm in size in the paratracheal , subcarinal , and intrapulmonary areas ( figure 1a ) . a ct scan of the abdomen and pelvis displayed multiple lymph nodes of varying size , which were enhanced in the hepatic hilum , peripancreatic area , celiac axis , and paraaortic area ( the largest was 4.5 cm ) ( figure 1b ) . a tumor scan using gallium-67 demonstrated more noticeable increased uptake lesions in the left lower cervical , left axillary , paraaortic , right iliac , and both inguinal lymph nodes ( figure 2 ) . the findings from fine needle aspiration cytology were inconclusive with regard to diagnosis , thus an open biopsy was recommended . results of histopathological examinations of the neck mass and lymph nodes revealed dense infiltration of eosinophils , lymphocytes , and histiocytes , along with many small vessels , mild fibrosis , and results consistent with kd , with no evidence of malignant lymphoma ( figure 3 ) . thereafter , the patient has received no specific treatment , as his symptoms , with the exception of the mass , were clinically unremarkable . after two months , physical examination revealed no neck masses , and a follow - up abdominal ct scan showed that the numerous lymph nodes of varying size had subsided spontaneously ( figure 4 ) . although its etiology remains unknown , it has been tentatively suggested that kd is the result of an aberrant allergic or chronic inflammatory response to viral , bacterial or parasitic infection3 - 5 ) . kd usually manifests as a tumor - like lesion , showing a predilection for head and neck sites . systemic manifestations of kd are characterized by elevated serum ige , eosinophilia , and renal diseases , including focal segmental glomerulosclerosis , iga nephropathy , minimal change disease , membranous nephropathy , and igm nephropathy6 - 8 ) . clinical symptoms of kd normally precede or coincide with the development of renal disease2,8 ) . neck masses that were incidentally detected in end - stage renal disease patients were first considered in terms of differential diagnoses , possibly as neoplastic disease or infection , such as tuberculosis , in asian patients . clinically , kd may often be confused with malignant lymphoma or other metastatic cancers9 ) . consequently , a patient with kd is often unnecessarily evaluated for symptoms of far more serious diseases10 ) . it is difficult to diagnose kd without a tissue biopsy , and fine needle aspiration cytology has only limited value in such cases . in the present case , , we were also unable to differentiate these lesions from malignant lymphoma or metastasis . unlike most cases , our patient exhibited multiple lymphadenopathy , including thoracic , abdominal , neck , axillary , and inguinal lymph nodes . histopathological analyses of the neck mass and lymph nodes revealed no signs of malignant lymphoma . in contrast , alhe occurs in all racial groups , showing a slight predominance in females11 ) . regional lymphadenopathy , serum eosinophilia , and elevated ige levels are rare in cases of alhe . kd typically manifests several histologic features , such as predominant eosinophilic infiltration with follicular hyperplasia , fibrocollagenous change , and vascular proliferation . however , vascular proliferation is more significant in alhe . in alhe , vessels are aggregated and lined by plump cuboidal , or occasional hobnail , endothelial cells , with frequent cytologic atypia and vacuolization . however , these angiomatoid features are never observed in cases of kd12 ) . in our case , we observed no vessels lined by plump cuboidal endothelial cells suggesting alhe , and there were characteristic and distinctive clinical features suggesting kd . we have no evidence that would explain this relationship between kd and end - stage renal disease in our patient . the treatment of kd involves one of three major approaches : surgical excision , irradiation , or steroid therapy . our patient had no complaints or symptoms , with the exception of the aforementioned palpable masses . thus , the patient has received conservative treatment while undergoing regular checkups . in conclusion , a high index of suspicion regarding kd the early diagnosis and recognition of kd may spare both patient and doctor from the need for unnecessary invasive diagnostic procedures . to our knowledge , this is the first case of kd occurring during hemodialysis , involving thoracic and abdominal lymph nodes , which resolved itself both spontaneously , and nearly completely , after two months .

we report the first observed case of kimura 's disease occurring during hemodialysis , involving the thoracic and abdominal lymph nodes , which spontaneously resolved nearly completely after two months . early diagnosis and recognition of kimura 's disease may spare both the patient and doctor from the need for unnecessary invasive diagnostic procedures . therefore , we emphasize that we need to have a high index of suspicion regarding kimura 's disease .

cervical cancer represents the third most common cancer in women worldwide , with 86% of all deaths occurring in developing countries , where there is lack of access to prevention , early diagnosis and treatment ( jemal et al . , 2011 ) . in brazil , cervical cancer ranks as the second most frequent cancer among women between 15 and 44 years of age ( who / ico , 2010 ) . most cervical cancers can be detected early through a routine exfoliative cytology test ( papanicolaou test ) , a screening which has been used for more than 50 years in an effort to decrease the number of deaths from cervical cancer ( stack , 1997 ) . dna testing has also been reported as an important tool for detecting hpv ( mayrand et al . , 2007 ) and is being introduced in some countries as an adjunct to the papanicolaou test or as the primary screening test ( castle et al . , 2012 ) . in developing countries , this introduction has been controversial , mainly because cytology - based screening programs suffer from lack of basic healthcare infrastructure ( bradford and goodman , 2013 ) . in a meta - analysis study , hpv types 16 , 18 , 31 , 33 and 45 were shown to be the most prevalent types associated with cervical carcinomas in latin america ( ciapponi et al . , 2011 ) . chromosomes or chromosome segments that fail to be incorporated into nuclei during cell division configure micronuclei ( mn ) . the mn test , readily performed via microscopy , has been successfully used to screen population groups at risk for cancer , representing a sensitive indicator of genetic damage ( samanta and dey , 2012 ) . the frequency of mn appears to increase in carcinogen - exposed tissue before there are any clinical symptoms ( gayathri et al . , 2012 ) . considering the fact that oncogenic hpv viral proteins may induce cytogenetic changes in exfoliated cells of the uterine cervix , a positive correlation between micro - nucleated cells and dysplasia in papanicolaou smears has been reported ( gandhi and kaur , 2003 ; guzmn et al . , 2003 ; corts - gutirrez et al . , 2010 ; aires et al . , 2011 ) . taking this into account , the aim of the present study was to investigate the association between hpv - dna and mn in women from southern brazil with normal cervical cytology in order to contribute additional information to cervical cytology analysis . additionally , some of the most prevalent high - risk hpv types were investigated . a total of 158 normal cervical smears were analysed cytologically for hpv - dna and mn comparisons . the smears were collected through the use of a cytobrush in a gynecology clinic at a healthcare medical centre ( posto de sade modelo ) in porto alegre , rio grande do sul , southern brazil from march to december 2009 . all women who agreed to participate signed an informed consent form . this study was approved by the ethics committee of universidade luterana do brasil ( number 2008 - 601h ) . two slides were made , one for the conventional papanicolaou exam and another for mn analysis . after the slides were prepared , the cytobrush was placed in a tube containing 2 ml te 1x and stored at 20c for later dna extraction . for the papanicolaou test , the analyses were based on the bethesda system ( solomon et al . , 2002 ) . the slides for detecting and counting mn were stained with giemsa , and evaluated four times , twice by each of two observers independently . a total of 1000 cells were counted under a light microscope at a 1000 magnification following the criteria described by tolbert et al . a non - organic method developed in our laboratory was used to extract the dna from the clinical specimens ( michelon et al . , 2011 ) . the resulting sediment was resuspended in 50 l of 1x te and incubated at 99 c for 10 min . the dna was then purified using 5 l of a glass matrix ( concert extraction systems ; life technologies , rockville , md , usa ) . the amplification of a 150 bp fragment of the l1 region of the hpv genome was performed using the gp5+/biogp6 + consensus primers ( de roda husman et al . , 1995 ) . the pcr was carried out in a final volume of 50 l containing 50 mm kcl , 10 mm tris - hcl ph 8.5 , 2.5 mm mgcl2 , 0.1 mm of each deoxynucleoside triphosphate , 50 ng of each primer , 2.5 u of taq dna polymerase ( invitrogen ) and 10 l of extracted dna . a negative control ( no dna ) was included in each pcr run to ensure that there was no cross contamination . samples were amplified under the following conditions : initial denaturation step at 95 c for 5 min , 40 cycles at 95 c for 1 min , 52 c for 1 min and 72 c for 1 min , and a final elongation step at 72 c for 10 min . dna of caski ( hpv-16 positive ) cells were used as a positive control in all pcr reactions . the final pcr product ( 10 l ) was visualized in electrophoresis agarose gel ( 1.5% ) under uv light . hpv dna genotyping of high - risk types 16 , 18 , 31 , 33 , 39 , 45 and 59 was carried out using a microplate colorimetric hybridization assay ( mcha ) developed in our laboratory ( barcellos et al . , 2011 ) . seven dna plasmids containing the l1 gene of a high - risk hpv type ( hpv16 , 18 , 31 , 33 , 39 , 45 and 59 ) were used as positive controls . the absolute and relative frequencies of the categorical variables and the distribution of the continuous variables were evaluated to define the profile of the population under study . chicago , il , usa ) . the test was used to study differences in categorical parameters the mean age of the 158 women was 42.7 13.9 years , the mean age of menarche was 11.6 1.7 years and the mean number of children per woman was 1.4 1.2 children . in terms of other baseline characteristics , 107 ( 65.5% ) had a stable marital status , 119 ( 73% ) were caucasian , 25 ( 25.2% ) smoked , 58 ( 35.6% ) used oral contraceptive , and 78 ( 47.9% ) were post - menopausal . the mean age of hpv - dna positive women ( 34.2 12.6 ) was significantly lower than the mean age of hpvdna negative women ( 43.9 13.7 ) ( p = 0.003 ) . the positive samples were tested for the presence of hpv 16 , 18 , 31 , 33 , 39 , 45 and 59 . fourteen of the 20 positive samples ( 70.0% ) were positive for hpv 16 , with 7 out of 20 ( 35.0% ) being positive for hpv 31 ; 4 out of 20 ( 20.0% ) for hpv 33 ; 2 out of 20 ( 10.0% ) for hpv 39 ; 3 out of 20 ( 15.0% ) for hpv 45 ; and 2 out of 20 ( 10.0% ) for hpv 59 . infection by one and multiple hpv types was found in 11 out of 20 ( 55.0% ) and 9 out of 20 ( 45.0% ) samples , respectively . the cellular changes consistent with the presence of mn were observed in 47 ( 29.7% ) of 158 slides , of which 11 were hpv - positive and 36 were hpv negative . the presence of mn was significantly associated with hpv - dna positivity ( p = 0.016 ) ( table 1 ) . on the other hand , the absence of mn observed in a considerable number of hpvdna negative samples ( 102 ) may be of great value in predicting the absence of hpv . in developed countries , the variability of performance in cytology - based screening has led to the development of more effective alternatives , such as reliable molecular testing . several large randomized controlled trials have concluded that hpv testing is more sensitive than cytology for cervical cancer screening ( mayrand et al . , 2007 ; castle et al . , 2012 ) . despite the importance of hpv testing , its use requires advanced technology and still has a high cost , limiting the possibility of its introduction in developing countries . considering the importance of cervical cancer control programs and the limited number of studies on mn scoring in normal cervical cytology ( aires et al . 2012 ) , the present study was intended to evaluate whether mn is a suitable test to complement the results of the papanicolaou smear in a low - resource setting , analyzing the association between hpv - dna and mn in normal cervical cytology of women from southern brazil . mn scoring on the cytology smear is easy , cheap , reproducible and can be performed on routinely stained papanicolaou smears as a biomarker of chromosomal damage ( gayathri et al . , 2012 ; samanta and dey , 2012 ) . in the present study , the prevalence of hpv - dna was 12.7% and was similar to that found in a meta - analysis study , in which the estimated global hpv prevalence in women with normal cytology was 11.7% ( bruni et al . , brazil has the highest incidence of cervical cancer , with a prevalence of hpv infection among women with normal cervical cytology of 21.1% , being the northern and northeastern regions with higher mortality than eastern and southern states ( dutra et al . , 2012 ) . in another study developed in rio grande do sul state , the prevalence of hpv - dna found in women with normal cytology was of 32.7% ( coser et al . , 2013 ) . it is reasonable to assume that these differences in hpv prevalence can be due to risks factors associated to the characteristics of populations in different countries , sensibility of the study method used to detect dna , and/or the number of women included in each study ( sample size ) . this finding supports previous research , which concludes that hpv prevalence is higher in women younger than 35 years of age , decreasing in women of more advanced age ( sanjos et al . , 2007 ) . this result corroborates earlier findings that hpv 16 is the most prevalent type of hpv woldwide ( guan et al . , 2012 ) . in the present study , the occurrence of mn was associated with the presence of hpv - dna in normal cervical cytology , thus corroborating data obtained by other authors ( aires et al . , 2011 ; this finding suggests that the presence of mn , even with no cytological signs of hpv , can be used by the physician as a criterion for repeating the test within a shorter interval of time . on the other hand , the high number of samples with negative results in both tests ( mn and hpv - dna ) suggests that these women are at low risk of hpv infection and can be called in for a new round of screening at the normal interval . other authors have used the micronucleus test as a biomarker for chromosome instability and malignancy , observing higher frequencies of micronucleated cells in samples with cervical cancer than in controls ( majer et al . , 2001 ; , 2008 ; corts - gutirrez et al . , 2010 ; gayathri et al . , finally , there is a consensus that the most clinically effective and cost - effective methods for reducing the incidence of cervical cancer are those that limit the number of required visits ( hoppenot et al . , 2012 ) . since cervical screening is usually based on cytology alone , the study of mn in papanicolaou smears can improve the quality of diagnosis and screening .

the aim of the present study was to investigate the association between hpv - dna and micronucleus ( mn ) frequency in women with normal cervical cytology . a total of 158 normal cervical smears were analyzed cytologically . the hpv genome was amplified using the gp5+/biogp6 + consensus primers . hpv - dna of high - risk types 16 , 18 , 31 , 33 , 39 , 45 and 59 were also investigated . of the 158 samples , 20 ( 12.7% ) and 47 ( 29.7% ) were positive for hpv - dna and mn , respectively . evidence for mn was found in 11 out of 20 ( 55% ) hpv - dna positive samples and in 36 out of 138 ( 26.1% ) hpv - dna negative ones . mn presence was significantly higher in hpv - dna positive samples ( p = 0.016 ) . on the other hand , the absence of mn observed in a considerable number of hpv - dna negative samples ( 102 ) may be of great value in predicting the absence of hpv . the mean age of hpv - dna positive women ( 34.2 12.6 ) was significantly lower than the mean age of hpv - dna negative women ( 43.9 13.7 ) ( p = 0.003 ) . infection by one or multiple hpv types was found in 11 out of 20 ( 55.0% ) and 9 out of 20 ( 45.0% ) samples , respectively . the evaluation of mn using cervical smears collected for cytology tests could , thus , be used as additional information to monitor a population s exposure to hpv .

although edentulism has been described to be on the decline in many developed countries , tooth loss continues to be a major public health problem globally , and causes of tooth extractions had large geographical and cultural differences among various regions in a country , and from one country to another . in order to facilitate planning for dental health services and to progress strategies to continue the reduction in tooth loss , it is important to identify the factors that result in such loss . extraction of permanent teeth is carried out for several reasons , including caries , periodontal disease , orthodontic treatment , traumatic injuries , prosthetic indications , and tooth impaction . however , caries and periodontal disease have been shown as the 2 main reasons for tooth loss . reported caries to be the main reason for tooth loss , whereas another study reported that periodontal disease was the main reason , while others found that caries and periodontal disease were equally responsible , and it was generally believed that dental caries was the main cause of tooth loss in the young , whereas periodontal diseases turned out to be more prominent after 40 years of age , whereas socioeconomic and cultural aspects may also be related with wish and possibility of patients to seek dental care . hence , the aim of the study was to investigate the major cause for tooth extraction , and the objective was to examine whether the major reason for tooth extraction was dental caries or periodontal disease . this was a cross - sectional study , examining the reason for tooth extraction , and the study was carried out in the department of periodontics , narayana dental college and hospital , nellore , andhra pradesh . the samples were taken from the individuals attending oral surgery department in our college , and general dental practitioners in nellore district , andhra pradesh . the dentists were requested to complete a specially designed study form ; on every extraction , they were to undertake within 1 month period ( february 2014 ) . the study form included age , gender , and number of teeth that were planned for extraction , and reason for tooth extraction that included the periodontal problems , dental caries , failed root canal therapy , orthodontic purpose , preprosthetic or esthetic purpose , root fractures , and patient 's refusal of alternative treatments , and space was also provided for listing other reasons which were not mentioned in the study form . in addition , the periodontal conditions that are associated with the tooth planned for extraction , i.e. , mobility , recession , malpositioning , food impaction , and sensitivity are included in the study form . study forms were collected by the principal investigator at the end of the study period from each center . the data were calculated using statistical analysis system , and the descriptive data were expressed by means of numbers and percentages . the data were calculated using statistical analysis system , and the descriptive data were expressed by means of numbers and percentages . a total of 502 patients were enrolled during the study period , and a total of 1055 teeth were extracted for several reasons . the distribution of patients and the extracted teeth according to age range and gender are presented in [ tables 1 and 2 ] , where males had fewer teeth extracted than females , and the number of extractions increased with increasing age . distribution of study population based on age distribution of study population based on gender factors affecting extraction the majority of extractions are due to periodontal problems followed by dental caries [ table 3 ] . other reasons frequently involved were root fractures , abscess , impaction , and apical periodontitis . when periodontal parameters that are associated with the tooth that is going to be extracted are taken into consideration , mobility was the primary reason followed by mobility associated with recession [ table 4 ] . reason for extraction periodontal parameters that are involved with the extracted tooth while comparing the age and reason for tooth extraction , we found that chronic periodontitis and dental caries were the 2 main reasons for tooth extraction in all the age groups followed by root fracture . in patients aged above 40 years , periodontal problems were the main reason for extraction , whereas , in 2030 years age group dental caries was the primary reason [ graph 2 ] . ap : apical periodontitis , pd : periodontal disease , rct : root canal treatment , rf : root facture graph 3 describes the comparison between gender and reason for tooth extraction . though the main cause of extraction in males was due to periodontal problems , it was dental caries in females . ap : apical periodontitis , pd : periodontal disease , dc : dental caries , failed rct : root canal treatment , rf : root fracture the results of this study indicate that caries and periodontal disease are the main reasons for tooth extractions in our district , which was similar to a previous study that caries was the dominant reason for extraction in patients with 2030 years of age , while periodontal disease accounts for the majority of tooth extraction in patients older than 40 years whereas other study reported that caries and its sequel remains the most important cause of tooth loss throughout adult life in scotland . we also found that males accounts for 46.02% of the sample size and had fewer teeth extracted than females , which was in agreement with the study conducted by barbato et al . , kalyanpur and prasad , who assessed the tooth mortality among the urban and rural adult population of dharwad district ( india ) and found that females compared to males had higher tooth loss . significant gender differences were also noted in this study such that extractions due to caries were more common in females , extractions due to periodontal disease were more common in males , which is in agreement with the previous investigation . this could be because of deleterious habits such as smoking , ( where smoking is considered as a potential risk indicators for periodontal disease ) , alcoholism , and also poor oral hygiene maintenance . we also noted that 40.24% of total extractions were due to periodontal diseases , i.e. , more teeth per patient were lost due to periodontal disease than for any other reason . this confirms the findings of 2 previous studies that periodontal disease is responsible for the loss of more teeth than any other cause , among which mobility is responsible for extraction , and it accounts for 47.5% of all the periodontal conditions , followed by mobility associated with gingival recession , i.e. 44.5% , which was similar to the findings of moreira et al . , who stated that mobility and attachment loss are indicated as the criteria for extraction in case of periodontally involved tooth . this could be due to the lack of awareness and negligent oral hygiene maintenance , hence periodontal problems . this is because of the poor socioeconomic status , which leads to lack of awareness of the conditions due to lower levels of education , and also less affordability of these individuals for treatment , which is in agreement of the previous study by manski and magder , who stated that demographic data such as race , socioeconomic conditions are the predictors of dental care utilization , whereas in the present study , sample was taken from the same region without much cultural differences . therefore , we conclude that caries is the dominant reason for extraction in patients with 2030 years of age while periodontal disease accounts for the majority of tooth extraction in patients older than 40 years

aim : in order to facilitate planning for dental health services and to progress strategies to continue the reduction in tooth loss , it is important to identify the factors that result in such loss . therefore the aim of the study is to investigate the major cause for tooth extraction.objective:to examine whether the major reason for tooth extraction is dental caries or periodontal disease.materials and methods : the study is carried out among the dental practitioners in our district . a questionnaire containing 10 items was distributed to the dental practitioners , which included age , gender , no of teeth indicated for extraction , the reason for extraction , and the periodontal parameters that are involved with the extracted tooth and were requested to complete the form on every extraction they were to undertake . the study form was collected at the end of the study period and data was subjected to statistical analysis.results:a total of 502 patients were enrolled during the study period , and a total of 1055 teeth were extracted for several reasons . we found that 51.14%extractions are due to dental caries in case of 20 - 30years age groups , which is more when compared to tooth loss due to periodontal diseases in this age group . whereas in case of > 40years of age group periodontal diseases account for 54.11% , and dental caries accounts for only 29.11% . showing more teeth were lost due to periodontal disease.conclusion:therefore we concluded that , caries is the dominant reason for extraction in patients with 2030 years of age while periodontal disease accounts for the majority of tooth extraction in patients older than 40 years .

the mesu presents an innovative solution to accessibility by providing a stable , self - sufficient mobile platform that guarantees a controlled and sterile environment for performing cataract surgery in rural locations with no basic amenities . 1 , consists of a set of two custom - built vehicles as follows : layout of the mobile eye surgical unit preparatory vehicle : houses a preoperative room with a couch to administer anesthesia and changing roomsurgery vehicle : that houses a scrubbing station , operation theater ( ot ) with an operating microscope , phaco machine , electrocardiogram monitor with defibrillator , oxygen concentrator and sterilization room with tabletop autoclave machine , eto sealer machine , and fogging machine . preparatory vehicle : houses a preoperative room with a couch to administer anesthesia and changing room surgery vehicle : that houses a scrubbing station , operation theater ( ot ) with an operating microscope , phaco machine , electrocardiogram monitor with defibrillator , oxygen concentrator and sterilization room with tabletop autoclave machine , eto sealer machine , and fogging machine . to minimize the risk , initial surgeries were carried out on the premises of the base hospital . mock trials without patients were carried out to optimize patient flow and ensure that surgeons and theater personnel were comfortable with the environment . permission for the camp was sought from the district blindness control society ( dbcs ) for the notified period . awareness meetings and group discussions were held with the help of local authorities for smooth conduct of the camp . the mesu was functional from january 2012 for conducting cataract surgeries at various places in tamil nadu . mesu was started with many challenges such as high capital cost , the running cost , feasibility , and safety of a new system . permission from the dbcs was given for the first 500 surgeries to know about safety and feasibility , which was renewed after 18 months by the dbcs after evaluating the safety and the feasibility . the outpatient screening is set up nearby in a fixed facility such as a hall or schoolroom near the site . the equipment required for outpatient examination were transported in a separate vehicle which is used for the transportation of team members . for every patient , demographic details , ophthalmic and medical history , blood pressure ( bp ) recording , random blood sugar , hemoglobin estimation by copper sulfate method , and physical examination preoperative visual acuity , slit - lamp findings , lens status , applanation tonometry , and fundus evaluation were carried out . all patients received preoperative antibiotics for 1 day , and povidone - iodine 5% was applied 10 min before the surgery . surgeries have been performed by four surgeons so far by a single surgeon in a day . phacoemulsification , manual small incision cataract surgery ( sics ) , and extracapsular cataract extraction were performed under local anesthesia , monitoring vital parameters . all patients vision was recorded with pin hole , and a slit - lamp examination was done . a team consisting of ophthalmologist , optometrist , and ophthalmic assistant visited the site after 1 week and 1 month postoperatively . visual acuity with pin hole , handheld slit - lamp examination , refraction and fundus evaluation were done , and glasses were dispensed at a later date . of the 2021 patients operated in mesu , 937 ( 46.4% ) were males and 1084 ( 53.6% ) were females ; the mean age ( standard deviation ) was 61.36 9.313 as shown in fig . 2 , and 107 age and sex distribution phacoemulsification was performed for 146 ( 7.2% ) patients , manual sics for 1849 ( 91.5% ) , and extracapsular cataract extraction for 26 ( 1.3% ) patients . nearly 119 ( 5.5% ) patients had diabetes , 159 ( 7.9% ) were hypertensive , 102 ( 5% ) had diabetes and were hypertensive , and the remaining 1617 ( 80% ) were without systemic illness . the present study showed a low percentage of good outcome [ table 1 ] at presentation based on the world health organization ( who ) definitions - visual acuity > 20/60 was seen in 85 patients ( 4.1% ) and 1218 patients ( 60.4% ) had visual acuity < 6/60 . poor vision was seen more in females may be due to their traditional inaccessibility to health - care system . posterior capsular rupture was noted in 18 patients ( 0.9% ) , zonular dialysis in 7 ( 0.3% ) , iridodialysis in 5 ( 0.2% ) , whole bag removal in 2 ( 0.1% ) , and partial descemet 's membrane detachment in three patients ( 0.14 ) . totally 2010 patients received posterior chamber iols , 6 ( 0.25% ) patients received anterior chamber iol , s and 5 ( 0.2% ) patients were aphakic . the postoperative complication rates were lower compared to a similar study though the sample size reported was smaller ( 209 patients ) than the present study . the complication rates were low compared to various studies as surgeries were done by experienced surgeons and rigid adherence to protocol for infection control and sterility . visual acuity < 6/60 in 19 ( 0.93% ) patients [ table 2 ] was due to high myopia with chorioretinal degeneration , pigmentary alteration at fovea , retinitis pigmentosa , and stargardt disease . one hundred and seven ( 5.29% ) patients were lost to follow - up at the final visit . postcataract surgery final visual outcome there were two untoward incidents noted among 2021 surgeries . the first case , a 49-year - old female with no systemic illness , developed hypotension with bp of 97/42 mmhg for 5 min after peribulbar block with 2% lignocaine . she was conscious , alert , and well oriented with no neurological deficit ; saturation was 100% , so she was kept under observation . the patient 's bp stabilized to 120/74 mmhg over the next 45 min and underwent uneventful sics + iol . in the second instance , a 67-year - old female on treatment for diabetes and hypertensive developed breathlessness with orthopnea during surgery with signs of pulmonary edema . the following findings were noted : pulse , 118/min ; respiratory rate , 32/min ; bp , 230/138 mmhg ; po2 , 78% ; and the patient was unresponsive , with tongue falling back and had basal crepitation and rhonchi . she was managed medically and bp brought down to 180/110 mmhg , saturations increased to 99% , wheeze and rhonchi decreased , and became conscious oriented and comfortable in 30 min . she was shifted to intensive care unit in district headquarters hospital 45 km away in an ambulance for further evaluation and management and was discharged the following day after 24 h of observation . cortical wash with secondary iol implantation was done in the base hospital after 3 weeks under anesthetic care . it was notable that there was no incidence of endophthalmitis among the patients who underwent cataract surgery in mesu . the present study is underpowered to report the endophthalmitis rate with the small sample size of 2021 . the mesu was developed on two separate standard bus chassis ( ashok leyland 222 viking ) so as to enable them to travel independently to access remote villages . they are connected on - site by a detachable double - walled interconnecting vestibule to make a single compact surgical unit . the mesu was lifted off its wheels through independently controllable hydraulic cylinders to ensure stability during surgeries . locally available electrical power was supplemented by an onboard 20 kva diesel generator supported by a 5 kva uninterrupted power supply unit . the sterility of the ot was maintained by air handling unit that filters particles > 0.3 micron and by providing positive pressure ( 35 pa ) . the entry to the surgery area was through twin air curtains , isolating the sterile environment thereby preventing contamination . the modular nature of the system with adequate storage space for the consumables ensures fast repair and update of the subsystems with minimal operational downtime and low maintenance cost . the capital cost for the unit was 3 crores which includes the vehicle , fabrication , and the equipment cost . being a pilot project , per surgery cost varies depending on the number of surgeries conducted per camp from rs . all efforts are continuing to bring down the cost without compromising the quality by increasing the number of surgeries per camp . mobile eye surgical unit camp statistics the team consisting of operating surgeon ( 2 ) , trainee ophthalmologist ( 2 ) , optometrist , camp administrator , ot technicians ( 4 ) , outpatient staff ( 4 ) , and electrical maintenance staff ( 2 ) was identified and trained during the trial phase . for safe surgical environment , washing and disinfecting of ot was done for 3 consecutive days along with culture by settle plate method and air sampling . surgeries were started only after obtaining negative culture for 3 consecutive days . at the end of each surgery , used articles were removed from the theater , instruments were sent for cleaning and sterilization , disposable items and the theater wastes were disposed as per the protocol . after the pilot phase of the first 500 surgeries , duration of each camp was planned for 10 days , starting with patient selection for the first 3 days during which time ot was made ready [ table 4 ] . all surgeries were done free of cost , the tubings and phaco probes were changed for each case , all consumables were disposed after each surgery , and disposable drapes were used . after understanding the logistics , 25 surgeries per day can be done safely by an experienced surgeon in the mesu in spite of no availability of anesthetist and vitreoretinal surgeon in camp site . costing of the mobile eye surgical unit camp various studies have noted that people readily do not accept eye care surgeries when offered free of cost . the common barriers for cataract surgeries encountered were attitudinal barriers related to service delivery , cost , and affordability . the attitudinal barriers were could manage daily work ( 71% ) , cataract not mature ( 68% ) , could see clearly with other eye ( 64% ) , too busy ( 57% ) , female gender ( 37% ) , fear for surgery ( 34% ) or death ( 13% ) , old age ( 33% ) , and worry about cost of surgery ( 27% ) . the barriers relating to service delivery , cost , and affordability included insufficient family income ( 76% ) , not knowing anybody who had undergone cataract surgery ( 26% ) , no one to accompany ( 20% ) , and inaccessibility ( 20% ) . lack of an attendant was relevant in a rural setup mainly due to transportation cost , loss of labor during hospital stay , and the miscellaneous expense for the attendant . fear as a barrier is not without reason , especially for illiterate in rural areas , fear of hospital , surgery , and its consequences is natural . mesu provides accessibility that addresses the concerns of rural illiterates to avail the services without fear and undue expenses . the who has provided guidelines for cataract surgery outcomes 85% should have visual acuity of 20/60 or better , 10% must have < 20/6020/200 , and 5% should have visual acuity of < 20/200 . in the present study , postoperatively , 1862 patients ( 92.11% ) had best - corrected visual acuity above the visual acuity of 6/18 which was comparable to other studies at 94% or 89.8% . the visual recovery in patients who had undergone surgery in mesu is comparable with other reports from india . mesu provides an alternative to the base hospital approach by giving the same standard eye care in a peripheral eye camp in rural and remote areas . the ophthalmologists are trained in basic and advanced life support and are trained with physicians and anesthetists for careful selection of patients to identify any warning sign and to manage acute emergencies if needed . the ot is equipped with emergency medicines , endotracheal tube with laryngoscope , and ambu bag . a vehicle is kept ready during the time of surgeries , preferable an ambulance , if available for shifting the patient . bupivacaine has not been used for cataract surgery in mesu due to its longer duration of action and intense toxicity . mesu is a safe and useful alternative in combating preventable blindness due to cataract in far - off villages and tribal areas by providing quality eye care at the patients doorsteps and to those who are inaccessible for quality eye care . the results suggest that performing cataract surgeries in a mobile bus under all asepsis is indeed a viable complimentary method to achieve the singular objective of combating blindness in the underprivileged population . careful selection of the team , strict adherence to protocol , and averaging above 25 surgeries per day to decrease per surgery cost will allow mesu a safe and viable alternative in community eye care .

aim : the aim of this study was to evaluate the utility and safety of a mobile eye surgical unit ( mesu ) in providing quality cataract surgery for the indigent rural population with poor access to quality eye care.materials and methods : two buses connected by a vestibule were built to meet the requirements for a self - sufficient operation theater ( ot ) . in every camp , safe transportation of units , good alignment of buses , safe water , and maintenance of sterile environment were achieved with optimal utilization of ot.results:two thousand and twenty - one patients in 21 remote locations underwent cataract surgery in mesu between 2012 and 2015 . visual outcome was 6/9 or better in 79.3% , posterior capsular rupture in 0.91% , zonulardialysis in 0.3% , aphakia in 0.2% , iridodialysis in 0.2% , and there was no incidence of endophthalmitis.conclusion:mesu is a safe alternative in combating preventable blindness due to cataract in far - off villages and tribal areas by providing quality eye care at the patient 's doorstep . this model has a great potential for duplication in other parts of india .

central nervous system ( cns ) inflammatory demyelinating disease ( idd ) is characterized by inflammatory lesions associated with loss of myelin and eventually leading to axonal damage . idd includes a variety of clinical syndromes , the most common include multiple sclerosis ( ms ) , neuromyelitis optica and acute disseminated encephalomyelitis [ 1 , 2 , 3 ] . we report the clinical evaluation and treatment of a previously healthy patient with tumefactive idd . a 35-year - old caucasian male presented with complaints of memory loss , confusion , headaches and inability to work for the past 2 weeks . prior to this , the patient was completely normal with no significant medical or neurological history and was gainfully employed as a computer programmer . general physical examination was normal , the patient was well nourished and in no acute distress . his neurological examination demonstrated a fluctuating mental status and he had an expressive aphasia and was not able to consistently follow a simple or complex command . he could not perform the serial 7 test and was not able to recall any words after 5 min even with prompting . routine serum chemistries showed the following tests were normal or negative : complete metabolic panel , urinalysis , prothrombin , and partial thromboplastin time , tuberculosis test , lyme serology , serology against cysticercosis , varicella , cytomegalovirus , epstein - barr virus , cryptococcal antigen , hepatitis b and hepatitis c , human immunodeficiency virus test , rapid plasma reagin , ssa and ssb antibodies , blood cultures , angiotensin - converting enzyme level and erythrocyte sedimentation rate . a cell blood cell count with differential showed lymphopenia with an absolute lymphocyte count of 400 cells/l ( reference range : 8503,900 cells/l ) . abnormally low cd4 and cd8 were noted , with 48% cd4 ( 3061% ) with a cd4 count of 193 cells/l ( 4901,740 cells/l ) , 26% cd8 ( 1242% ) with a cd8 count of 103 cells/l ( 1801,170 cells/l ) , and cd4/cd8 ratio of 1.88 ( 0.865.00 ) . a lumbar puncture was performed and cerebrospinal fluid ( csf ) analysis showed a white blood cell count of 200/l ( 05/l ) with a differential count of 96% lymphocytes , 4% monocytes and with 0 neutrophils . the csf myelin basic protein was 5.1 g / l ( 0.00.4 g / l ) with five oligoclonal bands ( reference range : 0 bands ) . both csf and serum toxoplasma antibody and herpes simplex tested by polymerase chain reaction were negative . a computerized tomography ( ct ) scan of the chest , abdomen and pelvis revealed no abnormalities . a ct scan of the head on admission showed several ill - defined , nonspecific hypodense lesions in the cerebral hemisphere bilaterally . a magnetic resonance imaging ( mri ) of the brain performed with and without contrast showed multiple supratentorial ring - enhancing lesions bilaterally , distributed throughout the cerebral hemispheres , with both deep and superficial cortical lesions , measuring up to 16 mm in diameter . the cerebellum was spared and there was no midline shift or extra - axial collection . the patient underwent left frontal craniotomy and open biopsy of the brain lesion , and a diagnosis of an inflammatory demyelinating process was made ( fig . the patient was started on methylprednisolone 1,000 mg intravenously daily for 5 days and subsequently transferred to a rehabilitation program for intensive physical and occupational therapy . initially the patient showed some neurological improvement but he relapsed and was readmitted to hospital 2 weeks after completing the course of steroids with complaints of headache and confusion . his neurologic examination at this time showed predominantly abnormalities related to his mental status and with personality changes . a repeat mri of the brain with and without contrast showed multiple foci of mixed signal abnormalities within the cerebral hemispheres . there were some new lesions noted , and some of the lesions seen on the prior images were smaller and showed less enhancement . the patient 's condition improved with intravenous steroids , and he was discharged home 10 days later with tapering steroids orally . he was readmitted 10 days later with a generalized tonic - clonic seizure and increased confusion and was started on lacosamide ( 50 mg a day orally ) and also intravenous methylprednisolone 500 mg daily for 5 days . he also received therapeutic plasma exchange of six treatments over 2 weeks and he started to improve . he was discharged home with lacosamide 100 mg twice a day orally and oral prednisolone starting at 20 mg a day tapering with reduced doses , which was finished in a week . a repeat spinal tap 3 months later showed the following csf results : glucose 98 mg / dl ( 4070 mg / dl ) , protein 31 mg / dl ( 1545 mg / dl ) , white blood cell count 2/l ( 25/l ) and three oligoclonal bands were noted ( reference range : 0 ) . additional tests performed at this time for csf basic myelin protein and igg synthesis were negative or normal . repeat tests of the cd4 and cd8 parameters were performed 7 months after onset of symptoms and were as follows : lymphocytes 1,555 cells/l ( 8503,900 cells/l ) , cd4 660 cells/l ( 4901,740 cells/l ) , and cd8 289 cells/l ( 1801,170 cells/l ) . serial cranial mri scans done with and without gadolinium monthly for 3 months following initial evaluation and then yearly showed evolution of the existing lesions without the development of new lesions . over the next 2 years , the patient was maintained on the regimen of monthly therapeutic plasma exchange and had no further recurrence of symptoms . ultimately , his neurological examination returned to normal and , at present , 6 months later with no treatment , he has been stable . one reports a patient with a diagnosis of relapsing - remitting ms presenting with aggressive disease with multiple tumefactive lesions and not responding to standard treatment with corticosteroids who was successfully treated in hospital with a total of five plasma exchanges that were performed every other day . another article discusses a patient who failed to completely resolve with initial therapy with steroids and was then treated with azathioprine , mycophenolate mofetil , rituximab and cyclophosphamide . interestingly , in contrast to our patient , he was not treated with plasma exchange . in our patient , plasma exchange was initially performed a total of 6 times over 2 weeks with 1.01.5 plasma volume exchange ( 4,000 ml ) per procedure with replacement fluid of 5% human albumin . . there have been previous reports of the utility of plasma exchange in patients with cns idd but not specifically tumefactive ms . a unique aspect of our investigation of this patient are the immunological parameters tested in the patient upon initial presentation and not on any treatment . his cd4 and cd8 counts were low , and to our knowledge , this is the first time this laboratory abnormality has been observed in a patient with idd . there have been studies of the role of cd4 and cd8 cells in ms , where the implications of low levels of both of these cell types is not clear [ 7 , 8 , 9 ] , although a low cd4 count has been described in a number of conditions such as hiv disease and levels of cd8 cells are reduced in patients treated with dimethyl fumarate . however , the combination of reduced values of both the cd4 and cd8 levels has not been reported in any disorder [ 9 , 11 ] . in this patient , this abnormality could be due to a prior viral infection which may have initiated the process of cns demyelination . alternatively , it may represent the response of the immune system to the beginning of the disease process . whether abnormally low cd4 and cd8 levels are involved in the pathophysiology of idd will require further confirmation with studies investigating cd4 and cd8 parameters in patients early in the clinical course prior to initiation of any therapy . if our results are confirmed , levels of cd4 and cd8 could represent a biomarker for tumefactive cns idd . regardless of the specific pathophysiology , therapeutic plasma exchange should be a consideration in atypical cases of idd consistent with tumefactive ms . informed consent was obtained from the patient , and the study was conducted following local institutional review board - approved policies and procedures . the authors declare that there is no conflict of interest regarding the publication of this paper .

we report a 35-year - old healthy male who developed central nervous system inflammatory demyelinating disease consistent with tumefactive multiple sclerosis . about 2 weeks after onset of symptoms and prior to initiation of therapy , the patient had lymphopenia and low cd4 and cd8 levels . his lymphocyte count was 400 cells/l ( 8503,900 cells/l ) , cd4 was 193 cells/l ( 4901,740 cells/l ) and cd8 was 103 cells/l ( 1801,170 cells/l ) . he was treated with intravenous methylprednisolone followed by therapeutic plasma exchange , the levels of cd4 and cd8 normalized , and ultimately , he recovered completely .

fibroblast growth factor-23 ( fgf-23 ) is a hormone secreted by the bone cells - osteocytes and osteoblasts . its levels increase as the stage of chronic kidney disease ( ckd ) advances , reaching very high levels in ckd stage 5 . many studies over the last decade have reported fgf-23 as a factor of prognostic significance in ckd . very little data about the significance of this biomarker exists in indian scientific literature and our study report the results of the levels of fgf-23 in stable maintenance hemodialysis patients . all patients who were continuing in our maintenance hemodialysis program in january 2012 were enrolled as a prospective observational cohort . this group was longitudinally followed for 2 years till january 2014 . at the beginning of the study , the demographic profile , native kidney disease , and comorbidities were noted . left ventricular hypertrophy and ischemic heart disease where defined based on standard criteria . the hematochemical parameters and serum fgf-23 levels were tested at the beginning of the study . fgf-23 levels were measured in our biochemistry laboratory using the kit ezhfgf-23 - 32 k human fgf-23 elisa kit ( merck millipore corporation , billerica , ma 01821 , usa ) . it is a colorimetric fluorescent assay . for the analysis of the association of fgf-23 with various studied variables , the levels were divided into two groups ( group i , fgf 23 < 300 pg / ml and group ii fgf-23 300 pg / ml ) . all statistical analysis was performed using the statistical software for windows version 20.0 spss version 20.0 ( ibm corp . no patient dropped out of the study . the mean standard deviation ( sd ) age of 91 patients ( females 34 ) was 60.6 10.8 years . during follow - up , in the next 48 months , five patients were transplanted and are doing well . two patients were shifted to peritoneal dialysis who are also alive and healthy until till the end of the study period . fifty - six of these patients had type 2 diabetes mellitus as the cause of their ckd . the body mass index ( bmi ) of the group is shown in table 1a . body mass index of the cohort the mean sd duration of dialysis in months was 47.2 24.8 months . dialysis details of the cohort the mean sd and the range of the major biochemical and hematological parameters are given in table 2 . serum parathyroid hormone ( pth ) level was consistently high , and the vitamin d level was low in general for the whole cohort . hematological and biochemical parameters of the cohort fgf-23 level was high in the whole cohort . patients with higher fgf-23 levels tend to be older , have higher bmi and on dialysis for a shorter duration [ table 3a ] . association between fibroblast growth factor-23 and demographic , and comorbidity details association of fibroblast growth factor-23 and dialysis there was a strong association between fgf-23 and serum phosphorus levels and pth levels . there was a trend to an inverse relationship with fgf-23 and vitamin d levels [ table 4 ] . a multivariate analysis confirmed the results noted in the univariate analysis [ table 5 ] . association of hematochemical variables and fibroblast growth factor-23 levels multivariate analysis of association between fibroblast growth factor-23and various clinical variables these levels start rising in early stages of ckd and have an exponential increment in levels in stage 5 ckd , especially patients on dialysis . the rise in pth correlated with fgf-23 in ckd patients and this is attributed to the suppressive effect of fgf-23 on vitamin d levels . fgf-23 level was independently associated with a higher risk of myocardial infarction , stroke , coronary , carotid , and lower limb revascularization , lower extremity amputation and death . in some studies , a significantly higher rate of congestive heart failure in patients with higher fgf-23 levels was noted . our study re - emphasizes the strong association between serum phosphorus and pth levels in both univariate and multivariate analyses . simple statistical analyses ( both univariate and multivariate ) did not show any link between fgf-23 and cardiovascular comorbidities ( both the presence of left ventricular hypertrophy and ischemic heart disease ) . the strength of our study is that it is the first of its kind which addresses the issue of fgf-23 levels in relativelyhomogenous stable hemodialysis patients . the limitation of our study is that it is a relatively small study with a short duration ( 2 years ) follow - up . the cohort of patients also is not fully representative of dialysis patients in india as they came from a relatively higher socioeconomic background . our study did not show any link between fgf-23 and cardiovascular morbidity and overall mortality .

fibroblast growth factor-23 ( fgf-23 ) levels start rising early in patients with chronic kidney disease and is implicated in cardiovascular and overall mortality of hemodialysis patients . we conducted a prospective observational cohort study in stable dialysis patients looking into the levels of fgf-23 in hemodialysis patients and its association with various demographic and biochemical variables and mortality . a total of 91 patients were enrolled in the study . the mean fgf-23 levels were very high ( 1152.7 pg / ml ) . fgf-23 levels were significantly associated with serum phosphorus and parathyroid hormone ( pth ) levels in univariate and multivariate analysis . no significant association between fgf-23 and cardiovascular comorbidities and overall mortality was seen . fgf-23 levels rise exponentially in maintenance hemodialysis patients . there is a strong association between fgf-23 and phosphorus and pth levels . no association between fgf-23 and mortality was noted in our patients .

red eye is a common eye sign / symptom presenting to the general physicians , other eye care workers , and the ophthalmologist . this symptom accounts for approximately 15% of consultations for ophthalmologists and 6% for general medical practitioners in eastern europe . it also accounted for 40% of all outpatients seen in bawku hospital ghana in 2004 and 10 district hospitals in pakistan . in nigeria , lawan reported 14.8% of patients attending their teaching hospital eye clinic presenting with red eye . studies done in port harcourt and ile - ife in nigeria showed that red eye accounted for 19.61% and 54.9% of pediatric ophthalmic eye diseases , respectively . a major cause of concern to health workers is the late presentation of patients with the condition at a standard health facility . oftentimes , in developing countries such as nigeria , individuals commence various forms of medications , both orthodox and traditional , which they consider as first aid measures . the causes of red eye are many including mild to serious conditions that may threaten vision . some even are managed as emergencies when it is being treated by an ophthalmologist . these include conjunctivitis , corneal ulcer , iritis , trauma , acute glaucoma , and use of traditional eye medicine ( tem ) . by far , the most common cause is conjunctivitis which could be infective or allergic . in a study done in ile - ife nigeria , among pediatric age group , ocular trauma was the most common cause of red eye , followed by allergic conjunctivitis and infections of the eye and its adnexa . however , in developing countries , individuals and communities often commence first aid before presenting themselves to the health practitioner . researchers in ghana studied the pattern of eye care services sought outside the orthodox health system . cataracts , eye injuries , and other ocular conditions were reportedly managed by herbalists , who often instilled the herbal mixtures directly into the eyes . the knowledge and attitude of a community regarding a disease often influence members practices including health - seeking behavior . studies carried out in developing countries of sub - saharan africa showed a sub - optimal level of knowledge , attitude , and perception of ocular conditions and eye health in general . in cape coast , ghana , a study of the eye care seeking behavior of the populace , showed 23.3% of respondents having practiced self - medication during the last episode of eye disorder whereas 5.5% visited a traditional healer . only 32.5% reported at a health facility for the management of the last episode of an eye disorder . the main reason for self - medication among respondents was a poor perception of the severity of the ocular condition . abubakar found 62.3% of secondary school students in kano , having poor knowledge and 58.2% with a poor attitude toward ocular disorders , especially blindness and its prevention . in limpopo province of south africa , the perception of ocular manifestation of hiv / aids was assessed among 2659 high school students with results showing a need for better health communication involving this population group . almost two - third ( 65.6% ) of respondents , felt an ophthalmologist or an optometrist should be consulted for ocular problems whereas 16.5% felt traditional healers could be considered . researchers in ile - ife , southwest nigeria , reported 49% of secondary school students participating in a screening exercise , to have allergic conjunctivitis ; 6% had infective conjunctivitis . more females than males had one form of ocular disorder or the other . among those with allergic conjunctivitis , only 12.5% had visited an eye specialist prior to conducting the research . in addition , health habits formed during this period is often carried on to adulthood and passed to the next generation , which can be largely influenced by their perception and attitude toward disease conditions when in school . early detection and quality treatment often positively influence the outcome of an episode of red eye . period of presentation at a health facility is dependent on several factors , including patients knowledge and perception of the symptom involved . no previous study has examined the perception and practice of senior secondary ( ss ) school students in sagamu , concerning the red eye . findings on perception and practice regarding health and related conditions can be tools to provide education and treatment plans , which ultimately improve patient care and quality of life . this study , therefore , planned to determine the attitude of ss school students in sagamu local government to red eye . the result will be useful to health planners in planning interventional programs to reduce blindness and visual impairment from red eye within the local government area ( lga ) , state , and the country at large and in the other developing countries . sagamu is a peri - urban area consisting of 15 wards with a diverse population in terms of ethnicity , occupation , age structure , and socioeconomic status . the town serves as a transit zone between the southwest and south - south regions of the country . ss school students attending public secondary schools in sagamu lga were recruited into the study . ss-3 students were exempted from participating in the study because their final examinations were on - going and were thus unavailable . a cross - sectional , descriptive study was carried out among 1082 ss ( ss ) school students in sagamu lga . using the formula for descriptive studies and assuming a prevalence of 50% ( since no previous study has been carried out on the subject matter in our environment ) as well as a nonresponse rate of 10% , a sample size of 420 was calculated . however , this was exceeded , and 1082 students were recruited into the study . multi - stage sampling technique was used for selection of study participants . the first stage involved the selection of three wards from the 15 existing wards in sagamu lga by simple random sampling . the second stage involved the selection of one ss school in each of the preselected wards also by simple random sampling . the third stage involved the selection of three arms from the five existing arms of ss-1 and ss-2 in each school . all consenting students in the selected arms were recruited into the study . a validated , semi - structured , self - administered questionnaire was used for data collection among the study participants . the questionnaire obtained information on sociodemographic data , perception , and attitude toward red eye from respondents . data were analyzed with ibm statistical package for the social sciences ( spss ) version 20 ( ibm corp . a score of 50% was graded as good whereas that < 50% was graded as poor . attitude scores were also calculated on a scale of 100% , with a good attitude being a score of 50% and above whereas a score of < 50% was graded as poor . chi - square test was used to test the association between categorical variables , with the level of significance ( p ) set at < 0.05 . approval was obtained from the zonal education office of the state ministry of education , science , and technology . this study followed the ethical standards issued by the nuremberg code and the declaration of helsinki on research in humans . participation was fully voluntary , and respondents were free to withdraw from the study if they so wished . sagamu is a peri - urban area consisting of 15 wards with a diverse population in terms of ethnicity , occupation , age structure , and socioeconomic status . the town serves as a transit zone between the southwest and south - south regions of the country . ss school students attending public secondary schools in sagamu lga were recruited into the study . ss-3 students were exempted from participating in the study because their final examinations were on - going and were thus unavailable . a cross - sectional , descriptive study was carried out among 1082 ss ( ss ) school students in sagamu lga . using the formula for descriptive studies and assuming a prevalence of 50% ( since no previous study has been carried out on the subject matter in our environment ) as well as a nonresponse rate of 10% , a sample size of 420 was calculated . the first stage involved the selection of three wards from the 15 existing wards in sagamu lga by simple random sampling . the second stage involved the selection of one ss school in each of the preselected wards also by simple random sampling . the third stage involved the selection of three arms from the five existing arms of ss-1 and ss-2 in each school . a validated , semi - structured , self - administered questionnaire was used for data collection among the study participants . the questionnaire obtained information on sociodemographic data , perception , and attitude toward red eye from respondents . data were analyzed with ibm statistical package for the social sciences ( spss ) version 20 ( ibm corp . , amonk , ny ) . a score of 50% was graded as good whereas that < 50% was graded as poor . attitude scores were also calculated on a scale of 100% , with a good attitude being a score of 50% and above whereas a score of < 50% was graded as poor . chi - square test was used to test the association between categorical variables , with the level of significance ( p ) set at < 0.05 . approval was obtained from the zonal education office of the state ministry of education , science , and technology . this study followed the ethical standards issued by the nuremberg code and the declaration of helsinki on research in humans . participation was fully voluntary , and respondents were free to withdraw from the study if they so wished . the female students were 593 ( 54.8% ) while males were 489 ( 45.2% ) in the study . many of the students were christians ( 66.5% ) and in ss-2 ( 51.1% ) [ table 1 ] . demographic characteristics of respondents majority ( 81% ) had heard of red eye and this was mainly from neighbors [ table 2 ] whereas 216 ( 19% ) had not . four hundred and fifteen ( 38.4% ) did not know the cause of red eye , while 99 ( 9.1% ) thought trauma was a cause , 147 ( 13.6% ) infection , 73 ( 6.7% ) allergy , 21 ( 1.9% ) sunlight whereas other causes such as drugs forms 327 ( 30.2% ) . two hundred and seventy - six ( 25.5% ) knew that they can be infected by someone with red eye , 632 ( 58.4% ) says they can not be infected by someone with red eye whereas 174 ( 16.1% ) did not know whether they could be so infected or not [ figure 1 ] . about 35% would instill onion when they have red eye [ figure 2 ] , followed by urine ( 21.9% ) and breast milk ( 12.9% ) . other things that they were likely to instill are salt water ( 4.6% ) , sugar water ( 4.6% ) , and battery water ( 1.5% ) whereas 19.4% will not use any of the substances . though majority says that a doctor is the one that takes care of red eye , 24 says self , 19 says their parent , 55 says chemist , 58 nurses whereas 12 says a herbalist can care for red eye . source of respondent 's information about red eye can someone with red eye infect you ? traditional medications used in red eye awareness of red eyes was associated with age ( p = 0.005 ) , but not with sex and religion [ table 3 ] . perception grade was good in 49 ( 4.5% ) and poor in 1033 ( 95.5% ) . five hundred and forty - three ( 50.2% ) felt that red eye could lead to blindness [ figure 3 ] . perception of red eye was associated with age ( p = 0.027 ) and class ( p 0.001 ) . the factors associated with attitude toward red eye are shown in table 3 ; this is statically significant for class ( p 0.001 ) . factors associated with awareness , perception , and attitude toward red eyes can red eye lead to blindness ? attitude refers to the feelings toward a subject , as well as any preconceived ideas ; one may have toward it . practice refers to the ways in which people demonstrate their knowledge and attitudes through their actions on the subject matter . it is not surprising that many of the respondents have heard of red eye because epidemic conjunctivitis called apollo is a very common cause of red eye in nigeria and , especially the west africa coast . in this study , majority heard about red eye from neighbors which show the impact of community on people 's health . that only 13.9% heard from health workers shows that there is a need for eye care workers to intensify health education , especially among students . only 13.6% were aware that red eye could be caused by infections which may also influence their attitude to red eye . this might explain why more than half of the students say they can not be infected by someone with red eye . it is comparable to findings from limpopo , south africa , where only 31.4% felt hiv infection and its sequelae could result in red eyes . most ( 96.2% ) respondents attitude toward red eye was poor , a finding quite different from that reported in kano , where 52.8% of students had a poor attitude toward severe ocular disorders . the observed difference might be due to the fact that this study focused solely on red eyes whereas the study carried out in kano assessed knowledge and attitude toward causes of blindness and its prevention . usually in the developing countries , people usually use traditional eye medication and unprescribed medications to treat their red eye . these medications that are being used for red eye as found in this study include onion , urine , breast milk , salt water , sugar water , and battery water . these can cause chemical conjunctivitis , infective conjunctivitis , especially gonococcal conjunctivitis when infected urine is used and if not detected and treated early , it can result in blindness . this finding also confirms the report of other researchers who have shown that people seek alternative eye care treatment instead of orthodox treatment with implications for ocular health . there was a report of a usage of herbal preparation on the eye with resultant blindness . health education done in schools during assembly especially by eye care workers will go a long way to help reduce this among the students and in the communities as these children will , in turn , tell their parents about what they are taught at school . furthermore , incorporation of school eye health program into the existing school health program will be of immense benefit . perception grade and attitude of this population were poor , this may mean that the perception and attitude to red eye , even though very common is low in the general population as the students are actually reflecting what they have learnt from their homes . intensive effort to enlighten the population will therefore help to reduce blindness / visual impairment in our community . these enlightenment programs can be taken to the religious houses , i.e. , mosques and churches for a wider coverage . we therefore conclude that secondary school students in sagamu have poor perception and attitude to red eye . appropriate eye health services and education should be included in school health services and early presentation to eye care centers for its treatment should be encouraged .

background : red eye is a very common presenting complaint in clinical practice among all age groups , including adolescents . health habits formed during adolescence is carried to adulthood and is often a consequence of their perception . this study , therefore , determined the perception of students toward the red eye.aim:to determine the perception of red eye and its associated factors among secondary school students in sagamu.methods:a cross - sectional descriptive study was carried out among 1082 senior secondary school students in sagamu local government area , using a semi - structured self - administered questionnaire . data were analyzed using spss version 20 . relevant descriptive and inferential statistics were calculated.results:the mean age of respondents was 15.27 1.48 years . there were more females ( 54.8% ) than males . majority ( 81% ) had heard of red eye , and this was mainly from neighbors ; 58.4% felt they could not contact red eye from an infected person . about 35% would instill onion if they had a red eye . about 50.2% felt red eye could lead to blindness . awareness of red eye was associated with age ( p = 0.005 ) , but not with sex and religion . among respondents , 95.5% and 96.2% had a poor perception as well as a poor attitude toward red eye , respectively.conclusion:the perception and attitude of senior secondary school students in sagamu to red eye is poor . appropriate eye health education and promotional services , including periodic eye examination of students , should be carried out in school health services . early presentation to eye care centers for its treatment should be encouraged .

the vacuum sealing drainage ( vsd ) technique is a therapeutic concept to achieve secure and rapid wound healing in traumatic soft wound and chronic infections . its use is widespread among the surgical specialties , many of which employ negative - pressure wound therapy to varying degrees as part of their armamentarium against challenging wounds . the tubes are either drawn transcutaneously through the tissue or placed epicutaneously , depending on the condition of the wound . the wound including the adjacent skin and the drainage tubes is covered by a transparent vapor transmitting polyurethane film . when the drainage tubes are connected with a vacuum bottle , anatomically difficult body regions such as buttocks and perianal infection , it is still questionable whether these dressings have similar beneficial effects . in this case a 58-year - old man suffered from a severe buttocks and perianal infection after injection ( fig . he was admitted to our emergency department after a failure conservative treatment of another hospital . he had a little bit fever ( 38.5 c , 101.3f ) , the wbc was 12 10/l with a normal ecg . a colostomy was applied first to prevent defecation and keep the perianal region clean . after the tissue culture was taken , 3 ) , the drainage tubes became obstructed by a substantial amount of waste ( fig . the infection was controlled 9 days after the first surgery by prompt surgical debridement , the application of vsd treatment , and the use of narrow - spectrum antibiotics based on tissue culture result . finally , granulation tissues on the buttock surface grew well and grafted skin was conducted to close the wound ( fig . four days after the second surgery . after 3 applications of vacuum sealing drainage ( vsd ) treatment , granulation tissues on the wound surface grew well and free dermatoplasty was conducted to close the wound . after 8 weeks , the skin graft had completely survived and the wound had healed well . the colon was sent back to abdominal cavity . a 58-year - old man suffered from a severe buttocks and perianal infection after injection ( fig . he was admitted to our emergency department after a failure conservative treatment of another hospital . he had a little bit fever ( 38.5 c , 101.3f ) , the wbc was 12 10/l with a normal ecg . a colostomy was applied first to prevent defecation and keep the perianal region clean . after the tissue culture was taken , 3 ) , the drainage tubes became obstructed by a substantial amount of waste ( fig . the infection was controlled 9 days after the first surgery by prompt surgical debridement , the application of vsd treatment , and the use of narrow - spectrum antibiotics based on tissue culture result . finally , granulation tissues on the buttock surface grew well and grafted skin was conducted to close the wound ( fig . four days after the second surgery . after 3 applications of vacuum sealing drainage ( vsd ) treatment , granulation tissues on the wound surface grew well and free dermatoplasty was conducted to close the wound . after 8 weeks , the skin graft had completely survived and the wound had healed well . the colon was sent back to abdominal cavity . we found that injection leading to such severe buttocks and perianal infection has never been reported . the management of the perineal skin graft wound is complex , because it has an irregular skin surface and is close to the urethra anteriorly and the anus posteriorly , which can easily contaminate the wound . the vsd technique has been widely used for treating various types of wound surfaces and deep wounds , such as soft tissue in the foot , prosthetic infections , and large - area skin defects , but there are no reports on severe buttocks and perianal infections . the vsd technique combined with a colostomy showed an advantage to treat severe buttocks and perianal infections . first , it is close to the urethra anteriorly and the anus posteriorly , which can easily be contaminated . second , the perineum is irregular . finally , the perineum is too mobile to fix the wound dressing . it has been found to be useful in the treatment of various types of wound surfaces . recently , wu et al have reported the first use of vsd as a convenient and effective alternative to manage the complications of extensive polyacrylamide hydrogel ( paag ) migration after breast augmentation . the mechanism of vsd for prompting granulation growth and accelerating wound healing has been proven at the cellular level . vac therapy is also an excellent alternative for managing complicated wounds after head and neck reconstruction . it has been proven to be safe and comfortable for the patient and provides good results regarding infection control , dead space obliteration , and improvement of wound healing . perianal infections are difficult to treat because of the fecal contamination and the anatomical characteristics . in our study , vacuum - based therapy appears to be safe , effective , and convenient for the patient and nursing staff and allows for less frequent dressing changes .

abstractvacuum sealing is a therapeutic concept to achieve secure and rapid wound healing in traumatic soft tissue damage . its application and effect in the treatment of severe buttocks and perianal infection are unclear.we describe a case of buttocks and perianal infection using the vacuum sealing drainage ( vsd ) technique . a 58-year - old man was admitted with buttocks and perianal severe infection , which was caused by injection . the size of the wounds was 40 30 cm . colostomy was applied prior to the prompt surgical debridement to prevent defecation and keep the perianal region clean . emergency debridement was then conducted . after the wounds were thoroughly washed with conventional disinfection solution , they were then covered by vsd system.the infection was controlled 9 days after the first surgery by prompt surgical debridement , the application of vsd treatment , and the use of narrow - spectrum antibiotics based on susceptibility result . after 3 applications of vsd treatment , skin grafting harvested from the left leg was conducted . all free skin grafts survived at 8 weeks . colon was placed back into the abdominal cavity finally.initial colostomy and debridement , the temporary vsd cover followed after several days by skin grafting is a reliable treatment regimen for severe buttocks and perianal infection .

a 43-year - old man ( a welder living in lopburi province , central thailand ) sought treatment at king chulalongkorn memorial hospital , bangkok , on november 30 , 2010 . fifteen months before hospital admission , he experienced a low - grade fever and generalized muscle pain , especially in his lower back and both thighs . despite several courses of medication , hospital ten months before admission , weakness of lower and upper limbs developed in his proximal muscle , primarily on the left side . two months before admission , his entire left leg was swollen , and he was confined to bed . during this illness , he did not smoke , drank alcohol occasionally , and did not use illicit drugs . physical examination showed no keratoconjunctivitis , but indicated engorged jugular veins and right ventricular heave with loud pulmonic valve closure sound . complete blood count showed the following : hematocrit 43.5% , leukocyte count 5,230/mm ( 79% neutrophils , 14% lymphocytes , 4% eosinophils , and 3% monocytes ) , platelet count 209,000/mm . liver function test showed the following results : total bilirubin 0.34 mg / dl , alkaline phosphatase 57 u / l ( reference value 42 u / l121 u / l ) , alanine transaminase 101 u / l ( 4 u / l36 u / l ) , albumin 3.1 g / dl , and creatine phosphokinase 4,308 u / l ( 60 u / l400 test results were negative for antibody against nuclear antigen and hiv ( 2 tests , 1 month apart ) . cd4 cell count was 368/l ( 24% ) , and serum protein electrophoresis showed polyclonal gammopathy . severe pulmonary hypertension without left ventricular dysfunction or left - to - right shunt was evident on electrocardiogram . computed tomographic scan showed an enlarged pulmonary trunk ( 4 cm in diameter ) and right and left main pulmonary arteries ( thrombosis was not shown in the lumens ) . a biopsy of left deltoid and both vastus lateralis muscles showed necrotizing granulomatous inflammation without any organisms by gram , acid - fast bacilli , wright , and gomori methenamine silver staining . bone marrow biopsy showed normal cellularity with increased plasma cells and histiocytes and focal aggregation of microsporidial spores with characteristic belt - like stripe ( figure 1 ) . a 24-hour urine sample ( centrifuged ) yielded characteristic microsporidial spores on modified trichrome stain , 1.01.5 m 1.22.2 m , similar to those observed in the bone marrow sample . because of an overgrowth of candida yeast microsporidium species from bone marrow aspiration specimen ( wright stain ) from a 43-year - old man , thailand . the image shows focal aggregations of microsporidia - like microorganisms with a belt - like stripe ( 1.01.5 m x 1.2 - 2.2 analysis of the small subunit rrna gene spanning 797 bp of dna from microsporidial spores isolated from this patient showed a novel sequence ( genbank accession no . phylogenetic reconstruction using the maximum - likelihood method placed the patient s microsporidium sp . within the cluster of the genera endoreticulatus , cystosporogene , and vittaforma ( figure 2 ) ( 2 ) . notably , the guanine - cytosine content of the ssu rrna locus of microsporidia within the genus endoreticulatus varied from 51.4% to 51.8% , with the base composition distance 0.0010.029 . however , the small subunit rrna sequence of microsporidium from our patient ( genbank accession no . jn619406 ) contained 52.4% guanine - cytosine , and the base composition distance differed from endoreticulatus spp . from 0.0940.170 , making it unlikely that the patient was infected with an organism from this genus . phylogenetic tree inferred from the small subunit rrna sequences of microsporidia in this study and those in the genbank database by using the maximum - likelihood method as implemented in mega5.05 software ( 2 ) . red circle indicates a novel microsporidium identified in this study ( microsporidium cu ) that caused myositis . the tree is drawn to scale , with branch lengths measured in the number of nucleotide substitutions per site . he was discharged on a regimen of oral albendazole ( 800 mg/1/d ) but died unexpectedly from aspiration pneumonia 1 month later . microsporidia can cause either localized or disseminated infection in humans . the true prevalence of microsporidiosis in humans may be underestimated because of asymptomatic infection in most healthy persons , clinician unawareness , and difficulties in diagnosis . myositis caused by microsporidia is rare ; only 12 patients ( including our patient ) have been reported in the literature ( table a1 ; 312 ) . among these 12 patients , 9 were male and 3 were female ( age range 4 months to 67 years ) . patients were from all continents except europe : united states ( 7 patients ) , australia ( 2 ) , haiti ( 1 ) , the gambia ( 1 ) , and thailand ( 1 ) . ( 6 patients ) is the most common causative agent of myositis , followed by brachiola sp . however , the species of microsporidia originally described in 2 reports ( 5,6 ) was changed from pleistophora sp . although ultrastructural study of the microsporidium from this patient has not been performed , the ssu rrna sequence clearly supports the finding that it is a novel species , closely related to endoreticulatus spp . the patient described here had pulmonary hypertension , likely caused by microsporidia ; several reports have shown that these organisms can cause pulmonary infection ( 13 ) . the routes of microsporidial infection are still uncertain , but the species that can infect humans have been identified in water sources and in farm , domestic , and wild animals . furthermore , trachipleistophora spp . however , on the basis of the feature of bisporous sporophorous vesicles , t. anthropophthera was proposed to be related to telomyxa spp . t. anthropophthera was reported to be the causative agent of keratitis in an hiv - infected patient from thailand ( 14 ) . ( formerly nosema spp . ) are known to be pathogens of several kinds of insects , including mosquitoes ( 10 ) . have been found in fish and reptiles , but p. ronneafiei has never been identified in any hosts other than humans . both species were reported from the patients with keratitis from sri lanka and africa , respectively , although their natural hosts remain unknown . to our knowledge , the microsporidium possessing a novel ssu rrna sequence closely related to endoreticulatus spp . has never been identified in patients with myositis . notably , certain lepidopteran microsporidia can produce various responses in nontarget hosts , from refractory to severe infections . although we have no evidence regarding the route or source of this patient s infection , the close phylogenetic relationship of this microsporidium and lepidopteran microsporidia suggests that these non blood - sucking insects could be natural hosts . water or foods contaminated with lepidopteran insects could not be excluded as the source of infection . likewise , recent reports that trachipleistophora extenrec can cause myositis in anteaters ( 15 ) and that tubulinosema sp . can cause myositis in an immunosuppressed patient ( 12 ) further support the role of insect microsporidia as human pathogens .

we describe a case of microsporidial myositis in a healthy man from thailand . the small subunit rrna sequence of this microsporidium is novel and has a close phylogenetic relationship with endoreticulatus , a genus of lepidopteran microsporidia . myositis could be caused by more genera of microsporidia than previously known .

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

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

descending controls pathways originating in midbrain and brainstem regions that project onto the spinal cord have long been recognised as key links in the multiple neuronal networks that interact to produce the overall pain experience . the potential for higher cognitive function through cortical controls that project to the cells of origin of descending controls to influence spinal function allows for top - down processing of pain . the major transmitter systems implicated in the descending controls are the monoamines , noradrenaline ( na ) and 5-hydroxytryptamine ( 5-ht ) , and so the comorbidities of sleep problems , anxiety , and depression result from the dual roles of na and 5-ht in these functions and also in pain . a number of analgesic drugs interact with descending controls , including opioids , which have direct supraspinal interactions with these systems , pregabalin and gabapentin , whose actions are regulated by descending pathways , and also the tricyclic antidepressants ( tcas ) and serotonin and noradrenaline reuptake inhibitors ( snris ) , which alter synaptic levels of na and 5-ht . tramadol and the newer tapentadol have mixed mu - opioid receptor and reuptake inhibition actions , the former with dual na/5-ht actions and the latter with na only . tcas and snris have greater efficacy than selective serotonin reuptake inhibitors ( ssris ) in neuropathic pain , and tapentadol is more powerful than tramadol . thus , the potential pronociceptive effects of increasing levels of 5-ht may counter the analgesic effects of various molecules . preclinical data can explain this on the basis that descending na actions clearly mediate inhibitions through spinal 2 adrenoceptor , whereas 5-ht , via 5-ht2 and 5-ht3 receptors , is a key transmitter in descending facilitations . research has moved on significantly from the early idea that pain is the product of nociceptive signals linearly impacting on an alert and responsive brain . our current understanding is of a plastic , integrative , and highly individualised nociceptive system that is subject to many internal and external influences . because considerable processing of nociceptive signals occurs in the spinal cord , it was reasonably assumed that plasticity ( which enables sensitisation ) was an intrinsic function of the dorsal horn , yet when seminal experiments in rodents showed that electrically stimulating an area of the midbrain , the periaqueductal grey ( pag ) , resulted in no overt behavioural signs of distress to an otherwise painful procedure , it became apparent that the brain could influence pain . it was further shown that stimulation - produced analgesia could be triggered downstream of the pag in the rostral ventromedial medulla ( rvm ) , an area of the brainstem that integrates information that passes from limbic areas of the brain to the spinal cord . the pag and the rvm are therefore key components of the descending modulatory repertoire , a system of neuronal pathways that enables the brain ( and thus cognitive and emotional states ) to control pain processing at the first relays within the spinal cord . descending systems depend on feedback circuitry that relays between the spinal cord and supraspinal areas . hence , nociceptive signals that arrive in the dorsal horn from the periphery synapse with spinal neurones that project to thalamic and parabrachial areas that respectively attach sensory - discriminative ( that is , the quality , intensity , and location of the stimulus ) and emotional / contextual meaning to the signal . partly on the basis of this received information , limbic , cognitive , and somatic areas in turn send out signals that converge and feed into descending pathways to either increase or decrease the influence of further incoming input into the dorsal horn , causing the feedback cycle to continue . the neural bases for this bidirectional modulation from the brainstem are the on and off cells ; on cells burst - fire in response to peripheral noxious stimuli , enhance nociception , and are implicated in the hypersensitivities associated with a range of pain states , whereas off cells undergo a pause in firing in response to peripheral noxious stimuli and are involved in inhibiting spinal neuronal activity . incidentally , and importantly , the responses of these rvm neurones to noxious stimuli are inversely predictive of their responses to systemic or brainstem opioid administration , and hence on cells are inhibited by morphine whereas off cells are disinhibited . the original notion of descending controls was that they were predominantly inhibitory in nature , but this has been broadened and refined so that we now know that the brainstem s output ( likely via the on cells ) can be predominantly facilitatory ( particularly with respect to high - intensity stimuli ) and that this may be the main physiological function . the balance between supraspinal inhibition and facilitation can , however , be altered , either transiently or durably ( for example , in some cases of chronic pain ) . with respect to the former , descending inhibitory pathways can be activated and endogenous analgesia recruited so that nociception and protective responses to noxious stimuli are temporarily suppressed in situations of threat and danger . in terms of longer - lasting alterations in descending output , the rvm may serve a protective , or masking , role during some pain states by increasing its inhibitory output ( for example , during inflammatory pain and potentially during the early stages of cancer ) . the descending system may , however , become maladaptive so that pain outlasts its biological usefulness ; after neuropathy , aberrant neuronal activity can increase the descending facilitatory drive to maintain the pain state , yet after the injury is healed , descending facilitatory neurones may fail to disengage , which means that they continue to enhance the transmission of sensory input . these mechanisms not only contribute to the neuropathic pain state but also are permissive for the efficacy of gabapentinoid drugs . because one mechanism by which descending neurones achieve this is through enhancing the evoked transmitter release from peripheral nerves , the feed - forward compensatory circuit between the periphery , spinal cord , and supraspinal structures becomes self - sustaining and indeed , these supraspinal influences appear to be prominent in the maintenance of persistent pains but not in their induction , suggesting that at first the pain states are driven by peripheral processes but that with time the pain drive moves higher up the neuraxis . in addition to providing insight into neuropathic pain , abnormal activity in this loop may shed some mechanistic light on diffuse pain states that lack simple peripheral causal explanations , such as fibromyalgia . the specialised role of midbrain and brainstem areas in pain processing has been demonstrated not only in animal studies but in human subjects too ; human imaging studies have shown that supraspinal activations during painful stimulation significantly localised in regions consistent with the nucleus cuneiformis and pag , areas that collectively form the major source of input to the rvm . furthermore , when the pattern of brain activity evoked by cold pain versus cold allodynia is compared in human volunteers , areas within the dorsolateral pons ( that are consistent with the parabrachial area ) are recruited in the processing of the latter , which verifies the role of the brainstem during central sensitisation . this is consistent with analyses of brainstem activity during dynamic mechanical allodynia , which highlighted neuronal changes and increased activity in the ipsilateral dorsal medulla / upper cervical cord in an area consistent with the location of the rvm . thus , together with diffusion tractography techniques that confirm anatomical pathways mediating top - down control of nociceptive processing in humans , these imaging studies provide a clear picture of the brainstem s representation of pain and central sensitisation in humans and reinforce the importance of descending modulatory systems , first mapped out in animals , to human correlates of the pain experience . pain doctors should therefore be aware that descending controls can have a major impact on the patient s pain experience where top - down modulation can be influenced by mood , fear , or sleep , for example . plausibly , the balance between facilitatory and inhibitory controls could be influenced by coping or catastrophising . preclinical data show descending facilitations dominating inhibitions in disparate models that include peripheral neuropathy , spinal cord injury , cancer - induced bone pain , and opioid - induced hyperalgesia . currently , the role of descending facilitations in clinical pains can be surmised by human imaging studies ( as discussed above ) in which activation of midbrain and brainstem structures in situations in which the pain rating is high is indicative of their facilitatory roles . on the other hand , the functional status of inhibitions can be evinced in some clinical situations , such as in their failure in patients with fibromyalgia . even here , the reduction in inhibition could be secondary to enhanced facilitations . some diffuse pain conditions may therefore be underscored by a malfunction of central neuronal systems that control mood , sleep , and pain such that a generalised pain state could be generated in the absence of overt peripheral pathology . in pains of peripheral origins , descending facilitations act alongside spinal mechanisms of hypersensitivity to further shift the pain score upwards . clinicians should also be aware that descending controls do not just modulate the pain state but are permissive for the actions of several important drug classes . the analgesic effects of tcas , snris , and the new mu - opioid receptor agonist and noradrenaline reuptake inhibitor tapentadol , for example , rely on altering activity at monoamine synapses and therefore are dependent on activity in the descending circuits ( the weaker analgesic efficacy of ssris is explicable in terms of the established noradrenergic inhibitory tone that contrasts with certain pronociceptive effects of 5-ht ) . furthermore , because gabapentin and pregabalin have efficacies that are dependent on activity within descending circuits , individual variations in pain comorbidities may explain why there are variable responses to treatments such as gabapentin and pregabalin in seemingly uniform pain groups . indeed , despite consistent efficacy in most animal models of neuropathic pain in which these co - morbid factors and societal influences may have less of an impact than in chronic pain patients , there is an ill - defined link between the presence of nervous system lesions or abnormal sensory phenomena and the responsiveness to gabapentinoid drugs in the clinic . clinical investigations relating the analgesic efficacy of tcas , snris , and gabapentinoids with affective measures may therefore be a step toward predicting treatment responsiveness in patients .

brainstem and midbrain areas engage descending facilitatory and inhibitory neurones to potentiate or suppress the passage of sensory inputs from spinal loci to the brain . the balance between descending controls , both excitatory and inhibitory , can be altered in various pain states and can critically determine the efficacy of certain analgesic drugs . there is good evidence for a prominent 2 adrenoceptor - mediated inhibitory system and for 5-ht3 receptor - mediated excitatory control of spinal cord activity that originates in supraspinal areas . given the multiple roles of these transmitters in pain and functions such as sleep , depression , and anxiety , the link between spinal and supraspinal processing of noxious inputs ( via the monoamine transmitters ) could be pivotal for linking the sensory and affective components of pain and their common co - morbidities , and also may potentially explain differences in pain scores and treatment outcomes in the patient population .

external - beam radiation therapy ( ebrt ) with intracavitary high - dose - rate ( hdr ) brachytherapy is the standard treatment modality for advanced cervical cancer . although long - term survival rates in patients with cervical cancer treated with definitive radiotherapy ( rt ) have improved considerably in recent years , the incidence of late gastrointestinal complications has also increased . the rectum is a major organ at risk during treatment planning because of its close proximity to the pelvic organs and relative immobility ; radiation proctitis has been reported in 5% to 11% of patients treated for gynecological cancer . sigmoid complications such as obstructive sigmoiditis and perforation are rarely reported , although some previous studies have estimated they occur in 0.6 - 6.4% of cases . herein we report two uncommon cases of radiation sigmoiditis mimicking sigmoid colon cancer after ebrt with intracavitary hdr brachytherapy for uterine cervical cancer with dosimetric consideration . we also discuss the importance of radiation dose to the sigmoid colon in three - dimensional image - based brachytherapy . a 79-year - old woman received definitive rt for international federation of gynecology and obstetrics ( figo ) stage iiib cervical cancer . ebrt was performed at a total dose of 50.4 gy in 1.8 gy fractions for five days each week using a 15-mv photon . intracavitary hdr brachytherapy ( microselectron - hdr ) of 24 gy in six fractions was conducted twice each week using a tandem and colpostat . following the completion of rt , the cervical cancer completely disappeared . after one year , the patient returned to the hospital complaining of intermittent rectal bleeding . a barium study revealed a 3-cm - long severe narrowing of the sigmoid wall , which was suspicious for sigmoid colon cancer ( fig . sigmoidoscopy revealed luminal narrowing with a friable hyperemic nodular mucosal change 15 cm from the anal verge ( fig . a 58-year - old woman received definitive rt with concurrent chemotherapy for figo stage iiia cervical cancer . ebrt was performed at a total dose of 50.4 gy in 1.8 gy fractions for five days each week using a 15-mv photon . intracavitary hdr brachytherapy ( microselectron - hdr ) of 24 gy in six fractions was conducted twice each week using a tandem and colpostat . six cycles of weekly cisplatin ( 30 mg / m ) were given during rt . after five years , the patient visited our emergency department with complaints of poor oral intake , lower abdominal pain and no stool passage over ten days . sigmoidoscopy revealed an approximately 5-cm - long section of diffuse luminal narrowing in the sigmoid colon and hyperemic mucosal nodularities with mucosal edema ( fig . a computed tomography ( ct ) scan also revealed thickening of the wall of the rectosigmoid colon probably caused by radiation or inflammation ; however no evidence of any cancer recurrence was found ( fig . she has been managed conservatively with laxatives and has been clinically followed with improved symptoms . we estimated an irradiated dose of brachytherapy of 518.7 to 642.3 cgy at the sigmoid colon point , which was 29.5% to 60.5% higher than prescribed dose at point a per fraction . a 79-year - old woman received definitive rt for international federation of gynecology and obstetrics ( figo ) stage iiib cervical cancer . ebrt was performed at a total dose of 50.4 gy in 1.8 gy fractions for five days each week using a 15-mv photon . intracavitary hdr brachytherapy ( microselectron - hdr ) of 24 gy in six fractions was conducted twice each week using a tandem and colpostat . following the completion of rt , the cervical cancer completely disappeared . after one year , the patient returned to the hospital complaining of intermittent rectal bleeding . a barium study revealed a 3-cm - long severe narrowing of the sigmoid wall , which was suspicious for sigmoid colon cancer ( fig . sigmoidoscopy revealed luminal narrowing with a friable hyperemic nodular mucosal change 15 cm from the anal verge ( fig . a 58-year - old woman received definitive rt with concurrent chemotherapy for figo stage iiia cervical cancer . ebrt was performed at a total dose of 50.4 gy in 1.8 gy fractions for five days each week using a 15-mv photon . intracavitary hdr brachytherapy ( microselectron - hdr ) of 24 gy in six fractions was conducted twice each week using a tandem and colpostat . six cycles of weekly cisplatin ( 30 mg / m ) were given during rt . after five years , the patient visited our emergency department with complaints of poor oral intake , lower abdominal pain and no stool passage over ten days . sigmoidoscopy revealed an approximately 5-cm - long section of diffuse luminal narrowing in the sigmoid colon and hyperemic mucosal nodularities with mucosal edema ( fig . a computed tomography ( ct ) scan also revealed thickening of the wall of the rectosigmoid colon probably caused by radiation or inflammation ; however no evidence of any cancer recurrence was found ( fig . she has been managed conservatively with laxatives and has been clinically followed with improved symptoms . we estimated an irradiated dose of brachytherapy of 518.7 to 642.3 cgy at the sigmoid colon point , which was 29.5% to 60.5% higher than prescribed dose at point a per fraction . acute and late gi complications are a major concern during and after rt . radiation sigmoiditis is not well - known compared to other gi complications such as proctitis and enteritis because it has been rarely reported . galland and spencer . reported 23 cases of sigmoid complications among 80 cases of radiation colitis induced by pelvic rt . ramirez et al . reported that a total of 35 patients developed sigmoid perforation among over 5,000 patients who were treated with rt for stage ib - iiib cervical cancer . in this report the sigmoiditis occurred one year after rt completion for one patient and five years after rt completion for the other patient . both cases showed obstructive symptoms , which make clinicians suspicious of sigmoid colon cancer or recurrent cancer . during the follow - up of cancer patients who received rt previously , clinicians need to keep the possibility of rt complications in mind . holloway et al . reported that the sigmoid - to - tandem distance is significantly related to sigmoid dose using 3d imaging techniques . concordantly , the simulation films of case 1 showed close proximity between the sigmoid colon and the tandem , which suggests the possibility of a high sigmoid dose during brachytherapy ( fig . the estimated dose at the sigmoid colon point during brachytherapy was 518.7 to 642.3 cgy , which was 29.5% to 60.5% higher than prescribed dose at point a ( 400 cgy ) per fraction . the international commission on radiation units ( icru ) 38 did not describe this hot spot in the sigmoid colon . the rectal and bladder reference dose points are only standard for reporting normal tissue doses with brachytherapy . indeed , these points are based on plain films and two - dimensional ( 2d ) brachytherapy planning . as ebrt is moving from conventional to conformal planning , the incorporation of three - dimensional ( 3d ) sectional imaging such as ct and mri into brachytherapy planning is under active investigation . recently , there has been a proposal to establish image - guided intracavitary brachytherapy guidelines for cervical carcinoma . in the group european de curietherapies and european society for therapeutic radiology and oncology ( gec - estro ) recommendations , the rectum and bladder , as well as the sigmoid colon , are highlighted as organs at risk . many studies have reported a sigmoid dose in 3d image - based planning for the treatment of cervical carcinoma with hdr brachytherapy . kim et al . reported that the sigmoid dose was higher than the rectal dose in 8 of 13 ( 61% ) patients and its volume was discontinuously located as multiple " hot spots " in 9 of 13 ( 69% ) patients on dosimetric analysis of 3d image - based planning of intracavitary brachytherapy for cervical cancer . currently at our institution , 3d image - based brachytherapy is implemented to decrease the radiation dose to organs at risk , including the sigmoid colon ( fig . 3 ) . 3d image - based brachytherapy planning can be helpful , especially for patients who have risk factors . patients who have a history of abdominal surgery , pelvic inflammatory disease , or diverticulosis are at a greater risk of developing radiation - induced gi complications because such conditions may create adhesions to the uterus , which prevent the loops of the bowel from moving during rt . in conclusion , radiation sigmoiditis is characterized by obstructive symptoms and its radiological findings can mimic sigmoid colon cancer . radiation oncologists should acknowledge the sigmoid colon as well as rectum and bladder as organs at risk . 3d image - based brachytherapy could be an optimal modality to reduce the radiation - toxicity associated with treatment for uterine cervical cancer .

external - beam radiation therapy with intracavitary high - dose - rate brachytherapy is the standard treatment modality for advanced cervical cancer ; however , late gastrointestinal complications are a major concern after radiotherapy . while radiation proctitis is a well - known side effect and radiation oncologists make an effort to reduce it , the sigmoid colon is often neglected as an organ at risk . herein , we report two cases of radiation sigmoiditis mimicking sigmoid colon cancer after external - beam radiation therapy with intracavitary high - dose - rate brachytherapy for uterine cervical cancer with dosimetric consideration .

poikiloderma is characterized generally by erythema , atrophy , telangiectasias , hypo , and hyperpigmentation in a reticulate pattern . it is usually considered a manifestation of varied dermatoses and seen commonly in association with ( 1 ) genodermatoses such as kindler syndrome , rothmund - thomson syndrome , dyskeratosis congenita , xeroderma pigmentosa , bloom syndrome , cockayne syndrome , and so on ; ( 2 ) collagen vascular disorders like dermatomyositis or systemic sclerosis ; or ( 3 ) as an early stage of mycosis fungoides ( mf ) or poikilodermic mf . poikiloderma vasculare atrophicans ( pva ; synonyms : parakeratosis variegata , parapsoriasis lichenoides , lichen variegates , parapsoriasis poikilodermique ) usually manifests clinically as asymptomatic or sometimes mildly itchy , red brown papules with mild scaling , coalescing into net - like patterned lesions . the sites of predilection are the breast , abdomen , and buttocks , or flexures . we describe a typical case of pva having a prolonged clinical course without actual progression to mf , suggesting its benign nature . this 48-year - old female presented with asymptomatic , generalized brownish - red papulo - macules in a network - like pattern interspersed with atrophy and prominent telangiectasias predominantly over the breasts , abdomen , back , and extremities [ figure 1 ] . upper limbs , especially extensors , and front of the trunk were involved more severely than the lower limbs and back . the lesions had begun over the thighs and progressed to involve the entire body in a period of 10 years . laboratory investigations including complete hemogram , serum biochemistry , antinuclear antibody ( ana ) , urinalysis , and x - rays / computed tomography scans of chest , abdomen , and pelvic organs showed no abnormality . histologic features of effaced rete ridges , hydropic degeneration of basal cells , focal dense band - like infiltrate of lymphoid cells ( prominently perivascular ) , dilated capillaries and extravasation of red blood cells , melanin incontinence and a few melanophages in the upper dermis , and no pautrier 's microabscess or atypical lymphoid cells were suggestive of pva [ figure 2 ] . immunohistochemical staining was negative for cluster of differentiation ( cd ) 3 , cd4 , and cd7 and positive for cd8 . molecular / polymerase chain reaction ( pcr ) studies were not done because of economic reasons . she was treated with puva - sol ( oral methoxsalen 20 mg followed by sunlight exposure ) on alternate days . she did not continue treatment after 3 months and discontinued follow - up after another 2 years despite counseling for the need of repeat future biopsies . the status of her skin lesions during follow - up had remained unchanged both clinically and histologically . poikiloderma vasculare atrophicans erythematous and brownish - red papulo - macules in a network - like pattern interspersed with atrophy and prominent telangiectasias predominantly over the abdomen and breasts . similar lesions were present over the back and extremities orthokeratosis , moderate - to - marked epidermal thinning , effacement of the rete ridges , and focal band - like dense cellular infiltrate of lymphoid cells in upper dermis ( a ) . hydropic degeneration of basal cells , melanin incontinence , dermal edema with focal exocytosis ( arrow ) , and a few melanophages in the upper dermis ( b ) . arrows indicate prominent perivascular infiltrate , dilated capillaries , and extravasation of red blood cells within the upper dermis ( c ) [ stain : hematoxylin and eosin ( h and e ) , 40 ] . a positive immunohistochemical staining of cells with cd8 surface markers in the upper dermis ( d ) several clinicopathologic forms of pva ( hypopigmented , vesiculobullous , erythrodermic , pustular ) have been described . however , its pathogenesis and status within the spectrum of cutaneous t - cell lymphoma remains poorly elucidated . some workers consider pva as a rare variant of early - stage mf as its histologic features are similar to those of long - standing patch or plaque stage of classic mf with poikiloderma . another view is that pva is per se a premycosis , an early - stage mf or poikilodermic mf presenting clinically with hypopigmentation and hyperpigmentation in reticulate pattern , dryness , atrophy , and telangiectasias . in view of its prolonged benign clinical course without progression to tumor stage after several years , even 30 years in some cases however , mf ( particularly its poikilodermic variant ) , being the commonest of cutaneous t - cell lymphomas , remains the most crucial differential of the more benign pva . repeated biopsies and clinicopathologic correlation , of course , is of crucial value in the early diagnosis of mf . however , immunohistologic features of mf are not distinct and may be observed in other inflammatory dermatoses as well . staining for cd3 or cd4 highlights epidermotropic t cells , but staining for cd7 has a limited usefulness in early - stage mf as partial loss of cd7 in t cells is usual in other inflammatory dermatoses . on the other hand , cd8 + phenotype of mf is reportedly observed having a long , mild , indolent , and benign clinical course . the recent pcr techniques with enhanced sensitivity have limitations of low specificity as they may detect a population of monoclonal t lymphocytes present in other benign inflammatory dermatoses as well . hence , the absence of clonality or negative immunohistochemical results is not construed to exclude the diagnosis of mf . similarly , monoclonal rearrangement of the t - cell receptor ( tcr ) gene or immunohistochemical analysis of tcrs are not considered useful in differentiating mf from other chronic benign inflammatory dermatoses ( psoriasis , chronic contact dermatitis , lichen planus , lichen sclerosis , etc . ) as monoclonal rearrangement in mf is seen in only 50%-60% cases . hence , the presence or absence of monoclonal pattern of tcr gene rearrangement is not an absolute criterion to diagnose mf in early stage . moreover , all these sophisticated techniques are too complex , expensive , and have limited availability in routine clinical settings . our patient had characteristic clinicopathologic presentation of pva with an observed long benign clinical course without progression to tumor stage of mf . however , it remains unclear whether pva actually is mf , a forme fruste of mf , a cd8 + mf phenotype , or a distinct and benign entity that can perhaps be labeled as pva . the last one appears more meaningful to us as distinguishing benign cases of pva from pokilodermic mf will save these patients from unnecessary psychological distress and expensive therapy for mf . however , regular long - term clinicopathologic and immunohistochemical follow - up studies of these patients will perhaps clear some of these unresolved issues . poikiloderma vasculare atrophicans ( pva ) with a characteristic histopathology , cluster of differentiation ( cd ) 8 + cell infiltrate on immunohistochemical staining , and long benign clinical course can perhaps be labeled as a distinct and benign pva phenotype .

this paper describes a typical case of poikiloderma vasculare atrophicans ( pva ) in a 48-year - old female . histologically , the features were suggestive of pva with the absence of pautrier 's microabscess or atypical lymphoid cells . the biopsy specimen was positive for cluster of differentiation ( cd ) 8 on immunohistochemical staining . its exact pathogenesis remains obscure , and it remains unclear whether pva actually is mycosis fungoides ( mf ) , a forme fruste of mf , or a distinct and benign dermatosis with cd8 + phenotype that can perhaps be labeled as pva . however , it has a long benign clinical course without progression to tumor stage of mf in most cases , and its status within the spectrum of cutaneous t - cell lymphoma remains poorly understood . yet it is imperative to distinguish pva from poikilodermic mf .

obesity is associated with a number of diseases , such as type 2 diabetes ( t2d ) , cardiovascular disease ( cvd ) , cancers , asthma , osteoarthritis , chronic back pain , and sleep apnoea . as childhood obesity prevalence has risen markedly in recent decades , indicators of early development of some of these diseases are increasingly being seen in childhood and adolescence . for example , the lowest estimated prevalences of impaired glucose tolerance , hypertension , and raised total cholesterol in obese 518-year - old children in the european union in 2006 were 8.4% , 21.8% , and 22.1% , respectively . obesity and its associated health risk factors track strongly from childhood into adulthood . therefore , identification of children at an increased risk of developing obesity - related diseases is critical for early prevention . various algorithms have been developed for adults to provide individual predictions of risk of obesity - related diseases , particularly of cardiometabolic risk leading to cvd [ 515 ] . these include the widely used framingham risk score [ 6 , 7 ] , which uses information on age , sex , blood pressure , total cholesterol ( tc ) , high density lipoprotein cholesterol ( hdl - c ) , diabetes , and current smoking behaviour to give an estimate of 10-year cvd risk in adults aged 20 years . attempts have also been made to develop similar algorithms to predict cardiometabolic risk in children [ 1627 ] , and most of them focus on identifying the metabolic syndrome ( mets , the clustering of abnormal metabolic traits associated with cvd risk ) [ 28 , 29 ] . there is little consensus on the criteria for defining the mets in children and adolescents , and most algorithms have not been validated . the existing childhood mets definitions have been derived from adult definitions assuming that the conditions are related over the life course , while the utility and predictive value of mets in children have not yet been fully established . in this review , we examine the benefits and limitations of mets scores and algorithms that have been developed to predict later cardiometabolic risk in children and adolescents and offer suggestions for developing clinically useful algorithms in this population . such algorithms could aid primary care professionals in the identification of children at high risk of obesity - related diseases and would be an important tool in childhood obesity management . the mets in adults is characterised by obesity ( often assessed by large waist circumference ( wc ) ) , high triglycerides ( tg ) , low hdl - c , high blood pressure , and high glucose levels . the prevalence of the mets increases with age . in children and adolescents , the thresholds for the individual variables to define these high and low levels depend on the age of the population and the mets definition applied . notably , because there is no consensus about the definition of mets in children , it can be difficult to make consistent and accurate diagnoses . due to the lack of universal mets definition and for the sake of retaining statistical power , construction of continuous mets scores ( cmets ) has gained popularity . many algorithms which predict cardiometabolic risk in children are based on these mets scores , with children who are classified as having mets or children with a high value of cmets being flagged as having an increased future cardiometabolic risk . studies that have used either continuous or binary [ 24 , 26 , 27 ] mets definitions / scores to assess or predict future cardiometabolic risk have been reviewed previously . these studies do not always explicitly state the future disease that they are trying to predict ( e.g. , cvd ) ; instead , terms such as cardiovascular or cardiometabolic risk are widely used . the association between mets characteristics in childhood and increased adult risk of cvd may largely be due to tracking of obesity and other mets characteristics from childhood into adulthood . one recent example of a mets definition is from the international diabetes federation ( idf ) , which modified a definition originally developed for adults . the idf has age - specific definitions of mets ( 6<10 , 10<16 , and 16 years ) [ 25 , 26 ] which is an improvement over earlier definitions that did not include age stratification [ 26 , 27 ] . except for the youngest age group ( where mets is not defined , but further measurements for obese children with a family history of cvd or related conditions are recommended ) , the idf definition produces a binary outcome identifying children as having mets if the child has high wc and exceeds threshold levels for at least two of the following four risk factors : high tg , low hdl - c , high sbp / dbp , and high glucose . in that sense , it is similar to earlier mets definitions in paediatrics [ 16 , 24 , 26 , 27 ] . however , the idf definition has been regarded as the most appropriate binary mets definition in children since it applies different criteria for each age group , acknowledging that blood pressure , lipid levels , and anthropometric variables change with age and pubertal development . if the idf definition in children becomes widely accepted , it could be used to aid in the identification of children at an elevated cardiometabolic risk . alternatively , to maximise the use of information and statistical power , the underlying continuous risk factors that compose the idf definition from age 10 years could be turned into a cmets . the threshold indicating a high value of this score could then be defined for each age group or ever for each age ( in years ) to increase accuracy . some algorithms for predicting cardiometabolic risk in children include additional characteristics to metabolic traits that are established risk factors of cvd . examples include models which additionally use ethnicity , family history of disease , fitness level , or smoking status to compute a final risk score ( table 1 ) [ 1823 , 3236 ] . in these algorithms , however , the choice of additional non - mets components is rarely justified and in many cases appears to be based solely on availability of data or characteristics identified in studies restricted to adult populations . diagnostic test results for most of the algorithms developed in children have not been published , in most cases due to the lack of current or subsequent clinical outcomes ( such as cvd ) against which they could have been tested . one study which predicted the probability of developing atherosclerotic lesions in the coronary artery and abdominal aorta based on age , sex , smoking , bmi , hypertension , hyperglycemia , hdl cholesterol , and non - hdl cholesterol reported an area under the receiver - operating curve ( auc ) of 0.78 for the risk of coronary artery lesions and of 0.84 for abdominal aorta lesions . another study tested a score based on the refined american diabetes association ( ada ) criteria for glucose intolerance in a clinical high - risk population from birmingham ; this study reported sensitivity of 100% , specificity of 57% , and positive predictive value ( ppv ) of 36% . we did not identify any validation studies of these risk algorithms in populations other than those in which they were first developed or applied . without these two important steps of testing and validation , it is impossible to compare the performance of different algorithms to one other . testing and validation are needed to develop consensus on what is the best method for predicting cardiometabolic risk in children . using a summary score to predict cardiometabolic risk in children , like all the mets scores reviewed here , is appealing because it reduces different metabolic dimensions into a single variable . each item included in the score is assumed to be equally important ( unless weighting is used ) and exchangeable with any other item . for example , 1 sd increase in blood pressure is assumed to be equivalent with 1 sd increase in tg or 1 sd decrease in hdl - c . these assumptions are unlikely to reflect reality , and they may be difficult to validate in real datasets . instead of using a binary mets outcome , which is a common practice , a continuous mets score ( cmets ) may be preferable . this can be a sum of individual rankings , sum or mean of z - scores , principal components , or sum of standardised residuals . this approach overcomes problems such as misclassification and low statistical power often related to binary scores . however , if the resulting cmets is subsequently grouped using cutoffs , like the age - specific idf mets definition , misclassification may still occur . there are also some general issues concerning screening tools that need to be taken into account when they are applied in clinical practice . if the sensitivity of the tool is not adequate , a considerable proportion of children at risk will not be detected . on the other hand , if specificity of the tool is limited , some children who are not at an increased risk will be captured and may have to go through unnecessary further testing which may cause anxiety to the children and their families . a test with reasonably good sensitivity and specificity may be useful for early identification of children with increased future risk , which in turn may create opportunities for early intervention . for example , in the study which predicted the probability of developing atherosclerotic lesions , auc based on sensitivity and specificity was fairly good , but the results of this study were not replicated . the applicability of an algorithm should always be piloted in the target population before implementing it , since an algorithm developed in one population may not be useful in another population without modification . for example , some algorithms have been developed in selecting clinical populations or in ethnic groups of a higher risk . this is especially a concern when cmets is used and when cut - off points for an increased risk are defined without a clinical basis . we suggest development of an algorithm which fully utilises the continuous distributions of metabolic features ( e.g. , by calculating z - scores ) . for example , a two - step approach may have advantages in terms of cost - effectiveness . the first step would target a wider range of overweight / obese children , perhaps through primary care , and those who were flagged as overweight ( using age , sex , and potentially ethnicity standardised bmi z - score ) could be assessed for other easily measurable factors predictive of later cardiometabolic disease , for example , blood pressure . the small group of children that exceed a stringent threshold for a standardised summary score for estimated risk could then be taken forward to the next step . in this next step , more complex , costly , or time - consuming clinical measurements ( e.g. , lipids , insulin , and glucose ) could be taken from referred children and an updated standardised risk score could be calculated . score should be offered specialised weight management interventions if these are available or be monitored regularly and treated when necessary . this approach combines the benefits of the use of continuous metabolic features in the first step while retaining usability through the application of cutoffs for flagging children who are predicted to be at the highest risk . the suggested algorithm could be based on a fitted prediction model in a large , longitudinal , population - based dataset that covers anthropometric and metabolic data and other relevant risk factors from childhood and adolescence as well as clinical outcomes ( t2d , hypertension , and cvd ) from adulthood . once validated , it should be an improvement over existing algorithms because it uses complete information from the continuous distributions of the metabolic risk factors . our work using a large uk cohort suggested that age , sex , and ethnicity standardised bmi z - score was the best predictor of having cardiovascular risk factors ( elevated glucose , ldl - c , and/or sbp / dbp ) present in childhood ( submitted manuscript ) . based on this work , we created a simple online tool that gives primary care providers guidance on how to treat and appropriately refer children who are overweight . validation against clinical cardiometabolic outcomes in adulthood was not possible using the same cohort due to its young age , but we hope to validate our models in larger , more diverse datasets in the future . several different mets scores and algorithms which predict adult cardiometabolic risk in children have been developed , but diagnostic test results against a clinical outcome , such as cvd , have not been published for most of them , and they have not been validated in other populations . we suggest a simple two - step approach for predicting risk of adult cardiometabolic disease in overweight children and piloting and validating any new algorithms .

clustering of abnormal metabolic traits , the metabolic syndrome ( mets ) , has been associated with an increased cardiovascular disease ( cvd ) risk . several algorithms including the mets and other risk factors exist for adults to predict the risk of cvd . we discuss the use of mets scores and algorithms in an attempt to predict later cardiometabolic risk in children and adolescents and offer suggestions for developing clinically useful algorithms in this population . there is little consensus in how to define the mets or to predict future cvd risk using the mets and other risk factors in children and adolescents . the mets scores and prediction algorithms we identified had usually not been tested against a clinical outcome , such as cvd , and they had not been validated in other populations . this makes comparisons of algorithms impossible . we suggest a simple two - step approach for predicting the risk of adult cardiometabolic disease in overweight children . it may have advantages in terms of cost - effectiveness since it uses simple measurements in the first step and more complex , costly measurements in the second step . it also takes advantage of the continuous distributions of the metabolic features . we suggest piloting and validating any new algorithms .

in high volume centers , partial pancreaticoduodenectomy ( pd ) can be performed with acceptable morbidity and mortality . while the outcome is clearly associated with surgeon and center experience , the rate of pancreatic fistulas seems not to drop below a certain level [ 2 , 3 ] . even after thousands of pd , highly experienced surgeons in high - volume centers report an almost constant or even increasing rate of pancreatic fistulas . depending on the definition , the published rate of postoperative fistulas after pd is estimated to be 2030% . numerous interventions and techniques have been introduced and a number of standardized anastomotic techniques exist , but there is little evidence for superiority of one anastomotic technique over the other [ 513 ] . isolation of the pancreaticojejunostomy ( pj ) using dual - loop reconstruction has been discussed as possible intervention to decrease the rate of pancreatic fistulas but seems not to be superior to single - loop reconstruction . in multivariate analyses , some risk factors for anastomotic leakage soft pancreatic texture , a history of weight loss , intraoperative blood loss , diameter of the pancreatic duct , and decreased preoperative albumin seem to be associated with leakage . renal insufficiency has been shown to be associated with increased complication rates after pancreatic resection . for some types of abdominal surgery , a restrictive fluid regimen is considered common sense : as far as liver resection is concerned , fluid management at a low central venous pressure below 5 cm h2o is made use of to decrease intraoperative blood loss [ 2023 ] . anesthesiological guidelines may vary between institutions but usually consider hemodynamic parameters , blood values , blood loss , and duration of surgery to be triggers that guide the intraoperative regimen . interstitial fluid overload due to infusion of large amounts of fluid can lead to visible edema and might compromise the anastomotic integrity . for rectal resections , an increased risk of anastomotic leakage after excessive perioperative infusions has been shown . in pancreatic surgery , there is evidence pointing out that the same mechanisms might be relevant . in a study focusing on normovolemic hemodilution to decrease blood loss in pancreatic surgery , no effect on blood loss was identified but an increased rate of 21.5% versus 7.7% anastomotic complications was apparent after 6250 ml versus 3900 ml of intraoperative intravenous fluid . as far as postoperative fluid management is concerned , a restrictive management aiming at a fluid balance of less than 1 liter on postoperative day has been shown to be associated with decreased complication rates . this study was designed to identify associations between renal function , intraoperative infusions , and occurrence of clinical relevant postoperative pancreatic fistulas after pd with pj . data extraction , handling , and analysis were performed in accordance with national and institutional guidelines . all pds with pj performed from 12/2011 till 02/2015 were analyzed and data on patient age , indication to surgery , concomitant diseases , preoperative laboratory values , duration of surgery , blood loss , intraoperative infusions , postoperative infusions during the first 72 hours after surgery , occurrence of pancreatic fistulas , and interventions ( both surgical or other ) was extracted from patient folders . pf were considered to be clinically relevant when drainages had to be kept longer than 72 h and pancreatic enzyme levels in the drainage fluid were at least three times higher than in the serum , drainages had to be reintroduced ( e.g. , guided using computer tomography or ultrasound ) , and pancreatic enzymes were detected in the drainage fluid or patients had to undergo reoperations for complications caused by pf . while duct diameter and pancreatic texture have been discussed as factors associated with postoperative fistula , these parameters lack clear definitions : duct wideness and tissue softness strongly depend on the individual surgeon 's definition and experience . without clear definition of both parameters prior to documentation , including this type of data in a retrospective analysis can not be considered to be reliable . thus , we did not include this in our analysis and have assumed an equal distribution of both parameters between groups . for descriptive statistics , median and interquartile range ( iqr ) or range are used unless stated otherwise . to determine a meaningful cutoff for the infusion rate : gfr ratio , receiver operating characteristics ( roc ) were employed , and the area under the roc curve ( auc - roc ) and youden 's j were calculated . testing for statistical significance was performed using anova and fisher 's exact test as appropriate . p values were two tailed and a value of p < 0.05 was considered statistically significant . in our institution , usually , single - loop reconstruction with a warren - cattell end - to - side pj using poly - p - dioxanone ( pds 5.0 , johnson & johnson medical gmbh , ethicon , norderstedt , germany ) is performed . a pancreaticogastrostomy may be performed depending on the surgeon 's choice . a surgical drain is routinely placed to the pancreatic anastomosis . patients are extubated in the operating room and transferred to the intensive care unit where mobilization is started and oral fluids are introduced on the day of surgery . as soon as patients have been stable for at least 24 hours , they are transferred to the intermediate care ward . drains are removed as soon as the fluid is less than 500 ml and is serous . if there is suspicion of a pf , drains are kept in place and enzyme levels are monitored in the drainage fluid . . in total , n = 18 ( 21% ) relevant pancreatic fistulas occurred ( table 1 ) . median age was 66 years ( range 3484 years ; 60% male ) , gfr was 93 ml / min ( iqr 78113 ml / min ; figure 1 ) , and surgery time was 259 min ( iqr 217307 ; table 1 ) . intraoperatively , 13.6 ml / min ( range 731 ml / min ) was infused ( figure 2 ; table 1 ) . crystalloids were used in all patients during surgery and during the first 72 h after surgery . colloids were infused in 46% of patients during surgery ( 56% and 43% in patients with and without fistulas ; p = 0.4264 ) , while 24% of patients received colloids during the first 72 h after surgery ( 0% versus 31% in patients with and without fistulas ; p = 0.0046 ; table 1 ) . the amount of postoperative infusions had no effect on occurrence of pancreatic fistulas ( table 1 ) . except for creatinine , gfr , and postoperative infusion of colloids , no statistical differences were identified between patients with or without pancreatic fistulas ( table 1 ) . there was no correlation between the amount of intraoperatively infused volume and gfr ( figure 3 ) . roc analysis identified an infusion rate : gfr ratio of 0.15 as threshold for occurrence of pancreatic fistulas ( figure 4 ) . a significant increase of pancreatic fistulas from 11% to 34% was detected for patients below and above the identified threshold ( p = 0.0157 ; table 2 ) . . this can be quite demanding and needs experience on the anesthesiologists ' side similar to surgical experience needed when complex surgery is performed . without a balanced and careful fluid regimen , the surgery 's success is jeopardized . it is a common misconception that fluid management has little effect on surgical complication rates , although this has been demonstrated frequently [ 22 , 23 , 2628 , 31 ] . in abdominal surgery , restrictive fluid management has repeatedly proven to be superior over dilutive regimens . in liver resection , restrictive fluid management is used to achieve a low central venous pressure and leads to decreased intraoperative blood loss , which is known to be associated with increased morbidity [ 22 , 23 ] . in rectum resection , both intraoperative and postoperative amounts of infusions have been linked to anastomotic complications [ 27 , 28 ] . excessive ( and in this context : mindless ) infusion management can be linked to increased postoperative complications including impaired wound healing , pulmonary complications , and intestinal paralysis [ 3135 ] . it seems obvious that successful fluid management in pancreatic surgery needs to be balanced : while excretory renal function can visually be monitored during surgery and hemodynamic parameters are constantly made use of as triggers for infusions and pharmacological interventions , renal function is usually only considered important when already compromised . most of our patients had a normal renal function with a gfr within normal values ( table 1 , figure 1 ) . nonetheless , it is quite clear that even the hardest working and healthiest kidney can be overloaded by volume excess . interstitial fluid shifting can result from generous substitution during surgery and is aggravated by increased vascular permeability . in these cases , resulting edema is visible for surgeons and should be considered an alarm signal and threat to the patient , especially when risky anastomoses with known potential of fistulas need to be carried out . in the authors ' opinion , this mechanism , which is supported by the findings presented in this study , seems intuitive and quite obvious . consequently , anesthesiologists need to hand over part of the responsibility for adequate fluid management to surgeons and need to be aware that misguided fluid management can increase risk of surgical complications . the bottom line is that there is a good share of responsibility for surgical complications for the anesthesiologist and every discipline involved in the teamwork necessary to carry out complex surgical procedures needs to understand any intraoperative action contributes to success or failure . fluid overload needs to be avoided , while fluids lost need to be replaced and hemodynamic parameters need to be manipulated to stabilize the patient during and after surgery . during induction of anesthesia , a starting bolus volume is very often applied and is considered necessary to compensate for both hypovolemia of the fasting patient and vasodilatation during anesthesia or caused by epidural catheters [ 3638 ] . this has been considered good practice for years but may be inappropriate and the foundation to postoperative complications even before surgery starts . during surgery , excessive volumes are infused to compensate loss to the third space , which has been an accepted concept for decades but may not even exist [ 39 , 40 ] . very often , sympathomimetic medication will be avoided since an impaired renal function is feared and crystalloids and colloids will be applied . intraoperatively , no significant difference was seen for the type of infusion solutions ( i.e. , crystalloids versus colloids ) in our patients . most interestingly , there was a striking difference in postoperative regimens : none of the patients with fistulas had received colloids during the first 72 h after surgery . smaller volumes of colloids are needed to achieve the same effect compared to crystalloids ; thus crystalloid substitution using colloids might be a worthwhile intervention , but data on this topic remains controversial . it has to be remarked that in large meta - analyses no positive effect on survival and complications rates of colloids versus crystalloids could be identified ; consequently , the usage of colloids has decreased over the last decade while the rate of pancreatic fistulas after pd with pj remained unchanged [ 2 , 43 ] . in a study from 2014 , a threshold of 1 l positive fluid balance on postoperative day one was identified to be associated with an increased risk of complications after pancreatic surgery . since fluid balance during the first 24 h after surgery exceeded 1 l in any of our patients , this finding was not reproducible using our data . pancreatic surgery involves both sophisticated surgical and anesthesiological management , amongst other prerequisites [ 4446 ] . fluid management , which is within reach for interventions , needs to be considered as surgical and anesthesiological teamwork [ 30 , 47 ] . our analysis has demonstrated a clear association between intraoperative fluid excess and occurrence of pancreatic fistulas after pd with pj even in patients with normal renal function . when in our patients the intraoperative infusion rate : gfr ratio exceeded 0.15 , the rate of postoperative pancreatic fistulas was more than tripled . our analysis points at an increased use of intra- and postoperative colloids as a possible intervention . high quality randomized clinical trials comparing different fluid regimens are needed to generate evidence in this important aspect of pancreatic surgery .

background . after pancreaticoduodenectomy ( pd ) , pancreatic fistulas ( pf ) are a frequent complication . infusions may compromise anastomotic integrity . this retrospective analysis evaluated associations between intraoperative fluid excess and pf . methods . data on perioperative parameters including age , sex , laboratory findings , histology , infusions , surgery time , and occurrence of grade b / c pf was collected from all pd with pancreaticojejunostomy ( pj ) performed in our department from 12/2011 till 02/2015 . the glomerular filtration rate ( gfr ) , infusion rate , and the ratio of both and its association with pf were calculated . roc analysis was employed to identify a threshold . results . complete datasets were available for 83 of 86 consecutive cases . median age was 66 years ( 3484 ; 60% male ) , gfr was 93 ml / min ( iqr 78113 ) , and surgery time was 259 min ( iqr 217307 ) . intraoperatively , 13.6 ml / min ( 731 ) was infused . in total , n = 18 ( 21% ) pf occurred . when the infusion : gfr ratio exceeded 0.15 , pf increased from 11% to 34% ( p = 0.0157 ) . no significant association was detected for any of the other parameters . conclusions . this analysis demonstrates for the first time an association between intraoperative fluid excess and pf after pd with pj even in patients with normal renal function . a carefully patient - adopted fluid management with due regard to renal function may help to prevent postoperative pf .

inguinal hernia repair is one of the most commonly performed surgical procedures with approximately 20 million inguinal herniorrhaphies repairs performed yearly around the globe . the operative approach to inguinal herniorraphy overtime has evolved from primary tissue - based repairs to open tension - free mesh repairs and finally more recently laparoscopic mesh repairs . the latter has gained favor due to the substantial decrease in pain experienced by patients and an earlier return to activity . moreover , within the realm of laparoscopy , robotic assistance offers the operating surgeon considerable advantages in terms of superior visualization , stabilization of instruments and improved ergonomics , making this application an attractive alternative to conventional laparoscopic inguinal herniorraphy . robotic - assisted inguinal hernia repair utilizes the transabdominal preperitoneal approach ( tapp ) which entails development of a peritoneal flap ( pf ) , dissection and reduction of the hernia sac and placement of a mesh in the preperitoneal space thus created . following hernia repair pf should be closed thereby partitioning the mesh from the viscera consequently reducing the risk of mesh erosion into the viscera and bowel obstruction secondary to herniation through the peritoneal defect . there are many methods available for closure of the pf including sutures , tacks , adhesive sealants and staples ; however , suture closure is preferred particularly in robotic tapp as it allows complete exclusion of the preperitoneal space with an improved short - term quality of life . in recent years , self - anchoring barbed sutures have been developed and gained popularity for a variety of tissue applications due to the simplicity of use and knotless application . herein we report an unusual case of post - operative small bowel obstruction following robotic - assisted inguinal hernia repair emanating from the self - anchoring suture used for pf closure . a 61-year - old male with a weight of 88 kg and a bmi of 27 kg / m presented with symptomatic right - sided reducible inguinal hernia . he was offered and subsequently underwent a robotic - assisted tapp inguinal herniorraphy . during the operation , a right - sided direct inguinal hernia was identified , the sac was completely reduced and hernia repaired with right - sided 15 10 cm monofilament polyethylene terephthalate mesh ( progrip ; covidien dublin ireland ) . following successful placement and fixation of the mesh pf was closed using 02 - 00 self - anchoring - barbed suture ( v - loc 180 absorbable wound closure device ; covidien dublin ireland ) . total operative time was 124 min with 5 ml estimated blood loss and the patient was discharged home from post - anesthesia care unit . the patient presented to the emergency department on post - operative day 3 with complaints of nausea , vomiting , abdominal distention and obstipation . physical examination revealed a tender and distended abdomen , further evaluation with cross - sectional imaging revealed a transition point in the right lower ( fig . he subsequently underwent diagnostic laparoscopy where a free end of the barbed suture was noted to be adherent to the small bowel creating a sharp angulation in the bowel leading to obstructive symptoms ( fig . the suture was lysed close to the peritoneum , which led to the relief of bowel obstruction . post - operatively the patient had return of bowel function the following day and was discharged home . figure 1:ct scan demonstrating transition point between dilated proximal and collapsed distal small bowel . figure 2:laparoscopic view of self - anchoring suture adherent to the small bowel causing the obstruction . laparoscopic view of self - anchoring suture adherent to the small bowel causing the obstruction . complete closure of the pf following a tapp inguinal hernia repair is important to prevent post - operative complications . available evidence suggests that closure of pf with running suture is preferable due to a reduction in post - operative pain and incidence of bowel obstruction secondary to herniation through the peritoneal defect or displaced tacks [ 4 , 7 ] . self - anchoring knotless - barbed sutures offer an easier and faster option for pf closure . while these devices facilitate pf closure given their propensity of adherence to intra - abdominal viscera , there remains a risk of adhesive bowel obstruction . there have been some previous reports of small bowel obstruction following ventral rectopexy , sacral colpopexy and laparoscopic tapp suggesting that if these devices are used maximal efforts should be made to ensure that the suture material is not exposed to any intra - abdominal viscera [ 810 ] .

laparoscopic inguinal herniorraphy is a commonly performed procedure given the reported decrease in pain and earlier return to activity when compared with the open approach . moreover , robotic assistance offers the operating surgeon considerable ergonomic advantages , making it an attractive alternative to conventional laparoscopic herniorraphy . robotic herniorraphy utilizes the transabdominal preperitoneal approach where following repair peritoneal closure is necessary to avoid mesh exposure to the viscera . self - anchoring sutures are frequently used to this end given the ease of use and knotless application . we present an unusual case of post - operative small bowel obstruction following robotic inguinal hernia repair caused by the self - anchoring suture used for peritoneal closure . this patient presented 3 days post - procedure with symptoms and cross - sectional imaging indicative of small bowel obstruction with a clear transition point . underwent laparoscopic lysis of a single adhesive band originating from the loose intraperitoneal end of the suture leading to resolution of symptoms .

since 1984 , in an attempt to maintain at least part of the splenic function when the removal of the spleen is recommended , we have performed subtotal splenectomies , preserving the superior splenic pole supplied by the splenogastric vessels . this procedure was successfully used for the treatment of 130 patients with portal hypertension , 93 patients with severe splenic trauma , 18 patients with myeloid metaplasia , nine patients with gaucher s disease , five patients with retarded growth and sexual development associated with splenomegaly , five patients with chronic lymphocytic leukemia , three patients with severe splenic pain due to intraparenchymal thrombosis , one patient with splenic hemangioma , one patient with splenic abscess , and one patient with a cystadenoma of the pancreatic tail , , , , , , , , , , , , , , . splenectomy has a very limited role in the treatment of hodgkin s lymphoma ( hl ) and is recommended only to control hl activity that does not respond to chemo- and radiotherapy , . since the purpose of a splenectomy is not to make the patient asplenic , a partial splenectomy may achieve the objectives without the adverse side effects of the total removal of the spleen , , . this is the first report of subtotal splenectomy preserving the inferior splenic pole without the maintenance of the splenic vascular pedicle . the treatment performed on this patient was approved by the ethical committee of the federal university of minas gerais under the protocol nr . caae 03990.203.000 - 11 and has been performed in accordance with the ethical standards laid down in the 1964 declaration of helsinki and its later amendments . this work has been reported in line with the scare criteria . a 53-year - old white man with hl was submitted to chemotherapy and radiotherapy at hospital of clinics of the federal university of minas gerais , brazil and referred to the department of surgery for splenectomy . the indications for spleen removal were abdominal and breathing discomfort caused by a huge spleen due to hl refractory to adjuvant oncologic therapy . to avoid surgical induced asplenic immune depression , the abdominal cavity was entered through a left transverse laparotomy ; the splenic artery was tied in the retrogastric space . at laparotomy , a very large spleen with a tumor restricted to the superior pole was found ( fig . the superior splenic vessels , including the splenogastric vessels , the superior splenic pole vessels and the splenic hilum were tied and cut . care was taken to preserve the left gastroepiploic and the inferior splenic pole vessels to maintain the vitality of the inferior splenic pole . the spleen was cut at the dividing line between the normal color of the inferior portion of the organ and the darker colored superior portion ( fig . two wide flaps ( anterior and posterior ) of the 5 splenic capsule were retained . a continuous 3 - 0 chromic catgut suture closed the two flaps of the splenic capsule ( fig . the inferior pole was returned to its normal position and sutured to the diaphragm with one stitch using 2 - 0 chromic catgut . 1surgical view of subtotal splenectomy for treatment of a man with hodgkin s lymphoma.a the very large spleen mobilized within the surgical field after the section of the splenic ligaments . observe the tumor in the superior pole ( * ) and the transition ( arrow ) between the inferior pole ( red ) supplied by the left gastroepiploic and inferior pole vessels and the rest of the devascularized spleen ( dark color).b the inferior splenic pole ( * ) after subtotal splenectomy . observe the left gastroepiploic vessels ( long thin arrow ) inside the grater omentum , and the inferior pole vessels ( short thick arrow).fig . 1 surgical view of subtotal splenectomy for treatment of a man with hodgkin s lymphoma . a the very large spleen mobilized within the surgical field after the section of the splenic ligaments . observe the tumor in the superior pole ( * ) and the transition ( arrow ) between the inferior pole ( red ) supplied by the left gastroepiploic and inferior pole vessels and the rest of the devascularized spleen ( dark color ) . b the inferior splenic pole ( * ) after subtotal splenectomy . observe the left gastroepiploic vessels ( long thin arrow ) inside the grater omentum , and the inferior pole vessels ( short thick arrow ) . histopathological analyses of the spleen confirmed the hl restricted to the superior pole with wide margins free of tumor . the patient had uneventful postoperative recovery and was discharged from the hospital on the fifth postoperative day . during the eleven - year follow - up scintigraphic images of the splenic remnant were positive in all postoperative exams , confirming the splenic vitality and the phagocytic function . the dimensions of the splenic remnant , according to ct exams , remained unchanged during the follow - up period ( table 1).table 1hematological exams one week before and three months after subtotal splenectomy to treat hodgkin s g / l141 g / lhematocrit36.0%42.5% white blood cells total3.6 10/l12.4 10/l neutrophils61%78% lymphocytes31%17% eosinophils1%0% basophils1%0% monocytes6%5% platelets78 10/l478 10/l hematological exams one week before and three months after subtotal splenectomy to treat hodgkin s lymphoma . chemo- and radiotherapy are the usual treatments of hl , and most of patients survive many years under control , . however , the huge growth of the spleen , which may occur in some patients , leads to abdominal discomfort and therapeutic resistance . it is well - known that total splenectomy reduces the immune defenses and may be followed by severe sepsis associated with precocious and sudden deaths . this complication is more frequent in previously immune suppressed patients , such as those with lymphomas , . chemo- and radiotherapy worsen organic defenses and enhance mortality . since the total removal of the spleen is not necessary to treat hl , partial splenectomy should be enough to reduce the influence of splenic growth on both the symptoms and the hematologic system , . however , the early good results are transitory , given that the spleen may regrow due to the blood flow through the splenic vascular pedicle . to avoid this inconvenient follow - up , we have proposed the subtotal splenectomy , which preserves a pole of the spleen without the vascular pedicle . usually , the subtotal splenectomy maintains only the superior pole supplied by the splenogastric vessels , but in this case , the tumor was located in the superior pole and had to be removed . therefore , we decided to perform the subtotal splenectomy , preserving the inferior splenic pole supplied by the left gastroepiploic vessels . prior to the present case report , the use of this technique had never been published . thus , we decided to follow the patient a least for ten years before publishing the case to detect all complications of this procedure when in the presence of hl . its main advantage is to preserve the splenic functions in a normal size spleen without the risk of its regrowth and resistance to oncologic treatment . as limitation of this study , the lower number of patients with hl confined to a single pole must be emphasized . this procedure should not be attempted for staging purpose in hl because the disease may be present in the preserved spleen even without its macroscopic evidence . a subtotal splenectomy that preserves the inferior splenic pole is efficacious in maintaining splenic functions and preventing the adverse effects of a large spleen in the treatment of hodgkin s lymphoma confined to superior pole and producing significant abdominal symptoms and hematological effects . the treatment performed on this patient was approved by the ethical committee of the federal university of minas gerais under the protocol nr . informed consent was obtained from the patient in written for the surgical procedure and for publication of his case with picture of the splenic procedure . informed consent was obtained from the patient in written for the surgical procedure and for publication of his case with picture of the splenic procedure revision of the literature , proposal of the surgical procedure , surgeon who performed the procedure , surgeon responsible for the patient during the perioperative period and all the follow - up , author who wrote the manuscript . i accept full responsibility for the work and/or the conduct of the study , had access to the data , and controlled the decision to publish .

highlightsfirst published case of subtotal splenectomy preserving the inferior splenic pole without the maintenance of the splenic vascular pedicle.a very large spleen hodgkin s disease was successfully treated using a partial splenectomy.a successful surgical treatment on a hodgkin s lymphoma refractory to chemo and radiotherapy.the patient is still alive after more than 11 years from the subtotal splenectomy.subtotal splenectomy is efficacious to preserve the splenic functions and to prevent adverse effects of a large spleen on the treatment of hodgkin s lymphoma.subtotal splenectomy is sufficient to reduce the inconvenience of a huge spleen on patient symptoms and disorders of the hematological and immunological system .

nonalcoholic fatty liver disease ( nafld ) is among the most common causes of chronic liver disease worldwide . the prevalence of nafld in the general population of western countries is 2030% . within the spectrum of nafld , only nonalcoholic steatohepatitis ( nash ) most patients with nafld have risk factors such as insulin resistance , obesity or other indications of metabolic syndrome . insulin resistance , oxidative stress , and inflammatory cascades are believed to play integral roles in the pathogenesis and progression of nafld . as such , a multi - hit ( formerly double - hit ) hypothesis has been used to describe the pathogenesis of nafld . as a result of the first insulin resistance arises and increased fatty acid levels in the blood enter the liver ( and/or are not removed from the liver ) , thus leading to hepatosteatosis . the second hit occurs as a result of the inflammation caused by the hepatosteatosis . the criterion standard method for the diagnosis of nafld , which most frequently presents with an asymptomatic increase of transaminase enzymes , is a liver biopsy . despite evidence that weight loss , dietary modifications , bariatric surgical operations , exercise and several drugs result in the biochemical and histological resolution of nafld , there is no current treatment regimen supported by valid , long - term studies that were properly randomized and controlled [ 710 ] . currently , the basis for treatment includes managing risk factors such as hyperlipidemia through steps such as lifestyle modification and weight loss . sirt1 is an nad - dependent deacetylase and acts as a modulator of various metabolic pathways . in this article , we focus on the sirtuin 1 ( sirt1 ) protein , which has important effects on glucose homeostasis , lipid mobilization , -oxidation , oxidative stress , insulin secretion and sensitivity , inflammation , cellular aging and apoptosis . we discuss the expression of sirt1 in cases of nafld , the results of sirt1 activation and the potential therapeutic role for sirt1 in treating nafld . silent information regulator 2 ( sir2 ) proteins , or sirtuins , are a class of proteins that possess either histone deacetylase or mono - adp - ribosyl transferase activity . they are found in organisms ranging from bacteria to humans . sirt1 , an nad - dependent protein deacetylase , is an important regulator of energy homeostasis in response to nutrient availability . currently , the best - studied sirtuin homolog , sirt1 , is expressed in metabolic tissues such as liver , skeletal muscle , adipose tissue , pancreas and brain ; its actions in these tissues include regulation of -cell and neuron survival , hepatic gluconeogenesis , insulin secretion and adiposity . resveratrol ( trans-3,5,4-trihydroxystilbene ) is a polyphenol found in red wines and a wide variety of plants including grapes , berries and peanuts . resveratrol has been shown to be a potent agonist of sirt1 [ 1315 ] . in mammalian cells , resveratrol promotes cellular expression of the sirt1 protein and dramatically stimulates sirt1 activity . furthermore , small - molecule sirt1 activators with structures unrelated to resveratrol but with 1000 times the potency have been identified . the effects of sirt1 activation , especially in metabolic tissues , lead to the inhibition of various pathways important for nafld pathogenesis . the liver is the central metabolic organ and regulates several key aspects of lipid metabolism ( fatty acid -oxidation , lipogenesis and lipoprotein uptake and secretion ) in response to nutritional and hormonal signals . nutritional intake in excess of the -oxidation capacity of the cell , lipoprotein synthesis and defects in excretion form the foundation of hepatosteatosis . over time , the transcriptional network of the liver contributes to an inflammatory process that progressively leads to nash associated with fibrosis , liver cirrhosis , hepatocellular carcinoma and death due to liver disease . in several recent studies , sirt1 has been shown to play an important role in the dynamics of nafld pathophysiology . using an experimental nafld model consisting of rats fed a high - calorie diet , another study in rats with nafld showed a significant increase in hepatic sirt1 expression and histological improvement with calorie limitation . in a study by purushotham et al . , hepatocyte - specific loss of sirt1 ( through hepatocyte - specific deletion of sirt1 ) was shown to cause peroxisome proliferator - activated receptor ( ppar ) signal failure and a decrease in fatty acid -oxidation . however , sirt1 overexpression increased levels of ppar and its coactivator ppar coactivator 1 ( pgc-1 ) . pgc-1 impairs ppar signaling and decreases fatty acid -oxidation , whereas overexpression of sirt1 induces the expression of ppar s targets . sirt1 interacts with ppar and is required to activate the ppar coactivator pgc-1. in a recently reported study in rats , sirt1 was shown to confer protection against age - associated metabolic damage , lead to healthier aging , decrease the frequency of liver cancer related to metabolic syndrome and protect the liver from carcinogenic damage . studies performed at the molecular level have demonstrated that sirt1 plays an important role in the regulation of the transcriptional networks controlling various critical metabolic processes in the liver [ 2426 ] . along those lines , sirt1 has been shown to deacetylate many nonhistone proteins , including p53 , nuclear factor kappa b ( nf-b ) , forkhead box class o 3 ( foxo3 ) transcription factors , pgc-1 , liver x - receptor ( lxr ) , clock , per2 and torc2 [ 2736 ] . in a study by yamazaki et al . , treatment of mice modeling nafld with a sirt1 activator ( srt1720 ) resulted in decreases in expression of lipogenic genes ( such as those encoding sterol regulatory element - binding protein-1c [ srebp-1c ] , acyl - coa carboxylase [ acc ] and fatty acid synthase [ fas ] ) , serum lipid profile , fat accumulation in the liver , expression of genes related to oxidative stress and the production of inflammatory cytokines . in a study of bariatric surgical cases performed by costa et al . , morbidly obese patients with severe hepatosteatosis were determined to have reduced expression of sirt1 in adipose tissue when compared to patients with mild hepatosteatosis . recent studies have shown that sirt1 plays important roles in both insulin resistance and insulin regulation in diabetics ( such as increasing insulin secretion from pancreatic -cells , stimulating lipolysis in adipose tissue and increasing glucose utilization in muscle tissue ) . in pancreatic -cells , sirt1 has been shown to increase insulin secretion through the repression of uncoupling protein 2 ( ucp2 ) . it was also demonstrated that sirt1 activation increases atp production in -cells and improves glucose - dependent insulin secretion , which typically decreases with age . a recent study demonstrated that inhibiting sirt1 overexpression and nf-b signaling decreases cytokine - induced pancreatic -cell damage . as a result , sirt1 activation prevents the development of insulin resistance and limits the pancreatic -cell dysfunction that develops in response to insulin resistance . it has been shown that sirt1 activation increases lipolysis by repressing ppar in adipose tissue , thereby inhibiting adipogenesis . sirt1 also regulates the production and/or secretion of insulin - sensitizing factors such as adiponectin and fgf21 through the regulation of foxo1 and ppar [ 4345 ] . lxrs regulate the transfer of cholesterol from peripheral tissues to the liver ( reverse cholesterol transport ) . pgc-1 deacetylation by sirt1 in skeletal muscle is necessary for the activation of mitochondrial fatty acid oxidation genes . as further evidence of the important of sirt1 in muscle , patients with type 2 diabetes show reduced expression of pgc-1 and mitochondrial oxidative phosphorylation ( oxphos ) genes in skeletal muscle . based on these data , the sirt1-dependent activation of pgc-1 sun et al . showed that sirt1 improves insulin sensitivity in skeletal myotubes through transcriptional repression of the protein tyrosine phosphatase 1b ( ptp1b ) gene . ptp1b is a key insulin receptor phosphatase , and ptp1b - deficient mice have been shown to be more insulin - sensitive and more resistant to diet - induced obesity compared to controls . recent studies have begun to address the relationship between sirtuins and age - related metabolic and cardiovascular diseases , antiinflammatory properties , anticarcinogenic effects , effects on oxidative stress and the cell cycle and anti - aging effects . epidemiological evidence gathered from nafld patients demonstrates that both cardiovascular disease risk and mortality are significantly increased when compared to a normal population [ 5355 ] . the cause of these effects may include vascular relaxation ( both by increasing endothelial nitric oxide synthase activity and by potassium channel - mediated vasorelaxation ) , inhibition of thrombocyte aggregation or increasing cardiac myocontractility ( by pgc-1 regulation ) [ 5660 ] . in addition , individuals with a single nucleotide polymorphism in the sirt1 gene exhibit a lower incidence of cardiovascular mortality , myocardial infarction , myocardial ischemia , stroke , arterial surgery and intermittent claudication . one of the important stages in the pathophysiology of nafld is the inflammatory process , which is considered the . one important effect of sirt1 activation , which was discovered recently , is its anti - inflammatory effect . an important aspect of this effect is performed through regulation of nf-b ( a master transcription factor involved in the regulation of proinflammatory cytokines and a key part of nafld pathogenesis ) . recent studies have shown that sirt1 also deacetylates and suppresses the transcriptional activity of activator protein-1 ( ap-1 ) , leading to a down - regulation of cyclooxygenase-2 ( cox-2 ) gene expression . in addition , the expression of multiple proinflammatory mediators , such as intracellular adhesion molecule 1 ( icam1 ) , mcp1 , rantes ( also known as ccl5 ) , macrophage colony stimulating factor ( m - csf ) , granulocyte - macrophage csf ( gm - csf ) , g - csf , and transforming growth factor- ( tgf- ) , is reduced by the sirt1 activator resveratrol . thus , sirt1 activity results in antiinflammatory effects through its regulation of multiple inflammatory pathways . another characteristic of sirt1 activation , discovered in the last few years , is its effects on tumorigenesis . the antiproliferative , proapoptotic and tumor suppressing effects of sirt1 activation have been elucidated by studies performed in rats . additionally , use of sirt1 in cancer chemotherapy , based on its chemopreventive effects , has been considered . resveratrol has been shown to have anti - carcinogenic effects both in vitro and in vivo . sirt1 has been shown to indirectly reduce the cellular oxidative stress burden through deacetylation of foxo3 ( deacetylation of foxo3 leads to upregulation of catalase and mnsod ) . sirt1 has also been shown to control the cell cycle , cell differentiation , cell proliferation and cell senescence by its regulation of the foxo and p53 proteins . a sedentary lifestyle and variations in dietary habits has significantly increased the frequency of metabolic syndrome and its hepatic component , nafld , and the number of patients with this condition continues to rise . currently , there is no validated evidence - based treatment algorithm , and patients are currently treated with recommendations for caloric limitation and increased physical activity . in recent years , the positive effects of sirt1 activation have been shown in the metabolic activities related to nafld pathophysiology . these activities include glycemic regulation , lipid homeostasis , insulin secretion and sensitivity , inflammatory processes , oxidative stress , endothelial dysfunction , mitochondrial biogenesis and -oxidation , cellular senescence , autophagy / apoptosis and skeletal and heart muscle function . from these results , we believe that sirt1 activation has potential as a therapeutic target to prevent both the progression and development of nafld . recent studies have demonstrated the positive effects of sirt1 activation on these metabolic activities after induction by resveratrol , a natural polyphenol . in addition , sirt1 activators that are 1000 times more efficient than resveratrol are currently being developed and studied . current policy requires that therapeutic efficiency and security profile evaluations in randomized controlled studies be performed for new pharmaceutical agents .

summarysirtuins are members of the silent information regulator 2 ( sir2 ) family , a group of class iii histone / protein deacetylases . there are 7 different sirtuins in mammals ( sirt1 - 7 ) , of which sirt1 is the best known and most studied . sirt1 is responsible for the regulation of protein activation by means of deacetylating a variety of proteins that play important roles in the pathophysiology of metabolic diseases . recently , it has been shown that sirt1 plays key roles in the regulation of lipid and glucose homeostasis , control of insulin secretion and sensitivity , antiinflammatory effects , control of oxidative stress and the improvements in endothelial function that result due to increased mitochondrial biogenesis and -oxidation capacity.nonalcoholic fatty liver disease ( nafld ) is currently the most common liver disease , and it has been accepted as the hepatic component of metabolic syndrome . recent studies have shown that sirt expression in the liver is significantly decreased in an nafld model of rats fed a high - fat diet , and moderate sirt1 overexpression protects mice from developing nafld . in addition to resveratrol , a natural sirt1 activator , small - molecule pharmacologic sirt1 activators have positive effects on metabolic diseases . these effects are particularly promising in the case of diabetes mellitus , for which phase studies are currently being performed . with this information , we hypothesized that the pharmacologic activation of sirt1 , which has been implicated in the pathogenesis of nafld , will be a potential therapeutic target for treating nafld . in this paper , we review the metabolic effects of sirt1 and its association with the pathophysiology of nafld .

west syndrome is characterized by hypsarrhythmia on electroencephalography ( eeg ) examination , infantile spasms , and mental retardation . west syndrome is classified according to the underlying etiology into ( 1 ) an acquired west syndrome , ( 2 ) a congenital / developmental west syndrome , and ( 3 ) west syndrome of unknown etiology . the reported percentage of total cases of congenital / developmental infantile spasms has increased in recent years as the causes of west syndrome have become more readily identified . we report on a patient , carrying a derivative chromosome originating from the reciprocal unbalanced translocation t ( 8;9 ) ( p11.2;p22 ) , presenting with macrocephaly , west syndrome , severe mental motor retardation and hypotonia . as far as we know , the patient was a boy , now 3 years of age , born to healthy non - consanguineous parents after an unremarkable pregnancy . he presented at 5 months of age with hypotonia and craniofacial anomalies , including macrocephaly ( head circumference ; 48 cm ) , low - set ears , coarsened appearance and downslanting palpebral fissures , long eyelashes , long philtrum , hypertelorism and a short , broad nose [ figure 1 ] . we have obtained consent from both parents for publication of pictures of patients in this journal . family medical history was remarkable for the presence of severe mental motor retardation , epilepsy and macrocephaly in one paternal aunt , one uncle , and one paternally related male cousin . laboratory analyses revealed a normal complete blood count and normal blood chemistry values , including levels of lactate , pyruvate , and ammonia . magnetic resonance imaging revealed a dysmorphic corpus callosum with an underdeveloped splenium and absent rostrum together with volume loss of white matter and dilated perivascular spaces [ figure 2 ] . he began to display clusters of sudden flexions of the head , trunk , arms , and legs that occurred several times daily and particularly soon after arousal from sleep at 8.5 months of age . we examined the affected 5-year - old paternally related male cousin whose physical and neurologic examination was similar to that of our patient and whose medical history was consistent with west syndrome . including macrocephaly low - set ears , coarsened appearance , downslanting palpebral fissures , long eyelashes , long philtrum , hypertelorism and a short , broad nose sagittal t1-weighted image shows dysmorphic corpus callosum with an underdeveloped splenium and absent rostrum cytogenetic analysis of both the patient and his cousin was performed on peripheral blood lymphocyte cultures . to obtain metaphase spreads , peripheral blood lymphocyte cultures were performed in rpmi 1640 culture medium containing 20% fetal calf serum , l - glutamine , and penicillin - streptomycin . the cultures were incubated for 72 h at 37c and colcemid were added after 70 h to arrest cell division . chromosomes were harvested after incubation in a hypotonic solution and fixed with carnoy 's fixative containing acetic acid and methanol in a 1:3 ratio . the results of chromosome analysis revealed a karyotype reported as 46 , xy , der ( 9 ) t ( 8;9 ) ( p11.2;p22 ) [ figure 3a ] . the origin of the derivative chromosome was a familial translocation detected in our patient 's father and his cousin 's mother [ figure 3b ] . the derivative chromosome 9 originating from t(8;9 ) ( p11.2;p22 ) is seen in the middle ( b ) partial karyotype of the patient 's father with the translocation chromosomes der ( 8) and der ( 9 ) as well as normal 8 and normal 9 genetic causes should be considered as the standard program for evaluation of the etiology of infantile spasms . the best - documented chromosomal anomalies associated with west syndrome include 1p36 monosomy , chromosome 15 anomalies , trisomy 21 , partial duplication of chromosome 2p , monosomy 4p , williams syndrome , smith magenis syndrome , pallister - killian syndrome and monosomy 18p . both subjects had an unbalanced karyotype with a derivative chromosome 9 resulting from a familial translocation between chromosomes 8p and 9p . the karyotypes of the parents were 46 , xx , t ( 8;9 ) ( p11.2;p22 ) and 46 , xy , t ( 8;9 ) ( p11.2;p22 ) , which means that the translocation is of maternal origin in one case and of paternal origin in the other . ( 2008 ) have distinguished two different groups of patients : the first group encompasses those patients that have the clinically recognizable phenotype of 9p deletion ( consensus phenotype consisting of trigonocephaly , small palpebral fissures , flat nasal bridge with anteverted nostrils , long philtrum , and micro-/retrognathia ) ; the second group encompasses those patients who , although they have 9p deletion , do not meet the criteria for the consensus phenotype ( in particular , they lack the trigonocephaly ) . our patient does not present with trigonocephaly but presents with other facial dysmorphisms considered characteristic for the 9p deletion phenotype , such as a flat nasal bridge and long philtrum . in partial trisomy 8p , the clinical picture of the patients comprises hypotonia , structural brain abnormalities , facial anomalies that include a large mouth with a thin upper lip , a highly arched palate , a broad nasal bridge , an abnormal maxilla or mandible , malformed , low - set ears , and orthopedic anomalies . the phenotypes of our patient and his cousin were not similar to both described phenotypes , with the exception of some similarities . we also know that the 8p deletion phenotype differs according to the partner translocation chromosome . thus , we believe that these siblings are the first in the literature with west syndrome and derivative chromosome 9 , which emphasizes the importance of chromosome analysis in cases with congenital abnormalities . an etiologic diagnosis of west syndrome is very important because it may lead to initiation of a specific therapy that could markedly improve the long - term developmental outcome . another important reason , for establishing an etiologic diagnosis , is that some of the disorders are genetic in nature , which may carry a significant risk of recurrence in offspring like in our patient . in conclusion , although west syndrome is not a rare finding among chromosomal abnormalities , partial trisomy 8p together with partial monosomy 9p , resulting from a familial translocation , has not , to the best of our knowledge , previously been reported .

west syndrome is classified according to the underlying etiology into an acquired west syndrome , a congenital / developmental west syndrome , and west syndrome of unknown etiology . causes of a congenital / developmental west syndrome are extensive and include chromosomal anomalies . we report on a patient carrying a derivative chromosome originating from the reciprocal unbalanced translocation t ( 8;9 ) ( p11.2;p22 ) and presenting with macrocephaly , west syndrome , severe mental motor retardation and hypotonia . as far as we know , this is a new chromosomal anomaly associated with west syndrome .

they constitute 2% of all skin tumors and reported incidence rates differ from 0.7% to 9.0% . msc originate most commonly from breast , lung and gastrointestinal tissues , and are recognized as a poor prognostic factor . in this paper , we present a case of relapsing gastric adenocarcinoma with signet - ring cell ( src ) morphology , which presented itself as cutaneous nodular lesions about 4 months after the cessation of chemotherapy . a 57-year - old woman presented with a 2-month history of asymptomatic , steadily growing lesions on her face , neck and shoulders . her medical history revealed that she was diagnosed with stage iiia ( t3n2m0 ) gastric src adenocarcinoma ( srcc ) 12 months prior in an oncology clinic . at that time her surgical pathology reports revealed cancer - free margins and surgery was followed by adjuvant chemotherapy [ infusional folinic acid + 5-fluorouracil ( fufa ) ] and radiotherapy directed to the gastric lodge . about four months later after the end of the combined chemotherapy and radiotherapy , the patient had noticed several small lumps on her face and shoulders . since then , these lesions had been consistently growing . at the time of physical examination , multiple asymptomatic skin lesions consisting of two erythematous papules on her forehead , one solitary nodule on the right preauricular area , another one on her right shoulder and two prominent bright red , fleshy nodules on her neck ranging from 1.01.0 to 3.04.0 cm ( figure 1a - c ) were found . immunohistochemical staining were negative for hmb45 , cd45 , er , pr , gcdfp-15 stains , lowering the possiblity of an melanoma , a metastatic tumor of hematopoietic origin and a metastatic breast cancer , respectively- and positive for ae1/ae3 and mucicarmine indicating a glandular epithelial origin for the srcs ( figure 2 ) . since the patient was operated in another clinic , original resection material was unavailable to us for a comperative histological and immunohistochemical staining . a working diagnosis for metastatic signet - ring cell carcinoma was made on the basis of the last skin biopsises and patient s medical history , and the patient was referred to the oncology department for further evaluation . tests performed by the oncology department , including complete blood count , urea and electrolytes , liver function tests , plasma proteins , tumor markers , chest x - ray , breast , abdominal and suprapelvic ultrasound , bilateral mammography , complete abdominal magnetic resonance imaging , bilateral mammography , upper gastrointestinal endoscopy and colonoscopy , revealed no other internal focus , from which the skin lesions could originate . after the completion of the oncological examination and tests , diagnosis of the patient was established as metastatic cutaneous signet - ring cell carcinoma and she was scheduled for a second round of chemotherapy ( figure 1d - f ) . signet - ring pattern defines a specific cell shape change , during which the nucleus of the cell is pushed to the periphery due to the cytoplasmic accumulation of mucin , vacuoles or inclusion bodies , causing the cell to bear a resemblance of a signet - ring . although srcs are usually associated with malignancies ( i.e. , gastric , prostatic , breast cancers , melanoma , etc ) , and accepted as a poor prognostic factor , they can also be observed in various nonneoplastic conditions ( e.g. , pseudomembranous colitis , cystic fibrosis , ulcerative colitis ) , or after formalin fixation as a cytoplasmic shrinkage artifact . in cases without an apparent source for cutaneous srcs , first step in the differential diagnosis should be to determine whether the cells are neoplastic or not . wang et al . indicated that even in the setting of a previously diagnosed nonneoplastic disease , benign src change can be easily confused with malignant transformation and proposed that lack of the infiltration of lamina propria , rare mitosis and apoptosis and certain histochemical and immunohistochemical staining patterns ( positive for e - cadherin and negative for p53 and ki-67 ) may be in favor of a nonneoplastic origin for the said srcs . other studies about src pathogenesis have shown that malign srcs posses particular qualities , which may be helpful in developing new diagnostic techniques and treatment modalities . kobayashi et al . found out that highly differentiated colon adenocarcinoma cells were transformed into srcs , when phosphatidylinositol 3-kinase ( pi3k ) was activated . they also showed that the activation of pi3k was induced by the activation of erbb2/erbb3 complex ( a member of cell surface receptor family for epidermal growth factor ) . at the further steps of the erbb2/erbb3 pi3k cascade , p38 mitogen activated protein kinase ( mapk ) is activated , resulting in the loss of intercellular tight junctions . activation of pi3k is also known to enhance the mucin secretion ( muc4 ) , and transcriptional upregulation of muc4 is recognized to have antiapopitotic and mitogenic effects in various tumors . pik3 activation and muc4 overexpression have also been found in gastric adenocarcinomas , which further supports the role of erbb2/erbb3 mentioned above , reported incidence rates of metastatic skin cancers from internal malignancies vary between 0.7 - 9.0% . a metaanalysis including 22,297 patients with visceral malignancies by krathen et al . revealed the incidence of skin metastases as 5.3% . according to this study , the most common primary visceral cancers to metastasize to skin were breast cancers ( 24.0% ) , renal cancers ( 4.0% ) , ovarian cancers ( 3.8% ) , bladder cancers ( 3.6% ) , lung cancers ( 3.4% ) , colorectal cancers ( 3.4% ) and prostate cancers ( 0.7% ) respectively . gastric cancers , despite being one of the most common cancers in the world , ( ranking 5th in worldwide frequency and 3th in the leading causes of cancer relateddeaths ) , do not develop skin metastases frequently . most common sites for metastatic spread of the gastric cancers were found to be liver , peritoneoum , lung and bone . rare skin metastases of gastric cancers are usually observed as umbilical or periumbilical papules or nodules . signet - ring cell carcinoma ( srcc ) is a histologic subtype of gastric cancers which accounts for 8 - 30% of all stomach cancers and is usually associated with advanced stage cancer and recognized as poor prognostic factor . srcc has a similar metastatic spread pattern like the other gastric cancers and tends to metastasize particularly to peritoneum and intraabdominal organs ( liver , ovaries , etc . ) . cutaneous metastases of srcc are also very rare and may present as nodular lesions , such as in this case , mimick benign other nonneoplastic or benign entities such as erysipelas , scars or contact dermatitis , complicating the diagnostic process in the absence of an known primary tumor . due to their mucin content and epithelial origin , malignant cells of srcc can be identified with certain stains . mucicarmine , periodic acid - schiff stains ( pas ) are helpful in identifying the mucin content and ae1/ae3 pancytokeratin antibody can be used to confirm the epithelial origin of the srcs and to distinguish normal , metaplastic and neoplastic cells . since adenocarcinomas originating from tissues other than gastric mucosa may also present with srcs , other immunohistochemical investigations may be required in the differential diagnosis . immunohistochemical staining can be particularly helpful , if malignant cells of the primary tumor have conserved adequate level of differentiation , these cells will continue to synthesize tissue specific proteins , which can be identified by immunohistochemcial staining [ i.e. , thyroid transcription factor ( tff-1 ) is heavily expressed in lungs and gross cystic disease fluid protein-15 ( gcdfp-15 ) may be found in well - differentiated breast cancers ] . identification of the tumoral cytokeratin and mucin expression profiles may also help particularly to distinguish adenocarcinomas [ i.e. , mucin5a ( muc5a ) , muc2 and cytokeratin 20 ( ck20 ) are commonly expressed in colorectal carcinomas , muc1 and ck7 can be found in breast cancers ] ( table 1 ) . signet - ring cell may be seen in various neoplastic and nonneoplastic diseases , but these uncommon cells are frequently associated with malignancies and usually develop due to increased intracellular mucin content . when srcs are found in a skin biopsy , a high level of suspicion for a cancer should be aroused . since skin metastases can be observed as the first sign of a clinically - silent malignancy , a detailed medical history should be taken and a thorough physical examination must be conducted for a possible tumor . appropriate tests should be ordered considering the age and sex specific risk factors for the patient . in case of a cancer of unknown primary origin , histological and immunohistological staining methods would be useful to determine the primary tumor . in very rare instances , when the common histological staining methods are inadequate to distinguish a benign signet - ring change from a malign signet - ring cell transformation , observation invasion of lamina propria and a high intracellular pi3k activity may favor a malign cellular transformation . actually , mapk and pi3k signaling pathways are now considered as possible therapeutic targets in various cancers and various methods including western blotting , phospho - flow cytometry and immunofluorescence staining have been proposed for measuring mapk and pi3k activity . unfortunately , there is nt yet an established and universally accepted method and the proposed methods require specific laboratory equipment and medical laboratory technicians with certain qualifications , preventing the widespread routine use . for similar reasons , we also could not measure the pi3k activity in our specimen . but , despite these facts , mapk and pi3k pathways seem to be as promising targets for future diagnostic and therapeutic interventions .

up to 10% of patients with visceral malignancies develop skin metastases during their clinical course and these metastases constitute about 2% of all skin cancers . skin metastasis may be the first sign of a clinically silent visceral cancer or represent recurrence of an internal malignancy . in both situations , they are associated with poor prognosis , which can partly be attributed to underdiagnosis . in this paper , a case of relapsing gastric adenocarcinoma , which manifested itself as asymptomatic cutaneous papules and nodules on a patient s head and neck , is reported and histopathological approach to the cutaneous lesions containing signet - ring cell is briefly reviewed .

end stage renal disease ( esrd ) is a serious health problem among children , especially among children aged < 2 years . it has particular features in terms of etiology and therapeutic modalities . the management of infants with esrd aims , on the one hand , at increasing patients longevity and , on the other hand , at improving growth and life - quality . esrd incidence among children is estimated at 5.5 new cases per million inhabitants per year in europe , 10.6 in canada , and 4 in japan . in developed countries , prognosis of pediatric esrd has improved ; most children can have access to chronic peritoneal dialysis ( pd ) , hemodialysis , or kidney transplantation . conversely , in developing countries , esrd is a serious cause of morbidity and mortality . managing esrd is particularly challenging due to patients late presentation , poor socioeconomic conditions , and inadequate health care infrastructure support . some data found in nigerian series report an incidence of 4 cases / million inhabitants per year . in tunisia , a single epidemiological study , in 1993 , examined the esrd epidemiological aspects , since then no data about ersd among infants has ever been collected . the aim of our study was to describe esrd etiologies and outcomes among tunisian infants . this retrospective study included all infants with the esrd diagnosis who presented to the department of pediatric nephrology at charles nicolle hospital in tunis from january 1998 to december 2013 . esrd patients were defined as those who needed renal replacement therapy ( rrt ) to sustain life . we excluded foreign - born patients , those whose death occurred within a short time . individual patient data included date of birth , gender , primary renal disease , starting rrt date , treatment modality at start of rrt , and important events such as death . we studied 157 children with esrd who were treated in the pediatric department at charles nicolle hospital . 24 children ( 15.2% ) were infants ; the sex ratio was equal to 2 . the mean age of infants with esrd at presentation was 8 months ( range , 121 months ) . laboratory findings were as follows : mean serum creatinine : 5.6 ( 3.19 ) mg / dl , mean blood urea nitrogen : 95 ( 18243 ) mg / dl , and hemoglobin : 6 ( 3.512 ) g / dl . hypocalcemia was noticed in 13 infants and hyperphosphatemia in 20 infants [ table 1 ] . patient 's characteristics at presentation the main causes were congenital anomalies of the kidneys and urinary tract ( cakut ) ( 9 infants ) , inherited renal disease ( 9 infants ) , hemolytic and uremic syndrome ( 3 cases ) , and unknown origin ( 3 cases ) . all patients were treated by pd , all infants had double - cuff straight tenckhoff catheter , 20 infants were treated with continuous ambulatory pd and 4 infants with automated pd ; 17 infants had peritonitis . this study presents esrd etiology and outcome among tunisian infants . to the best of our knowledge , none of the studies have so far focused exclusively on infants with esrd and , therefore , our study adds new insights to esrd etiologies and outcome among tunisian infants . it has particular characteristics in terms of etiology and therapeutic modalities . over the last few years the rising incidence of rrt was attributed to the increase of dialysis provision to younger children by virtue of improvements in techniques for nutritional and dialysis support . the male predominance noted in this study is similar to observations in many other reports . as in the other studies , male predominance is due to the higher proportion of males among patients with cakut . in our series , growth retardation was noticed in 14 patients , but only 9 patients received growth hormone . reports from europe , australia , japan , kuwait , turkey , and the united states show that cakut are the leading causes of esrd and are responsible for between 34% and 52% of esrd cases among children ; esrd in younger children is mostly due to cakut . the high prevalence of inherited renal disease among infants in our study is attributed to the high proportion of consanguinity ( 58% ) . environmental , ethnic , and other differences might explain the different occurrences of primary renal diseases in europe and in other parts of the world as compared with our findings . access to chronic rrt has improved the esrd outcome in developed countries . a tunisian research dated 1997 found that the therapeutic abstention rate attained 19% . in our study , all infants received rrt . a korean study reported a frequency equal to 21.7% of peritonitis among infants undergoing pd . a british study published in 2010 reported that the peritonitis incidence was estimated at 66.66% . long - term survival rate for children with chronic rrt in developed countries is 79% at 10 years and 66% at 20 years . major death causes identified in this study were infections , followed by cardiovascular causes as is reported in the literature . in tunisia , management of children with esrd has known progress in recent years ; yet , mortality rate in infants with esrd is high . the current high rate of mortality can be improved by earlier referral , better nutrition , family support , and enhanced access to treatment modalities .

end stage renal disease ( esrd ) in infants has particular features in terms of etiologies and therapeutic modalities . the aim of our study is to describe the etiologies and the esrd outcomes among tunisian infants . this retrospective study was conducted over 15 years ( from january 1998 to december 31 , 2013 ) in the pediatric department at charles nicolle hospital . in total , 157 pediatric patients had esrd . the mean incidence was 4.25 million children . the study involved 24 infants ; the sex ratio was equal to 2 . the mean age at diagnosis of esrd was 8 months ( range , 121 months ) . growth retardation was noticed in 14 patients . the main causes were congenital anomalies of the kidneys and urinary tract ( 9 infants ) and hereditary renal disease ( 9 infants ) . all patients were treated with peritoneal dialysis ; 16 infants presented peritonitis . mortality rate was about 28% . the leading causes of death were cardiovascular diseases and infections .

regular physical activity is an important strategy to improve glycemic control and reduce cardiovascular risk factors in people with type 2 diabetes . systematic reviews found that aerobic exercise such as walking , jogging , and gardening reduced the hemoglobin a1c value by about 0.6% . many studies showed that diabetes mellitus is a major risk factor for cardiovascular disease(cvd ) . mortality associated with cvd in people with type 2 diabetes is significantly higher than in nondiabetes people . dyslipidemia in diabetes mellitus can include all the types of dyslipidemia identified in the general population . these metabolic factors are high plasma triglyceride , low high - density lipoprotein ( hdl)-cholesterol , and increase in small dense low - density lipoprotein ( ldl)-cholesterol particles . physical activity interventions for people with type 2 diabetes have frequently been based on the transtheoretical model ( ttm ) . the model proposes that exercise behavior change is a dynamic process , in which individuals progress or relapse between five main stages . the five stages of motivational readiness to change are precontemplation , contemplation , preparation , action , and maintenance . for example , a person who is not even thinking about increasing his physical activity is considered to be in the precontemplation stage . if the person is thinking about becoming more active but has not taken any actual steps toward that goal is considered to be in the contemplation stage . in preparation , the person is engaging in some physical activity , but not yet meeting the national guidelines of physical activity . other clients may be exercising regularly ( action ) and can be considered in maintenance once regularly active for at least 6 months . it is important to note that this model is considered cyclical as people tend to move back and forth through these stages of change . we conducted an 8-week physical activity program with 50 type 2 diabetes female patients and referred to diabetes research center in hamadan . patients who were physically inactive and in precontemplation , contemplation , and preparation stages were selected and divided into intervention and control groups ( 25 participants in each group ) . data were collected using physical activity stage of change questionnaire and measuring of the metabolic factors including hba1c , hdl , ldl , total cholesterol , and triglycerides ( tgs ) by laboratory tests . after need assessment from participants and determination of physical activity stage of change , stage - matched physical activity program was conducted for interventional group but control group were not educated about regular physical activity . the questionnaire included two parts : first part assessed demographic variables of patients such as age , weight , height , marital status , job , education , and membership in a sport club . second part was marcus algorithm ( with yes / no answers ) physical activity stage of change . first , patients were educated about physical activity by attending three - session educational programs . we applied several methods in these sessions such as lecturing , question and answer meetings , group discussion , and providing pamphlet and handout educational booklets . sessions related to benefits of regular physical activity , importance of planning in physical activity , and introduction to amplifiers of regular physical activity . second , stage - matched physical activity program was planned for 8 weeks ( three sessions per week ) in the women 's sport garden . effectiveness of educational intervention was evaluated using international physical activity questionnaire ( ipaq ) , physical activity stage of change algorithm , and laboratory tests of metabolic factors after 3-month follow - up . finally , data were entered into spss software version 16 and analyzed using one - sample t - test , chi - square , fisher 's exact test , mann whitney , wilcoxon , kruskal wallis , and friedman tests . the age range of the participants was 3560 years with a mean age of 50.7 years . measurements of body mass index ( bmi ) showed that 16% of participants had standard bmi , 2% were underweight , and 82% had nonstandard bmi ( overweight and obese ) . investigation of physical activity stage of change in both groups before intervention showed that 14 patients ( 28% ) were in the precontemplation , 21 ( 42% ) in the contemplation , and 15 ( 30% ) in the preparation stages of change . no significant differences were found between the groups before educational intervention ( p - value > 0.05 ) . our findings showed no significant differences in metabolic factors between both the intervention and the control groups before education . after the physical activity program , the mean of metabolism factors had decreased in the intervention group . therefore , the reduction in glycosilated hemoglobin , hdl , ldl , and cholesterol was significant compared with that before the educational program ( p - value < 0.05 ) . however , significant decrease in tg levels was not found [ table 1 ] . comparison of metabolism factors after physical activity program showed significant decrease in glycosilated hemoglobin in the intervention group than in the control group ( p - value < 0.05 ) . comparison of metabolic factors before and after educational intervention in intervention group the finding of physical activity stage of change showed patients in the intervention group significantly moved through stages of change in physical activity after educational program ( p - value < 0.05 ) than those in the control group . before implementing the educational program evaluation of physical activity after educational program in the control group showed that 22 ( 88% ) patients had low - intensity physical activity and 3 patients ( 12% ) had moderate - intensity physical activity , whereas in the intervention group , 11 ( 44% ) patients had low - intensity physical activity , 10 patients ( 40% ) had moderate - intensity physical activity , and 4 patients ( 16% ) had vigorous physical activity . hence the difference between the groups in regular physical activity was statistically significant ( p - value < 0.05 ) . findings indicate a significant relationship between physical activity intensity and moving in stage of change ( p - value < 0.05 ) . findings showed that patients with low - intensity physical activity ( physical inactivity ) were in the early stages of change and those with moderate intensity or vigorous physical activity were in the final stages [ table 2 ] . considering the importance of bmi in diabetes management and its role in the development of cvd risk factors , majority of these patients had nonnormal bmi and 82% of them were overweight and obese . maori et al . reported abnormal bmi ( overweight and obese ) in diabetes patients in a population study . metabolic control improved in the intervention group than in the control group [ table 1 ] . sigal et al . did not find significant differences in levels of tg , cholesterol , hdl , and ldl after 22 weeks physical activity intervention . this may be due to other factors that affect blood lipids , such as nutrition and eating habits . long - term physical activity program should be followed to reduce blood lipid profile ; however , the decrease in lipid profile was not significant . kevin and hughes investigated the impact of educational program in preparation for changes in diabetes patients and have reported significant reduction in glycosilated hemoglobin . allen , kim , and kirk , in similar studies , report significant reduction in glycosilated hemoglobin after 3 - 6 months of physical activity program . the results of the present study are consistent with their studies . according to the ttm , participation in educational interventions he / she passes through a series of steps that can be progressive , backward , or rotative . after 3 months of educational intervention , 4% of the patients in control group entered action stage and 44% in intervention group entered action stage . studied 272 women during 28 weeks and 1 year follow - up training program based on stages of change model and showed positive impact of educational program in transition participants from early to late stages of change . after 1 year follow up , 83% in the intervention group and 17% in the control group were in action and maintenance stages . study of iranian women with osteoporosis . in our study , transition of patients in early stage to late stage could be related to educational strategies used . stage of change is based on the hypothesis that educational programs can improve people through stage of change . regular physical activity is strongly associated with metabolic control improvement , reduction in cvd risk factors , and increasing quality of life in type 2 diabetes patients . in addition , to maintain and improve general health , diabetes patients must participate in moderate - intensity physical activity for five sessions per week for at least 30 minutes . however , 80% of type 2 diabetes patients are not physically active and the rate of relapse is higher than in normal population . although , diabetes patients have reported that they received less support , education , and encouragement than others . according to our findings , educational program show a great impact on physical activity level in the intervention group , that is , 56% have at least moderate - intensity physical activity . studies on inactive diabetes patients showed significant differences in physical activity between intervention and control groups . allen et al . reported significant increase in physical activity level after 8 weeks of physical activity program based on the theory of self - efficacy . according to the ttm , adoption of healthy behavior increased with progress in stage of change . findings of our study indicate a positive relationship between physical activity level and stage of change . design and implementation of physical activity intervention can promote metabolic control in diabetes patients and help them cope with diabetes .

background : regular physical activity has an important role in reducing cardiovascular risk factors and improving metabolic control in patients with type 2 diabetes . this study aims to investigate the effect of physical activity stage - matched intervention on metabolic control in type 2 diabetes patients.materials and methods : an 8-week physical activity program conducted with 50 type 2 diabetes females who were physically inactive and in precontemplation , contemplation , and preparation stages of change . participants were divided into intervention and control groups ( each group , n = 25 ) . data were collected by physical activity stage of change questionnaire and metabolic factors were measured by laboratory tests before initiation program . subsequently , stage - matched physical activity program was conducted for the interventional group . control group received routine education from the diabetes center . after 8 weeks , physical activity questionnaire filled out by participants and metabolic factors were evaluated by a laboratory test.results:findings showed patients in the intervention group and compared with control group significantly moved through stages of change after physical activity program ( p - value < 0.05 ) . evaluation of physical activity after educational program demonstrated that the intervention group adopted regular physical activity more than the control group and also the difference between groups was significant ( p - value < 0.05 ) . our findings indicate a significant relationship between physical activity level and moving in stages of change in the intervention group ( p - value < 0.05 ) . comparison of metabolism factors after physical activity program showed significant decrease in glycosilated hemoglobin in the intervention group than the control group ( p - value < 0.05 ) . however , significant differences between groups were not observed in other metabolism factors.conclusion:designing and implementing physical activity stage - matched intervention can improve metabolic control and management of type 2 diabetes .

nonspecific low back pain ( nslbp ) is a widespread problem with major social and economical consequences2 , 3 . nslbp comprises 85 to 90% of low back pain diagnoses and is defined as low back pain not attributable to a recognizable , known specific pathology , e.g. , infection , tumor , osteoporosis , or fracture1 , 4 , 5 . the majority of patients with low back pain are successfully treated in primary care ; approximately 10 to 15% will develop chronic ( more than three months ) symptoms6 . in the general population , the prevalence of lbp ranges from 12 to 33% , the one - year prevalence ranges from 22 to 65% , and the lifetime prevalence ranges from 11 to 84%7 . nslbp is a mechanical pain of musculoskeletal origin in which symptoms vary with the nature of physical activities8 . nslbp manifests as pain , muscle tension , or stiffness that is localized below the costal margin and above the inferior gluteal folds and is not attributed to a specific pathology with or without leg pain involvement10 , 11 . it is estimated that 80 to 90% of patients with acute lbp disorders recover within six weeks13,14,15 . however , 10 to 20% will develop chronic lbp ( clbp)14 , 16 , 17 . approximately 70 to 80% of health care and social costs are attributed to the 10 to 20% of patients with clbp14 , 18,19,20,21,22 . once lbp becomes chronic , it can be a significant source of long - term disability and absence from work and consequently represents a high socioeconomic burden on health - care systems in developed countries4 , 20 , 23 . nonspecific chronic low back pain ( nsclbp ) limits activity in individuals younger than 45 years of age in industrialized countries and is considered to be one of the most common reasons for individuals to consult a physician23 . in general , the aims of conservative treatment for lbp are to reduce pain , improve activities of daily living ( adl ) , and to teach patients how to cope with pain15 . commonly prescribed treatments for nsclbp such as acupuncture , traction , transcutaneous electrical nerve stimulation , facet injections , laser therapy , massage , therapeutic ultrasound , and lumbar supports have little or no evidence to support their use24 . none of the commonly used interventions can truly offer a solution to the problem of nsclbp . in most patients , reductions in the number of clbp - related complaints are minimal while pain continues unabated1 , 25 , 26 . several types of tape and their associated application methods are available , with different underlying philosophies regarding their modes of action . a new approach for the treatment of nsclbp is to support the affected area , relax the muscles , and reduce pain sensation and is referred to as kinesio taping ( kt ) . unlike conventional athletic tape , kinesio tape is thin and has elastic mechanical properties , similar to the skin , to allow a normal range of motion . kinesio tape was originally developed in japan by kase and wallis27 and its use has recently increased28 . it was observed that kt has multiple functions : 1 ) improvement of muscle function ; 2 ) gathering fascia to align tissue in the desired position ; 3 ) activation of the circulation ( blood and lymph ) by lifting the skin over areas of inflammation , pain and edema ; 4 ) deactivation of the pain system by stimulating cutaneous mechanoreceptors ; 5 ) supporting the function of the joints by stimulating proprioceptors , correcting the direction of movement and increasing stability ; and 6 ) segmental influences28 , 29 . the aim of the present study was to compare the effects of kinesio taping and traditional treatment of nonspecific chronic low back pain . the present study was conducted in an outpatient physical therapy clinic in cairo university hospitals . a total 40 patients with nsclbp diagnosed by orthopedic physicians were referred to the outpatient physical therapy clinic ( 30 male and 10 female ) with a mean age of 34.87.54 years , mean weight of 80.2515.88 kg , and mean height of 168.78.6 cm and randomly divided into two groups . the inclusion criterion for nsclbp was a duration of at least three months with no other pathological problems . the study design was a randomized , single - blinded clinical trial with a pre- and post - test groups design . this study was reviewed and approved by the ethical committee of king saud university . group 1 ( n=20 ) undergwent conventional physical therapy with kinesio taping ( kt ) , whereas group 2 ( n=20 ) underwent conventional physical therapy without kt . the conventional physical therapy management consisted of stretching exercises for the back , iliopsoas , and hamstring muscles and strengthening exercises for the abdominal muscles . three sets of stretching exercises , each involving a 30-sec hold and 30-sec of rest repeated three times , were performed in three sessions per week over four weeks . one set of strengthening exercises , consisting of 10 repetitions with a 5-sec hold , was performed in three sessions per week over four weeks . the kt technique : curetape ( tapeconcept ltd . , the two i - tapes were applied from the origin of the lumbar erector spinae ( iliocostalis lumborum ) to its insertion . the area to be treated was clean , and free of hair , and the tape was measured while the lumbar spine was flexed to the maximum . in the case of flexion disturbances , the first 4 cm to 5 cm of tape was carefully removed from its paper backing . the base of the tape was applied to the sacrum in the neutral position . the patient was asked to perform maximum flexion of the spine , and the paper backing of the tape was removed , except for the final 4 cm to 5 cm ; the tape was then used on one side paravertebrally in the direction of the cranium under slight traction . finally , the final 4 cm to 5 cm of the tape was applied without traction . the tape was rubbed by hand several times to warm the adhesive film to achieve adhesion29 . the intervention sessions for both groups were three times per week for four weeks . outcomes of interventions were assessed for adl using the roland - morris disability questionnaire ( rmdq)30 , 31 , pain severity using a visual analogue scale ( vas)32 , and ranges of motion ( roms ) of trunk flexion and extension using the modified schober s test33 . chicago , il , usa . means , sds , t - values and p values were determined from the collected data . the unpaired t - test there were significant differences in pre- and post - intervention measures of pain , adl , and trunk flexion and extension roms in each group ( p<0.05 ) ( table 1table 1 . pre - and post - intervention scores of pain ( vas ) and activities of daily living ( rmdq ) and roms of trunk flexion and extensionstudy groupspain mean sdrmdq mean sdflexion ( cm ) mean sdextension ( cm ) mean sdpretestpost - testpretestpost - testpretestpost - testpretestpost - testgroup 16.21.461.8 * 10.33.2110.85 * 61.16.31.1 * 1.40.61.40.5*group 22.91.43.724.72.975.56.41.26.611.70.61.630.4group 1 , conventional pt + kinesio taping : group 2 , conventional pt only . * within - group comparison ( p<0.05 ) . between - group comparison ( p>0.05 ) . ) . however , comparison between groups showed no significant differences ( p>0.05 ) in pre- and post - intervention measures of study outcomes such as pain ( 0.571 ) , adl ( 0.671 ) , flexion ( 0.538 ) , and extension ( 0.765 ) . group 1 , conventional pt + kinesio taping : group 2 , conventional pt only . the aim of this study was to compare physical therapy exercise interventions and use of kt in the treatment of clbp using the changes in clinical outcome ( pain , disability ) and physical function ( range of motion , strength ) . mechanical lbp is due to abnormal short or prolonged stresses that affect the muscular components of the lumbar and pelvic regions34 . muscle imbalances of the lumbopelvic region , as a result of repetitive injury or physical stress , may contribute to the lengthening and weakening of the phasic muscles , while the postural muscles ( antigravity ) become tight and overactive35 . hypertonic postural muscles can lead to ischemia and reduced blood circulation , further aggravating pain35 . this imbalance modifies body movement , putting strain on muscles , tendons , ligaments , and joints ; consequently , the end result is often lbp36 . it has been suggested that a normal lumbar lordosis protects the posterior spinal structures from excess strain and acts as a shock absorber during sudden applied vertical forces37 , 38 . therapeutic exercise programs therefore include stretching of tight muscles , and strengthening of weak muscles , thus restoring muscle balance , strength , and flexibility . group 1 , there was improvement in pain , adl , and trunk flexion and extension roms between before and after intervention , as exercises can be useful for ( 1 ) improving impairments in function , including reduced back flexibility , strength , and cardiovascular endurance ; ( 2 ) reducing back pain intensity when performed regularly ; and ( 3 ) reducing back pain - related disability because it may be used as a tool to lessen excessive fear and concerns about back pain and to alter stifling pain attitudes and beliefs . in group 2 , there was improvement in pain , adl , and trunk flexion and extension roms between before and after the intervention , as the flexibility of the tape results in the skin being lifted ( convulsion ) , which creates a wider space between the skin and the muscle , leading to improvement of blood circulation and drainage of lymphatic fluids in the taped area and dramatically decreased pain and improved roms and adl . chronic nonspecific low back pain is a significant health condition with high prevalence worldwide and is associated with enormous costs to society . clinical practice guidelines show that many interventions are available to treat patients with chronic low back pain , but the vast majority of these interventions have a modest effect in reducing pain and disability . an intervention that has been widespread in recent years is the use of elastic bandages called kinesio taping38 . kinesio tape is a more elastic tape that does not restrict movement and can be stretched up to 120% to 140% of its original length compared with conventional tape , allowing a full rom . in recent years , kt has been commonly used in the field of physical therapy , orthopedics , and sports medicine39 . , that investigated the effect of a combination of exercise and kt on pain and adl in patients with clbp40 . our findings in terms of reducing lbp were consistent with the results of paoloni et al . , who observed a highly significant reduction in pain , measured using a vas , after four weeks of treatment with kt in conjunction with exercise . although the mechanism through which kt acts on musculoskeletal conditions is not yet clear , it is hypothesized that kt applies pressure to the skin or stretches the skin and that this external load may stimulate cutaneous mechanoreceptors ( large myelinated fibers ) and thus inhibit pain transmission according to the gate control theory28 , 29 . melzack and wall proposed the gate control theory , which posits that the spinal cord contains a neurological gate that either blocks pain signals or allows them to continue on to the brain41 . , we observed a highly significant reduction in disability , measured using the rmdq , in the kt group . this reduction in disability could be attributed to the younger age of the subjects in the kt group ( 34.8 years ) in our study when compared with the age of the subjects ( 62 years ) in the studies of paoloni et al28 , 29 . previous studies have suggested that kt may enhance proprioceptive afferent feedback28 , 29 , 46 , 47 . improved trunk rom may be attributed to an increased recruitment in the motor units of the lumbar erector spinae muscles to perform the activity due to increased proprioceptive stimulations . applying pressure and stretching the skin at the extremes of motion , similar to joint mechanoreceptors , can stimulate cutaneous mechanoreceptors and signal information of joint movement or joint position48 , 49 . when applied to clbp patients , kt leads to pain relief and lumbar muscle function normalization after application , although these effects persisted over a short period50 . a physical therapy exercise program that involves stretching of the back , hamstring , and iliopsoas muscles and strengthening of the abdominal muscles combined with use of kt may be effective in the treatment of nsclbp in terms of relieving lbp , increasing the ranges of pain - free active trunk flexion and extension , and improving adl51 . comparison between the two groups revealed that there were no significant differences in pain , adl , and rom of trunk flexion and extension . a physical therapy exercise program that involves stretching of the back , hamstring , and iliopsoas muscles with kt or without kt may be effective in the treatment of nsclbp in terms of relieving lbp , increasing the ranges of pain - free active trunk flexion and extension , and improving adl .

[ purpose ] nonspecific low back pain ( nslbp ) is a very common but largely self - limiting condition . several types of tape and their associated application methods are available for different conditions . the aim of the present study was to observe the effect of kinesio taping ( kt ) compared with traditional management of nslbp . [ subjects and methods ] forty male and female patients with a mean age of 34.87.54 years were randomly divided into two groups ; group 1 ( n=20 ) which underwent conventional physical therapy with kt , and group 2 ( n=20 ) , which underwent only conventional physical therapy . the intervention sessions for both groups were three times per week for four weeks . outcomes were assessed for activities of daily living ( adl ) using the roland - morris disability questionnaire , pain severity using a visual analogue scale , and ranges of motion ( roms ) of trunk flexion and extension using the modified schober s test . [ results ] significant differences in measures of pain , adl , and trunk flexion and extension roms were observed post intervention within each group . in comparison , there were no significant differences in measures of pain , adl , and trunk flexion and extension roms post intervention between groups . [ conclusion ] a physical therapy program involving strengthening exercises for abdominal muscles and stretching exercises for back , hamstring , and iliopsoas muscles with or without kinesio taping was beneficial in the treatment of chronic low back pain .

goniometry , the measurement of joint angles , has been used as a staple in human physical therapy since the 1970s [ 15 ] . it is commonly used as an objective measure of joint and muscle disease in addition to being used for patient assessment following joint or muscle trauma [ 68 ] . goniometry is also regularly used in the human sector as an objective assessment of healing / improvement in cases of neurologic rehabilitation . specifically , goniometry has successfully been used in patients receiving rehabilitation for diseases ranging from cerebral palsy [ 9 , 10 ] , to duchenne muscular dystrophy , to spinal cord injury . in veterinary medicine , goniometry is used to assess outcome objectively in canine and feline patients undergoing physical therapy while recovering from orthopedic and neurologic disease [ 1316 ] . in the veterinary literature , there remain only a few published reports related to physical rehabilitation and the neurologic patient [ 1719 ] . one of the most common neurologic diseases for which rehabilitation is a component of therapy is type 1 intervertebral disc disease . type 1 intervertebral disc disease was originally described by hansen in the 1950s [ 20 , 21 ] . disc desiccation leads to weakening of the annulus fibrosus and eventual herniation of the nucleus through the annulus and subsequent spinal cord compression . dachshunds are the most common breed of dog affected by disc disease and herniation [ 22 , 23 ] . between 19 and 24% of dachshunds , within their lifespan , will suffer from thoracolumbar disc disease [ 22 , 23 ] . the majority of disc herniation occurs in the thoracolumbar spine and results in pelvic limb weakness , leading to possible surgery and postoperative rehabilitation therapy . for this reason , there is a significant need for reported range of motion measurements in miniature dachshunds , as a breed . having published joint angle measurements for the pelvic limbs in miniature dachshunds would allow veterinary physical rehabilitation practitioners an objective means to guide and assess physical rehabilitation in their patients . having objective data on limb girth measurements for miniature dachshunds presenting with various degrees of pelvic limb paresis would also be prudent as muscle atrophy is a realized sequela to neurologic injury including thoracolumbar disc extrusion . one difficulty with joint angle measurements in animals versus humans is the variety of limb shape and girth differences among breeds and between animal species . joint angles differ not only between dogs and cats but also between different dog breeds [ 13 , 14 , 25 , 26 ] . to date , the use of goniometry has been validated in both labrador retrievers and cats . joint angles have also been measured and reported for mixed breed dogs and greyhounds . a study by benson et al . compared joint angles between two breeds of dog , this study determined that there was variability between values for both dog breeds ; the final conclusion being that one universal table for normal joint angle values may not be applicable between dog breeds . thus , there is a need for published range of motion measurements in a variety of dog breeds . the aims of this paper are ( 1 ) to report the mean and median pelvic limb joint angles and limb girth measurements in miniature dachshunds presenting with ambulatory paraparesis , nonambulatory paraparesis , and paraplegia secondary to thoracolumbar intervertebral disc extrusion and ( 2 ) to compare joint angle and limb girth measurements between miniature dachshunds who present with ambulatory paraparesis , nonambulatory paraparesis , and paraplegia secondary to thoracolumbar intervertebral disc extrusion . it is our hypothesis that we will be able to successfully report the mean and median goniometry and limb girth measurements in miniature dachshunds with varying degrees of neurologic dysfunction and that there will be no significant difference in these values between groups . dachshunds that presented to the washington state university veterinary teaching hospital between april 2011 and february 2012 for thoracolumbar disc extrusion were included in the study . dogs were being recruited for a physical rehabilitation study involving surgically addressed thoracolumbar disc herniation and hydrotherapy . the project was approved by the animal care and use committee at the washington state university . dogs were excluded from the study if they did not have a thoracolumbar disc extrusion on mr imaging and if they were not taken to surgery . group 1 consisted of 3 dogs ; these dogs were ambulatory with pelvic limb paresis at the time of study inclusion . group 2 consisted of 6 dogs ; these dogs were nonambulatory with pelvic limb paresis at the time of study inclusion . group 3 consisted of 6 dogs ; these dogs were paraplegic at the time of study inclusion . all measurements were taken within 24 hours of presentation , diagnostic imaging , and surgery . awake dogs were put in lateral recumbency ; the angles of extension and flexion on the up pelvic limb were measured at the hock , stifle , and hip ( see figures 1 and 2 ) . the dog was rotated to the contralateral side and the measurements were repeated on the opposite leg . joint angle measurements were performed utilizing a previously published and validated technique . while in lateral recumbency , the girth of both the right and left pelvic limb was also measured in centimeters using a spring tape measure ( gulick ii tape measure , fitness mart , gays mills , wi ) . the technique utilized to perform girth measurements was based on a previously published and validated technique . thigh length from the greater trochanter to the distal femur at the level of the lateral fabella was measured using the spring tape measure . the thigh circumference was measured 70% distal to the greater trochanter ( see figure 3 ) . measurements were conducted by one of two certified physical rehabilitation individuals ( lal , sat ) , or a resident in neurosurgery , or a board certified neurologist ( avc , sat ) . the statistical analyses were performed using a statistical software package ( sas , version 9.3 , sas institute , cary , nc ) . mean and standard deviation as well as median values for joint flexion and extension in addition to thigh girth were calculated . mean and median flexion and extension angles were compared between groups 13 for each joint . each value was viewed independently : dog 1 left limb hock extension was one variable and right limb hock extension was a second variable . the mean and median values for joint flexion and extension in addition to thigh girth were calculated regardless of group . a standard t - test joint angle values were compared for hip , stifle and hock flexion , and extension ; girth was also compared . both goniometry values and girth were compared with a paired t - test . the median and mean angles of flexion at the hip , stifle , and hock for all three groups of dogs are recorded in table 1 . flexion angles differed between groups to a greater degree when measurements at the hip ( median values of 49 to 55 degrees and mean values of 49.1 to 54.3 degrees ) and stifle ( median values of 43.5 to 54 degrees and mean values of 46 to 56 degrees ) were made as compared to measurements at the hock ( median values of 39 to 40 degrees and mean values of 39.2 to 39.5 degrees ) . the median and mean angles of extension at the hip , stifle , and hock for all three groups of dogs are recorded in table 2 . similar to flexion angles , extension angles differed between groups to a greater degree when measurements at the hip and stifle were made as compared to the hock . median extension values ranged from 151.5 to 160 degrees for the hip and mean values ranged from 152.5 to 156.5 degrees . median values ranged from 160 to 163.5 degrees for stifle extension , while mean values were 157.3 to 164.2 degrees . median values for hock extension were 167.5 to 172.5 degrees , while mean values were 167.5 to 171.5 degrees . the median and mean pelvic limb girth measurements for all three groups of dogs are recorded in table 3 . median limb girth ranged from 22.5 to 24 cm , while mean girth ranged from 22.7 to 23.7 cm . there were no significant differences in joint angles or girth among the three groups ( ambulatory paraparetic , nonambulatory paraparetic , or paraplegic ) ; however , statistical significance was not reached ; p values ranged from 0.27 to 0.99 . when group was disregarded and values for extension , flexion , and girth combined , no differences existed . we were able to successfully measure joint angles and girth in miniature dachshunds in this study . it was found that when angles of flexion and extension between the three groups of dogs were compared , there was a trend toward measurements being more similar when made at the hock versus the stifle or hip . in our study , a variety of individuals made joint angle measurements , the trend in the data would support the idea of less variability when measurements of flexion and extension at the hock are made as compared to measurements at the stifle or hip in miniature dachshunds . this finding is different than previous canine goniometry studies wherein measurements at all joints were found to be repeatable between individuals . . found there to be high intraobserver agreement between staff members when goniometry was performed in labrador retrievers . one explanation for this difference in miniature dachshunds could be the shape of the pelvic limb in this breed and its associated muscle mass . in this chondrodystrophoid breed , the bony landmarks utilized to make reliable goniometry measurements are more challenging to palpate and reliably locate as compared to the same structures in a long - legged breed , such as the labrador retriever . similarly , the location of the thick pelvic limb thigh musculature in relationship to the inguinal fold , inherent to the miniature dachshund pelvic limb , made acquisition of limb girth measurements challenging . it is unlikely that the trend toward increased range of joint angles measured in the hip and stifle as compared to the hock between groups was secondary to the neurologic status of the patients . there was no trend toward one group of dogs having greater or lesser joint angles at one joint as compared to the next . additionally , there was no significant degree of variability in limb girth between groups of miniature dachshunds enrolled in our study . patients in this study suffered from thoracolumbar disc herniation and presented acutely after injury for work up and surgery . thus , it is unlikely either disuse or neurogenic atrophy , both of which would affect limb girth measurements , was contributing to limb girth values in these dogs . limb girth measurements proved to be challenging in this population of dogs . in this study , a previous study looking at circumference as measured at two separate locations along the femur ( 50% versus 70% of femur length ) showed it to be technically easier to make reliable measurements at a distance 70% of femur length . the researchers postulated that because this more distal location is farther from the skin of the flank it is easier to get reliable measurements . the unique shape of the dachshund leg and the close proximity of flank skin to the stifle made measurement of girth challenging . some major goals of rehabilitation in neurologic patients are maintenance of muscle strength and joint mobility in addition to the reduction of muscle atrophy . objective data such as joint angle and limb girth measurements is vital to gaging rehabilitation success in miniature dachshunds suffering from both orthopedic and neurologic injuries . we conclude that joint angle and limb girth measurements can successfully be made in the miniature dachshund but that the unique shape and muscle distribution of the breed 's pelvis make obtaining these values challenging . we also conclude that miniature dachshunds , with varying neurologic dysfunction at the time of range of motion and limb girth assessments , show no significant difference in values when measurements are made within 24 hours of acute onset of neurologic signs .

purpose . to report the mean and median pelvic limb joint angles and girth measurements in miniature dachshunds presenting with varying degrees of pelvic limb weakness secondary to thoracolumbar intervertebral disc extrusion . methods . 15 miniature dachshunds who presented to wsu - vth for thoracolumbar disc extrusion . dachshunds varied in neurologic status from ambulatory paraparetic to paraplegic at the time of measurements . results . there were no significant differences in joint angles or girth among the three groups ( ambulatory paraparetic , nonambulatory paraparetic , or paraplegic ) ( p > 0.05 ) . when group was disregarded and values for extension , flexion , and girth combined , no differences existed . conclusions . goniometry and limb girth measurements can successfully be made in the miniature dachshund ; however , the shape of the dachshund leg makes obtaining these values challenging . there were no differences in joint angle or girth measurements between dogs with varying neurologic dysfunction at the time of measurement .

in 1901 , a german surgeon , kelling , reported his views of the abdominal viscera after filling a dog 's abdomen with air and inserting a cystoscope . since then , several innovative advancements have been made in the field of laparoscopic surgery . it has also accelerated the introduction of endoscopic and laparoscopic procedures in the field of urology , general surgery , and gynecology . the advantages of laparoscopic donor nephrectomy have been well documented and include less patient discomfort , shortened hospital stay , quicker recovery and return to usual activities , and more pleasing cosmetic results . increasing experience with the technique has prompted its use for more complicated procedures , such as bilateral laparoscopic nephrectomy in adult patients with polycystic kidney disease ( adpkd ) before transplantation . we present our experience with the use of the laparoscopic technique for bilateral nephrectomy before transplantation in adpkd patients . we retrospectively reviewed the charts of all the patients who underwent pretransplant bilateral hand - assisted laparoscopic nephrectomy for adpkd between february 2000 to april 2002 . we recorded patient demographics , such as age , race , sex , renal size , indication for bilateral laparoscopic nephrectomy , and perioperative complications ( table 2 ) . all patients had end - stage renal disease ( esrd ) and were on maintenance hemodialysis . the indications for the nephrectomy were massive kidney size , uncontrolled hypertension , recurrent cyst hemorrhages with macroscopic hematuria , and frequent urinary tract infections . all procedures were performed by a single surgeon at our institution along with surgical residents assisting under direct supervision . laboratory workup included a complete blood count ( cbc ) , basal metabolic panel ( bmp ) , prothrombin ( pt ) , and partial thromboplastin time ( ptt ) . oral intake was stopped 12 hours before the procedure . a bowel preparation consisting of a gallon of polyetheleneglycol ( golytely ) hemodynamics is monitored with a central venous catheter , swan - ganz catheter , and arterial - line as needed . a pneumoperitoneum is created with the patient in the supine position . due to the lateral tilting of the operating table , repositioning of the patient the handport incision was central at the level of the umbilicus , and then this was connected to the co2 insufflactor . three to 5 trocars are placed after transillumination of the inside abdominal wall ( figure 2 ) . gerota 's fascia is then incised to visualize the kidneys . in situ aspiration of the anterior nonhilar cysts is done to reduce the size of the kidney and thereby facilitate further mobilization of the kidney to access the renal vessels . dissection is continued along the lower and upper pole of the kidney , additionally draining large cysts , until complete mobilization of the kidneys . hand - assisted laparoscopy ( hal ) as used in these cases provides the surgeon with tactile sensation and spatial orientation not available with standard laparoscopy . the kidney is manipulated into the device and morcellated with either mechanical forceps or an electrical tissue morcellator ( cook urological inc , spencer , in ) . reduction of renal size through aspiration of cyst fluid in situ precludes the need to make a sizable incision . the fascia is closed with absorbable sutures , and the skin is closed with nonabsorbable ones . port placement for left nephrectomy : 1 is the hand port . 2 and 4 are 10-mm ports . port - site needle closure system is used for closure ( a ) operative setup during laparoscopic nephrectomy . laboratory workup included a complete blood count ( cbc ) , basal metabolic panel ( bmp ) , prothrombin ( pt ) , and partial thromboplastin time ( ptt ) . oral intake was stopped 12 hours before the procedure . a bowel preparation consisting of a gallon of polyetheleneglycol ( golytely ) hemodynamics is monitored with a central venous catheter , swan - ganz catheter , and arterial - line as needed . due to the lateral tilting of the operating table , repositioning of the patient is not required ( figure 1 ) . the handport incision was central at the level of the umbilicus , and then this was connected to the co2 insufflactor . three to 5 trocars are placed after transillumination of the inside abdominal wall ( figure 2 ) . gerota 's fascia is then incised to visualize the kidneys . in situ aspiration of the anterior nonhilar cysts is done to reduce the size of the kidney and thereby facilitate further mobilization of the kidney to access the renal vessels . dissection is continued along the lower and upper pole of the kidney , additionally draining large cysts , until complete mobilization of the kidneys . hand - assisted laparoscopy ( hal ) as used in these cases provides the surgeon with tactile sensation and spatial orientation not available with standard laparoscopy . the kidney is manipulated into the device and morcellated with either mechanical forceps or an electrical tissue morcellator ( cook urological inc , spencer , in ) . reduction of renal size through aspiration of cyst fluid in situ precludes the need to make a sizable incision . the fascia is closed with absorbable sutures , and the skin is closed with nonabsorbable ones . port placement for left nephrectomy : 1 is the hand port . 2 and 4 are 10-mm ports . port - site needle closure system is used for closure ( a ) operative setup during laparoscopic nephrectomy . laparoscopic nephrectomy in patients with adpkd was first reported in 1993 with intact removal of a 2200-g specimen from a 15-cm incision . laparoscopic procedures may require more operative time to complete in patients with adpkd because of the massive renal size , surrounding fibrosis , and proximity to several vital structures . with the advent of hand - assisted techniques , hand - assisted laparoscopic surgery is associated with rapid dissection and a significantly shorter learning curve when compared with that of traditional laparoscopy . also , hal shortens the laparoscopic learning curve of the technique . longer operative times have been reported for standard laparoscopy and hal in the literature as compared with operative times with the open procedures . it is an additional option in more complex cases , allowing the surgeon to convert to hand assistance . because laparoscopic surgery is minimally invasive , it confers upon the patient superior cosmetic results , shorter hospitalization , lower morbidity , and shorter convalescence . in addition , a decrease in analgesic use , hospital stay , and convalescence will make this technique more accepted and practiced . recent literature has documented the problems experienced by adpkd patients after transplantation ( pain , recurrent infection , hemorrhage ) . nephrectomy before transplantation improved the 5-year graft survival and patient survival by 19% and 18% , respectively , among those adpkd patients undergoing pretransplantation nephrectomy . bilateral laparoscopic nephrectomy may be undertaken before transplantation in those patients with cyst - related signs and symptoms . we feel that in - situ cyst drainage , entrapment , and morcellation eliminate the need for a large incision and wound hernia formation . this also reduces blood loss , operative time , and postoperative use of parenteral analgesics . given the effectiveness and excellent convalescence associated with the laparoscopic approach , we believe more patients with adpkd may become candidates for pretransplantation bilateral laparoscopic nephrectomy . the ages ranged from 39 years to 65 years with a mean of 49.44.7 years . the mean bmi ( body mass index ) was 27.61.78 ( range , 23 to 33 ) . the average estimated blood loss was 345ml ( range , 100ml to 600ml ) per case . the operative time ranged from 150 minutes to 210 minutes , with an average of 185 minutes per case . the use of laparoscopy in general and transplantation surgical procedures has increased in recent years as more studies show the safety and efficacy of this approach . bilateral laparoscopic nephrectomy in adpkd patients appears to be safe in experienced hands . in this article , we have illustrated the use of the laparoscopic technique for bilateral nephrectomy in adpkd patients with good results . we feel that these data support the efforts to incorporate laparoscopic procedures as an alternative to open nephrectomy in pretransplant adpkd patients for bilateral laparoscopic nephrectomy

laparoscopic procedures continue to gain popularity over traditional open procedures for a number of abdominal and pelvic surgeries . with increasing experience , the application of this technique is rising because it provides an alternative , less invasive , approach to various surgical procedures . herein , we report our experience with adult patients with polycystic kidney disease , requiring bilateral laparoscopic nephrectomy before renal transplantation .

a 9-year - old male child came to the pediatric specialty dental clinic along with parents with the chief compliant of swelling in left lower lip region . the presenting illness showed that swelling present in the inner aspect of the lower lip in 73 , 74 regions [ figure 1a and b ] for past 3 months , which was initially small and progressed to the present stage . swelling was painless , and no past medical history like fever or malaise was present . ( a and b ) mucocele in lower lip , in relation to 73 , 74 ( c ) , 21 in cross bite relation on examination of the lesion , it was soft , fluctuant and palpable with no increase in temperature , oval in shape . on intra - oral examination , erupting 11 , 21 seen in which 21 was in cross bite relation [ figure 1c ] . routine blood investigations were done , and the values were in the normal range . finally , the case was diagnosed as a mucocele on the basis of the history of trauma and clinical features . the treatment was planned and explained to the parents . surgical removal of the lesion was planned and performed by placing an incision vertically ; therefore splitting the overlying mucosa and then resecting the mucocele from the base was done [ figure 2a and b ] . acrylic inclined plane was given for correction of crossbite in relation to 21 and periodically monitored and removed once cross bite corrected . parents were instructed to come for regular recall visit and patient regularly reviewed at 3 months interval for more than 30 months and no recurrence were noted [ figure 3b ] . ( a ) surgical removal of the lesion ( b ) surgically removed mucocele ( a ) sutured area ( b ) review after 7 days mucocele is a common lesion of the oral mucosa , which can affect the general population . mucocele can arise from an alteration of minor salivary glands due to a mucous accumulation . 1990 highlighted two etiological factors in mucocele : traumatism and obstruction of salivary gland ducts . mucocele of the minor salivary gland are very rarely larger in diameter and moreover always superficial . extravasation mucocele are caused by a leaking of fluid from ducts or acini to surrounding tissue . diagnosis is mainly based on clinical findings ; the appearance of mucoceles is pathognomonic and location of the lesion , history of trauma , rapid appearance , variations in size , bluish - color , and the consistency are some of the important factors to be considered before the final diagnosis are made . literatures showed oral habits such as lip biting / sucking is one of the etiologic factors for the oral lesions such as irritation fibroma and mucocele . radiographic evaluation is needed to rule out if sialoliths are considered a contributing factor in the formation of oral and cervical ranulas . the localization and determination of the origin of the lesion can be done by computed tomography scanning and magnetic resonance imaging . lipomas and tumors of minor salivary glands present no fluctuation while cysts , mucoceles , abscess , and hemangiomas show fluctuation . conventional treatment is the surgical extirpation of the surrounding mucosa and glandular tissue below the muscle layer . with a simple incision of the mucocele , the content would drain out but the lesion would reappear as soon as the wound heals . surgical excision with removal of the involved accessory salivary gland the excised tissue must be submitted to the pathological investigations to confirm the diagnosis and rule out the salivary gland tumors . in our case , mucocele once removed and submitted to the pathological department to confirm the diagnosis . laser ablation , cryosurgery , and electrocautery are approaches that have also been used for the treatment of the conventional mucocele with variable success . mucocele are mostly benign and self - limiting nature , primarily diagnosed based on clinical findings followed by definitive diagnosis based on the histopathological investigation . most of the reported literature showed lesion arose followed by trauma and habitual lip biting . hence , a school based educational awareness program for both children and parent at a 6 months interval and interception of the oral habit among children is the key factor . patient undergoing orthodontic therapy should be monitored periodically for areas of irritation in the oral mucosa . complete excision has been the easiest way of treatment choice , and recurrence has been associated if the lesion removed incompletely . our patient reviewed properly at 3 months interval for more than 30 months . during review , prognosis was excellent , and no recurrence was found .

mucocele is the most common lesion of the oral mucosa , which results from the accumulation of mucous secretion due to trauma and lip biting habits or alteration of minor salivary glands . mostly they are two types based on histological features which as follows : extravasation and retention . mucoceles can appear at anywhere in the oral mucosa such as lip , cheeks and the floor of the mouth , but mainly appear in the lip . diagnosis is mostly based on clinical findings . the most common location of the extravasation mucocele is the lower lip . mucoceles most probably affect young patients but can affect all the age groups . they may have a soft consistency , bluish , and transparent cystic swelling , history of bursting and collapsing due to which resolves themselves then refilling which may be repeated . the treatment of choice is surgical removal of the mucocele .

bilateral sagittal split osteotomy ( bsso ) is one of the most common orthognathic surgical procedures for the correction of mandibular deformities . the obwegeser - dal pont osteotomy and hunsuck modifications are widely used1 - 3 . when performing bsso , it is crucial to control the lingual split because it may result in an unfavorable fracture or inferior alveolar nerve ( ian ) damage . conventional radiographs , such as panoramic views and cephalograms , have limitations in regard to evaluation of the lingual split pattern . using cone - beam computed tomography ( cbct ) and three - dimensional ( 3d ) reconstruction plooij et al.4 and muto et al.5 evaluated the mandibular ramus split pattern in a symmetric mandible using 3d - ct . in an asymmetric mandible , the morphology and anatomy of each side differ . the length of the ramus and body , the inclination of the ramus , and the ramal volume are significantly different between the deviated side and the contralateral side6,7 . therefore , the aim of this study was to evaluate the lingual split line when performing bsso in asymmetric mandibular prognathism ; we used cbct and a 3d software program . the study group comprised 40 patients with asymmetric mandibular prognathism ( 20 males and 20 females ) who had undergone bsso from january 2012 through june 2013 in pusan national university dental hospital . patients ' age ranged from 18 to 31 years ( mean age : 23.2 years ) . the inclusion criterion comprised chin deviation > 3 mm compared to the facial midline ( mean deviation : 5.7 mm ; right / left : 17/23 ) . this study protocol was approved by institutional review board of pusan national university dental hospital , yangsan , korea ( pnudh-2013 - 036 ) . preoperative and postoperative cbct images were acquired using dct pro ( vatech co. , hwaseong , korea ) . the images were post - processed to a digital imaging and communications in medicine ( dicom ) 3.0 file ( simplant ; materialise inc . , leuven , belgium ) . the mandible was digitally isolated from the maxilla and skull and split up the midline . the deviated and contralateral sides of the mandible were rotated along the vertical axis to visualize the lingual surface of the ramus . the frankfort horizontal plane was set as the horizontal reference plane , and the mid - sagittal plane was set as the sagittal plane.(fig . b ) measurements were performed at the level of the mandibular lingula which is the reference point for horizontal osteotomy.(fig . c ) to evaluate contributing factors , we observed the position of the lateral cortical bone cut end using 3d reconstructed images . type a was positioned lingually , type b was inferior , and type c was located on the buccal side of the mandibular inferior border . all statistical analyses were conducted with pasw statistics 18.0 ( ibm co. , armonk , ny , usa ) . to evaluate intraobserver reliability , the kappa - coefficient was used for the lingual split pattern and the vertical osteotomy end . following the measurement of the ramal thickness , a paired t - test was performed to identify any significant differences between the deviated side and the contralateral side . all parameters were measured twice by one examiner 48 hours apart using the paired t - test for intraobserver reliability . preoperative and postoperative cbct images were acquired using dct pro ( vatech co. , hwaseong , korea ) . the images were post - processed to a digital imaging and communications in medicine ( dicom ) 3.0 file ( simplant ; materialise inc . , leuven , belgium ) . a 3d image analysis program was used to reconstruct the 3d images . the mandible was digitally isolated from the maxilla and skull and split up the midline . the deviated and contralateral sides of the mandible were rotated along the vertical axis to visualize the lingual surface of the ramus . the frankfort horizontal plane was set as the horizontal reference plane , and the mid - sagittal plane was set as the sagittal plane.(fig . b ) measurements were performed at the level of the mandibular lingula which is the reference point for horizontal osteotomy.(fig . to evaluate contributing factors , we observed the position of the lateral cortical bone cut end using 3d reconstructed images . type a was positioned lingually , type b was inferior , and type c was located on the buccal side of the mandibular inferior border . all statistical analyses were conducted with pasw statistics 18.0 ( ibm co. , armonk , ny , usa ) . to evaluate intraobserver reliability , the kappa - coefficient was used for the lingual split pattern and the vertical osteotomy end . following the measurement of the ramal thickness , a paired t - test was performed to identify any significant differences between the deviated side and the contralateral side . all parameters were measured twice by one examiner 48 hours apart using the paired t - test for intraobserver reliability . the lingual split line pattern was categorized into five groups according to the path of the fracture line on the lingual surface of the ramus.(table 1 , fig . 2 ) the kappa - coefficient of the intraobserver reliability was 0.91 ( p=0.000 ) . intended split pattern ( type i ) comprised 60.00% ( n=48 ) . type ii , iii , and iv accounted for 11.25% ( n=9 ) , 16.25% ( n=13 ) , and 5.00% ( n=4 ) , respectively , and a bad split ( type v ) occurred in 7.50% ( n=6 ) . there was no split pattern difference between the deviation and contralateral sides.(table 2 ) the ramal thickness at the level of the mandibular lingula was measured . on the deviated side , no significant difference was found between thicknesses on the deviated and the contralateral sides ( p<0.864 ) ; however , males had a statistically significant difference in ramal thickness.(table 3 ) the position of the lateral bone cut end was related to the lingual split pattern . in type a , type i was predominant ( 41/48 ) , and type v was absent . however , in type c , the buccal side end was observed in types iii , iv , and v.(table 4 , fig . bsso is a widely used orthognathic surgical procedure for the correction of mandibular deformities . since its initial description by obwegeser , modified procedures proposed by dal pont and hunsuck are currently in common usage1 - 3 . the important aspect of this technique is that it safely separates the proximal and distal segments in an intended direction ; it is difficult to identify the separation pattern precisely using a conventional cephalogram or a panoramic view . cbct and 3d reconstruction software provide effective means for evaluation of the facial skeleton and are currently used in large - scale studies of the maxillofacial region8,9 . due to its 3d mandibular bone reconstruction capability , cbct enables accurate assessment of the lingual surface of the ramus , which is hard to evaluate with traditional radiography . the 3d evaluation of the lingual split line pattern in a bsso procedure was first reported by plooij et al.4 they categorized the lingual split line pattern of 40 consecutive patients with symmetric mandibular hypoplasia who underwent advanced bsso into four groups . only 51% of the splits coursed as described by hunsuck3 ; 13% extended to the posterior border , 33% coursed along the outer side of the mandibular canal , and 2.5% had an unfavorable split pattern . he noted the length and position of the medial bone cut during horizontal osteotomy and reported that the likelihood of splitting according to hunsuck 's description increases when the bone cut end lies behind the mandibular foramen ; however , it decreases if the bone cut end extends through the mandibular canal . a study of mandibular prognathism performed by muto et al.5 reported a relatively high prevalence among asian populations . thirty patients were categorized into five types of lingual split patterns , and 33% were in the range of hunsuck 's description ; however , 15% suffered a buccal fracture . the most important factor influencing such a split tendency is the location of the lateral bone cut end during vertical osteotomy ; the lateral bone cut was on the buccal side of all incidences of buccal fracture . the deviated side appears to have a shorter ramal and body length than the contralateral side ; in addition , it has a smaller degree of ramal inclination , measured in the sagittal plane , and a smaller ramal volume6,7,12,13 . these measurements are based on orthodontic reference points or landmarks ; however , information regarding the thickness of the ramus or its relationship with the ian , which should be considered for bsso , can not be obtained . the aim of this study was to evaluate whether the lingual split line pattern during bsso in patients with asymmetric mandibular prognathism is affected by anatomic differences . we observed that there was no differences in the split pattern between the deviated and the contralateral sides ; 60% of split lines were type i , in agreement with hunsuck 's description , and 7.5% had an unfavorable fracture . to verify contributing factors , ramal thickness and the location of the lateral bone cut end were investigated . ramal thickness was not significantly different between the deviated side ( mean : 7.10 mm ) and the contralateral side ( mean : 7.00 mm ) . yamamoto et al.14 measured the distance from the mandibular canal to the buccal cortex and the distance from the mandibular lingula to the inferior border of the ramus . in cases where the distance was < 0.8 mm , the incidence of neurosensory disturbance increased significantly . for a medial osteotomy , we measured the ramal thickness only at the level of lingula ; however , the need to evaluate the entire ramus following the split requires further investigation . the lateral cortical bone cut end had a correlation with the split pattern . in case of type i , type a was the most common ( 41/48 ) . in addition , six cases of type v ( either type b or type c ) were observed ; these results concurred with those of muto et al . lee et al.15 studied mandibular body anatomy in patients with asymmetric prognathism . in that study , the distance from the mandibular canal to the buccal cortex was not significantly different between deviated and contralateral sides . wolford and davis16 reported the use of a reciprocating saw to cut the inferior border of the mandible , without using a mallet , to achieve mandible splitting . with preoperative cbct and a 3d program to locate the lateral bone cut end lingually , it is important to analyze the cross - sectional view of the mandible , the pathway of the ian , and the distance between the mandibular canal and buccal cortex . other studies17 - 19 have reported an incidence of bad splits during bsso ranging from 0.9% to 20% ; the incidence in this study was 7.5% ( 6 splits ) . the risk factors for bad splits were old age , the presence of a third molar , a thin mandibular ramus , a high mandibular lingula , and an incomplete split of the inferior border of mandible20 - 23 . in this study , in six cases of unfavorable fracture , the factors were presence of a third molar ( 2 cases ) , a high mandibular lingula ( 2 cases ) , and a buccaly - positioned lateral bone cut end ( 2 cases ) . this study was conducted to evaluate whether there is any difference in the split pattern that occurs with bsso in an asymmetric mandible . pre- and post - operative cbct data and a 3d reconstruction program were used to analyze the lingual split pattern , lateral bone cut end , and to measure the thickness of the ramus . 1 . we categorized the lingual split pattern of the asymmetric prognathic mandible into five types , and there were no differences in split pattern . the ramal thickness , which was measured at the level of the lingula was not significantly different between the deviated and contralateral sides . the lateral bone cut end was categorized into three types ; a correlation with ramal thickness and split pattern was found .

objectivesthe aim of this study was to evaluate the pattern of lingual split line when performing a bilateral sagittal split osteotomy ( bsso ) for asymmetric prognathism . this was accomplished with the use of cone - beam computed tomography ( cbct ) and three - dimensional ( 3d ) software program.materials and methodsthe study group was comprised of 40 patients ( 20 males and 20 females ) with asymmetric prognathism , who underwent bsso ( 80 splits ; n=80 ) from january 2012 through june 2013 . we observed the pattern of lingual split line using cbct data and image analysis program . the deviated side was compared to the contralateral side in each patient . to analyze the contributing factors to the split pattern , we observed the position of the lateral cortical bone cut end and measured the thickness of the ramus that surrounds the mandibular lingula.resultsthe lingual split patterns were classified into . the true " hunsuck " line was 60.00% ( n=48 ) , and the bad split was 7.50% ( n=6 ) . ramal thickness surrounding the lingual was 5.551.07 mm ( deviated ) and 5.661.34 mm ( contralateral ) ( p=0.409 ) . the position of the lateral cortical bone cut end was classified into three types : a , lingual ; b , inferior ; c , buccal . type a comprised 66.25% ( n=53 ) , type b comprised 22.50% ( n=18 ) , and type c comprised 11.25% ( n=9).conclusionin asymmetric prognathism patients , there were no differences in the ramal thickness between the deviated side and the contralateral side . furthermore , no differences were found in the lingual split pattern . the lingual split pattern correlated with the position of the lateral cortical bone cut end . in addition , the 3d - ct reformation was a useful tool for evaluating the surgical results of bsso of the mandible .

the dentigerous cyst initially is always associated with the crown of an impacted , embedded , or unerupted tooth . it develops around the crown of the unerupted tooth by the expansion of the follicle when fluid collects or space occurs between the reduced enamel epithelium and the enamel of an impacted tooth . the proportion of 6- to 7-year - old children affected with dentigerous cysts is only 9.1% . dentigerous cysts occur predominantly in the third molar region of the mandible , followed in frequency by maxillary canine , maxillary third molar , and rarely in relation to maxillary central incisor . a 7-year - old boy reported to the department of paediatric dentistry at our institute with the chief complaint of a painless swelling in the left upper jaw since 6 months [ figure 1 ] . on asking for a detailed history , the patient 's guardian reported that the kid was treated for the same problem by a local dentist by the extraction of few teeth in the same area with no relief of problem few months back . on general physical examination , a clinical intraoral examination revealed a diffuse swelling extending from the buccal vestibule distal to the maxillary left deciduous lateral incisor to the maxillary left permanent first molar . the swelling was ill defined , firm on palpation , non - tender , and measured about 3.5 2.5 cm extending into the maxillary vestibule . these teeth were probably extracted by the local dentist assuming it as a case of dental abscess arising from these teeth . preoperative intraoral view the patient had a pre - existing lateral cephalometric radiograph and an orthopantomograph [ figures 2 and 3 ] . both the radiographs revealed a partially formed and unerupted tooth resembling canine with a radiolucent area surrounding it . on aspiration of the swelling , it yielded straw - colour fluid which was sent for biochemical investigation , the result of which was consistent with the diagnosis of a cystic lesion . a provisional diagnosis of the dentigerous cyst was arrived at based on clinical and radiological features . lateral cephalometric view enucleation of the cyst was chosen as the treatment of choice as the patient 's guardians were not ready for a prolonged treatment period . the treatment consisted of extraction of the maxillary left permanent canine , along with en masse removal of the dentigerous cyst . the cystic lining was attached to the cementoenamel junction of the maxillary left permanent canine . the gross specimen consisted of an irregular , wrinkled soft grey piece of a cystic sac measuring approximately 4.5 3.5 0.5 cm , containing the developing canine tooth bud within it [ figures 4 and 5 ] . the patient was asked to return for clinical follow - up once in 15 days . after 7 months , intra - oral healing was normal it [ figure 6 ] and no evidence of bone resorption or radiolucent lesion were observed [ figure 7 ] . the patient was advised for longer follow - up periods for prosthetic and orthodontic rehabilitation . dentigerous cysts of maxilla are commonly associated with the maxillary third molar and not with a canine tooth . in the present case , there have been previous case reports of a dentigerous cyst with a deciduous tooth and with a supernumerary tooth . a case of a large maxillary cyst involving the whole sinus and producing epiphora has been reported by atlas et al . dentigerous cysts are usually solitary , benign odontogenic cysts associated with the crowns of unerupted teeth . it is stated that the dentigerous cyst develops by the accumulation of fluid either between the reduced enamel epithelium and the enamel or in between layers of the enamel organ . this fluid accumulation occurs as a result of the pressure exerted by an erupting tooth on an impacted follicle , which obstructs the venous outflow and thereby induces a rapid transudation of serum across the capillary wall . toller stated that the likely origin of the dentigerous cyst is the breakdown of proliferating cells of the follicle after impeded eruption . . these cysts usually occur in the late second and third decades , are discovered on routine radiography , and predominantly involve mandibular third molars . the second type is inflammatory origin and occurs in immature teeth as a result of inflammation from a non - vital deciduous tooth . bloch suggested that the origin of the dentigerous cyst is the overlying necrotic deciduous tooth . the resultant periapical inflammation will spread to involve the follicle of an unerupted permanent successor ; inflammatory exudates ensue and result in dentigerous cyst formation . these cysts are diagnosed in the first and early part of the second decade either on routine radiographic examination or when the patient complains of swelling or pain . we believe that our case might be classified as the second type of dentigerous cyst . treatment of a dentigerous cyst depends on size , location , and disfigurement and often requires variable bone removal to ensure a total removal of the cyst . even though marsupialisation of the cyst is the treatment of choice for dentigerous cyst in children in order to give a chance to the unerupted tooth to erupt , the major disadvantage of marsupialisation is that pathologic tissue is left in situ , without a thorough histologic examination . although the tissue taken from the window created can be submitted for pathologic examination , there is a possibility of a more aggressive lesion in the residual tissue . but , in this case , as the tooth was almost displaced up to the roof of the developing maxillary sinus far from the alveolar arch with a questionable viability , enucleation with the removal of the displaced tooth was favoured . in summary , dentigerous cyst development associated with an unerupted permanent tooth is not uncommon . dentigerous cysts of maxilla are usually associated with the maxillary third molar and not with a canine tooth . in the present case , the cyst was associated with canine and was almost involving the developing maxillary sinus of the 7-year - old child . these findings are not common in dentigerous cysts , and hence , this case is reported .

dentigerous cysts are the most common odontogenic and developmental cysts arising in the jaws . in this article , we report a rare case of dentigerous cyst arising from an unerupted canine which had invaded a part of the maxilla in a 6-year - old child . the clinical features , radiographic presentation , and the treatment modality are described .

ltfi krdar training and research hospital ( klktrh ) ethics committee , hospital files of patients in icu of klktrh between january 1 , 2011 and december 31 , 2012 were retrospectively reviewed . from among these patients , details of age , gender , type of cancer , presence of any statistical analysis of study data was performed using spss software ( version 13.0 ; ibm corp . , malignancies with fold change of 2 were associated with male gender , while those with fold change of between 0.5 and 2.00 were evaluated as unrelated to gender . statistical analysis of study data was performed using spss software ( version 13.0 ; ibm corp . , malignancies with fold change of 2 were associated with male gender , while those with fold change of between 0.5 and 2.00 were evaluated as unrelated to gender . from total of 2240 patients , 482 ( 23.9% ) cases with cancer ( male : n=293 , 60.8% ; female : n=189 , 39.2% ; male : female ratio : 1.55 ) were hospitalized and treated in icu between january 1 , 2011 and december 31 , 2012 . cancer patients were aged between 3 and 93 years , with mean age of 59.915.06 years ( table 1 ) . patients were categorized as 70 ( n=138 ; 28.6% ) or < 70 ( n=344 ; 71.4% ) years of age . age distribution graph demonstrated accumulation of cancer patients within age interval of 40 to 80 years , and majority in age bracket of 60 to 69 years ( figure 1 ) . indication for icu hospitalization of cancer patients was most often respiratory distress or deterioration of general state of health . patients were also admitted to icu for closer monitoring , metastatic complications , adverse effects of oncological therapy , and advanced life support after cardiopulmonary resuscitation ( cpr ) . rectosigmoid cancer ( 19.7% ) was most prevalent type of cancer seen among cancer patients hospitalized in icu , followed by lung ( 15.7% ) , and gastric ( 11.6 % ) cancers ( figure 2 ) . cancer patients distribution . among a total of 482 cancer patients hospitalized in intensive care unit , 225 died while in hospital , and forty - three patients who were transferred were subsequently re - admitted to icu between 2 and 5 times ( table 1 ) . total number of icu hospitalizations for 482 patients was 536 . in the present study , 87 ( 18.0% ) patients were observed to have metastasis or comorbidity ( n=176 ; 36.5% ) , and 285 ( 59.1% ) patients consulted to icu following surgical intervention . cpr was performed on 17 ( 3.5% ) patients who were admitted to icu for advanced life support ( table 1 ) . sixteen of those patients died ; mortality rate for cpr patients was calculated at 94.1% . based on fold changes , lung , rectosigmoid , hematological , bladder , and cutaneous malignancies were associated with male gender , while esophageal cancer was seen in more female patients than male patients . stomach , brain , and pancreatic cancers , as well as unclassified tumors , were not found to be correlated with gender . in our analysis , laryngeal cancer was malignancy with highest ( 15.00 ) fold change ( table 2 ) . gender - related malignancies , such as gynecological , breast , and prostatic cancers were not included in this analysis . relationship between gender and malignancy gender - related cancers , such as prostate , breast , and gynecological malignancies were not included in this analysis . cancer is still a leading health problem worldwide , and cancer patients constitute substantial number of icu patients . these patients are generally in the terminal phase of their disease , and they are hospitalized in icu most often due to respiratory distress , deterioration of general health , complications related to metastasis , adverse effects of oncological treatment , and close postoperative monitoring . based on 2008 data of the ministry of health , in turkey , lung cancer was most frequent type of cancer seen in men , followed by prostate , bladder , and colorectal cancers . in women , most frequently observed cancer type was breast cancer , followed by thyroid , colorectal , and uterine cancers . in a study of cancer patients of the medical oncology clinic of van yuzuncu , most frequently seen was gastric cancer , followed by esophageal , breast colorectal , and lung cancers . in women , breast cancer was most common , followed by gastric cancer , while in men , gastric cancer was predominant , followed by esophageal cancer . tow et al . performed a retrospective study based on registries of oncology department and reported gastrointestinal , lung , and breast cancers as most frequently seen cancer types . these studies evaluated patients hospitalized in services ; however , our study analyzed cancer patients hospitalized in icu , and most frequently observed were colorectal , followed by lung and gastric cancers . among both male and female patients , most often seen was colorectal cancer ( male : 22.94% ; female : 22.14% ) . lung cancer ( 21.86% ) was second among men , while in women , next most often seen was gastric cancer ( 16.43% ) . these findings on cancer patients hospitalized in icu are consistent with data of the ministry of health as well as other studies . a multicenter study was performed by taccone et al . with the aim of evaluating characteristics and outcomes of cancer patients hospitalized in european icus . from total of 3147 icu patients , they reported 473 ( 15% ) patients with malignancy and male : female ratio among them of 1.27 . determined male : female ratio of 1.19 ( male : 861 ; female : 723 ) . in our study we observed that 23.9% of hospitalized icu patients were cancer patients and male : female ratio of 1.55 ( male : 293 ; female : 189 ) . in parallel with higher frequency of cancer among male patients , dominancy of male gender among cancer patients admitted to our intensive care units is remarkable . our study also revealed that percentage of cancer patients hospitalized in icu is significant and should not be underestimated . reported that among their study participants , 151 ( 9.53% ) were cancer patients aged 70 years , and 1433 ( 90.46% ) cases were aged < 70 years . in our study , 140 ( 29.04% ) , cancer patients were aged 70 years , while 342 ( 70.95% ) patients were younger than 70 . these rates suggest that cancer is now detected and treated at an earlier age thanks to development of new diagnostic tools and treatment alternatives . laryngeal cancers are most often seen among people aged 45 to 75 years , and male : female ratio is 10:1 . in present study , 15 of 16 patients with laryngeal cancer were male , which is consistent with epidemiological data , and also explains high fold change in laryngeal cancer . it was also blinded to stage , histological type , and other characteristics of cancer cases . status and ultrastructure of hospital and whether or not cancer center focuses on certain types of cancer will also affect results . regarding retrospective nature of our study , selection bias may be present . in conclusion , cancer is most often observed in older people , and cancer patients generally stay in icu longer than other , younger patients . slow improvement in their state of health , and in many cases , advanced age , requires additional workforce . we think that palliative approaches for many advanced cancer patients hospitalized in icu , rather than interventional therapies , will increase patient satisfaction as well as be more efficient use of icu resources . multicenter , long - term studies should be conducted to further delineate demographic characteristics of cancer patients in icu . in conclusion , cancer is most often observed in older people , and cancer patients generally stay in icu longer than other , younger patients . slow improvement in their state of health , and in many cases , advanced age , requires additional workforce . we think that palliative approaches for many advanced cancer patients hospitalized in icu , rather than interventional therapies , will increase patient satisfaction as well as be more efficient use of icu resources . multicenter , long - term studies should be conducted to further delineate demographic characteristics of cancer patients in icu .

objective : the present study is an analysis of cancer patients who received follow - up treatment for either cancer - related complications or treatment - associated side effects while hospitalized in the intensive care unit ( icu).methods : records of cancer patients treated at dr . ltfi krdar kartal training and research hospital icu between january 1 , 2011 and december 31 , 2012 were retrospectively reviewed . demographic data and type of cancer were recorded in prepared forms and subsequently analyzed.results:among 2240 icu patients treated and hospitalized between january 1 , 2011 and december 31 , 2012 , 482 cancer patients were identified and included in the study . percentage of cancer patients in icu was 23.9% . male to female ratio was determined to be 1.55 . first 3 most common cancers found were colorectal ( 19.7% ) , lung ( 15.7% ) , and stomach cancers ( 11.6% ) . mortality rate of cancer patients hospitalized in icu was 46.6% . larynx , lung , urinary bladder , skin , rectosigmoid , hematological , and kidney cancer were more prevalent in male patients , whereas esophageal cancer was seen in more female patients than male patients . incidence of stomach , brain , and pancreatic cancers , as well as unclassified tumors , was found to be unrelated to gender.conclusion:rectosigmoid cancer was most common type of cancer observed in our icu . esophageal cancer was observed in more females than males , while larynx cancer was more frequently present in males .

neocortical epilepsy has comprised only a minor portion of epilepsy surgical series until now.1 it has not homogenous clinical manifestations . widely different seizure semiologies could be found depending on the location of the epileptogenic foci . scalp eeg often misleads or falsely localizes the ictal onset zone due to inaccessible location or widespread ictal onset . a focal structural lesion on mri is a reliable indicator of the seizure onset.24 concordance of electrophysiological studies and mri findings has high predictive value for good surgical outcome.5,6 however , mri is ineffective in many partial epilepsy patients , even patients with cortical dysplasia . surgical outcome has usually been known to be less well satisfactory.1,7,8 in the context of all these issues , determining the prognostic factors for good surgical outcome and suggesting the guideline of successful epilepsy surgery are very important for the this special group of patients . extratemporal resections are known to be generally less successful than are temporal lobe resections . by multivariate analysis , the median proportion of long - term seizure - free patients ( more than five years ) was 66% with temporal lobe epilepsy ( tle ) , 46% with occipital and parietal lobe epilepsies ( ole and ple ) , and 27% with frontal lobe epilepsy ( fle).9 however , the recent series suggested that many neocortical epilepsy patients are likely to benefit from surgical treatment , and 57.5% became seizure free more than two years after surgery ( 41.0% in fle , 71.2% in neocortical tle , 57.5% in ple , and 68.1% in ole).10 it has been a consistent finding that the presence of focal mri lesion indicated good surgical outcome in epilepsy surgery including temporal and extratemporal lobe epilepsies.1,1114 the seizure free rate ranged from 20 to 50% in nonlesional epilepsy depending on the lobes ( table 1 ) . a meta - analysis to assess predictors of epilepsy surgery found out that a good outcome was related with presence of febrile convulsion , mesial temporal sclerosis , tumors , abnormal mri , eeg / mri concordance , and extensive surgical resection.15 the resection of an epileptognic lesion with an ictal onset zone is recognized as the most important factor for a good surgical outcome . the majority of surgical series suggested that the identification of a specific lesion usually leads to a favorable outcome.24 our recent study using multivariate analysis of a large series of patients also showed that a focal lesion on mri , focal hypometabolism on pet , and localized ictal onset on eeg were independent significant positive prognostic factors.10 in another large series of fle , mri - negative malformation of cortical development , any extrafrontal mri abnormality , generalized / non - localized ictal eeg patterns , occurrence of acute post - operative seizures , and incomplete surgical resection were correlated with poor surgical outcome.16 mri is also an important factor to make the patients have epilepsy surgery after presurgical evaluations . up to 30% of patients who underwent presurgical evaluations for respective surgery ultimately did not have this form of surgery.17 localized mri abnormality and consistently localized eeg findings were most strongly associated with leading to surgery.17,18 there is inherent difficulty in identifying the epileptogenic zone in nonlesional neocortical epilepsy , which leads to the incomplete resection . until recently , only a minority of patients have been known to be seizure free after the resection . however , the seizure free rate of the patients even with normal mri who underwent surgery was significantly superior to that of the patients who did not have surgery.18 seizure free outcome ranged from 31 to 70% for nonlesional temporal lobe epilepsy , and from 17% to 57% for extratemporal nonlesional epilepsy ( table 2).1924 two recent large studies including ours demonstrated that seizure free outcomes were 47 and 55% for nonlesional tle , and 41 and 43% for nonlesional extratemporal lobe epilepsy patients.23,24 our study also showed that localization by fdg - pet or interictal eeg was correlated with a seizure - free outcome . concordance with two or more presurgical evaluations among interictal eeg , ictal eeg , fdg - pet , and ictal spect was significantly related to a seizure - free outcome.24 as for long - term outcome of patients with mri negative tle , only non - congruent fdg - pet results could be identified to be associated with poor surgical outcome.25 in another study with the tle patients with normal mri , the absence of contralateral or extratemporal interictal spikes and concordant subtraction ictal spect were associated with good surgical outcome.26 with careful interpretation of other studies including functional neuroimaging and the presence of concordant results , surgical treatment can benefit selected patients with nonlesional neocortical epilepsy . ictal spect and fdg - pet can be critical for localizing the seizure focus , especially in nonlesional patients . we analyzed 33 consecutive patients with nonlesional neocortical epilepsy who had a scalp ictal onset zone localized in the temporal lobe and good surgical outcome after focal neocortical resection.27 epileptogenic zone outside the temporal lobe was not infrequently encountered in the patients who were diagnosed as non - lesional lateral temporal lobe epilepsy on long - term scalp video - eeg monitoring . some studies demonstrated that fdg - pet and subtraction spect were valuable in the diagnosis of non - lesional neocortical epilepsy.2833 however , in the patients with intracranial ictal onset zones outside the temporal lobe , their values were limited . fdg - pet and subtraction spect had localizing value in no more than half of patients , which even showed false localizations occasionally . careful placement of intracranial electrodes on the presumed epileptogenic zone and adjacent areas should be needed for these patients . accurate localization of ictal onset zone by intracranial electrodes is one of the most sensitive and important method in the success of epilepsy surgery.3437 in the presurgical evaluation of non - lesional neocortical epilepsy , intracranial monitoring is indispensable but has the limitation of the possibility of insufficient sampling . one recent study showed that stereo - eeg was equally effective in the presurgical evaluation of both mri - negative and lesional epilepsies . 38 to get the appropriate information from intracranial monitoring , many intracranial electrodes may be needed . nevertheless , because these electrodes cover only limited portion of brain , the true ictal onset zone can sometimes be missed3941 and sometimes the repositioning or additional electrode can be needed . to avoid missing true ictal osnet zone , it is important to make strong hypothesis derived from congruent results of presurgical evaluation . sometimes , the repositioning or adding intracranial electrodes is helpful to find the true ictal onset zone after the failure of identifying it at the initial evaluation . our group recruited 18 cases underwent a second invasive study consisting of repositioning or additional implantation of intracranial electrodes performed a week after the initial invasive study.42 the repositioning of intracranial electrodes identified a new ictal onset zone in 13 patients . in another four cases seven of 11 patients who were ultimately found to have focal ictal onset zone by the second evaluation became seizure free after the operation . these results support consideration of one - week interval repositioning of intracranial electrodes in selected patients . the objectives of intracranial eeg are to define interictal abnormalities and the ictal onset zone , and to map the cortical function . based on these results the surgical outcome depends strongly on the identification and complete resection of a well - defined epileptogenic zone . therefore , the extent of the resection may contribute to the surgical outcome.43 intracranial eegs were analyzed in 177 consecutive patients who had undergone resective epileptic surgery.44 based on the results of invasive evaluations , slow propagation and focal or regional ictal onset were associated with a seizure - free outcome . a seizure - free outcome was significantly associated with a resection that included the area showing ictal spreading rhythm during the first three seconds or included all the electrodes showing pathological delta waves or frequent interictal spikes more than 0.2 hz . presurgical evaluations other than mri including functional neuroimagings can correctly localize the epileptogenic lobe in these patients . we should know the usefulness and limitations of various presurgical diagnostic modalities and their meanings in combination including intracranial eegs . the strength of hypothesis based on the results of non - invasive evaluation is a key to successful epilepsy surgery for these patients .

there is inherent difficulty in identifying the epileptogenic zone in nonlesional neocortical epilepsy , which leads to the incomplete resection . however , with careful interpretation of other studies including functional neuroimaging and the presence of concordant results , surgical treatment can benefit selected patients with nonlesional neocortical epilepsy . two recent large studies including ours demonstrated that seizure free outcomes were 47 and 55% for nonlesional tle , and 41 and 43% for nonlesional extratemporal lobe epilepsy patients . concordance with two or more presurgical evaluations among interictal eeg , ictal eeg , fdg - pet , and ictal spect was significantly related to a seizure - free outcome . however , we should be cautious to the possibility of false localization of ictal eeg or functional neuroimaging in nonlesional neocortical epilepsy . careful placement of intracranial electrodes on the presumed epileptogenic zone and the adjacent areas should be needed for these patients . the repositioning of intracranial electrodes after the failure in identifying ictal onset zone at the initial intracranial study might identify a new ictal onset zone . consideration of one - week interval repositioning of intracranial electrodes could be helpful in selected patients . intracranial eeg is one of the most important procedures in planning surgery and achieving a good surgical outcome in resective epilepsy surgery . slow propagation and focal or regional ictal onset rather than widespread onset were associated with a seizure - free outcome . complete resection including the area with initial three second ictal rhythm and interictal abnormalities predicts a good surgical outcome .

in dentistry the role of endodontics has greatly broadened in scope in the past decade . although many factors are responsible , the most important reason behind this growth is the extremely high predictability of endodontic success . false assumptions about the root canal anatomy of teeth may lead to misdiagnosis , improper debridement , step formation and breakage of instruments during root canal treatment . problems during endodontic treatment of permanent maxillary molar teeth indicate the need for increased knowledge of the anatomy of root canal systems . the mesiobuccal root of maxillary first molars has prompted more research and clinical investigation than any other tooth in the mouth . green reported that two foramina were present in 14% of the mesiobuccal roots in his study of upper first molars , and two orifices were noted in 36% of the casies . kulid and peters indicated that a second canal was present in the coronal half of 95.2% of the mesiobuccal roots examined . the root canal configuration , according to the classification of vertucci , is usually type ii ( two separate root canals with a single apical exit ) ; however , the presence of two root canals of type iv configuration with two separate apical foramina has been reported to be as high as 42% . other investigators have reported the prevalence of maxillary first molars with four canals to be 28 - 62% in caucasians.7 - 9 weine et al reported that the mesiobuccal roots of maxillary first molar teeth of a japanese subpopulation had two root canals ( 54% ) of type ii or type iv configuration . because of this complexity , the clinician should always assume there are two canals in the mesiobuccal root until it is proven there is only one . the purpose of this in vitro study was to investigate variations in the root canal system of maxillary first molars in an iranian population in the north - west of iran . one hundred thirty - seven maxillary first molar teeth were collected from a large supply of recently extracted teeth from dental faculty clinics and private offices in tabriz , a city in the north - west of iran . teeth that demonstrated fully - formed roots and intact external morphology were selected for the study . the teeth were collected in a period of one year and were stored in 10% formalin . each tooth was cleaned of any adherent soft tissues , bone fragments and calculus by scaling and polishing . an endodontic access cavity was then prepared in each tooth with diamond fissure burs ( d&z , wisbaden , germany ) . the anatomic dark lines in the floor of the pulp chamber were examined with a dg16 endodontic explorer ( hu freiday , chicago , il , usa ) to identify the root canal orifices . after locating the orifices , the teeth were placed in 5.25% sodium hypochlorite solution ( golrang , tehran , iran ) for 48h to dissolve debris and pulp remnants . all the specimens were then thoroughly rinsed in running water for 4h to clean the root canals of any debris . once washed , the teeth were demineralized for 3 days in 5% nitric acid ( merck , darmstadt , germany ) at room temperature . india ink ( ab chemi , england ) was injected into the root canals before dehydration of the teeth . the dehydration process consisted of a series of ethyl alcohol ( ararat , tehran , iran ) rinses starting with 80% solution over night , followed by 90% for 1h and then 100% ethyl alcohol rinse for 1h . the dehydrated teeth were placed in methyl salicylate ( bp.63 , poland ) for 2h to render them transparent . the cleared teeth were examined using a magnifying - glass ( lumagny , no.7540 , hong kong ) at 5 magnification . the root canal systems were classified according to the classification of vertucci ( 1984 ) as follows : type . one single root canal extending from the pulp chamber to the apex type ii . separate root canals leaving the pulp chamber and joining short of the apex to form one canal type iii . one root canal leaving the pulp chamber before dividing into two canals within the root and then merging to exit as one single canal type iv . one root canal leaving the pulp chamber and dividing short of the apex into two separate and distinct root canals with separate apical foramina type vi . two separate root canals leaving the pulp chamber , merging in the body of the root , and again dividing short of the root apex to exit as two separate and distinct canals type vii . one root canal leaving the pulp chamber , dividing and rejoining within the body of the root canal and finally re - dividing into two distinct canals short of the apex type viii . out of 137 maxillary first permanent molar teeth studied , the mesiobuccal roots with a single canal were of type i ( 37.96% ) or type v ( 9.5% ) configuration . those with two canals were of type ii ( 24.08% ) , type iv ( 24.18% ) or type vi ( 4.38% ) configuration . the distal and palatal roots that presented with a single canal were of type i or v configuration . no type iii , vii or viii canal configurations were found in the roots of these teeth . the percentage distribution of accessory canals was 16.78% in the mesiobuccal roots , 2.91% in the distobuccal roots and 2.18% in the palatal roots . false assumptions about the root canal anatomy of teeth may lead to misdiagnosis , improper debridement , step formation and breakage of instruments during root canal treatment . problems faced during endodontic treatment of permanent molar teeth indicate the need for increased knowledge of root canal systems . the results of this study differ from those reported in investigations of samples obtained from caucasians ( table 2 ) . these differences relate principally to the presence of type v and type vi configurations , with a relatively low incidence of , in particular , type i configuration in the mesiobuccal root . there was a relatively high prevalence of type v configuration in the distal and palatal roots of maxillary first permanent molar teeth ( table 1 ) . wasti et al in a study ( 2001 ) on maxillary first molars in asian pakistanis found two canals in the mesiobuccal roots in 53% and one canal in 46.5% of cases . the configuration of root canal system in the study carried out by wasti et al in the mesiobuccal root was type i ( 33.3% ) , type ii ( 23.3% ) , type iv ( 23.3% ) , type v ( 13.3% ) and type vi ( 6.8% ) . they found type v root canal system in the distobuccal and palatal roots of maxillary first molars in 16.7% and 33.3% of cases , respectively . the results of this study are consistent with the results of the study carried out by wasti . regarding the diversity and the number of the teeth studied ( e.g. our study on 137 teeth and a study by wasti et al on 30 teeth ) , it seems that racial / ethnic differences are important factors in the differences observed in the root canal configuration , as sert and bayirli concluded that both gender and ethnic origin should be considered during preoperative evaluation of root canal therapy . therefore , further studies are warranted in different parts of the world to prove that there is a relationship between the racial / ethnic differences and the anatomic differences in the first maxillary molars . according to the results of the present study , there is a high prevalence of four root canals in the maxillary first permanent molars in the north - west of iran . the distribution of different configurations of root canal system in the maxillary first permanent molars in north - western iranians differs from that in caucasian groups .

background and aims it is critical to have a proper knowledge of the normal anatomy of the pulp and its variations for the success of endodontic treatment . the purpose of this study was to investigate variations in the root canal system of maxillary first permanent molars in an iranian population . materials and methods in this study , 137 maxillary first molars were decalcified , dye - injected , cleared and studied . results the results demonstrated that 37.96% of the maxillary first molars under study had three canals , 58.4% had four canals and 3.64% had five canals . conclusion according to the results of this study and considering variations in the root canal systems of maxillary first molars , it seems that great care should be taken in the root canal treatment of these teeth .

while physical activity improves glucose metabolism of patients with type 2 diabetes mellitus ( t2 dm ) adherence is often transient and/or partial . neuromuscular electrical stimulation ( nmes ) is a physical treatment routinely used in functional rehabilitation it should also be an alternative to conventional activity for improving metabolic control in sedentary t2 dm patients . although few studies have investigated this potential application , a study of sharma et al . on sedentary t2 dm patients showed that 2 weeks of nmes at 50 hz , which are the most common protocol for human study , improved insulin sensitivity and glucose regulation . however , many patients complained of pain , discomfort , and/or constraints during nmes sessions . more recently , jouber et al . demonstrated significantly improved insulin sensitivity with t2 dm patients after 1 week of daily nmes training at 35 hz and a total of 11 patients ( of 18 ) reported moderate pain in the muscles during nmes . while there is any existent standard protocol concerning patient with metabolic diseases , the major interest today is to provide safety and efficacy of nmes therapeutic application , which may serve as a valuable adjunct in the treatment of individuals with glucose intolerance that are limited in their ability to perform physical activities . the purpose of this study was to determine the acute influence of low - frequency nmes ( 8 hz ) on glucose metabolism in middle - aged mobile patients with t2 dm . low - frequency nmes elicits significant muscle contractions that are well tolerated in asymptomatic populations for extended periods of time . five men and three women were included , and the average age was 5213 years . these participants were identified by a physician as having met the current diagnosis of t2 dm with mean diabetes duration of 6.258.75 years . participants continued their hypoglycemic medications as prescribed for all testing and exercise days . except for one subject treated with diet alone , all other participants ( n=7 ) were treated with diet plus oral hypoglycemic agents ( glyburide [ actavis pharma manufacturing , parsippany , nj , usa ] , and/or metformin [ actavis pharma manufacturing ] , and/or actos [ takeda pharmaceuticals inc . , deerfield , il , usa ] ) . the first session was a screening session that gave participants the opportunity to familiarize themselves with the low - frequency nmes protocol used . during the second and third sessions , a standardised glucose tolerance test ( gtt ) assessed glucose metabolism . after an overnight fast ( 12 hours ) , the gtts were performed at 7:30 am for both conditions . the participants were then asked to drink a solution containing a known amount of glucose ( 75 g ) within 5 minutes . two further blood samples were collected 60 and 120 minutes after consumption of the glucose load . blood was drawn from a vein ( venipuncture ) , usually from the inside of the elbow or the back of the hand . in addition , in either the second or the third session , participants completed the 1-hour nmes protocol via randomized assignment during the first hour of the session . the electrical stimulation was delivered to the knee extensor muscles of the right and left legs to induce a rhythmic contraction using a portable battery - powered stimulator ( respond select ; empi inc . , henderson , nv , usa ) and two round 7.5-cm in diameter reusable adhesive electrodes ( pals plus ; empi inc . ) . on each thigh , one electrode was placed over the proximal part of the knee extensor muscles ( 3 cm under the ilioinguinal region ) while the other was applied over the motor point of the vastus lateralis ( 5 cm above and lateral to the patella ) . the current used was a balanced rectangular symmetrical biphasic pulse , with a frequency of 8 hz and pulse duration of 200 s . within the first 2 minutes , the participants increased the intensity of the contraction to the maximum tolerable level . the portable stimulator ranged from 0 to 120 ma , with the tolerable level of these eight participants ranging between 30 to 60 ma . in the present study , none of our experimental subject reported pain , discomfort or fatigue in the muscles during nmes . after testing for normality ( kolmogorov - smirnov test ) , statistical comparisons were made using a 2 ( condition : nmes or control ) by 3 ( time : 0 , 60 , 120 minutes ) repeated measures analysis of variance to determine whether significant changes in absolute glucose levels occur with time or groups . the student - newman - keuls method test was used to make multiple comparisons when appropriate . the strength of the association between nmes intensity ( ma ) and the change in blood glucose during stimulation ( 0 to 60 minutes ) was investigated using a pearson correlation . a significant increase ( p<0.01 ) in blood glucose was observed after 60 minutes of the control and the nmes sessions , respectively . this was followed by a significant ( p<0.01 ) decrease from 60 to 120 minutes of the control and the nmes sessions , respectively . our results showed significant lower blood glucose in the nmes than in the control sessions at times 60 ( p<0.01 ) . moreover , glucose decreases at the 120 minutes following nmes was significantly higher in the nmes compared to control session ( p<0.01 ) ( fig . positive correlation ( r=0.9 ) was found between nmes intensity and the change in blood glucose between 0 and 60 minutes . to our knowledge , the present study is the first to examine the effect low - frequency nmes ( 8 hz ) on glucose metabolism in middle - aged mobile patients with t2 dm . despite lower nmes frequency , the plasma glucose concentrations determined after 60 minutes of nmes and at 120 minutes following nmes were significantly lower to those observed in control condition . these results seem to suggest that there occurs a large activation of glycolytic type ii fiber by low frequency nmes resulting in a significant decrease in blood glucose level and thereby possibly improving insulin sensitivity as previously suggested by sinacore et al . . poole et al . evaluated acute glucose uptake during highfrequency ( 50 hz ) stimulation nmes in neurologically intact individuals with t2 dm and observed no overall differences between control and nmes conditions . since high - frequency nmes can be particularly fatiguing , we reasoned that a well - tolerated low - frequency stimulation paradigm might be necessary to induce significant glucose uptake . in the present study a significant correlation between stimulation intensity and blood glucose levels suggests that factors related to the intensity of skeletal muscle contraction greatly contribute to glucose metabolism during electrical stimulation . indeed , the intensity of contraction might in fact be so high as to bring about an increase in blood glucose , similar to the response observed during intense bouts of exercise . this result may add novel knowledge in term of nmes procedure such as , ensuring an optimal combination between lower frequency and stimulation intensity . while stimulation parameters used in previous studies were quite diverse and physiological responses were difficult to compare , low - frequency nmes ( 8 hz ) , which are tolerated by all experimental individual , may be an appropriate strategy in t2 dm rehabilitating process . however , evaluation of the chronic effect of low - frequency nmes with particular attention on the interaction between stimulation intensity and muscle fatigue parameters , on glucose regulation and on other metabolic , hormonal and muscle parameters in t2 dm patients remains an interesting future study .

the purpose of this study was to examine the effect of low - frequency neuromuscular electrical stimulation ( nmes ) on glucose profile in persons with type 2 diabetes mellitus ( t2 dm ) . eight persons with t2 dm ( 41 to 65 years ) completed a glucose tolerance test with and without nmes delivered to the knee extensors for a 1-hour period at 8 hz . three blood samples were collected : at rest , and then 60 and 120 minutes after consumption of a glucose load on the nmes and control days . in nmes groups glucose concentrations were significantly lower ( p<0.01 ) than in the control conditions . moreover , a significant positive correlation ( r=0.9 , p<0.01 ) was obtained between the intensity of stimulation and changes in blood glucose . our results suggest that low - frequency stimulation seem suitable to induce enhance glucose uptake in persons with t2 dm . moreover , the intensity of stimulation reflecting the motor contraction should be considered during nmes procedure .

cytomegalovirus ( cmv ) retinitis is an opportunistic infection in patients with acquired immunodeficiency syndrome who are receiving immunosuppressive therapy , which causes progressive retinal destruction or retinal detachment with severe visual impairment , and affects quality of life.13 the primary treatment for cmv retinitis is intravenous ganciclovir . in recent years , oral valganciclovir has been reported as being as effective as intravenous ganciclovir and is convenient for the long - term management of cmv retinitis in patients with acquired immunodeficiency syndrome.3 cmv retinitis in patients with wegener s granulomatosis is rare.4 therefore , therapeutic reporting on cmv retinitis in wegener s granulomatosis is inadequate.57 to our knowledge , there have been no previous reports on oral valganciclovir therapy for cmv retinitis in wegener s granulomatosis . we report a case of cmv retinitis in a patient with wegener s granulomatosis treated with intravenous ganciclovir as induction therapy and oral valganciclovir as maintenance therapy . a 68-year - old man presented to the department of ophthalmology , jikei university of medicine , katushika medical center complaining of vision loss in his right eye for the previous month . the patient had been diagnosed with anti - proteinase-3 anca - positive wegener s granulomatosis eight years previously , and was receiving immunosuppressive therapy with methylprednisolone , cyclophosphamide , and azathioprine . he developed glomerulonephritis , rhinitis , pulmonary nodules as coin lesions , and nodules on the elbow . on fundus examination , the right eye showed yellowish - white retinitis surrounding the inferior and temporal aspect of the macula and along the superior vascular arcades as typical changes of cmv retinitis , angiostenosis of the inferior vascular arcades , and retinal hemorrhage ( figure 1 ) . retinal hemorrhage was observed around the inferior and temporal aspect of the macula in the left eye . polymerase chain reaction of the aqueous sample was positive for cmv retinitis and negative for herpes simplex virus , herpes zoster virus , and toxoplasmosis . from these clinical findings , the laboratory results , and treatment with immunosuppressive therapy , we diagnosed cmv retinitis . after providing informed consent , the patient received intravenous ganciclovir 5 mg / kg twice a day for 25 days as induction therapy with monitoring of retinitis , followed by oral valganciclovir 900 mg once a day as maintenance therapy . at 1 month from onset , there was no further progression of retinitis . three months afterwards , development of retinal pigment epithelial changes and reduction of retinal hemorrhage were observed in the right eye ( figure 2 ) . there was no recurrence of retinitis after 8 months , but visual acuity was not improved . valganciclovir is an orally administered prodrug that is rapidly hydrolyzed to ganciclovir , the active compound.8,9 the absolute bioavailability of ganciclovir from valganciclovir is 60%,10 and a dose of 900 mg results in ganciclovir blood levels similar to those obtained using an intravenous ganciclovir dose of 5 mg / kg body weight.11 adverse effects associated with valganciclovir include pancytopenia , nausea , vomiting , diarrhea , peripheral neuropathy , seizures , and confusion.9 this patient developed only transient diarrhea . previously , the only treatment for cytomegalovirus retinitis was via the intravenous route , so patients are at risk of catheter - related complications.1 oral valganciclovir can reduce the risk of catheter - related complications in particular infections , which is beneficial for patients with wegener s granulomatosis.3 wegener s granulomatosis causes a variety of ophthalmic symptoms,12 but the development of cmv retinitis is rare.4 according to previous reports of cmv retinitis in wegener s granulomatosis , intravenous ganciclovir and intravitreal implant treatment have been described.57 the ganciclovir implant is more effective than intravenous ganciclovir , but patients treated with a ganciclovir implant alone remain at greater risk for the development of cytomegalovirus disease outside of the treated eye.2 therefore , a ganciclovir implant is administered ; it is done in combination with intravenous ganciclovir or oral valganciclovir.8 there are risks of complications associated with implant insertion,2,13 so ganciclovir implant adaptation should be carefully considered . in this patient , we selected intravenous ganciclovir as the initial treatment given the involvement of both eyes , the severity of cmv retinitis , and his general condition , followed by oral valganciclovir as maintenance treatment , and achieved a remission . from this time forward , we will consider alternative treatments , ie , a ganciclovir intravitreal implant , intravenous foscarnet , and intravenous cidofovir,8 according to the patient s condition . we report a case of cmv retinitis in a patient with wegener s granulomatosis treated with intravenous ganciclovir as induction therapy and oral valganciclovir as maintenance therapy . there were no serious adverse effects associated with oral valganciclovir , which was convenient and effective for the management of cmv retinitis in a patient with wegener s granulomatosis . in the future , use of oral valganciclovir for the treatment of cmv retinitis in wegener s granulomatosis is likely to increase .

a case of cytomegalovirus ( cmv ) retinitis in a patient with wegener s granulomatosis treated with oral valganciclovir as maintenance therapy is reported . a 68-year - old male patient with anti - proteinase-3 anca - positive wegener s granulomatosis who was receiving immunosuppressive therapy with methylprednisolone , cyclophosphamide , and azathioprine developed cmv retinitis . the patient received intravenous ganciclovir as induction therapy and oral valganciclovir as maintenance therapy . the patient responded to treatment and showed no recurrence for 8 months . there were no serious adverse effects associated with oral valganciclovir . oral valganciclovir is convenient and effective for the management of cmv retinitis in the patient with wegener s granulomatosis .

endoscopic ultrasound - guided fine needle aspiration biopsy ( eus - fna ) has enhanced the diagnostic capabilities of endoscopic ultrasonography ( eus ) by providing additional pathologic findings 1 . however , confirming the presence of a target specimen within a sample is often difficult because specimens collected with these fine needles are microscopic and contain blood . rapid on - site evaluation ( rose ) during eus - fna is beneficial , but many health care facilities are unable to provide this service due to a lack of cytopathologists . because fine - gauge needles are associated with fewer complications , easier to use than thicker needles , and equally effective for diagnosis , 25-g needles are commonly used for eus - fna of pancreatic tumors 2 . given the tendency to perform eus - fna using fine - gauge needles , evaluation of the target specimen in eus - fna samples of pancreatic lesions , therefore , may be even more difficult . to identify the wavelength that provided the optimal absorption specifically by blood covering the target specimen , single wavelengths from 435 nm to 695 nm were projected by light - emitting diodes onto eus - fna samples of dog pancreas . we found that we were able to confirm the target specimen most clearly with observation using the 605-nm wavelength . we then developed a device equipped with a 605-nm wavelength light source , referred to as the target sample check illuminator ( tsci ) ( fig . 1 ) . we developed a device equipped with a 605-nm wavelength light source , referred to as the target sample check illuminator ( tsci ) . the current study verified the potential usefulness of this device , both in collecting the minimum necessary target specimens within eus - fna samples of pancreatic tumors , and in eliminating the need for further procedures , even without performing rose . fifty - eight consecutive patients ( 33 men , 25 women ; mean age 70.4 years ; range , 42 87 years ) were included in this prospective study ( table 1 ) , which took place from july 2012 to october 2013 . the research protocol was reviewed and approved by the institutional review board of tottori university hospital . samples of eus - fna were observed using the tsci prior to histologic diagnosis to determine whether the presence of target specimens could be confirmed . eus - fna was performed using a 7.5-mhz , convex linear array echoendoscope ( gf - uct260 ; olympus optical , tokyo , japan ) and a 19-g ( m00550040 ; boston scientific corporation , natick , ma ) , 22-g ( na-200h-8022 ; olympus optical ) , or 25-g needle ( m00550020 ; boston scientific corporation ) . patients were referred for eus - fna based on the need to perform evaluations for any malignancies . no algorithm was used to decide whether to use a 19-g , 22-g , or 25-g needle . the final diagnosis was verified histologically with either subsequent surgery or treatment based on the clinical course . patients without a malignant disease , including those with chronic pancreatitis , a neuroendocrine tumor , or an accessory spleen , were followed up with imaging examinations . the data recorded include sample adequacy , final diagnosis , agreement rate between the tsci and histopathology , and procedure - related complications . in the examinations , areas that included target specimens appeared orange ( yellow arrows ) , and those without appeared dark brown ( blue arrows ) when examined with the tsci ( fig . 2 a ) . examinations with a tsci were performed when we were unable to detect target specimens with a white light ( fig . 2 b ) . we were only able to detect target specimens using a white light in about 28 out of 57 cases , compared with 57 out of 58 cases when a tsci was used ( p < 0.001 ) . the mean number of total needle punctures was 2.4 ( range , 1 5 ) , and the agreement rate between tsci and histopathology in 142 samples was 93.7 % ( 133/142 ) . no differences were observed between cancerous and non - cancerous lesions in detection capacity . there were no differences between 19-g , 22-g and 25-g needles in detection capacity . when the presence of the target specimen was confirmed by tsci , 91.4 % ( 53 /58 ) of patients were able to finish tests ( table 2 ) . the percentage of cases that only required 1 eus - fna pass to yield a diagnosis was 84.5 % ( 49/58 ) , and the mean number of necessary needle punctures was 1.2 ( 67/58 ) . an adequate specimen was obtained by eus - fna in 98.3 % of cases . the sensitivity , specificity , positive predictive value , negative predictive value , and accuracy for eus - fna were 97.7 % , 100 % , 100 % , 93.3 % , and 98.3 % , respectively ( table 3 ) . only one case was misdiagnosed , a metastatic pancreatic carcinoma ( renal cell carcinoma ) that measured 15 mm and existed in the body of the pancreas . we could get only pancreas parenchyma ; tumor cells were not included in the sample . therefore , a difference in ability to diagnose due to the puncture site was not found . areas with target specimens appeared orange ( yellow arrows ) , and those without appeared dark brown ( blue arrows ) when observed with the tsci . b we could not always detect target specimens in eus - fna samples under white light . ppv , positive predictive value ; npv negative predictive value materials for which a final diagnosis was obtained via surgery or clinical follow up . this study verified the utility of the tsci previously developed by us , which is based on the absorption spectrum of human oxyhemoglobin reported by zijlstra et al 3 . when a target specimen was present in a sample observed with a light with a wavelength of 605 nm , the blood appeared dark brown due to light absorption , and the target specimen appeared orange because it did not absorb the light . the tsci was designed to detect the presence of pancreatic tissue and not necessarily malignant specimens , thus a specimen considered adequate by a tsci may not be representative of a tumor . however , the concordance rate between the tsci and histopathologic examination of eus - fna samples was 93.7 % . therefore , we were able to confirm that with the introduction of the tsci in eus - fna , it was possible both to collect the minimum necessary target samples by eus - fna and to end further procedures , even without performing rose . the difference between the mean number of total needle punctures and the mean number of necessary punctures was due to the need to maintain a high standards and accuracy for our patients . however , in the future , we will be able to finish sessions earlier based on evaluation of a tsci . specifically , by using a tsci , results will be better than when using the standardized approach based on a minimum of two passes for all pancreatic masses . the overall complication rate for eus - fna has been reported as 0 % to 2 % 1 4 . we finished eus - fna with an average of 1.2 punctures using the tsci , therefore , this approach seems likely to contribute to a decreased complication rate because many health care facilities are unable to perform rose due to lack of cytopathologists . in conclusion , the introduction of use of a tsci with eus - fna enabled both the collection of the minimum number of necessary samples by eus - fna and an end to further procedures , even without rose .

background and study aims : specimens collected by fine needle are microscopic and contain blood ; therefore , the presence of a target specimen within a sample is often difficult to confirm . although rapid on - site evaluation ( rose ) during endoscopic ultrasound - guided fine needle aspiration biopsy ( eus - fna ) is beneficial , many health care facilities are unable to apply this technique due to a lack of cytopathologists . the aim of this study was to develop and validate a device that detects the target specimen within pancreatic tumor eus - fna samples . patients and methods : fifty - eight consecutive patients with solid pancreatic masses were studied for a preliminary case series at a tertiary - care university hospital ( tottori university hospital , yonago , japan ) . the material collected was checked with a target sample check illuminator ( tsci ) and was evaluated by one cytopathologist . results : the agreement rate between the tsci and histopathology was 93.7 % . further testing procedures were not needed in 91.4 % of patients , and the mean number of needle punctures was 1.2 after a single pass using tsci . no adverse events were encountered with the procedure . conclusions : with the introduction of the tsci in eus - fna , it became possible to both collect the minimum necessary target samples by eus - fna and to end further procedures , even without performing rose .

over the past decade , the development of high - speed , wide - bandwidth tuneable light sources in conjunction with high - speed photodetectors has resulted in major gains in the horizontal and depth resolution of optical coherence tomography ( oct ) based instrumentation , thereby dramatically improving visualization capabilities during retinal and optic nerve examination [ 1 , 2 ] . as a result , oct has found its place as a widely accepted imaging technique , especially in ophthalmology . the principle of oct is based on interferometry [ 3 , 4 ] . in a typical early generation oct system , visible light ( i.e. , to visualise the beam ) and broadband , short - coherence length , near - ir light are coupled into one branch of a michelson interferometer . the light is then split into two paths , one leading to a reference mirror and the second is focused onto the retina . light is reflected and backscattered from refractive index interfaces within the retina according to the optical properties of each interface . the reflected light from the retina ( i.e. , the sample arm ) and from the reference mirror is recoupled into the interferometer , to ultimately be detected after interference in the spectrometer . using time domain oct , reflection sites at various depths in the tissue 400 a - scans / s ) , is prone to motion artifacts because of the slow scan speed , and makes real - time imaging impossible . the reference - arm mirror is also scanned at a constant velocity , allowing depth scans to be made pixel by pixel across the retina . broadband interference is measured with spectrally distinct detectors using fourier analysis ( i.e. , light signal frequency is modulated as a function of depth ) , thereby avoiding path length adjustment of the reference arm . the avoidance of depth scanning results in dramatic gains in imaging speed ( i.e. , 20,000 to 40,000 a - scans / s ) and improved signal - to - noise ratio , with an axial resolution of approximately 7 m , thereby permitting the acquisition of high - resolution , histological detail of the retina captured from the living human eye over a wide field of view . the much improved scan speed of sd - oct also permits 3d scanning , with minimal impact of eye movements . the sd - oct scans can also be referenced to simultaneously acquired 2d en - face images , thereby ensuring the accurate spatial location of each oct a - scan within the 3d image . an example of sd - oct imaging of a healthy retina is shown in figure 1 . in this study , we report on the clinical application of sd - oct using a series of case reports of patients with clinically defined common and/or classic eye diseases in order to highlight some of the potential , the limitations , and the clinical utility of this technology . patients were imaged using the heidelberg spectralis hra + oct ( heidelberg engineering , heidelberg , germany ) in sd - oct mode , using a scan field of 30 degrees horizontally and 15 degrees vertically and 19 to 25 oct horizontal sections ( one section at least every 240 m ) . digital fundus photography was undertaken using a canon digital fundus camera ( canon cr - dgi , canon inc . , japan ) with a resolution of 12.8 mega pixels . clinical assessment comprised visual acuity , stereo fundus biomicroscopy , and binocular indirect ophthalmoscopy , as appropriate . the heidelberg spectralis hra and oct ( heidelberg engineering , heidelberg , germany ; software version-1.6.1.0 ) can be used in any one of six imaging modes , that is , sd - oct , fluorescein angiography , indocyanine green angiography , autofluorescence , and red - free and infrared imaging . the heidelberg spectralis utilizes a broadband light source centered at 870 nm ( i.e. , no visible light beacon ) to simultaneously measure multiple wavelengths , a prerequisite of sd - oct imaging ( heidelberg retina angiograph 2 operating instructions ) . simultaneous confocal scanning laser ophthalmoscopy is used to generate high - resolution images of the retinal surface , thereby providing precise location information of each a - scan within a cross - sectional sd - oct image . sd - oct scanning generates 40,000 a - scans / second with an axial resolution of 3.5 microns / pixel digital ( 7 microns optical ) and a transverse resolution of 14 microns . alignment software continuously tracks any eye movement during image acquisition and then adjusts the position of the a - scan on the retinal surface to ensure accurate registration of cross - sectional oct images . using eye tracking and registration technology , multiple images are obtained from a precise location to then be averaged and filtered to remove random noise from the final image . the same eye tracking / registration technology is used to ensure that the instrument automatically rescans images that are influenced by blink artifacts . similarly , follow - up images are derived from the same area of retina , thereby eliminating subjective placement of the scan by the operator . this series comprised four selected cases ( one case each ) of age - related macular degeneration ( armd ) , diabetic retinopathy ( dr ) , central retinal artery occlusion ( crao ) , and branch retinal vein occlusion ( brvo ) . a 81-year - old female patient had a 20-year history of hypertension and a one - year history of type 2 diabetes . at first presentation , her best corrected visual acuity ( va ) in the right ( od ) and left ( os ) eyes was 20/50 and 20/70 , respectively . intraocular pressures ( iops ) were 18 mmhg od and 20 mmhg os . retinal examination revealed a large choroidal neovascular membrane ( cnvm ) and a probable serous pigment epithelium detachment ( ped ) od and soft macular drusen os ( not shown ) . a 51-year - old male patient presented with a 15 year history of type 2 diabetes , having taken oral medications for the first 11 years and having used insulin for the past 4 years . at the initial visit , the best corrected visual acuity was 20/30 ( od ) and 20/70 ( os ) with iops of 20 mmhg od and os . a 69-year - old male patient had a medical history of stroke and type 2 diabetes for fifteen years . the patient complained of blurry vision os for the past 4 months . at the initial visit , the visual acuity was counting fingers at 0.07 meters od and 20/200 os with an intraocular pressure of 24 mmhg and 18 mmhg . sd - oct imaging technology was used to acquire images of patients with various retinal diseases in order to evaluate the clinical utility , potential , and limitations of the technique . both sd - oct and conventional clinical techniques showed choroidal neovascular membrane and pigment epithelial detachment ( case of armd ) ; neovascularisation at the disc and elsewhere , fibrosis , epiretinal membrane , and laser scars ( case of dr ) ; retinal edema and haemorrhages ( case of brvo ) . in some circumstances , sd - oct provided visualization of morphological changes associated with retinal diseases that were either not immediately visible or not at all visible , using conventional clinical techniques . for example , sd - oct revealed neurosensory retinal detachment and bruch's / retinal pigment epithelium wrinkling ( case of armd ) ; cystoid spaces localised in the outer retina ( case of dr ) ; thickening and increased reflectance of inner retina ( case of crao ) ; localisation of depth of macular edema and of haemorrhages ( case of brvo ) . thus , sd - oct revealed structural retinal changes that are not visible by 2-dimensional limited fundus photography . conversely , the presence of colour information within the digital fundus photography images may be advantageous , while sd - oct uses a narrow spectrum of wavelengths and therefore has limited colour information . for example , in the case of the crao , conventional digital fundus photography showed the presence of infarction more prominently than the cslo and sd - oct imaging . previous studies have shown that sd - oct reveals retinal pathology that was not visible using td - oct , such as intra - retinal cysts and subretinal fluid . sd - oct also adds information to complete the clinical picture providing more detailed resolution of retinal changes , such as full - thickness folds of the rpe and intraretinal edema in case of rpe detachment , brvo , toxoplasma chorioretinitis , and polypoidal choroidal vasculopathy . a feature of the heidelberg spectralis instrument is the ability to undertake multiple mode imaging in addition to sd - oct , including fluorescein angiography , indocyanine green angiography and autofluorescence , and red - free and infrared imaging . these additional imaging modes also provide further information about retinal pathology that can aid diagnosis and management . the ability of sd - oct to clearly and objectively elucidate subtle morphological changes within the retinal layers provides information that could potentially be useful in the treatment of retinal diseases . this feature provides sd - oct with a clear superiority over other clinical techniques that do not possess the same resolution . first , high - resolution cross - sectional images allow better visualization of the vitreoretinal interface , the vitreous , retinal structures , and the choroid . furthermore , 3d images depict volumetric topographic retinal morphology that can be registered relative to images acquired at a different time point and , therefore , change in retinal morphology can be calculated . second , while taking a follow - up image of a particular patient , the software is capable of automatically and accurately registering images so that the identical retinal area is used to calculate change . this added functionality eliminates the possibility of human error and makes it easier to analyze the data with greater validity . however , automated segmentation of the internal limiting membrane and bruch 's membrane sometimes requires manual adjustment prior to analysis in patients with retinal diseases . this paper clearly demonstrates that hyperreflective lesions such as exudates and haemorrhages , as well as major retinal vessels , resulted in shadowing of the underlying retinal structures , and thereby details of the underlying morphology are lost . in the case exhibiting choroidal neovascular membrane ( i.e. , case 1 ) , and diabetic retinopathy / macular edema where the retinal thickness was over 400 m , it was hard to discern the underlying pathology and choroid the ability of sd - oct to clearly and objectively elucidate subtle morphological changes within the retinal layers provides information that can be used to potentially formulate diagnoses earlier and with greater confidence . the current generation of sd - oct instruments will not replace clinical retinal evaluation but do offer further information that can be valuable from a clinical perspective . it demonstrated the ability of sd - oct to clearly and objectively elucidate subtle morphological changes within the retinal layers that are not visible using conventional clinical techniques .

purpose . to present a series of retinal disease cases that were imaged by spectral domain optical coherence tomography ( sd - oct ) in order to illustrate the potential and limitations of this new imaging modality . methods . the series comprised four selected cases ( one case each ) of age - related macular degeneration ( armd ) , diabetic retinopathy ( dr ) , central retinal artery occlusion ( crao ) , and branch retinal vein occlusion ( brvo ) . patients were imaged using the heidelberg spectralis ( heidelberg engineering , germany ) in sd - oct mode . patients also underwent digital fundus photography and clinical assessment . results . sd - oct imaging of a case of age - related macular degeneration revealed a subfoveal choroidal neovascular membrane with detachment of the retinal pigment epithelium ( rpe ) and neurosensory retina . using sd - oct , the cases of dr and brvo both exhibited macular edema with cystoid spaces visible in the outer retina . conclusions . the ability of sd - oct to clearly and objectively elucidate subtle morphological changes within the retinal layers provides information that can be used to formulate diagnoses with greater confidence .

on anterior segment examination , she had iris abnormalities of hypoplasia , corectopia , and sclerocornea prominent at the lateral limbus of both eyes ( fig . cycloplegic retinoscopy was -3.5 diopters ( d ) in the right eye and -4.0d in the left eye . ocular alignment revealed 20 prism diopters ( pd ) of exotropia with 30pd of a - pattern deviation , more than 20pd of dissociated vertical deviation ( dvd ) , and severe so overaction ( sooa ) ( fig . dvd was frequently manifested in the left eye and sooa was also more severe in the left eye . after detaching the superior rectus ( sr ) during surgery , we observed that the so inserted more posteriorly than would normally be expected . the distances between the medial insertion of the so and that of the sr and between the lateral insertion of the so and that of the sr were 16 mm and 11 mm in the right eye , respectively , and 15 mm and 11 mm in the left eye , respectively ( fig . the so was composed of a fibrous band along its whole course under the tenon tissue . there was no ' whitish , fanned - out fiber ' temporal to the sr . the scleral insertions and the structures of the other rectus muscles were within normal limits for both eyes . we performed a 6 mm resection of the left medial rectus , an 8 mm recession of the sr , and a 4/5 posterior tenectomy of the so in both eyes . six months after surgery , the patient showed 6pd of exotropia in the primary position , 12pd of a - pattern deviation , dvd ( especially in the left eye ) , and moderate sooa ( especially in the right eye ) ( fig . ars is a clinical entity exhibiting anterior segment dysgenesis of schwalbe 's line , iris hypoplasia , corectopia , iris strands to the iridocorneal angle , glaucoma , and sclerocornea.1 non - ocular anomalies including a broad flat nose , maxillary hypoplasia , hypertelorism , dental hypoplasia , periumbilical skin folds , and heart defects are also manifested in ars.2 all of the associated ocular and systemic anomalies are known to arise from the maldevelopment of the neural crest . to date , three chromosomal loci ( 4q25 , 6p25 , 13q14 ) and two genes ( pitx2 and foxc1 ) have been linked to ars.3 in particular , pitx2 is known to encode a homeodomain transcription factor expressed in both the neural crest and mesoderm during eye development.4,5 pitx2 regulates the expression of other genes during embryonic development.6 extraocular muscles are known to derive from the periocular mesoderm.4,6 we therefore think that the development of the extraocular muscles is influenced by pitx2 , although the underlying genetic cascades have not been fully identified . diehl et al demonstrated that the morphogenesis of all extraocular muscle bundles is highly correlated with pitx2 gene expression and that the so and inferior oblique muscles were the most sensitive to pitx2 expression.4 based on these observations , we hypothesize that pitx2 influences the development of both the anterior segment and extraocular muscles in ars . to our knowledge , no study has reported anomalous extraocular muscle insertion in conjunction with ars in patients with strabismus . we believe that our findings are beyond the normal anatomic variations.7 in conclusion , we think that the anomalous structure and insertion of the so in our patient is an abnormal manifestation of the development of the extraocular muscles in ars . many patients with similar findings will need to be examined to elucidate the exact genetic mechanism behind this finding .

axenfeld - rieger syndrome ( ars ) is associated with ocular and systemic anomalies . pitx2 is known to be a major controlling gene in the pathogenesis of ars and is associated with differentiation in both the neural crest and mesoderm during eye development.a 4-year - old girl with bilateral ars had 20 prism diopters ( pd ) of exotropia with 30pd of a- pattern deviation , more than 20pd of dissociated vertical deviation ( dvd ) , and severe superior oblique overaction ( sooa ) . during surgery we observed that the so inserted more posteriorly than normal.we believe this finding is one of the abnormal manifestations of the development of the extraocular muscles in ars .

cat scratch disease ( csd ) is a worldwide zoonosis caused by bartonella henselae or possibly by bartonella clarridgeiae ( 1 - 3 ) . it is characterized usually a self - limiting regional lymphadenopathy , associated with a cat scratch or bite . originally considered rare , it is now recognized as a common cause of lymphadenopathy in children and young adults ( 2 ) . classic systemic disease includes a cutaneous inoculation by a scratch or bite followed by a regional lymphadenopathy after a variable period , ranging from 1 to 8 weeks . the number of pet cats is increasing in developed countries including korea . according to the increase in number of pet cats , zoonosis like csd has risen as a health problem in human society . in the past most cases of csd were diagnosed by clinical manifestations and intradermal reaction with specimens taken from patients before isolation of the causative organisms . due to the difficulty of isolation of b. henselae from csd patient , the diagnosis is usually based on serologic data and clinical history when informative . recently polymerase chain reaction ( pcr ) is used as a confirmative method with biopsy or aspiration specimen of lymph nodes from csd patients ( 4 - 6 ) . in korea this report deals with a case of csd confirmed by pcr assay using different sets of primers . a 25-yr - old previously healthy woman visited sanggyepaik hospital with high fever over 7 days and painful mass in the left neck . in spite of medication of oral antibiotics at a private clinic , her symptoms were not improved . she had been keeping a dog for 4 months before admission but had no history of contact with a cat . on admission the masses were 2 cm and 1.5 cm in diameter , and were tender . on physical examination liver and spleen was not palpable . there was no skin lesion or scratched wound in the face , extremity and trunk . she had a white cell count of 3,49010/l ( neutrophil , 87% ; lymphocyte , 8.6% ; monocyte , 3.2% ) , with platelets 10010/l , a hemoglobin of 12.1 g / dl . blood chemistry revealed : ast 71 iu / l , alt 62 iu / l , total bilirubin 0.3 mg / dl , bun 8 mg / dl , creatinine 0.7 mg / dl . laboratory findings showed elevated crp , but esr was 3 mm / hr . ana and anti - ds dna was negative . the computed tomography of the patient 's neck showed multiple variable - sized lymph nodes ( maximum 1610 mm ) . the serum sample from the patient was tested for b. henselae antibodies by using a commercial immunofluorescent assay ( bartonella ifa igg ; focus technologies , cypress , ca , u.s.a . ) . the fever and pain in the left neck area persisted during the treatment . under the impression of reactive lymphadenitis she had remained asymptomatic for 3 months . to prepare template dna from the lymph node aspirate , qiaamp dna tissue mini kit ( qiagen gmbh , hilden , germany ) was used . we selected the primer sets ( tn-1 , tn-2 , and ip ) for the glta gene used by margolis et al . ( 5 ) and the primer sets ( papn1 , papn2 , and papns2 ) for the pap 31 gene used by zeaiter et al . ( 6 ) . seminested pcr protocols for amplification of the b. henselae glta and pap31 genes were applied to the sample ( table 1 ) . the size of the amplified dna fragments was 139 bp and 211 bp for the glta and pap31 genes respectively ( 6 , 14 ) . ip and tn-1 were used ( 5 ) and for pap31 , papns2 and papns1 were used ( 6 ) . they were sequenced at both directions with bigdye terminator v3.1 cycle sequencing kit ( applied biosystems , foster , ca , u.s.a . ) . sequencing products were resolved with abi 3,730 xl autoanalyzer ( applied biosystems , foster , ca , u.s.a . ) . the sequences were aligned with the glta or pap31 sequences available in genbank for b. henselae isolates . the patient 's pcr product for glta had a consistent sequence of b. henselae and for pap31 gene showed a consistent sequence corresponding to main genogroup of b. henselae houston ( fig . to prepare template dna from the lymph node aspirate , qiaamp dna tissue mini kit ( qiagen gmbh , hilden , germany ) was used . we selected the primer sets ( tn-1 , tn-2 , and ip ) for the glta gene used by margolis et al . ( 5 ) and the primer sets ( papn1 , papn2 , and papns2 ) for the pap 31 gene used by zeaiter et al . ( 6 ) . seminested pcr protocols for amplification of the b. henselae glta and pap31 genes were applied to the sample ( table 1 ) . the size of the amplified dna fragments was 139 bp and 211 bp for the glta and pap31 genes respectively ( 6 , 14 ) . were used ( 5 ) and for pap31 , papns2 and papns1 were used ( 6 ) . they were sequenced at both directions with bigdye terminator v3.1 cycle sequencing kit ( applied biosystems , foster , ca , u.s.a . ) . sequencing products were resolved with abi 3,730 xl autoanalyzer ( applied biosystems , foster , ca , u.s.a . ) . the sequences were aligned with the glta or pap31 sequences available in genbank for b. henselae isolates . the patient 's pcr product for glta had a consistent sequence of b. henselae and for pap31 gene showed a consistent sequence corresponding to main genogroup of b. henselae houston ( fig . csd , caused by bartonella henselae , is a worldwide zoonosis associated with a variety of clinical manifestations . typically , a nontender papule develops in the scratch line , three to 10 days after exposure , healing without scarring in two or three weeks . regional lymphadenopathy follows in more than 80% of cases , but resolves usually within two to three months ( 7 ) . atypical csd are reported up to 25% of cases ( 8) . the manifestations of atypical csd are fever of unknown origin , neuroretinitis , encephalopathy , hepatosplenic granuloma , juvenile rheumatoid arthritis . nowadays , b. henselae infection is regarded as a common cause among patients with fever of unknown origin ( 9 ) . the epidemiological and clinical characteristics of csd have been well delineated in countries other than korea ( 2 , 8) . domestic cats or dogs are the reservoirs for b. henselae and it is transmitted through scratches or bites ( 7 , 11 , 12 ) . however , no history of animal contact can be elicited in small percentage of csd patient . cat scratch disease is usually a self - limiting disease and does not require therapy . but , some patients with multi - system involvement may benefit from antibiotics treatment , so it is necessary to identify the organism rapidly by clinical laboratory assay . the diagnosis of csd is made currently on the basis of clinical criteria in addition to a recent history of cat or dog exposure , a scratch or a flea bite plus bacteria culture , histologic examination of tissue biopsies and serologic test . although serologic analysis by immunofluorescence or enzyme linked immnuosorbent assay is a useful tool for the diagnosis of b. henselae infection , the specificity of serological assay has been questioned due to the cross reactivity between b. henselae and other species ( 13 ) . also antigenic variability within the species pcr assays appear to be very useful in confirming clinically suspected csd and have advantage of rapid diagnosis with the reliability since it is independent on the patient 's humoral response . recent studies relied on pcr amplification to improve diagnosis of csd ( 4 - 6 , 14 ) . earlier assays targeted amplification of 16s rrna gene which is present in all bacteria with species polymorphism ( 14 ) . pcr assay using the amplification of a portion of the citrate synthase gene ( glta ) followed by taqi restriction digest of the products is a sensitive tool for the detection of b. henselae dna in tissue biopsy specimens and pus aspirates from lymph nodes of patients with csd , but require large amounts of clinical material . the pap 31 gene encodes a major protein associated with a phage from b. henselae and allowed the classification of its strains into two clusters , b. henselae houston-1 and b. henselae marseille ( 6 ) . avidor et al . ( 14 ) demonstrated that pcr diagnosis of csd from fine needle aspiration and primary lesion specimens can be minimally invasive and highly accurate , so precluding the necessity for excision biopsy . in this case , antibody titer to b. henselae was positive ( 1:64 ) and corresponding sequence to major genogroup b. henselae houston was detected by pcr analysis of lymph node tissue by fine needle aspiration . pcr offers a rapid and specific means to detect the organism directly from clinical specimens in csd patients . and it is more sensitive than isolation when performed on suitable clinical samples such as fresh or frozen lymph node tissues . in conclusion , when presented with lymphadenopathy , physicians should inquire about recent cat , dog , or pets contact and/or animal scratches considering the possibility of csd .

we report a case of cat scratch disease caused by bartonella henselae in korea . a 25-yr - old woman developed left cervical lymphadenopathy with history of contact with a dog . the cervical lymphadenopathy persisted for 1 month and resolved gradually and spontaneously . serologic test was not done during the acute stage of the disease . immunofluorescent antibody test performed during the convalescent stage was positive for b. henselae . to confirm b. henselae infection , polymerase chain reaction ( pcr ) analysis using aspirates of cervical lymph node was performed and the presence of b. henselae dna was demonstrated . this is the first reported case of cat scratch disease in korea confirmed by pcr for b. henselae dna .

cerebral palsy ( cp ) is defined as non - progressive brain damage that occurred when the brain was immature . children with cp experience stiffness , contractures , weakening muscle strength , sensory defects , and difficulties in balancing and motion control , which can lead to functional disabilities1 . in the type of cp , spastic diplegic cerebral palsy affects stiffness of the limbs on both sides anatomically and kinematically , and affects the lower extremities more than the upper extremities2 . children with spastic diplegic cerebral palsy experience decrease of muscle strength in their lower extremities due to reduced functional activities for a long time , which is followed by reduced motor ability3 . in particular , the severe decrease of muscle strength occurs at the knee extensors , dorsiflexors , and plantar flexors of children with spastic diplegic cerebral palsy4 , 5 . in previous studies , a number of training methods such as muscle strengthening training , isotonic muscle strengthening training , and isokinetic muscle strength training using resistance have been reported in order to improve muscle strength in lower extremities of children with spastic diplegic cerebral palsy6 . however , it is difficult for children with cp to continue monotonous muscle strengthening training because monotonous training methods are difficult to keep interest and motivate in children . on the other hand , a multisensory dynamic balance training can overcome the monotonous training methods by allowing the children to perform active exercise while watching the monitor7 . furthermore , most muscle evaluation methods conducted in south korea s clinical fields are not based on objective analysis methods , but rather employ a scoring method after observing the performance of patients8 . to overcome this subjective scoring method , ultrasonography produces ultrasound images , which are compared and analyzed , thereby influencing treatment mechanisms and methods in clinical fields9 . thus , the purpose of the present study was to investigate the effects of a multisensory dynamic balance training on ultrasonographic muscle thickness such as the rectus femoris , tibialis anterior , medial gastrocnemius , and lateral gastrocnemius in children with spastic diplegic cerebral palsy . this study was conducted from july to october 2015 after receiving approval from the bioethics committee of daegu university . all study participants and guardians were informed of the study s purpose and procedures methods and gave consent for participation . the participants were 15 children diagnosed with spastic diplegic cerebral palsy who were outpatients of the d hospital in daegu ( 5 female and 10 male children ) . the selection criteria were children with spastic diplegic cerebral palsy who belonged to gmfcsi iii and who had a level of stiffness that was less than 2 on the mas , children without visual and auditory deficits , and children who had not had orthopedic surgery or botuline toxin treatment in the last six months ( table 1table 1.general characteristics of subjectsexperimental groupcontrol groupgenderm64f23age ( years)14.88 3.8014.14 3.67height ( cm)153.75 17.98154.29 20.68weight ( kg)48.75 16.0746.29 12.94gmfcs ( score)1.75 0.711.57 0.53 ) . in this study , the subjects were divided into each group by using randomized control traial with a blinded evaluator . an experimental group consisting of eight subjects who conducted only a multisensory dynamic balance training and control group consisting of seven subjects who conducted only general physiotherapy that focused on dynamic balancing and muscle strengthening exercises based on neurodevelopmental treatment . the intervention period was six weeks for both groups and the exercises were conducted 30 minutes per day , three times per week . an examination was conducted prior to the intervention and a post examination was conducted after the 6-week intervention . a bal pro ( man & tel co. , korea ) was used as the dynamic balance trainer and knee joint movements were applied . the balance trainer consists of a screen , a pressure sensor that can sense the horizontal movements of weight loads on the foothold , a tilt sensor that can perceive the angle of the knee joint , and a main body that contains programs that process the information perceived by the tilt sensor . the pressure sensor on the foothold can sense the body weight centers of the patients to help them move horizontally using a finger - shaped cursor on the screen during the exercise as the body weight moves to the right or left . the training involves using the cursor to touch various pieces of fruit arranged randomly on a tree on the screen10 . an accuvix v10 ( samsung medicine co. , south korea ) and 10 mhz linear probe were used as the ultrasonic measuring system for the examinations . all measurements were conducted by a physical therapist who was blinded to this study s purpose and which group the subjects belonged . the thicknesses of the rectus femoris , which is a knee extensor group ; the tibialis anterior , which is an ankle joint dorsiflexor group ; and the medial and lateral gastrocnemius , which are plantar flexors ; were measured . all measurements were conducted while the subjects were in a comfortable position without muscle contraction11 , 12 . a paired t - test was performed for the intragroup comparison , and an independent t - test was done for the intergroup comparison . the measurement results of the muscle thickness in the rf , mgcm and lgcm muscle showed that the experimental group had a significant increase in the thickness values before and after the exercise ( p<0.05 ) , and the control group had no significant increase in the thickness values before and after the exercise ( p>0.05 ) . the measurement results of the muscle thickness in the ta showed that both the experimental and control groups had a significant increase in the thickness values before and after the exercise ( p<0.05 ) . the test results of the rf , mgcm and lgcm muscle thickness values between the groups showed a significant difference ( p>0.05 ) ( table 2table 2.comparison of muscle thickness for each group at pre - test and post - testexperimental groupcontrol grouppre - testpost - testpre - testpost - testrectus femoris ( cm)1.96 0.432.11 0.43**1.57 0.511.59 0.49tibialis anterior ( cm)1.61 0.421.80 0.45 * 1.47 0.361.58 0.35*medial gastrocnemius ( cm)1.16 0.261.28 0.26**1.08 0.341.04 0.14lateral gastrocnemius ( cm)1.09 0.211.16 0.17**0.90 0.210.95 0.21mean se.*significant difference within the group ( p<0.05 ) , * * significant difference between the groups ( p<0.05 ) ) . * significant difference within the group ( p<0.05 ) , * * significant difference between the groups ( p<0.05 ) thus , the present study aimed to determine the effects of a multisensory dynamic balance training on muscle thickness in the lower extremities of children with spastic diplegic cerebral palsy and whether the multisensory dynamic balance training can be proposed as a new treatment method . the study results showed that the multisensory dynamic balance training significantly and statistically increased the thicknesses of all four muscles ( rectus femoris , tibialis anterior , medial gastrocnemius , and lateral gastrocnemius ) . this result indicated that balance training that applies knee joint motions stimulates a proprioceptor , thereby increasing sensory nerve signaling from the pressure receptors of ankle joints , which led to an increase in the motion control of the surrounding muscles of the ankle and knee joints13 . moreover , the comparison results of muscle thickness between the experimental and control groups in this study showed a significant difference in the thickness of the rectus femoris , medial gastrocnemius , and lateral gastrocnemius after the training . this result indicated that the rectus femoris played a role in the extension of the knee joint as well as the flexion of the hip joint while gastrocnemius played a role in the plantar flexion of the ankle joints as well as the flexion of the knee joints . these muscles are two - joint muscles and they were considered more effective to increase in the muscle thickness of rectus femoris , medial gastrocnemius , and lateral gastrocnemius in the multisensory dynamic balance training of the experimental group than in the control group due to the motions of flexion and the extension of the knee joints . moreover , gastrocnemius and rectus femoris were positioned in an extended location in a relative sense due to the feet located at the posterior of the knee during knee joint flexion . here , the extended muscle was combined with the balance training equipment , thereby improving the gastrocnemius and rectus femoris more significantly than the other muscles due to the relationship between length and tension14 . as a result , children with spastic diplegic cerebral palsy should focus on the functions of all muscles and joints in the lower extremities rather than focusing on each individual muscle and joint . the limitation in this study include a lack of functional outcome measurement , a small subject size and a lack of accessibility to the balance training machine . through the study results , knee joint motion - applied balance training was found to be effective for improving the musculoskeletal structure of children with spastic diplegic cerebral palsy .

[ purpose ] this study aimed to investigate the effects of multisensory dynamic balance training on muscles thickness such as rectus femoris , anterior tibialis , medial gastrocnemius , lateral gastrocnemius in children with spastic diplegic cerebral palsy by using ultrasonography . [ subjects and methods ] fifteen children diagnosed with spastic diplegic cerebral palsy were divided randomly into the balance training group and control group . the experimental group only received a multisensory dynamic balance training , while the control group performed general physiotherapy focused balance and muscle strengthening exercise based neurodevelopmental treatment . both groups had a therapy session for 30 minutes per day , three times a week for six weeks . the ultrasonographic muscle thickness were obtained in order to compare and analyze muscle thickness before and after in each group . [ result ] the experimental group had significant increases in muscle thickness in the rectus femoris , tibialis anterior , medial gastrocnemius and lateral gastrocnemius muscles . the control group had significant increases in muscle thickness in the tibialis anterior . the test results of the rectus femoris , medial gastrocnemius and lateral gastrocnemius muscle thickness values between the groups showed significant differences . [ conclusion ] in conclusion , a multisensory dynamic balance training can be recommended as a treatment method for patients with spastic diplegic cerebral palsy .

spinal cord injury patients , who manage their bladder using a condom catheter , are at risk of developing urine retention when they consume large volumes of alcoholic drinks within a short period of time . he went out socializing during which he consumed large volumes of alcohol but did not take any recreational drugs . the following morning , he noticed distension of the lower abdomen and passed urine in dribbles . after 8 days , he referred himself to a spinal unit at regional spinal injuries centre , southport . the blood test results showed the following : blood urea : 19.8 mmol / l ; creatinine : 172 mol / l ; and c - reactive protein : 336.4 mg / l . a computed tomography scan revealed an enlarged , swollen left kidney , indicating acute bacterial nephritis . spinal cord injury patients using condom catheters should be made aware of the risk of urine retention when they consume large amounts of alcoholic drinks in a short period of time . patients and caregivers should be informed to consider intermittent catheterizations for 2448 hours or insert indwelling urethral catheter when planning for an evening out . condom catheter is indicated in male spinal cord injury patients with urinary incontinence provided that they have no penile lesion , and intravesical pressures during storage and voiding are urodynamically safe.1 however , detrusor function may be influenced by other factors such as consumption of large volumes of alcohol and other fluids within a short period of time . alcohol - induced bladder dysfunction has been reported , but the mechanism of its development is varied and unclear.2 we report a spinal cord injury patient using condom catheter , who developed urinary retention following a social get - together . adequate drainage of the urinary bladder was not provided for 8 days ; consequently , this patient developed sepsis and acute kidney injury . a 21-year - old british male sustained c-5/c-6 complete tetraplegia in 1998 . since 2006 , this patient had been managing his bladder by condom catheter and had no problems . this patient was reviewed in a spinal unit at regional spinal injuries centre , southport in november / december 2013 . an x - ray of the abdomen revealed no urinary tract calcification ; urinary bladder was not distended ( figure 1a ) . mmol / l ) of urea and 49 mol / l ( 0135 mol / l ) of creatinine . ultrasound examination of the urinary tract revealed normal kidneys and no hydronephrosis or calculi . the urinary bladder contained 62 ml of urine with moderate wall thickening ( figure 2 ) . this patient had a well - established bowel regime and was doing all right with his neuropathic bowels and bladder . in 2014 , this patient went for an evening out with his friends and had several drinks within a short period of time . he did not take any recreational drugs during partying . following this social get - together the next morning , he noticed swelling of the lower abdomen and passed urine in dribbles . this patient continued to feel unwell , and he came to the spinal unit 8 days after he went for an evening out with his friends . on clinical examination , it was found that the urinary bladder was distended ; bowel sounds were feeble ; temperature : 36.4c ; heart rate : 109 bpm ; and blood pressure : 90/43 mmhg . an x - ray of abdomen revealed large distended urinary bladder ( figure 1b ) . blood tests showed the features of sepsis and acute kidney injury ; urea : 19.8 mmol / l ( 2.37.5 mmol / l ) ; creatinine : 172 mol / l ( 0135 mol / l ) ; potassium : 5.7 mmol / l ( 3.55.2 mmol / l ) ; c - reactive protein : 336.4 mg / l ( < 5.0 mg / l ) ; white cell count : 18.410 ( 4.011.0 ) ; and neutrophils : 16210 ( 2.07.5 ) . a computed tomography scan of the abdomen revealed mildly enlarged and swollen left kidney with some perinephric fluid . after decompression of the urinary bladder , urethral catheter started draining blood - stained urine . the sample of urine sent for cytology showed abundantly mixed inflammatory cells , some red blood cells , squamous epithelial cells , macrophages , and scattered urothelial cells in which there was focal atypia in the form of nuclear enlargement , which was probably reactive in nature . following drainage of the urinary bladder , blood urea decreased to 9.5 mmol / l ( 2.37.5 ) ; creatinine decreased to 62 mol / l ( 0135 ) ; and potassium decreased to 3.3 mmol / l ( 3.55.2 ) . a week after instituting bladder drainage by urethral catheter , blood urea decreased further to 5.4 mmol / l ( 2.37.5 ) ; creatinine level also decreased to 46 mol / l ( 0135 ) ; c- reactive protein decreased to 31.4 mg / l ( < 5.0 ) ; and white blood cell count decreased to 9.810 ( 4.011.0 ) . seventeen days after urethral catheterization and decompression of urinary bladder , catheter - free trial was given . but this patient could not pass urine ; therefore , indwelling urethral catheter drainage was reestablished . alcohol consumption increases the volume of urine held within the bladder and dulls the senses such that the patient has a reduced urge to void , despite the increased bladder volume.3 alcohol - induced diuresis causes bladder distension and thinning of the bladder wall . jairam et al reported a patient developing spontaneous rupture of urinary bladder and oliguric renal failure after an alcohol binge.4 our patient developed urinary retention following consumption of several drinks within a short spell of time during social get - together ; subsequently , he developed a temperature and acute kidney injury ; fortunately , he did not sustain a rupture of the urinary bladder . this case illustrates the need to educate male spinal cord injury patients using condom catheters , their caregivers , and health professionals the risk of urinary retention when large amounts of alcoholic drinks is taken in a short period of time . when planning for a party that involves consumption of several drinks , spinal cord injury patients using condom catheter for bladder drainage should remember that they may require either intermittent catheterization for 2448 hours or indwelling catheter . otherwise , such patients can develop urinary retention , which in turn predisposes to urine infection , sepsis , acute kidney injury , and very rarely , rupture of urinary bladder . spinal cord injury patients who manage their urinary bladder by condom catheters run the risk of urine retention if they consume large amount of alcoholic drinks in a short spell of time . spinal cord injury patients and carers should be made aware of this eventuality when they plan an evening out ; they should consider performing intermittent catheterization for the next 2448 hours or insert indwelling urethral catheter to ensure adequate drainage of urinary bladder . written informed consent was obtained from the patient for publication of this case report and any accompanying images .

backgroundspinal cord injury patients , who manage their bladder using a condom catheter , are at risk of developing urine retention when they consume large volumes of alcoholic drinks within a short period of time.case presentationa male tetraplegic patient had been managing satisfactorily penile sheath drainage for 8 years . he went out socializing during which he consumed large volumes of alcohol but did not take any recreational drugs . the following morning , he noticed distension of the lower abdomen and passed urine in dribbles . he then developed a temperature and became unwell . he was seen by district nurses and a doctor , who prescribed antibiotics . he continued to feel unwell . after 8 days , he referred himself to a spinal unit at regional spinal injuries centre , southport . the blood test results showed the following : blood urea : 19.8 mmol / l ; creatinine : 172 mol / l ; and c - reactive protein : 336.4 mg / l . urethral catheterization led to immediate drainage of 1,400 ml of urine . a computed tomography scan revealed an enlarged , swollen left kidney , indicating acute bacterial nephritis . he was prescribed intravenous fluids and meropenem . creatinine decreased to 46 mol / l.conclusionspinal cord injury patients using condom catheters should be made aware of the risk of urine retention when they consume large amounts of alcoholic drinks in a short period of time . patients and caregivers should be informed to consider intermittent catheterizations for 2448 hours or insert indwelling urethral catheter when planning for an evening out .

cachexia is a wasting syndrome for which descriptions may be found as far as 2000 years ago , and is a consequence of cancer and other diseases , such as chronic obstructive lung disease , multiple sclerosis , congestive heart failure , tuberculosis , and aids , among others , with a high impact on quality of life . in this review , we focus primarily on cancer cachexia , which affects approximately half of all patients with cancer . in advanced stages the condition compromises the responsiveness to cancer treatment and represents , per se , the direct cause of death of up to 20% of all patients . the syndrome is characterized by unintentional significant reduction in body weight and , among other symptoms , reduced energy intake , fatigue , systemic inflammation , and metabolic abnormalities are frequently reported . despite the long search for etiologic factors underlying cachexia , and the fact that many scientific efforts have been devoted to its understanding , researchers agree that we are still a long way from knowing the whole truth about the exact mechanisms behind its etiology , which makes it very hard to diagnose and treat the syndrome , frustrating physicians and patients . the most widely accepted hypothesis is that cachexia would appear as the result of tumor - host interactions ( figure 1 ) , being deeply related to the increase and release of proinflammatory factors ( figure 2 ) [ 8 , 9 ] . marked weight loss is the central symptom in many of the proposed diagnostic criteria [ 1012 ] . in 2011 , the syndrome would thus develop through three different and specific stages : precachexia , when anorexia and metabolic changes may be observed before weight loss ; cachexia itself , with a weight loss 5% or bmi 20 and weight loss 2% or sarcopenia and weight loss > 2% and often reduced food intake and systemic inflammation ; and , finally , refractory cachexia , in which survival expectance usually does not exceed three months . in the wasting scenario in cancer cachexia neuroendocrine changes play an important part , provoking early satiety and aversion to food and leading to undernutrition . these , combined with diminished food absorption and hypermetabolism , lead to a negative energy balance [ 14 , 15 ] and contribute to the loss of mass , specially of adipose tissue and of skeletal muscle . nevertheless , peripheral tissues are highly affected by cachexia even before the presence of anorexia . thus , the loss of adipose tissue and skeletal muscle mass precedes any decrease in food intake , which at the initial period of wasting can be normal or even increased [ 17 , 18 ] . these tissues exhibit impaired homeostasis and altered metabolism , resulting in increased lipolysis in the adipose tissue and augmented proteolysis in the skeletal muscle . the white adipose tissue seems to be importantly adding to the inflammatory status in cachexia . several studies showed that circulating levels of cytokines are altered in cachectic patients [ 1922 ] . these cytokines elicit an inflammatory response in the adipose tissue , which then releases chemoattractant proteins , which in turn will recruit immune cells from the blood stream ; these cells infiltrate the tissue , provoking further release of proinflammatory mediators . as a consequence , lipolysis is activated , causing adipocytes and immune cells to secrete , in a vicious cycle , proinflammatory mediators such as tumor necrosis factor ( tnf - alpha ) , interleukin- ( il- ) 1 , interferon - gamma ( inf - gamma ) , and il-6 . these cytokines may reach other tissues through the circulation and are associated with increased muscle catabolism and reduced muscle protein synthesis . on the other hand , this organ responds by increasing the uptake of these substrates , which , ultimately , may lead to the onset of steatosis and the induction of acute phase protein secretion . recently , changes in metabolism and in aspects of the inflammatory response have been found to be modulated by mirnas , which are small noncoding rnas of approximately 1925 nucleotides ( nt ) , known to be regulatory molecules for some of the most important levels of genome function , including chromatin structure , chromosome segregation , transcription , rna processing , rna stability , and translation . these molecules are widely found in organisms including plants , nematodes , fruit flies , and mammals and are highly conserved among evolution . mirna biogenesis involves the transcription of genomic dna by rna polymerase ii to produce primary mirna transcripts ( pri - mirna ) . in sequence , the drosha - dgcr8 rnase complex initiates mirna maturation through the cleavage of a stem loop into the primary transcript . this generates a 60- to 70-nucleotide - long mirna precursor , the pre - mirna , characterized by the presence of an overhang of 2 - 3 nucleotides , still in the nucleus . the newly produced pre - mirna is then transported to the cytoplasm by exportin5 and processed to a double - stranded rna molecule of about 19 to 25 nucleotides in length by yet another enzyme , the dicer . once incorporated into the effector complex mirisc ( mirna - induced silencing complex ) , one strand of the recently produced rna molecule remains as a mature mirna [ 26 , 27 ] , while the other strand may be either degraded , incorporated into another mirisc , or exported to the periphery by exosomes to exert its effects in a paracrine or endocrine way [ 28 , 29 ] . the complex mirisc , together with the recently incorporated mature mirna , acts directly on the mrna to repress the translation of target genes by cleavage ( perfect or near - perfect binding ) or by forming a hairpin in the 3utr , through imperfect base pairing . the binding site may also not be in the 3utr , but in the orf or 5utr region of the target . according to the mirbase , over 6,000 mirna genes were identified in more than 223 known species , including viruses , plants , fungi , and animals . in humans , computational analysis estimates that more than 50% of human protein - coding genes are putatively regulated by mirnas . the expression of mirnas is highly dependent on tissue type , metabolic status , and presence of disease . several studies describe mirnas as important regulators of biological processes as cellular differentiation , proliferation , tissue development , and cell - type specific function and homeostasis . nowadays , an increased number of diseases have been found to be associated with altered mirnas expression [ 3436 ] . several mirnas have been studied and confirmed as having a role in inflammatory processes in peripheral tissues such as adipose tissue and muscle . moreover , there is strong evidence that mirnas would function as an effective system that regulates the magnitude of inflammatory responses , by displaying effects on cellular development and aspects of cellular function . mirnas such as mir-1 , mir-133a , mir133-b , mir-206 , mir-208 , mir208b , mir486 , and mir-499 are part of this group and are associated with cell growth and differentiation , stress responsiveness , and protection against apoptosis [ 39 , 40 ] . muscle protein degradation in cachexia is mainly mediated by the ubiquitin proteasome system , which is induced through the activation of e3 ligases , atrogin-1/mafbx , and murf-1 . the forkhead box o ( foxo ) signaling pathway participates in this process by the induction of the transcription of e3 ubiquitin ligases and has three members in skeletal muscle ( foxo1 , foxo3 , and foxo4 ) . muscle - specific overexpression of these proteins is described as sufficient to cause skeletal muscle atrophy in vivo ; and inhibition of foxo transcription activity prevents muscle fiber atrophy during cachexia . xu and colleagues verified that the mirna-486 decreases foxo1 protein expression and promotes foxo1 phosphorylation to suppress e3 ubiquitin ligases , presenting an excellent candidate for future studies on the mechanisms of regulation of muscle atrophy by mirnas in cachexia . mir-206 and mir-21 were also recently described as having a role in muscle wasting in catabolic conditions . mir-21 has been already confirmed as being produced and exported from tumor cells of rodent and humans and uptaken by the skeletal muscle , in exosomes . the effect of this process is the onset of proteolysis through toll - like receptor 7 signaling , in a jnk dependent manner . moreover , the detection of aberrant mirna expression in body fluids , that is , blood , urine , and saliva , opens ways to explore these molecules as diagnostic and prognostic tools for cancer cachexia . mirnas are also known to play a major role in the regulation of the transcription of several genes involved with key aspects of white adipose tissue metabolism . to date , one study involving cachectic patients , white adipose tissue , and mirna profile is available in the literature . in this study , mir-378 is strongly involved with catecholamine - stimulated lipolysis in adipocytes and modulates the expression of key lipolytic proteins such as lipe , plin1 , and pnpla2 . no information is available in the literature about mirnas expression and the modulation of inflammation in the white adipose tissue in specific wasting conditions . however , xie et al . , 2009 , demonstrated that a chronic inflammatory environment characterized by high cytokine concentration may , per se , change mirna pattern expression in the white adipose tissue , both in cultured differentiated adipocytes and in rodent models . potential mirna candidates for studies regarding adipose tissue inflammation and cachexia would be mir-155 , mir-146a , mir-21 , and mir-9 , whose expression is induced by the activation of innate immune system through toll - like receptors . considering that mirnas are known to regulate the expression of genes involved in several types of diseases as cancer and autoimmune disorders [ 34 , 35 ] and play a pivotal role in the regulation of inflammatory responses , the study of mirnas in cachexia is a promising field of research , and patients could benefit not only from the development of new targets for treatments , but also from earlier diagnosis . the discovery of noncoding rnas and the improvement of molecular biology techniques have changed the concept that inflammation could be understood and explained by the study of signaling pathways and by the contribution of specific proteins . knowledge on the regulation of gene and protein expression has changed profoundly , and mirnas are nowadays established as pivotal components of the signaling networks that modulate inflammatory processes , leading to wasting conditions such as cachexia . based on such evidence , we propose that mirnas participation in the onset and maintenance of cachexia should be added to the study of the syndrome ( figure 3 ) .

cancer cachexia is a paraneoplastic syndrome compromising quality of life and survival , mainly characterized by involuntary weight loss , fatigue , and systemic inflammation . the syndrome is described as a result of tumor - host interactions characterized by an inflammatory response by the host to the presence of the tumor . indeed , systemic inflammation is considered a pivotal feature in cachexia progression and maintenance . cytokines are intimately related to chronic systemic inflammation and the mechanisms underlying the release of these factors are not totally elucidated , the etiology of cachexia being still not fully understood . therefore , the understanding of cachexia - related mechanisms , as well as the establishment of markers for the syndrome , is very relevant . micrornas ( mirnas ) are a class of noncoding rnas interfering with gene regulation . different mirna expression profiles are associated with different diseases and inflammatory processes . mirnas modulate adipose and skeletal muscle tissue metabolism in cancer cachexia and also tumor and tissue derived inflammation . therefore , we propose a possible role for mirnas in the modulation of the host inflammatory response during cachexia . moreover , the establishment of a robust body of evidence in regard to mirnas and the mechanisms underlying cachexia is mandatory , and shall contribute to the improvement of its diagnosis and treatment .

eccrine syringofibroadenoma ( esfa ) is a very rare benign tumour of the acrosyringeal part of the eccrine duct . since its first description by mascaro , in 1963 , only around 50 cases it usually involves distal extremities , presenting as solitary or multiple , coalescing , firm , pink or skin - coloured verrucous nodules of variable sizes in a it is presently classified into five types depending on its number , pattern , and associated features . diagnosis on clinical background is very difficult , and therefore , histopathological evaluation is imperative to confirm the diagnosis . a 65-year - old male presented with single , painful , non - healing ulcer on the right sole with multiple , pink verrucous nodules at the lateral margin of the ulcer , involving the right lateral malleolus and lateral border of the right sole since two years . on detailed history taking , it was revealed that two years ago , patient had a traumatic injury on his right sole for which he did not consult any registered medical practitioner and applied some homemade chemicals on the wound . surgical intervention was done to debride the wound by local , untrained , nonmedical personnel without proper antibiotic coverage , which led to secondary infections and nonhealing ulceration . within the next 6 months , after developing a fully - formed ulcer , multiple small pinkish nodular lesions appeared at the lateral margin of the ulcer , which increased in size with time , coalesced with other nodular lesions , and became verrucous . on local cutaneous examination , a deep seated ulcer of 6 cm 4 cm 2 cm size was seen over the right sole , whose floor was clean ( because of previous antiseptic cleaning ) and the margin was hyperkeratotic and macerated [ figure 1 ] . along the lateral border and on the lateral malleolus of right foot , multiple , coalescing , firm , pink - coloured verrucous nodules of varying sizes ( largest measuring 3 cm 2.5 cm ) in a there was no regional lymphadenopathy , no loss of sensation , nerve thickening , or any other cutaneous signs of leprosy . the family history , past medical history , routine laboratory investigations , and systemic examinations were non - contributory . deep ulcer over the right sole ( hyperkeratotic and macerated margin with clean floor ) multiple , coalescing , firm , pink - coloured verrucous nodules of varying sizes in a streusel - bread-like appearance to reach a final diagnosis , a wedge - shaped incisional biopsy was performed and the sample was sent for histopathological evaluation , which demonstrated vertically oriented , multiple , thin , anastomosing strands centred around the acrosyringium [ figures 3 and 4 ] forming a lattice of double - layered acrosyringeal ductal structures embedded in delicate fibrovascular stroma , extending into the reticular dermis [ figure 5 ] . vertically oriented proliferation of epidermis centred around acrosyringium extending into the reticular dermis ( h and e , 20 ) thin , anastomosing , vertical strand comprising acrosyringeal structures including ductal cuboidal epithelial cells ( arrow ) and lumina embedded in fibrovascular stroma ( h and e , 40 ) well - formed eccrine ducts with double - layered cuboidal cells ( h and e , 40 ) on the basis of detailed history , clinical presentations , and distinct histopathological features , diagnosis of esfa was made , and it was considered to be reactive in nature due to the traumatic nonhealing ulcer . it was first classified into the following four types by starink : solitary , multiple esfa associated with hidrotic ed - like schopf passarge syndrome ( eyelid cysts , hypotrichosis , hypodontia , nail hypoplasia ) or clouston syndrome ( palmoplantar keratoderma , patchy alopecia , nail dystrophy ) , multiple esfa without associated cutaneous findings , and nonfamilial unilateral linear esfa . in 1997 , the fifth type was recognized as reactive esfa by french as a ductal hyperplastic or hamartomatous process initiated by repeated damage to the eccrine structures by chronic inflammatory or neoplastic dermatoses such as diabetic foot ulcer , leprous neuropathy , venous stasis or insufficiency , burn scar , bp , eb , naevus sebaceous , stoma of ileostomy , palmoplantar erosive lp , trauma , chronic plaque type psoriasis , epithelioid haemangioendothelioma , and squamous cell carcinoma . reactive esfa is usually single and acrally located , but if multiple sites are involved , it is termed as apart from these five types , another clear cell variant was also reported by hu et al . in 2005 . its exact pathogenesis is not yet completely understood but there must be some alteration in the cellular growth and differentiation of epidermal and adnexal structures . based on few molecular studies , wnt/-catenin signalling pathway has been claimed to play the central role whose loss of inhibition or overexpression can lead to abnormal epidermal cellular differentiation and proliferation . clinically , esfa may have a variable presentation but usually it presents as asymptomatic , solitary or multiple , coalescing , firm , pink / skin - coloured verrucous nodules of variable sizes in a other less common sites of predilection are the face , back , abdomen , buttocks , palm , and nails . the clinical differential diagnoses are tuberculosis verrucosa cutis ( tvc ) , other atypical mycobacterial infections , deep mycoses , and squamous cell carcinoma ( scc ) . histopathological differential diagnoses will include eccrine poroma , acrosyringeal nevus , syringofibroadenocarcinoma , fibroepithelial tumor of pinkus , scc , and reticulated seborrheic keratosis ( sk ) . in case of acrosyringeal nevus , strong pas positivity and plasma cell infiltrate are the distinguishing features , whereas eccrine poroma shows a more uniform small epithelial cell proliferation with vertical thick strands of cells extending into the dermis . in syringofibroadenocarcinoma , there is an area of transformation where a malignant phenotype emerges displaying cytological atypia . fibroepithelial tumor of pinkus shows focal changes , which are typical of basal cell carcinoma with peripheral palisading and clefting artefact and loose fibrous stroma . histopathologically , it is characterized by distinct diagnostic features , which are observed as multiple , thin , anastomosing strands of cuboidal epithelial cells with ductal structures forming a lattice embedded in loose fibrovascular stroma and connected to the undersurface of the epidermis extending into the dermis . on immunohistochemistry , ductal cells stain positively with s-100 , carcinoembryonic antigen ( cea ) , and ck-19 , but in the presence of scarring , cea and ck-19 may be negative . this disease generally pursues a benign course , although malignant transformation to eccrine syringofibroadenocarcinoma has been reported in nonreactive esfa . complete surgical excision is the treatment of choice if the lesion is solitary , not very large , and not in close proximity to vital areas . other treatment options include co2 laser ablation or radiotherapy for lesions at difficult to treat sites . because of the risk of malignancy , regular follow up and close observation should be done if lesions are left without treatment . in previously reported cases of reactive type of esfa , neuropathic ulcer has been the most common underlying aetiology . trauma complicated by wrong surgical intervention followed by nonspecific secondary infections is a very rarely reported inciting factor for reactive esfa in the literature , as in our case .

eccrine syringofibroadenoma is a very rare benign tumour of acrosyringium of eccrine sweat duct . based on the evidences of known etiological factors , two forms have been proposed ; reactive and nonreactive . reactive forms are rarer , and on even rarer occasions , trauma complicated by secondary nonspecific infections may lead to the development of reactive eccrine syringofibroadenoma , as in our case . here , we are documenting a case of reactive solitary eccrine syringofibroadenoma in a 65-year - old male presenting with coalescing , firm , pinkish , verrucous nodules and painful deep ulceration on the right sole preceded by trauma and secondary infection . histopathologic revelation of distinctive microscopic findings confirmed the diagnosis in our case .

alcoholism is one of the major health and social problems faced in developing countries . although there are various drugs , none of them proved to be efficacious in the long run owing to the cost , adverse effects and the inadequate compliance for the long term management of alcohol de - addiction . for naltrexone and acamprosate , though approved in the west , their cost effects are a burden for the lower and middle class in the indian society . but its compliance rates are considerably affected due to the large number of adverse effects contributing to the high percentage of default rates . although majority of adverse effects was noted by poulsen et al , they also stated that it could not be differentiated from sobriety or manifestations of alcohol abuse . since efficacy of a medication depends on its mode of action , seriousness of illness and its toxicity , this cross - sectional study is aimed at noting the efficacy of 125 mg od dsm in contrast to the study conducted on 250 mg od dsm by srinivasan et al , on patients , initially in the hospital and later at the home setup under supervision . this study concentrated mainly on adverse effects , change in laboratory parameters and compliance rates . this cross - sectional study was conducted on alcohol - dependent patients who were undergoing detoxification for alcoholic de - addiction therapy in a private hospital for 40 days . dsm iv criteria , alcohol - dependent patients.alcoholics 20 - 60 years of age with normal liver function test 's after detoxification . alcoholics 20 - 60 years of age with normal liver function test 's after detoxification . relapse cases.liver function test 's above normal range . liver function test 's above normal range . patients satisfying inclusion criteria were examined and routine investigations like complete hemogram , lipogram , blood glucose , serum electrolytes , liver function test and occult blood in stool along with psychiatry evaluation before the administration of dsm and on the 30 and 60 days of dsm administration . patients received 125 mg of dsm od after lunch initially under supervision of hospital staff and later by the family members , to enhance the compliance rates . patients were followed up regularly during hospital stay for the first 30 days and later weekly up to the 60 day . at each follow up , drug adverse effects , alcohol consumption and default rate was noted . days of abstinencedropout rate ( > 5 alcoholic drinks/40 g alcohol in 24hr).adverse effects complainedalterations in the lab parameters dropout rate ( > 5 alcoholic drinks/40 g alcohol in 24hr ) . adverse effects complained alterations in the lab parameters statistical analysis was done using spss package , kruskal - wallis test , wileoxon - segned rank sum test , anova ( fishers test ) and students paired - t - test . dsm iv criteria , alcohol - dependent patients.alcoholics 20 - 60 years of age with normal liver function test 's after detoxification . alcoholics 20 - 60 years of age with normal liver function test 's after detoxification . liver function test 's above normal range . patients satisfying inclusion criteria were examined and routine investigations like complete hemogram , lipogram , blood glucose , serum electrolytes , liver function test and occult blood in stool along with psychiatry evaluation before the administration of dsm and on the 30 and 60 days of dsm administration . patients received 125 mg of dsm od after lunch initially under supervision of hospital staff and later by the family members , to enhance the compliance rates . patients were followed up regularly during hospital stay for the first 30 days and later weekly up to the 60 day . at each follow up , drug adverse effects , alcohol consumption and default rate was noted . days of abstinencedropout rate ( > 5 alcoholic drinks/40 g alcohol in 24hr).adverse effects complainedalterations in the lab parameters dropout rate ( > 5 alcoholic drinks/40 g alcohol in 24hr ) . adverse effects complained alterations in the lab parameters statistical analysis was done using spss package , kruskal - wallis test , wileoxon - segned rank sum test , anova ( fishers test ) and students paired - t - test . the results of this study indicated that there were few adverse drug reactions ( adr ) with dsm [ figures 17 ] . this may be due to either fallacious reporting or symptoms present in sobriety which was aggravated with dsm and those were tiredness , depression , nausea and anxiety . this is similar to the findings by zawar and nerliers vide figures 89 , where a thirty - three year old male developed pustular lesions after 42 - 43 days of dsm therapy . a forty seven year old male had an aggravation of psoriatic lesion after 32 days of dsm therapy shown in figure 10 . no instance of psychosis which is common in india was noted with 125 mg dsm when compared to the study conducted by srivasan et al . in our study , psychiatric clinical examination was done on admission , 30 , and 60 days . among these , 5 of them had depressive symptoms , 16 had hallucination and 10 of them had both the symptoms vide figure 1 . there were significant changes in lab parameters of sgpt(p=0.007 ) , sgot(p=0.001 ) , ggt(p=<0.001 ) , mcv(p=0.001 ) , serum cholesterol ( p=0.002 ) , serum hdl(p=0.05 ) , serum ldl(p=0.014 ) especially between first and third samples showing in dsm playing an important role in altering liver functions . figure 5 shows sgot having significant change in samples between 0 - 30 day and 0 - 60 day . in figure 6 , the variation in ggt values between 0 - 30 , 30 -60 , and 30 -60 days were significant as per wileoxon - segned rank sum test . mcv values between 0 - 30 , 30 - 60 , and 30 -60 days were significant based on students paired - t - test as shown in figure 7 . the adr was not of severe magnitude that necessitated withdrawal of drug or institution of life saving measures which was similar to the findings of liskow et al , and contrary to borup et al . no hepatic dysfunction was noted though it is a well known adr for which liver function tests were done during dsm treatment as per recommendations by wright et al , at 2 week interval at initial 2 months and later at 3 - 6 month interval . it may be due to careful selection of patients , low dose of dsm and short period of assessment . histogram of adverse drug reaction group - comparison values of individual lab parameters comparison between sgot samples taken on 0 , 30 , and 60 day comparison between ggt samples taken on 0 , 30 , and 60 day comparison between mcv samples taken on 0 , 30 and 60 day patient having a pustule in the anterior abdomen wall along left mid - clavicular line pustular lesion from a close view patient with dsm induced aggravated skin reaction dsm was well tolerated and had lesser dropout rate . the reason for dropouts includes easy availability of alcohol , failure of supervision and deceleration of motivation . patients find it difficult to differentiate between the symptoms of alcohol withdrawal and those due to adr of dsm none of the patients blamed adr in particular , for the default which is similar to the findings of srinivasan et al , and contrary to borup et al . although nitrazepam was used for the detoxification in the study , its influence in the de - addiction therapy per se is minimal . the effect of various drugs like naltrexone , dsm , acamprosate , fluoxetine and serotonergic agents like ondansetron used in the present day alcoholic de - addiction therapy is literary disappointing . ssri like fluoxetine has no effect on drinking behaviour per se , but it may treat underlying depression leading to drinking . benzodiazepines are effective as an adjuvant and are not the mainstay treatment in de - addiction therapy . studies showed that ondansetron is useful only in cases of early onset of alcohol dependence and topiramate is more efficacious than placebo but not as a long - term treatment option . the complex interplay of various systems like dopamine , opiod , serotonin , glutamate , gaba on addiction makes its treatment , a daunting possibility . this is reflected in the varied drugs that are used in alcohol de - addiction i.e. nalmefene , tiapiride , metronidazole , lithium , and ondansetron . presently dsm , naltrexone and acamprosate are approved drugs for alcohol de - addiction therapy . naidu et al , in their study , concluded that naltrexone had less craving for alcohol along with significant decline of ggt level when compared to dsm . also naltrexone had better outcome in reducing relapse rates when compared to that of acamprosate . a study by staffen et al , showed that dsm was better than naltrexone and acamprosate both on cost , efficacy and in reduction of alcohol craving and binge drinking.[1921 ] thus playing an important role in long term management in alcohol de - addiction along with effective psychotherapy and counseling unlike to the writings of mann and williams . other studies supporting for long term dsm management and it being better than other treatment protocols are petrakis et al , and de souza . although there were some adr , 76.5% of patients had taken full course of treatment and thereby it shows that adr werent the reason for default and dsm achieved better compliance without losing its primary deterrent action and psychological effects . since usage of dsm needs repeated physician 's advice and active decision process by the patient , fear and experience of dsm - ethanol reaction further helps him to continue sobriety . dsm - ethanol reaction noted in this dosage was of mild intensity which could be taken care at a primary care setting . to increase the efficacy of de - addiction management , combination of pharmacotherapy acting on various neuronal pathways one such methodology is usage of dsm implants alone or in combination with naltrexone for higher abstinence rates . long - term acting injectables are another way to look forward in order to avoid supervision and achieve long - term compliance rates . molecular and behavioral advances can be utilized interfering with alcohol metabolism based on genetic characteristics of the individuals . the concerns with alcohol addiction are wide and appropriate regulations and treatment protocols have to be formulated mainly by addictive medicine , a specialty subject which is the need of the hour . moreover it 's safe and effective.dsm as an unsupervised domiciliary therapy for the larger part of 6 the months therapy is a cause for concern as there is a point where deceleration in motivation , overwhelming temptation and easy availability crack the de - addiction course leading to relapse . supervised domiciliary therapy for a 6-month period along with active participation at psychosocial and alcoholic anonymous meetings is advocated.occurrence of adr is not the reason for default.patient finds it confusing to differentiate adr from symptoms of alcohol manifestation.dsm-ethanol reaction at this dosage can be managed at primary care setting.use of long acting dsm , injectables , implants , combination of drugs , pharmacotherapy based on genetic characters is another option to look for . dsm as an unsupervised domiciliary therapy for the larger part of 6 the months therapy is a cause for concern as there is a point where deceleration in motivation , overwhelming temptation and easy availability crack the de - addiction course leading to relapse . supervised domiciliary therapy for a 6-month period along with active participation at psychosocial and alcoholic anonymous meetings is advocated . use of long acting dsm , injectables , implants , combination of drugs , pharmacotherapy based on genetic characters is another option to look for .

aim : assessment of safety and efficacy profile of disulfiram ( dsm ) in the alcoholic de - addiction regimen.objectives:a . assessment of adverse drug reaction ( adr ) profile ; b. evaluation of effectiveness of various deaddiction regimen ; c. defaulters and dropoutspatients and methods : fifty - one patients in a de - addiction center were investigated on 0th , 30th and 60th day along with psychiatric evaluation , adr surveillance was made . statistical analysis was done thereafter.results:125 mg dsm given od for 2 months . 76.5% patients had taken full course of treatment , 45% did n't complain of any adr . of adr reported 27.4% had drowsiness , 21.4% tiredness , 7.8% skin manifestation.conclusion:dsm is the main drug among naltrexone , acamprosate , nalmefene and other drugs used in alcoholic de - addiction . relative and effectiveness is lost by the degree of dropouts and hence relapses . low - dose dsm had decreased adverse effects with 76.5% patients taking the full course of treatment . dsm alters liver functions as there were significant changes in the lab parameters of sgpt(p=0.007 ) , sgot(p=0.001 ) , ggt(p=<0.001 ) between first and third samples . occurrence of adr is not the cause of default ; patients find it confusing to differentiate between the symptoms of alcohol withdrawal and those due to adr of dsm .

in a previous issue of critical care , wells and colleagues report on their retrospective cohort study examining the relationship between serum sodium and intracranial pressure ( icp ) with severe traumatic brain injury ( tbi ) . this is an ongoing topic of interest to neurointensivists as hyperosmolar therapy remains a treatment option for elevated icp . we commend the authors for their contribution to a fundamentally important issue in neurocritical care ; however , several issues deserve further discussion . a critical limitation of observational methodology is confounding by indication , which exists when variables associated with exposure are also associated with outcomes in the study base . clinicians administer hyperosmolar therapy and induce hypernatremia on the basis of measured and unmeasured characteristics of patients . lack of a formalized tbi protocol , including indications for hypertonic saline ( hts ) , can exacerbate this bias . for example , clinicians in the study by wells and colleagues used both boluses and infusions of hts with a range of administered concentrations ( 3% versus 7.5% ) . furthermore , although regression is an important method to help reduce bias , several assumptions must be met for the analysis to be valid . linear regression is predicated upon independence of data . with 1,230 paired sodium and icp measurements in 81 patients , there is likely to be marked within - subject correlation of data that is not taken into account by this analysis . consequently , a linear mixed model or other analysis is warranted to specifically model and account for this correlation . failing to do diana l wells , joseph m swanson , g christopher wood , louis j magnotti , bradley a boucher , martin a croce , charles g harrison , michael s muhlbauer and timothy c fabian we thank griesdale and colleagues for their thoughtful letter describing concerns with our study , specifically the retrospective design and statistical tests . owing to the lack of literature supporting the benefits of hts to induce hypernatremia in patients with tbi we agree with the limitations mentioned by griesdale and colleagues in regard to the lack of a formalized tbi protocol and the inclusion of various doses of hts , and we addressed this in our discussion . importantly , patients in our study were treated with the same general approach to hyperosmolar therapy ( 84% of patients received 3% nacl boluses ) . in regard to adjustment for baseline characteristics , we performed linear regression in important subgroups divided by baseline icp and glasgow coma scale score . furthermore , to account for within - subject correlation of data , we conducted linear regression for each individual patient as described in table 2 of the article . in none of the many analyses performed was there an indication of a general correlation between serum sodium and icp . nonetheless , we agree that other statistical methods such as a linear mixed model could have possibly shed more light on these data . recognizing the limitations of our study is important and should serve as a call to the medical community for the need of a well - designed , prospective randomized controlled trial evaluating the use of hts to induce hypernatremia in tbi . this is essential before we can truly include or limit this therapy as a valid option in our treatment armamentarium for these patients . hts : hypertonic saline ; icp : intracranial pressure ; tbi : traumatic brain injury .

the observational literature suggests that hypernatremia is associated with worse outcomes in patients with traumatic brain injury . in a previous issue of critical care , wells and colleagues add to this literature by failing to show an association between hypernatremia and reduced intracranial pressure . however , we must bear in mind many limitations of observational methods before eliminating hyperosmolar therapy from our armamentarium .

type 2 diabetes mellitus ( t2 dm ) is rapidly becoming one of the major health issues of the 21st century [ 1 , 2 ] . a recent survey performed by the ministry of health , labor and welfare projected that approximately 8.9 million people have diabetes and another 13.2 million people are at high risk for the disease in japan [ 3 , 4 ] . obesity and upper body / abdominal fat distribution are associated with increased risk of type 2 diabetes , hypertension , hyperlipidemia [ 5 , 6 ] , heart disease , and overall mortality . indeed , visceral adipose tissue was found to be more strongly linked with the risk of hyperlipidemia [ 10 , 11 ] , insulin resistance [ 1214 ] , and diabetes [ 15 , 16 ] than subcutaneous fat . in these studies , computed tomography ( ct ) scans at the umbilical level were used for the assessment of visceral fat accumulation ( vfa ) . this method is not cost - effective , however , and leads to radiation exposure . a new noninvasive medical device that measures visceral fat by area has recently been under development . using a web - based weight - loss program , the aim of this study was to compare the effects of information on visceral fat accumulation ( vfa ) on waist circumference ( wc ) , body weight ( bw ) , bmi , and healthy workplace behavior . the study protocol was approved by the ethics committee of the national hospital organization kyoto medical center ( approval no . the present study was an assessor - blinded randomized clinical trial ( rct ) design with a 12-week followup . subjects were allocated to 1 of the following 3 groups : ( 1 ) control , ( 2 ) web - based weight - loss program ( web ) , and ( 3 ) web plus visceral fat measurement and education focused on increased health risks associated with visceral fat accumulation ( web + vfa ) . overweight and obese subjects were recruited from 8 health facilities run by 3 companies between july 2009 and march 2011 . pamphlets , posters , and other recruiting media that were specifically targeted at subjects of various age groups were prepared . regional medical staff participants in this study comprised men and women , 2065 years of age who were either overweight ( bmi : 2324.9 ) or obese ( bmi 25 ) according to who regional office for western pacific ( wpro ) criteria , and had given written informed consent . individuals were excluded from the study if they had steel - based medical implants such as coils and/or plates , were pregnant or planning a pregnancy , or did not receive approval from medical doctors to participate in the study . the primary outcome of the present study was change in wc ( cm ) at 12 weeks . in order to detect a 3.4 cm reduction in wc with 90% power at a significance level of 0.05 ( two - sided ) , more than 174 participants with 58 in each study arm were required , assuming an expected dropout rate of 0.18 . subjects were allocated to groups as follows by a quasirandomized design based on their date of birth : control , born between the 21st and the 31st of the month ; web , between the 11th and the 20th ; or web + vfa , between the 1st and the 10th . therefore , the division of subjects was not influenced by age , sex , or any other factor . waist circumference at the umbilical level was measured with nonstretchable tape in the late expiration phase while standing . the subjects were weighed in light clothing using a calibrated scale , and bmi was calculated as kg / m . measurements were performed prior to the start of the study and at every 4 weeks after starting the intervention . age and other demographic variables were collected , as well as variables including readiness to engage in physical activities and healthy eating habits . achievement of readiness was assessed by a self - reported questionnaire at baseline and again at 12 weeks according to the following four stages reported in stages of change model by prochaska and diclemente : ( 1 ) precontemplation , ( 2 ) contemplation , ( 3 ) preparation , and ( 4 ) action / maintenance . the 12-week intervention program was conducted with a focus on modification of physical activities and healthy eating habits through the use of behavioral strategies and self - management skills . anthropometrical measurements and brief face - to - face counseling sessions were conducted by industrial health nurses at the beginning of the study and every 4 weeks throughout the intervention period . subjects were instructed to select special items from 20 suggestions for weight control ( table 3 ) . to standardize the information given during the intervention , industrial health nurses were advised to use original educational tools . between monthly counseling sessions , participants were supported by industrial nurses via a web - based program ( qupio , heath care committee ltd . , the intervention tools and web - based programs both included figures and cartoons and offered practical information for weight and visceral fat reduction in a fun and enjoyable manner . it was designed based on social cognitive theory ( sct ) , which focuses on the four following factors identified by bandura as influencing self - efficacy : mastery experiences , social modelling , social persuasion , and both physical and emotional reactions . for example , a mastery experience within the web - based program consisted of participants setting their target weight and then selecting a special agenda of healthy activities that would enable them to achieve it . in a continuous process of self - regulation , participants were able to monitor their own physiological changes daily and record their achievements on a personal web page . to support establishment of social modelling , participants were given suggestions for 9 ideal lifestyle models , including enjoying sports , wearing stylish clothes , going on a date with your spouse , and others . additionally , participants were able to obtain social persuasion and emotional reactions through participation in an online chat room with other participants . visceral fat area was estimated by bioelectrical impedance analysis ( bia ) as reported previously . briefly , the voltage at the umbilicus position correlates significantly with visceral fat area and is negligibly influenced by subcutaneous fat ; therefore , the area can be calculated based upon voltage . after measurement of vfa , subjects received health counseling on the increased health risks associated with visceral fat obesity . by using 15 original educational leaflets , the subjects were guided to recognize subconscious issues that negatively influenced their dietary habits and physical activities . another tool used was a booklet composed of 3 categories , success stories , and diet and exercise tips , each of which consisted of 101 agendas . 3 booklet was supplied to every subject in order to facilitate alternate selection of their self - selected healthy activities from 10 agendas on healthy eating habits and 10 agendas on physical activities ( table 3 ) . subjects were allowed to change these self - selected healthy activities if they found it difficult to incorporate them into their daily routine . the first was an intent - to - treat ( itt ) analysis including all randomized participants , in which missing values were imputed by last - observation - carried - forward for participants who either did not satisfy inclusion criteria ( bmi < 23 ) or deviated from the protocol . the second analysis was a completers - analysis limited to participants who completed the study . descriptive statistics were performed on the data collected in this study and continuous variables are presented as means standard deviation ( sd ) . groups were compared by analysis of variance ( anova ) or analysis of covariance ( ancova ) . post hoc comparisons were conducted by either tukey 's hsd test or dunnett 's t3 test , depending on results from the distribution test ( levene 's ) . results are discussed based on a significance level of 5% ( p < 0.05 ) . all analyses were performed using statistical package software ( spss version 19 for windows ; spss , chicago , il , usa ) . statistical analyses were validated by a third party ( department of medical statistics , cimic co. , ltd . , achievement of readiness was assessed by a self - reported questionnaire at baseline and again at 12 weeks according to the following four stages reported in stages of change model by prochaska and diclemente : ( 1 ) precontemplation , ( 2 ) contemplation , ( 3 ) preparation , and ( 4 ) action / maintenance . achievement scores were calculated as follows : ( 1 ) count stages 13 as 0 and stage 4 as 1 ; ( 2 ) ( sum of achievement scores , 12 weeks ) ( sum of achievement scores , 0 week ) ; ( 3 ) improvement scores were calculated by averaging the achievement scores in each group . of the 291 people assessed for eligibility in this study , 270 ( 236 males ) were randomly allocated into the trial ( figure 1 ) . most of the participants were overweight ( 51 , 21.6% ) or obese ( 155 , 65.7% ) . no significant difference in completion rate was observed among the control ( 68/73 , 93.2% ) , web only ( 59/74 , 79.7% ) , and web plus vfa ( 65/78 , 83.3% ) groups ( figure 1 ) . subjects in the web and web plus vfa groups showed significant reductions in wc and body weight , based on both bmi and kilograms lost ( table 2 ) . wc decreased significantly more in the web + vfa group than in the web and control groups . a significant reduction in body weight was observed in the vfa + web group compared to the control group . the decreases observed in both bw and bmi between groups were statistically significant according to analysis by anova , while the decreases in wc were significant according to ancova ( figure 2 ) . of the 192 completers , the percentages of those who lost 5% or more of their initial body weight were 6% , 18% , and 30% , respectively , in the control , web , and web + vfa groups ( anova , p < 0.01 ) . post hoc comparisons showed that a significantly greater number of participants lost 5% of their initial body weight in the web + vfa than in the control group ( tukey 's hsd test , p < 0.01 ) . the percentages of those who lost 5% or more of their initial wc were 13% , 12% , and 27% , in the control , web , and web + vfa group , respectively . after 12 weeks , a statistically significant improvement in healthy diets in those randomly assigned to the web only group compared to control ( figures 3(a ) and figure 3(b ) ) was seen . this study demonstrated that participating in either a web - based weight - loss program alone or a web program accompanied by information on visceral fat accumulation can lead to significant reductions in both wc and bw , variables that are of high clinical importance . these findings suggest that both programs lead to reductions in visceral fat , due to the fact that wc is a simple indicator of visceral fat accumulation . the weight loss in the web and web + vfa groups averaged about 2 to 3 kg ( approximately 5% of initial body weight ) , and 15.9% of the randomized participants achieved weight loss of 5% or more . few studies have examined the use of fully automated computer or internet programs for weight loss that do not involve human contact . supplementation of an internet - based weight - loss treatment with monthly in - person meetings did not result in greater weight loss over 12 months . suggested that the dynamic , socially supportive , and interactive elements of websites may eliminate the need for further interpersonal behavioral counseling . the mass media campaign increased awareness of the link between obesity and cancer and the specific waist sizes indicative of risk and increased behavioral intentions with respect to weight and cancer . however , it did not have an effect on self - awareness of weight status , perceived personal risk of cancer , or weight loss behavior . on the other hand , weight loss in the web + vfa group averaged about 2.7 to 1.7 kg ( approximately 3% of initial weight ) , and 15.9% of participants randomized into this group achieved weight loss of 5% or more . these findings suggest that a web - based weight - loss program accompanied by a vfa program enhances weight loss through the promotion of healthy eating habits . second , since the duration of this study was short , we did not have data on weight maintenance and regain after the intervention . third , we did not have laboratory measurements and therefore did not know the prevalence of metabolic syndrome before and after the intervention . a simple intervention that included measurement of vfa and brief counseling , in addition to a web - based weight - loss program , promoted modest weight loss in workplace settings .

a reduction of visceral fat is important for improvement of metabolic risk . this study was designed to compare the effects of a web - based program alone or together with measurement and self - awareness of accumulated visceral fat in japanese workers . a new noninvasive device to measure visceral fat accumulation was introduced , and efficacy on weight - loss and improvement of healthy behaviors were examined . this study was conducted according to helsinki declaration and approved by the ethical committee of japan hospital organization , national kyoto hospital . two - hundred and sixteen overweight and obese males with bmi of more than 23 participated from 8 healthcare offices of 3 japanese private companies . subjects were randomly allocated into control group , web - based weight - loss program ( web ) , or web + visceral fat measurement group ( web + vfa ) . eighty - one percent of participants completed the study . reductions of body weight , waist circumference , and bmi were the largest in web + vfa group , and the differences between groups were significant by anova . improvements of healthy behaviors were the largest in web + vfa group , and the differences of healthy eating improvement scores between web + vfa and control groups were significant . our findings suggest that measurement and awareness of visceral fat are effective in weight reduction in overweight and obese males in the workplace .

a 29-year - old woman with known cardiac amyloidosis suddenly developed three episodes of transient left hemiparesis . the patient had first been seen at our hospital three months earlier because of dyspnea on exertion ( nyha class iii ) . electrocardiogram ( ecg ) revealed sinus rhythm with low voltage qrs and q waves in leads v2 - 3 . transthoracic echocardiography ( tte ) showed thickened left ventricular ( lv ) wall with high left ventricular end - diastolic pressure ( lvedp ) and inferior vena cava ( ivc ) plethora that reflected the high pressure of right atrium ( ejection fraction=40% ) . microscopical examination of a specimen from endomyocardial biopsy , stained with congo red , showed amyloid deposition ( fig . she had never smoked and did not drink alcohol . on examination , cardiac murmur and ecg showed sinus rhythm with occasional premature ventricular complexes , low voltage qrs and q waves in leads v2 - 3 . diffusion - weighted magnetic resonance imaging ( mri ) 6 hours after the onset showed a high signal lesion in the right basal ganglia and corona radiata . mr angiography ( mra ) showed near total occlusion ( or severe stenosis ) of the distal m1 and proximal m2 portion of the right middle cerebral artery ( mca ) ( fig . tte showed thickened lv wall with granular sparkling and both atrial filling pressure ( ejection fraction=28% ) . these findings were compatible with cardiac amyloidosis and aggravated lv dysfunction compared to previous study three months before . there was mild spontaneous echo contrast ( sec ) without thrombi on transesophageal echocardiography ( tee ) . a 73-year - old woman suddenly developed global aphasia , right hemiplegia and visual disturbances . the patient had first been seen at our hospital one year earlier because of dyspnea on exertion . ecg revealed st elevation in leads v2 - 3 and inverted t waves in leads v2 - 5 . two months before admission , the patient visited our hospital because of pretibial pitting edema . ( proteinuria ; 4.2 g / day , hypoalbuminemia ; 2.7 g / dl , hypercholesterolemia ; 294 mg / dl ) serum protein electrophoresis showed an abnormal zone of restriction in the gamma region , identified as an igg m component with lambda light - chain restriction on immunofixation . urine protein electrophoresis revealed an abnormal zone of restriction in the gamma region , identified as bence - jones protein and igg lambda m component , respectively , on immunofixation . kidney biopsy , stained with congo red , demonstrated amyloid deposition and apple - green birefrigence with polarized light ( fig . skeletal survey showed diffuse osteopenia of the bony structures , but no lytic foci on the skull . base on these findings , a diagnosis of multiple myeloma with amyloidosis was made.2 further history taking revealed that there was no family history of amyloidosis . ecg revealed a sinus rhythm with multiple atrial premature complexes . on neurologic examination , she was alert . there were global aphasia , right hemiparesis ( i / v ) , right facial paresis and left homonymous hemianopia . brain computed tomography ( ct ) 2 hours after the onset showed a low density lesion in the right posterior cerebral artery ( pca ) territory , but no evidence of early ischemic change in the left mca territory . brain ct angiography showed missing of some of the left mca cortical branches , suggesting distal mca occlusion . after the intravenous infusion of tpa ( 0.6 mg / kg ) , transfemoral cerebral angiography showed the recanalization of most of the left mca branches except for an occlusion of one of the frontal branches , probably due to emboli migration . on the fifth hospital day , follow - up mri revealed acute infarcts in the right pca and left mca territories ( fig . 4 ) . mra showed no abnormality of intracranial arteries , suggesting complete recanalization of the vessel . tte showed symmetrical thickening of the lv wall with high lvedp and ivc plethora that reflected the high pressure of the right atrium ( ejection fraction=50% ) . both atria were enlarged and transmitral doppler flow revealed typical restrictive pattern . these findings were consistent with restrictive cardiomyopathy , and the cardiac involvement of amyloidosis was strongly suspected ( fig . 5 ) . there were left atrial appendage thrombi ( 17 * 16 mm ) with vigorous biatrial sec on tee . cardiac biopsy was not performed because this procedure was considered too invasive for her condition . motor nerve studies revealed low amplitude of compound muscle action potentials in left ulnar and left peroneal nerves and normal velocity in all tested motor nerves . her neurological condition improved and there were mild mixed aphasia and no hemiparesis at one week after the onset . a 29-year - old woman with known cardiac amyloidosis suddenly developed three episodes of transient left hemiparesis . the patient had first been seen at our hospital three months earlier because of dyspnea on exertion ( nyha class iii ) . electrocardiogram ( ecg ) revealed sinus rhythm with low voltage qrs and q waves in leads v2 - 3 . transthoracic echocardiography ( tte ) showed thickened left ventricular ( lv ) wall with high left ventricular end - diastolic pressure ( lvedp ) and inferior vena cava ( ivc ) plethora that reflected the high pressure of right atrium ( ejection fraction=40% ) . microscopical examination of a specimen from endomyocardial biopsy , stained with congo red , showed amyloid deposition ( fig . she had never smoked and did not drink alcohol . on examination , cardiac murmur and ecg showed sinus rhythm with occasional premature ventricular complexes , low voltage qrs and q waves in leads v2 - 3 . diffusion - weighted magnetic resonance imaging ( mri ) 6 hours after the onset showed a high signal lesion in the right basal ganglia and corona radiata . mr angiography ( mra ) showed near total occlusion ( or severe stenosis ) of the distal m1 and proximal m2 portion of the right middle cerebral artery ( mca ) ( fig . tte showed thickened lv wall with granular sparkling and both atrial filling pressure ( ejection fraction=28% ) . these findings were compatible with cardiac amyloidosis and aggravated lv dysfunction compared to previous study three months before . there was mild spontaneous echo contrast ( sec ) without thrombi on transesophageal echocardiography ( tee ) . a 73-year - old woman suddenly developed global aphasia , right hemiplegia and visual disturbances . she had hypertension and had been treated with medications during the last 5 years . the patient had first been seen at our hospital one year earlier because of dyspnea on exertion . ecg revealed st elevation in leads v2 - 3 and inverted t waves in leads v2 - 5 . two months before admission , the patient visited our hospital because of pretibial pitting edema . ( proteinuria ; 4.2 g / day , hypoalbuminemia ; 2.7 g / dl , hypercholesterolemia ; 294 mg / dl ) serum protein electrophoresis showed an abnormal zone of restriction in the gamma region , identified as an igg m component with lambda light - chain restriction on immunofixation . urine protein electrophoresis revealed an abnormal zone of restriction in the gamma region , identified as bence - jones protein and igg lambda m component , respectively , on immunofixation . kidney biopsy , stained with congo red , demonstrated amyloid deposition and apple - green birefrigence with polarized light ( fig . skeletal survey showed diffuse osteopenia of the bony structures , but no lytic foci on the skull . base on these findings , a diagnosis of multiple myeloma with amyloidosis was made.2 further history taking revealed that there was no family history of amyloidosis . ecg revealed a sinus rhythm with multiple atrial premature complexes . on neurologic examination , she was alert . there were global aphasia , right hemiparesis ( i / v ) , right facial paresis and left homonymous hemianopia . brain computed tomography ( ct ) 2 hours after the onset showed a low density lesion in the right posterior cerebral artery ( pca ) territory , but no evidence of early ischemic change in the left mca territory . brain ct angiography showed missing of some of the left mca cortical branches , suggesting distal mca occlusion . after the intravenous infusion of tpa ( 0.6 mg / kg ) , transfemoral cerebral angiography showed the recanalization of most of the left mca branches except for an occlusion of one of the frontal branches , probably due to emboli migration . on the fifth hospital day , follow - up mri revealed acute infarcts in the right pca and left mca territories ( fig . 4 ) . mra showed no abnormality of intracranial arteries , suggesting complete recanalization of the vessel . tte showed symmetrical thickening of the lv wall with high lvedp and ivc plethora that reflected the high pressure of the right atrium ( ejection fraction=50% ) . both atria were enlarged and transmitral doppler flow revealed typical restrictive pattern . these findings were consistent with restrictive cardiomyopathy , and the cardiac involvement of amyloidosis was strongly suspected ( fig . there were left atrial appendage thrombi ( 17 * 16 mm ) with vigorous biatrial sec on tee . cardiac biopsy was not performed because this procedure was considered too invasive for her condition . motor nerve studies revealed low amplitude of compound muscle action potentials in left ulnar and left peroneal nerves and normal velocity in all tested motor nerves . her neurological condition improved and there were mild mixed aphasia and no hemiparesis at one week after the onset . patient 1 had a cerebral infarct in the right basal ganglia and corona radiata , and near total occlusion of the mca . although there was no mca recanalization , this young lady had neither vascular risk factors nor remarkable atherosclerotic changes in mra . these findings suggest that cardiac embolization was the etiology of their stroke . in patient 1 , the echocardiographicy findings in our patients included symmetrical thickening of the left ventricle wall with high lvedp and ivc plethora . both atria were enlarged and transmitral doppler flow revealed severe restrictive pattern . although characteristic diffuse hyperrefractile " granular sparkling " appearance.3,4 was not observed in patient 2 , these findings are consistent with restrictive cardiomyopathy secondary to cardiac amyloidosis . because patient 2 had hypertension , one may argue that the cardiomyopathy was caused by long standing hypertension . first , ecg demonstrated low voltage signals , despite increased thickness of lv walls on tte . third , high right atrial pressure was associated with ivc plethora , which was not consistent with hypertensive cardiomyopathy . moreover , the rapid progression of the echocardiographic findings one year after the first examination ( lv posterior wall thickening , 17 mm vs. 14 mm ; interventricular septum thickening , 17 mm vs. 14 mm ; left atrial size , 48 mm vs. 41 mm ; increased myocardial echogenecity for one year ) was not consistent with usual hypertensive cardiomyopathy , either . other causes of restrictive cardiomyopathies such as sarcoidosis , endomyocardial fibrosis , radiation , toxin5 were ruled out by the history , physical examination and laboratory findings . therefore , it is highly likely that patient 2 had cardiac involvement of amyloidosis . although definitive diagnosis should be based on biopsy findings , this invasive procedure was not performed in patient 2 who developed acute stroke . on the other hand , deposition of amyloid fibrils results in reduced ventricular compliance with impairment of relaxation and eventually contraction.6 - 8 second , amyloid may infiltrate into the intima of coronary arteries , which may cause myocardial ischemia , endocardial damage , mural thrombosis and subsequent cerebral embolism.6 third , arrhythmia may develop in these patients . atrial fibrillation occurs in about 20% of amyloid cardiomyopathy due probably to left atrial dilatation and failure with increased wall stress.9,10 the most likely mechanism for embolization in patient 2 was the first one , since she had mural thrombus without evidence of myocardial ischemia or atrial fibrillation . in patient 1 , neither thrombi nor atrial fibrillation was observed . although only sec was observed on tee of patient 1 , prophylactic anticoagulation was administered because of the severe lv dysfunction and global lv hypokinesia . in patient 2 however , anticoagulants should be used cautiously in these patients as systemic amyloidosis may be associated with coagulation abnormalities predisposing to bleeding.5,12 although patient 1 remained asymptomatic , and patient 2 improved after thrombolysis and anticoagluation , the ultimate prognosis of these patients is considered poor . according to previous literatures , symptomatic heart involvement is the most powerful prognostic factor , associated with a median survival of only 6 months.3,11

embolic cerebral infarction due to cardiac amyloidosis is rare . we report two patients with amyloidosis who developed cerebral infarcts . these embolic infarcts were probably related to cardiac involvement of amyloidosis , which was based on results of myocardial biopsy ( patient 1 ) , and kidney biopsy and characteristic echocardiographic features including granular sparkling , restrictive cardiomyopathy and the presence of mural thrombus ( patient 2 ) . diffuse amyloid infiltration of the heart may have lead to impairment of myocardial function and subsequent mural thrombosis . cardiomyopathy due to cardiac amyloidosis should be recognized as one of the causes of cardioembolic infarction .

as diffusing capacity of the lung has been used widely as one of the routine pulmonary function tests , many studies have been done to establish a standardized technique for examination and normal predicted values . two methods for estimating dlco have been reported , one of which is the single - breath test , a modified krogh s breath - holding maneuver , and the other is the steady state method , using filey s maneuver . it has been known that values of carbon monoxide - diffusing capacity of the lung vary according to the hemoglobin concentration , the height , the body position , exercise , and attitude . in 1975 the intermountain thoracic society ( its ) proposed a standardized modification of the technique of krogh , and in 1981 crapo et al . established prediction equations for dlco and dlco / va , using , the its technique in normal nonsmoking adults . in this study , in order to establish normal predicted values for the pulmonary - diffusing capacity in koreans , dlco and dlco / va were measured in 90 healthy nonsmoking adults , and the correlation between diffusing capacity and various physical characteristics , such as age , height , weight , and body surface area were observed . they were mainly members of the chonnam university hospital , medical students , relatives of patients , and persons visiting the hospital for regular physical checkups . normal was defined as having no history of ( 1 ) smoking , ( 2 ) asthma , chronic bronchitis , pneumonia or cardiac disease , ( 3 ) persistent cough , ( 4 ) recent treatment for any respiratory or cardiac symptoms , ( 5 ) chest injury or operation , ( 6 ) working in a polluted atmosphere for any extended period , finally , no evidence of cardiopulmonary disease on a physical examination , an ekg , or a chest radiograph . the dlco was measured by the modified krogh s single - breath method , using the srl 1000iv computerized pulmonary function laboratory , gould co. , usa . with the subjects in the sitting position , their noses were clamped and initial maximal exhalation was followed by maximal inhalation of the test gas ( contained 0.3%co and 10%he ) . after a 10-second holding of the breath the exhaled gas was collected in a sample bag , and the sampling was analyzed for co and he . then the dlco was calculated as follows : dlco = va60(pb47 ) ( t2t1 ) ln(facot 1)(facot 2 ) va : alveolar volume ( stpd)60 : correction from seconds to minutespb : barometric pressure47 : water vapor pressure ( ph2o)t2t1 : breath holding intervalln : natural logarithmfacot1 : fraction of co in alveolar gas before diffusionfacot2 : fraction of co in alveolar gas at the end of diffusion va : alveolar volume ( stpd ) 60 : correction from seconds to minutes pb : barometric pressure 47 : water vapor pressure ( ph2o ) t2t1 : breath holding interval ln : natural logarithm facot1 : fraction of co in alveolar gas before diffusion facot2 : fraction of co in alveolar gas at the end of diffusion because the inspired gas was dry , an atpd to btps correction factor was used . units for dlco were ml co(stpd)/min / mmhg , and for dlco / va , ml co(stpd)/min / mmhg / l(btps ) . because changes in the hemoglobin concentration have a calculable effect on total co diffusion , the measured dlco and dlco / va were normalized to a standard hemoglobin value according to cotes equation . corrected dlco = hgb+10.221.7 hgb measured dlco the correlations based on the diffusion capacity of the lung and the physical characteristics , such as age , height , weight and body surface area were observed . and prediction formulas were derived from the variables for both sexes , using a computer system ( spss batch system ) . the mean and standard deviations for age , height , weight , body surface area , dlco , dlco / va , and hemoglobin concentration for each sex are listed in table 2 . the mean dlco was higher in men than in women , but there was no significant difference for dlco / va . correlation coefficients between dlco and each physical characteristic for each sex are shown in tables 3 and 4 . negative correlations were obtained between dlco and age ( tables 3 and 4 , fig . 1 and 2 ) . because dlco and dlco / va showed correlation with age and height , prediction equations were derived for the variables for both sexes . comparisons of the present study with previous studies reported from abroad regarding prediction formulas are shown in tables 7 and 8 , which indicate the differences between the predicted mean and the observed mean values . the mean values of age and height from the present study were substituted in the formulas of previous studies in calculating the predicted mean . the observed means are those that were calculated from the total sample of the present study . the predicted mean using the formulas of the present study was lower than those using the formulas of previous studies for western peoples . the percentage of predicted values above which 95 per cent of the normal population fell were calculated as lower limits of the normal ( table 9 ) . as an index of pulmonary gas exchange , the test for dlco , as well as the other lung function tests has been widely accepted in clinical practices or epidemiologic studies of disease of the respiratory system . it is quite valuable in the early diagnosis and evaluation of severity of pulmonary interstitial diseases and it may be used in epidemiologic studies of occupational lung diseases , such as asbestosis and berylliosis . because the diffusing capacity of the lung depends chiefly on the area and thickness of the alveolar - capillary membrane available for diffusion ( dm ) and the pulmonary capillary blood volume ( vc ) , it may decrease in patients with various cardiopulmonary disorders that affect dm , vc , or both . and it depends also on changes in the hemoglobin concentration , altitudes , and the partial pressure of carbon monoxide in the blood . for example , anemia reduces dlco , the increased vc by elevated pulmonary arterial pressures in persons who live at high altitudes increase and the high carbon monoxide blood level in smokers lowers it . they include the variability of the breath - hold - interval , and the difficulties in estimating the amount of exhaled gas , and the concentration of carbon monoxide . many studies have been done to establish normal predicted values for the diffusing capacity of the lung , but the normal standard values have not been settled on yet . an agreed upon set of normal standard values for koreans is needed . ( 1979 ) have reported normal values already , but they selected subjects irrespective of smoking history . normal values for dlco and dlco / va varied with sex , age and height , and the values for women were lower than those for men of the same age and height , and the values decreased with advancing age and increased with height . now , the use of the regression equations for normal predicted values by crapo et al , and miller et al , are widely recommended , and the normal values in these studies are slightly higher than those of authors . although these differences are presumed to be due to racial difference , cotes et al . claimed that the estimated values for dlco had no racial differencies ; the inverse was the case in the estimated values for lung volumes and spirometry . miller et al . reported that correlation coefficients between dlco and age were 0.55 for men and 0.35 for women , and between dlco and height , 0.27 for men and 0.28 for women . however , in the present study , the correlation coefficients between dlco and age were 0.66 for men and 0.58 for women , and between dlco and height , 0.55 for men and 0.43 for women . thus , the values for dlco showed negative correlation with age and positive correlation with height . ogilvie et al . and burrow et al . reported that values for dlco had significant correlations with body surface area , but in this study the correlation coefficients were low : 0.33 for men and 0.23 for women . double correlation coefficients for dlco with age and height were slightly higher ( 0.727 for men , 0.621 for women ) than those of single correlations with age , and a similar result was obtained with age and body surface area . as crapo et al . and miller et al . have suggested , better regression of dlco could be obtained by using both age and height .

prediction equations for the carbon monoxide diffusing capacity of the lung ( dlco ) and diffusing capacity per liter of lung volume ( dlco / va ) were derived from 90 normal nonsmoking subjects ( 40 men and 50 women ) , using a standardized single - breath technique for determining carbon monoxide diffusing capacity.the results obtained are as follows : the mean values for dlco and dlco / va were 28.055.07 ml / min / mmhg , 4.5690.694 ml / min / mmhg / l for men and 20.794.03 ml / min / mmhg , 4.6950.743 ml / min / mmhg / l for women , respectively.the values for dlco and dlco / va disclosed significantly negative correlation with advancing age and positive correlation with height.normal prediction formulas were obtained for diffusing capacity , using age and height . men : dlco=0.3504 h0.2156 a23.168dlco / va=0.0205 h0.0283a+9.0919women : dlco=0.2491 h0.1533 a11.662dlco / va = 0.0140 h 0.0216 a+3.413

basal cell carcinoma ( bcc ) accounts for 75% of non - melonoma skin cancers and peaks in the seventh decade . although it is frequent in the elderly , bcc is extremely rare in children under 15 years of age . basal cell carcinoma seen in the pediatric age group is associated with inherited syndromes like basal cell nevus syndrome , xeroderma pigmentosum , bazex syndrome , vitiligo , albinism , and congenital lesions like nevus sebaceous . severe or increased sun exposure has been most often implicated in the etiology of nongenetic bcc [ 26 ] . ultraviolet rays induce dna damage leading to overexpression of the oncogens together with the depression of tumor suppressor genes ( sonic hedgehog and p53 ) . other than the ionizing radiation , arsenicals and polyaromatic hydrocarbons play a role in etiology as well . an 11-year - old boy was admitted to our clinic with the complaint of a lesion of 15-month duration on the hairy scalp . physical examination revealed an erythematous , slightly pigmented plaque lesion approximately 3 4 cm in diameter on the posterior scalp ( figure 1 ) . on histopathologic examination , there were typical nodular basal cell carcinoma tumor islands with ulceration localized in the dermis . asymmetrically growing solid nodules in the dermis with connections to epidermis at some zones were seen . no other signs or symptoms of syndromes have been encountered in the patient and his family . in a large study of 36207 children done by de la luz orozco - covarrubias et al . , 53 types of skin tumors were demostrated in which 36 were primary and 17 were metastatic . among these 36 primary tumors the incidence of bcc was only 1.9 in 10,000 patients . in another wide series of 6264 chilhood cancers , 21 primary malignant skin tumors were diagnosed and only 9.5% of them were reported to be bcc . in an article published in 2007 , 107 idiopathic bcc cases were reviewed and the head was ( 90.4% ) the most often site . the scalp accounted for 14.5% of the cases . in the same study , nodular , adenocystic , follicular nodulocystic , superficial , and typical nonaggresive variants were reported to constitute 80% of all cases . remaining cases were defined as sclerosing , infiltrating , and basosquamous type of aggressive variants . any correlation between the histopathologic variant and the prognosis was not mentioned . in the case we presented , localization was the posterior scalp and the histopathologic variant was nodular . major risk factors for bcc are increased sun exposure , vitiligo - albinism , immunosuppression ( aids , drug use due to organ transplantation ) , and radiation . gorlin - goltz syndrome ( basal cell nevus syndrome ) is an autosomal dominant inherited disorder , which is characterized by multiple basal cell carcinoma , maxillary keratocysts , multiple pits of palms and soles , ectopic calcification of cranial membranes , cysts of jaw , and musculoskeletal malformations . xeroderma pigmentosum is an autosomal recessive inherited disorder , which is characterized by sun sensitivity , increased freckling , pigmentation , and dryness of sun - exposed skin and increased risk of cutaneous neoplasms ( bcc , squamous cell carcinoma , and melanoma ) . nevus sebaceous should be kept in mind for a tumor on scalp localization at infancy , childhood , and puberty periods . sebaceous glands in nevus sebaceous follow the pattern of normal sebaceous glands during these periods . in pubertal age , nevus sebaceous histologically manifests as large numbers of mature sebaceous glands overlying papillomatous epithelial hyperplasia , small hair structures , and ectopic apocrine glands in dermis . in the presented case , the lesion was diagnosed as idiopathic form of basal cell carcinoma , both clinically and histopathologically . electrodessication , curettage , topical chemotherapy ( 5-fluorouracil , methotrexate , bleomycin , and interferon ) , radiotherapy , radium plate or radon mould might be used to treat lesions . excision with or without the mohs micrographic technique is the main treatment of basal cell carcinoma . the mohs technique is very useful in cosmetically sensitive regions such as the nose , lips , eyelids , and ears . nevertheless skin grafts and flaps ( range from local flaps to free tissue transfer ) may be used to repair for larger defects [ 10 , 11 ] . in view of the information so far known , increase in the childhood bcc incidence in recent years should be ascribed to high - level uv radiation exposure . it is not difficult to estimate that the diseases associated with increased uv radiation exposure will rise in the future . given that the age of bcc appearance is decreased , this tumor should be considered in the differential diagnosis of childhood skin lesions .

basal cell carcinoma is the most commonly seen nonmelanoma skin cancer which is rarely encountered in the childhood period . an 11-year old child was admitted to our clinic due to an erythematous and a slightly pigmented lesion with a 3 4 cm diameter on his posterior scalp . macroscopically , the lesion was excised with a 10 mm safety margin . pathologic examination revealed a basal cell carcinoma . no symptoms or signs of a syndrome were observed both in the patient and his family .

breast cancer after its removal is not a physical disability but perhaps an altered psychological effects on patients . during the treatment process of this disease the patient has to deal with multiple issues . the impact of breast cancer and its treatment methods , such as mastectomy , on patients , include adverse effects on mental health , particularly mood disorders ( depression , anxiety , and anger ) , hopelessness , changes in body esteem , relapse of the illness , and death . several studies showed that the loss of the breast for women is considered as a major mental injury and this has significant psychological effects on them . the impact of physical disability on body esteem is an important issue . according to mayer and eisenberg valuing the body refers to the positive and negative assessment of the body . breast cancer can highly impact the body esteem and feeling of attractiveness in the patient . after mastectomy , the patient can not encounter their desired body and match it with their previous ideal body ; thus , their assessment of themselves will change . physical nature , identity formation , self - esteem , hope , mental health , and eventual success in different aspects of life are among the factors which are affected by body esteem . humans have physical , psychological , and social needs , with the fulfillment of which the body 's internal equilibrium is established . if this balance is thwarted , many problems will follow . psychological stress after treatment can cause emotional distress , such as anger , depression , and hopelessness , in the patient . based on conducted research , hope is a quantifiable quality which can be used in the stage of reviewing and understanding the nursing process . this stage can be followed by intervention to promote hope . without the promotion of hope , grounds for the acceptance of treatment and care - education will not be established . experts from the world health organization ( who ) , have defined mental health as the capability of having harmonious relationships with others , change and modification of individual and social environment , and the logical , fair , appropriate resolving of conflicts and personal desires . they also believe that mental health is not merely the absence of mental illness , but it is the flexible and meaningful reaction against a variety of life experiences . today , mastectomy is the routine surgical treatment of breast cancer and its appearance as well as psychological and social consequences are not considered ; thus , the repeated evaluation of mood and psychological aspects of patients are of higher importance . on the other hand , it is certain that women are the most important pillars of the family and society . thus , improving the psychological status of women not only improves their survival , but also the mental health of their family and results in more consistency of family structure . therefore , the present study aimed to identify the relationship between body esteem , hope , and mental health in patients with breast cancer after mastectomy . this was a descriptive cross - sectional study aimed to investigate the relationship between body esteem , hope , and mental health in breast cancer patients after mastectomy . the study population included 100 breast cancer patients who had undergone mastectomy and referred to sayed al - shohada medical center in isfahan , iran . the data gathering tools included the body esteem scale ( bes ) , herth hope index ( hhi ) , and symptom checklist 25 ( scl-25 ) mental health questionnaire . the valuing body questionnaire was used for the first time by ghoudusi et al . in their study , to determine the reliability of this instrument , the internal reliability method was used . moreover , using cronbach 's alpha coefficient , the reliability coefficient was estimated at 0.80 . this questionnaire included 13 general terms and was scored based on a 5-point likert scale ( totally agree ( 1 ) , agree ( 2 ) , no comment ( 3 ) , disagree ( 4 ) , and totally disagree ( 5 ) ) . this instrument assessed four subscales that include : ( 1 ) physical attractiveness ( questions 1 and 9 ) ; ( 2 ) feeling comfortable about your body ( with questions 3 , 7 , and 13 ) ; ( 3 ) comparing your body with a healthy body ( questions 2 , 5 , 6 , 10 , and 12 ) ; and ( 4 ) sexual attraction based on one 's own and others opinion ( questions 4 , 8 , and 11 ) . the mean and standard deviation ( sd ) was calculated for each of the questions separately , and for the total of the questions for each subscale . valuing the desired body was measured based on the body esteem score of each item , the total score of body esteem , and the overall mean of body esteem . the overall mean score ranged between 13 - 65 ; total mean closer to 65 showed higher body esteem , and lower and closer to 13 showed lower body esteem . it should be noted that the questionnaire is designed so that single people can also respond to the questions . the hhi contained 12 items and was based on a 3-point likert scale , graded from 1 - 3 ( 1 ) disagree , ( 2 ) not sure , and ( 3 ) agree ) . total score ranged from 12 - 36 and higher scores indicated higher level of hope . the scl-25 ( the short form of scl25-r ) was used to measure the mental health of the patients . the scl25-r scale had nine dimensions of somatization , obsessive - compulsive , interpersonal sensitivity , depression , anxiety , phobic anxiety , psychosis , paranoid ideation , aggression , and a few additional questions . this scale consisted of 25 items , and each item was assessed based on a 5-point likert scale ; none ( 0 ) , low ( 1 ) , somewhat ( 2 ) , high ( 3 ) , and intensity ( 4 ) . lower scores indicated better mental health and scores above 65 indicated psychological disorders . in the present study , the researcher referred to the study environment and distributed the questionnaires among 30 patients . after collecting the questionnaires , using spss for windows ( version 16 ; spss inc . , chicago , il , usa ) , cronbach 's alpha coefficients of the bes was calculated as 0.85 , the hhi as 0.90 , and scl-25 as 0.92 . characteristics of the study population include : patients who referred to the hospital to receive health care or medical advice ; at least 6 months had past their one - sided mastectomy ; they had no other physical or mental illness ; the patient was able to respond to the questions ; patient was not undergoing chemotherapy ; the mastectomy could not be reconstructed ; and all the subjects were over 30 years of age . after selecting the eligible subjects , the researcher introduced himself to them , and explained the purpose of the study . after obtaining an informed consent from each participant and assuring them that their information will be kept confidential , the questionnaires were handed to them . it should be mentioned that the researcher personally read the questions for the participants and recorded their responses without any manipulation . the sampling was continued until the completion of the required number and lasted for 3 months . based on the results of this study , the highest frequency ( 52% ) was in the age group of 50 - 70 year olds . moreover , the majority of patients ( 32% ) were high school graduates , 33% of them had a history of abortion , and 17% had the experience of cancer in other organs . additional information about the status of the subjects is shown in [ table 1 ] . the results indicated that with respect to the bes ( 2.80 ) and its overall mean score ( 36.46 ) , patients had low body esteem . according to the findings , the highest mean ( 65.2 ) in the subscales of body esteem was related to physical attractiveness and the lowest mean ( 51.73 ) was related to comparing the body with a healthy body . the phrases if someone told me i am an attractive person , i would doubt it and if i did not have this disability , i would be better looking , respectively , had the highest ( 3.23 ) and lowest ( 2.41 ) body esteem scores . based on the results obtained in this study , 27% of the patients had low hope , 49% had moderate hope , and 24% high levels of hope [ table 2 ] . furthermore , based on the overall score of mental health , 69 patients were suspected to have mental disorder . in addition , regarding the nine dimensions of mental health , the highest mean ( 3.05 ) was associated with depressive disorders in the study units [ table 3 ] . in this study , according to the results of the spearman correlation coefficient , there was a direct linear relationship between appreciating the body , hope , and mental health . this relationship was stronger between body esteem and hope ( p < 0.001 , rs = 0.583 ) [ table 4 ] . demographic distribution of the study subjects frequency distribution of hope among the study subjects mean and standard deviation of the mental health subscale of study subjects relationship between body esteem and hope , body esteem and mental health , and hope and mental health the results of this study showed that patients had low body esteem . based on the results , the bes was 2.80 1.14 . body esteem in people with chronic diseases , such as breast cancer , can be interpreted as a psychological understanding . negative social attitudes and their internalization will affect the value of the body in women with breast cancer . if people have bad judgment about the value of their own body , they will have a negative and destructive understanding about their body and its different aspects . feeling of body esteem is the result of the value created in one 's mind due to that which one hears , observes , and feels . seynaeve and den heijer , and pinto and trunzo also confirm these findings in their studies . based on their findings , breast cancer and mastectomy have a negative effect on body esteem . fallbjork et al . , argue that society places high value on physical attractiveness and can affect individuals opinions about their body ; therefore , one can have negative assumptions towards their body based on their society 's beliefs . this is how patients come to the conclusion that if they did not have this disability they would be seen as more attractive . however , the results of the study by ghoudosi et al . , on the relationship between body esteem in people with multiple sclerosis was inconsistent with these results . people with disabilities or limitations have more difficulty in adaptation to different situations than people without disabilities . disabled people do not have difficulties in adapting but it is the environment that is not conducive to allow for this and one of the most effective methods of improving their adaptation to their physical and mental limitations is to help them gain hope . the results of this study showed that only 24% of the patients had high levels of optimism and hope ; however , most of them had moderate levels of hope . in this regard , aydine avci and okanli , in their study on reviewing the judgments of marriage and hopelessness levels after mastectomy , reported low levels of hope in patients . the results of this study confirmed the findings of the study by hagerty et al . , on the relationship between hope and realism in patients with breast cancer . in this study , it is important to note that 27% of the patients had low levels of hope , and researchers believed that the first patients lost hope and then became depressed . disappointments had negative effects on the health and psychological aspects of patients , and were risk factors for the impairment of these dimensions . therefore , it is necessary to increase patients hope , because hope is the most valuable resource that patients can rely on for immunity to any mental and physical damage . other findings of this study , regarding the mental health of these patients , showed that based on the nine dimensions of mental health most patients had depression ( 1.63 0.72 ) . it appears that mastectomy not only affects physical functioning , but it also has a negative impact on emotional , psychological , and social functions . many of the problems in patients with breast cancer due to mastectomy and its impacts on their quality of life occur after surgery . because patients after mastectomy experience circumstances similar to that of an amputation ; an organ the amputation of which causes women great stress , changes their attitude towards their body after surgery , and renders them prone to mood disorders . , and isern and tengrup also confirm these findings . results of spearman correlation coefficients showed that there was a direct linear relationship between body esteem , hope , and mental health , and the intensity of this relationship was greater between body esteem and hope ( p < 0.001 , rs = 0.583 ) . the results of the present study confirmed the findings of the study by fallbjork et al . , on the dimensions of mental image and mental health of women with breast cancer after mastectomy . in a study on mental health and hope in women with breast cancer showed a significant relationship between the mentioned variables . , on health - related quality of life , gender assessment , and mental image of the body in women after mastectomy showed consistent results with the present study . after mastectomy patients have negative valuation of their body . because they believe that with this type of treatment , their physical appearance and function will change to the extent that they do not believe in their body . knowing the physical value of the body has great impacts on the meaning of being hopeful and mental health of the person . hope is a symbol of mental health and the ability to believe in a more positive feeling in the future . nevertheless , hopelessness is the opposite of hope and the main characteristic and manifestation of depression . hopelessness has negative impact on the health and psychological aspects of a person and is a risk factor for impairment of these dimensions . the impacts of mastectomy on body esteem , other psychological aspects , and in general the mental health is undeniable . thus , providing the above results can be useful for health care organizations and women 's health planners and managers who can implement them in the health system planning . it is also necessary that the treatment team assess the psychological dimensions of their patients . meanwhile , there is an emphasis on the role of nurses , because nurses play an important role in the care of cancer patients after mastectomy and have a suitable situation to educate the patients and their families and provide emotional support .

background : breast cancer and its treatment , including mastectomy , can cause feelings of mutilation , depreciation in the value of the body , reduction in attractiveness , and lead to mental disorders and hopelessness.objective:the present study aimed to determine the relationship between appreciating the body , hope and mental health in women with breast cancer after mastectomy.materials and methods : this study was a descriptive study of 100 breast cancer patients who had undergone mastectomy and referred to the sayed al - shohada medical center in isfahan , iran . the subjects were selected by convenient sampling . data gathering tools were the body esteem scale ( bes ) , herth hope index ( hhi ) , and symptom checklist 25 ( scl-25 ) mental health questionnaire . data analysis was performed using spss software.results:most of the patients had low body esteem . there was a significant direct linear relationship between body esteem and hope and mental health . this relationship was stronger between valuing the body and hope.conclusion:body esteem has a significant linear relationship with hope and mental health .

each stage in the development and progression of cancer is the result of cross - talk between the tumor and the host s immune system . the constant selective pressure of the immune system promotes the emergence of tumor cells that are highly resistant to immune rejection . , including cell - mediated immune tolerance , loss of some antigens , defective death receptor signaling , and immunosuppressive cytokines . various immune cell types ( e.g. , tregs , mdscs , and tams ) have been shown to contribute to the establishment and maintenance of immune tolerance . tumor cells frequently downregulate expression of hla class i antigens , which play an important role in antigen presentation to cd8 + t cells . nk cells express activating receptors , such as nkg2d , which bind to stress - induced ligands ( mica and micb ) that can be up - regulated in a variety of tumors , making the tumor susceptible to nk cell - mediated cytotoxicity , which means that their paucity in the tumor may prevent nk - cell recruitment to the tumor site . evidence shows that the expression of mica and micb can be suppressed in the hypoxic environment of the tumor . as one of the death receptors , down - regulation or loss of fas expression in tumors may also contribute to their resistance to tumor immunity . tumor cells also produce a variety of cytokines ( e.g. , vegf , il-10 , tgf- , and pge2 ) that can negatively affect maturation and function of immune cells . as a consequence , these negative regulators create a balance between immune activation and immune inhibition , resulting in tumor escape and tumor progression . however , this balance has been proven to be upset by interventions such as radiotherapy that contribute to systemic antitumor immunity . enhanced expression of death receptors , mhc class i molecules , costimulatory molecules , adhesion molecules ( icam-1 and vcam-1 ) , and stress - induced ligands on tumor cells after radiation increased their recognition and killing by t cells or nk cells in vitro and/or in vivo in several cancer models . interestingly , although many phenotypic changes have been observed and demonstrated to benefit antitumor immunity , some negative regulators have also been reported to be induced in some trails , like tgf- and tregs . this means that the effects of radiation should not be simply considered as promoting antitumor immunity , but may be a tendency of the tumor to regain the balance . in fact , the phenotypic changes are not persistent , so there is a chance to enhance the immune effects of radiotherapy by prolonging the phenotypic changes . here , we concentrate on hif-1 , a factor which increases after radiation and has recently been shown to suppress antitumor immunity . although hif-1 is mostly known as a transcription factor activated by hypoxia in tumors , it can also elevate in other situations , for example after radiotherapy in cancer treatment . within hours after irradiation , intratumoral hif-1 activity decreases due to von hippel - lindau however , during reoxygenation , free radical species accumulate in tumor tissue and lead to overexpression of hif-1 . as a result , hif-1 expression increases in a hypoxia - independent manner 18 to 24 h after radiotherapy . , accumulating evidence has indicated that hif-1 can act as a suppressor of antitumor immunity . reported that hypoxia dramatically alters the function of mdsc in the tumor microenvironment and redirects their differentiation toward tams via hif-1 . ben - shoshan et al . found that hif-1 increases the number and suppressive properties of naturally occurring cd4(+)cd25(+ ) treg . suggested that intratumor hypoxia promotes immune tolerance by inducing tregs via tgf- 1 in gastric cancer . it has also been shown that tgf- is a hif-1 target gene , and introduces the possibility that hypoxia induction of tregs involves a coordinated response involving hif-1 and tgf- . in addition to promoting the generation of tregs , hif-1 can also negatively regulate functions of t cells directly by regulating t cell receptor signal transduction . a study found a mechanistic link between hif-1 , increased expression of adam10 , and decreased surface mica levels . the expression of hif-1 in nk cells also seems impair their ability to upregulate the surface expression of the major activating nk - cell receptors ( nkp46 , nkp30 , nkp44 , and nkg2d ) . the association of hif-1 and fas expression has been implied in some experiments . andrew et al . showed that a vegf / jak2/stat5 axis may decrease the apoptosis of endothelial cells by repression of proapoptotic fas / fasl , and vegf can be induced by hif-1. in summary , accumulating evidence shows that the immune suppression effects of hif-1 and the elevating of hif-1 after irradiation could prevent the immune effects of irradiation ( figure 1 ) . therefore , we speculate that inhibition of hif-1 following radiotherapy may prolong and enhance the immune effects of radiotherapy . in the past decades , the immune effects of radiotherapy in tumors have been investigated extensively . however , tumors are so clever that they can remodel themselves and reverse the immune effects of radiotherapy , which makes the effects temporary . hif-1 may be one of factors taking part in the remodeling , and inhibition of hif-1 following radiotherapy may prevent the process .

tumor local immune escape is one of the hallmarks of cancer leading to poor prognosis . the effects of local radiotherapy on tumors are rapidly emerging as opportunities to remodel and enhance immunity against cancer . however , this immunity remodeling and enhancing are not permanent after local radiotherapy . high expression of hif-1 following local radiotherapy for tumor cell reoxygenation has been confirmed , and recently accumulating evidence shows the tumor immune suppression effects . these research findings suggest a new direction in the investigation of methods to enhance the efficacy of local radiotherapy . we speculate that by blocking hif-1 , the immune effects of radiotherapy might be prolonged and enhanced .

dry eye syndrome or keratoconjunctivitis sicca is one of the most common diseases in ophthalmology [ 1 , 2 ] . according to published investigations , its prevalence ranged from 5% to 6% in the general populations , and it reached 34% in the elderly . severe cases can cause serious complications , even loss of visual acuity . in the past three decades , submandibular gland transplantation has been demonstrated as an effective method for treating severe dry eye syndrome [ 412 ] . some published papers declared that the prevalence of epiphora after smg transplantation was about 40% [ 4 , 13 , 14 ] . although several methods , including atropine gel and operation , have been used to treat epiphora , the clinical outcomes remain unsatisfied [ 4 , 1315 ] . botulinum toxin type a ( btxa ) , a neurotoxic protein produced by clostridium botulinum bacteria , has been widely used in clinic to treat the excessive gland secretion including drooling , hyperlacrimation , and hyperhidrosis . in 2002 , keegan and his colleagues reported that btxa was an effective treatment for hyperlacrimation in spite of side effects . after then , yu and his colleagues also confirmed the effect of btxa on epiphora after smg transplantation [ 4 , 18 ] . however , both of them included few samples and no further investigations were reported about its mechanisms . in this study , we constructed a new model of smg transplantation in rabbit and aimed to investigate the effect of btxa on excessive secretion after smg transplantation and its underlying mechanisms . 35 male new zealand white rabbits ( weighing 2.3 0.2 kg ) were used to establish new smg transplantation models . all experimental procedures were approved by the institutional ethics committee of animal research ( peking university health science center ) . btxa used in this study was as gifts by lanzhou institute of biological products , china . the titer of one - unit btxa from this institute is about equal to 3 - 4 units of dysport ( ipsen , slough , uk ) and one unit of botox ( allergan , irvine , ca , usa ) . fitc , antibodies to aquaporin-5 ( aqp5 ) and -actin , were purchased from santa cruz biotechnology ( santa cruz , ca , usa ) . the rabbit models of submandibular gland transplantation in previous researches were intricate and the transferred gland secretion was interrupted by rabbit accessory lacrimal gland [ 2024 ] . to simplify and better simulate the operation , we established a novel model based on the previous models . the key operation steps were showed in figure 1 . for operation , all rabbits were anesthetized with sodium pentobarbital ( 20 mg / kg according to rabbits ' body weight ) . after three months of smg transplantation , we detected whether the transferred smgs were successful . during the three months , one died of disease and one was infectious . besides , three were excluded because the smg transplantation failed . then , all the good transplantation models including 30 rabbits were randomly assigned to five groups ( six per group ) , including one control group and four experimental groups ( 2 weeks group , 4 weeks group , 12 weeks group , and 24 weeks group ) . all transferred glands in the experimental groups were injected with 0.1 ml btxa with the concentration of 100 u / ml . in experimental groups , the salivary secretion outputs were detected and the transferred smgs were removed under anesthesia at 2 , 4 , 12 , and 24 weeks after btxa injection . as for the control group , salivary secretion outputs were tested and the transferred smgs were collected after three months of smg transplantation . saliva flow was measured for five minutes in rest ( one minute for feeding ) , and we statistically calculated the length of wet filter paper with saliva ( 35 5 mm ) . we performed the measurements of salivary secretion between 9:00 am and 12:00 am while rabbits were awake . to observe the morphological and structural changes , ultrathin section was stained with uranyl acetate and lead citrate and ultrastructure were acquired under a transmission electron microscope ( h-7000 electron microscope ; hitachi , tokyo , japan ) . proteins were extracted from the transferred smgs and quantified by bca method as previous description . 40 g proteins extracts were separated on 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis and transferred to polyvinylidene difluoride ( pvdf ) membranes . the membranes were blocked with 5% nonfat milk for two hours and then probed with aqp5 antibody at 4c overnight . the membranes were washed with pbst for 10 min ( 3 times ) and then incubated with horseradish peroxidase- ( hrp- ) conjugated secondary antibody ( 1 : 4000 dilution ) . frozen sections of transferred smg were fixed in cold acetone for 15 minutes and were immunostained with anti - aqp5 antibody ( 1 : 100 ) overnight at 4c and incubated with fitc- or tetramethylrhodamine isothiocyanate - labeled secondary antibodies as described previously [ 6 , 26 ] . fluorescence images were captured by confocal microscope ( tcs sp5 ; leica , heidelberg , germany ) . statistical analysis was performed by graphpad prism software ( graphpad prism , la jolla , ca , usa ) . differences among groups were analyzed by one - way analysis of variance ( anova ) and then bonferroni testing . a value of p < 0.05 was considered as statistical significance . to observe the role of btxa in treating excessive secretion outputs of transferred smg , we injected 0.1 ml btxa with concentrations of 100 u / ml into transferred gland in the experiment groups ( 10 u btxa mixed with 0.1 ml 0.9% saline ) . compared with the control group , a significant decrease of secretion output was observed in the btxa - treated group at 2 weeks and 4 weeks , whereas there was no significant difference in 12 and 24 weeks groups ( figure 2(a ) for rest in 5 minutes and figure 2(b ) for feeding in one minute ) . normal acinar and ductal cells were observed in the transferred smg without btxa injection ( control group , figure 3 , con ) . compared with control group , the 2 and 4 weeks groups had more fibrous tissues in the glandular lobules and smaller acinar cells ( figure 3 , 2 w , and figure 3 , 4 w ) . after 12 and 24 weeks of btxa injection , the morphological appearance of gland recovered gradually ( figure 3 , 12 w , and figure 3 , 24 w ) . tem indicated that massive secretory granules could be observed in the acinar cell of control group ( figure 4 , con ) . compared with the control group , the volume of acinar cells was smaller and the number of secretory granules was less at the time of 2 and 4 weeks ( figure 4 , 2 w , and figure 4 , 4 w ) . however , at 12 weeks , the morphological appearance of gland recovered gradually , and , at 24 weeks , it recovered to the normal control gland ( figure 4 , 12 w , and figure 4 , 24 w ) . aqp5 is a water channel protein , which plays a role in the generation and secretion of saliva [ 2729 ] . proper aqp5 expression and subcellular localization are necessary to maintain water homeostasis [ 29 , 30 ] . to explore whether btxa directly affects aqp5 protein , western blot and immunofluorescence were performed to detect the aqp5 expression and subcellular localization in acinar cells . results suggested that aqp5 protein expression was decreased at the time of 2 weeks and 4 weeks but almost returned to the levels of control group at 12 and 24 weeks ( figure 5(a ) ) . immunofluorescent analysis showed that aqp5 was mainly located at the apical and lateral membranes of the acinar cells in transferred smgs of control group ( figure 5(b ) , con ) . in the experimental groups , results suggested that the fluorescence intensity of aqp5 reduced significantly and the aqp5 protein distributions were changed at 2 and 4 weeks group . however , all the changes almost recovered at the time of 12 and 24 weeks after btxa injection ( figure 5(b ) ) . smg transplantation has been considered as one of the most effective treatments for severe xerophthalmia [ 4 , 11 , 31 , 32 ] . however , about 40% of patients suffered from epiphora after smg transplantation [ 13 , 14 , 33 ] , which reduced patients ' life quality and increased their social embarrassments . current therapeutic strategies of epiphora after smg transplantation include surgery , a variety of drugs , and other therapies [ 15 , 31 , 34 ] thus , it is necessary to find a better therapeutic method with safety and efficacy . btxa has been widely used in oral and maxillofacial surgery for almost 20 years , including treating muscular spasm , drooling , frey 's syndrome , and produced encouraging results [ 16 , 35 , 36 ] . our previous animal experiments had also demonstrated that btxa could reduce the secretory output of smg of rabbits and rats [ 19 , 26 ] . thus , it is likely to be a good candidate for the treatment of epiphora after smg transplantation . although keegan had reported that btxa treated epiphora with good results in 2002 , only one case was included and there is no high quality evidence to support its applications . as is well known , drugs ' safety and efficacy should be comprehensively estimated before it could be used in clinical treatment , including btxa therefore , the efficacy and safety of btxa should be well demonstrated in animal models before we could use it in patients . considering that the previous models were intricate and did not well reflect the truth of salivary secretion [ 21 , 22 , 25 , 37 ] , we established a new transplanted smg model in rabbits . in this model , we injected 10 u btxa ( 100 u / ml ) into the transferred gland and found btxa also inhibited the salivary secretion temporarily . at the time of 2 and 4 weeks after btxa injection , however , the glandular output of smg transplantation recovered gradually at the time of 12 weeks and 24 weeks after btxa injection , suggesting that the drug wore off over this time period , which are consistent with the previous studies [ 19 , 26 ] . besides , he and tem results showed atrophic and less granules of acinar cells in transferred smgs , which might help to explain the reduced function of smg . it was reported that btxa injection reduced the size of acinar cells and aqp5 expression in rabbits and rats , and aqp5 localization plays a significant role in salivary fluid secretion [ 19 , 26 , 28 , 3840 ] . the translocation of aqp5 from the cytoplasm to the apical plasma membrane is required to promote secretory capacity [ 29 , 41 , 42 ] . besides , our previous study also found that btxa could directly affect aqp5 expression and distribution in smg cell without innervation , which indicates that btxa could directly inhibit smg cell secretion by affecting aqp5 . in this study , western blot and immunofluorescence results suggested that btxa reduced the aqp5 protein expression and promoted aqp5 expression transposition from the cell membrane to cytoplasm after btxa injection . based on what was mentioned previously , we speculated that btxa might share a similar role in the treatment of epiphora after transplanted smg and btxa could directly inhibit the secretion of the denervated gland . in summary , our experiments have demonstrated that btxa injection could effectively control the epiphora after autologous smg transplantation in rabbits more for than 4 weeks . btxa injection reduces aqp5 expression and promotes redistribution of aqp5 in the transplanted smg , which suggests that btxa inducing aqp5 protein expression reduction and redistribution might be a therapeutic target for controlling glandular secretion .

objectives . to investigate whether botulinum toxin type a ( btxa ) could control excessive secretion after submandibular gland ( smg ) transplantation in rabbits and its possible mechanisms . methods . a new smg transplantation model was established in rabbit . 30 successfully constructed models were randomly assigned to five groups including control group and four experimental groups . secretion outputs were used to analyze the effect of btxa injection on excessive secretion . hematoxylin and eosin ( he ) staining , transmission electron microscopy ( tem ) , western blot , and immunofluorescence were performed to analyze its possible mechanisms . results . after btxa injection , a significant decrease of excessive secretion after smg transplantation was found in 2 and 4 weeks groups , but no significant effect on 12 and 24 weeks groups . he and tem results showed that btxa led to morphological and ultrastructural changes of acinar cells of transplanted smg . western blot results suggested that btxa decreased the aquaporin-5 ( aqp5 ) protein expression after btxa injection for 2 and 4 weeks . immunofluorescence results showed that aqp5 protein was mainly expressed in the cytoplasm after btxa injection for 2 and 4 weeks , which might indicate that btxa promoted aqp5 expression from the cell membrane to cytoplasm . conclusion . btxa could effectively control excessive secretion after smg transplantation in rabbits .

malgr lampleur des recherches au canada , la mise en uvre de la modlisation na pas encore atteint son plein potentiel en sant publique dans la prise de dcision et la pratique . il y a matire mieux intgrer la diversit de la population canadienne et dutiliser les rsultats de la recherche dans les contextes pertinents . pour renforcer les liens avec lexercice de la sant publique et en largir la porte , lquipe de pandemic influenza outbreak research modelling sest associe au centre de collaboration nationale des maladies infectieuses pour organiser un atelier national . cet atelier visait dterminer les secteurs o la terminologie , les mthodo - logies et les rsultats de la modlisation manquent de clart , transmettre de linformation sur lutilisation optimale de la modlisation pour tayer les politiques et amliorer la pratique , notamment en accordant plus dimportance aux questions dquit en sant , et maintenir et faire progresser la collaboration pour laborer et mettre en uvre la modlisation en sant publique . latelier sur lutilisation de la modlisation mathmatique dans la prise de dcision relative aux maladies infectieuses en sant publique a runi des chercheurs modlisateurs , des professionnels de la sant publique , des dcideurs et dautres experts du pays . les confrenciers ont mis en contexte les discussions dans le cadre de trois sances . une dernire sance a suscit des rflexions et des recommandations sur les futures tches et possibilits . les lacunes en matire de contenu et de recherche incluent labsence de cadres standardiss et de glossaire de la modlisation des maladies infectieuses . une terminologie uniforme , la formulation claire des paramtres et des hypothses de modlisation ainsi quune collaboration soutenue contribueront corriger lcart entre la recherche et la pratique . sessions 1 and 2 of the workshop began with a presentation regarding the development of infectious diseases modelling in canada . before the 2003 sars epidemic , modelling activities were largely driven by research interests of individuals or small groups , with a significant emphasis on the theoretical aspects of exploring complex mathematical phenomena . for the most part , these activities were carried out in isolation , with minimal communication and engagement with public health professionals and policymakers ( 2 ) . during and following the sars epidemic , various groups of disease modellers were formed to engage with , and develop models for application to public and population health in more specific contexts . despite the importance and relevance of these initiatives , knowledge translation remained a challenge that the pan - inform was established in part to address ( 9 ) . the canadian institutes of health research supported the establishment of pan - inform to address the limited knowledge exchange between modelling researchers and those who could potentially make use of models to inform health policy and improve practice . since its inception , pan - inform has undertaken several national initiatives for knowledge brokering , including the evaluation of canada s response to the spring and winter waves of the novel h1n1 pandemic , identification of strategies for protecting vulnerable populations from emerging infectious diseases , and development of approaches that can enrich existing links with aboriginal health organizations and foster multijurisdictional collaborative efforts in canada ( 24 ) . in canada situations are often very complex for a number of reasons including the availability and adequacy of health resources ; inconsistent or absent evidence regarding the effectiveness and cost effectiveness of intervention strategies ; pressure from the public , media and government under which public health must operate ; other competing public health services ; and ethical considerations to balance the protection of community health against individuals rights and freedoms . other pertinent challenges include the lack of data to estimate potential outcomes of a public health program , paralysis resulting from having too much information on occasion , differing opinions and short timelines . in this context , as one presenter put it , there are three questions decision makers face : what is the benefit of the public health program or intervention ; who will benefit from the program and ; is the program cost - effective ? often , the evidence to answer these questions is not available in a timely manner . however , controlled trials may not be feasible or ethical , and can also be time consuming , laborious , expensive or inconclusive . models provide a useful tool to overcome these challenges and systematically evaluate possible effects by using existing data and knowledge , generating quantitative outcomes and mapping out interdependencies that may be key factors for determining policy needs . given these capabilities , models can be used to identify key uncertainties in the parameters and generate qualitative predictions , such as the effect of behavioural changes on the trends and distribution of an infection in the population . indeed , the overarching goal of modelling is to support evidence - based public health policy . to enhance the utility of models , communication and collaboration between modellers and public health leaders must take place early in a decision making process . models are more valuable when end users are engaged in formulating the questions because models are built so that they truly reflect a public health question . end users who understand a model are likely to be better able to assess the results . during the construction and validation of a model , the relevance and importance of input parameters must be understood , and the sources for their values and ranges , uncertainty about the parameters , and sensitivity of the model outcomes with respect to parameter variation and original model assumptions , must be determined . new knowledge generated by a model should address the target question and be translated and disseminated for uptake and action appropriate to the context . furthermore , when data are limited , it is essential to quantify any uncertainty in parameterization , because different sets of parameters may fit equally well . ideally , the process to improve the model structure and its outcomes is iterative . the value of direct conversations between modellers and public health leaders , in particular with regard to the availability and access to data and other critical information that are essential for model inputs of real - time scenarios ( 10 ) , was exemplified in the use of modelling and the implementation of model recommendations for antiviral use and vaccination in canada s response to the 2009 h1n1 pandemic ( 11,12 ) . table 1 summarizes key issues presented and discussed for modelling in public health during the workshop . the international society for pharmacoeconomics and outcome research guidelines highlight the importance of a common language for drafting a health decision question and addressing it through a modelling framework . the guidelines for transparency and validation state : every model should have non - technical documentation that is freely accessible to any interested reader . at a minimum , it should describe in nontechnical terms , the type of model and intended applications ; funding sources ; structure of the model ; inputs , outputs , other components that determine the model s function and their relationships ; data sources , validation methods and results ; and limitations ( 1 ) . every model should have non - technical documentation that is freely accessible to any interested reader . at a minimum , it should describe in nontechnical terms , the type of model and intended applications ; funding sources ; structure of the model ; inputs , outputs , other components that determine the model s function and their relationships ; data sources , validation methods and results ; and limitations ( 1 ) . good communication flows to and from knowledge producers and users , and requires a common language to build effective partnerships and understanding of the groups respective concerns . there are a number of challenges to developing a common language : determining a common lexicon ; understanding priorities and contributions , which may shift depending on the political climate or population health status ; asking the right questions that are appropriate to the given context ; knowing the right audience ; and being able to communicate findings to others outside the research community . the lack of such common language may have been an impediment to addressing key parameters in determinants of health and health equity. in the canadian context , one needs to take into account differential health status and population structure of first nations , inuit and mtis people , population - level patterns of abuse , poverty and historical trauma , challenges regarding access to health services in rural and remote areas , and limits in identifying building partnerships and an iterative exchange allows for goals and facts to be clearly identified , and outcomes to be assessed for their value to inform decisions about the potential benefits and risks of policy development and program delivery . effective partnerships require willingness and commitment , alignment of values , mechanisms to engage early and continuously , and plans to regularly review goals , objectives , roles , and responsibilities and outcomes . a recent review of literature highlights the inconsistency in definitions and interpretations of epidemiological terms in several modelling studies and the need for common language to sustain and enhance the application of models in public health ( 13 ) . the review found that disparate outcomes and interpretations for policy decisions may arise from inconsistent use of terms in model structures , even when the assumptions and input parameters are identical . discrepancies in how terms are used for modelling are generally associated with two main reasons . first , it is often assumed that the particular terms are well defined or well understood . infectiousness and infectious were found to be used interchangeably ; the former describes a characteristic of the disease and/or how readily the disease is transmitted , while the latter describes a patient state ( 13 ) . second , definitions of some terms have drifted over time as understanding of the mechanisms of disease processes and control has evolved . reduced susceptibility are used related to communicable disease may lead to different results depending how they are used in modelling . developing a common language this will in turn decrease misinterpretation of the outcomes by allowing for comparisons of scientific evidence from multiple disciplines involving health research , and helping knowledge users and policymakers to better understand research outcomes and their applicability to policy and practice . there are other factors responsible for variation in model findings , including different strategies or approaches and assumptions , different population demographic variables , and the objectives for evaluating policy effectiveness that can vary from one situation to another . the latter can be exemplified in two recent studies on the effectiveness of school closure during pandemic influenza outbreaks . when assessing the effect of school closure strategies in reducing community attack rates , halder et al ( 14 ) found that due to the difficulty in determining the true degree of epidemic spread and its severity in the early stages of an outbreak , a strategy of individual school closures would be more effective than simultaneous closures across a region . the outcomes are drawn from an agent - based simulation model of albany , a small community in western australia with a population of approximately 30,000 individuals . in contrast , to evaluate the impact of local reactive school closures on critical care provision in the united kingdom population setting , house et al ( 15 ) concluded that school closures should be coordinated in time ( simultaneous ) and location ( all schools within a school district ) to become an effective strategy to reduce infection transmission and , consequently , relieve capacity pressures of hospital intensive care unit admissions . the population demographics and the objectives for closing schools are distinctly different between the two studies , suggesting that different modelling approaches are required for measuring the effectiveness of school closures . understanding scenario - specific outcomes and their applications requires a critical evaluation to address the following questions : is the methodology appropriate for the specific population setting?do the assumptions and parameters address the reality of demographic and geographic characteristics?can the outcomes be compared with other studies and validated with observed data?how generalizable are the outcomes to address different scenarios or population settings ? is the methodology appropriate for the specific do the assumptions and parameters address the reality of demographic and geographic characteristics ? can the outcomes be compared with other studies and validated with observed data ? a consensus emerged during the workshop regarding the need to develop a common language for modelling to enhance its application in a public health context and promote bidirectional communication ( table 2 ) . to address this need , the fourth session of the workshop provided an opportunity for participants to discuss the establishment and potential impact of a community of practice . during the final discussion session , a number of important issues related to the development of a cop network were discussed , including its structure and governance , leadership and research capacity , memberships and partnerships , strategic plans for sustainability and resources , and the impact and uptake of outcomes ( table 3 ) . the october 2014 national workshop propelled new discussion on the value of mathematical models in public health planning and the need for greater cohesion and collaboration among stakeholders . the workshop concluded with a consensus among participants that there is work to be done and a willingness to continue to work together . the creation of a common lexicon is a tangible , initial task that should be undertaken as an immediate response to the workshop discussions . we expect that through sustained cross - disciplinary dialogues , a cop will initially produce a book of terminology that describes current usage and proposes common terminology ( community standards ) in different areas , including medical and infectious diseases epidemiology , public health and disease modelling . this reference book can then be updated regularly when new terms need clarification for shared understanding and agreement in use . furthermore , in times of uncertainty , the virtual cop network will provide opportunities to access , analyze , synthesize and utilize reliable information and databases in a timely fashion , and drive a broad consensus around plausible alternatives and integrated courses of action . it is also true , however , that ongoing discussions between modellers and public health personnel will help to clarify language use and break down perceived barriers . within a number of weeks after the workshop , a new virtual community of practice , created by national collaborating centre for infectious diseases through linkedin , called mod4ph ( modelling for public health ) ( 16 ) was launched generating questions and comments to further the workshop discussions . within a number of weeks after the workshop , a new virtual community of practice , created by national collaborating centre for infectious diseases through linkedin , called mod4ph ( modelling for public health ) ( 16 ) was launched generating questions and comments to further the workshop discussions .

infection transmission models have been applied in the canadian public health system to create modelling frameworks and knowledge translation methods that inform public health by linking theory , practice and policy . the use of mathematical modelling in public health decision making for infectious diseases workshop was held by the pandemic influenza outbreak research modelling team and the national collaborating centre for infectious diseases to establish the infrastructure , expertise and resources necessary for building a community of practice . the authors discuss the key presentations , as well as summarize the outcomes and action plans that emerged .

when oxygen supply to the fetus is significantly disrupted , tissue oxygenation deprivation develops , acids begin to accumulate and acidemia develops . umbilical cord blood gas measurement in comparison with the fetal scalp ph monitoring could better detect a hypoxic baby . in 1952 , virginia apgar , proposed a scoring system to assess the condition of newborns during the first minutes of life , and to evaluate anesthetic and obstetrical practices . she proposed five objectives and easily - measured clinical signs : heart rate , respiratory effort , muscle tone , reflex irritability , and color . it has been used to assess asphyxia , predict neurological damage and vitality of a neonate during the first minute of life . umbilical cord blood gas assessment seems to be the most objective determination of the fetal metabolic condition at the time of birth [ 47 ] . manganaro and colleagues suggested that the 5 minute apgar score is useful for immediate clinical assessment and care of the neonate . they found 5 minute apgar score had a high concordance with metabolic acidemia , but anyaegbunam and colleagues ' study revealed that in 20.7% of neonates delivered had an abnormal ph ( less than 7.20 ) and normal apgar . the present study was carried out to determine the correlation between umbilical cord ph and apgar score in high - risk pregnant mother . this was a prospective cross sectional study conducted in a teaching hospital during february 2004 to september 2005 . the study was approved by the research ethics committee of babol university of medical sciences . study population consisted of mothers who came with labor pain according to the sample size . at the time of admission , they were assigned to high or low risk group according to whether or not they had any perinatal risk factor that categorized them as high - risk pregnancy . high - risk pregnancy was defined as a pregnant mother who is at risk to deliver a neonate with birth asphyxia according to the definition by american academy of pediatrics . all normal vaginal and cesarean section ( c / s ) deliveries included in this study were chosen in accordance with this definition . all mothers who delivered a baby with a major congenital anomaly or had intra uterine fetal death ( iufd ) were excluded from the study . immediately after delivery , umbilical cords were clamped on both ends and an arterial blood sample was collected anaerobically in a pre - heparinized insulin syringe . ph , base excess , carbon dioxide pressure ( pco2 ) , po2 and hco3 were measured at 37c by ph and gas analyzer ( avl , compact3 , australia ) . apgar score was assessed by a trained physician at 1 and 5 minute after birth . in case of an apgar score less than 8 , advanced resuscitation means that a baby required positive pressure ventilation , chest compression and/or drugs administration . all resuscitated babies were transferred to neonatal intensive care unit or newborn services for post resuscitation care . demographic data like gestational age , birth weight , apgar score , need for resuscitation and/or newborn ward admissions were collected by a questionnaire in both groups . sample size calculated 96 mother - fetal pair for each group ( if we consider 1-=0.95 , r=0.25 and 1-=0.80 ) . for each high - risk mother , a low risk mother was selected as control . student 's t - test , the mann - whitney and test were used for analysis . during a 6-month period , 96 mother - fetus pairs , 49 in high risk , and 47 in low risk group participated in the study . frequency of perinatal risk factors in high - risk groups is shown in table 2 . demographic characteristics of neonates of high and low risk groups nicu= neonatal intensive care unit the frequency of perinatal risk factor in high - risk pregnant mothers af = amniotic fluid ; fhr= fetal heart rate ; iugr = intra uterine growth retardation ; c / s= cesarean section the most common perinatal risk factors accompanied with low umbilical artery ph were prolonged rupture0 of membranes , breech presentation , and meconium stained amniotic fluid . the apgar score at 1 and 5 minutes in high - risk patients were significantly lower than in the low risk group ( table 3 ) . ph values in mothers were significantly lower than those in low risk counterpart ( p<0.001 ) . apgar score at 1 , 5 , 10 and 15 minutes after birth in high and low risk group ( mean sd ) umbilical arterial blood ph , base excess and gas values in high and low risk mothers immediately after birth ( mean sd ) according to kendal correlation coefficient , there was no significant correlation between apgar score at 1 and 5 minute and umbilical cord ph in low risk group ( r=0.212 , p=0.1 ) , whereas in high - risk group , a significant correlation between apgar score at 1 and 5 minute and umbilical cord ph was found ( r=0.01 , p=0.036 and r=0.176 , p=0.146 respectively ) . in the current study , we studied correlation of umbilical cord measures of acidosis at birth and the presence of risk factors in pregnancy . the meansd value of umbilical ph in high - risk group was lower than that in low risk group . there was also a significant relation between umbilical cord ph and low apgar score with the incidence of selective neonatal outcomes like nicu admission and need for advanced resuscitation . other authors reported similar short - term outcomes for hospital based patients ' populations giving birth at term [ 11 , 12 ] . meansd for umbilical cord ph , nahco3 and pco2 in neonates delivered to a high - risk pregnant mother differ significantly with those in low risk mothers but mean ( sd ) values for po2 and base excess did not differ between the two groups . this finding may emphasize the importance of the latter values on prediction of the occurrence of neonatal outcome . in fact metabolic and respiratory acidosis and hypoxia may jeopardize the baby more than a respiratory acidosis alone [ 13 , 14 ] . apgar score at 1st and 5th minute in high - risk group was lower than that in the low risk group . but there was no significant difference in apgar score at 10th and 15th minute between the two groups . this finding emphasizes the impact of the perinatal risk factors on the immediate general condition of the babies at birth and also the effect of immediate intervention on the improvement of the neonatal condition . in our study , there was no significant correlation between apgar score at 1 and 5 minute and the umbilical artery ph in low risk group . these two parameters , apgar score at first minute and umbilical cord ph , behave independently . if immediate intervention and resuscitation commence , there would not be enough time to develop persistent hypoxemia and acidosis . on the other hand , in high - risk group both the apgar score and umbilical cord ph should be employed to interpret the actual condition of the neonate . socol and colleagues showed that neonates with an apgar score less than or equal to 3 at five minutes and a complicated clinical course were more likely to have lower umbilical cord arterial ph measurements and higher base deficit values than did their counterparts with an uncomplicated clinical course . vargas - origel found a significant difference in the apgar score at one and five minute , as well as in umbilical cord ph between asphyxiated babies and control group . in a newly published study , locatelli and colleagues evaluated the predictors of umbilical artery acidemia in term infants and found that evidence of acidemia is present in only 38% of term babies with low apgar score and it is predominantly associated with intrauterine vascular disease like preeclampsia , abruptio placenta , birth weight less than 10 percentile and placental vascular pathologies . although apgar score provides a convenient short hand for the status of the newborn , it is often incorrectly used as a correlate of neonatal acidosis . in fact , only a minority of neonates with low apgar scores at 5th minute have cord evidence of metabolic acidosis . in order to evaluate how often low 5 minute apgar score at term is associated with asphyxia , hogan and their colleagues studied 183 term infants with apgar score below 7 and concluded that in the absence of malformations , the majority of apgar scores below 4 and at least half of scores 4 - 6 could be attributed to birth asphyxia . signs of hypoxia usually appeared during labor but they were present at admission in 38% of cases with apgar score below four . the most common risk factor found in high - risk group in our study was emergency c / s . in a local study , no relation was found between the mode of delivery and umbilical cord blood gases . in another local study there was a significant correlation between c / s , low apgar score and acidemia . emergency c / s can result in acidemia because of the underlying condition that necessitates the emergency c / s . our study highlights a correlation between the presence of perinatal risk factors and umbilical cord ph in high - risk mothers . so we recommend assessing the umbilical cord ph in any mother who has a perinatal risk factor in her history or physical examination .

objectivethe apgar score as a proven useful tool for rapid assessment of the neonate is often poorly correlated with other indicators of intrapartum neonatal well - being . this study was carried out to determine the correlation between umbilical cord ph and apgar score in high - risk pregnancies.methodsthis is a prospective cross - sectional , analytic study performed on 96 mother - fetal pairs during 2004 - 2005 at shahid yahyanejad hospital , which is affiliated to babol university of medical sciences . apgar score at 1 and 5 minutes after birth was taken and an umbilical cord blood gas analysis was done immediately after birth in both groups . mothers came with a labor pain and were divided into high - risk and low risk if they have had any perinatal risk factors . other data like gestational age , birth weight , need for resuscitation and admission to the newborn ward or neonatal intensive care unit was gathered by a questionnaire for comparison between the two groups . p - value less than 0.05 was considered being significant.findingsthe gestational age and birth weight were the same in high - risk and low risk mothers . mean umbilical artery blood ph in high - risk mothers was significantly lower than in low risk mothers ( p=0.004 ) . mean apgar scores at 1 and 5 minutes were significantly lower in high - risk mothers than in low risk mothers ( p<0.05 ) . according to the kendal correlation coefficient there was no significant correlation between apgar score at 1 and 5 minutes and umbilical cord ph in low risk group ( r=0.212 , p=0.1 ) . but in high - risk group there was significant correlation between apgar score at 1st and 5th minute and the umbilical cord ph ( r=0.01 , p=0.036 and r=0.176 , p=0.146 , respectively).conclusioncombination of apgar score and umbilical cord ph measurement in high - risk pregnant mother could better detect jeopardized baby .

facet dislocations are part of a spectrum of cervical spine flexion / distraction - type injuries . flexion distraction injuries are described as anterior displacement of the vertebral body due to tensile or shear failure of the posterior elements coupled with facet fractures or dislocations . facet fractures were classified by allen et al and later modified by harris et al . it is agreed that bilateral facet dislocations ( df3 ) disrupt the posterior ligamentous complex and facet capsule and require operative stabilization as the definitive treatment . the treatment of distractive flexion injuries with halo immobilization or external orthoses has been associated with a high rate of radiographic failure defined as re - dislocation , neurological deterioration , or failure of osseous or ligamentous healing . cadaveric biomechanical studies that have simulated bilateral facet injuries report superior stabilization with lateral mass fixation posteriorly compared with anterior cervical plate fixation . despite biomechanical advantages with posterior fixation , anterior cervical discectomy and fusion ( acdf ) for the treatment of bilateral facet dislocations has also been reported as clinically successful . hundred percent fusion rates and low infection rates have been reported with anterior fixation and fusion . the anterior approach enables the surgeon to decompress the spinal canal by removing the intervertebral disc and preventing potential neurological deterioration from disc sequestration . several authors have reported poor outcomes with acdf in the treatment of bilateral facet dislocations . henriques et al reported 7 of 13 ( 54% ) patients with bilateral facet injuries suffered re - displacement or loss of alignment with anterior plating alone . conversely , in a review of 87 patients with facet ( 75% bilateral , 25% unilateral ) dislocations , johnson et al reported a 13% radiographic failure rate with single - segment acdf in traumatic cervical flexion distraction injuries that correlated with the presence of endplate compression fracture and facet fractures on injury radiographs . the optimal approach and treatment of cervical facet dislocations remains a controversial topic . we hypothesize that in select patients with a single - level unilateral or bilateral facet fracture - dislocation , a single - level acdf has a low radiographic failure rate . the purpose of this case series is to examine the rate of reoperation due to treatment failure in patients treated with an acdf in the setting of cervical facet dislocations . we retrospectively identified patients through billing data and radiology records from january 2004 to september 2014 at harborview medical center , seattle , washington , usa . this is a retrospective cohort study of consecutive patients with allen and ferguson classification , unilateral ( df2 ) and bilateral ( df3 , df4 ) facet dislocations from harborview medical center , seattle , washington , usa treated with acdf . all patients under 70 years of age at the time of admission , treated for unilateral and bilateral facet dislocations with acdf , were included . all patients were placed in a miami - j collar for a minimum of 6 weeks postoperatively . those with a pathologic facture due to neoplasm , or infection , and those with less than 30-day follow - up were excluded . using electronic medical records , we reviewed all identified patients charts for age , sex , mechanism of injury , and level of neurologic compromise as determined by their american spinal injury association ( asia ) impairment scale on admission and on last obtainable follow - up examination . we analyzed radiographs to assess patterns , fixation , angles , and presence of disc herniation , and pseudoarthrosis . the presence or absence of a facet fracture and/or a fracture of the endplate was recorded . the postoperative distance of translation ( in mm ) and degree of kyphosis was measured . the translation was measured from the posterior inferior edge of the cephalic vertebrae to a tangential line of the posterior body of the subjacent vertebrae ( figure 1 ) . the degree of kyphosis was recorded as the angle between the superior endplate of the injured vertebrae and the inferior endplate of the subjacent intact vertebrae ( figure 2 ) . we also recorded the presence or absence of a neurologic ( spinal cord or root level ) injury . if magnetic resonance imaging was completed prior to reduction , the presence of a disc herniation was recorded . ( note that the screws in this failure are relatively short and did not measure to be within 2 mm of the posterior cortex of the vertebral body . ) the follow - up assessment included a medical chart review looking at complications including re - dislocation , neurologic change , and need for further operative stabilization after discharge . the latest follow - up radiograph postsurgery was the one used for analysis , except in the case of early radiographic failure . one or more of the following defined a biomechanical failure : dislodgement of the interbody graftbreakage of the plate or screwsrecurrent facet dislocationincrease in kyphosis greater than 11increase in anterolisthesis greater than 3.5 mm dislodgement of the interbody graft breakage of the plate or screws recurrent facet dislocation increase in kyphosis greater than 11 increase in anterolisthesis greater than 3.5 mm bivariate analyses were performed to examine the relationships between treatment failure and qualitative and quantitative variables relating to the patient . the presence of a facet or endplate fracture was examined using the fisher exact test ( table 5 ) . abbreviations : mva , motor vehicle accident ; glf , ground - level fall ; asia , american spinal injury association . we identified 38 patients that were treated for unilateral or bilateral facet dislocations between january 2004 and september 2014 . of the 38 patients , 2 ( 5% ) had less than 90-day follow - up and were excluded . these were all done within 24 hours of injury and as soon as possible within admission to the emergency room . this patient was subsequently reduced intraoperatively after a discectomy with the use of caspar pin assisted distraction . all patients had a single - level injury , and they lacked clear radiographic features of osteoporosis and/or diffuse idiopathic skeletal hyperostosis / ankylosing spondylitis . sixteen patients with unilateral and 20 with bilateral facet dislocations who underwent acdf were identified ( male - female ratio 27:9 ; average age 35 years ; age range 13 - 58 years ) . were present in 7 patients ( 19% ) . mechanisms of injury included 20 motor vehicle accidents , 7 ground - level falls , 3 dives into water , 2 assaults , and 4 falls from height . the most common level of dislocation was c5-c6 ( n = 14 ; table 1 ) . ten patients ( 28% ) had complete tetraplegia ( asia a ) and 10 patients ( 28% ) had an incomplete spinal cord injury ( asia b , c , d ) on admission . of the 10 patients with compete tetraplegia , 5 ( 50% ) had an improvement in their asia score postoperatively . of the 10 patients with incomplete spinal cord injury , 5 ( 50% ) had an improvement in their asia score postoperatively ( table 2 ) . immediately postoperatively , the mean anterolisthesis measured 0.1 mm ( range 2.5 mm to 1.9 mm ) , the kyphosis averaged 0.5 ( range 15 to 16 ) . at final follow - up , the mean change in translation measured 0.9 mm ( range 1.6 to 9.5 mm , sd 2.24 mm ) and change in kyphosis measured 2.6 ( range 7.8 to 16 , sd 5.4 ; table 3 ) . three of 36 patients ( 8% ) had a treatment failure resulting in a second operation , which entailed a posterior fusion for enhanced stability . two of 3 patients had a recurrent dislocation associated with pullout of the screws from the inferior vertebral body . the third patient developed graft subsidence and focal kyphosis of 16 as well as facet subluxation without dislocation ( figure 3a - d ) . on postoperative day 30 , the surgeon elected to return to the operating room to perform posterior fixation and fusion . change in angulation greater than 11 and anterolisthesis greater that 3.5 mm were both present in all 3 patients ( table 4 ) . ( a ) preoperative mid - sagittal ct reformat showing kyphosis and translation at c5-c6 with subtle endplate fracture at c6 in 36-year - old male alcoholic who fell down the stairs . ( d ) four - week postoperative radiograph showing increased kyphosis . ( e ) six - month follow - up lateral radiograph after posterior lateral mass screws placed bilaterally at c5-c6 . three of 7 ( 43% ) endplate fractures failed ( p < .01 ) and 1/28 ( 4% ) facet fractures failed ( p = .13 ) . the mean time to failure was 4 weeks ( 1 - 7 weeks ; table 5 ) . cervical flexion distraction injuries are potentially devastating injuries that involve a predominant flexion force with disruption of the posterior tensile elements of the spine . despite several biomechanical studies demonstrating the superiority of combined anterior - posterior approach , compared to posterior spinal instrumented fusion ( psif ) or acdf alone anterior fixation is associated with shorter operation room time , less blood loss , permits discectomy , and obviates the need to place patients in the prone position with unstable spinal injuries . the reported results of acdf in patients with unilateral and bilateral cervical facet dislocations and fracture - dislocations have varied considerably . this variability in results could be explained by studies with small numbers of patients , variability in techniques , and instrumentation . to our knowledge , there have been few publications over the past 10 years investigating the efficacy of acdf for flexion - distraction injuries with jumped facets . we hypothesize that in single - level jumped facets , acdf is associated with low rates of radiographic and clinical failure as reflected by reoperation rates . our results are consistent with those reported by johnson et al that acdf in the setting of an endplate fracture is associated with treatment failure . however , johnson et al also reported that facet fractures are associated with treatment failure . of the 28 patients with facet fractures , only one had a treatment failure and that patient also had an endplate fracture . it is possible that our results differ because of a smaller number of patients in our study . nonetheless , according to our series there are few studies examining the clinical outcomes of acdf for single - level flexion - distraction injuries . henriques et al reported the fusion results of a cohort of 36 patients with flexion - distraction injuries . they identified severity of flexion distraction injuries as a potential risk factor for acdf failure as 4/5 failures had df grade 3 injuries . they concluded that acdf was clinically appropriate for patient with df grade 1 - 2 without neurologic deficits . in contrast to that report , we did not find a correlation between our fixation failures as 2 of 3 failures had df grade 2 injuries and 1 failure grade 3 injury . furthermore , 2 of our failures had asia e scores and one asia d. endplate and facet fractures have been reported as risk factors for acdf failure . johnson et al followed a cohort of patients after acdf for flexion distraction injuries and found that 65% of their failures were associated with end plate fractures . there were 7 patients in our cohort with associated endplate fractures , of which 3 patients had a failure of fixation . however , fractures involving the facets do not appear to be correlated with treatment failure . although facet fractures are a harbinger of less intrinsic stability , it appears that acdf provides sufficient fixation leading to low failure rates . the authors feel the several technical pearls may contribute to a low rate of treatment failure . modern designs of anterior cervical plates with locking screw plate interfaces have led to greater application of anterior fixation to cervical trauma . we feel that positioning screws within 2 mm of the posterior vertebral cortex will optimize fixation and could decrease failure rates . also , it is important to accentuate the lordosis in order to optimize intrinsic stability . finally , in the setting of posterior facet injures , we aim to place small interbody grafts in order to prevent facet distraction and subluxation . however , independent researchers were not involved in patient care and should not have influenced the results performed data collection . a potential for selection bias could influence surgeon preference , particularly in cases of highly unstable injuries or comminuted facet fractures , which may have led surgeons to opt for posterior fixation . second , the collection of data and treatment are not standardized and controlled in the manner of a prospective study . finally , patients subjective outcomes were not assessed and were not inclusive of our definition of treatment failure . treatment failure occurred in 8% of facet fracture dislocations treated with anterior cervical discectomy , fusion , and plating . rates of failure are lower than has been previously reported . as suggested by johnson et al , endplate fractures of the inferior level in jumped facets appears to be a major risk factor of biomechanical failure . however , our series suggests that a facet fracture may not be a risk factor for failure . concern regarding mechanical failure of flexion distraction injuries should be high when they are associated with fractures of the endplate . in the absence of an endplate fracture , acdf is a reasonable treatment option in this sample of patients with single - level cervical facet dislocation .

study design : retrospective radiographic and chart review.objective:to define the rate and associated risk factors of treatment failure of anterior cervical fusion for treatment of cervical facet dislocations.methods:between 2004 and 2014 , a retrospective review at a single level 1 trauma center identified 38 patients with unilateral or bilateral dislocated facet(s ) treated with anterior cervical discectomy and fusion ( acdf ) . two patients were eliminated due to less than 30-day follow - up . demographic data , initial neurological exams , surgical data , radiographic findings , and follow - up records were reviewed.results:of the 36 patients with facet dislocations treated with acdf using a fixed locking plate , 16 were unilateral and 20 were bilateral . the mean age was 35 years ( range 13 - 58 ) . mean follow - up was 323 days ( range 30 - 1998 ) . there were 3 treatment failures ( 8% ) . three of 7 ( 43% ) endplate fractures failed ( p < .01 ) , and 1/28 ( 4% ) facet fractures failed ( p = .13 ) . the mean time to failure was 4 weeks ( 1 - 7 weeks ) . one treatment failure had a facet fracture , and all 3 failures had an associated endplate fracture.conclusion:treatment failure occurred in 3 out of 36 ( 8% ) patients with facet fracture dislocations treated with anterior cervical discectomy , fusion , and plating . rates of failure are lower than has been previously reported . endplate fractures of the inferior level in jumped facets appears to be a major risk factor of biomechanical failure . however , a facet fracture may not be a risk factor for failure . in the absence of an endplate fracture , acdf is a reasonable treatment option in patients with single - level cervical facet dislocation .

anemia in malaria is caused by hemolysis of the infected red blood cells ( rbc 's ) , sequestration of the erythrocytes in the spleen and other deep organs , and suppression of erythrocytes production in the bone marrow by the malarial pyrogen - induced cytokines.12 it has been estimated that severe malarial anemia causes between 190,000 and 974,000 deaths each year among children below 5 years of age . although blood transfusion may be life - saving in this situation , it also exposes children to the risk of hiv and other blood - borne diseases.3 normal hematological indices in the newborn have been established in the caucasians and have been found not to be the same for african neonates.456 studies done by onwukeme et al . in jos,4 scot - emuakpor et al.5 in benin , and effiong et al . in ibadan 6 documented values for nigerian neonates and showed variations in hematocrit values in full term newborns within same country which was thought to be due to several factors such as site and time of sampling , vessel used , fetal - maternal , or maternal - fetal transfusion . the lower values in african newborns compared to the caucasian values was attributed to genetic ( intrinsic ) factors . also noted is the definite pattern of progressive drop which is obtainable in the caucasians . there is need to evaluate the hemoglobin concentration ( hb conc . ) and other hematological indices of febrile newborn with emphasis on those with malaria parasitemia and to correlate it with the malaria parasite density . this is to determine if there is a relationship between malaria parasite density and hb conc . in newborns with fever to avert delays in early laboratory diagnosis of anemia and treatment . this prospective , cross - sectional , and analytical hospital - based study was conducted among neonates admitted in into the newborn unit of the university of calabar teaching hospital ( ucth ) from the november 3 , 2010 to the may 8 , 2011 . the unit had earlier been described by udo et al.7 sample size was calculated using the formula n = z pq / d . inclusion criteria were neonates with temperature 37.5c or recent history of fever , who had not received antimalarials or antibiotics at least 2 weeks prior to the enrolment into the study and whose parent(s ) or guardians had given consent . ethical clearance was obtained from the ethical review committee of the ucth before commencement of the study . a statement of the study was made available to the parents so that they could understand what the study entailed and a signed informed consent was obtained from the parents or guardians who gave consent . all consecutive babies ( 0 - 28 days ) who met the inclusion criteria were recruited until the desired sample size was obtained . detailed clinical history , covering both the antenatal and perinatal periods , was obtained for every baby enrolled . two blood films ( thick and thin film ) for malaria parasite and samples for full blood count were taken before commencement of treatment and 4 weeks after treatment at follow - up . both thick and thin blood films were prepared and stained with 2% freshly prepared giemsa stain . thereafter , it was read using 100 objective lens with oil immersion 9 within 24 hrs of collection of blood by the first investigator , assisted by the laboratory scientist . these slides were validated independently by the microscopist with institute for tropical disease research and prevention and a world health organization certified laboratory scientist attached to the department of pediatrics research laboratory.9 the parasite density was derived by the formula : parasite per microliter = number of parasites / number of leucocytes 8000 , where 8000 represents the mean leucocyte count of children , which when multiplied with the ratio of parasites to leucocytes in a given field equals the parasite density.9 parasite density was classified for the purpose of categorization of the babies into ; + ( 1 parasite/ field ) , + + ( 2 - 19 parasites / field ) and + + + ( > 20 parasites / field ) . the thin films were used for speciation of plasmodium.9 two milliliters of blood was collected in a labeled edta bottle by the investigator and sent to the hematology laboratory within 30 min of collection . where this was not possible , the samples were refrigerated at 4 - 8c for a period not > 12 hrs . this was used to determine the total white blood cell count and differentials , hb level , packed cell volume , and platelets , using an automated machine : particle counter , model pce - -210 , erma inc . , tokyo , japan . an experienced clinical hematologist , stained , viewed , and reported the blood film picture following standard procedure,10 with the active participation of the first investigator . correction for total white cell count , when numerous nucleated erythrocytes are counted , was calculated as follows : total differential white blood cells counted total white blood cell divided by total differential white cell counted total nucleated a working diagnosis of neonatal sepsis and neonatal malaria was considered in every febrile neonate . all the babies were commenced on first - line antibiotics therapy for neonatal sepsis in the unit and antimalarial drug in line with the national malaria treatment policy for newborns.11 results were collected with the aid of the case record form designed for the study . pearson 's correlation was used to determine the relationship between malaria parasite density and the values of the hb conc . of the babies . statistical significance of difference was determined using chi - square ( ) for dichotomous variables and t - test for continuous variables . the study population was made of 87 ( 58.0% ) males and 63 ( 42.0% ) females with a male : female ratio of 1.4:1 . the mean age of the study population was 4.2 5.9 days and was not normally distributed , with the median of 2.0 days . one hundred thirty- six ( 90.7% ) mothers booked for the antenatal care either in ucth or at other health facilities . four ( 66.6% ) of the six babies with malaria parasitemia were aged under 7 days , indicating that they were congenital infections . the age - related differences in malaria parasitemia were not statistically significant ( fisher 's exact = 0.15 ) table 1 shows the hematological indices in the febrile neonates . the mean hb conc . of the mean hb conc . for those with malaria only was 12.3 1.0 g / dl while it was 12.8 3.2 g / dl for those with septicemia in addition . the hb conc . were lower than that of other categories of newborns , but the differences were not statistically significant ( p = 0.91 ) . comparison of the mean hematological indices in the neonate with malaria parasitemia and those without the total white cell count was the highest ( 19.15 8.13 ) in newborns with malaria alone compared to that for newborns with malaria / septicemia co - infection then followed by those with septicemia only . neutrophils values were higher in the newborn with co - infection while lower than the mean in those with malaria alone , while the lymphocytes were highest in newborns with malaria alone . all the 150 newborns recruited in the study were seen at follow - up at the newborn outpatient clinic as scheduled . none of the babies had symptoms , and all suckled actively at the breast . repeat hb conc . was all within the normal range for age and blood film for malaria parasite was negative . the mean hb conc . for the parasitized babies was lower than those of nonparasitized babies although the differences did not reach statistical significance . these observations are , however , inconclusive since the number of those with parasitemia was quite small . the malaria parasite density in this study was low and is similar to that obtained by other authors.121314 this could be explained by the high maternal immunity from prior malaria infection in endemic areas , high rate of antimalarial prophylaxis used by the mothers of the study population , maternal use of artemisinin - based combination therapy to treat malaria in pregnancy , the fetal hb that does not support malaria parasite growth , and low transmission rate in dry season as the climatic conditions and period of the year , influence intensity of malaria transmission in a given locality.1516 good proportion of the subjects in this study was assessed long after delivery and it was therefore not feasible to include the cord parasitemia as a variable in the study , to ascertain if it was associated with the drop in hb conc . neonatal malaria does occur in our environment . while it does not affect the white cells indices it is recommended that hemoglobin concentration be estimated in newborns with malaria to reduce infant morbidity and mortality in our environment . in addition blood film for malaria parasite microscopy should be done for neonates with fever in our environment .

background : normal hematological indices has been determined in nigerian newborns and found to be lower compared to their caucasian counterparts . this was attributed to genetic factors . malaria is endemic in nigeria and is one of the major causes of ill health and death . anemia is an important manifestation of malaria . resistance by malaria parasites to antimalarial drug exacerbates the situation by continuous hemolysis.aim:to determine the hematological indices in febrile newborn with malaria parasitemia.materials and methods : one - hundred fifty neonates ( 0 - 28 days ) with fever admitted into the newborn unit of university of calabar teaching hospital , over a 6 months period , were recruited consecutively . blood film for malaria parasites and samples for full blood count were obtained and sent to the laboratory before commencement of the treatment . data analysis was with spss version 14.results:one-hundred fifty babies were recruited into the study . most ( 85.3% ) of the babies were aged 7 days . six babies ( 4% ) had malaria parasitemia . plasmodium falciparum was the only species identified . all the babies that had parasitemia were anemic ( mean hemoglobin [ hb ] concentration of 12.6 g / dl ) even when parasite count was low ( average of 30.6/l ) though this could not be attributed solely to malaria . none of these neonates was transfused . all the other hematological indices were within the normal range of healthy newborn population irrespective of parasitization.conclusion:neonatal malaria does occur in our environment . while it does not affect the white blood indices , it lowers neonatal hb . it is recommended that hb concentration be estimated in newborns with malaria to reduce infant morbidity and mortality in our environment .

the reconstruction of the elbow area is always a challenge in the field of plastic surgery . a very soft skin is covering noble anatomical tissues that include the brachial , radial and ulnar arteries as well as the ulnar , radial and median nerves [ 13 ] . moreover , the elbow joint is very sensitive to trauma and immobilization , showing a susceptibility to stiffness . traditionally the gold standard for covering medium to large elbow defects were the free flaps . in recent years the pedicled propeller flaps become more and more an alternative to the microsurgical free transfer . the advantages of the propeller flaps include a shorter intraoperative time , reduced costs and the lack o microsurgical anastomoses that make possible a rapid postoperative physiotherapy . nevertheless , there are skeptics that are not convinced by the role of propeller flaps . still , in our experience in covering elbow soft tissue defects we had a 100% success rate . to emphasize the role of propeller flaps in covering elbow defects we present the case of a 35-year - old male patient from a rural area , who was suffering from an old contractile post burn scar in the cubital fossa . the maximum extension in the elbow joint was 120 both for active and passive motion . no other major pathological modifications were observed . in order to obtain a normal extension of the elbow we decided to replace the scar with a propeller perforator flap . because of the many false positive and false negative doppler signals we decided to rely on the intraoperative identification of the perforator pedicle . under general anesthesia the noble anatomical structures that lie in the cubital fossa were identified and showed no sign of pathological modifications at inspection . the post - excisional defect that was obtained had an area of 60 square centimeters . a longitudinal incision at the lateral margin of the future flap was performed . under loupe magnification a large caliber perforator bundle arising from the inferior cubital artery was chosen as a pedicle for the flap . after the pedicle was chosen , the flap design was extended , to obtain a complete insular flap . the flap was eventually rotated 180 around its bundle axis so that the larger pad could cover the defect . the donor area was covered with a split - thickness skin graft harvested from the ipsilateral thigh . due to the lack of microsurgical anastomosis , four weeks after surgery the patient was able to perform a full active extension of the elbow joint . to emphasize the role of propeller flaps in covering elbow defects we present the case of a 35-year - old male patient from a rural area , who was suffering from an old contractile post burn scar in the cubital fossa . the maximum extension in the elbow joint was 120 both for active and passive motion . no other major pathological modifications were observed . in order to obtain a normal extension of the elbow we decided to replace the scar with a propeller perforator flap . because of the many false positive and false negative doppler signals we decided to rely on the intraoperative identification of the perforator pedicle . the noble anatomical structures that lie in the cubital fossa were identified and showed no sign of pathological modifications at inspection . the post - excisional defect that was obtained had an area of 60 square centimeters . a longitudinal incision at the lateral margin of the future flap was performed . a large caliber perforator bundle arising from the inferior cubital artery was chosen as a pedicle for the flap . after the pedicle was chosen , the flap design was extended , to obtain a complete insular flap . the flap was eventually rotated 180 around its bundle axis so that the larger pad could cover the defect . the donor area was covered with a split - thickness skin graft harvested from the ipsilateral thigh . due to the lack of microsurgical anastomosis , four weeks after surgery the patient was able to perform a full active extension of the elbow joint . the range of movement was in normal limits with a neutral position in full extension at 0 and a full flexion till 150. the patient was reintegrated in his social and professional life . searching the literature we observed and increased number of papers dealing with propeller flaps reconstruction for the upper limb in the last five years . this is partly because some of the propeller flaps surface can not be predicted and partly because of the elaborated pedicle dissection technique [ 911 ] . from our own experience the literature results are encouraging : all the authors reported a 100% survival rate of the flap . in this clinical case however , donor areas that are tighter than 56 cm may be closed by direct suture [ 1,3,1416 ] . a big advantage of propeller flaps is that they are harvested from the same anatomical segment as the defect . this responds to a basic principle in plastic surgery , to replace like with like . the cosmetic results are superior to covering alternatives that bring tissue from distant regions of the body . another important advantage of the pedicled propeller flaps is the possibility to start the physiotherapy on the first postoperative day without risking to compromise the flap vascularization . firstly , for the patients with polytrauma it reduces the critical anesthesia time . secondly , by reducing the operation time , it automatically reduces the operative costs . soft tissue defects in the elbow region require a good coverage to protect the vessels and nerves that lie superficially in these area . the propeller perforator flap are capable of offering a good coverage in the elbow , by replacing like with like . this is the key of a successful cosmetic result in comparison with the free transfer that is covering the defect with tissue situated at a distance . also , the absence of the microsurgical anastomosis allows an early physiotherapy in order to avoid joint stiffening .

covering the elbow soft tissue defects is a difficult task for the plastic surgeon . because of , the important anatomical structures situated superficially and the high tendency for stiffness of the elbow , the reconstructive method must be chosen carefully . traditionally the free flaps were the choice method for elbow reconstruction . in our department , we use the perforator pedicled flaps for covering elbow defects , as a viable alternative to the free microsurgical transfer . this paper presents a successful case of covering an elbow soft tissue defect in a male patient . by using a local pedicled flap we replaced like with like to obtain a very good cosmetic result . the lack of microsurgical anastomosis allowed an early physical therapy .

an internal hernia ( ih ) is an infrequent cause of small bowel obstruction ( sbo ) , with a reported autopsy incidence of 0.2 to 0.9% , and is the cause of small - bowel obstruction in 0.6 to 5.8% of the cases [ 1 , 2 ] . abdominal computed tomography ( ct ) plays an important role in the evaluation and management of patients with sbo . an 84 year - old woman visited the emergency room presenting with 2 days of abdominal distension and vomiting . recently , she had been admitted to the orthopedic hospital with the chief complaint of back pain . clinical examination revealed abdominal distension , but no visible or palpable abdominal mass or wall hernias . leukocytosis ( 12.9 10/l ) with a predominance of neutrophils ( 86.8% ) was noted on routine hematology . intravenous contrast - enhanced abdominal ct scan showed dilatation of small bowel loops and herniation of a short segment of the small bowel through the right cecal fossa ( figs . 1 , 2 ) . the patient was taken immediately for an exploratory laparotomy , which revealed a segment of the distal jejunum entrapped in the cecal fossa . the entrapped jejunum was released , and lysis was done between two peritoneal folds ( figs . 3 , 4 ) . internal hernias may infrequently cause sbo , which may be fatal because of the risk of strangulation of the hernial content . paracecal hernias account for a minority of ih - related sbos [ 3 , 4 ] . these hernias are the result of alterations in the normal process of intestinal rotation during embryonic development . the embryological development of the cecum includes budding , exteriorization into the umbilicus and subsequent retraction onto the posterior abdominal wall , which usually predisposes the paracecal fossa to the formation of a number of pockets or recesses . an excellent classification for boundaries of hernias was formulated by meyer [ 6 , 7 ] , who described six : paracecal sulci , cecal fossa , cecal recess , superior ileocecal recess , inferior ileocecal recess , and retrocecal recess . paracecal sulci are lateral depressions of the peritoneum invested on the cecum , but recesses may be absent . the lateral fold is a continuation of the white line of toldt and the medial fold originating from the ileocecal angle , medial aspect of the cecum . the cecal recess is formed by folds described for the cecal fossa , but in this instance , the cecum is entirely retroperitoneal . superior and inferior ileocecal recesses are formed by a peritoneal fold originating from the terminal ileum to the cecum . a retrocecal recess is formed by the cecum anteriorly , the iliac fossa posteriorly , the right colic gutter laterally and the mesentery medially . in our case , the clinical symptoms of internal hernias may range from intermittent mild digestive complaints to acute - onset incarceration . the major symptoms are obstructive symptoms of abdominal pain , nausea , vomiting , constipation and obstipation . ct allows advanced diagnosis of intestinal obstruction because it provides more information about the cause than do either x - ray or contrast studies . in addition to demonstrating the presence of extraluminal lesions , such as masses , adenopathy , soft tissue infiltration , fluid collections , abscesses and vascular anomalies [ 9 , 10 ] , the greatest advantage of ct is the diagnosis of early or partial obstruction , closed loop obstruction and multiple segments of obstruction . dilatation of small intestine loops with a transitional zone adjacent to the cecum or an edematous small bowel located lateral to the cecum allows a paracecal hernia to be diagnosed with high certainty . almost always the treatment for small bowel obstruction caused by a paracecal hernia is surgical intervention . recently , the laparoscopic technique has been found to be useful for the diagnosis and treatment of bowel obstructions .

internal hernias are rare causes of small bowel obstruction , and one such internal hernia is the paracecal hernia . we report a case of a small bowel obstruction related to a paracecal hernia in which a preoperative diagnosis was made on computed tomography . a laparotomy was performed for definitive diagnosis and treatment . the surgery achieved a good outcome .

we report the case of a 27-year - old indonesian chinese male who was referred to the dermatology unit for a non - pruritic rash on the upper and lower limbs for approximately 10 months duration . he has a significant past medical history of chronic myeloid leukaemia with a bcr - abl kinase mutation diagnosed 3 years ago . he was first started on imatinib 3 months after the diagnosis with a change to nilotinib 3 years later due to imatinib resistance . the patient had been receiving nilotinib 400 mg twice a day for 3 days prior to the onset of the rash , which persisted throughout the course of nilotinib . , the patient had extensive rough , brown , follicular papules over the trunk , upper and lower limbs ( fig . 1 , fig . the rash was more widespread over the extensor portion of the upper limbs ( fig . keratosis pilaris was diagnosed and the patient was started on a topical ammonium lactate cream . nilotinib was continued in view of the critical role of the medication in the treatment of his chronic myeloid leukaemia . keratosis pilaris is a common genetic skin disorder characterised by keratinisation of the hair follicles of the skin . it is inherited in an autosomal dominant fashion , although no specific gene has been identified . it typically presents as small , rough , brown folliculocentric papules distributed over characteristic areas of the skin , particularly the outer - upper arms and thighs . it has been associated with ichthyosis vulgaris as well as other atopic conditions like asthma or atopic dermatitis . nilotinib is a second - generation bcr - abl tyrosine kinase inhibitor ( tki ) that is approved for the treatment of imatinib - resistant chronic myeloid leukaemia expressing the bcr - abl mutation . although structurally similar to imatinib , it is approximately 1030 times more potent than imatinib at inhibiting bcr - abl tyrosine kinase activity . it also inhibits other kinases important in the proliferation of malignancies , e.g. abl - src9 , which helps it overcome bcr - resistance in cases of advanced chronic myeloid leukaemia . although these medications are generally well tolerated , cutaneous adverse drug reactions occur in approximately 34.3% of patients receiving nilotinib , with 2.6% of them exhibiting a high - grade rash . notably , compared to a previous case series report , our patient did not have any pruritus nor alopecia . the mechanism of these reactions are not well understood , although c - kit , which is one of the targets of tkis , has been possibly attributed since it is not only expressed in cancer cells , but also similarly in basal skin cells and melanocytes . such reactions may influence the compliance to nilotinib therapy , thereby affecting the oncologic outcome . although it is reported to be present in approximately 23% ( n = 9 ) of cases of adverse cutaneous reactions following such drug therapy , we believe greater emphasis is needed in the recognition of such an association , especially in the absence of accompanying suggestive symptoms , e.g. pruritus . appropriate treatment should be instituted in order to increase compliance to therapy and achieve a good oncologic outcome .

nilotinib is a second - generation bcr - abl tyrosine kinase inhibitor ( tki ) that is approved for the treatment of imatinib - resistant chronic myeloid leukaemia expressing the bcr - abl mutation . cutaneous adverse drug reactions occur more frequently in patients using this medication . we present a case of nilotinib - induced keratosis pilaris that did not have accompanying symptoms of alopecia or pruritus . greater recognition of this association is needed so that appropriate treatment can be instituted to ensure a good oncologic outcome .

in africa , 15% of blindness is due to glaucoma and it is also the region with the highest prevalence of blindness relative to other regions worldwide.1 socioeconomic deprivation , poor access to health care , and suboptimal diagnosis and management are contributing factors and this often leads to late presentation . due to difficulties previously encountered in case detection and uncertainties about how to manage the disease in a blindness prevention program , it was not included as a priority disease in the first phase of vision 2020 planning for africa . vision 2020 is the global initiative for the elimination of avoidable blindness , a joint program of the world health organization ( who ) and the international agency for the prevention of blindness ( iapb).2 automated perimetry has been established as the standard method of testing by which patients at risk for glaucoma and those with documented field loss are followed in research studies and in clinical practice . there are a number of visual field analyzers available on the market , but many landmark clinical studies utilized the humphrey field analyzer ( carl zeiss meditec ag , jena , germany ) to assist with glaucoma diagnosis and progression.37 many eye units in africa are not equipped with visual field analyzers and there have been no reports of the contribution of visual fields to glaucoma management in those centers that do have the equipment . the use of visual field analyzers has been recommended for glaucoma management in african clinics , specifically to assist in screening , diagnosis , and monitoring of progression as part of the vision 2020 program . the eye clinic at groote schuur hospital is a tertiary - level referral center that treats patients with primary , secondary , and tertiary eye diseases . the clinic is equipped with two humphrey visual field ii - i - series analyzers , which have been in use for approximately 15 years . other tools available in this unit to assist with the management of glaucoma are disc photography and goldmann applanation tonometry . therefore , the aim of this study was to determine the contribution of humphrey visual field testing to the management of glaucoma cases in our specialist glaucoma clinic . we conducted a retrospective , consecutive case note review of 446 patients attending the glaucoma clinic for the 6 months between january and june 2010 . ethical approval was obtained from the research ethics committee of the faculty of health sciences , university of cape town ( cape town , south africa ) . the diagnosis of glaucoma was based on the findings noted by the clinician in the clinical notes , namely disc findings in keeping with glaucoma a vertical cup - to - disc ratio of 0.7 or more raised intraocular pressure a visual field defect suggestive of glaucoma . visual field reliability was defined as per the manufacturer s guidelines for standard threshold testing : less than 20% fixation losses or less than 33% false - negative responses or less than 33% false - positive responses . a visual field was indicative of glaucoma if the hemifield test was outside normal limits and there was a cluster of three contiguous points at the 5% level on the pattern deviation plot . visual field progression was defined as deterioration of three or more points at the same location at the p<0.05 level on three consecutive visual fields . data was captured on an excel spreadsheet and then analyzed using stata ( v10.0 ) . of the 446 case notes reviewed , 344 patients had performed humphrey visual fields at some stage during their attendance at the clinic . table 1 provides a summary of the sex and diagnosis groups of the subjects . the median age ( interquartile range ) at diagnosis was 58 ( 18 ) years ( range 1793 years ) . the visual field testing strategies that were used are presented in table 2 . the median number of field tests performed per patient was six ( iqr 8 ; range 132 ) . of the total 2,604 field tests performed , 1,931 ( 74.2% ) were found to be reliable and 725 ( 28% ) tests were unreliable based on analysis of a single parameter , ie , fixation losses alone , false - negatives alone , or false - positives alone . the most common reason for unreliability was fixation losses ( 60% ) , followed by false - negative responses ( 34% ) , and false - positive responses ( 6% ) . 57 subjects were diagnosed elsewhere , 21 subjects were diagnosed before humphrey visual fields were in use in the clinic , and 16 had ocular hypertension or were glaucoma suspects . optic disc cupping with raised intraocular pressure was used more than any other criteria to diagnose glaucoma . the median time between diagnosis of glaucoma and the first visual field test was 5.6 weeks . eighty patients were excluded in the assessments of the baseline and evidence of progression because they had only performed one field test . the number of subjects showing evidence of visual field progression was 24 ( 9% ) . treatment changes were based on a number of factors as presented in table 4 . in 90% of subjects , the decision to change treatment was based on inadequate intraocular pressure control alone . this is the first clinic - based study describing the contribution of humphrey visual field testing to the management of glaucoma in africa . our results may be summarized as follows : 1 ) the majority of visual fields performed in this patient population were reliable ; 2 ) most patients with glaucoma are diagnosed without the use of visual field tests ; 3 ) only half the patients reach a baseline ; and 4 ) there was evidence of visual field progression in a minority of patients and this contributed to changes in management in only a small number of patients . various population - based surveys assessing the prevalence of glaucoma in africa included automated perimetry as part of the assessment.812 however , only two of these used the humphrey field analyzer.8,12 in all these studies , the majority of subjects were diagnosed based on advanced structural changes with unproven field loss . we found that the sita - fast testing strategy was the most commonly used testing strategy in our clinic . it has been reported to have excellent sensitivity and specificity for glaucomatous visual field loss and is much faster than the full threshold testing strategy.13,14 however , it has also been reported to have variable repeatability.14 for this reason , some authors do not recommend the use of sita - fast for glaucoma follow - up , while others suggest that it can be used , provided that all subsequent fields are performed using the same strategy to allow for comparison.15 current literature suggests that no consensus exists regarding the reliability criteria that should be used for the sita testing strategy . the manufacturer recommends the following criteria for reliability when using the sita testing strategy : less than 20% fixation losses and less than 15% false - positive errors . there is no limit displayed on the machine for false - negative errors with sita testing , but the machine prints these errors out as a percentage . bengtsson16 published a report on the reliability of sita - standard testing , stating that the reliability of a visual field can be predicted by the amount of field loss alone and that reliability indices contributed very little in this regard . a study by budenz et al17 comparing full threshold testing to sita used the reliability criteria similar to those recommended by the manufacturer ( < 33% fixation losses , false - negative errors , and false - positive errors ) and found that glaucomatous defects are measured shallower using the sita algorithms but are approximately the same size and severity compared with full threshold measurements . we used the original guidelines recommended by the manufacturer : less than 20% fixation losses , less than 33% false - positive responses , and less than 33% false - negative responses . although the majority of humphrey visual field tests performed were reliable , they assisted in the diagnosis of glaucoma in only 34 ( 10% ) subjects in this study group . furthermore , the first visual field was performed after the diagnosis of glaucoma had already been made in over half of the subjects in this study . there was no difficulty in making the diagnosis of glaucoma in the majority of subjects as it was clinically evident in 190 ( 55% ) subjects the intraocular pressure was high and disc changes in keeping with glaucoma were present . in our study , katz and sommer18 initially reported unreliability rates of 45% in glaucomatous subjects and 30% in normal controls . most test results were unreliable because they failed to meet the criterion for fixation losses . katz et al19 found that 19% of normal subjects , 28% of those with ocular hypertension , and 37% of patients with glaucoma were unreliable on initial automated testing . an analysis of reliability indices of an urban glaucoma population by birt et al20 showed 59.9% overall reliability . the most common cause of unreliability was fixation loss ( 39% ) , followed by false - negative errors ( 9% ) , and false - positive errors ( 5% ) . several landmark glaucoma trials have discussed the importance of having baseline fields to be able to compare future fields for progression.5,6,21,22 in our study , baseline was reached in half the subjects and visual field progression was evident in only 10% of subjects who had performed two or more visual field tests . the lack of usefulness of visual field testing was further demonstrated by the fact that visual field progression contributed to changes in management in only 15 ( 4.4% ) subjects . there were no reports found in the literature of similar studies performed in eye clinics elsewhere in the world . furthermore , a number of subjects were excluded from the subgroup analyses for various reasons ; however , we believe that the numbers remained large enough to provide reliable statistical analysis . some may also argue that this was a biased sample as most glaucoma is managed in non - subspecialty clinics patients referred to the subspecialty clinic already have the disease and are often those who have complex management issues . this patient population is most likely skewed to the severe end of the spectrum and probably represents the worst of the worst patients in our clinic , but all these patients , including those with advanced disease , presented initially to ophthalmologists working in general clinics and not to glaucoma specialists . in our glaucoma clinic , humphrey visual field testing makes little contribution to the management of the majority of glaucoma cases seen . although our clinic is better equipped than many other clinics on the continent , a significant proportion of our patients still present with advanced disease , which is easily diagnosed without the use of visual fields . progression of fields seldom contributes to monitoring , and intraocular pressure is mainly used to monitor the adequacy of treatment . ocular hypertensives , glaucoma suspects , and those with early glaucoma are also seen in our clinic and they continue to benefit from visual field testing . we do not know if the findings from this study necessarily represent the status quo of visual field testing in other african centers , but population - based surveys have also shown that the majority of glaucoma cases in africa present with advanced structural disease , which can be diagnosed without a visual field . further research should be carried out to determine the usefulness of visual field testing in other centers in africa this will assist in planning for future blindness prevention programs .

purposeto investigate the usefulness of visual field testing in the diagnosis and subsequent management of glaucoma in a specialist glaucoma clinic at groote schuur hospital , cape town , south africa.methodsa retrospective case note review of 344 patients who attended the glaucoma clinic between january and june 2010.resultsthe study population consisted of 201 ( 58% ) females and 143 ( 42% ) males . the diagnoses included 207 ( 60% ) cases with primary open - angle glaucoma , 58 ( 17% ) cases with chronic angle closure glaucoma , 46 ( 13% ) cases with secondary glaucoma , 17 ( 5% ) cases with normal pressure glaucoma , ten ( 3% ) cases with ocular hypertension , and six ( 2% ) glaucoma suspects . visual field testing contributed to the diagnosis of glaucoma in only 34 ( 10% ) cases . a total number of 2,604 fields were performed . of these fields , 1,931 ( 74% ) were reliable . a baseline was reached in only 141 ( 53% ) patients . there was evidence of field progression in only 24 ( 9% ) cases . changes to glaucoma treatment were based on inadequate control of intraocular pressure alone in 309 ( 90% ) patients . visual field progression contributed to changes in treatment in only 15 ( 4% ) cases.conclusionvisual fields are not used in the diagnosis and management of glaucoma in the majority of patients in our clinic . patients present with advanced disease , which is easily diagnosed without the use of visual fields . progression of fields seldom contributes to monitoring and intraocular pressure is mainly used to monitor the adequacy of treatment .

the spleen is the greatest single mass of lymphatic tissue that lies between the left kidney , stomach and diaphragm ( 1 ) . it has three surfaces : diaphragmatic , gastric and renal surface and the two borders : superior and inferior ( 1 ) . this surface meets gastric and diaphragmatic surfaces respectively on the inferior border and a margin close to the splenic hilum ( 2 ) . it plays vital roles in regard to blood storage , formation of lymphocyte and defense against foreign particles ( 3 ) . accessory spleen is an ectopic splenic tissue develops result from the imperfect fusion of the splenic masses during embryonic life ( 4 ) . it is found in 10 - 30 percent of the population ( 4 , 5 ) . accessory spleens are found near the splenic hilum , in the gastrosplenic ligament , in the splenorenal ligament , in the mesentery , in the greater omentum , around the pancreatic tail and along vascular pedicle of the spleen , but rarely in the gonads ( 6 ) . spleen primordium develops from the mesoderm of the dorsal mesogastrium in the fifth week of development . accessory spleens rise from the dorsal mesogastrium as a result of failure fusion of the separate splenic nodules ( 4 ) . in the text book of moore s anatomy has been mentioned the incidence of the accessory spleen was in 10% of the population ( 7 ) . in the usa , the incidence of accessory spleen was found at autopsy in 10 - 30% of american population ( 4 ) . in a european study was found that the accessory spleen was present in 11% of patients undergoing abdominal ct - scan ( 8) . the incidence of accessory spleen ranged between 4.5% and 24.28% in asian population ( 9 - 11 ) . hence , it is critical to correctly differentiate accessory spleens from tumors of the abdominal organs like adrenal tumor , pancreatic tumors or tumors of the retroperitoneal space ( 5 , 12 , 13 ) . for example , when it is at pancreas region , it may mimic a pancreatic tumor . in addition , the present of the accessory spleen is important to avoid a recurrence of symptoms of the disease when spleen should be removed in hematological disorders ( 5 , 12 , 13 ) . hence , the objective of this study was evaluation the incidence of accessory spleen in iranian cadavers . this study was carried out in the dissection hall of the forensic medicine organization , razavi khorasan province , from june 2014 to july 2015 . the protocol of the research was approved by the ethics research committee of mashhad legal medicine organization . sixty hundred and ninety three spleens ( 541 males , 152 females ) were excised from cadavers in the dissection hall of mashhad forensic medicine organization cadavers . inclusion criteria were as follows : fresh iranian cadavers with no history of alcohol , poisoning or drug abuse , and no evidence of pathologic abnormality or injury to the spleen . the presence of accessory spleens investigated near the splenic hilum , in the gastrosplenic ligament , in the splenorenal ligament , in the mesentery , in the greater omentum , and around the pancreatic tail . , the spleen weight was measured with the help of an electronic weighing machine ( pand azma 3100 , iran ) . a 20-year - old female , with no history of personal or family diseases that had been referred to autopsy laboratory of forensic medicine , khorasan razavi province , iran , for medicolegal autopsy on august 3 , 2014 . the height , weight and bmi of cadaver were 162 m , 75 kg and 28.58 kg / m , respectively . an accessory spleen in the splenic hilum , measuring 3.5/2.5 cm , was observed ( figure 1 ) . ( a - e ) are images of the spleens in case numbers 1- 5 , respectively . one accessory spleen was found in a female cadaver ( age : 24 y , height : 165 m , weight : 69 kg , body mass index : 25.34 kg / m ) that was under examination to determine a cause of death . the accessory spleen was located in the hilum with 3 cm long and 1.5 cm wide ( figure 1 ) . a 42-year - old male , with no history of poisoning , alcohol or drug abuse and no evidence of trauma or abnormality of spleen that had been referred to the mashhad legal medicine on august 27 , 2014 . the height , body weight and bmi of cadaver were 163 m , 59 kg and 22.21 kg / m , respectively . its length was 2.5 cm and its width was 1.5 cm ( figure 2 ) . an accessory spleen was observed in a female cadaver ( age : 34 y , height : 170 m , weight : 79 kg , bmi : 27.34 kg / m ) with no gross abnormality and injury of the spleen that needed autopsy . the measurements using a vernier caliper showed that it was 2 cm in length and 1 cm in width ( figure 1 ) . a 61-year - old male , with no history of pathologic abnormality or injury to the spleen was subjected to an autopsy on february 21 , 2015 , by the mashhad legal medicine , iran . the values obtained for height , weight and bmi were 169 m , 68 kg and 23.81 kg / m , respectively . the accessory spleen was measured 2.7 cm in length and 0.5 cm in width ( figure 1 ) . the main finding of this study was the present of accessory spleen at the hilum of the spleen in five cadavers of razavi khorasan province , mashhad , iran . in the text book of snell s anatomy has been reported the incidence of the accessory spleen 10 percent of the normal population and it may exist in the gastrosplenic ligament or in the lienorenal ligament ( 1 ) . the incidence of accessory spleen was 10 - 30% of american population with a predominant site of the splenic hilum ( 4 ) . in another american study found that the accessory spleen was present in 15.6% of cases undergoing abdominal ct - scan ( 14 ) . their length ranged between 4 and 29 mm and the range of their width was from 4 to 25 mm ( 14 ) . similarly , the most common site of accessory spleen was near the hilum of the spleen and the maximum its width was 25 mm . however , our findings showed that the incidence of accessory spleen was lower than that in this study ( 0.7% vs. 15.6% , respectively ) . in addition , the maximum length of accessory spleen was more than that in american people . romer and wiesner studied ct - examination of 1735 patients in switzerland , the accessory spleen was found in 11% of patients ( 8) . in a study by rayhan , the incidence of accessory spleen has reported 24.28% in bangladeshi people ( 9 ) . in another study in india , 4.5% of the splenic samples exhibited an accessory spleen ( 10 ) . in a study by zhang and colleagues have reported that most there is one accessory spleen in which was consistent with our finding ( 11 ) . our results showed that the incidence of accessory spleen was less than that in indian population . the limitation of this study was that there was not available data about accessory spleen in our population for comparison in this paper . an accessory spleen has clinical significance in that they may result in diagnostic errors for the oncologists or the persistence of the symptoms after splenectomy . hence , this report may help surgeons , oncologists , radiologists , and the anatomists regarding the incidence of the accessory spleen .

aim : an accessory spleen is an additional tissue of the spleen that may be found near the spleen . it is a congenital anomaly of the spleen that its incidence has been reported 10 - 30% of the population . hence , the objective of this study was evaluation the incidence of accessory spleen in iranian cadavers.method:sixty hundred and ninety three spleens ( 541 males , 152 females ) were excised from cadavers in the dissection hall of mashhad forensic medicine organization cadavers . inclusion criteria were as follows : fresh iranian cadavers with no history of alcohol , poisoning or drug abuse , and no evidence of pathologic abnormality or injury to the spleen . the presence of accessory spleens , its dimension and weight investigated in cadavers.results:during routine postmortem examination , five cases with an accessory spleen were found in the autopsy laboratory of mashhad legal medicine organization between june 2014 and july 2015 . of the cases , 3 were male and 2 were female . the accessory spleens were observed at the splenic hilum . the length of the accessory spleens ranged from 2 - 3.5 cm , while the range of width was between 0.5 and 2.5 cm . the accessory spleens were confirmed by histological examination.conclusion:an accessory spleen has clinical importance in some locations . when an accessory spleen is situated in another site , it may mimic some tumors such as pancreatic tumor and adrenal tumor . in addition , accessory spleen may cause hyperplasia after splenectomy and be responsible for a recurrence of the hematological disorders .

some surgeons use straight bowman probes6 and some suggest curved bowman probes to mimic the curve of the bony nasolacrimal pathway in children.7 the aim of this study was to evaluate the effect of the shape of bowman probes on the success rate of initial probing for cnldo in children < 2 years of age . group a comprised 42 cnldos in 37 children who underwent probing with straight bowman probes ( katena products , nj , usa ) and group b comprised 128 cnldos in 110 children who underwent probing with bowman probes ( size one ) manually bent approximately 15 degrees to mimic the natural curve of the bony nasolacrimal pathway between january 2007 and march 2011 . the diagnosis of cnldo was based on a history of epiphora and discharge since the first months of life and delayed fluorescein disappearance time . a detailed ophthalmological examination was performed to eliminate any other ophthalmological problem which may cause epiphora such as congenital glaucoma , trichiasis , conjunctivitis , keratitis , and metabolic disorders . patients with congenital craniofacial and lid abnormalities , punctal agenesis , a history of trauma , nasolacrimal surgery , previous probing or other nasolacrimal intervention , and postoperative follow - up <3 months were excluded from the study . a , straight bowman probes ( katena products ) were used ; in group b , bowman probes gently curved to mimic the bony nasolacrimal pathway were used ( figure 1 ) . the surgeon dilated both puncta with a fine punctal dilator ( infant lacrimal dilator , katena products ) . the probe was inserted through the upper punctum into the ampulla of the upper canaliculus and then rotated horizontally to fit in the canaliculus . after a hard stop was felt , the probe was slightly retracted and rotated 90 degrees . at this point , in group a , the straight bowman probe was directly advanced toward the nld ; in group b , the curve of the probe was turned posteriorly and medially while advancing toward the nld.7 after a popping sensation was felt , passage into the nose was confirmed by metal - to - metal contact under the inferior turbinate with another probe . the same procedure was repeated from the lower punctum to exclude any lower canalicular obstruction . after the operation , all patients received a topical steroid and antibiotic treatment four times daily for 10 days and a nasal decongestant for 5 days . successful probing was defined as a complete resolution of signs and symptoms at 3 months postoperatively . the mean age of the patients was 16.4 4.1 months ( range 824 months ) in group a and 16.8 4.2 months ( range 724 months ) in group b. both groups were similar regarding age characteristics . the success rate was 76.2% ( 32/42 ) in group a and 91.4% ( 117/128 ) in group b. the difference was statistically significant ( p < 0.01 ) . nld probing is an effective therapeutic procedure in the management of cnldo ; however , different success rates were reported in the same age groups by different authors . limbu et al reported a success rate of 90.2% in a group of children < 2 years of age;8 however , repka et al reported a success rate of 78% in children 612 months of age and 79% in children 1224 months of age.9 in children > 2 years of age , success rates of probing is much more controversial . robb reported that the success rate of probing was 94.5% in patients aged 2 years.10 in contrast , in sturrock et al s study the success rate was 42% in patients probed after 2 years of age and young et al reported a cure rate of 54% in the same age group.11,12 the reason for the different success rates reported previously is unclear . some authors performed simple nld probing and some combined probing with inferior turbinate fracture.11,13 nasal endoscopy was also used in some studies.6,14 patient characteristics may affect the surgical results of probing.15 additionally , the anatomy of nld , surgical techniques , and tools chosen by different surgeons during probing may affect the results of probing and have not yet been studied . in children , the nld slopes downwards medially and posteriorly.7 some surgeons use straight bowman probes and some suggest gentle recontouring of the probe to suit the configuration of the bony nasolacrimal pathway in children;6,7 however , no comparative studies have been conducted yet . in this study , probing with manually curved bowman probes was performed in 110 children and the results compared with those performed by the same surgeons with straight probes before october 2008 . for effective probing , an ophthalmologist must pass the probe through the bony nasolacrimal canal and perforate the embryological membrane without traumatizing other anatomical structures or creating a false passage . in the current study , a complete resolution of signs and symptoms was achieved in 76.2% of eyes with a straight bowman probe and in 91.4% of eyes with a curved bowman probe and the difference was statistically significant ( p < 0.01 ) . in children , the slope of the nld may make it difficult to pass a straight bowman probe through the nld without trauma . strenuous attempts to pass a straight bowman probe through a curved nld may cause mucosal damage , submucosal passage , and synechia formation in the duct . in group b , the bowman probe was gently bent to mimic the curve of the bony nasolacrimal pathway , as suggested by robb.7 this may lead to an easy introduction of the probe into the duct , and advancement through the duct without rubbing and traumatizing the mucosa or the bony structures of the canal may be possible and this may be the reason of the high success rate of probing with recontoured probes . some authors classify cnldo into two main groups membranous and complex ( firm ) based on the sensation while passing the bowman probe.16 if the passage of the probe produces a popping sensation with subsequent free passage , it is called a membranous obstruction and if the passage of the probe produces a bony sensation similar to passing the probe through sandpaper , it is called a complex ( firm ) obstruction . however , this classification is subjective and depends on the feeling during probing and different rates of obstruction types were reported in the same age groups by different authors.17,18 the medially and posteriorly directed nld can make it difficult to pass a straight bowman probe through the nld in children . therefore , it may be a misdirected bowman probe that produces the bony sensation , which might result in a membranous obstruction being misdiagnosed as a firm or complex obstruction . this may be one of the reasons for the controversy that exists regarding the rates of obstruction types and the outcomes in different studies . with a curved bowman probe , the probability of misdirection and false passage formation may be reduced and success rates of probing may be increased . according to the results , using a curved bowman probe in children with cnldo is more effective in the management of clndo than a straight probe . curved probes that mimic the slope of the nld can be used efficiently during probing . production and usage of tools that mimic the nld anatomy also for silicone intubation or balloon dacryocystoplasty may be taken into consideration for possible higher success rates . anatomical studies of the nasolacrimal system in children are required to further evaluate the effectiveness of surgical techniques and tools used for the management of clndo .

purposeto evaluate the effect of the shape of bowman probes on the success of primary probing for congenital nasolacrimal duct obstruction.materials and methodsrecords of 42 nasolacrimal duct obstructions in 37 children who underwent probing with straight bowman probes ( group a ) and 128 nasolacrimal duct obstructions in 110 children who underwent probing with bowman probes manually bent to mimic the natural curve of the bony nasolacrimal pathway ( group b ) were evaluated and compared . all children were under 2 years of age . the main outcome was successful probing . successful probing was defined as a complete resolution of signs and symptoms.resultsthe mean age of the patients was 16.4 4.1 months ( range 824 months ) in group a and 16.8 4.2 months ( range 724 months ) in group b. no canalicular or nasolacrimal sac pathologies were diagnosed during probing . the success rate was 76.2% ( 32/42 ) in group a and 91.4% ( 117/128 ) in group b. the difference was statistically significant ( p < 0.01).conclusionmanually curved probes can be used efficiently during probing and increase the success rates .

standard - of - care management of advanced and metastatic non - small - cell lung cancer currently includes examination of the solid tumor for the presence of specific molecular abnormalities , which may have substantial impact on the choice of therapy [ 1 , 2 ] . for patients presenting with advanced disease where surgical resection is not a therapeutic option , the overriding goal is to obtain a histologic diagnosis in as noninvasive a manner as possible and subsequently initiate therapy . however , the legitimate aim to avoid unnecessary risk to a patient secondary to invasive procedures may conflict with the requirement to obtain sufficient viable cancer tissue to perform critical laboratory based analysis . it is in this setting where so - called liquid tumor biopsies may be particularly relevant in disease management [ 3 , 4 ] . the clinical course of a patient with advanced non - small - cell lung cancer recently seen in our cancer program demonstrates the critical importance of this rapidly developing paradigm . a 50-year - old african - american male never - smoker with no significant past medical history presented to his physician with a chief complaint of a dry cough during the summer of 2015 . a ct scan of the chest revealed a cavitary mass / infiltrate centered in the left lower lobe and left hilum . the left pulmonary artery was narrowed by the left hilar mass with a positron emission tomography scan revealing intense activity in this region . further evaluation revealed multifocal metastases , including bilateral supraclavicular lymph nodes , mediastinal lymph nodes , left lateral 8th rib , and left ischium osseous metastases . a ct - guided lung biopsy revealed a poorly differentiated non - small - cell carcinoma with both adenocarcinoma and squamous cell carcinoma features . from the outside institution report , there was inadequate tissue sample for genomic testing . the patient was treated with whole - brain radiation and a chemotherapy regimen consisting of cisplatin plus gemcitabine . restaging scans in march 2016 , after 3 cycles of cisplatin / gemcitabine , revealed progressive disease in the lungs . mri of the brain demonstrated a decrease in all intracranial metastases . in early march 2016 , the patient was started on second - line treatment with the immunotherapeutic agent nivolumab , but subsequent evaluation revealed progression of the disease throughout the chest and new metastatic disease in the right adrenal gland . positron emission tomography / ct documented multiple new bony metastatic lesions and innumerable metastatic nodules throughout the right lung . the patient presented to our institution in july 2016 for a second opinion . due to significant respiratory distress , he was admitted to the hospital where his performance and respiratory status continued to decline significantly ( fig 1 ) . the patient had had a liquid biopsy ( foundation act ) ordered by his prior oncologist shortly before he came to our institution , which revealed an epidermal growth factor receptor exon 19 deletion . when this was learned , he was started on afatinib , but unfortunately , his respiratory status deteriorated further the same day , requiring intubation . lung cancer is the leading cause of cancer - related death . despite advances in the discovery of genomic alterations , the overall 5-year survival rate is currently less than 20% . given the remarkable advances in targeted therapies for metastatic lung adenocarcinomas , tumor molecular profiling is essential at the time of diagnosis or at the time of relapse . obtaining adequate tissue from the lung or metastatic sites can be limited due to patient 's performance status or due to risks involved with the procedures . liquid tumor biopsies have stirred much excitement in the oncology world [ 3 , 4 ] . liquid biopsy involves a noninvasive approach to obtaining circulating tumor cells and nucleic acids including cell - free rna , microrna , and circulating cell - free dna . cancers that have 50 million malignant cells can release enough dna for the detection of circulating tumor dna in the blood . tumor size , type , stage of disease , sites of metastasis , and histologic grade may affect the levels of circulating dna . while blood - based testing can have a shorter turnaround time compared to tissue - based molecular analysis , existing data suggest that they have lower overall sensitivity . currently , liquid biopsies should be considered only when tumor tissue is inadequate for molecular analysis and/or when the risk of a repeat biopsy is significant . the case presented here demonstrates the potential major utility associated with liquid tumor biopsies in lung cancer . actionable mutation present within our patient 's cancer was not discovered until progressive cancer and rapid deterioration of his performance status prevented him from receiving a targeted approach that may have favorably influenced the clinical course . the routine use of validated liquid tumor biopsies in the management of non - small - cell lung cancer should be considered in any case where the available

a 50-year - old male with advanced non - small - cell lung cancer was unable to have standard - of - care molecular testing performed at diagnosis as a result of inadequacy of the available tissue . a subsequently performed commercial liquid tumor biopsy ( foundation act ) revealed an epidermal growth factor receptor exon 19 deletion , but due to the progression of the tumor and rapid deterioration in the patient 's performance status , a meaningful attempt at therapy directed to this recognized therapeutic target was not possible . this case provides important support for the relevance of liquid tumor biopsies in documenting highly clinically relevant molecular targets , particularly in the setting where limited solid tumor tissue is available for analysis .

the initial diagnosis of thrombotic thrombo - cytopenic purpura ( ttp ) may be uncertain because other disorders that can cause microangiopathic hemolytic anemia and thrombocytopenia , the principal diagnostic criteria , may not be initially apparent . disseminated malignancy is an important consideration in the differential diagnosis of ttp since cancer has been well described for many years as a cause of microangiopathic hemolytic anemia and thrombocytopenia . although in most patients the disseminated malignancy that causes microangiopathic hemolytic anemia and thrombocytopenia is easily recognized , in some patients , the malignancy is not clinically apparent , and therefore ttp is diagnosed and plasma exchange treatment is begun . failure to diagnose disseminated malignancy exposes the patient to the major risks of plasma exchange and causes delay of appropriate chemotherapy . however , failure to urgently initiate plasma exchange treatment in a patient with ttp may result in death . the thrombotic microangiopathies are a group of syndromes characterized by small - vessel thrombosis , microangiopathic hemolytic anemia , thrombocytopenia and organ failure . the most common of these disorder , hemolytic uremic syndrome ( hus ) and ttp , were once considered 2 distinct disease etiologies . in consideration of their extensive pathophysiologic overlap , they are now termed the hus / ttp syndrome . the classic clinical pentad of ttp includes i ) fever , ii ) neurologic symptoms , iii ) microangiopathic hemolytic anemia , iv ) thrombocytopenic purpura , and v ) the presence of thrombi in glomerular capillaries and afferent arterioles . although hemolytic anemia is a universal feature , all 5 classic findings are present in only 40% of cases . thrombotic thrombocytopenic purpura is seen more often in women , with most of the patients younger than 40 years , the diagnosis rests on evidence of microangiopathic hemolytic anemia and thrombocytopenia in the absence of dic or other known causes of thrombotic microangiopathy . there are no clinical features or laboratory tests that can confirm the diagnosis of ttp - hus ; the most important diagnostic criterion , but also the most difficult , is the exclusion of alternative etiologies . adamts13 ( a disintegrin and metallo - protease with thrombospondin-1-like domains ) , an enzyme required for normal proteolytic processing of von willebrand factor ( vwf ) , is important in the pathophysiology of ttp , but patients may have characteristic presenting features and clinical courses without severe adamts13 deficiency . even after a diagnosis of thrombotic thrombocytopenic purpura is made , continuing evaluation is important . in the oklahoma thrombotic thrombocytopenic purpura - hemolytic uremic syndrome ( ttp - hus ) registry , 10 percent of patients with an initial diagnosis of idiopathic thrombotic thrombocytopenic purpura were subsequently found to have sepsis or systemic cancer ( table 1 ) . table 1clinical features that may suggest disseminated malignancy as an alternative diagnosis in patients with assumed ttp-hus.clinical featurecommenthistory of cancereven when the clinical evaluation and results of imaging studies are normal metastatic cancer must be suspectedpulmonary infiltratesrare in ttp - husrespiratory failureacute respiratory symptoms are rare in ttp-hus.disseminated intravascular coagulation ( dic)although dic is commonly associated with metastatic carcinoma , coagulation tests may be normal.nucleated red blood cells and immature myeloid cells on peripheral blood smearthese abnormalities may accompany the marrow response to severe hemolysis , but they commonly indicate marrow infiltration by tumor.extreme elevation of lactate dehydrogenase ( ldh ) levelalthough an elevated ldh level , caused by hemolysis and tissue ischemia , is characteristic of ttp - hus , levels exceeding 5,000 u / l are more commonly cause by tumor lysisno response to plasma exchange therapypatients with ttp - hus typically respond promptly to plasma exchange . no response should cause concern about the diagnosis.extreme elevations of d - dimerd - dimers were found severely increased in all cases of disseminated cancer presenting as ttpadamts13 activityadamts13 activity may be normal or lower than normal in cancer - associated ttp . a 34-yer - old man without significant past medical history was found lethargic in bed early morning and sudden onset of respiratory failure . the patient was transferred to the emergency department ( ed ) by ambulance . upon arrival at the ed his consciousness level was rated on the glasgow coma scale as 6/15 , ( e2v1m3 ) , he was somnolent and unable to follow commands . his mental status worsened , and the trachea was intubated for airway protection with use of rapid - sequence induction . his vital signs were : temperature , 38,5c ; pulse , 125 beats / min ; respirations , 24 breaths / min ; and blood pressure 90/50 mmhg . the skin was mottled , without petechiae ; the extremities were cool and clammy , with acral cyanosis . the patient was sedated and mechanically ventilated with an inspiratory oxygen concentration of 60 percent . results of laboratory tests on admission were as follows ; leukocyte , 6400/ml ; hematocrit , 23.6% , hemoglobin , 7.7 g / dl ; peripheral smear showed moderate - to - severe schistocytosis and marked red cell fragmentation ; platelet 60,000/ml , serum glucose 123 mg / dl , serum urea 86 mg / dl , serum creatinine 2.86 mg / dl , serum sodium 139 mg / dl , serum potassium 6.2 mg / dl , total bilirubin 6.8 mg / dl , aspartate aminotransferase , 5318 u / l , alanine aminotransferase 1947 u / l , lactate dehydrogenase 19,758 blood coagulation tests ; prothrombin time , 23,1 sec , activated partial thromboplastin time 53.2 sec . ; fibrinogen 3.9 g / l ( 2.06.0 ) all within normal values ; d - dimer 5250 ng / dl . a coomb s tests showed a negative result . toxicologic screening of serum was negative for ethanol , acetaminophen , and salicylates , and toxicologic screening of urine was also negative . specimens of blood and urine were taken for bacterial and viral cultures and testing for viral antigens . toraco - abdominal computed tomography ( ct ) revealed enlarged esophageal and paracardiac lymph nodes , bilateral posterobasal lung consolidations , hepatosplenomegaly , multiple enlarged retroperitoneal and paraaortic lymph nodes ( figure 1 ) . figure 1abdominal ct scan demonstrates a ) pathological hepatic lymph nodes and b ) retroperitoneal lymph nodes . abdominal ct scan demonstrates a ) pathological hepatic lymph nodes and b ) retroperitoneal lymph nodes . a definite diagnosis could not be determined on admission because of the complexity of signs and symptoms , the diagnosis of ttp was suggested based on the presence of fever , neurologic symptoms , microangiopathic hemolytic anemia , thrombocytopenia , renal failure , increased serum levels of lactate dehydrogenase and indirect - reacting bilirubin , and negative direct coomb s test . the importance of prompt diagnosis of the systemic malignancy was to provide an opportunity for treatment with appropriate chemotherapy . in the intensive care unit treatment with dopamine to maintain a systolic blood pressure of 140 was started , and aggressive fluid resuscitation was continued . two hours later the blood pressure decreased to 90/45 mm hg ; norepinephrine was added . twenty - nine hours after presentation the axillary temperature was 40.4c ( 104.8f ) and the blood pressure 82/55 mm hg despite increasing doses of dopamine , epinephrine , and norepinephrine . laboratory evaluation demonstrated severe anemia ( hematocrit 23% ) despite blood transfusion , thrombocytopenia ( platelet count 20,000/ml ) , coagulation tests ( internationalized normalized ratio ( inr ) , 1.2 ; activated partial prothrombin time , 25 s ; fibrinogen concentration , 3.3 g / l ( 2.06.0 ) were normal . results of microbiologic and serologic tests were received , blood culture negative , urine culture negative , cytomegalovirus antigenemia assay negative , epstein - barr virus anti - vca igg postive , epstein - barr virus anti - vca igm negative , epstein - barr virus early antigen negative , epstein barr virus antinuclear antigen negative , herpes simplex virus type 1 antibody igg positive , herpes simplex virus type 2 antibody igg negative , carcinoembryonic antigen ( ng / ml ) 1.4 , prostate - specific antigen ( ng / ml ) 4.6 , ca-125 ( u / ml ) 36 , ca 19 - 9 ( u / ml ) 6.1 , rheumatoid factor ( iu / ml ) < 30 , antinuclear antibody negative , antineutrophil cytoplasmic antibody negative , hepatitis b surface antigen negative , hepatitis c antibody negative , adamts13 ( < 20% ) thirty - one hours after presentation , bradycardia developed , followed rapidly by asystole , and cardiopulmonary resuscitation was initiated . the marrow aspirate results were received with occupation by neoplastic cells of large size and frequent syncytia . the autopsy revealed a tumor at the ileum 10 cm proximal from the ileocecal region . peritoneal dissemination was recognized around the ileocecal region , pathological diagnosis of the specimen was adenocarcinoma with lymph nodes metastasis . microangiopathic hemolytic anemia and thrombocytopenia caused by systemic malignancies have been well described , but it is uncommon for microangiopathic hemolytic anemia and thrombocytopenia to be the predominant presenting clinical features in patients whose systemic malignancy is not initially apparent . although occult malignancy causing microangiopathic hemolytic anemia and thrombocytopenia may be uncommon , it is an important consideration in the evaluation of patients for ttp . in the oklahoma ttp - hus registry , 10 ( 3% ) of 351 patients who were initially diagnosed as having ttp and treated with plasma exchange were subsequently and unexpectedly diagnosed with disseminated malignancy . only systemic infections have been a more common cause of an incorrect initial diagnosis of ttp in the oklahoma registry . many different malignancies may mimic ttp ; the importance of prompt diagnosis of the systemic malignancy is to provide an opportunity for treatment with appropriate chemotherapy . early recognition of cancer may not benefit many patients who present with microangiopathic hemolytic anemia and thrombocytopenia since these patients often have widely disseminated cancer . even though treatment success may be limited , prompt diagnosis is important for appropriate management . prompt diagnosis of systemic malignancy is also important in avoiding unnecessary risks of plasma exchange treatment for ttp . the difficulty of diagnosing a systemic malignancy presenting with microangiopathic hemolytic anemia and thrombocytopenia is evidence in literature . the diagnosis of disseminated malignancy excludes the diagnosis of ttp or hus ; these patients should not be considered to have cancer - associated ttp . although multiple etiologies may contribute to the syndromes recognized as ttp and hus , disseminated malignancy is a pathologically and clinically distinct disorder . disseminated malignancy can cause microangiopathic hemolytic anemia and thrombocytopenia , in the absence of dic , by microvascular tumor emboli . adamts13 activity is not severely deficient but may be lower than normal in some patients with disseminated malignancy due to high plasma levels of von willebrand factor . clues that may suggest the presence of an occult systemic malignancy include presenting symptoms of dyspnea , cough , and pain other than abdominal pain . although increased serum ldh is characteristic of patients with ttp , extreme elevations are not typical and may suggest tumor lysis . median ldh level was 4.5 times upper the normal values ( range , 3.28.9 ) . d - dimers were found severely increased in all cases of disseminated cancer presenting as ttp in a recent report of several cases of disseminated cancer . perhaps the most convincing clue that a patient with presumed ttp may have a disseminated malignancy is failure to respond to plasma exchange . the evaluation and management of patients who present with an acute onset of microangiopathic hemolytic anemia and thrombocytopenia remain critical challenges for clinicians . although the diagnosis of ttp and urgent treatment with plasma exchange must be considered in patients with microangiopathic hemolytic anemia and thrombocytopenia , the possibility that all of the clinical features of ttp may be caused by an occult disseminated malignancy must be appreciated . with increased awareness of the possible diagnosis of disseminated malignancy , the diagnosis can be made sooner , avoiding unnecessary plasma exchange treatment and allowing appropriate chemotherapy treatment

thrombotic microangiopathies ( tmas ) represent a heterogeneous group of diseases characterized by a microangiopathic hemolytic anemia , peripheral thrombocytopenia , and organ failure of variable severity . tmas encompass thrombotic thrombocytopenic purpura ( ttp ) , typically characterized by fever , central nervous system manifestations and hemolytic uremic syndrome ( hus ) , in which renal failure is the prominent abnormality . in patients with cancer tmas may be related to various antineoplastic drugs or to the malignant disease itself . the reported series of patients with tmas directly related to cancer are usually heterogeneous , retrospective , and encompass patients with hematologic malignancies with solid tumors or receiving chemotherapy , each of which may have distinct presentations and pathophysiological mechanisms . patients with disseminated malignancy who present with microangiopathic hemolytic anemia and thrombocytopenia may be misdiagnosed as thrombotic thrombocytopenic purpura ( ttp ) only a few cases of ttp secondary to metastatic adenocarcinoma are known in the literature . we present a case of a 34-year - old man with ttp syndrome secondary to metastatic small - bowel adenocarcinoma . patients with disseminated malignancy had a longer duration of symptoms , more frequent presence of respiratory symptoms , higher lactate dehydrogenase levels , and more often failed to respond to plasma exchange treatment . a search for systemic malignancy , including a bone marrow biopsy , is appropriate when patients with ttp have atypical clinical features or fail to respond to plasma exchange .

this year the 2nd summer school in computational biology organized by the queen 's university of belfast took place 1618 september 2013 in belfast ( uk ) . the event gathered a total of 25 students from 5 different countries , making it so far the largest summer school since its establishment in 2012 . the purpose of the summer school was to provide the participating students with a systematic introduction to quantitative analysis methods for high - throughput data that are needed to analyze genomics data from biological or biomedical experiments , . due to the fast paced progress of the field genomics , many university curricula have difficulties in catching - up with these developments , leaving room for a summer school like ours to provide the needed understanding for basic analysis principles and methods to the students to equip a new generation of scientists with the necessary skill set . in order to emphasize our goal for the summer school clearly we chose the subtitle : statistical and computational methods to analyze high - dimensional data in biology. the summer school consisted of 18 lectures that were provided by 10 instructors , covering topics from introductory lectures for the statistical programming language r , microarray and next - generation sequencing ( ngs ) data to advanced analysis methods , including clustering , classification and survival analysis . in this paper , we provide a report about this summer school , including a discussion of student feedback we received after the completion of the summer school . the underlying goal of our summer school was to teach students the necessary skill set for computational biology so these can be applied to , e.g. , biological , biomedical or clinical data ; see fig . 1 . due to the interdisciplinary character of computational biology , which consists of a mixture of skills and knowledge from statistics , machine learning , computer science , biology and medicine , this is usually a long - lasting and challenging endeavor , because no student can have a background in all subjects . for this reason , we provided an introduction to all three basic subjects ( see fig . 1 ) . 2 we show the schedule of the summer school , comprising 18 lectures distributed over 3 days . we emphasize the main purpose of each lecture by the same color code as used in fig . 1 . the covered topics range from a basic introduction to the statistical programming language r ( lectures 2 , 4 & 5 ) to advanced statistical analysis methods , including classification , clustering , pathway analysis , survival analysis and connectivity mapping ( lectures 9 , 10 , 11 , 15 , 16 & 17 ) , , , , , . for each lecture , we aimed for a clear and hands - on explanation of a topic . for this reason we sacrificed a more comprehensive coverage , which would have forced us to extend the duration of the summer school considerably . the actual need for such a wide range of topics and difficulty levels becomes clear from the educational background of the students . in fig . 3a , we show an overview of the subjects studied by the participating students of the summer school . as one can see , the majority of the students have an educational background in biology and biochemistry , however , there are also 29.5% of the students studying quantitive subjects ( computer science , mathematics , statistics or physics ) . furthermore , about half of the students are at the beginning of their university education ( bsc student or msc student ) whereas the other half is on an advanced stage ( phd student or postdocs ) , see fig . this education diversity makes it challenging to provide an optimal level of the summer school lectures that fits all students equally . for this reason , we decided to provide basic lectures to give the students with a biology background the chance to catch - up basic skills that every student of a quantitative subject already has , and also to provide basic biology knowledge ( lecture 3 ) , e.g. , computer science students to counterbalance their deficits . in order to obtain feedback from the students regarding their experience from the summer school , we asked the students to fill in a questionnaire via survey monkey after the completion of the summer school . in fig 3c we show the results for the question please describe the difficulty level of the summer school for you. it is reassuring to see that the majority of students ( 70.6% ) felt comfortable with the difficulty level of the provided lectures and none ( 0% ) considered the summer school as very difficult. the next three questions we asked the students addressed their gained understanding from the summer school on different levels:have you gained a basic understanding of the programming language r ? overall , the majority of the students are of the opinion that they gained a basic understanding in these 3 categories . given the educational diversity of the students , see fig . 3a and b , it is probably hard to improve these numbers substantially without increasing the duration of the summer school that would allow one to cover more basic and advanced grounds in considerably more depth . we would like to emphasize that the above discussion is not intended as a strict data analysis , but as a quantitative discussion of the feedback we received from the students . aside from the actual topic of the summer school , teaching students the basics of computational biology , we intended to generate an awareness of the students for reproducible research , , . in this respect , the key role of the statistical programming language r was discussed as a natural and efficient mediator between data , analysis methods and the conservation of the whole analysis process in a way that allows an error - free exchange / communication of a conducted analysis . given the fact that it is anticipated to see in the next years an even increasing amount of data from more than one high - throughput technology , the reproducibility of a genomic data analysis , and means to realize it , is certainly becoming even more important in the near future . another feature of the summer school was to give the students the opportunity to see the application of the taught methods to real problems . for this reason , we invited benjamin haibe - kains , from the institut de recherches cliniques de montreal ( canada ) , to provide a talk at the summer school . this talk was given at the end of the second day ( see fig . 2 ) . benjamin haibe - kains gave an interesting and exciting talk with the title significance analysis of prognostic signatures , which was based on recent results of his research , . this allowed the students to experience the translation of analysis methods into clinical practice and to engage into a lively discussion , which helped them to realize the importance of computational biology . in this role to provide a lecture for the student , benjamin haibe - kains is the successor of simon tavare , from the statistics and computational biology laboratory , cancer research uk cambridge research institute , who provided last year 's talk for our first summer school . aside from the actual topic of the summer school , teaching students the basics of computational biology , we intended to generate an awareness of the students for reproducible research , , . in this respect , the key role of the statistical programming language r was discussed as a natural and efficient mediator between data , analysis methods and the conservation of the whole analysis process in a way that allows an error - free exchange / communication of a conducted analysis . given the fact that it is anticipated to see in the next years an even increasing amount of data from more than one high - throughput technology , the reproducibility of a genomic data analysis , and means to realize it , is certainly becoming even more important in the near future . another feature of the summer school was to give the students the opportunity to see the application of the taught methods to real problems . for this reason , we invited benjamin haibe - kains , from the institut de recherches cliniques de montreal ( canada ) , to provide a talk at the summer school . this talk was given at the end of the second day ( see fig . 2 ) . benjamin haibe - kains gave an interesting and exciting talk with the title significance analysis of prognostic signatures , which was based on recent results of his research , . this allowed the students to experience the translation of analysis methods into clinical practice and to engage into a lively discussion , which helped them to realize the importance of computational biology . in this role to provide a lecture for the student , benjamin haibe - kains is the successor of simon tavare , from the statistics and computational biology laboratory , cancer research uk cambridge research institute , who provided last year 's talk for our first summer school . overall , the experience we made during the last two years from organizing the summer school in computational biology is very positive . we see not only a clear benefit for the students but also for ourselves , allowing us to provide more efficient lectures that can reach students with a heterogeneous educational background and professional level . for this reason the preparations for next year 's summer school have already started and we anticipate the 3rd summer school in computational biology to take place in september 2014 .

in this paper , we present a meeting report for the 2nd summer school in computational biology organized by the queen 's university of belfast . we describe the organization of the summer school , its underlying concept and student feedback we received after the completion of the summer school .

breast cancer is the most common malignancy in females , accounting for 1 of 4 cancers diagnosed , and it is the second leading cause of deaths due to cancer among north american women . the american cancer society predicted that cancer of the breast would be diagnosed in 254,650 women and that 40,170 women would die secondary to breast cancer in 2009 . moreover , the american cancer society estimated that 25,100 new breast cancers would be diagnosed , with 2,820 deaths secondary to breast cancer , occurring in american women under 45 years of age in 2009 . the incidence of initial presentation of breast cancer is known to peak between the ages of 45 and 55 years , and although women 40 years of age and under account for less than 5% of those developing this disease , we observed that during the last ten years , the incidence of breast cancer has increased most markedly in this younger population . changes in diet , an escalating incidence of obesity , and an increased exposure to endogenous and exogenous hormones may have contributed to this increase , together with the decisions by larger numbers of women in the developed world to delay their first pregnancy until later in life . finally , the 5-year survival rate is lower for women diagnosed with breast cancer before age 40 ( 83% ) compared with women diagnosed at ages 40 years or older ( 90% ) . these observations prompted us to examine the differences that might exist between young women 40 years of age and younger , and older women , with breast cancer . a fundamental difference in the pathophysiology is that young women tend to present with a more advanced stage of breast cancer than do older women , and , hence , the earliest possible detection is crucial to their optimal prognosis . it is important to emphasize that a malignant breast neoplasm which has grown to a palpable size usually presents as a painless mass . many studies have shown that women who regularly practice breast self - examination initially present with smaller tumors and with neoplasms that less frequently involve the axillary lymph nodes [ 310 ] . despite these facts , the american cancer society decided to change their previous guideline for regular breast self - examination ( bse ) , recommending instead that bse now be optional because benefits of performing the self - examination had not been substantiated unequivocally in the literature . the guidelines advocated by the american cancer society in 2003 for early breast cancer detection in asymptomatic women over 40 years of age were very specific : annual mammography , annual clinical breast examination , and an optional monthly breast self - examination . the guidelines are less stringent for females under 40 years of age and consist of a clinical breast examination every three years and an optional monthly breast self - examination . the american cancer society eliminated its recommendation that all women perform monthly bse after publication of studies such as the randomized trial of 266,062 women in shanghai , which concluded that intensive instruction in bse does not reduce the mortality rate of breast cancer . nonetheless , the society still recommends that women be informed of the potential benefits and limitations of bse and that those women who wish to do so should receive instruction in proper bse from their health care providers . we hypothesized that younger women are more concerned with breast disease as it relates to their breast image and appearance , to their lifestyle , and to longer life expectancy . the various considerations and observations concerning young women and their breast disease led us to attempt to understand several concepts more clearly , including the relationships between breast carcinoma biology and age , breast carcinoma management patterns and age , and outcomes and age . the purpose of this study was to evaluate the characteristics that are unique to women 40 years of age and under , who present with breast cancer , in order to assess the role and potential benefits of bse more meaningfully . presumably , diagnosis and treatment of breast lesions are delayed in young women due to a low index of suspicion . thus , we evaluated the detection , incidence , and treatment patterns of women 40 years of age and under with breast cancer who presented to our community teaching hospital over a 10-year period . the clinical and pathological characteristics of cancer in this patient population and the role of bse as a screening tool in detecting malignancy in these patients were also examined . young women were defined as those 40 years old or younger . after approval by the institutional review board , a retrospective review of a total of 822 women diagnosed with breast carcinoma during the decade between the years of 1994 and 2005 was completed at our community teaching hospital . of those , 64 women were below 41 years of age , accounting for 7.7% of all breast cancers . retrospective clinical information , which was obtained from the tumor registry , the hospital medical records , and office charts , was analyzed . in order to create a uniform basis for comparison , the tumors of all patients were restaged according to the tnm classification advocated by the american joint committee on cancer ( ajcc ) . tumor size and the status of the axillary nodes were ascertained from review of the original pathology reports . mann whitney , fisher exact , and chi - squared tests were used as appropriate to compare the two age groups of breast cancer patients , and p < .05 was considered statistically significant . all of the 822 women with breast cancer were treated in our institution , and none were referred elsewhere . throughout the decade - long study period , a statistically significant increase in age - adjusted incidence of breast cancer among women 40 years of age and younger became obvious ( p < .005 ) . the number of patients having a significant family history for breast cancer in both groups ( > 40 years and < 41 years ) could not be derived accurately from the family history data recorded on the charts , especially during the 1990s . the entries for these data improved remarkably in the 21st century but were sufficiently inconsistent to be of significant value in this group of patients . similarly , the situation was comparable regarding genetic testing in these patients during the time period of the study ( 19942005 ) . of the 758 older patients , over the age of 40 , three hundred eighty two ( 49% ) discovered their cancer by mammography , 278 ( 39% ) by self - examination , and 98 ( 14% ) by a clinical breast examination . magnetic resonance imaging ( mri ) was not available for use in the diagnosis of patients with breast cancer during the decade of this study . estrogen and progesterone receptor status was known in 660 ( 80% ) patients and unknown in 166 ( 20% ) . lymph nodes were positive in 156 ( 21% ) patients and unknown in 154 ( 21% ) of the older patients . at the time the older patients had their breast cancers diagnosed , 122 ( 16% ) patients had stage 0 disease , 331 ( 44% ) had stage i , 212 ( 28% ) had stage ii , 48 ( 6% ) had stage iii , 21 ( 3% ) had stage iv , and 24 ( 3% ) had an indeterminate stage . of 822 women diagnosed with breast cancer in our hospital from 1994 to 2004 , sixty four ( 7.7% ) were 40 years of age or younger . the ages of the 64 young patients ranged from 19 to 40 years , with a mean age of 36.4 years . forty four ( 69% ) of these younger women discovered their breast cancers by breast self - examination , 17 ( 18% ) by mammography , and 3 ( 5% ) by professional clinical breast examination . this series spans 10 years , and the surgical procedures chosen reflect the dominant influences of that time period . thirty three ( 50% ) of these young patients underwent a modified radical mastectomy , and 2 ( 3% ) underwent a simple mastectomy . only 28 ( 44% ) of the patients chose to have a breast conservation procedure . there were 14 ( 22% ) patients with stage 0 , 14 ( 22% ) patients with stage i disease , 25 ( 39% ) patients with stage ii , 9 ( 14% ) with stage iii , 0 with stage iv , and 2 ( 3% ) young patients with an unknown stage . the number of young patients diagnosed per year appeared to be increasing , even in this relatively small cadre , as follows : 5 ( 1994 ) , 5 ( 1995 ) , 2 ( 1996 ) , 3 ( 1997 ) , 6 ( 1998 ) , 7 ( 1999 ) , 6 ( 2000 ) , 8 ( 2001 ) , 6 ( 2002 ) , 6 ( 2003 ) , and 10 ( 2004 ) . when compared with women under 41 years of age , a higher percentage of women over 40 years of age discovered their breast cancers by mammography ( 49% ) and had a higher number of hormone sensitive tumors ( 87% ) . the frequency of lymph node metastases reported in the older women was one - half that in the younger women ( 21% versus 42% ) , and a higher percentage of younger women presented with more advanced disease , a difference which was statistically significant ( p < .05 ) . many of the patients ( in the unknown lymph node status category ) had undergone simple mastectomy in the 1990s , thus accounting for the overall 20% unknown lymph node status , which was 20% in the > 40 year - old and 19% in the < 41 year - old group ( table 1 ) . carcinoma of the breast in young women is a relatively uncommon occurrence , with our data depicting an incidence of approximately 8% of all women with breast cancer . this correlates with findings of other authors who have reported incidences of 0.3% to 25% [ 1 , 1214 ] . mammography remains the premier screening tool for older women ; however , it is of questionable value in young women primarily because small lesions tend to be undetectable or interpreted as benign secondary to the increased density of the breasts of young women , which renders radiographic differentiation of normal from abnormal tissue difficult . ashley and colleagues found that 77% of mammograms in young women produced an x - ray suspicious for malignancy , and only 23% were obviously benign . ultrasonography identified the pathology correctly in 58% , while fine - needle aspiration ( fna ) cytology was most precise , identifying 78% of tumors as definitely malignant and 15% as suspicious , for an overall accuracy of 93% . the most frequent lesion noted in this cadre of patients , as well as in other series , is infiltrating duct carcinoma . the prognosis of women with cancer of the breast is related to a variety of clinical findings and pathological factors , especially the status of the axillary lymph nodes and the tumor size . studies have also shown that young women with breast cancer have a lower 5-year relative survival rate than older women [ 1214 , 18 , 19 ] . it has been postulated that the tumors in younger women are more aggressive and less responsive to hormone therapy and that these characteristics account for the differences in 5-year survival between the age groups ( table 2 ) . however , it remains unclear whether the dismal outcome in the younger age group is a reflection of more advanced disease at the time of diagnosis and/or is due to a difference in underlying tumor biology [ 12 , 14 , 15 , 18 ] . finally , it has been observed commonly that breast carcinoma appears to be more indolent generally in older women , and most particularly in the elderly . in 2003 , the american cancer society recommended that breast self - examination be optional primarily because of a lack of unequivocal supporting evidence of benefit . hence , the only screening guideline currently suggested for women 1840 years of age is a clinical breast examination every three years . however , 5-year survival among young women diagnosed with breast cancer is clearly related to the stage of the disease at the time of diagnosis [ 17 , 22 ] . breast self - examination has not been encouraged or recommended , in part , because it has not been consistently associated with a decrease in morbidity or mortality , and because it purportedly can cause increased patient anxiety , especially when biopsies of breast masses that are discovered on self - examination are performed . we propose that the anxiety can be dispelled or ameliorated by quality time spent properly counseling and supporting the patient . our data confirm that young women with breast cancer are likely to present with a more advanced stage of the disease compared with older patients . in response to increasing breast cancer in young women under 41 years of age in recent years , further investigation focused on this age group is indicated , and encouragement of proper breast self - examination is warranted and should be advocated as a quality health maintenance practice .

in 2003 , the revised american cancer society guidelines recommended that breast self - examination ( bse ) be optional . of 822 women diagnosed with breast cancer in our hospital from 1994 to 2004 , sixty four ( 7.7% ) were 40 years of age or younger . forty four ( 68.7% ) of these young women discovered their breast cancers on bse , 17 ( 18% ) by mammography , and 3 ( 4.7% ) by clinical breast examination by medical professionals . of 758 women over 40 years of age diagnosed with breast cancer , 382 ( 49% ) discovered their cancer by mammography , 278 ( 39% ) by bse , and 98 ( 14% ) by a clinical breast examination . lymph node metastases in the older women was one - half that in the younger women ( 21% versus 42% ) , and a higher percentage of younger women presented with more advanced disease . in response to increasing breast cancer in young women under 41 years of age , encouragement of proper breast self - examination is warranted and should be advocated .