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next to the frequency of appearance of dyslipidemia , a subject of interest were changes in the composition of lipids . in most studies , statistically , the amount of overall cholesterol has been increased , ldl cholesterol and/or triglycerides in those affected by psoriasis relating to the control groups , and a lowered hdl cholesterol ( 2 ) . although the precise relation between psoriasis and dyslipidemia has never been established , those affected by psoriasis had their proinflammatory cytokines elevated : example . tnf il-1 or il-6 , and they can besides all else also affect the metabolism of lipids ( 3 ) . appearance of dyslipidemia can also be attributed to the subject s life style , such as physical inactivity , inadequate nutrition , stress . dyslipidemia as a comorbidity can also appear during the treatment of psoriasis with cyclosporine and acitretin ( 1 ) . appearance of dyslipidemia in those affected by psoriasis is meaningful considering that dyslipidemia can be a factor of risk for other ailemnts , mainly cardio - vascular ones . to establish the frequency of dyslipidemia in those affected by psoriasis , and to establish the severity of psoriasis with the occurrence of dyslipidemia . this perspective research has occurred in the period between november of 2011 and june of 2013 , it consisted of 70 consecutively chosen patients affected by psoriasis , of both genders , older than 18 years of age . average age of the respondents was 47.14 ( sd= 15.41 ) , which consisted of 36 men ( 51.43% ) and 34 women ( 48.57% ) . research also included patients with documented cases of diagnosed psoriasis , ambulatory or hospital reports from dermatologist , and pathophysiological report , of those who were treated at the clinic for skin diseases of university clinical center tuzla . research did not include patients which besides psoriasis suffered from some other skin disease , and those which suffered from psoriasis for less than a year . research has been approved from the side of ethics committee of university clinical center tuzla . firstly , all examinees were explained the purpose of the research , asked for a written consent to participate in the research , taken anamnesis , got their skin and visible mucous membranes dermatologically tested and had their pasi score values determined , after which they were subjected to the research , and lastly , had the values of their complete cholesterol , hdl cholesterol and triglycerides tested . 1.7mmol / l , hdl cholesterol ( in men 1.03mmol / l ) and in women < 1.29mmol / l ) . for determining the severity and outspread of psoriasis , psoriasis area and severity index ( pasi ) was used . in four regions body - head , torso , upper and lower extremities . in the four regions of the body - head , torso , upper and lower extremities evaluated the characteristics of the disease , severity of erythema , infiltration and desquamation with the score 1 - 4 , and the affected area of skin psoriatic changes with the score 1 - 6 ( table 1 ) . in assessing the severity of erythema scales we calculate : buttocks as a part of lower extremities , that is , region of the leg ( l)armpits and shoulders as a part of upper extremities , that is , region of the arm ( a)the neck is calculated as a part of the head ( h)torso ( t ) buttocks as a part of lower extremities , that is , region of the leg ( l ) armpits and shoulders as a part of upper extremities , that is , region of the arm ( a ) the neck is calculated as a part of the head ( h ) for calculating the pasi , the summation of erythema , infiltrations and desquamation of single region is multiplied with the numerical value of the region of the body and with the percentage by which the lesions have spread at a single region . form for calculating pasi : pasi=0.1(eh+ih+dh)ah+0.3(et+it+dt)at+0.2(ea+ia+da)aa+0,4(el+il+dl)al for data processing and hypothesis testing was used statistical package arcus quickstat biomedical version 1.0 . the relationship between variables was estimated correlation test . as the minimum value of the level of significance was taken as p < mostly it was hypertriglyceridemia ( 39% ) and hypertriglyceridemia with a lowered value of hdl ( 36% ) . the average age of those affected by dyslipidemia was 48.76 years ( sd= 14.72 ) , and the average duration of the basic disease was 16.15 years ( sd= 12.63 ) . clinical characteristics of the patients were estimated based on the index of severity of psoriasis on the affected area , ( pasi ) . in this research , the frequency of dyslipidemia in those affected by psoriasis was 62.85% . other studies have also shown an increased frequency of dyslipidemia by reviewing literature , which were analyzed by 25 studies , 20 studies showed that psoriasis is connected with dyslipidemia ( 5 ) . in brazil around 67% of those affected by psoriasis also had dyslipidemia ( 6 ) . study in japan also showed that dyslipidemia is closely connected with psoriasis , respectively , dyslipidemia occurs in those affected by psoriasis at around 34.3% and in the control group , 16.2% ( p < 0.01),(7 ) . in the research in israel , the frequency of dyslipidemia was statistically higher in those affected by psoriasis ( 56.9% ) , compared to the control group ( 47.3% ) ( p<0.001 ) ( 8) . hypertriglyceridemia was present in 39% of examinees , and hypercholesterolemia was present in 36% of examinees . other studies also discovered an increased frequency of hypertriglyceridemia and hypercholesterolemia in those affected by psoriasis . in denmark , prevalence of hypercholesterolemia was higher in those affected by psoriasis , compared to the control group ( 9 ) , and in great britain , an increased number of triglycerides was discovered in those affected by psoriasis compared to the control group ( 36% vs 28% ) ( 10 ) . the average age of those affected by psoriasis with dyslipidemia was 48.76 years ( sd = 14.72 ) and was similar to the average age of all examinees which was 47.14 years ( sd = 15.41 ) . and the average duration of psoriasis in those affected by dyslipidemia was 16.15 years ( sd= 12.63 ) and was similar to the average duration of psoriasis on all examinees , which was 15.52 years ( sd = 12.54 ) . this research contained a positive correlation between pasi values and dyslipidemia ( r=0.41 p=0.001 ) , that is , the severity of psoriasis and frequency of dyslipidemia , which is confirmed by tests of other research , so in a research conducted in middle east , prevalence of dyslipidemia in those affected by psoriasis is 14.1% for mild to medium psoriasis , ( pasi<10 ) , 22.48% for severe psoriasis ( pasi>10 ) , and in the control group 4,96% ( 11 ) . it is considered that proinflammatory cytokines in those affected by psoriasis can also affect the metabolism of lipids , but diet and medicines used for treatment of psoriasis are also important . connection between psoriasis and dyslipidemia has been confirmed , and the effect of severity of psoriasis on the frequency of dyslipidemia , but further research is required to determine the precise mechanisms of that connection . further research will illuminate the connection between psoriasis and metabolism of fats . based on the current findings , it is necessary to follow lipid status in those affected by psoriasis , in a goal to prevent lipid disorders , diagnostics and treatment of already existing disorders of fats , considering it contains risk factors and can lead to development of other ailments , especially cardiovascular ones . psoriasis is connected with dyslipidemia , but it is necessary to further research the precise mechanism of that connection .

introduction : psoriasis is a chronic skin ailment , which can be connected with other ailments including dyslipidemia.examinees and methods : research included 70 patients affected by psoriasis . both genders , above 18 years of age . average age of the respondents was 47.14 ( sd= 15.41 ) , which consisted of 36 men ( 51.43% ) and 34 women ( 48.57% ) . the average duration of psoriasis was 15.52 ( sd= 12.54 ) years.results:frequency of dyslipidemia on those affected by psoriasis was 62.85% . most often it was hypertriglyceridemia ( 39% ) and hypertriglyceridemia with a lowered value of hdl ( 36% ) , average age of those affected by psoriasis with dyslipidemia was 48.76 years ( sd= 14.72 ) , and the average duration of the basic disease was 16.15 years ( sd= 12.63 ) , the average values of the pasi score were 16.65 . increase in values of pasi score and dyslipidemia were statistically significantly connected ( r=0.41 ; p=0.0001).conclusion : psoriasis is connected with dyslipidemia .

it has been well known that about half of the patients with lung cancer have metastases at the time of initial diagnosis . the common sites of distant metastases are the bone , liver , adrenal glands , and lymph nodes . the clinical symptoms of the metastases of bone , liver , and lymph nodes usually occur relatively earlier . therefore , these metastases are often diagnosed at the same time the diagnosis of lung cancer was made . however , in the case of metastases to the kidneys , adrenal glands , gastrointestinal tract , and skin , the clinical symptoms of metastasis do not appear early and are usually found at postmortem examination . in particular , the intestinal metastases of primary lung cancer are hardly diagnosed until the development of intestinal obstruction , perforation or hemorrhage ; these cases usually show high mortality rate on operation . since morgan s first report in 1961 of small intestinal metastasis from lung cancer , 27 cases with the clinical symptoms of perforation , obstruction and/or hemorrhage have been reported . among them , only 1 case was intestinal hemorrhage . we here present a case of intestinal hemorrhage that progressed to intestinal perforation and caused by small intestinal metastasis of carcinoma of the lung , large cell type . a 31-year - old korean male patient was transferred to our hospital from a local hospital because of persistent melena of undetermined origin . four months ago , the patient visited the hospital with complaints of chest tightness and productive cough . an x - ray film of the chest at that time showed a patch infiltration in the right lower lung field . studies of the sputum for acid fast bacilli were negative but anti - tuberculosis medications were started under the impression of pulmonary tuberculosis . three months later , he was admitted to the same hospital because of melena and underwent extensive work - ups including gastroscopic examination , barium studies of the colon and small bowels , and a gastric mucosa scan for meckel s diverticulum , but no bleeding focus was found . during the stay in that hospital , he did fairly well until 10 days prior to this admission when recurrent melena developed . additional studies including 99mtc - sulfur colloid scintigraphy were carried out , but no bleeding focus was found . on admission , the patient appeared pale and acutely ill . the blood pressure was 130/70 mm / hg , pulse rate 120/min , respiratory rate 20/min , and the temperature 36.5c . the urea nitrogen was 22.4 mg / dl , the creatinine 1.5 mg / dl , the protein 2.5 g / dl ( the albumin 1.3 g / dl and the globulin 1.2 g / dl ) , the bilirubin 0.4 mg / dl , the alkaline phosphatase 53 iu , the aspartate aminotransferase ( ast ) 10 iu , and the alanine aminotransferase ( alt ) 10 iu . chest x - ray film revealed an ill defined dense infiltrate with air bronchogram in the right lower lung field ( fig . however , a large amount of hematochezia persisted even after the operation and signs of serious disseminated intravascular coagulopathy ( dic ) follwed . on the 10th hospital day while the dic improved , on operation , multiple polypoid masses of various sizes were palpated intraluminally in the jejunum from 10 cm below the treitz ligament to the 120 cm distally . a large perforation of the jejunum ( 8 cm in diameter ) probably caused by necrosis of the bowel wall was found on the antemesenteric border of the jejunum 2025 cm below the treitz ligament . multiple mass lesions including hematomes were also found in the mesenteric root of the small intestine . small bowel resection and end - to - end anastomosis were performed . on section , 36 polypoid masses were scattered grossly along the full length of the resected jejunum . the cells in the polypoid mass lesion were consistent with large round cells of undetermined origin . bronchoscopic examination , which was done on the 10th postoperative day , revealed an obstructing round mass at the entrance of the right main bronchus ( fig . 5 ) . histologically , this lesion was diagnosed as large cell carcinoma of the lung ( fig . it has been reported that 41% of all patients with lung cancer are found to have evidence of distant metastases at the time of initial diagnosis , but the clinical symptoms of the metastases to the gastrointestinal tract are rarely present . the distant metastases of lung cancer are usually found at the lymph nodes , brain , bone , adrenal glands , and liver through lymphatic spread . mcneill et al . reported that primary lung cancer metastases to the small intestine was mainly from large - cell type carcinoma as our case . the peak incidence was in the sixth and seventh decade , similar to those of patients with primary lung cancer . most of the metastatic small intestinal tumors originated from the cervix , skin , ovaries , and kidneys . the clinical symptoms were usually those of bowel obstruction , perforation or rarely hemorrhage . by reviewing the literature of the 27 cases reported , 18 had intestinal perforation , 8 had obstruction and only 1 had hemorrhage(table 1 ) . postmortem examinations of 431 lung cancer patients studied over an 11-year period(1 ) showed that 46 patients ( 11% ) had metastases to the small intestine . among the 46 patients who received exploratory laparotomy with the symptoms and signs of intestinal obstruction or perforation , all of these 6 patients died within 16 weeks after the operation . on the other hand , according to the report of arianha et al . , 10% of patients with suspected metastasis were found to have benign lesions as the cause of small bowel obstruction . also , in the other 2 reports , 25% and 38% of patients with a history of cancer who underwent exploratory laparotomy because of intestinal obstruction were found to have either a benign disease or a new primary cancer as the cause of the obstruction . according to the report by woods iv et al , 8 out of 13 patients who underwent emergency exploratory laparotomy experienced successful palliation by surgical intervention . these data suggested that the cancer patients with intestinal obstrcution who do not have a proven abdominal cancer should undergo exploratory laparotomy . report a case of perforation caused by metastatic cancer after chemotherapy and they suggested that there might be a close relationship between the chemotherapy and perforation . inalsingh et al . also explained that local factors , such as trauma and/or irradiation , which could influence the immune response were related to the metastases . among 17 cases with intestinal perforation , 7 presented with perfortion after chemotherapy and radiotherapy . in conclusion , with increasing use of chemotherapy and radiotherapy for the treatment of cancer , the possibility of perforation of the small intestine from the metastatic tumor should be considered more carefully than before .

although intestinal metastases from lung cancer are not rare at postmortem studies , the development of clinically significant symptoms from the gastrointestinal metastases is very unusual . we report a case of small intestinal hemorrhage leading to intestinal perforation secondary to metastases from a large cell carcinoma of the lung in a 31-year - old man along with a review of the literature .

tobacco smoking is known to be an important contributor to a wide variety of chronic diseases including chronic obstructive pulmonary disease , lung cancer , cardiovascular disease , and cancers of various organs . tobacco smoking also negatively affects several other respiratory diseases , including pneumonia and pulmonary tuberculosis.1 giving up smoking permanently has been shown to reduce loss of pulmonary function.25 the reason for high smoking rates , despite the well - known hazards of smoking , is attributable to addiction caused by nicotine dependency as well as habitual addiction . smoking is now viewed and managed as a drug addiction or chronic disease rather than as a personal habit or hobby.6 thus , effective treatment of tobacco addiction has become essential , and a wide range of pharmacologic and non - pharmacologic treatments have been used with varying degrees of success . the most effective approach to smoking cessation appears to result from an appropriate combination of these modalities.7,8 non - pharmacologic interventions to support smoking cessation could be successfully delivered via clinical approaches and through broader public health programs . certain interventions such as self - help programs , telephone counseling , and cognitive - behavioral therapy are amenable to either individual delivery in the clinical setting or broad dissemination to geographic communities and workplaces.9 smoking cessation rates reported in the literature are usually derived from studies in younger populations , and few studies have been conducted to determine the effectiveness of smoking cessation intervention in older individuals.1012 in thailand , the prevalence of current smokers in rural areas was significantly higher than urban areas ( 29.2% vs 22.9% ) with a trend toward increasing prevalence with age.13 the prevalence of smoking among thai adults was 45.6% for men and 3.1% for women . 15.8% of men and 1.7% of women were current users of roll - your - own ( ryo ) cigarettes , most of whom were elderly living in rural areas.14 users of ryo cigarettes appeared to be more addicted to smoking than the users of manufactured cigarettes as measured by time to first smoking of a cigarette after waking.14 the elderly were reported to be less aware of the harmful effects of smoking , and have higher rates of nicotine dependence.15 behavioral group therapy for smoking cessation is widely reported , but to our knowledge , there is no related information on community - dwelling elderly groups.16 our aim was to evaluate behavioral group therapy and an education - alone program for elderly smokers living in rural communities . a health risk - screening questionnaire was administered to elderly members ( age > 60 years ) of the chiang dao elderly club , chiang dao district , chiang mai province . quit smoking within a month were invited to a smoking cessation exhibition at chiang dao hospital . the design of the study was observational , including convenience sampling of these elderly smokers . the inclusion criteria were age more than 60 years , current smokers with a smoking history of at least 10 pack - years , and readiness to quit state of mind . exclusion criteria were current pharmacological use to quit smoking , the presence of an unstable or life - threatening medical condition , current unstable psychiatric illness , and alcohol addiction . participants were allocated into two groups based on their preference : behavioral group therapy ( group a ) and education alone ( group b ) ( figure 1 ) . both groups attended an education program that included a lecture on the health consequences of smoking for 2 hours . only group a participants further attended behavioral group therapy sessions for 3 hours per day in the following 3 days , totaling 9 hours . the first was a demonstration of formalin - preserved specimens of smoking - related diseases like lung cancer , emphysematous lung , and myocardial infarction with coronary artery occlusion , as well as slides and video clips showing the adverse effects of cigarette smoking in the form of advanced diseases . the second part included coping and social skills training , contingency management , self - control , cognitive - behavioral interventions , reinforcement , and relaxation with a focus on sharing experiences the participants were equally divided and rotated daily into three stations of video training , behavioral therapy , and socialization , each supervised by two staffs . subjects who could quit smoking at the end of each day were commended and rewarded with an origami star . demographic data were collected by face - to - face interview and included age , sex , history of smoking , level of education , economic status , and type of cigarettes smoked . three levels of economic status were determined based on annual household income : low income ( 70,000 baht ) , moderate ( 70,001195,749 baht ) , and high income ( 195,750 baht).17 the average number of cigarette smoked was , therefore , calculated by dividing the average native cigarette weight by standard manufactured cigarette weight which was equivalent to 412 standard manufactured cigarettes.18 in addition , native cigarettes consist of crudely cut tobacco mixed with grinded tamarind pod in a loose roll . all participating subjects had their level of nicotine dependency measured by the fagerstrom test for nicotine dependence ( ftnd ) questionnaire which was validated in many studies,19,20 the scale of which consists of six items.21 the questionnaires were explicit and informative , and the participants were able to fill them by themselves without supervision . total possible scores ranged from 0 ( no dependence ) to 10 ( very high dependence ) and were categorized as low dependence ( score 03 ) , medium dependence ( score 46 ) , or high dependence ( score 710).6,22,23 measuring carbon monoxide ( co ) in exhaled breath is an immediate , noninvasive , and well - established method used to classify smokers from nonsmokers.2426 exhaled co level was measured using a standardized instrument ( the micro co meter , micro medical ltd , kent , uk ) in an open - air environment,27 using the standard recommended cut - off value , whereby a reading of 10 parts per million ( ppm ) or more signifies smoking.24 self - reported smoking status and exhaled co level were measured at baseline and every follow - up visit at 3 , 6 , and 12 months post - target quit date ( tqd ) . the primary outcome measured was continuous abstinence rate ( car ) from smoking at the end of month 12 after tqd . continuous abstinence in this study was defined as self - report of not smoking even a single cigarette since tqd and a negative biochemical test ( exhaled co < 10 ppm)25 at each of the three follow - up visits at months 3 , 6 , and 12 . a participant was defined as a smoker if he / she self - reported smoking 1 cigarette or had an exhaled co level 10 ppm at each of the three follow - up visits . sample size calculation was based on the hypothesis from our pilot study ( n=30 ) in a previous year in which a 12-month cessation rate of 40% for a behavioral group therapy ( group a ) and 15% for an education - alone group ( group b ) was found . based on this report , 88 subjects in each group were required in order to reject the null hypothesis with 95% power . the type i error probability associated with this null hypothesis was 0.05 , and anticipating a drop - out rate of 15% , it was projected to randomly assign 102 per group . results for numerical and categorical data were expressed as mean standard deviation and absolute frequencies with percentages , respectively . all analyses were carried out using the spss statistical package , version 16 for windows . sample size calculation was based on the hypothesis from our pilot study ( n=30 ) in a previous year in which a 12-month cessation rate of 40% for a behavioral group therapy ( group a ) and 15% for an education - alone group ( group b ) was found . based on this report , 88 subjects in each group were required in order to reject the null hypothesis with 95% power . the type i error probability associated with this null hypothesis was 0.05 , and anticipating a drop - out rate of 15% , it was projected to randomly assign 102 per group . results for numerical and categorical data were expressed as mean standard deviation and absolute frequencies with percentages , respectively . independent t - tests were used to compare baseline mean differences between the groups . statistical difference in primary outcome was analyzed using chi - square tests . all analyses were carried out using the spss statistical package , version 16 for windows . six hundred and twenty out of 2,668 elderly subjects initially screened by the health risk questionnaire were responders , and 372 attended our smoking cessation exhibition . two hundred and twenty - four out of 372 attendants demonstrated their readiness to quit within a month by face - to - face interview and were allocated into group a and group b based on their preferences . all study participants smoked ryo native unregulated cigarettes ( called kee - yo cigarettes ) with varying diameters and lengths and had never attempted to quit smoking prior to this study . demographic characteristics and smoking history were similar between groups , and there was no significant difference between the groups in terms of age , age of onset of smoking , years of smoking , smoking pack - years , level of education , economic status , and nicotine dependence as measured by the ftnd scale ( table 1 ) . self - reported smoking status and exhaled co < 10 ppm at months 3 , 6 , and 12 between group a and group b are shown in table 2 . car at the end of the study ( month 12 ) was significantly higher in group a than group b ( 40.1% vs 33.3% , p=0.034 ) . similar results were also found throughout all follow - up visits at months 3 ( 57.3% vs 27.0% , p<0.001 ) and 6 ( 51.7% vs 25% , p<0.001 ) ( figure 2 ) . this study revealed that the behavioral group therapy program in elderly smokers resulted in significantly higher cars , both in short ( 3-month ) and long ( 6-month and 12-month ) terms , than education alone . to our knowledge , there is limited literature on controlled trials comparing behavioral group therapy with education alone . one found no significant differences between the hypnosis , education , or behavioral therapy groups.28 another comparing behavioral group therapy with 1-hour education revealed that behavioral therapy was more effective than education ; however , the rates of continuous abstinence for both groups were much lower than our study ( 25% vs 13% at month 3 and 16% vs 11% at 1 year).29 the major limitation of this study is that participants were not randomly allocated but were self - selected into treatment groups . setting up a randomized controlled trial ( rct ) would be problematic in the community dwellers as there was no travel support or daily wage compensation for those randomized to the behavioral therapy group , which required 3 days attendance . although this study was randomized , it was designed to simulate a more naturalistic process as subjects could make their own decision in choosing a program most suitable for them . the advantage of this approach was reflected in our study which had very few drop - outs for both groups during the entire study period . although rcts are considered to be the gold standard for determining the absolute efficacy of a therapeutic intervention , they do have limitations.30 the rct design can only be applied when it is both feasible and ethical to perform a comparison with the control treatment , and when the patient / subject consents to that element of experimentation.31 thus , most rcts might not be reliably extrapolated to the real - world situation of patients with multiple problems and variable adherence.31 car , not point prevalence rate , was used as an indicator for evaluation of the effectiveness of the two interventions for the entire study period because it disposed more closely toward the treatment goal : to stop smoking and to maintain abstinence . in contrast to continuous abstinence , point prevalence could ignore extended periods of posttreatment smoking if smoking events did not occur within the point window ( eg , the last 7 days ) , thereby considerably overestimating the total number of abstinent subjects.24 the high car in both groups could be explained by low - to - moderate nicotine dependency in most subjects even though their smoking pack - years were considerably high . the possible reason for low nicotine dependency despite high smoking pack - years was most likely due to error in estimating number of cigarettes smoked . at the end of the study , finding higher car in the education - alone group at month 12 than at months 3 and 6 was unexpected . this phenomenon most probably resulted from increased motivation for quitting due to the strong social influence around their workplaces and neighborhoods . the promising results of behavioral group therapy with its relatively short course ( 3 days ) and minimal manpower ( handling a minimum of 100 participants with only six staff members ) as seen in this study highlight that this program can be implemented in resource - limited health agencies like community hospitals . firstly , participants were homogeneities for elderly age group without previous attempts to quit , low level of education , low economic status , and smoking the same type of cigarette ( ryo cigarette ) . secondly , we used biochemical verification by monitoring exhaled co level for smoking status to confirm self - reported abstinence at every follow - up visit . thirdly , the study was designed for long - term follow - up with a negligible percentage of patients lost to follow - up compared to a previous study.29 fourthly , the study was designed to simulate real - world practice based on community approach for smoking cessation . firstly , our study could not be designed as an rct for the reasons mentioned earlier , and participants in the behavioral therapy group might have more self - control and enthusiasm for coping with their smoking tendencies than the education - alone group . thirdly , the selection of members from the elderly club could affect the external validity of the study and possibly limit our study result for application in different elderly populations . based on our results , further studies are recommended to evaluate smoking cessation programs in general or other specified elderly populations , and with various cigarette brands . finally , rct should be conducted if it is feasible to study the effectiveness of the program for elderly populations . behavioral group therapy focused on elderly smokers in real - world practice resulted in significantly higher short- and long - term cars than the education - alone group . this promising result could potentially contribute to the widespread smoking cessation policy and research for community - dwelling elders .

backgroundtobacco smoking is known to be an important contributor to a wide variety of chronic diseases , especially in older adults . information on health policy and practice , as well as evaluation of smoking cessation programs targeting older people , is almost nonexistent.purposeto compare the real - world implementation of behavioral group therapy in relation to education alone for elderly smokers.materials and methodselderly smokers ready to quit smoking were identified from a cohort who completed a questionnaire at a smoking exhibition . they were allocated into two groups , behavioral therapy ( 3 days 9 hours ) and education ( 2 hours ) , depending on their preferences . demographic data , the fagerstrom test for nicotine dependence ( ftnd ) score , and exhaled carbon monoxide level were recorded at baseline . smoking status of all subjects was followed at months 3 , 6 , and 12 . statistical differences in continuous abstinence rate ( car ) between the two groups were analyzed using chi - square tests.resultstwo hundred and twenty - four out of 372 smoking exhibition attendants met the enrollment criteria ; 120 and 104 elected to be in behavioral group therapy and education - alone therapy , respectively . demographic characteristics and smoking history were similar between both groups , including age , age of onset of smoking , years of smoking , smoking pack - years , education level , and nicotine dependence as measured by the ftnd scale . the car of the behavioral therapy group at the end of the study ( month 12 ) was significantly higher than the education group ( 40.1% vs 33.3% , p=0.034 ) . similar results were also found throughout all follow - up visits at month 3 ( 57.3% vs 27.0% , p<0.001 ) and month 6 ( 51.7% vs 25% , p<0.001).conclusionbehavioral group therapy targeting elderly smokers could achieve higher short - and long - term cars than education alone in real - world practice .

small intestinal malignancies have been diagnosed in advanced stages due to their non - specific clinical presentations as well as difficulties with endoscopic examinations of the small intestine . in recent years , the preoperative diagnosis for small intestinal malignancy has been dramatically improved due to the advance in endoscopic technologies such as double - balloon enteroscopy ( dbe).1,2 here , we describe a 53-year - old woman with a stage i jejunal adenocarcinoma diagnosed by dbe with a review of the relevant english literature with specific reference to their diagnostic modalities . a 53-year - old woman presented to our hospital with a 13-month history of recurrent vomiting , which aggravated in frequency 10 days ago . other complaints included anorexia , epigastric pain , and weight loss of 3 kg over 3 months . laboratory findings revealed a white cell count of 8,900/mm , hemoglobin of 14.1 g / dl , and hematocrit of 40.6% . findings of routine blood chemistry , serum carcinoembryonic antigen and serum carbohydrate antigen 19 - 9 were within normal limits . abdominal computed tomography ( ct ) revealed significant localized thickening of the jejunal wall with marked dilatation proximal to the lesion ( fig . as there was no clue to differentiate these two diagnoses , we decided to perform an endoscopy for the direct visualization of the lesion and a preoperative histological diagnosis , if possible . push enteroscopy was initially performed because the lesion was observed at proximal jejunum , however , visualization of the lesion by push enteroscopy was impossible because of the acute angulation of a bowel loop . for the next step , dbe using oral route was done under the conscious sedation with an intravenous bolus injection of midazolam 2 mg and propofol 20 mg . dbe of the proximal jejunum revealed an infiltrative tumor causing concentric luminal narrowing ( fig . extensive biopsy samples were obtained , and the tumor location was marked using a hemoclip and injecting india ink ( fig . laparoscopic partial jejunectomy and removal of regional lymph nodes were performed , and a 45258 mm , constricting tumor ( fig . 3 ) was identified at a site 20 cm distal to the ligament of treitz . histopathological examination revealed a stage i jejunal adenocarcinoma ( t2n0m0 ; classified according to the american joint committee on cancer staging system ) ; without invasion through the muscularis propria , lymphovascular invasion or lymph node metastasis ( fig . small intestinal adenocarcinoma accounts for 0.3% of all malignancies of the gastrointestinal tract and 30% to 50% of all malignancies of the small intestine.3 despite a thorough history , physical examination and complete diagnostic workup , the correct diagnosis of small intestinal malignancy has been established preoperatively in only 50 percent of cases , with the remainder diagnosed at exploratory laparotomy . since clinical presentations of small intestinal adenocarcinoma the rarity of this tumor and the difficulties with endoscopic examinations in small intestine may also attribute the delayed diagnosis . as a result , survival is generally poor , with most series reporting five - year survival rates of 20 - 30%.3 we reviewed reports of primary jejunal adenocarcinoma identified using a computerized search of pubmed database ( articles in english between 2000 and 2009 ) . primary jejunal adenocarcinomas associated with crohn 's disease , celiac disease or duplication cyst were excluded in this analysis . three cases of primary jejunal adenocarcinoma in children were also excluded . under this definition , 20 of the cases identified by the computerized search were reviewed ( table 1).4 - 22 there were 10 men and 9 women with a median age of 55 years . solitary bone metastasis and primary ovarian carcinoma was the first clinical manifestation in two of them.8,22 seven of them were diagnosed without regional or distant metastasis , however , none of them were diagnosed in stage 1 as in our case . approximately 45% of cases were diagnosed by exploratory laparotomy ( n=9 ) and 45% of cases were diagnosed by endoscopy ( push enteroscopy , n=6 ; dbe , n=2 ; capsule endoscopy , n=1 ) . recent advances in dbe may facilitate preoperative histological diagnosis of small intestinal malignancy as in our case . in the present case , the jejunal wall thickening could be attributed to the tumor , ischemic change , or inflammation as there were no symptoms , signs , and laboratory findings suggestive of a malignancy . although some do recommend operation for a possible jejunal cancer without preoperative histological confirmation , confirming malignancy in equivocal cases may greatly increase both the compliance of patients for an operation and confidence of the physician planning a surgical resection . dbe successfully revealed an infiltrative mass with concentric luminal narrowing and facilitated correct histological diagnosis in this case . in addition , tumor marking using india ink for the exact location during dbe was helpful for the subsequent laparoscopic resection . as only dbe allows direct , controlled visualization of small bowel tumors and its histological confirmation preoperatively , it may be considered the gold standard for the diagnosis of such tumors . in conclusion , dbe is a safe and accurate method to make a preoperative histological diagnosis of jejunal cancer . confirming malignancy using dbe in equivocal cases may greatly increase both the compliance of patients for an operation and confidence of the physician planning a surgical resection .

despite a thorough history , physical examination , and complete diagnostic workup , the correct diagnosis of small - intestinal malignancy is established preoperatively in only 50% of cases ; an exploratory laparotomy is often required . however , recent advances in endoscopic technologies , such as double - balloon enteroscopy ( dbe ) , have been shown to facilitate the preoperative diagnosis of these tumors . confirmation of malignancy using dbe in equivocal cases may greatly increase both patients ' acceptance of surgery and the confidence of the physician planning a surgical resection . we describe herein the case of a 53-year - old woman with a stage i jejunal adenocarcinoma that was diagnosed by dbe and treated by laparoscopic jejunectomy . histopathological examination revealed a stage i jejunal adenocarcinoma ( t2n0m0 ) without muscularis propria invasion , lymphovascular invasion , or lymph - node metastasis .

a left renal vein passing behind the abdominal aorta is termed a retroaortic left renal vein ( rlrv ) , and this anomaly is a relatively uncommon condition . recent advances in computed tomography and magnetic resonance imaging techniques make it possible to visualize the vascular structures in detail . additionally , the congenital anomalies of the inferior vena cava ( ivc ) and its tributaries have become more frequently encountered in asymptomatic patients . rlrv anomalies , although usually overlooked , are not rare . however , only a few cases showing clinical symptoms with this anomaly have been reported . compression of the rlrv between the aorta and the vertebra is known to be the cause of urological problems such as hematuria , varicocele , and ureteropelvic junction obstruction ( upjo ) . we retrospectively evaluated the type , frequency , clinical significance , management , and long - term follow - up of rlrv in 9 patients who were examined with multidetector computed tomography ( mdct ) owing to urological problems . twelve patients with urological problems , such as hematuria , flank and abdominal pain , varicocele , and upjo , were studied with mdct at our institution from january 2003 to december 2009 . we retrospectively reviewed these patients ' medical records and analyzed their clinical characteristics including sex , age , type of rlrv , urologic symptoms , concomitant disease , treatment , and follow - up results ( table 1 ) . type i , ii , iii , and iv of rlrv join the ivc in the orthotopic position , join the ivc at level l4 - 5 , join at the circumaortic or collar left renal vein , or join the left common iliac vein , respectively ( fig . 1 , 2 ) . the mean age and follow - up duration of the 9 patients were 46.020.1 years ( range , 17 - 65 years ) and 32.820.1 months ( range , 15 - 69 months ) , respectively , and the male to female ratio was 5 to 4 . the urologic symptoms of the initial diagnosis were various ( microscopic hematuria : 5 of the 9 patients ; left flank pain : 4 of the 9 patients ; inguinal pain : 1 of the 5 male patients ; and gross hematuria : 1 of the 9 patients ) , and the concomitant diseases were upjo in 2 of the 9 patients and varicocele in 2 of the 5 male patients . the number of patients with type i , ii , iii , and iv of rlrv were 6 , 2 , 1 , and 0 patients , respectively . in type ii , all patients had upjo and 1 of the patients had varicocele . one of these patients underwent laparoscopic pyeloplasty , and the other patient underwent laparoscopic nephrectomy owing to a nonfunctional kidney with varicocelectomy . symptoms in the five patients with microscopic hematuria continued , whereas 1 patient with gross hematuria had resolved gross hematuria after nephrectomy . the two patients with upjo who underwent pyeloplasty and nephrectomy were treated successfully , and in the other 2 patients , the pain spontaneously resolved . the symptoms in the one patient with varicocele also spontaneously improved ( table 1 ) . however , the microscopic hematuria was not resolved with conservative management for long - term follow - up . the development of the renal veins is a part of the complex developmental process of the ivc . the process starts from the fourth week of conception and ends at about the eighth week . the ivc is formed from a vast network of three pairs of parallel veins in communication . the posterior cardinal veins , the subcardinal veins , and the supracardinal veins are in the order of appearance . during the development of the ivc , there are anastomotic communications between the subcardinal and supracardinal channels that form a collar of veins encircling the aorta . if the dorsal portion of this collar persists , then the left renal vein is posterior to the aorta , forming a rlrv . the diagnostic methods for detecting ivc anomalies in previous reports were autopsy study , renal venography , color doppler ultrasonography , computed tomography , and magnetic resonance imaging . with recent advances in computed tomography technology , mdct has replaced conventional angiography and venography in most clinical conditions . mdct is a reliable , easily applicable , and noninvasive tool for demonstration of abdominal organs and vascular structures . in type i , the ventral preaortic limb of the left renal vein is obliterated , but the dorsal retroaortic limb persists and joins the ivc in the orthotopic position . type ii results from the obliteration of the ventral preaortic limb of the left renal vein , and the remaining dorsal limb turns into the rlrv . the left renal vein lies at the level of l4 to l5 and joins the gonadal and ascending lumbar veins before joining the ivc . this type is due to the persistence of subsupracardial and intersupracardial anastomoses and the dorsal limb of the left renal vein . if all small retroaortic veins that empty into the ivc are considered , the incidence of a circumaortic left renal vein could be as high as 16% . in type iv , the ventral preaortic limb of the left renal vein is obliterated , and the remaining dorsal limb becomes the rlrv . then , the rlrv courses obliquely and caudally behind the aorta to join the left common iliac vein . the incidences of left ivc , double ivc , and retrocaval ureter are 0.2 - 0.5% , 0.3 - 2.8% , and 0.1% . the incidences of rlrv type i , ii , iii , and iv are 0.3 - 1.9% , 0.4 - 0.9% , 1.5 - 8.7% , and 0.16% , respectively . rlrv type i , ii , iii , and iv in our cases occurred in 6 , 2 , 1 , and 0 patients , respectively . during the renal surgery , this kind of anatomical variation influences the technical feasibility of the operation . failure to recognize these anomalies the posterior " nutcracker phenomenon " occurs when a decreased space between the aorta and the vertebra causes compression of the rlrv . it is postulated that compression of the left renal vein leads to hematuria because of elevated pressure in the left renal vein , resulting in congestion of the left kidney and the venous communications [ 15 - 18 ] . it is well known that the gonadal , ascending lumbar , adrenal , ureteral , and capsular veins are potential collateral venous pathways in cases of renal vein compression or obstruction . in addition , vascular dilatation of the afferent venous system can result from increased drainage pressure , which men can suffer from left - sided varicocele and women from pelvic congestion syndrome [ 19 - 21 ] . in our series , 3 patients with microscopic hematuria had type i , 1 had type ii , and 1 had type iii . symptoms continued in all patients with microscopic hematuria , maybe because of increased pressure in the renal vein , that is , the posterior nutcracker phenomenon . in two patients with varicocele , symptoms spontaneously improved in one patient ( type i ) , and the other patient ( type ii ) resolved his problem after nephrectomy . in the two cases of type ii with a left - sided upjo , it was postulated that dilatation of the renal pelvis led to the upjo directly posterior contacting the dilated left gonadal vein ( fig . one patient with partial obstruction underwent pyeloplasty because of severe left flank pain , and the other patient underwent nephrectomy for a nonfunctioning kidney . in adult upjo , the incidence of aberrant vessels is 35 - 39% [ 22 - 24 ] . three of 12 patients were related to dilated gonadal vessels and 1 patient had rlrv type iii . cho et al reported the congenital absence of the ivc as a rare cause of pulmonary thromboembolism . gibo and onitsuka reported a case of rlrv that showed left renal vein hypertension by pullback pressure measurement from the rlrv to the ivc . therefore , congenital anomalies of the venous system might easily induce the congestion of the renal bloodstream , and these anomalies might be the predisposing conditions of clinical symptoms such as hematuria , flank pain , and pelvic congestion . unawareness of this situation during retroperitoneal surgery can result in bleeding , nephrectomy , and even death . surgeons prefer the left renal vein in renal transplantation because of its longer length . because of this , it is important to know the course of the left renal vein and whether it is pre - aortic or not . it is also important to be aware of anomalies of the renal vein for distinctive diagnosis of retroperitoneal tumors , retroperitoneal lymph node pathologies , and aortic dissection . before the renal surgery , careful reading of the preoperative rlrv imaging study helps to avoid fatal complications during the operation . this study was limited by the fact that it was performed retrospectively , and the data were analyzed in selected patients who had urologic symptoms . , we could not reveal the korean incidence , follow - up results , concomitant diseases , or a casual relationship between rlrv and urologic symptoms . it may sometimes cause hematuria , flank pain , and vascular dilations ( varicocele ) . the most common type of rlrv was type i. the microscopic hematuria due to rlrv is thought to be continued in the long - term follow - up . for patients with gross hematuria or flank and inguinal pain , individualized treatment such as conservative care , pyeloplasty , varicocelectomy , and nephrectomy widespread use of diagnostic mdct in retroperitoneal diseases , particularly kidney tumors , can identify changes in the renal vascularization more easily , and thus allows urologists to plan a safe and less complicated surgery .

purposea retroaortic left renal vein ( rlrv ) is located between the aorta and the vertebra and drains into the inferior vena cava . urological symptoms can be caused by increased pressure in the renal vein . to evaluate the clinical importance of rlrv , we reviewed patients ' medical records and radiologic findings.materials and methodsnine patients who were studied with multidetector computed tomography at our institution from january 2003 to december 2009 had urologic symptoms with rlrv . we retrospectively reviewed these patients ' medical records and analyzed their clinical characteristics.resultsthe patients ' mean age was 46.020.1 years ( range , 17 - 65 years ) and the male to female ratio was 5 to 4 . the urologic symptoms of the initial diagnosis were various ( hematuria : 5 of the 9 patients ; left flank pain : 4 of the 9 patients ; inguinal pain : 1 of the 5 male patients ; and gross hematuria : 1 of the 9 patients ) . the distribution among the type i , ii , iii , and iv of rlrv was 6 , 2 , 1 , and 0 patients , respectively . the concomitant diseases were ureteropelvic junction obstruction ( upjo ; 2 of the 9 patients ) and varicocele ( 2 of the 5 male patients ) . one patient with upjo underwent pyeloplasty and the other patient with upjo underwent nephrectomy due to a nonfunctional atrophied kidney . the microscopic hematuria was not resolved with conservative management for long - term follow-up.conclusionshematuria and inguinal or flank pain seem to be common in patients with rlrv . the most common type of rlrv was type i. it appeared that the microscopic hematuria continued in the long - term follow - up .

essential thrombocythemia ( et ) is one of the bcr - abl negative myeloproliferative neoplasms . diagnosis is made when 1 ) platelet count is higher than 450 10/ ; 2 ) patients have the jak2 v617f mutation or another clonal mutation such as in the gene encoding the thrombopoietin receptor ( mpl ) ; 3 ) bone marrow reveals megakaryocyte proliferation with large and mature megakaryocytes in the bone marrow . recent discovery of the calreticulin ( carl ) gene is likely going to modify the diagnostic criteria of et as there are et patients who have the carl mutation but do not bare jak2 v617f and mpl mutations . thrombosis can be life - threatening , so it is important to identify patients at risk for thrombotic complications . thrombosis risk assessment is still a matter of debate as different research groups use different risk criteria . to date , the most widely used are the conventional evidence - based criteria . based on them , high - risk factors for thrombosis are age > 60 years and a history of previous thrombosis . the intermediate - risk group encompasses patients whose age is between 4060 years , whereas patients under 40 years fall into the low - risk stratum . however , the british committee for standards in haematology ( bcsh ) uses a platelet count of > 1500 10/l as an additional high - risk factor ( table 1 ) . for comparison , the czech collaborative group for ph negative myeloproliferative diseases ( czemp ) identifies high - risk patients by additional factors such as platelet count > 1000 10/l , thrombophilic status and microcirculatory symptoms . bcsh risk stratification in 2012 the international working group of myelofibrosis research and treatment ( iwg - mrt ) developed the international prognosis score for et ( ipset ) to help predict survival for et patients at diagnosis . additionally , the international prognosis score for thrombosis ( ipset - t ) risk stratification was proposed by barbui and colleagues . it includes not only the patient 's age and history of thrombosis as risk factors but also jak2v617f mutation and cardiovascular risk factors ( table 3 ) . in contrast to jak2v617f mutation , carl positive patients showed decreased thrombosis risk , and incorporating it in the ipset - t model does not modify the thrombosis risk . ipset risk stratification * low risk , score 0 ; intermediate risk , score 12 ; high risk , score 34 ipset - thrombosis risk stratification low risk , score 01 ; intermediate risk , score 2 ; high risk , score 3 the purpose of this study was to compare the outcomes of patients with et based on different risk stratification systems . we evaluated 185 who - defined et patients at the hospital of lithuanian university of health sciences kaunas klinikos . our survey included 185 patients who were diagnosed with et according to 2008 who essential thrombocythemia diagnostic criteria . patients diagnosed with et before 2008 according to polycythemia vera study group ( pvsg ) criteria were revaluated for who diagnostic criteria . data were collected from medical records and interviews obtained during patients visits to a hematologist . all patients were asked to complete a cardiovascular events and risk factors questionnaire . on repeated visits during follow - up , the history of thrombosis was taken . cardiovascular risk factors were arterial hypertension , overweight , smoking , diabetes mellitus , and hypercholesterolemia . thrombotic events were defined as major : acute myocardial infarction , unstable angina pectoris , ischemic stroke and venous thrombosis . all patients were evaluated for risk factors using four different systems ( table 4 , fig . the mean age of our study cohort was 62 years ( range 1790 ) ; they were predominantly female patients ( 67.2% ) . the mean platelet count was 765 10/l ( range 4502268 10/l ) , mean hemoglobin concentration 132 g / l ) , and mean leukocyte count 9.9 10/l ( range 422 10/l ) . there was thrombosis history in 47 ( 25.4% ) patients , thrombosis before diagnosis in 35 ( 18.9% ) patients , and after diagnosis in 12 ( 6.5% ) patients . most events were arterial ( 41 , 87.2% ) , 5 ( 10.6% ) were venous , and 1 ( 2.1% ) patient had both arterial and venous events . one or more cardiovascular risk factors were identified in 66 ( 35.7% ) patients , 2 of them have 3 risk factors ( arterial hypertension , diabetes mellitus and overweight ) , 35 patients have 1 risk factor , and the other 66 patients have 2 risk factors . according to conventional thrombosis criteria we identified 126 high- and 59 low - risk patients in our cohort . from the high - risk group 23 patients had thrombosis history and were older than 60 years at diagnosis , 91 patients were older than 60 at diagnosis with no thrombosis , and 13 patients were younger than 60 with thrombosis . according to the prognostic model ipset , we identified 56 patients as high - risk , 87 patients as intermediate - risk and 42 patients as low - risk group . according to the ipset - thrombosis model , 118 patients were high - risk , 44 were intermediate- , and 23 low - risk . according to the bcsh risk stratification 127 patients were high - risk , 28 intermediate- , and 20 low - risk . therefore it is important to establish thrombosis risk factors at the time of diagnosis in order to decide proper treatment options . the purpose of our survey was to evaluate the clinical usefulness and relevance of four thrombosis scoring systems ( conventional , ipset , ipset - t , bcsh ) in our cohort of 185 2008 who - defined et patients . patients under 60 years old without previous thrombosis are low - risk . in our cohort 59 ( 31.9% ) patients from 185 are low - risk using these aforementioned risk factors not requiring cytoreductive treatment . according to ipset - t only 8 ( 13.6% ) patients without any other factors ( score 0 ) from those 59 and 4 ( 6.8% ) patients with cardiovascular risk factors only ( score 1 ) belong to the low - risk group . younger than 60 remain in the low - risk group when applying the new ipset - t criteria . the majority of these 59 low - risk patients from our cohort transfer to the intermediate - risk group : 36 patients ( 61.0% ) with jak2v617f positive only ( score 2 ) . ten patients ( 16.9% ) from 59 patients are younger than 60 , jak2v617f positive with one of the cardiovascular risk factors ( score 3 ) . they would be categorized as high - risk according to ipset - t . in this case these aforementioned 16.9% of patients probably would require cytoreductive treatment already , despite being under 60 years old and having no previous thrombosis , if we use the ipset - t model at diagnosis . nevertheless , our data show that almost 80% of low - risk patients under 60 years old are reclassified to the ipset - t intermediate- and high - risk group category . this group of patients would benefit from a prospective , randomized clinical trial in order to define optimal treatment modality . when using bcsh criteria this low - risk group decreases even more , because only 20 ( 10.8% ) patients are younger than 40 years with no other risk factors . patients older than 60 either have thrombosis history belong to the high - risk group using conventional risk factors . there are 126 ( 68.1% ) high - risk patients according to conventional risk factors in our cohort . this group consists of 91 ( 72.2% ) patients older than 60 with no thrombotic events , 23 ( 18.3% ) older than 60 with thrombosis history , and the remaining 12 ( 9.5% ) patients are younger than 60 with previous thrombosis . 11 ( 12.1% ) patients from all who are older than 60 without jak2v617f mutation , with no cardiovascular risk factors and with no previous thrombosis would belong to the low - risk category according to ipset - t ( score 1 ) . actually this group could be even higher , but our cohort is 82% jak2v617f positive . it is contrary to the risk model with conventional risk factors , because these 11 patients would belong to the high - risk group . it means that these 12.1% of patients from the conventional high - risk group would transfer to low - risk ipset - t , probably requiring observation only or possibly antiplatelet therapy . only patients older than 60 with leukocytosis more than 11 10/l and previous thrombosis belong to the high - risk group according to ipset . from our patients , 56 ( 30.3% ) fell into the high - risk category based on the ipset classification . interestingly , this number of patients is the smallest when comparing all other risk models ( bsch , ipset - t , conventional ) . only one third of 185 patients ( 44 ; 23.8% ) according to ipset - t belong to the intermediate - risk group . one ( 2.3% ) patient is under 60 years old with previous thrombosis , jak2v617f negative and with no cardiovascular risk factors ( score 2 ) . seven ( 15.9% ) from these 44 patients are older than 60 with one or more cardiovascular risk factors ( score 2 ) . almost half of all patients ( 47.6% ) are categorized as intermediate - risk according to ipset . 30 ( 34% ) of these 88 patients are younger than 60 : 10 ( 11.4% ) patients ( score 1 ) had previous thrombosis , 17 ( 38.6% ) patients ( score 1 ) had leukocytosis more than 11 10/l , and 3 patients ( 6.8% ) ( score 3 ) had both risk factors . it seems that adding leukocytosis more than 11 10/l as an independent risk factor for thrombosis scoring doubles the intermediate - risk group in the ipset model . the high - risk group in ipset seems to be the smallest when compared with other risk models . to date , 12 patients from our cohort have had thrombosis after diagnosis . adopting the ipset - t model , 1 patient was in the low - risk , 1 in the intermediate - risk and 10 patients in the high - risk group . due to small numbers of thrombotic events we were unable to perform a statistical analysis . there is no prospective randomized clinical trial for aspirin use , although a retrospective study favors aspirin use compared to observation only . if patients have extreme thrombocytosis with platelet count > 1000 10/l causing acquired von willebrand syndrome or increased risk of bleeding , antiplatelet agents should be avoided . there is no consensus in management approaches for patients in the intermediate - risk group . the group of experts of the italian society of hematology ( sie ) and the affiliate societies sies ( italian society of experimental hematology ) and gitmo ( italian group for bone marrow transplantation ) agree that at present there is no evidence to treat with cytoreductive medications these intermediate - risk patients and for further improvement of evidence - based data controlled randomized trials are needed . hydroxycarbamide ( hu ) together with low dose aspirin or anagrelide monotherapy is becoming a standard of care [ 11 , 13 , 14 ] . in patients aged under 40 , interferon is recommended . use of busulfan or pipobroman is usually restricted to et patients older than 75 and only as second or third line therapy . in conclusion : our results show that different risk assessment models stratify patients to different risk groups . there is a subset of patients that varies from the low- ( 20.7% ) to high-/intermediate - risk group and from the high- ( 12.1% ) to low-/intermediate - risk group according to different scoring systems that we use at diagnosis . in our opinion , ipset - t would be more rational to use , whereas it is based on four thrombosis criteria including jak2 v617f mutation and determined the largest group of patients that need treatment compared with other models . new prospective randomized clinical trials are crucial , especially for et patients older than 60 who have no other risk factors and et patients younger than 60 years with no previous thrombosis but with other risk factors , in order to avoid over - treatment as well as insufficient treatment .

thrombosis risk in essential thrombocythemia ( et ) patients can be assessed using different prognostic systems . conventional risk factors include age more than 60 years and history of previous thrombosis . in addition , other factors such as jak2 v617f mutations , cardiovascular risk factors , leukocytosis more than 11 109/l , thrombophilic factors and platelet count more than 1500 109/l are used in different hematology centers as high - risk features for thrombosis . our study compared different risk model groups for thrombosis in 185 who - defined et patients at the hospital of lithuanian university of health sciences kaunas klinikos . we found that patient distribution in low , intermediate- and high - risk groups varies using different risk stratification models . the biggest difference in risk assignment is evident in patients who are older than 60 years and have no other risk factors and in patients who are younger than 60 years but have other risk factors.this observation suggests that new prospective randomized clinical trials are needed to better stratify patients at risk for thrombosis .

fine needle aspiration ( fna ) of salivary gland represents one of the most challenging areas of cytopathology due to a wide variety of reactive and neoplastic lesions . pathologically , salivary gland tumors have been described as one of the most heterogeneous groups of human tumors . there is marked cytomorphologic diversity and overlap between benign , malignant , and metastatic tumors . a 45-year - old male complained of bloody discharge from the right ear with progressive weakness of the right side of the face since 2 months ( right facial nerve palsy ) . on examination , a diffuse , firm swelling measuring 4 3 cm was present in right retroauricular region since 1 year which was fixed to the underlying occipital bone . another swelling was present in the infraauricular region since 3 months measuring 2 1 cm which was well - defined , globular , soft to firm , with glistening red surface . ultrasonography ( usg ) of the neck showed a well - defined mass in posterior auricular region , eroding the mastoid bone , and a possibility of malignancy was given . contrast enhanced computed tomography ( cect ) of the head and neck showed similar mass in right temporooccipital region with both extra and intracranial extension . cytological smears from both the swellings were stained with giemsa and papanicolaou stains and showed similar morphology . smears were highly cellular with cells arranged in large flat sheets , three - dimensional papillae , and cohesive clusters [ figure 1a , inset ] . at places , cells were round - to - oval showing mild - to - moderate nuclear pleomorphism , low nuclear cytoplasmic ratio , eccentric nucleus , prominent nucleolus , and granular abundant cytoplasm [ figure 1a ] . cytology smears ( a , inset ) cells arranged in three - dimensional papillaroid cohesive clusters ( giemsa 200 ) , ( a ) apocrine - like cells ( pap stain 200 ) , tissue sections ( b , inset ) tumor cells arranged in solid - cystic , glandular , cribriform , and infiltrative patterns ( h and e 100 ) , ( b ) lumen of the cysts showed mucin and muciphages ( h and e 400 ) in view of the normal salivary gland on usg , absence of normal salivary gland tissue on smears and presence of pleomorphic round cells arranged in papillae and adenoid pattern with bony and cranial extension , a possibility of metastasis from epithelial malignancy ( adenocarcinoma ) was reported on cytology . magnetic resonance imaging ( mri ) of the brain , reported later , showed lytic destruction of the right occipitotemporal bone with intracranial component . another lesion was seen in the auricular region , which was inseparable from the deep lobe of the right parotid gland . however , the infraauricular swelling that was adherent to the underlying deeper structures was not excised . the tumor was hard , vascular , extradural , adhered to dura , and involved the temporal bone . subsequently , a single soft - to - hard tissue mass measuring 9 6 3 cm was received . sections stained with hematoxylin and eosin ( h and e ) showed a partly encapsulated tumor with cells arranged in solid - cystic , glandular , and cribriform patterns [ figure 1b inset ] . the cysts were lined by single - to - multilayered ( 23 cells ) apocrine - like cells and lumen showed mucin and muciphages [ figure 1b ] . these cells had abundant eosinophilic granular cytoplasm , eccentric nucleus , vesicular chromatin , and prominent nucleolus . the following differentials were considered : salivary duct carcinoma , oncocytic carcinoma , low grade cribriform cystadenocarcinoma , mucoepidermoid carcinoma , and metastatic adenocarcinoma . mucicarmine and an immunohistochemistry ( ihc ) panel comprising of cytokeratin ( ck ) 7 , ck20 , panck , epithelial membrane antigen ( ema ) , thyroid transcription factor ( ttf-1 ) , her2/neu , s100 , smooth muscle actin ( sma ) , carcinoembryonic antigen ( cea ) , and p63 were performed . ck7 and ema were positive [ figure 2a and b ] whereas the rest of the markers were negative . ihc ( a ) ck7 ( 40 ) , ( b ) ema ( 100 ) in view of the presence of cysts lined by multilayered cells along with cribriform pattern , possibility of oncocytic carcinoma was excluded . possibility of metastasis was excluded on the basis of immunonegativity for ck20 , cea , and ttf-1 . low grade cribriform cystadenocarcinoma was excluded because cysts were multilayered with apocrine - like cells and markers like s-100 and sma were negative . a final diagnosis of salivary duct carcinoma was given and the patient was referred for radiotherapy . salivary duct carcinoma is a distinctive primary neoplasm of salivary gland , which was first described by kleinsasser et al . in 1968 . it is a rare tumor with an estimated incidence of 13% of all malignant salivary gland tumors . three - fourth of the patients are males , with peak incidence in sixth to seventh decade . this tumor is considered to be high grade , with mortality up to 70% . in the present case , facial palsy and lymph node metastasis were present , however , the patient was relatively young . histomorphologically , this tumor shows similarities with intraductal cribriform and comedocarcinoma of the female breast , thus , known as salivary duct carcinoma . the cellular yield varies from low to high , depending on the degree of desmoplasia and necrosis . the cells are arranged singly in loosely cohesive groups , three - dimensional clusters , flat sheets , papillae , and cribriform pattern . on account of its apocrine features and high nuclear grade , if cribriform groups are noted in a salivary gland aspirate , the diagnosis of salivary duct carcinoma should at least be considered . however , in the present case , cribriform pattern was not noted cytologically . the absence of cribriform or papillary groups suggests an inconclusive diagnosis and the need to establish a differential diagnosis with other salivary gland tumors , in particular with adenocarcinoma not otherwise specified and high - grade mucoepidermoid carcinoma . despite the fact that the histomorphologic features are always necessary for its characterization , treatment modalities are nonconsensual , however , some authors advocate the necessity of aggressive approach . to conclude , the preoperative diagnosis of this type of neoplasm may warrant a more extensive radiological work - up . at present , fna has gained wide acceptance as a first line procedure in the evaluation of salivary gland mass lesions .

salivary gland cytopathology is a diagnostically challenging area with overlapping cytomorphological features between benign , malignant , and metastatic tumors . we report the case of 45-year - old male who presented with two swellings in right retroauricular and infraauricular region along with a palpable single right cervical lymph node . on ultrasonography of the neck , a possibility of malignant lesion was given . contrast enhanced computed tomography of the head showed a large well - defined space occupying lesion in right temporooccipital region eroding the skull bone with both extra and intracranial extension . fine needle aspiration was performed from both swellings and cervical lymph node . based on cytological features and clinicoradiological examination , a possibility of metastasis from epithelial malignancy ( adenocarcinoma ) was suggested . the retroauricular region swelling was excised , and a diagnosis of salivary duct carcinoma was given on histopathology . in this article , we discuss the diverse presentation , cytomorphological features , and differential diagnosis of this rare salivary gland tumor .

the trigeminal autonomic cephalalgias ( tacs ) are a group of headache disorders characterized by the cardinal combination of short - lasting pain and autonomic phenomena affecting the head . there is considerable overlap in the features of these entities , with individual defining characteristics predominantly relating to temporal factors and response or lack thereof to indomethacin . [ 13 ] rarely there have been reports of dissociation of the pain and autonomic symptoms / signs most such reports describe autonomic symptoms / signs without the pain , and not the reverse [ 46 ] . herein is described a case of pain without autonomic phenomena , with temporal features that are not entirely typical of any of the heretofore described tacs . to the author s knowledge , this is the first such case reported . he would have only a single occasional such episode until 2002 when they increased in frequency to a few times a week , then around 2004 they increased to daily , generally once a day , occasionally twice a day , and rarely 3 times a day , but never more than 3 times a day . when they were only occasional they would last up to 7 h. however , when the frequency increased , they changed in duration to 2030 min , occurring at any time of day , only rarely awakening him from sleep , with 60% occurring in mid - morning . the pain was described as like a screwdriver twisting invariably in the left orbit or temporal region , 8/10 in severity , with no associated aura , nausea , vomiting , photophobia , phonophobia , rhinorrhea , forehead or other facial sweating , nasal congestion , eyelid ptosis or edema , anisocoria , lacrimation or conjunctival injection . he would sit down and rub his eye during an episode ( this would not help ) . he was unaware of any triggers , including etoh , napping , neck movements or manual pressure on the neck . he had never been prescribed any medication or oxygen for these , having taken only otc s , which did not help . he had had a ct scan of the head 2 years previously , which he reported as having been unrevealing . he returned on 26th february 2007 , indicating that since the second day of taking indomethacin 25 tid he had not had a single episode , and he had continued on this dose , but wanted to switch to the slow release formulation . he returned on 24th october 2007 , indicating that a 75 mg dose taken every 36 h essentially completely prevented the episodes . upon telephone follow - up on 27th december 2007 , this same dosing schedule of indomethacin was continuing to completely control the episodes . during this conversation , he denied any ear pain or redness associated with the episodes , and also denied any associated unusual , non - pain symptoms whatsoever . this case is atypical in a number of aspects , most notably the complete absence of any autonomic symptoms or signs , therefore not meeting criterion c of the ichd - ii definition of paroxysmal hemicrania , which it most closely resembles . the temporal pattern , occurring in single episodes lasting up to 7 h each , only occasionally , for many years before increasing in frequency is atypical as well . the condition does meet criteria a , b , e and f , namely , regarding the total number of attacks , severity and location of pain ( including unilaterality ) , duration of attacks , complete prevention of attacks by indomethacin and lack of other cause . however , with a maximum of 3 episodes per day ( and this occurring only rarely , with the usual frequency being 1 episode per day ) , the condition does not meet criterion d . nor does it meet criteria for the other two tacs , ch or sunct . boes et al . reported a case of chronic paroxysmal hemicrania that presented with pain location restricted to one ear , and no typical autonomic symptoms or signs . however , this patient did experience associated ipsilateral ear redness and probable edema , therefore , she did have autonomic signs , albeit atypical ones . pareja reported partial attacks of chronic paroxysmal hemicrania with autonomic phenomena but mild or no pain however , this dissociation is the opposite of our patient s presentation furthermore this dissociation of symptoms occurred in his patient only after a course of indomethacin , possibly as a withdrawal type of phenomenon . bingel and weiller reported a case of indomethacin - responsive paroxysmal hemicrania without autonomic phenomena , with typical temporal characteristics . however , this was episodic and not chronic paroxysmal hemicrania , and also presented with bilateral rather than unilateral pain . ekbom and nappi each reported a small percentage of their cluster headache populations having no autonomic symptoms however , these patients were apparently otherwise typical cluster cases . assuming that the autonomic phenomena associated with the tacs are a result of the trigeminal - autonomic reflex , one might surmise the existence of a functional or anatomical disruption of this putative pathway in this patient . a literature search turned up no reports in this regard perhaps functional brain imaging will ultimately clarify the nature of cases like the abovementioned . in conclusion , a patient is described who demonstrates a syndrome with all the features of typical chronic paroxysmal hemicrania except for the frequency of episodes ( typically 1/day , maximum 3/day ) and with no associated autonomic phenomena whatsoever .

the trigeminal autonomic cephalalgias ( tacs ) are characterized by the cardinal combination of short - lasting unilateral pain and autonomic phenomena affecting the head , including cluster headache , paroxysmal hemicrania and sunct . infrequently reported have been cases with dissociation of these two cardinal features- usually with autonomic phenomena without pain , rather than the reverse . herein is described the case of a 56-year - old man presenting with an unusual form of tac resembling chronic paroxysmal hemicrania but with a lower frequency of occurrence , with temporal features not typical of previously described tacs , and consisting of severe unilateral head pain without any autonomic symptoms or signs , absolutely responsive to indomethacin

recent studies of individuals with bipolar disorder suggest that np impairment is prevalent , and intermediate in severity between patients with schizophrenia and healthy comparison participants . np impairments , particularly deficits in attention , processing speed , episodic memory , and executive functions ( eg , set - shifting , complex problem - solving ) , are thought to persist during euthymic states between episodes ( table i ) . hiv infection is characterized by an acute , often febrile , phase lasting days or weeks , a prolonged medically asymptomatic period , and a symptomatic phase of multisystem disease caused by immunosupression . hiv is also known to cause neuropsychological ( np ) impairments , particularly in the areas of attention / working memory , motor coordination , processing speed , learning , and attention ( table i ) . np impairment tends to worsen with disease severity , with the greatest np impairments observed among individuals with aids . hiv enters the central nervous system soon after infection , and mild cognitive impairment has been observed in approximately 30% of medically asymptomatic hivinfected patients , whereas some form of np impairment is observed in over 50% of individuals in later - stage hiv disease . although antiretroviral treatments have greatly improved the longevity and quality of life for persons living with hiv infection , the prevalence of hiv - associated neurocognitive disorders ( hand ) has not declined . persons with bipolar disorder and individuals with hiv are at increased risk for both alcohol and other substance abuse and dependence the np impairments associated with various drugs of abuse differ ; however , most illicit substances and alcohol , when used in significant quantities or over a substantial period of time , are likely to produce measurable neurocognitive deficits that may persist for extended periods , even after abstinence is achieved . here , we focus on the neuropsychological difficulties associated with methamphetamine use disorders because : ( i ) its use is on the rise in the united states ; ( ii ) cognitive impairments are common and substantial among abusers ; and ( iii ) it is the most frequently abused substance , aside from marijuana and alcohol , worldwide . a recent review and meta - analysis showed that methamphetamine abuse or dependence resulted in neuropsychological impairments of medium effect size in the domains of episodic memory , executive functioning , information processing speed , motor skills , language , and visuoconstructive abilities . the cognitive domains with the largest effect sizes are listed in table i. furthermore , evidence suggests that when methamphetamine abuse or dependence is combined with hiv infection , there is additive neuropsychological impairment : we recently began prospective research studies in order to understand better the neuropsychological and everyday functioning ( eg , medication adherence ) difficulties among persons with bipolar disorder and hiv infection . although these studies are ongoing and final results are not available , we show some of the descriptive data ( table ii ) for a group of hiv - positive ( hiv+ ) bipolar disorder ( bd ) participants ( hiv+/bd+ ) as compared with hiv+ persons without bipolar disorder ( hiv+/bd- ) . prospective bipolar participants were recruited for participation if they reported a previous diagnosis of bipolar disorder and were currently taking medications to treat their bipolar disorder and hiv infection . a diagnosis of bipolar i or it was assigned by administering the gold standard psychodiagnostic assessment ( structured clinical interview for dsm - iv ) ; alcohol and substance abuse and dependence diagnoses were determined via the composite international diagnostic interview . no other restrictions were placed on recruitment . demographically similar ( eg , age , education , ethnicity , sex , socioeconomic status ) hiv+ comparison participants were recruited if they were taking a medication to treat their hiv illness . demographic , psychiatric , and substance dependence information from these two groups are presented ( table ii ) . by design , participants were similar in terms of demographic characteristics including age , education , ethnicity , and sex . twelve of the participants had a diagnosis of bipolar i , and an additional 3 participants had a diagnosis of bipolar ii . half ( 9/18 ) of the participants in the hiv+ group without bipolar disorder met criteria for a lifetime diagnosis of major depressive disorder ( mdd ) ; however , only 11% ( 2/18 ) met criteria for a current depressive episode . twenty - seven percent ( 4/15 ) of participants in the bipolar group met criteria for a current depressive episode and an equivalent amount ( 27% ; 4/15 ) met criteria for a current manic episode ( 2 manic episodes , 1 hypomanic episode , 1 extreme irritability episode ) . also as anticipated , participants in the bipolar group tended to take a greater number of psychotropic medications ; 93% ( 14/15 ) in bipolar group were taking more than one psychotropic medication as compared with 33% ( 6/18 ) in the group without bipolar disorder . the bipolar group also had higher scores on both the young mania rating scale and the beck depression inventory - ii , and lower scores on global assessment , of functioning . the rates of current alcohol , marijuana , and methamphetamine dependence were relatively low in both groups ; however , rates of lifetime marijuana and methamphetamine dependence were elevated among participants with bipolar disorder and hiv infection as compared with those with hiv alone , and rates of lifetime alcohol dependence were elevated in both groups ( table ii ) . when examining abuse or dependence of methamphetamine instead of focusing exclusively on dependence , 65% ( 9/15 ) of the bipolar group met criteria for lifetime methamphetamine abuse or dependence as compared with 28% ( 5/18 ) in the group without bipolar disorder . detailed neuropsychological test results arc pending larger sample sizes ; however , with the cognitive impairments found in both bipolar disorder and persons with methamphetamine dependence , we anticipate significant neuropsychological impairments among our participants with both bipolar disorder and hiv infection , and possibly even greater impairments among those with bipolar disorder , hiv infection , and methamphetamine dependence . cognitive impairment , appears to be one of the strongest predictors of everyday functioning difficulties in several populations including bipolar disorder and hiv infection . medication adherence , an extremely important daily activity for persons with significant , medical or psychiatric problems , appears to be consistently related to cognitive abilities among individuals with hiv infection and persons with bipolar disorder . specific deficits in the np domains of executive functioning , attention , and memory have been shown to be associated with poor medication adherence . therefore , the convergence of risk for cognitive impairment , among persons with comorbid hiv , bd , and methamphetamine abuse or dependence may make persons with these multiple risk factors particularly susceptible to nonadherence and other everyday functioning difficulties ( figure 1 ) . persons with bipolar disorder are at risk for medical and psychiatric comorbidities , including those known to independently cause neuropsychological impairment ( eg , hiv infection , methamphetamine dependence ) . we suggest that these conditions may confer additional risk for the development of neuropsychological impairment among persons with bipolar disorder . we speculate that cognitive difficulties in bipolar hiv+ patients may impact medication adherence and other everyday functioning tasks . poor adherence to psychotropics may lead to mood destabilization , whereas inconsistent adherence to antiretroviral medications may lead to the development of treatment - resistant strains of hiv . substance abuse may further destabilize the care of these individuals and may additionally contribute to cognitive impairments . additional research is needed to better understand the neuropsychological abilities of patients with bipolar disorder and other serious comorbidities , including the extent of impairment , its features , likelihood for progression , relationship to hiv exposure , and impact on everyday functioning abilities among the multiply affected . the exact relationship between bipolar disorder and methamphetamine abuse and dependence also warrants further investigation . finally , targeted interventions for complex cases at risk for neuropsychological impairment , are needed ( see depp et al in this issue , p 239 ) ; improving medication adherence seems to be one area for intervention that , is important and attainable .

clinicians and clinical neuroscientists are aware that individuals with bipolar disorder are at greater risk for developing serious medical , psychiatric , and substance - use comorbidities as compared with the general population.1,2 less widely appreciated , however , is the observation that hiv infection appears to be more prevalent among persons with bipolar disorder and that both conditions pose significant risk for cognitive impairment.3 higher rates of hiv infection among persons with bipolar disorder should not be surprising , given that infection and transmission of hiv involves risk factors that converge with bipolar disorder ( eg , impulsivity , substance abuse ) . these factors likely also worsen adherence to treatment for both bipolar and hiv illness , and may adversely impact health - related quality of life and therapeutic outcomes . the public health consequence may be that nonadherence to antiretroviral therapy could lead to higher rates of transmission of treatment - resistant strains of hiv that can evolve with sporadic adherence . the intersection of bipolar disorder and hiv therefore merits discussion by clinicians , researchers , and policy makers .

pain , bleeding , infection , paresthesia , temporomandibular disorders , abscess formation , and dry socket have been known as common complications following extraction of impacted wisdom teeth [ 1 , 2 ] . this syndrome is characterized by severe pain in the extraction and periextraction site accompanying by blood clot lysis and halitosis . in nusair and abu younis study , 7.9% was the highest rate of dry socket syndrome that occurred in the range 1833 years old . the occurrence of this syndrome after extraction of other teeth than third molar is about 2% while the incidence of this syndrome after third molar extraction is 20% . also in haghighat study , it was concluded that there is a significant correlation between the use of oral contraceptive pills , traumatic extraction , and smoking cigarette with occurrence of postoperative dry socket syndrome . until now , different preventive and therapeutic methods have been proposed based on multifactorial and complex etiology of dry socket syndrome . some studies focused on antibiotics and antibacterial agents as an effective way in the management of dry socket syndrome . in swanson and akota et al . studies , the use of antibiotics was shown effective in the management of the syndrome . beside antibiotics , other studies concentrated on the effect of 12% chlorhexidine mouthwash , and it was declared that this agent significantly reduces the dry socket syndrome complications compared to control group . cai and lu investigated the efficacy of gelatamp colloidal silver gelatin sponge in prevention of postextraction complications and concluded that gelatamp was effective in prevention of dry socket syndrome . in keesling and keats study , zinc oxide eugenol ointment was compared with placebo , regarding the dry socket prevention , and it was shown that zoe is more effective than placebo . from different suggested methods , guaiacol , eugenol , chlorobutanol , and balsam peru mixture ( g.e.c.b ) is a new material , introduced by sultan company in the name of dentalone . this mixture is a paste , consists of 3% guaiacol , 3% eugenol , and 1.6% chlorbutanol as an effective agent and balsam peru as a base . according to therapeutic and alleviative effects of its ingredients , this paste was released by sultan chemists in the name of dry socket paste . dry socket syndrome is one of the most painful complications following impacted third molar extraction , and it can affect both patients and clinicians emotionally and financially . as there are no definite explanations for the occurrence of this syndrome and prevention of this syndrome is an important duty for clinicians , the aim of this study is to investigate the efficacy of the new form of gecb drug as pastille in management of dry socket syndrome - related complications . in this randomized clinical trial , 30 patients aged from 18 to 40 who referred to maxillofacial surgery department of isfahan university of medical sciences and diagnosed with dry socket syndrome after impacted lower third molar extraction were selected . patients with allergy to either of the dressing materials used in the study , infection in the site of tooth extraction and those who refused to participate in the study , were excluded . patients who met the inclusion criteria ( pain in the lower arch following tooth extraction which can refer to ears , exposure of alveolar bone , and empty alveolar socket ) were randomly divided into two groups . fifteen patients ( 11 males and 4 females ) undergone treatment with zoe , and fifteen patients ( 7 males and 8 females ) were treated with pastille gecb . an informed consent was signed by patients , and the study has been ethically approved by isfahan dental school ( no . gecb pastille was prepared according to official formula which has been released by sultan company and approved by fda . 3% eugenol ( merck ) , 3% guaiacol ( merck ) , and 1.6% chlorobutanol are the effective ingredients in the pastille . all mentioned ingredients were inserted in the gelatin pastille formulation containing gelatin , glycerin , and sugar . after mixing all together , molds were allowed to get cool , and then flexible pastilles were ready to use . first , patients ' pain was assessed by visual analog scale ( vas ) . in the case group , gecb pastille and in control group after pastille and zoe placement , the elapsed time for the patient 's pain to significantly relieve was recorded . patients were followed for 20 days , and the pain severity was assessed by vas , and the number of consumed pills was recorded after this period . data were analyzed by mann - withney and independent sample t - test using spss software versus 15 ( = 0.05 ) . in the present study , 30 patients with mean age of 29.87 6.00 were assessed . the mean age of patients was 28.80 5.52 and 30.93 6.64 in zoe and gecb group , respectively . the mean age of patients showed no significant difference between two groups ( p = 0.339 ) . 73% and 47% of the patients were male in zoe and gecb groups , respectively . also there was no significant difference between two groups regarding their gender ( p = 0.136 ) as illustrated in table 1 . in the present study , the severity of pain before any treatment was also assessed by vas scale in each patient . the mean score was 8.33 1.05 and 8.27 0.7 in zoe and gecb groups which showed no significant difference ( p = 0.839 ) . independent sample t - test revealed that there is a significant difference between two groups in terms of the time elapsed for the pain to significantly reveal after the treatments ( p = 0.019 ) . in the zoe and gecb groups , patients , who received zoe and gecb treatments , averagely used 0.53 0.74 and 0.07 0.26 400 mg ibuprofen pills during the follow - up period . mann - whitney test showed that there was a significant difference in the number of consumed pills between the two groups ( table 2 ) . despite the importance of the dry socket syndrome , many clinicians are not willing to discuss about a definite treatment approach toward this syndrome , as the etiology , and the treatment of this syndrome is highly controversial . until today considering the fact that the pain in dry socket syndrome will last for 1015 days regardless of the treatment method , all the suggested treatment has focused on the pain reduction [ 10 , 11 ] . some researchers believed that the use of dressing pastes , not only delivers the effective material to the involved site , but also acts as a barrier for the socket . it should be emphasized that dressing materials should not act as a hindrance for wound - healing procedure and the dressing must be replaced with socket rinsing [ 12 , 13 ] . in the present study , it is an important factor to consider , as some studies indicate that the incidence of dry socket syndrome increases with age . so to negate the effects of this factor as confounding variable , the patients were monitored regarding their age . moreover , the primary pain before treatment was not significantly different between the two groups which can not have any confounding effect on the results of the study . the pain rate in the gecb group was significantly lower , regarding its duration and the number of required pain killers . this material , for the first time , was used as cement in dentistry and also used as an adjunctive treatment for pains with pulp origin [ 17 , 18 ] . also like other phenolic combinations , guaiacol can induce cellular proliferation , and this feature limited the use of this material . as eugenol is present also in gecb pastille and the effect of gecb is superior to zoe , it can be concluded that the alleviative effect of guaiacol is more than that of eugenol . one of the major advantages of gecb over traditional zeo dressing is its convenience . as the treatment of dry socket syndrome by zoe needs dressing replacement each 3 days for 1 week , some researchers consider it as an impediment in the treatment procedure . in the present study , gecb pastille which is a mixture of medicament in gelatin and sugar this pastille is a solid , transparent material with pleasant taste , and it does not need preparation before its use . as the entire ingredients in the pastille have been approved by f.d.a , the mentioned pastille also can be approved and released in the market with different concentrations . the comparison of the present study with other studies is challenging as the pastille form of this drug was used for the first time in the treatment of dry socket syndrome . despite the conclusive results of the present study , further studies with bigger sample sizes and different concentrations of the medicament should be conducted . it can be concluded that there is a significant difference in the capacity of two different methods in pain alleviation . also because of gecb pastille convenience and its one session use with less chair time , compared to zoe , it can be an effective and reliable alternative for traditional zoe method .

background and purpose . dry socket syndrome is one of the most irritating complications after tooth extraction . this study aims to investigate the efficacy of pastille gecb compared to zoe . materials and methods . 30 patients with dry socket syndrome were selected and divided into two groups . gecb pastille was produced with 3% guaiacol , 3% eugenol 1.6% chlorobutanol , sized 3 7 10 mm . gecb was applied in one group , and zoe was used for the other group . duration of pain after treatment and painkiller intake values were recorded within 20 days . the data were analyzed with independent samples t - test , mann - whitney , and chi - square tests . results . pain persisted for 45.53 33.34 minutes in patients treated with zoe and 19.87 21.80 minutes in those treated with gecb ( p = 0.19 ) . patients in the zoe group reported more painkiller intake within 20 days ( p = 0.031 ) . conclusion . gecb showed more significant efficacy in reducing complications after tooth extraction .

colonoscopy is usually performed to identify or correct a problem in the colon and distal small bowel , and its clinical applications have increased enormously in recent years . intestinal perforation and hemorrhage are well - known complications of colonoscopy , but the incidence of these problems is very low1 , 2 ) . the first such case was reported in 1988 by houghton and aston3 ) , and there have been only a few reports since then . fecaliths , lymphoid hyperplasia , foreign bodies and parasites can block the inner lumen , leading to increased intraluminal pressure , impaired blood flow and inflammation . a 48-year - old woman underwent colonoscopy for colorectal disease screening at a health care center . she also had a computed tomographic ( ct ) scan of the abdomen performed before the colonoscopic examination , which revealed no abnormalities except for a 76 cm multilobulated left renal cyst ( figure 1 ) . before the procedure there was no sign of inflammation around the cecum or the appendicular orifice ( figure 2 ) . she felt well after the colonoscopic examination , and she was discharged promptly after passing bowel gas . however , that evening , she felt a right lower abdominal pain that gradually intensified . four days later , she visited our outpatient department with complaints of right lower abdominal pain . her vital signs were stable with a body temperature of 37. the abdomen was slightly distended with right lower quadrant tenderness and rebound tenderness . the initial white blood cell count was 7,300 cells / mm with 5,100 neutrophils / mm ; the other blood profiles ( hemoglobin , hematocrit and the platelet count ) and tests for liver function , electrolytes and urinalysis were within normal limits . acute appendicitis was suspected , and so ultrasonography was performed for making an accurate diagnosis . the results showed a swollen appendix with pericecal fluid accumulation and inflammation of the terminal ileum and cecum ( figure 3 ) . major complications such as bleeding , colonic perforation and postpolypectomy syndrome are rare . other minor complications such as abdominal pain , nausea , vomiting , bowel spasm and mucosal tears in the lining of the colon can occur frequently1 , 2 ) . this procedure can on rare occasions lead to splenic rupture , pneumomediastinum , pneumothorax , incarcerated hernia , ileus and diverticulitis . more often , hemodynamic alterations that occur during colonoscopy may be the cause of cardiovascular and cerebrovascular sequelae1 , 2 ) . houghton and aston3 ) firstly described appendicitis as a rare complication of colonoscopy , and only 12 cases of acute appendicitis following colonoscopy have currently been reported in the english medical literature ( table 1)3 - 9 ) . vender , et al.5 ) reported on three cases that occurred at two institutions where a total of about 8000 colonoscopic examinations were performed . therefore , the incidence of appendicitis following colonoscopy was about 0.038% . this is lower than the incidence of bleeding ( 0.21% ) , colonic perforation ( 0.1% ) or abdominal pain ( 0.09%)2 ) after colonoscopy . because abdominal pain after colonoscopy is generally caused by retained gas or colonic spasm secondary to colonoscopy2 ) , it is not easy to suspect acute appendicitis as the cause of this pain . it is also important to distinguish appendicitis from post - polypectomy syndrome , which is a combination of pain , peritoneal irritation , leukocytosis and fever after colonoscopy7 , 8) . among the 12 reported cases , there were eight men and four women with a mean age of 53.5 years ( range : 24 - 69 ) . this high mean age may be because colonoscopy is generally performed on patients during their fifth and sixth decades . most patients commonly present with right lower abdominal or suprapubic pain , with or without fever and chilling . one unusual case revealed only abdominal pain and distension with ileus10 ) . in nine patients , these symptoms developed between several hours and two days after colonoscopic examination , but the symptoms occurred after two days in the other three patients . four of the ten patients underwent surgery four days after the development of symptoms , and three showed a perforated appendix , which suggests that a delayed diagnosis may increase the likelihood of perforation . acute appendicitis is thought to be mainly caused by luminal obstruction , like the so called barium appendicitis after a barium enema , and this can occur by obstruction of the appendiceal orifice via the retention of barium11 , 12 ) . the suggested mechanisms of appendicitis after colonoscopy are 1 ) pre - existing subclinical disease of the appendix5 ) , 2 ) elevation of the intraluminal pressure with insufflated air can obstruct the luminal orifice by lengthening the appendix , 3 ) elevated intraluminal pressure can force bowel contents , and especially fecaliths , into the appendix6 ) , 4 ) direct intubation of the colonoscope into the appendiceal lumen can induce inflammation5 ) and 5 ) mucosal injury around the appendiceal orifice can cause local edema and obstruction of the appendiceal lumen10 ) . seven of the reported cases suggested the importance of the procedure 's duration because therapeutic procedures such as polypectomy and hemostasis are lengthy . the second and third mechanisms described above may be the causes in our case . in conclusion , appendicitis is a very rare but important complication of colonoscopy and this can be easily confused with other complications of the procedure . prompt recognition of this complication can lead to early , effective treatment , and delayed diagnosis can lead to serious results . therefore , clinicians should always keep the possibility of this complication in mind as the cause of abdominal pain after performing colonoscopic examination .

a 48-year - old woman who was without any abnormal past medical history underwent colonoscopy as a screening procedure for colorectal disease . the procedure was uneventful and there was no sign of inflammation around the appendicular orifice or the luminal surface of the cecum . the patient did not complain of pain or significant discomfort throughout the procedure . she then developed pain in the right lower quadrant of the abdomen that evening and this persisted for four days . she visited the outpatient department and underwent abdominal ultrasonography , which showed a swollen appendix with a collection of pericecal fluid . surgical exploration and appendectomy were performed ; the final diagnosis was acute suppurative appendicitis . colonoscopists should be aware of this rare complication and consider it when making the differential diagnosis of post - colonoscopy abdominal pain .

thrombolysis with recombinant tissue plasminogen activator ( rtpa , alteplase ) is the only effective specific treatment for acute ischemic stroke patients coming in window ( 4.5 h from onset of symptoms ) . a milestone study of national institute of neurological disorders and stroke in 1995 , demonstrated the benefits of rtpa in to patients of acute ischemic stroke ( ais ) who came within window period . these patients of ais who were thrombolysed were 30% more likely to survive with minimal disability resulting in a 12% absolute increase in the proportion having excellent functional outcomes at 3 months . stroke study iii trail ( 2008 ) window period was extended to 4.5 h. for every 15 min reduction in door to needle time ( dtnt ) there is 5% reduction in odds of in hospital mortality ( odd ratio , 0.95 ; 95% confidence interval , 0.92 - 0.98 : p = 0.0007 ) . all patients who presented with stroke to emergency department ( er ) from january 2011 to december 2013 were included in the study . after initial assessment by causality personnel a medical / neuro - resident evaluated the patient . radiological diagnosis was obtained with noncontrasted brain computed tomography and/or diffusion weighted magnetic resonance imaging ( dwi ) . after neuro physician opinion or after telephonic discussion by neuro - resident with neuro physician ( telestroke ) the treatment plan was decided . for the patients who presented within window period thrombolysis was planned . severity of stroke was documented by the national institutes of health stroke scale ( nihss ) contra - indications for thrombolysis were checked and consent of relatives / patient was taken . those patients who presented out of window period ( > 4.5 h after onset of symptom / symptom to door time [ std ] > 4.5 h ) , or patients who had hemorrhagic stroke and those who were not willing for giving consent were excluded [ figure 1 ] . algorithm for patient presenting with stroke in emergency room ( protocol used in the study ) patients record files and charts were used to extract retrospective data . the collected data use to evaluate er to needle [ door to needle time-(dtnt ) ] time and reasons for delay in thrombolysis therapy in acute stroke patients . the following parameters were studied onset of symptoms to er time , assessment by physician / medical chief resident time ( door to physician time [ dtpt])er to imaging time ( door to imaging time [ dtit]),er to needle time ( dtnt)contraindications for thrombolysis . onset of symptoms to er time , assessment by physician / medical chief resident time ( door to physician time [ dtpt ] ) er to imaging time ( door to imaging time [ dtit ] ) , er to needle time ( dtnt ) contraindications for thrombolysis . the onset of symptom time for patients with wake up was accepted as last time the patient was seen as healthy . the baseline characteristics of patient with acute ischemic stroke brought / admitted to er , clinical features , arrival time ( door time ) to er , severity of stroke , imaging time , radiological findings , contraindication for thrombolytic treatment , time of starting recombinant tissue plasminogen activator ( rt - pa ) and thereafter complications were recorded [ table 2 ] . the data abstracted were transferred to the spss 17.0 program ( spss statistics is a software package used for statistical analysis . it is statistical package for social science and is produced by spss inc . ) of the computer for statistical analysis . six hundred and ninety - five patients with symptoms of stroke were presented to our emergency department in the study period . out of these five hundred and forty seven ( 78.7% ) were excluded as they had come out of window period that is , they had arrived 4.5 h after the onset of stroke symptoms . algorithm for patient presenting with stroke in er ( protocol used in the study ) . further after imaging of these one hundred and forty eight patients , one hundred four ( 70.27% ) were excluded . sixty - two ( 59.6% ) had intra cerebral bleed , 1 ( 0.9% ) had hemoglobin - 3.1 g , 13 ( 13% ) of them had transient ischemic attack ( neurological symptoms improved ) and dwi images of these patient were normal . 6 ( 5.7 ) patients were diagnosed to have metabolic de - rrangement ( hypoglycemia , hyperglycemia , hyponatremia ) . other reasons for exclusion in our study were post - ictal status , financial problem , recent thrombolysis , recent surgery , and delay in contacting senior radiologist [ table 1 ] . distribution of contraindications for thrombolytic therapy of patients baseline clinical characteristics of thrombolysed patients ( n=44 ) total 44 ( 29.7% ) patients with ais were thrombolysed . thirty - four ( 79.5% ) were male and nine ( 20.45% ) were female . co - morbid illness in the form of hypertension 6 ( 13.6% ) , diabetes 2 ( 4.5% ) , ischemic heart diseases ( ihd ) 2 ( 4.5% ) , previous stroke cva 3 ( 6.5% ) , > 1 co - morbidity ( ht / cva / dm / ihd / hypothyriod ) 19 ( 43% ) , seizure 1 ( 2% ) and alcoholic liver diseases 1 ( 2% ) patients respectively . the mean time for arrival of patients from onset of symptoms to hospital ( std ) 1.23 h ( 15 min-3 h ) . the mean door to neuro - physician time dtpt was 32 min ( 5 min-2.23 h ) . the mean dtnt 1.44 h ( 40 min-3.3 h ) [ tables 3 and 4 ] , [ figures 24 ] . our study dtpt , dtit and dtnt compared with aha guideline interval number of patients thrombolysed per hour door to physician time door to imaging time ( recommended standard time : 45 min ) analysis of our study clearly states that stdt , dtpt , dtit , and dtnt time are significantly more . thus , we had many hurdles in delivering thrombolysis therapy to these 44 patients . only 7 ( 15% ) patients had dtnt 60 min . the problems / barriers in our study were categorized into three factors : mean symptom to door time was 83 min ( median : 69 ) . poor recognition of stroke signs , especially in older patients caused delay in arrival time to hospital . public and emergency medical services staff education play important role in shortening the pre hospital period . in our study - door to physician , door to imaging and door to needle time were significantly ore compared to standard recommendations ( aha ) [ table 3 ] . there was lack of handling stroke patients with high priority at each level er , imaging unit , stroke unit . thus lack of triaging stroke patient at all level of intervention was our weakest point . in one of the patients the on call doctor was very busy attending emergency calls so causing increase in dtpt time . the concept of having second on call doctor who takes care only of patients with acute stroke has being recommended by kobayashi et al . lack of triaging at radiology unit and performing entire sequences of magnetic resonance imaging ( mri ) scan lead to increase in dtit . thus again dwi has high sensitivity ( 88 - 100% ) and specificity ( 95 - 100% ) for detecting infarcted regions , within minutes of onset of symptoms . study suggested brain attack team mri sequence of < 10 min to confirm acute ischemia stroke and assess candidacy for iv - rtpa . lack of triaging of bed for stroke patients resulted in increase in dtnt time . to prevent these delay we started thrombolysing ais patient in er . to prevent delay due to inavailability of drug , we have started keeping rtpa in our drug stock our dtnt was 104 min ( door to needle time median - 100 ) . relatives with geriatric patient ( 79 years ) took longer time to give consent due to age of the patient and secondly due to financial burden . one of our patients had liver diseases so we had to wait for international normal ratio report for prothrombin time ( international normalized ratio ) . transient ischemic attack patients were not thrombolysed , but in latter half of study dwi images helped us to prevent delay . poor recognition of stroke signs , especially in older patients caused delay in arrival time to hospital . public and emergency medical services staff education play important role in shortening the pre hospital period . in our study - door to physician , door to imaging and door to needle time were significantly ore compared to standard recommendations ( aha ) [ table 3 ] . there was lack of handling stroke patients with high priority at each level er , imaging unit , stroke unit . thus lack of triaging stroke patient at all level of intervention was our weakest point . education of emergency medical services of stroke symptoms will help to triage stroke patient . in one of the patients the on call doctor was very busy attending emergency calls so causing increase in dtpt time . the concept of having second on call doctor who takes care only of patients with acute stroke has being recommended by kobayashi et al . lack of triaging at radiology unit and performing entire sequences of magnetic resonance imaging ( mri ) scan lead to increase in dtit . thus again dwi has high sensitivity ( 88 - 100% ) and specificity ( 95 - 100% ) for detecting infarcted regions , within minutes of onset of symptoms . study suggested brain attack team mri sequence of < 10 min to confirm acute ischemia stroke and assess candidacy for iv - rtpa . lack of triaging of bed for stroke patients resulted in increase in dtnt time . to prevent these delay we started thrombolysing ais patient in er . to prevent delay due to inavailability of drug , we have started keeping rtpa in our drug stock our dtnt was 104 min ( door to needle time median - 100 ) . relatives with geriatric patient ( 79 years ) took longer time to give consent due to age of the patient and secondly due to financial burden . one of our patients had liver diseases so we had to wait for international normal ratio report for prothrombin time ( international normalized ratio ) . transient ischemic attack patients were not thrombolysed , but in latter half of study dwi images helped us to prevent delay . poor recognition of stroke signs , especially in older patients caused delay in arrival time to hospital . public and emergency medical services staff education play important role in shortening the pre hospital period . in our study - door to physician , door to imaging and door to needle time were significantly ore compared to standard recommendations ( aha ) [ table 3 ] . there was lack of handling stroke patients with high priority at each level er , imaging unit , stroke unit . thus lack of triaging stroke patient at all level of intervention was our weakest point . education of emergency medical services of stroke symptoms will help to triage stroke patient . in one of the patients the on call doctor was very busy attending emergency calls so causing increase in dtpt time . the concept of having second on call doctor who takes care only of patients with acute stroke has being recommended by kobayashi et al . lack of triaging at radiology unit and performing entire sequences of magnetic resonance imaging ( mri ) scan lead to increase in dtit . thus again dwi has high sensitivity ( 88 - 100% ) and specificity ( 95 - 100% ) for detecting infarcted regions , within minutes of onset of symptoms . study suggested brain attack team mri sequence of < 10 min to confirm acute ischemia stroke and assess candidacy for iv - rtpa . lack of triaging of bed for stroke patients resulted in increase in dtnt time . to prevent these delay we started thrombolysing ais patient in er . to prevent delay due to inavailability of drug our dtnt was 104 min ( door to needle time median - 100 ) . patient with raised blood pressure requiring labetalol infusion caused delay . relatives with geriatric patient ( 79 years ) took longer time to give consent due to age of the patient and secondly due to financial burden . one of our patients had liver diseases so we had to wait for international normal ratio report for prothrombin time ( international normalized ratio ) . transient ischemic attack patients were not thrombolysed , but in latter half of study dwi images helped us to prevent delay . the barriers of thrombolysis in our study included : lack of public awareness and inaccessiblity to emergency medical serviceslack of prioritizing triage system at er , radiology unit and stroke unitlack of a multi - disciplinary stroke care team . lack of public awareness and inaccessiblity to emergency medical services lack of prioritizing triage system at er , radiology unit and stroke unit lack of a multi - disciplinary stroke care team . a multi - disciplinary stroke care team consists of well - established emergency medical services , physicians , neurologist , nurses , radiology staff , neuro - radiologist , and pharmacist . forming a one - call comprehensive stroke code will help in co - ordination at all level . time to time audit of quality indicator of stroke code team may help to overcome the factors for delay in dtnt .

aim:(1 ) to evaluate the number of patients thrombolysed within 1 h of arrival to emergency room ( er ) ( 2 ) to identify reasons for delay in thrombolysis of acute stroke patients.materials and methods : all patients admitted to er with symptoms suggestive of stroke from january 2011 to november 2013 were studied . retrospective data were collected to evaluate er to needle ( door to needle time [ dtnt ] ) time and reasons for delay in thrombolysis . the parameters studied ( 1 ) onset of symptoms to er time , ( 2 ) er to imaging time ( door to imaging time [ dtit ] ) , ( 4 ) er to needle time ( door to needle ) and ( 5 ) contraindications for thrombolysis.results:a total of 695 patients with suspected stroke were admitted during study period . 547 ( 78% ) patients were out of window period . 148 patients ( 21% , m = 104 , f = 44 ) arrived within window period ( < 4.5 h. ) . 104 ( 70.27% ) were contraindicated for thrombolysis . majority were intracerebral bleeds . 44 ( 29.7% ) were eligible for thrombolysis . 7 ( 15.9% ) were thrombolysed within 1 h. the mean time for arrival of patients from onset of symptoms to hospital ( symptom to door ) 83 min ( median - 47 ) . the mean door to neuro - physician time ( dtpt ) was 32 min ( median - 15 min ) . the mean dtit was 58 min ( median - 50 min ) . the mean dtnt 104 ( median - 100 min).conclusion : reasons for delay in thrombolysis are : absence of stroke education program for common people . lack of priority for triage and imaging for stroke patients .

postpartum depression with symptoms such as anxiety , depressed mood , forgetfulness , and irritability is similar to depression in other periods of life , but its incidence is three times more in the first 5 weeks after delivery . postpartum depression has serious consequences on the quality of life of the mothers and their children . it can also seriously affect the quality of the relationship between the mother and her newborn baby as well as damage the emotional , cognitive , motor , and behavioral development of the growing baby . according to several studies conducted in iran , some factors such as socioeconomic factors , maternal age , education and sex of the infant , previous history of depression , occupation , and number of children were reported to be effective in the development of postpartum depression . sleep patterns and sleep deprivation are other potential factors which can be associate with postpartum depression . delivery has physical , physiological , and psychological effects on women 's sleep , also taking care of a newborn with irregular sleep patterns will result in sleep disturbances during the postpartum period and women in the postpartum period experience high levels of sleep disturbances , especially in the first three postpartum months . on the other hand , insufficient and disrupted sleep affects memory , decision - making , psychomotor , and mood . depression may lead to disturbed sleep while sleep disorder can also be an independent risk factor for depression . the association between sleep status and depression may result from a neurological or psychological function which is similar in both cases . the previous studies showed sleep quality was associated with postpartum depression . because of the high prevalence of depression in this region and their serious side effects of this disorder and the limited number of studies which have been done on relation with sleep quality , we aimed to investigate the association between postpartum depression and sleep quality to add cross - cultural understandings of prenatal sleep and mental health . this was a cross - sectional study that was performed on a representative sample of 360 delivered women attending thirty health - care centers in ardabil , iran in 2012 . we included subjects who had delivered in the last 3 months and had a live birth . delivered women with the previous history of self - reported depression and other psychiatric disorders were excluded from the study . participants were selected based on a systematic random sampling method . after preparing the list of eligible individuals in each health - care center , the sampling starts by selecting a recorded number from the list at random and then , every fourth recorded number in the frame was selected . required data were collected from participants through their medical records such as age , education , type of delivery , the interval of the previous delivery , occupation , sex of the infant , birth order , physical activity , height and weight before pregnancy . other information collected from the questionnaires including the standard pittsburgh sleep quality index ( psqi ) , food frequency questionnaire ( ffq ) , and edinburgh postnatal depression questionnaire ( epds ) . the questionnaire is consisted of nine questions , and the fifth question contains 10-items . on the whole , the questions contain 18-items which can be classified into seven components which asses the seven aspects of sleep during the last 1 month of pregnancy including sleep quality , sleep onset latency , sleep duration , sleep efficiency , sleep disturbances , use of sleeping medication , and daytime dysfunction . each component has a score range of 03 and the total score scale varies from 0 to 21 . the sensitivity and specificity of the questionnaire have been reported as 98.7% and 84.4% , respectively . for calculation of energy intake , a 106-item willett - format dish - based semi - quantitative ffq that was specifically designed for the iranian adults was used to assess usual dietary intakes of study subjects throughout their pregnancy . it is a 10-item self - report scale , with four response categories for each item , ranging from a score of 0 ( no presence of the symptom ) to 3 ( marked presence or change ) . the questionnaire has a sensitivity of 78% , specificity of 75% , and reliability of 0.79 . after the selection of the sample from the list of eligible women , subjects were called by trained staff from the health - care centers and then , the objectives of the study were explained to them in detail . we explained to the participants that there is no obligation to participate in the study . the present study was approved by the ethics committee of isfahan university of medical sciences , isfahan , iran ( research number 392078 ) . spss software ( version 18 , pasw statistics for windows , chicago : spss inc . the student 's t - test was used to determine statistical differences in continuous variables between the two groups ( depressed and nondepressed also qualified and nonqualified sleep ) . the nonparametric mann categorical variables were examined using chi - square test and finally to examine the association of sleep quality with postpartum depression ( as a binomial independent variable ) , we applied the logistic regression model controlling for age , physical activity , education , house owner , body mass index ( bmi ) , sex of the infant , child order , delivery type , and total energy . p values were two - tailed and < 0.05 was taken as a significance level . this was a cross - sectional study that was performed on a representative sample of 360 delivered women attending thirty health - care centers in ardabil , iran in 2012 . we included subjects who had delivered in the last 3 months and had a live birth . delivered women with the previous history of self - reported depression and other psychiatric disorders were excluded from the study . participants were selected based on a systematic random sampling method . after preparing the list of eligible individuals in each health - care center , the sampling starts by selecting a recorded number from the list at random and then , every fourth recorded number in the frame was selected . required data were collected from participants through their medical records such as age , education , type of delivery , the interval of the previous delivery , occupation , sex of the infant , birth order , physical activity , height and weight before pregnancy . other information collected from the questionnaires including the standard pittsburgh sleep quality index ( psqi ) , food frequency questionnaire ( ffq ) , and edinburgh postnatal depression questionnaire ( epds ) . the questionnaire is consisted of nine questions , and the fifth question contains 10-items . on the whole , the questions contain 18-items which can be classified into seven components which asses the seven aspects of sleep during the last 1 month of pregnancy including sleep quality , sleep onset latency , sleep duration , sleep efficiency , sleep disturbances , use of sleeping medication , and daytime dysfunction . each component has a score range of 03 and the total score scale varies from 0 to 21 . the sensitivity and specificity of the questionnaire have been reported as 98.7% and 84.4% , respectively . for calculation of energy intake , a 106-item willett - format dish - based semi - quantitative ffq that was specifically designed for the iranian adults was used to assess usual dietary intakes of study subjects throughout their pregnancy . it is a 10-item self - report scale , with four response categories for each item , ranging from a score of 0 ( no presence of the symptom ) to 3 ( marked presence or change ) . the questionnaire has a sensitivity of 78% , specificity of 75% , and reliability of 0.79 . after the selection of the sample from the list of eligible women , subjects were called by trained staff from the health - care centers and then , the objectives of the study were explained to them in detail . we explained to the participants that there is no obligation to participate in the study . the present study was approved by the ethics committee of isfahan university of medical sciences , isfahan , iran ( research number 392078 ) . spss software ( version 18 , pasw statistics for windows , chicago : spss inc . ) was used for data analysis . the student 's t - test was used to determine statistical differences in continuous variables between the two groups ( depressed and nondepressed also qualified and nonqualified sleep ) . the nonparametric mann categorical variables were examined using chi - square test and finally to examine the association of sleep quality with postpartum depression ( as a binomial independent variable ) , we applied the logistic regression model controlling for age , physical activity , education , house owner , body mass index ( bmi ) , sex of the infant , child order , delivery type , and total energy . p values were two - tailed and < 0.05 was taken as a significance level . a total of 360 participants were enrolled , one participant did not complete the epds questionnaire , and seven subjects did not complete the psqi questionnaire . in 359 participants who filled out the epds , 125 ( 34.8% ) subject had epds score 13 or more and was considered as depressed subjects . demographic characteristic and other variables the association between the components of sleep quality and postpartum depression is shown in table 1 . there were significant associations between postpartum depression and sleep onset latency ( p > 0.001 ) , sleep quality ( p > 0.001 ) , sleep disturbances ( p > 0.001 ) , use of sleeping medication ( p = 0.019 ) , and daytime dysfunction ( p > 0.001 ) . there were no significant associations between postpartum depression and other components such as sleep duration and sleep efficiency . frequency ( % ) distribution and meanstandard deviation of characteristics postpartum women based on depression and sleep quality , ardebil , iran in 2012 of the 353 participants those who had filled out the psqi , 187 ( 53.1% ) scored more than five that is indicative of poor sleep quality . demographic characteristic and other variables were compared between those who have low sleep quality and good sleep quality [ table 1 ] . in the crude model and after controlling for covariates such as age , physical activity , education , owner of house , and bmi , we found a statistically significant association between postpartum depression and sleep quality based on the model 1 ( odds ratio [ or ] = 3.302 ; 95% confidence interval [ ci ] : 2.0625.287 ; p = 0.001 ) . it was not attenuated in the model 2 which was adjusted for covariates using in the model 1 plus sex of the infant , child order , and delivery type and also in model 3 adjusted for covariates using the model 2 plus total energy . the results confirm that the chance of depression in women suffering from low sleep quality is three times higher than in those who are not ( or = 3.34 ; 95% ci : 2.045.48 ; p = 0.001 ) [ table 2 ] . a cross - sectional population - based study showed sleep disturbances and poor subjective sleep quality was associated with depression in postpartum . findings of cohort study on 156 pregnant women in iran showed that the quality of sleep in weeks between the 28 and 38 week of pregnancy was significantly associated with postpartum depression . the cohort study that was applied on 51 nondepressed women with a history of postpartum major depression showed a significant association between sleep quality in late pregnancy and raped recurrence of depression in postpartum period . a prospective study on 273 women reported a significant correlation between sleep quality and depression during pregnancy . these studies have shown findings which are consistent with the results of the present study . low sleep quality can lead to depression , and depression can also lead to low sleep quality . the relationship between depression and sleep quality could be related to the various psychoneuroimmunologic and psychoneuroendocrinologic mechanisms . a major strength of this study is its potential to add to cross - cultural understandings of perinatal sleep and mental health . one of the limitations of the present study was the use of self - report questionnaires ( epds ) instead of using interviewers with the subjects by psychologists . other limitations of the study are factors such as unplanned pregnancy and also taking supplements such as folic acid which were prescribed by health center employees or physicians that could also have an impact on postpartum depression but were not included in the study . the prevalence of both postpartum depression and low sleep quality were relatively high in our study population . mrm contributed in the conception of the work , conducting the study , analysis and interpretation of data for the work , revising the draft , approval of the final version of the manuscript , and agreedfor all aspects of the work.si contributed in the design of the work , conducting the study , analysis of data for the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work.grk contributed in the conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work.mh contributed in the design of the work , analysis of data for the work revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work.ae contributed in the conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . mrm contributed in the conception of the work , conducting the study , analysis and interpretation of data for the work , revising the draft , approval of the final version of the manuscript , and agreedfor all aspects of the work . si contributed in the design of the work , conducting the study , analysis of data for the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . grk contributed in the conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . mh contributed in the design of the work , analysis of data for the work revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . ae contributed in the conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work .

background : the objective of this study was an investigation of the association between depression and sleep quality.materials and methods : this cross - sectional study was performed on 360 delivered women that referred to thirty health - care centers in ardabil , iran . the standard pittsburgh sleep quality index questionnaire was used to the investigation of sleep quality . we used the edinburgh postnatal depression questionnaire to assess postpartum depression . logistic regression was used to examine the association of sleep quality with postpartum depression.results:chance of depression in women with poor sleep quality was 3.34 times higher than those with good sleep quality ( odds ratio = 3.34 ; 95% confidence interval : 2.045.48 ; p < 0.001 ) . after controlling for some risk factors , an association observed between sleep quality and depression in postpartum women.conclusion:we found an association between sleep quality in women who had given birth in the last 3 months and symptoms of postpartum depression .

it is very important and significant for doctors to determine the status of vascular - related diseases such as thrombosis and arteriosclerosis and to precisely visualize the three - dimensional ( 3d ) structure of the vasculature before surgery [ 13 ] . in dental fields , understanding the 3d structure of the vasculature is necessary and important for surgical operations on tumors and cysts . the most precise evaluation technique is conventional angiography ( cr ) using contrast medium . in cr , if the treatment should be applied for the status of vessels , the technique was continuously followed by the interventional radiology such as the embolization of arteries with arteriosclerosis . therefore , the cr is a firm position for elucidating the status of vascular - related disease such as thrombosis and arteriosclerosis , and precisely visualization of 3d vasculatures at the preoperations . however , the risk of a new focal neurological deficit caused by cr is about 0.14% ~ 0.5% , and this risk rises to 1.3% ~ 2.6% in patients investigated for stroke and transient ischemic attacks . therefore , it is important to identify the 3d structure of the vasculature of the arterial and venous systems as noninvasively as possible . to determine the 3d structure of the vasculature as noninvasively as possible , ultrasonography ( us ) is easy to use clinically . furthermore , the 3d structure of the vasculature can not be visualized using computed tomography ( ct ) without contrast medium . of course , ct angiography ( cta ) using contrast medium was a very useful tool for the 3d structure of the vasculature . however , the risk of complications in cta should be higher because of iodine contrast medium . recent advances in magnetic resonance imaging ( mri ) , 3d data acquisition , and postprocessing technologies are expanding the potential applications of 3d displays [ 516 ] . as a noninvasive technique , magnetic resonance angiography ( mra ) has been developed to identify and characterize peripheral blood vessels located in the thoracic and abdominal regions and the lower extremity [ 1722 ] . of course , mra is very useful to visualize the 3d structure of the vasculature in the oral and maxillofacial regions , and it is clinically significant for evaluating the relationship between lesions and vessels in the oral region [ 14 , 16 , 2326 ] . general dentists should know and easily understand the clinical applications of mra in the oral and maxillofacial regions . therefore , the present paper provides a clear and easily understandable explanation of mra , the method , and its characteristics , as well as its clinical applications and characteristics , for general dentists . mra commonly uses a bright - blood method , in which the signal from the moving protons is accentuated relative to the stationary protons through pulse sequences and measurement parameters . in fact , mra is a technique using vessel flow or contrast agents such as gadolinium to detect vessel systems such as arteries and veins . therefore , mra has the least complication and is the easiest technique for 3d visualization of vessels , unlike cr using contrast medium such as iodine - related medium . at the same time , this technique is very useful for identifying vascular diseases and abnormalities , as well as the relationships between diseases and surrounding vessels . the various techniques of mra include mr sequences such as time of flight ( tof ) , phase contrast ( pc ) , fresh blood imaging ( fbi ) , and contrast - enhanced mra [ 511 , 13 , 15 , 16 , 2737 ] . mra using tof ( tof - mra ) is the most time - efficient method for obtaining mra images . a single measurement is performed , with the stationary tissue signal suppressed relative to the flowing tissue signal . mra using pc ( pc - mra ) is a technique in which the background tissue signal is subtracted from the flow - enhanced image to produce flow - only images , analogous to digital subtraction x - ray angiography . mra as a new technique using fbi that has been applied to the 3d evaluation of vasculature [ 811 , 13 , 15 , 16 , 3437 ] . fbi , which uses 3d half - fourier fast advanced spin echo ( fase)-triggered mr with electrocardiographic ( ecg ) gating , is one of the newest non - enhanced - mra techniques [ 811 , 13 , 15 , 16 , 3437 ] . contrast - enhanced mra makes good use of the contrast agent , which affects the relaxation times of the water protons in the nearby tissue . in mra with contrast medium , as disadvantages , intravenous injection should be applied such as cr , and gadolinium could induce many kinds of complications including nephrogenic fibrosing dermopathy . mra without contrast medium has no complications and no need of intravenous injections , and its technique can easily and additionally apply for many patients in whom vascular information should be evaluated . in the present paper , the focus is on three techniques ( tof , pc , and particularly fbi ) as the main mra techniques without contrast medium that are useful in the oral and maxillofacial regions . on tof- or pc - mra , arteries and veins which are to some degree slow appear as bright homogeneous linear structures and stationary tissues except vessels with flow which appear for the most part blurred(figure 1 ) . therefore , vessels with flow can be primarily visualized on mra with these two techniques ( figure 1 ) . on the other hand , vessels without flow can not be visualized at all using mra with tof and pc techniques . of the two techniques in use for patients , pc - mra is better for demonstrating slow - flowing blood vessels ( < 10 cm / s ) , owing primarily to an optimized velocity - encoding gradient ( venc ) and perhaps also to smaller saturation effects and better background suppression . this sequence offers a better examination of the external carotid system than tof - mra . though the main carotid artery and its branches can be visualized on pc - mra , tof - mra can visualize the main carotid artery , but not its branches ( figure 1 ) . in addition , 3d - pc - mra has a better signal - to - noise ratio and a better spatial resolution than 2d - pc - mra ( figure 2 ) . therefore , in the oral and maxillofacial regions , 3d - pc - mra routinely tends to be selected for additional and preoperative vascular evaluations in mr examinations . however , in the oral and maxillofacial regions , the vasculature is complex , with blood flow rates varying from high in the carotid arteries to low in the lingual arteries . thus , 3d visualization of the vasculature in these regions is very difficult to obtain even using 3d - pc - mra . therefore , in very recent reports , mra using fbi ( fbi - mra ) was used for the 3d evaluation of the vasculature in the oral and maxillofacial regions [ 10 , 16 , 23 ] . most prior studies using fbi primarily examined the main vessels of the chest , abdomen , and lower extremities [ 9 , 11 , 13 , 15 , 3437 ] . in previous reports , 3d - fbi - mra could provide better 3d visualization of the vasculature of thin blood vessels , including the lingual and facial arteries , than 3d - pc - mra ( figure 3 ) . the axes of the lingual and facial arteries are under 2 - 3 mm . 3d - fbi - mra permits the depiction of slow - flowing blood vessels by acquiring the images with ecg triggering during the slow - flow cardiac phase . 3d - fbi - mra can depict slow - flowing vessels due to the t2 effects , so that even relatively static blood vessels can be depicted on images , unlike imaging with 3d - pc - mra . therefore , 3d - fbi - mra can even visualize vessels with very slow flow that can not be visualized on 3d - pc - mra [ 7 , 9 , 13 , 16 ] . in addition , the depiction level of thick blood vessels such as external and internal carotid arteries using 3d - fbi is the same as that using 3d - pc - mra . in other word , peripheral small arteries look well visualized on 3d - fbi - mra compared to 3d - pc - mra , but not for large arteries . carotid , maxillary , facial , and lingual arteries can be more precisely visualized on 3d - fbi - mra without contrast medium than on 3d - pc - mra ( figure 3 ) . at the same time , the internal jugular , maxillary , facial , and lingual veins can also be better visualized on 3d - fbi - mra without contrast medium than on 3d - pc - mra ( figure 3 ) . 3d - tof- or pc - mra depicts only blood vessels , but not mass lesions such as hemangiomas ( figure 4 ) [ 16 , 23 ] . therefore , the 3d relationship between the mass lesions such as hemangiomas and surrounding blood vessels should be visualized by fusing fat - saturation t2-weighted images with 3d - pc - mra . by doing so , hemangiomas and surrounding vessels can be visualized on the fusion images ( figure 4 ) . the software to allow superimposition of both 3d - pc - mra and t2-weighted images is integral to the mr system . however , image resolution degradation is a disadvantage of fusion imaging ( figure 4 ) . deterioration of the contrast - to - noise and signal - to - noise ratios on superimposed views occurs because noise on the respective images is doubled without increasing the signal intensity of the tumor and vessels . in addition , production of the superimposed view might be unsuccessful if the patient should move in the time gap between capture of the respective images . on the other hand , both hemangiomas and thin blood vessels around tumors can be clearly visualized on 3d - fbi - mra without fusion of mra with tumor images ( figure 5 ) . the carotid arteries , internal jugular veins , lingual arteries , lingual veins , facial arteries , facial veins , maxillary arteries , and maxillary veins can be seen as bright homogeneous linear structures ( figure 5 ) . at the same time , hemangiomas are clearly visualized as masses with high signal intensity ( figure 5 ) . except for the carotid arteries , 3d - fbi - mra is better than 3d - pc - mra based on visual scores despite the short acquisition time . artifacts from patient movement and shortened acquisition times reduce image quality more with 3d - pc - mra than with 3d - fbi . another advantage of 3d - fbi - mra is that one can distinguish between arteries and veins without the use of contrast medium [ 811 , 13 , 15 , 16 , 23 , 3437 ] . the blood vessels depicted on 3d - fbi - mra are most of the arteries , including the carotid , maxillary , facial , lingual , and other arteries ( figure 6 ) . flow - spoiled gradient pulses do not affect the signal intensity of stationary background tissues . veins are similarly less affected by the flow - spoiled pulse during diastole and systole as a result of their relatively constant slow flow throughout the cardiac cycle . by applying the flow - spoiled pulses , thus , diastolic and systolic subtraction provides better delineation of the arteries . however , except for 3d - fbi , the distinction between arteries and veins has not been possible with mra sequences such as 3d - tof and 3d - pc without contrast medium so far . it is hoped that 3d - fbi - mra will be a significant , epoch - making technique . however , there are some potential disadvantages with 3d - fbi - mra for clinical applications in the oral and maxillofacial regions [ 16 , 3437 ] . the first is that the selection of the appropriate flow - spoiled gradient is important for determining the image quality of hemangiomas and surrounding vessels . even a slight mistake affects the visualization of branch arteries , such as the maxillary and lingual arteries [ 16 , 23 ] . to select the appropriate flow - spoiled gradient pulses is very difficult for operators , because blood vessels in the oral and maxillofacial regions have a wide range of flow rates , from high to static . therefore , the images tend to be degraded in patients with movements of the mandible and tongue . moreover , the third disadvantage is that patients with arrhythmias or tachycardias are not suitable candidates for fbi examinations , because ecg triggering is used . mra can not perfectly replace cr for examinations of vascular - related diseases and suspected hemangiomas in the oral and maxillofacial regions . that is why mra can not have more contrast between vessels and tissues except vessels and can not be more precisely visualized than cr . however , performing mra for diseases in the oral and maxillofacial regions should be recommended in addition to common mr examinations before cr . in particular , 3d - fbi - mra is relatively easy to perform and can precisely visualize thin vessels except a little difficulty of parameters setting . therefore , examinations using 3d - fbi - mra are very useful and important for preoperative evaluations for various kinds of diseases , in particular the 3d relationship between the vasculature and diseases . higher spatial resolution gadolinium - mra can be achieved at 3 tesla with a sustained or greater signal - to - noise ratio of enhanced vasculature , relative to 1.5 tesla . therefore , mra with higher resolution in the oral and maxillofacial regions can be achieved with a 3-tesla mr system . very recently , it has been found that existing mra is suboptimal for assessing the hemodynamics of arteriovenous malformations [ 4250 ] . as a completely noninvasive method , 4d dynamic mra offers hemodynamic information with a temporal resolution of 50100 ms for the evaluation of arteriovenous malformations and can complement existing methods , such as dynamic subtraction analysis and tof mra [ 4246 ] . therefore , the evaluation of hemodynamics in hemangiomas will be performed by mra in the oral and maxillofacial regions in the future .

the present paper provides general dentists with an introduction to the clinical applications and significance of magnetic resonance angiography ( mra ) in the oral and maxillofacial regions . specifically , the method and characteristics of mra are first explained using the relevant mr sequences . next , clinical applications to the oral and maxillofacial regions , such as identification of hemangiomas and surrounding vessels by mra , are discussed . moreover , the clinical significance of mra for other regions is presented to elucidate future clinical applications of mra in the oral and maxillofacial regions .

laparoscopic and thoracoscopic surgery have gradually become an accepted diagnostic and therapeutic modality in the treatment of pediatric trauma . in the hands of experienced surgeons and in appropriate situations , minimally invasive surgery ( mis ) has helped to eliminate the need for open procedures . physical examination can often be challenging and unreliable in the pediatric population . in children with equivocal laboratory or imaging findings , laparoscopy and thoracoscopy are better methods for establishing a diagnosis without the sequela of open surgery . one of the advantages of mis is that it avoids extensive open procedures that produce negative findings or identify injuries that do not require repair ( nontherapeutic ) . more important , mis leads to less pain , quicker recovery time , shorter hospital stays , and decreased financial burden . the purpose of this study was to review our institution 's experience in using mis as a first - choice modality in managing cases of pediatric trauma over the past 2 decades . a retrospective study reviewing the past 20 years was performed at the maria fareri children 's hospital of westchester medical center , a tertiary care center with an american college of surgeons level 1 pediatric trauma designation . after institutional review board approval was obtained , a list was compiled of all pediatric patients ( age range , 015 years ) who had sustained traumatic abdominal or thoracic injuries that required intervention . data included the age and sex of the patient , type and mechanism of injury , initial laboratory and imaging findings , and method of intervention ( mis vs open ) . the peritoneal cavity was accessed via an infraumbilical port . in cases of abdominal stab wounds , one of the wounds was used for initial port entry . in patients with prior abdominal or laparoscopic surgery , a fourth 5-mm port can be placed in the right side of the abdomen , if necessary . the liver and spleen are carefully inspected , and the stomach , duodenum , and diaphragms are evaluated . the whole intestine is inspected , from the ligament of treitz to the ileocecal valve , including the colon and rectum . it is important to evaluate the mesentery to rule out bleeding or mesenteric tear , which can cause internal hernia . blood and clots must be evacuated , to facilitate a thorough evaluation of some of the involved areas . the surgeon must be aware that some areas , such as the third and fourth portions of the duodenum , the pancreas , and the retroperitoneum , are difficult to evaluate . the peritoneal cavity was accessed via an infraumbilical port . in cases of abdominal stab wounds , one of the wounds was used for initial port entry . in patients with prior abdominal or laparoscopic surgery a fourth 5-mm port can be placed in the right side of the abdomen , if necessary . the liver and spleen are carefully inspected , and the stomach , duodenum , and diaphragms are evaluated . the whole intestine is inspected , from the ligament of treitz to the ileocecal valve , including the colon and rectum . it is important to evaluate the mesentery to rule out bleeding or mesenteric tear , which can cause internal hernia . blood and clots must be evacuated , to facilitate a thorough evaluation of some of the involved areas . the surgeon must be aware that some areas , such as the third and fourth portions of the duodenum , the pancreas , and the retroperitoneum , are difficult to evaluate . twenty - three patients were treated by mis at the maria fareri children 's hospital between 1994 and 2014 . there were 17 boys and 6 girls ( mean age , 9.3 4.47 years ) . the majority of the injuries ( 78% ) were caused by blunt mechanisms ; there were 5 ( 22% ) penetrating injuries . these frequencies are a reflection of the type of trauma that occurs in our catchment area . all patients , with the exception of those with stab wound trauma , underwent radiological imaging before they were taken to the operating room . positive findings on computed tomographic ( ct ) scans included hemoperitoneum ( figure 1 ) or pneumoperitoneum , active extravasation of contrast , and the presence of free fluid . twenty - one patients underwent diagnostic laparoscopy and 2 patients had diagnostic thoracoscopy ; 16 of 21 ( 76% ) diagnostic laparoscopies and 2 of 2 ( 100% ) diagnostic thoracoscopies had positive findings . the various types of injuries included bowel perforation ( figure 2 ) , abdominal wall defect , diaphragmatic laceration , intra - abdominal hematoma , mesenteric tear , lung laceration , and pancreatic injury . after positive findings on diagnostic laparoscopy , 6 ( 37.5% ) patients had laparoscopic repair , and the remaining 10 ( 62.5% ) underwent conversion to open repair . after diagnostic thoracoscopy ( n = 2 ) , 1 patient underwent thoracoscopic repair , and 1 had conversion to open repair . open repairs were also performed on bowel perforations , mesenteric tears , and abdominal wall defects detected on diagnostic laparoscopy ( figure 3 ) . results of the case review among the 5 negative diagnostic laparoscopies , there was 1 missed injury during the initial laparoscopy . the patient was a 12-year - old boy who was involved in a bicycle accident with a handlebar injury and was found to have a hemoperitoneum in the subhepatic and paracolic gutters on ct scan . after a negative diagnostic laparoscopy , a follow - up upper gastrointestinal ( gi ) series demonstrated contrast leak in the third portion of the duodenum . the duodenal injury was suspected during laparoscopy ; a decision was made not to convert to laparotomy but to continue careful observation and further imaging if clinically indicated . the length of stay in the hospital ranged from 1 to 55 days ( mean , 12.8 d 15.1 ) . after discharge from the hospital , follow - up outpatient visits were scheduled from 2 weeks up to 1 year . three complications were identified during the follow - up visits . a 13-month - old girl who was she was initially treated conservatively with abdominal washout and drain placement . however , over the next few months , the patient had persistent pancreatitis . at 10 months after the surgery , the patient was brought back to the hospital for a laparoscopic distal pancreatectomy . in our institution , the initial management of pancreatic injuries is conservative , unless the patient is clinically unstable . another case involved a 9-year - old boy who underwent conversion to open repair for a jejunal perforation and developed a wound infection at the incision site 2 weeks after the operation . last , a 5-year - old boy who sustained severe rectal injuries had perineal and rectal laceration with avulsion of the rectum and anus off of the pelvis . because of the severity of his injury , he was treated with a transverse colostomy . at his 3-month follow - up , severe stenosis of the rectum the paradigm for treatment of pediatric trauma is rapidly changing , as surgeons become more comfortable and competent in minimally invasive surgery . our institution 's experience over the past 20 years parallels the current literature in pediatric trauma . laparoscopic surgery in pediatric abdominal trauma has been shown to reduce negative and nontherapeutic laparotomy rates by 40% to 60% . in our study , 4 of 21 ( 19% ) one of the most common fears about the use of mis in pediatric trauma is the possibility of missing an injury that might have been found by laparotomy . however , the current literature has estimated missed injuries by diagnostic laparoscopy to be close to 0% in pediatric trauma . of the 21 diagnostic laparoscopies for trauma performed at our institution , we had 1 missed duodenal perforation on initial laparoscopy . although the duodenal injury was missed during laparoscopy , visualization of the duodenum raised enough suspicion of the injury to warrant careful follow - up and further imaging to exclude a duodenal injury . the outcome in this patient was excellent , and other injuries were excluded by laparoscopy . in addition to its diagnostic capabilities , mis therapeutic interventions are possible in up to 65% of cases without conversion to an open procedure . definitive repair using only mis techniques the management of solid - organ injury in pediatric patients continues to be mainly nonoperative . patients who were underwent mis repair stayed in the hospital for a mean of 7 1.9 days . for patients who required open repair , the difference in hospital stay between the two groups was not statistically significant ( p = .18 ) , most likely because of the great variability among our patients . patients who needed open repair may have presented with more critical injuries and hemodynamic instability . the use of laparoscopy and thoracoscopy in pediatric trauma can avoid unnecessary laparotomy and thoracotomy . if conversion is necessary , the use of these techniques can guide the placement and size of surgical incisions . we recommend that laparoscopy and thoracoscopy be the primary intervention in hemodynamically stable pediatric patients with traumatic injury , when clinically indicated .

background : minimally invasive surgery ( mis ) for trauma in pediatric cases remains controversial . recent studies have shown the validity of using minimally invasive techniques to decrease the rate of negative and nontherapeutic laparotomy and thoracotomy . the purpose of this study was to evaluate the diagnostic accuracy and therapeutic options of mis in pediatric trauma at a level i pediatric trauma center.methods:we reviewed cases of patients aged 15 years and younger who had undergone laparoscopy or thoracoscopy for trauma in our institution over the past 20 years . each case was evaluated for mechanism of injury , computed tomographic ( ct ) scan findings , operative management , and patient outcomes.results:there were 23 patients in the study ( 16 boys and 7 girls ) . twenty - one had undergone diagnostic laparoscopy and 2 had had diagnostic thoracoscopy . in 16 , there were positive findings in diagnostic laparoscopy . laparoscopic therapeutic interventions were performed in 6 patients ; the remaining 10 required conversion to laparotomy . both patients who underwent diagnostic thoracoscopy had positive findings . one had a thoracoscopic repair , and the other underwent conversion to thoracotomy . there were 5 negative diagnostic laparoscopies . there was no mortality among the 23 patients.conclusions:the use of laparoscopy and thoracoscopy in pediatric trauma helps to reduce unnecessary laparotomy and thoracotomy . some injuries can be repaired by a minimally invasive approach . when conversion is necessary , the use of these techniques can guide the placement and size of surgical incisions . the goal is to shift the paradigm in favor of using mis in the treatment of pediatric trauma as the first - choice modality in stable patients .

seven - transmembrane receptors are a family of signaling proteins that bind hormones , autacoids , and neurotransmitters to mediate a myriad of cellular functions . like all proteins , these exist in collections of tertiary conformations called protein ensembles ; receptors sample these conformations according to changes in the thermal energy in the system . some of these conformations can be designated as active states , denoting their ability to activate cytosolic signaling mechanisms . the current model of pharmacological seven - transmembrane receptor agonism describes the selective binding of agonists to these active states to enrich their presence within the ensemble through a process referred to as conformational selection . thus , through le chatelier s principle , upon agonist binding , the make - up of the ensemble is directed toward the conformations possessing the highest affinity for the agonist and these are stabilized at the expense of other conformations . the product of this thermodynamic process is a collection of membrane proteins that activate cellular signaling processes and agonism ensues . early discussions of this mechanism and agonist efficacy in general used the most simple assumptions that the receptor is the minimal unit of control for this process and that a receptor activated by any agonist triggers all cellular signaling processes mediated by that particular receptor type . first , it was observed that seven - transmembrane receptors pleiotropically interact with a wide range of cytosolic coupling proteins . second , new technology revealed multiple biochemical behaviors of receptors such as the propensity to be phosphorylated and to interact with multiple g - proteins and -arrestin , internalization , and desensitization . subsequent studies have indicated that not all agonists uniformly produce activation of these multiple receptor behaviors . for example , the peptides pacap1 - 27 and pacap1 - 38 activate pacap ( pituitary adenylate cyclase - activating polypeptide type 1 ) receptors to elevate cyclic amp and increase production of ip3 . however , the relative potency of these agonists for these responses is reversed ; the relative efficacy of pacap1 - 27 for cyclic amp elevation is higher than that of pacap1 - 38 but lower for elevation of ip3 . this indicates that the receptor is not the minimal unit of control of agonism , it is the agonist - receptor complex that controls the ultimate signaling event ; the data leading to this conclusion also clearly indicate that agonist activation of multiple signaling mechanisms is not uniform but rather is often this concept has been put into a formal model showing that agonist - selective states can produce biased agonism . in terms of the molecular mechanism of biased agonism , two additional factors are relevant to the discussion , namely the nature of the receptor - active state and the interaction of the activated receptor with multiple cytosolic signaling proteins . the selective activation of cellular pathways with biased agonists is consistent with there being agonist - specific ensembles of receptor conformations mediating these events ; subsequent studies have given independent corroboration of this mechanism through separate lines of experimentation that directly show that ligands can stabilize unique receptor conformations [ 4 - 9 ] . similarly , molecular dynamics predicts that when proteins such as receptors change conformation , different regions of the receptor change independently ( i.e. , the protein does not form uniform global conformations ) [ 10 - 13 ] . therefore , the fact that signaling proteins interact with different regions of the receptor ( e.g. ) suggests that different conformations would not produce uniform coupling to all signaling proteins ; that is , the unique receptor conformations stabilized by agonists most likely will result in differential ( biased ) activation of cell signaling pathways . in fact , the activation of a receptor that interacts with multiple signaling components in a cell most likely will never produce equal activation of all pathways ; therefore , from this standpoint , every agonist will have a bias in signaling . however , a useful point of reference is the natural agonist for the receptor ; this will have a natural signaling bias and can be used as a standard with which other agonists can be compared . within this scale , functionally selective agonists are defined as having a signaling bias different from that of the natural agonist . studies using a wide variety of technologies now indicate that biased agonism is a common phenomenon . agonists have been shown to differentially activate different g - proteins and -arrestin and have differing susceptibility to phosphorylation , desensitization , and internalization in a wide variety of receptor systems ( for reviews , see [ 17 - 23 ] ) . in particular , many studies now specifically show how differential activation of g - proteins versus -arrestin results from biased stabilization of receptor conformation . observed most often with synthetic agonist ligands , bias can also be detected in natural systems such as the chemokine ccr7 receptor . thus , ccl19 and ccl21 , two natural agonists for the ccr7 chemokine receptor , differ in the type of pathway stimulation they elicit ; although both agonists produce g - protein activation , only ccl19 ( not ccl21 ) causes receptor agonist - dependent phosphorylation and recruitment of -arrestin to terminate the g - protein stimulus . in addition to g - proteins and -arrestin , seven - transmembrane receptors have been shown to couple to many other signaling proteins such as jak / stats ( janus kinase / signal transducers and activators of transcription ) , src - family tyrosine kinases , g - protein receptor kinases ( grks ) , and pdz domain - containing proteins . for example , different proteases have been shown to differentially activate protease - activated receptors through stabilization of distinct conformation ( much like biased ligands ) . the discovery that some ligands can produce activation of some but not all receptor - linked stimulus mechanisms can introduce ambiguity in the classification of drugs . for instance , the active internalization of receptors by some antagonists indicates that a label of similarly , while propranolol is a well - known antagonist and inverse agonist of agonist activation of gs - coupled effects of -adrenoceptors , it has also been shown to be an active activator ( agonist ) of extracellular signal - regulated kinase ( erk ) . biased agonism can be complex and need not necessarily involve excitatory signaling events ; that is , some ligands can be positive agonists for one pathway and antagonists or inverse agonists for another . pluridimensional ; that is , ligands may have a range of different efficacies to cause a range of receptor behaviors . the emphasis has clearly shifted from does biased agonism occur? to when it does occur , how can it be harnessed therapeutically? this trend is consistent with the improving technology to detect whole - cell effects through label - free technology ; these data provide cell - specific and detailed information regarding signaling patterns of ligands [ 36 - 40 ] . thus , while assay technology is making it increasingly possible to detect and characterize agonist bias , focus is shifting to the mechanisms responsible for this effect . emphasis has also shifted from the cell surface to the cytosol in an effort to understand biased signaling . for example , detailed studies of biased ligand - induced -arrestin - mediated signaling indicate significant differences in functionally distinct pools of -arrestin accessed through conformational control of receptor sensitivity to phosphorylation by grk isoforms . bar coding of ligand - bound receptors that lead to further downstream instruction of -arrestin partners within the cell . moreover , just as receptors adopt different conformations to achieve selective signaling , it has now been shown that -arrestin itself forms different conformations and that these are associated with selective functions within the cell . the significance of biased signaling is increasingly appreciated as signaling pathways become linked to normal physiology and pathophysiology . for example , the reported erk activation through -arrestin by some antagonists ( i.e. propranolol ) is interesting in light of recent data that suggest that angiotensin receptor - mediated -arrestin stimulation may be beneficial in the treatment of heart failure or , alternatively , may be linked to the progression of heart failure through aldosterone pathways . biased signaling has been implicated in a unique profile of antagonism and agonism in breast cancer . specifically , substance - p analogues sp - d and sp - g have been shown to produce biased signaling at vasopressin v1a receptors and receptors for gastrin - releasing peptide to yield a profile of blocked gq - protein - mediated calcium release and concomitant activation of erk . this is postulated to produce a unique antiproliferative profile of activity . in terms of specific examples in which bias may be a practical aspect of drug activity , there are interesting divergences in activity for opioid agonists to produce analgesia with reduced propensity to produce desensitization and -opioid receptor internalization [ 46 - 50 ] and intriguing functionally selective dopamine and serotonin agonists for the treatment of psychiatric disorders . similarly , there are data that suggest that functionally selective thyrotropin agonists may be able to differentiate thyroid growth and thyroid hormone synthesis and orexin receptor functionally selective agonists may differentiate effects on catecholamine release and adrenal steroid production . the consequences of biased agonism currently are an intense subject of study . while initial work in the field considered acute effects such as desensitization , receptor internalization , and differential activation of g - proteins , more recent studies center on long - term effects of biased signaling such as prolonged signaling through -arrestin activation and effects such as g - protein regulation . in general , it is not yet clear to what extent these biased stimulations of cellular signaling pathways will yield favorable therapeutic phenotypic agonism . what is clear is that seven - transmembrane receptors can not be considered on / off switches and synthetic agonists can not be considered surrogates of natural agonists . stabilization of receptor - active states by different molecules has the potential to traffic receptor stimulus in unique ways to cause complex patterns of cellular activation .

seven - transmembrane receptors are commonly coupled to multiple signaling pathways in cells . the simple model describing agonists for these receptors as producing a common active state to induce uniform activation of the pathways linked to the receptor has been shown to be untenable in light of a large body of data that suggest that some agonists produce activation of some but not all available pathways . these agonists are referred to as biased in that they select which signaling pathways become activated upon binding to the receptor . the data to support this mechanism as well as ideas on the possible therapeutic application of this effect will be discussed .

on january 2 , 2011 , an 8-month - old girl with acute respiratory distress was seen in the emergency department of the children s hospital of the university of cologne . the girl s parents had noticed labored breathing , intercostal retractions , and fever for 1 day . no one else who had contact with the girl was sick . at admission , the girl was lethargic and inappetent with a fever of 38.3c and oxygen saturation of 86% . the patient had submandibular lymphadenopathy and mild pharyngitis but no rash or abnormalities of the heart or abdomen . the clinical signs were typical of an upper respiratory tract infection combined with severe obstructive bronchitis . chest radiographs showed diffuse bilateral infiltrates and total atelectasis of the right upper lung lobe . blood analysis indicated partial co2 concentration within normal limits and slightly elevated c - reactive protein level ( 10 mg / l ) . electrolytes and renal and hepatic markers were within reference ranges , as was complete blood count except for thrombocytosis ( 744,000 platelets/l ) . treatment with prednisolone and inhalation therapy delivering albuterol and ipratropium by vaporizor was initiated . because of the lung atelectasis , the child received cefuroxime as prophylaxis for 2 weeks . oxygen saturation could be restored to within reference limits with nasal cannula oxygen delivery at 4 l / min . during the next 2 days , the patient s body temperature was 38.0c39.0c , and she remained lethargic . a nasopharyngeal aspirate was obtained 4 days after symptom onset and screened for respiratory viruses by real - time pcr ( 2 ) and luminex xtag rvp panel ( abbott , wiesbaden , germany ) . each assay had positive results for hbov dna and negative results for influenza a virus ; influenza a virus subtype h1n1 ; influenza b virus ; parainfluenza viruses types 14 ; adenovirus ; human metapneumovirus ; coronaviruses nl63 , hku1 , 229e , and oc43 ; respiratory syncytial virus ( rsv ) ; rhinovirus ; and enterovirus . cultures of blood collected on the day of admission , before antimicrobial drug treatment was started , were negative . a second chest radiograph showed partial atelectasis of the left upper lung lobe , a retrocardial infiltrate , and pneumomediastinum . on hospitalization day 5 , oxygen saturation could be maintained at a lower flow rate . on day 6 , chest radiograph showed regression of atelectasis in both lobes and of the pneumomediastinum . temperature dropped to subfebrile levels , and the child s general condition was improving . on day 9 , no additional oxygen was needed . on day 10 , chest radiograph showed residual atelectasis in both upper lobes and residual infiltrates in both lungs , and the patient was discharged . two weeks later , at follow - up examination , the child was doing well , breath sounds were unremarkable , and the pathologic radiographic findings had resolved completely . to verify that the disease was caused by an hbov infection , we performed a real - time pcr targeting the nonstructural protein 1 region of hbov ; we detected 5,819 copies / ml hbov dna in the patient s serum 30 days after symptom onset ( 3 ) . the pcr was conducted with primers os1 and os2 as described ( 4 ) , and an hbov subtype 2 plasmid dilution series ( kindly provided by tobias allander , karolinska institute , stockholm , sweden ) was used as a quantitative control . sequencing was performed by an external sequencing service ( eurofins mwg , munich , germany ) ; the same primers from both directions were used . sequencing and blast analysis ( http://blast.ncbi.nlm.nih.gov/blast.cgi ) confirmed the virus to be hbov1 , not hbov24 . additionally , hbov - specific igm and igg and avidity of igg were measured by sensitive and specific enzyme immunoassays ( 5,6 ) . results were clearly positive for both : igm absorbance 0.385 and cutoff 0.167 ; igg absorbance 2.971 and cutoff 0.188 . igg was of low avidity ( 4% , cutoff 15% ) , indicating acute primary hbov infection . large - scale studies showed that hbov can be detected in children with signs and symptoms of respiratory tract infection . studies have detected hbov in 9% and 19.3% of all samples , indicating that it is the second or third most commonly detected virus , after rsv and rhinovirus ( 2,10 ) . thus , the overall contribution of hbov to all detected respiratory viruses lies well below that of rsv . high prevalence does not necessarily mean high clinical relevance , and proving its causative role has been difficult because the virus is often detected along with other viruses ; co - detection rates are as high as 75% ( 11,12 ) . hbov can also persist for months in the respiratory tract after resolution of disease , further complicating diagnosis ( 12 ) , which therefore should be based on detection of hbov dna in blood and measurement of hbov - specific antibodies . hbov is the most probable cause of respiratory tract disease if the patient has a high viral load in nasopharyngeal aspirates accompanied by viremia , if hbov is the only pathogen detected , and if an acute primary hbov infection is diagnosed by serologic testing ( 5,11,13 ) . the serologic assay developed earlier was validated in a series of studies and shown to reliably measure serologic response against hbov ( 58 ) . however , the contribution of bacteria to the course of the disease can not be completely ruled out . signs and symptoms for the patient reported here have been described as the most common signs and symptoms of hbov - infected children ( 14 ) and are typical of lower respiratory tract viral infections in general . in 1 study ( 14 ) , 18 patients had an hbov single infection and 2 had lobar atelectasis , as did the patient reported here . similarly , another case report described hbov infection that resulted in pneumomediastinum ( 15 ) . the age of the patient reported here is also typical of hbov , which mostly infects children 6 months to 3 years of age , but it does not usually infect young infants , as rsv does ( 14 ) . the case reported here shows that a lower respiratory tract infection caused by hbov can lead to severe and life - threatening disease .

human bocavirus ( hbov ) , discovered in 2005 , can cause respiratory disease or no symptoms at all . we confirmed hbov infection in an 8-month - old girl with hypoxia , respiratory distress , wheezing , cough , and fever . this case demonstrates that lower respiratory tract infection caused by hbov can lead to severe and life - threatening disease .

, it was initially referred to as the nerve of pinkus . in 1905 , it became classified as terminal because , in other animal species , it was observed to extend into the region of the lamina terminalis ( delineating the anterior wall of the third ventricle and , in its lower section , before the optic chiasma , forming the optic recess).1 from an osteopathic perspective , this area can develop into a dysfunction point with regard to cranial kinetics , with different clinical presentations.2 this gives us an insight into the importance and complexity of this nerve . recent textbooks , published after 1987 , have classified cranial nerve xiii as the zero nerve , given that it is more rostral than the other cranial nerves . although first formally mentioned in a paper on human anatomy in 1945,1 it has rarely been mentioned in the medical literature since . the probable reason for this is that , during anatomical dissection , when taking off the dura mater , this nerve is torn off and can not be found on subsequent examination . however , as long as the pia mater remains intact , the nerve can be located between the olfactory stalk and the rostral section of the optic chiasma.1 the nerve is attached to the pia mater by connective tissue,1 and this concept is useful for osteopaths in order to link dysfunction of the nerve to craniosacral movement . cranial nerve xiv was first identified in 1563 , but it was not until 1777 that it was mentioned in a textbook as the nerve of wrisberg.3 in modern textbooks , it is referred to as the nervus intermedius or intermediary nerve.3 its name is consistent with its intermediary location between the facial nerve ( cranial nerve vii ) and the superior section of the vestibulocochlear nerve ( cranial nerve viii).4 it is well known to cause otalgia and related surgical operations . this confirms that this nerve is an independent entity and not a mere ramification of cranial nerve vii . anatomy is still a field rich in findings , and as regards the data collected so far , nothing can be taken for granted . there are many reference texts on anatomical dissection that demonstrate numerous variations in the human body.58 in humans , nerve n is composed of a small tract of nerves with nonmyelinated fibers . unlike the other cranial nerves , nerve n lies in the most rostral area where the brainstem and olfactory bulb are located.1 nerve n passes through the medial region of the stria olfactoria ( ie , medial in relation to the anterior perforated space ) and , via the rectus gyrus of the orbital surface of the frontal lobe , reaches the crista galli laterally . finally , it passes through the cribriform plate of the ethmoid bone more medially and deeply than do the tracts of the olfactory nerve.1,9,10 nerve n is very thin in adults but is easily identifiable in the fetal stage.1 it has a small ganglion , with other as yet unidentified afferents,1 indicating that it might have some residual function to warrant consideration in diagnosis and treatment . as demonstrated by research in other species , the nerve is linked with the olfactory nerve11 in terms of its location and probably also its function . from an embryological perspective , it seems to have developed from the area of the olfactory cells , although some have hypothesized that it may originate from the neural crest.12 in any case , it would derive from the ectoderm.13 other textbooks assume it is related to the nasopalatine nerve , either directly or through the sympathetic trunk . it is important to remember that , at the level of the nose , there is the nasopalatine nerve which innervates the nasal cavity and belongs to the maxillary section of the trigeminal nerve . at the same level there is the ethmoidal nerve , which supplies the anterior nasal mucosa , and develops from the ophthalmic division of the trigeminal nerve.14 interestingly , this nerve is connected to small blood vessels,1 meaning that it could have direct contact with the entire body . furthermore , in some animal species , nerve n supplies the retina , indicating that this nerve may be responsive to light.15 so far , there are still differing opinions about the function of this nerve . however , these are only hypotheses and suggestions , none of which is definitely based on incontrovertible evidence.16 nonetheless , speculation is possible when considering what the medical literature offers at present . according to the numerous studies carried out to date , nerve n could somehow be connected with reproductive function . in several animal species , nerve n secretes or stimulates the secretion of luteinizing hormone - releasing hormone , also known as gonadotropin - releasing hormone.1,12,17 this hormone coordinates the hypothalamus - pituitary - gonadal axis.18,19 in animals , this nerve can be located without difficulty , and its functions are more evident , ie , it is presumed to control sexual behavior and reproductive activity.2023 stimulation of nerve n is believed to trigger a series of hormonal cascades from the nasal region to the reproductive system.11,24,25 therefore , one hypothesis is that nerve n might trigger an endocrine response , directly or jointly with other nerve structures , such as the kisspeptin neural network . in humans , particularly in females , this group of neurons can be identified as being mainly in the preoptic area and in the infundibular nucleus of the mediobasal hypothalamus.26 could this mean that women may be more affected by nerve n ? we still do not know . undoubtedly , a woman s sense of smell is stronger during ovulation.1 moreover , in the human model , the area in question is a source of interest regarding sexual behavior , although there are no decisive writings on this topic.27 generally speaking , stimulation of a hormonal response in men can be linked with the nasal epithelium ( through chemosensitive receptors or unidentified bonds with pheromones).22,2830 research in humans shows that nerve n is directly connected to the limbic system , at least in the fetus , and consequently to the olfactory system.1 further studies in the human model suggest that this nerve has the ability to store small polypeptides , including luteinizing hormone - releasing hormone , acetylcholine , and neuropeptide y.1 the latter can also be found in the amygdala , with a number of functions in influencing behavior , including nociception.31 the current view is that nerve n has the ability to affect sexual behavior , but the extent to which it does this is unknown as yet . it is believed to act by stimulating luteinizing hormone - releasing hormone on contact with pheromones , improving olfaction and identifying odors , and this series of events will affect sexual behavior.1 nerve n is suggested to have afferents that originate from the sympathetic ganglia of the superior cervical tract , or from the pterygopalatine ganglion.1 undeniably , these are interesting hypotheses , but await verification . finally , the trigeminal system can be stimulated by odors.14,32 if a connection between the cervical sympathetic ganglia , the trigeminal system , and the aforementioned nerve was confirmed , we might better understand and explain some cervical disorders , such as those related to the menstrual cycle or chronic rhinitis . many other hypotheses might be formulated , but what is certain is that the human body is a sole entity . in order for the body to maintain homeostasis , each and every part needs to be in harmonious and tensegritive collaboration , with regard to not only fascial but also immunological , neuroendocrine , and psychological functioning . recent research on the olfactory system theorizes a correlation between olfactory changes and certain psychiatric and behavioral disorders , and other neurological pathologies.3335 recently , some scientific articles have been published suggesting that the olfactory sense is a survival tool and essential for enabling attention in conscious individuals.36 a possible connection between the olfactory nerve and nerve n offers further clinical scenarios . the intermediary nerve has always been considered a ramification of the facial nerve , which is complex37,38 and all its connections have not been clearly revealed as yet . however , the intermediary nerve is actually a separate and independent nervous entity.39,40 one study has demonstrated at autopsy that this nerve has four different anatomical origins : the brainstem , where it is evident as a tract of nerve fibers ; the top of cranial nerve vii ; the top of cranial nerve viii ; and finally , multiple sites in the greater area of the brainstem.39 according to this study , its ramifications are between 2 and 5 , not 4 as we have always thought.39 it comprises visceral efferents comprised of preganglionic and parasympathetic fibers , which involve the submandibular and sublingual lacrimal glands as well as minor salivary glands . it is a short nerve , measuring no more than 21 mm in length.40,41 these efferents contact the pterygopalatine ganglion and pass through the base of the pterygoid process of the sphenoid bone , then extend into the pterygoid ( vidian ) canal , finally reaching the pterygopalatine fossa and developing synaptic connections with the homonymous ganglion.40 another portion of these preganglionic and parasympathetic efferents reaches the geniculate ganglion in the middle ear through a pathway that runs in parallel with the motor component of cranial nerve vii , and finally arrives at the tympanic section and the chorda tympani nerve , which develops from the facial nerve.40,42 in contrast , the afferents of the intermediary nerve derive from receptors known as the concha auriculae located in a small area behind the ear , from the external layer of the membrana tympani , and from part of the wall of the external auditory meatus.40 moreover , some afferents develop from the taste receptors on the anterior two thirds of the tongue , from the floor of the mouth and palate , from the nasal mucosa and nasopharynx ( presumably because of the connection with the lingual nerve , a branch of the mandibular division of the trigeminal nerve ) ; and finally , from the chorda tympani nerve that branches from the facial nerve.3,40 most textbooks report that this nerve has a sensory function , yet motor efferents of this nerve have also been identified , and electrophysiological studies carried out during surgery on patients have revealed that stimulation of this nerve can result in contraction of the orbicularis oris muscle , which has four segments . this has further confirmed its separation from the facial nerve.3 from an anatomical perspective , which involves taking into consideration its direct connections with the geniculate nucleus , the pterygopalatine ganglion , and the brainstem , and from an electrophysiological point of view , the intermediary nerve is now regarded as a nervous structure in its own right.3 this prompts some interesting considerations . first , the intermediary nerve is connected indirectly to the trigeminal system.40 moreover , when it comes into contact with the chorda tympani nerve , the two nerves become one and the same , and then , passing through the petrotympanic fissure , the intermediary nerve becomes an extra cranial nerve.4,40 further research suggests that if the temporomandibular joint does not move properly for whatever reason , the pterygopalatine ganglion will be affected , and may alter the functions of the aforementioned intermediary nerve . finally , looking more closely at the intermediary nerve , there are minute anastomoses with nerves vii and viii at the level of their origin.3 a logical deduction is that disorders in any of these nerves may affect the physiology of the intermediary nerve and vice versa , which may alter their function . the recent medical literature cites the intermediary nerve in terms of the problems it may cause , although these do not occur frequently . for example , paroxysmal otalgia ( lasting seconds or minutes ) , found in combination with alterations in lacrimation , salivation , and taste perception , is known as geniculate neuralgia , neuralgia of the intermediary nerve , or tolosa - hunt syndrome.4,40,41 its causes may be different , ranging from malignancy to vascular compression , but are mainly idiopathic.3,41,43,44 finally , it is important to consider the intermediary vein,39 which is adjacent to the intermediary nerve , which may alter the electrical function of this nerve in the event of anomalous venous drainage . as osteopaths , we know that anomalous drainage of the cranial venous system may cause dysfunction in the cranial nerves.2 these data can be useful to us in order to understand and treat the symptoms mentioned in this paper . in the light of the information currently available in the medical literature , the nomenclature for the cranial nerves should be revised . further studies are needed to improve our knowledge of the clinical scenarios that may arise from physiological alteration of their function , as well as a more detailed anatomical description of medical strategies which may be helpful in treating related problems .

it has been known for over a century that these cranial nerves exist , and that they are not typographical errors nor a sensational event reported in the medical literature . a number of scientific articles on anatomy highlight how textbooks on descriptive anatomy do not always consider variables such as differences related to the geographical areas where people live , and these differences do exist . this is an important concept not only for surgeons , but also for all medical professionals who use manual techniques when treating their patients , ie , osteopaths , chiropractors , physiotherapists , and other manual therapists . this paper highlights the latest developments regarding these cranial nerves , offering at the same time some ideas for further reflection when looking at clinical scenarios that appear to bear little relationship to each other . inclusion of these concepts in everyday anamnesis is encouraged .

since the groundbreaking study by favaloro was published in 1968 , the use of the great saphenous vein for coronary artery bypass grafting ( cabg ) has become a standard in the surgical treatment of ischemic heart disease . in poland , the first surgery involving direct cardiac revascularization was conducted by jan moll as soon as 1970 . the saphenous vein remains the most frequently used material for coronary artery bypass grafting , even though numerous studies indicate that arterial revascularization is of greater benefit to the patient , especially in long - term observation . an increasing number of reports underscore the advantages of total arterial revascularization ( tar ) over revascularization using mixed veno - arterial material . in contrast to arteries used for bypass grafting , veins situated in high - pressure systems , such as the coronary circulation , often undergo accelerated degenerative changes . the pathological changes leading to adverse restructuring of the vascular autograft result in flow impairment , which may cause the development of ectasia , thrombus , critical stenoses , or even loss of patency . repeat revascularization can be conducted either by performing a percutaneous coronary intervention or by repeating the cabg procedure ; the choice of the treatment method depends on the location of the changes in the coronary arteries and bypasses , concomitant diseases , the general condition of the patient , and their preference concerning the treatment method . the decisions undertaken by the heart team with regard to post - cabg patients are particularly important . the aim of this study is to present the case of a patient operated on in 1999 due to a giant aneurysm of a venous aorto - coronary bypass presenting with symptoms of superior vena cava syndrome ( svcs ) . the 66-year - old patient was referred from the regional hospital to the cardiac surgery ward in order to undergo treatment for a giant aneurysm developed on the basis of a degenerated venous aorto - coronary bypass , causing symptoms of superior vena cava syndrome and chronic pericardial tamponade . thirteen years earlier , the patient had undergone cabg at the same ward . during the procedure , four coronary bypasses were performed : one arterial lima - lad and three venous : to the first marginal branch ( lmrg i ) , second marginal branch ( lmrg ii ) , and right coronary artery ( rca ) in the region of the posterior descending artery ( pda ) . the patient was later hospitalized twice , in 2000 and 2004 , due to increasing anginal complaints in both cases , conservative treatment resulted in the improvement of his clinical condition . the intensification of pharmacological treatment in the form of increasing doses of already used medications ( a loop diuretic and a beta - blocker ) and ( during the second hospitalization ) the introduction of new agents from other groups ( a thiazide diuretic and a sartan ) were effective enough for the patient to be referred for out - patient treatment . in june 2012 , the patient was hospitalized again at the internal diseases department of the regional hospital due to anginal complaints of significantly increased intensity . based on physical examination , laboratory tests and clinical overview acute coronary syndrome without st - segment elevation ( acs nstemi ) was diagnosed ; angiographic examinations of the coronary arteries and bypasses were conducted via femoral artery access . angiography was hindered because of intensified atherosclerosis of lower - extremity arteries , but it revealed the occlusion of the rca ( fig . 1 ) , lad , lmrg i , and lmrg ii in segments proximal to the bypasses . normal flow was visualized in the bypasses leading to the lad , lmrg i , and lmrg ii ; when a critical constriction of the circumflex artery ( cx ) was revealed , therapy with the use of a bare metal stent ( bms ) was applied . aortic branching off of the rca , visible lack of flow in the superior trunk , contrast limited to small branches the venous bypass to the right coronary artery was visualized in the form of a giant aneurysm , partially filled with contrast and situated next to the right atrium ; the aneurysm was clearly exerting pressure on the atrium ( figs . 2 and 3 ) . based on transthoracic echocardiography , the size of the mass was estimated at approximately 6 cm 6 cm . the presence of the aneurysm was confirmed by angio - ct , which revealed the presence of a hypodense lesion , modeling the right atrium ( figs . 4 and 5 ) . the presence of pulmonary embolism , suspected due to significant dyspnea reported by the patient , was excluded . angiography of the venous bypass to the rca ( lao 55.0 caud 1.9 ) : red arrows the initial segment of the bypass and the aneurysm located on its more distal segment . yellow arrow a metal ring ( marker ) placed on the bypass during the initial cabg procedure to mark the aortic opening of the bypass angiography of the venous bypass to the rca ( lao 55.0 caud 1.9 ) : red arrows the venous bypass to the rca affected by aneurysmal changes the aneurysm pressing on the superior vena cava ( red arrow ) and , partially , on the right atrium ( yellow arrow ) the aneurysm with a fragment of the degenerated venous bypass ( red arrow ) and the visualized compressed superior vena cava ( yellow arrows ) after admission , standard laboratory and imaging tests were performed . the examinations revealed that the d - dimer level was 6-fold higher than the norm ( 3.07 g / ml , laboratory norm : up to 0.5 g / ml ) ; the tests also demonstrated elevated levels of bnp ( 234 pg / ml , norm : up to 100 pg / ml ) , urea ( 7.8 mmol / l , norm : 2.3 - 6.5 mmol / l ) , and creatinine ( 120 mol / l , norm : 60 - 106 the imaging examinations revealed the following : x - ray enlarged shadow of the mediastinum , especially of the right cardiac contour ; transthoracic echocardiography the aforementioned characteristics of the discovered mass , generalized hypokinesis of the left ventricle , and a reduction in ejection fraction to approximately 20% . after the analysis of the examination results , a two - stage invasive treatment was planned . multidirectional and non - functional flow was revealed during the evaluation of the venous bypass to the rca . a balloon catheter ( invatec admiral extreme pta balloon 4.0 mm 40 mm/130 cm ) was introduced into the proximal segment of the bypass in order to prevent contrast regurgitation . next , residual blood was aspirated from the aneurysm through the catheter , and thrombin was administered ( 400 units , biotrombina 400 ) in order to inhibit flow in the non - functioning bypass and to cause maximal clotting of the blood remaining inside . angiographic control , conducted after 15 minutes , visualized an almost complete reduction of flow through the bypass affected by aneurysmal changes . a second balloon catheter was introduced ( quantum maverick monorail 5.0 mm 15 mm ) and placed in the aortic opening of the aneurysm , after which the patient was transferred to the operating room . the second stage of treatment consisted in a surgical procedure . due to the location of the lesion and the presence of three patent bypasses supplying the left coronary artery , right - sided thoracotomy ( double - lumen intubation with right lung deflation ) was selected as the access type , which enabled the visualization of the degenerated bypass . thanks to the previous treatment stage and the use of thrombin , the risk of bleeding associated with mass rupture was significantly reduced . the actual size of the largely visualized degenerated bypass was estimated at approximately 14 cm 12 cm ( fig . the chronicity of the process of mass development was , paradoxically , a favorable circumstance , as it resulted in the creation of a pseudo - sac , which separated the formation from the surrounding tissues . the total content of the removed aneurysm was assessed at approximately 600 cm . both ends of the bypass ( proximal on the aorta and distal on the heart ) were closed with pledget sutures ( 5 - 0 prolene , ethicon ) ; next , the catheter remaining in the aortic orifice of the aneurysm was removed . subsequent patient management included hemostatic control , the introduction of drains into the right pleural cavity , right lung expansion under visual control , and layered closure of the chest . the incised sac of the aneurysm of the degenerated venous bypass unfortunately , during the described actions , as the patient 's skin was being sutured , ventricular fibrillation occurred without any preceding symptoms . the patient 's chest was immediately reopened , and internal defibrillation was attempted multiple times ; these attempts also proved unsuccessful . during internal cardiac massage , which was hindered by adhesions around the heart from the initial cabg procedure , extracorporeal circulation was introduced by inserting an arterial and a venous cannula into femoral vessels . inserting the arterial cannula was hindered by the aforementioned advanced atherosclerotic changes . despite several hours of reperfusion and the fact that the bleeding associated with the internal cardiac massage was controlled , the hemodynamic stability of the patient could not be maintained , and he died on the operating table . notwithstanding , aneurysm etiology includes such factors as dyslipidemia , generalized atherosclerosis , and vessel wall fragility . the natural progress of this pathology may be asymptomatic , and its diagnosis accidental , e.g. post - mortem . the rare complication of cabg described above is diagnosed most often through non - specific medical history analysis ( previous cabg employing venous material , dyspnea , fatigability ) and physical examination revealing stasis in the veins of the upper half of the body and enlarged circumference of the face and the neck . in turn , additional examinations reveal the presence of a previously absent mediastinal mass with location typical for venous bypass . in natural disease progression , its long duration favors the occurrence of fistulas between the bypass aneurysm and the left or right atrium , pulmonary artery , or the right ventricle . in the case study described above , the cooperation between specialists in the fields of interventional cardiology and cardiac surgery was assumed immediately after reaching the final diagnosis . on its own , occluding the aneurysm with methods of interventional cardiology ( coiling ) would not reduce the size of the mass or limit all the symptoms related to its presence ( svcs ) . on the other hand , removing the degenerated bypass surgically without limiting the multidirectional arterial blood flow present within its lumen therefore , employing the approach established at the meeting of the heart team enabled the localization of the degenerated bypass as well as the visualization and reduction of blood flow through the bypass . the administration of thrombin during angiography facilitated the surgical dissection of the aneurysm and reduced the flow through its lumen to a bare minimum . in spite of employing the described methods , the procedure was unsuccessful due to massive uncontrollable cardiac rhythm disruptions in the form of ventricular fibrillation . the ultimate result of the treatment was definitely influenced by numerous factors increasing the operative risk , which included : generalized atherosclerosis involving cephalad arteries and arteries of the lower extremities , enormous hypertension in the venous system ( especially in the upper body ) , previous cabg with three bypasses remaining patent after 13 years and hindering surgical access , long - standing , though stabilized type ii diabetes , and subclinical hypofunction of the thyroid gland . in the event of a similar clinical case , extracorporeal circulation should be considered despite relative contraindications for its use in order to increase the safety of the performed procedure .

a case of a 66-year - old patient 13 years after coronary artery bypass grafting ( cabg ) admitted to hospital with typical ischemic chest pain and symptoms of superior vena cava syndrome ( svcs ) is described . non - invasive diagnostics confirmed acute coronary syndrome : non - st - elevated myocardial infarction ( acs nstemi ) . trans - thoracic echocardiography ( tte ) revealed a gigantic tumor mass modeling the right atrium , causing chronic cardiac tamponade . angiography showed that the tumor mass was in fact the aneurysmatically changed venous bypass graft to the right coronary artery ( rca ) . computed tomography angiography ( ct - angio ) confirmed venous aneurysm size ( the longest diameters were 10.2 cm 8.7 cm ) . we also present treatment planning and the aneurysmal surgical removal procedure of this very rare case .

cochrane database of systematic reviews , published by the cochrane library provides the gold standard evidence for intervention , diagnosis , etc . , the standard of systematic review is maintained by uniform criteria of the research question , selection of studies , and data analysis including interpretation . after publishing in the database , each systematic review has to be updated every 2 years to include studies if followed the inclusion and exclusion criteria . although the prevalence of tooth loss is decreasing , a large proportion of patients visiting the dentists consist of partially or completely edentulous patients . they can be used to treat a variety of patients ranging from single tooth loss to complete oral rehabilitation . dental implants have shown promising success rate and have now become a routine treatment when dealing with the replacement of teeth . however , as the use of dental implants is increasing , so is the research . around 1300 different types of dental implants are available worldwide , with their manufacturers claiming their implants to be more successful than others . the clinicians are put in a perplexing situation to decide the ideal body shape of the implant , the ideal platform design , the ideal surface of the implant or the ideal material of the implant . it is important for the clinician to understand the difference between the facts and the marketing gimmicks by various implant manufacturers . this updated cochrane review presents evidence - based guidelines regarding different types of implants and their comparison in terms of various surface preparations , different shapes , and different materials . it attends to the question whether the different surface modifications or coatings or different shapes of implants or different implant materials lead to better clinical outcomes ? the cochrane handbook for systematic reviews of interventions is used as a guide to form the methodology of this review . randomized controlled trials ( rcts ) of the parallel group and split - mouth design in participants who received osseointegrated root form dental implants with at least 1-year of follow - up were included in this review . comparison was done between identical implants placed following the same protocol , but differing only in terms of ( 1 ) surface modification or ( 2 ) implant shape or ( 3 ) implant material or ( 4 ) any combination of these . the primary outcome was described in terms of biological or mechanical failure , and the occurrence of periimplantitis was the secondary outcome . electronic search was conducted in the cochrane oral health group 's trial register , the cochrane central register of controlled trials , medline through ovid and embase via ovid ; without any language filter , until january 17 , 2014 . the titles and abstracts of the reports identified through electronic and hand search were scanned by two independent reviewers and full report to check if they met the inclusion criteria . risk ratio and 95% confidence interval ( ci ) were used to describe the measurement of treatment effect for dichotomous data and mean difference along with 95% ci was used for continuous outcomes . heterogeneity assessment and sensitivity analyses were performed as per the cochrane handbook for systematic reviews of interventions . eighty - one trials were identified in the search ; however , most of them were nonrandomized or quasi - randomized studies , and many studies had a short follow - up , or the data were presented in an unusable way . twenty - seven rcts with either parallel group design or split mouth design , which met the inclusion criteria , were included in the review [ tables 1 and 2 ] . available evidence from the included trials comparing implant surfaces and implant shapes available evidence from trials comparing different implant materials and combination critical analysis of the included trials revealed that most of the studies were at unclear risk of bias for allocation concealment and low - risk of bias for sequence generation while a considerable number of studies were at high - risk of bias for blinding . meta - analysis was performed among studies of similar comparisons reporting the same outcome measures . however , a sensitivity analyses could not be performed due to the lack of a sufficient number of trials in the meta - analyses . the severity of the risk of bias on the final results could not be assessed due to the lack of sensitivity analyses . critical analysis of the included trials revealed that most of the studies were at unclear risk of bias for allocation concealment and low - risk of bias for sequence generation while a considerable number of studies were at high - risk of bias for blinding . meta - analysis was performed among studies of similar comparisons reporting the same outcome measures . however , a sensitivity analyses could not be performed due to the lack of a sufficient number of trials in the meta - analyses . the severity of the risk of bias on the final results could not be assessed due to the lack of sensitivity analyses . based on the data from the included trials , this cochrane review failed to show any superiority of a particular implant surface , shape or material over others in terms of implant failure and bone level changes . the review found 81 trials during the search but , only 27 fulfilled the inclusion criteria which clearly indicates a lack of properly designed and reported rcts . even after an extensive review and a meta - analysis , a definitive guideline on which implant system should be chosen by the clinician could not be established . nonetheless , it did become clear from the review that clinical outcomes are not significantly altered by various modifications put forth by different manufacturers . however , a strong evidence to support this statement is still missing [ table 3 ] . the review did fulfill its secondary objective and found weak evidence that roughened dental implants are more susceptible to periimplantitis than turned implants [ tables 4 and 5 ] . turned implants compared with roughened implants turned implants compared with roughened implants - individual data a very prominent fact that came to light in the review was that only one - third of the searched trials ( 27/81 ) met the inclusion criteria . those that did meet the inclusion criteria were at unclear or high - risk of bias . the number of studies included in the meta - analysis was too low to carry out sensitivity analyses which could have been significant . moreover , the included studies were from european , australian and , east - asian countries ; while none was an indian study . many of the different implant systems that formed the intervention group in these studies are not even available in india ; while those that are available and commonly used in india were not presented in the review . this clearly indicates the need for properly designed rcts with adequate sample size , a follow - up period of at least 5 years and a low - risk of bias ; that are reported according to the consolidated standards of reporting trials guidelines . a very prominent fact that came to light in the review was that only one - third of the searched trials ( 27/81 ) met the inclusion criteria . those that did meet the inclusion criteria were at unclear or high - risk of bias . the number of studies included in the meta - analysis was too low to carry out sensitivity analyses which could have been significant . moreover , the included studies were from european , australian and , east - asian countries ; while none was an indian study . many of the different implant systems that formed the intervention group in these studies are not even available in india ; while those that are available and commonly used in india were not presented in the review . this clearly indicates the need for properly designed rcts with adequate sample size , a follow - up period of at least 5 years and a low - risk of bias ; that are reported according to the consolidated standards of reporting trials guidelines .

around 1300 different types of dental implants are available worldwide and the implant manufacturers are resorting to aggressive marketing strategies ; claiming their implants to provide a superior outcome . the clinician is left with a constant dilemma on which implant to choose for better clinical outcome and welfare of the patient . moreover , in india , economical consideration is a concern too . the dentist has to select an implant that provides a good result and is economical . cochrane systematic reviews provide the gold standard evidence for intervention , diagnosis , etc . , and follow a strict quality control . a cochrane systematic review was done to shed light on whether the different implant surface modifications , shapes or materials significantly influence clinical outcomes . all randomized controlled trials ( rcts ) till january 17 , 2014 were searched and out of the 81 trials , only 27 met the inclusion criteria . this evidence summary from the review concludes that based on the available literature ; there is no evidence of any one type of implant being superior to another . there is weak evidence showing roughened dental implants are more prone to bone loss due to periimplantitis . this review indicated that there is a need for well - designed rcts , with long - term follow - up and low bias . moreover , none of the included studies was from india , which also points out the need for improving the quality of rcts conducted in india .

a hemangioma can rarely be pedunculated ; as a result , it may undergo torsion and infarction , which can make it symptomatic . we report the case of a 45-year - old woman with acute abdominal pain due to torsion of a giant pedunculated hepatic hemangioma around its vascular stalk . pedunculated hemangioma of the liver is an uncommon benign tumor , a rare differential diagnosis for a mass located in the upper abdomen . all incidentally detected pedunculated hemangiomas must be surgically managed , as these have a tendency to become torsioned , and there is also a risk of malignancy or rupture . hemangioma is the most common benign tumor of the liver , with an autopsy prevalence of 0.4% - 20% . women are more often affected , at a ratio of 5:1 - 6:1 ( 1 , 2 ) . hemangiomas can occur at any age , are usually solitary , and are found more commonly in the right lobe , especially in the posterior segment ( 3 ) . liver hemangiomas are asymptomatic in most cases , and are commonly detected incidentally by imaging modalities such as ultrasonography , ct , or mri ( 4 ) . hepatic hemangiomas are usually < 3 cm in diameter , and those measuring > 4 cm are classified as giant ( 5 ) . giant hemangiomas can become large enough to cause symptoms due to mass effect on the abdominal viscera , abdominal pain , discomfort , hemorrhage , jaundice , and nausea ( 5 - 8 ) . exophytic forms of hepatic hemangiomas , especially pedunculated forms , are extremely rare , with only a few cases reported in the literature ( 9 , 10 ) . this case study is a report of a patient with a giant pedunculated hepatic hemangioma , who was referred to the emergency ward with acute abdominal pain due to torsion of the hemangioma around its vascular stalk . a 45-year - old woman with acute abdominal pain presented to the emergency ward of a private general hospital in babol , northern iran , on may 4 , 2015 . her pain had originated in the epigastrium and had an incremental trend for two days prior to her admission . she had also experienced nausea , vomiting , and loss of appetite during that time . the patient had a history of chronic abdominal discomfort and upper gastrointestinal bleeding ( ugib ) due to gastritis . she also reported that she had taken oral contraceptive pills ( ocps ) for approximately 5 years , many years earlier . on examination , her vital signs were all normal : blood pressure 125/75 mmhg , pulse rate 78 beats / min , respiratory rate 18 breaths / min , and oral temperature 37.3c . there was a mild generalized tenderness , as well as severe tenderness in the upper part of the abdomen , prominently the epigastrium , but there was no rebound tenderness or guarding . complete blood count , basic metabolic profile , coagulation tests , and liver function tests were all within normal limits . there were no abnormal findings on the upright chest film and abdominal x - ray . ultrasonography revealed a 92 42 72 mm solid ovoid mass with exophytic features , originating from the anterior border of the left lobe of the liver . abdominopelvic ct scan with contrast media demonstrated a 100 64 mm lobulated oval mass showing central necrosis in the anterior aspect of the abdomen , suggesting a mesenteric mass lesion , such as gastrointestinal stromal tumor ( gist ) , as the first differential diagnosis . due to her past history of ugib , she underwent esophagogastroduodenoscopy by a gastroenterologist , and no mass or ulcer was observed . however , there was mass effect , most probably gastric compression due to an extragastric mass lesion , with a remote possibility of a submucosal lesion . , she had a low - grade fever and decreased hemoglobin ( from 10 to 8.3 g / dl ) . according to the clinical and paraclinical findings , the unknown etiology of the mass , the possibility of malignancy , and the risks of bleeding and hemoperitoneum , we decided to perform surgical management . in the operating room , under general anesthesia ( ga ) and with full monitoring in the supine position , a large , multilobulated , dark red mass was discovered attached to the anterior edge of the left lobe of the liver by a vascular pedicle . macroscopically , it measured 10.5 8.8 7 cm and weighed 316 g. the histopathological analysis confirmed a huge pedunculated hepatic hemangioma , with marked vascular congestion and focal hemorrhagic infarct , with no evidence of atypia . she was discharged from the hospital three days after surgery ( figures 1 - 3 ) . cavernous hemangioma is the most common benign tumor of the liver , probably with a congenital origin , and there is no potential for malignant transformation ( 1 ) . it predominates in females 5:1 to 6:1 , and is most common from age 30 to 50 years . it is usually discovered incidentally on imaging modalities such as ultrasonography , ct , and mri ( 2 ) . these tumors can measure from a few millimeters up to 20 cm in size , and are commonly classified as giant if they measure > 4 cm in diameter ( 1 ) . a pedunculated hemangioma can extend beyond the border of the liver ( 2 ) , but giant pedunculated hemangiomas , as in the present case , are very rare ( 11 - 13 ) . a good illustration of this is our patient , who experienced abdominal distention and a mass , abdominal pain , early satiety , nausea , vomiting , icterus , and thrombocytopenia ( 1 , 6 , 10 , 14 ) . the first reported case of a giant pedunculated hepatic hemangioma was by ellis et al . in 1985 ( 3 ) . another study reported a total of 24 cases of pedunculated , exophytic hemangiomas , which was consistent with the existing literature up to the year 2008 ( 2 , 9 ) . pedunculated hepatic hemangiomas are sometimes mistaken for other pedunculated tumors , such as hepatocellular carcinoma , hamartoma , focal nodular hyperplasia , and adenoma ( 3 ) . our patient had a history of ocp use , which could increase the incidence of adenoma . however , if the hemangioma is large or giant and pedunculated , it can cause mass effect , abdominal symptoms , and a potential risk of rupture ( 2 ) . very rarely , these hemangiomas can spontaneously rupture with intra - abdominal hemorrhage , which may also occur due to blunt trauma , creating acute abdominal symptoms . for this condition , surgery is the best treatment choice , especially for a giant symptomatic hemangioma with an uncertain diagnosis . a giant pedunculated hemangioma may undergo torsion around its pedicle , as in our case , and can become infracted , thereby becoming symptomatic . pain is the most frequent symptom , which is due to infarction or pressure on the adjacent organs ( 1 ) . torsion of a giant pedunculated hemangioma is extremely rare , and had not been reported more than once in the literature up to the year 2010 . as the majority of hemangiomas are asymptomatic , they do not require treatment . in symptomatic cases , the indications for surgical intervention include a palpable mass , rapid growth , thrombocytopenia , and rupture with intraperitoneal bleeding pain or epigastric discomfort , as demonstrated in our patient ( 4 ) . in the present case , we decided to perform surgical treatment after considering the symptoms , the large diameter of the mass , the inability to exclude malignancy , and the risk of rupture of the lesion . if surgery is contraindicated , other treatment modalities , such as radiation therapy , hepatic artery ligation , and arterial embolization can be used ( 10 ) . in conclusion , pedunculated hemangiomas of the liver are uncommon benign tumors that should be included in the differential diagnosis of any mass located in the upper abdomen . imaging modalities , such as ultrasound , ct , mri , radionuclide scintigraphy , and angiography , may be used to diagnose these tumors . this case report and other similar studies indicate that all incidentally detected pedunculated hemangiomas must be surgically managed , as they have a tendency to become torsioned . in conclusion , pedunculated hemangiomas of the liver are uncommon benign tumors that should be included in the differential diagnosis of any mass located in the upper abdomen . imaging modalities , such as ultrasound , ct , mri , radionuclide scintigraphy , and angiography , may be used to diagnose these tumors . this case report and other similar studies indicate that all incidentally detected pedunculated hemangiomas must be surgically managed , as they have a tendency to become torsioned .

introductionhemangioma is the most common benign tumor of the liver . most cases are asymptomatic and do not require treatment . a hemangioma can rarely be pedunculated ; as a result , it may undergo torsion and infarction , which can make it symptomatic.case presentationwe report the case of a 45-year - old woman with acute abdominal pain due to torsion of a giant pedunculated hepatic hemangioma around its vascular stalk.conclusionspedunculated hemangioma of the liver is an uncommon benign tumor , a rare differential diagnosis for a mass located in the upper abdomen . all incidentally detected pedunculated hemangiomas must be surgically managed , as these have a tendency to become torsioned , and there is also a risk of malignancy or rupture .

percutaneous endoscopic gastrostomy ( peg ) tube placement has been the minimally invasive procedure of choice for enteral access , or decompression , since the early 1980s . herniation through gastrostomy site is considered an extremely rare complication with only four cases reported . we present two unusual cases of gastrostomy site herniation , the surgical management thereof , and a corresponding review of the literature . the first patient is a 65 year old caucasian male who presented to the surgery clinic after a prolonged hospitalization for congestive heart failure exacerbation resulting in the need for gastrostomy tube placement . the patient had the peg tube in place for approximately a month and then it was removed by traction technique after no longer in use . the patient noticed an enlarging defect about 3 weeks after removal . at time of presentation he complained of epigastric pain and a bulge at his previous gastrostomy tube incision site . the hernia was easily reduced with gentle traction , and a gastro - cutaneous attachment resected ( fig . a polyester composite mesh was then used to repair the gastrostomy site ventral wall defect ( fig . 2 ) . the second patient is a 66 year old obese caucasian male who was hospitalized in the intensive care unit for lithium overdose . he required prolonged enteral feeding , and for that purpose he received a percutaneous endoscopic gastrostomy . subsequently he recovered well and had the tube removed by simple traction in the office . five months later he complained of continued pain in the midepigastric region around his gastrostomy site scar . on physical exam he was taken to the operating room and his hernia was repaired by open surgery with a composite mesh . both patients had non - complicated reducible hernias at presentation and no extra imaging or specific diagnostic modalities were required . authordatediagnosisremoval methodinterventionoutcomechuang 2003leakage from around peg tube , bulge with coughingtractionremoval of peg tube via traction method , plan for surgical interventionpneumonia , respiratory failure , and death before surgeryboldo - roda 2005leakage from around peg tube , bulge with physical activitytractionn / aunkkaplan 2006leakage from around peg tube , bulge with physical activitytractionreferral for surgical interventionunkozutemiz 2007bulgingtractionn / aunk peg site herniation has been described previously but without description of operative intervention received . with the increasing numbers of peg tubes being placed every year discussion of preventing this complication was presented by boldo - roda et al . and included avoidance of placement of peg tube through linea alba , as this is an area of potential weakness ; and possibly using cut and push technique rather than traction . it is possible that vigorous traction during removal may create a more permanent cavity than expected . however cut and push technique carries its own innate risks and clinicians should keep this in mind when deciding on the removal technique of choice . while gastrostomy site hernia is an exceedingly rare complication with only four other cases reported in the literature , it is likely , given the number of gastrostomy tubes placed per year , that it is simply underreported . clinicians should stay vigilant when performing physical exams or additional workup in patients with ongoing leakage , bulge or pain at the gastrostomy site ; as this is potentially a surgically correctable entity , and can be safely managed via laparoscopic or open techniques . written informed consent was obtained from the patients for publication of these two case reports and accompanying images . a copy of the written consents is available for review by the editor - in - chief of this journal on request .

highlightstow rare cases of herniation through gastrostomy site.percutaneous endoscopic gastrostomy is the minimally invasive procedure of choice for enteral access or decompression.while it s exceedingly rare , herniation through gastrostomy site is a possible complication that we should be aware of.in our two cases , epigastric pain around the site of the previous gastrostomy or the gastrostomy scar was the main complaint at presentation .

spermatozoa are rich in polyunsaturated fatty acids as well as susceptible to be attacked by ros or membrane lipid peroxide ion . the equilibrium between the amounts of ros produced and scavenged is related with the gamete cell stability and damage . free radicals have beneficial or detrimental effects upon sperm functions , which depend on their nature and concentration . the generations of ros , such as superoxide anion , hydrogen peroxide , and the hydroxyl radical can result in the damage to cell membranes . . excessive generation of ros in semen may be associated with reduced sperm fertilizing potentials . spermatozoa are rendered dysfunctional by lipid peroxidation and altered membrane function , together with impaired metabolism , morphology , and motility 2 . excessive generation of ros in semen , mainly by neutrophils but also by abnormal spermatozoa , could be linked with infertility . lipid peroxidation triggers the loss of membrane integrity , causing increased cell permeability , enzyme inactivation , structural damage to dna , and cell death 3 . polyunsaturated fatty acid in the phospholipids of the human spermatozooa is highly susceptible to peroxidation . oxygen free radicals generated by spermatozoa may be involved in the production of spermicidal cytotoxic end products 4 . human spermatozoa possess these defense enzymes , which might be useful in the prediction of sperm fertilizing potentials 5 . numerous antioxidants are related with the ros detoxification , including superoxide dismutase ( sod ) , catalase , malondialdehyde ( mda ) , and glutathione peroxidase ( gpx ) . mda , an end product of lipid peroxidation , represented the level of lipid peroxidation . high lipid peroxidation as represented by mda levels may cause changes in the sperm and diminish fertility 5 . gpx , a selenium - containing antioxidative enzyme scavenging system , act directly as an antioxidant and an inhibitor of lipid peroxidation . gpx also plays an important role in sperm maturation from the early events up to the onset of fertilization 7 . with the absence of gpx the activities of seminal gpx was lower in infertile patients than in fertile patients 9 . however , the correlation or real roles of mda and gpx with seminal quality remains controversial 10 . we noted that the sod activities of sperm and seminal plasma were non - significantly correlated with the seminal quality . herein we further tried to detect the relationship of the seminal mda and gpx activity with spermatozoal characteristics in subfertile men . to the best of our knowledge , semen samples were collected into sterile containers for immediate transportation to the laboratory within 30 minutes after ejaculation . this series was approved by the ethical committee and institutional review board of the china medical university hospital . after liquefaction , samples were analyzed for volume , leukocyte count , sperm motility and morphology according to who guidelines 12 . then an aliquot of 6 l of each specimen was loaded into a 30-mm microcell slide and subjected to computer - assisted semen analysis ( casa ) with the use of a htm - s motility analyzer ( hamilton - thorne research , beverly , ma ) . male infertility ( oligo- or asthenozoospermia , n=31 , count < 20x10/ml , motility < 50% ) . then the semen samples were loaded into the eppendorf tubes ( 3 ml ) and stored in the liquid nitrogen tank before mda and gpx analyses . briefly , one hundred l of seminal plasma was added in 0.9 ml of distilled water into glass tube . to each tube , 0.5 ml of thiobarbituric acid reagent ( 0.67 g of 2-thiobarbituric acid dissolved in 100 ml of distilled water with 0.5 g naoh and 100 ml glacial acetic acid added ) was added and then heated for 1 h in a boiling water bath . after cooling , each tube was centrifuged for 10 min at 4,000 x g and the supernatant absorbance was read on a spectrophotometer at 534 nm . gpx activity was measured in accordance with our previous report 14 . in brief , the 3 ml reaction consisted of 0.1 m pb ( ph 7.0 ) containing 1 mm edta , 1.5 mm nadph , 10 mm gsh , 0.4 u / ml gsh reductase , 12 mm tert - butyl hydroperoxide , and 1 mm nan3 to inhibit catalase activity in the sample . one unit is defined as the amount of gpx leading 1 mol gsh oxidized per min . the relationships of the mda levels and gpx activities with the sperm motility and concentrations were also compared . the sas system ( version 8.1 , sas institute inc . , cary , north carolina , usa ) with t - test and linear regression model were utilized for statistical analyses . the levels of mda in group 1 and 2 were 1.52 0.75 and 2.25 0.88 nm , respectively ( figure 1a , p = 0.0021 ) . in contrast , the activities of seminal plasma gpx in both groups were not significantly different . the values of gpx activities in group 1 and 2 were 0.48 0.11 and 0.47 0.12 u / ml , respectively ( figure 1b , p = 0.713 ) . the formula of their relationship was : mda = -0.0045 x sperm concentration + 2.23 ( figure 2a , p = 0.0166 ) . the formula of their relationship was : gpx = 0.0009 x sperm concentration + 0.42 ( figure 2b , p = 0.0696 ) . we establish the formula of their relationship : mda = -0.014 x sperm motility + 2.62 ( figure 3a , p = 0.017 ) . we also noted the positive , but non - significant correlation between the sperm motility and the gpx activity . the formula of their relationship was : gpx = 0.0012 x sperm motility + 0.42 ( figure 3b , p = 0.134 ) . oxidative damage is common for spermatozoa during epididymal maturation and storage . human spermatozoa are highly susceptible to oxidative injury but are naturally protected from such injury by the antioxidant properties of seminal plasma . excessive generation of seminal ros , mainly by neutrophils but also by immobile sperm , morphologically abnormal sperm , or morphologically normal but functionally abnormal sperm , could be a cause for male infertility 17 . in fact , ros have beneficial or detrimental effects on sperm functions depending on the nature and concentration of the ros involved , as well as the moment and the location of exposure 19 . antioxidants in semen serve to protect ejaculated spermatozoa from oxidative stress such as that which occurs in the female reproductive tract . the lipid peroxidation of unsaturated fatty acids in sperm membranes is one of the most important effects from ros - induced cell damage what may lead to persistent infertility 20 . lipid peroxidation was increased during in - vitro storage of spermatozoa , which might impair sperm motility 21 . 22 observed a significant positive correlation between seminal il-6 levels and lipid peroxidation of sperm membrane . the high level cytokines produced by human sperm and leucocytes might further stimulate the ros production . exposure of spermatozoa to ros has been associated with cellular injury , which includes dna damage and lipid peroxidation 23 . ros may affect the integrity of the sperm genome and induce high frequencies of single and double dna strand breaks 24 . ros is known to play a major role in the etiology of defective sperm function via mechanisms involving the induction of peroxidative damage to the plasma membrane 25 . ros production is negatively related with the sperm - oocyte fusion capacity of human spermatozoa 27 . ros at low concentrations may inhibit sperm - egg fusion via oxidation of the sh - proteins in the sperm membrane 28 . high lipid peroxidation may reduce the capacity of the sperm to undergo acrosomal reaction and to fertilize 27 . the spermatozoa capability for oocyte fusion was impaired with the addition of hydrogen peroxide 29 . antioxidant enzymes , such as sod and gpx , could dispose hydroperoxide and other ros . cellular damage arises when this equilibrium is disturbed , especially when the cellular scavenging systems can not eliminate the increased ros . lipid peroxidation could damage the cell plasma membrane , which leads to loss of cytosolic components and cell death . normally , a balance is maintained between the amount of ros and that scavenged by antioxidant . cellular damage arises when this equilibrium is disturbed , especially when the cellular scavenging systems can not eliminate the increased ros . among the various methods for detection of lipid peroxidation , we chose to measure spontaneous mda production , which reflects the peroxidation of polyunsaturated phospholipids , the major components of sperm membrane 2 . mda measurements are physiological and relevant because major loss of sperm function may occur with minimal damage to the membranes that envelop the sperm and/or divide key intracellular sperm compartments . 5 demonstrated that the high mda production in the male with low fertilization rates in their previous ivf cycles . they also found that the reduction of mda by using antioxidant therapy was correlated with the improvement of fertilization rates . 32 demonstrated that mda concentration in spermatozoa was significantly related to the number of immotile spermatozoa . 33 demonstrated that the mda concentration in the seminal plasma was not correlated with the sperm concentration and motility . in this series , we found the different concentrations of mda between the samples of normo- and oligoasthenozoospermoa . we observed the negative correlation between the mda activity and sperm motility or concentration , which was compatible with the findings of geva et al . it suggested that the lipid peroxidation , which was represented by the mda activity , might compromise the sperm viability . increased mda activity could represent the pathologic lipid peroxidation of spermatozoa membrane and the following inhibition of sperm motility and viability . administration of vitamin e may decrease the mda activity with concomitant increased sperm motility and viability 30 . administration of pentoxifylline could decrease the generation of ros , lipid peroxidation and mda in human spermatozoa 31 . these suggested that the vitamin e and pentoxifylline might improve the motility and fertilization rate of sperm by reducing the lipid peroxidation 5 . gpx , a ros scavenger , plays a role in protecting sperm membranes from the deleterious effects of lipid peroxidation 34 . gpx is related with the balance between the gssg ( reduced form of glutathione ) and gsh ( oxidized form of glutathione ) 10 . reduced glutathione could protect spermatozoa from oxidative stress 35 . through the interaction with gpx , reduced glutathione gpx activities were significantly elevated when the semen samples contained < 10 leukocytes / ml 36 . it has been suggested that higher ros production in infertile patients may be due to increased ros production rather than defective ros scavenging activity 37 . gpx activity in follicular fluid from infertile women was significantly lower than in fertile women 38 . gpx could scavenges lipid peroxides released form the plasma membrane and further protect the dna from oxidative attack 40 . suppressed gpx activity may allow the production of the peroxides from the sperm plasma membrane to the chromatin where they could induce dna strand breakage 40 . recently , dandekar et al . 41 demonstrated that the gpx concentration correlate positively with asthenozoospermia . these could interpret the positive but non - significant correlation between gpx and sperm motility and concentration in this study . 42 demonstrate that the seminal gpx activity from healthy subjects was 10 times greater than that from infertile males . , 43 demonstrated the non - difference of gpx activities between normo- and hypomotile human sperm samples . in this study , we could not observe their statistical correlations . it suggests that the seminal gpx is still not a useful tool in determining sperm fertilizing potential . this may be due to the case limitation or the complex interactions between the ros and numerous antioxidants . in fact , the regulation of sperm function and the mechanisms involved may be complex and multifactorial . in conclusion , the mda level representing lipid peroxidation is negatively correlated with the sperm motility and concentration . in contrast , the gpx activities are not significantly correlated with the sperm motility or concentration . this could provide the database about the effects of mda and gpx upon sperm . increased activity of seminal mda furthermore , seminal mda survey is a simple and useful screening tool in determining sperm fertilizing potentials . however , the regulation of sperm function and the mechanisms involved may be complex and multifactorial . real role of mda , gpx and other antioxidants upon the sperm qualities merits further surveys . comparisons of ( a ) malondialdehyde and ( b ) glutathione peroxidase activities in normal individuals and oligoasthenozoospermia patients the correlations of the sperm concentration with ( a ) malondialdehyde and ( b ) glutathione peroxidase activities the correlations of the sperm motility with ( a ) malondialdehyde and ( b ) glutathione peroxidase activities

objectives : reactive oxygen species ( ros ) induced lipid peroxidation is associated with sperm function . malondialdehyde ( mda ) concentration and glutathione peroxidase ( gpx ) activity represent the lipid peroxidation and spermicidal antioxidant , respectively . we aimed to evaluate the relationship of mda and gpx levels with sperm parameters.patients and methods : specimens were divided into two groups : group 1 . normospermia ( n=20 ) ; group 2 . oligoasthenospermia ( n=31 ) . seminal mda concentration was measured by thiobarbituric acid reaction method . seminal gpx activity was measured by oxidation of reduced nicotinamide - adenine dinucleotide . seminal mda levels and gpx activities in both groups were compared.results : mda concentrations in both groups were significantly different ( 1.52 0.75 vs. 2.25 0.88 nm , p = 0.0021 ) . gpx activities in both groups were non - significantly different ( 0.48 0.11 vs. 0.47 0.12 u / ml ) . mda levels were negatively correlated with the sperm motility ( mda = -0.014 x motility + 2.62 , p = 0.017 ) and concentration ( mda = -0.0045 x concentration + 2.23 , p = 0.0166 ) . gpx activities were positively but non - significantly correlated with the sperm concentration and sperm motility.conclusions : seminal mda concentrations are negatively correlated with sperm concentration and motility , which might provide a simple and useful tool in predicting sperm parameters . gpx activity is non - significantly correlated with the seminal quality . roles of seminal mda upon spermatogenesis merits further surveys .

ludwig 's angina is a known , yet a rare surgical emergency that is potentially life threatening unless early recognised and aggressively treated . we highlight these controversies with a brief review of the literature and a retrospective review of recent experiences with ludwig 's angina . a 56-year - old male presented with a 72-hour history of a worsening dysphagia and submandibular swelling . the onset was following a visit to the dentist where a dental abscess was drained . 24 hours later he revisited his dentist complaining of a submandibular swelling , and was commenced on oral co - amoxiclav . despite that , his symptoms progressed and he made his way to our facility 72 hours later . based on his history and symptoms the diagnosis of ludwig 's angina was suspected . he was not in respiratory distress ; his respiratory rate was 23 , and o2 saturation was 96% on room air . based on this initial assessment , the decision was to manage him conservatively with close airway observation . he was commenced on intravenous co - amoxiclav and clindamycin , and a contrast - enhanced ct scan of his neck and upper thorax was performed to rule out the possibility of a deep neck abscess . this showed an extensive submandibular soft tissue swelling and inflammation with moderate tongue elevation and posterior displacement causing a degree of oropharyngeal airway compromise . no abscess cavity or laryngeal airway compromise was evident . he was admitted to the ear , nose and throat ( ent ) ward for hourly airway observation and intravenous antibiotic treatment . his symptoms improved on a daily basis maintaining a normal breathing rate and pattern with no o2 desaturations below 97% on room air on pulse oximetry . by the 5th day following his admission , his symptoms have fully resolved , and he was discharged from hospital on oral co - amoxiclav . two weeks and 3 months out - patient department followups showed no recurrent soft tissue swelling or oedema , and he was discharged from our service . a 59-year - old male with a background history of noninsulin - dependant diabetes mellitus and sebopsoriasis presented with 24-hour history of mild right - sided facial swelling , a worsening submandibular swelling , and mild dysphagia . he had low - grade pyrexia of 37.8c , his respiratory rate was within normal limits , and his o2 saturation was 98% on room air . on physical examination he had a mild right - sided facial swelling , a significant submandibular swelling , and skin erythema extending inferiorly to the level of the upper border of the sternum . he was commenced on intravenous clindamycin , ciprofloxacin , and benzylpenicillin , and a contrast - enhanced ct scan of his neck and upper thorax ( figures 1 and 2 ) was performed to role out a deep neck abscess or a mediastinum extension . this showed a significant submandibular soft tissue inflammation and oedema with a degree of oropharyngeal compromise . his laryngeal airway was normal , and no deep neck abscess or fascial extension was evident . he was admitted to the ent ward for hourly airway observation and intravenous antibiotic treatment . on the third day after admission , on the other hand , a worrying inferiorly spreading skin erythema to the level of the 5th costal cartilage was noted . despite that , his respiratory rate and o2 saturation remained unchanged , and he had no cardiothoracic complaints to suggest a danger space extension or a necrotising fasciitis . a clinical assessment including a chest plain film and a neck ultrasound was performed . the dermatology service was consulted , and a secondary psoriatic flare up was suspected . a topical daktacort hydrocortisone cream ( miconazole and hydrocortisone ) was added . a gradual improvement of his symptoms occurred on daily basis . by the sixth day following his admission his symptoms two weeks and 3 months out - patient department followups showed no recurrent laryngeal oedema or skin erythema , and he was discharged from our service . ludwig 's angina is named after the german physician , wilhelm friedrich von ludwig who first described this condition in 1836 . it is a potentially life - threatening cellulitis , or connective tissue infection , of the neck and floor of the mouth which is characterised by progressive submandibular swelling with elevation and posterior displacement of the tongue [ 2 , 3 ] . early antibiotic treatment should be broad spectrum to cover gram - positive and gram - negative bacteria as well as anaerobes . the use of intravenous steroids has been proposed as a mean of reducing soft tissue swelling and oedema and minimising the likelihood for the need of a surgical airway in ludwig 's angina [ 1 , 5 , 6 ] . this remains controversial , as up to this date no randomised controlled trials that demonstrate the efficacy of corticosteroids in these patients exist . traditionally aggressive airway management by securing the airway with endotracheal intubation or surgically with a surgical tracheostomy was the norm . although no specific guidelines are present for managing acute ludwig 's angina , decisions regarding airway protection are largely dependant on the practice guidelines for management of the difficult airway that were adopted by the american society of anaesthesiologists in 1992 and updated in 2003 . in these guidelines , a difficult airway is defined as the clinical situation in which a conventionally trained anaesthesiologist experiences difficulty with face mask ventilation of the upper airway , difficulty with tracheal intubation , or both . the guidelines specify that these recommendations may be adopted , modified , or rejected according to the clinical needs and constraints as these guidelines are not intended as standards or absolute requirements and their purpose is to assist the practitioner in decisions about health care . recent reports have encouraged conservative management of ludwig 's angina in selected patients over the conventional aggressive airway management . larawin et al . retrospectively studied a total of 103 patients with deep neck space infections from 1993 to 2005 . ludwig 's angina was the most commonly encountered infection seen in 38 ( 37% ) patients of treatment . 13 ( 34% ) patients managed successfully with medical therapy and only 4 ( 10% ) patients required a tracheostomy tube . kurien et al . reported a 13-year review of patients with ludwig 's angina between 1982 and 1995 . 70% were controlled with conservative medical management while 81% of adults required incision and drainage . a 9-year review by greenberg et al . of 29 cases of deep neck space infections reported 21 patients ( 72 % ) treated conservatively following initial clinical assessment . of those treated nonconservatively at initial presentation , 7 ( 24% ) patients were able to be intubated using fiberoptic nasoendoscopy and 1(3% ) patient required tracheostomy under local anaesthesia . early detailed imaging is essential to evaluate the extension of tissue infection or necrosis and to guide decisions regarding surgical approaches when indicated . ct scan and mri are of invaluable importance in the assessment of deep neck space infections and collections . miller et al . reported that combined clinical evaluation and ct findings lead to accuracy of 89% , sensitivity of 95% , and specificity of 80 % in identifying drainable collection . plain chest radiographs are useful when looking for signs of mediastinum extension such as mediastinitis and pleural effusion . although ultrasound is not as easily interpreted by clinicians and surgeons as other imaging modalities , its availability , cost effectiveness , reduced risk of radiation , and accuracy in differentiating cellulites - related oedemas from abscess collections make it a reliable supplement modality to ct scan in resistant cases [ 12 , 13 ] . however , in cases of significant airway compromise where an immediate decision regarding the need of a definitive airway is required , clinical experience and judgment are superior to imaging . from our clinical experience and the literature review we conclude that conservative management of ludwig 's angina is acceptable in selective cases , provided that early antibiotic therapy is commenced and any collectable abscess is drained . initial airway assessment is based on respiratory rate , oxygen saturation , and findings on fiberoptic laryngoscopy . patients are then categorised as having either a severe airway compromise or a stable airway . in the severely compromised group ( patients unable to maintain saturation on room air above 95% , respiratory rate > 25 , or awake fiberoptic - assisted intubation should be attempted first ; if this fails then a surgical tracheostomy is performed under local anaesthesia . in the other group , where patients are able to maintain normal oxygen saturation and respiratory rate on room air and where no significant airway compromise is evident on fiberoptic examination , this involves close airway observation ( oxygen saturation , respiratory rate , and serial fiberoptic laryngoscopy ) in a high dependency unit ( hdu ) or ent ward . after the initial clinical assessment and airway decision all patients should undergo ct scanning of their neck and thorax for further detailed airway and deep neck spaces evaluation . any abscess or collection cavity should be drained , and both groups should be kept in an hdu or ent ward for hourly airway assessment for 2448 hours . this is based on close airway observation on a specialised airway unit and a serial clinical airway assessment . improved imaging modalities , antibiotic therapy , surgical skills , and clinical experience are the key factors behind this change in practice .

objectives . to review the current protocols used for management of ludwig 's angina and to assess the efficacy of conservative measures in these cases . methods . a retrospective review of patients who were admitted to our institution for management of ludwig 's angina between 2003 and 2010 . results . two patients were identified . both were managed successfully with conservative measures and close airway observation . none needed an emergency intubation or surgical tracheostomy . there were no mortalities , and both had a short hospital stay . conclusion . recently , management of ludwig 's angina has evolved from aggressive airway management into a more conservative one . this is based on close airway observation on a specialised airway unit and a serial clinical airway assessment . improved imaging modalities , antibiotic therapy , surgical skills , and clinical experience are the key factors behind this change in practice .

a giant ( 3 times of diameter of the coronary artery ) coronary cameral fistula ( ccf ) of the left main coronary artery ( lmca ) associated with patent ductus arteriosus ( pda ) is rare . the origin , course of the fistulous tract , size , neighboring structures , exit , shunt size , symptoms and associated with complications such as rapid growth , thromboembolism , infective endocarditis , and coronary steal are the variables those decide closure technique and follow up course . surgery is preferred to device closure because of very good , long - term , event - free survival . a 7-year - old female child presented to us with low - grade fever , chill , and loss of weight for last one month . she was treated outside as a case of pyrexia of unknown origin as was mentioned in the referral note with some antibiotics . history in detail revealed three to four episode of lower respiratory tract infection without expectoration per year . palpation and auscultation confirmed a systolic thrill with underlying a superficial cat purring continuous murmur in the right parasternal border . two - dimensional and color doppler echocardiography revealed a restricted pda of the narrowest diameter of 2 mm at the pulmonary arterial end . the dilated lmca measured 67 mm at aortic end with a large ( 2.5 cm 1 cm ) oscillating vegetation at the exit into the right atrium ( ra ) [ figure 1 and video 1 ] . the modified apical five - chamber view and parasternal short axis view showed a tortuous tract with the high - velocity turbulent flow . although we could not trace the fistulous tract completely , we made a provisional diagnosis of ccf connecting lmca to ra . there was mild dilatation of ra , right ventricle and pulmonary artery , mild pulmonary arterial hypertension ( pah ) , and good biventricular function . the definite diagnosis of infective endocarditis was made by clinical criteria under modified duke 's criteria . the criteria that qualify for definitive infective endocarditis in this case included one major ( large freely oscillating vegetation in echocardiography ) and three minor criteria ( fever 5 days , existing structural heart disease , and rheumatoid factor positive in very low titer ) . cardiac catheterization showed left to right ( l to r ) shunt size of 1.7:1 , mild pah . the fistulous tract was narrowest at the right atrial end with waist size 3 mm following an ampulla just before entry into ra . aortic root angiogram also showed left anterior descending ( lad ) , ramus intermedius , and left circumflex ( lcx ) coronary arteries were arising from dilated lmca [ figure 2 ] . both echocardiogram and coronary angiogram could not clarify the exact three - dimensional course of this tortuous fistula . cardiac magnetic resonance angiogram with contrast enhancement ( cmri-1.5 tesla ) showed a tortuous , giant aneurysmal dilated fistulous tract running posterior - superiorly and parallel to coronary sinus . the length of ccf was 4 cm , and the ostial opening was 7 mm in diameter . the coronary arteries from l to r from lmca in order were lcx coronary artery , ramus intermedius , and anterior descending coronary artery [ figure 3 ] . because of a large recently treated large vegetation and significantly large aneurysmal fistulous tract , we preferred surgical closure . incision on the right atrial free wall showed fistulous tract opening of size 34 mm just above and posterior to the coronary sinus . then , the ampulla part of fistula was marsupialized after closing the arterial end close to it , aiming maximum reduction of fistulous tract length . the vegetation at the exit was quite small because of healing [ figure 4 ] which was excised completely . the aneurysmal dilation lmca , tortuous tract , and the origin of all the three coronary arteries ( lad / lcx / ramus intermedius ) from left main were the major hindrances in closing this fistula from the aortic wall itself . she was discharged without any postoperative complication on the 10 postoperative day . the histopathology report showed healed vegetation with predominant collagen tissue and paucity of cellular elements . she was kept on warfarin aiming inr 2 - 3 to prevent thromboembolism from blind sac for first 3 months followed by ecosprin . two - dimensional echocardiography in apical modified five chamber view with anterior swipe shows vegetation marked by white arrow at the exit of the fistula in the right atrium just above the ostium of the coronary sinus coronary angiogram of the left main in the anterior posterior projection showed the fistula . the details of pathology were not obvious cardiac magnetic resonance angiogram shows aneurysmal dilatation of fistulous tract running parallel to coronary sinus posterior - superiorly . the coronary arteries from left to right from the left main coronary artery in order were left circumflex , ramus intermedius , and left anterior descending coronary artery right atrial approach to excise the vegetation and close the coronary cameral fistula was consistent with significantly healed vegetation ( very small size ) three cases left main ccf have been reported by mavroudis et al . including only one case of lmca ccf there are also some individual case reports of left main ccf . in the review article by said showed lmca fistula that drains into pulmonary artery ( 46% ) , coronary sinus or ra ( 29% ) , right ventricle ( 6% ) , superior vena cava ( 12% ) , and none into the left ventricle . of these cases , 18% had an aneurysm , 47% underwent surgical ligation , 41% medical management , and 12% had undergone catheter - based intervention . only 4% of 304 patients had infective endocarditis involving valves and at the venous exists but none of them had origin vegetation . the mere presence of vegetation is not an absolute contraindication for percutaneous closure of fistulous tract , if the vegetation is small , reduces to insignificant size on treatment . the timing of surgery in such situation should be as early as possible without waiting for the healing of the vegetation . therefore , we have done surgery without delay . the choice of technique to close the fistula depends on origin , exit , tortuosity , size , length , flow status , aneurysmal dilation , and the point of intended occlusion site and intra- or extra - cardiac course of fistula . management decision is also influenced by the presence or absence of several variables such as associated congenital malformation , complication ( infective endocarditic , thromboembolism , thrombosis rupture , and coronary steal ) , and the size of the fistulous tract . after operation , if the residual blind sac grows faster in size , the patient may need a redo operation . a large residual sac , especially after device closure , may need lifelong oral anticoagulation or surgery . therefore , a watchful follow - up is mandatory in either condition to watch for future enlargement of the residual sac . the active inflammation in the vegetation in this case could have been detected using pet scan prior to starting the antibiotic course . this rare case of lmca to ra ccf with pda illustrated a large oscillating vegetation at the right atrial exit in case of partially treated infective endocarditis .

a 7-year - old female child presented with pyrexia of unknown origin . she had received an empirical regimen of antibiotic for possible endocarditis . evaluation included multiple imaging supports and blood culture . she had left main coronary artery to right atrium coronary cameral fistula , restricted patent ductus arteriosus , vegetation at the right atrial exit of fistula and negative blood culture . ongoing fever more than 2 weeks , oscillating vegetation in the echo and histopathological evidence of healing vegetation suggested definite diagnosis of infective endocarditis . she was treated successfully by surgical closure of fistula from the right atrial approach . device closure in this case would have resulted in a large residual cul - de - sac with or without tiny residual high - velocity jets , either being a threat for future enlargement , rupture of the residual aneurysmal sac , thromboembolism , prolonged anticoagulation , and infective endocarditis .

bevacizumab is a recombinant humanized monoclonal antibody that targets the vascular endothelial growth factor ( vegf ) . vegf plays an important role in tumor angiogenesis and is overexpressed in a wide range of malignant tumors . inhibition of vegf reduces growth of new tumors supplied by vessels , and leads to normalization of existing tumor vessels . therefore , reducing the interstitial fluid pressure should result in an enhanced efficacy of chemotherapeutic drugs . bevacizumab is widely used to treat a variety of advanced solid tumors , including colorectal cancer , non - small cell lung cancer , breast cancer , and renal cell cancer ( rcc ) . it has been shown to improve progression - free survival ( pfs ) in patients with rcc and has been demonstrated to have clinically significant benefits as a first - line treatment for non - small cell lung cancer and breast cancer in combination with cytotoxic agents . in e2100 , a significant increase in pfs was observed in patients receiving bevacizumab plus paclitaxel compared with paclitaxel alone [ hazard ratio ( hr ) 0.42 ; p < 0.0001 ] . median overall survival ( os ) was 26.5 months with bevacizumab plus paclitaxel versus 24.8 months with paclitaxel alone ; the hr for os was 0.869 ( p = 0.1374 ) . the objective response rate more than doubled with the addition of bevacizumab , from 22 to 50% . in e2100 , avado , and both cohorts of ribbon-1 , pfs was significantly superior in the bevacizumab - containing arm compared with chemotherapy alone , thus meeting the primary objective of each trial . median os was 26.7 months in the bevacizumab arm compared with 26.4 months in the non - bevacizumab arm . there was no significant difference in os between the two arms ( hr 0.97 ) . the 1-year os rate was 82% in the bevacizumab - containing arm versus 77% in the non - bevacizumab arm ( p = 0.003 ) . many trials are currently underway evaluating its efficacy in various kinds of solid tumors [ 27 ] . the adverse effects of bevacizumab are hemorrhage/79.2% ( grade 3 , 1.7% ; grade 4 , 0.8% ) ; gastrointestinal tract perforation/0.6% ( grade 4 , 0.6% ) , wound dehiscence/5.0% , arterial and venous thromboembolism/0.8% , hypertension/51.7% ( grade 3 , 16.7% ) , reversible posterior leukoencephalopathy/0.5% , neutropenia/75.8% ( grade 3 , 31.7% ; grade 4 , 10.8% ) , proteinuria/59.2% , and congestive heart failure/1.7% [ 2 , 811 ] . , this drug was approved in november 2011 ; since then , an increasing number of patients have been treated with it . we report an apparently rare case with diverticular bleeding of the colon during chemotherapy with bevacizumab and paclitaxel for recurrent breast cancer . the characteristics of the cancer included invasive ductal carcinoma , with estrogen receptor and progesterone receptor being negative ( 0% positive cells ) . human epidermal growth factor receptor 2 was negative by immunohistochemistry , and ki-67 was 50% . after neoadjuvant chemotherapy with six cycles of fec ( fluorouracil , 500 mg / m ; epirubicin , 100 mg / m ; cyclophosphamide , 500 mg / m on day 1 every 21 days ) , partial resection of the left breast and sentinel lymph node biopsy were performed . the pathological findings were invasive ductal carcinoma , nuclear grade 3 ; absence of lymph node metastasis ; negative triple receptor , and high ki-67 ( 30% ) . one year and 8 months after surgery , redness and swelling developed in the conserved breast skin . the skin lesion was pathologically diagnosed as recurrence of inflammatory breast cancer with triple receptor negative . positron emission tomography revealed multiple metastases in the left supraclavicular lymph nodes and right axillary lymph nodes , with no distant metastasis . oxycodone hydrochloride hydrate 40 mg / day with 5 mg rescue ; diclofenac sodium 75 mg / day for pain control , and magnesium oxide 1,500 mg / day for constipation were associated with chemotherapy and narcotics . two cycles of docetaxel ( 75 mg / m on day 1 every 21 days ) were given , but a new skin lesion developed . the treatment was changed to capecitabine ( 2,400 mg / day ) for 3 weeks at 1-week intervals . after two cycles of capecitabine , a ct scan revealed the development of skin lesions , enlargement of the left breast mass , and lung metastasis . we changed the treatment to bevacizumab ( 10 mg / kg on day 1 every 14 days ) with weekly paclitaxel ( 80 mg / m ; bevacizumab and paclitaxel ) . after three cycles of bevacizumab and paclitaxel , the size of the skin lesion and the volume of the left breast mass were reduced . seven days after the three cycles of bevacizumab and paclitaxel , the patient noticed evident bloody bowel discharge from the rectum . she was found lying on the floor at home and was brought to our hospital by ambulance . when she was admitted , her blood pressure was 88/39 mm hg , and her heart rate was 71 beats / min . initial laboratory findings revealed hemoglobin 8.8 g / dl , and her coagulation tests were normal . her blood pressure then improved to 103/62 mm hg , and her hemoglobin was raised to 9.6 g / dl . colonoscopy demonstrated multiple diverticula in the ascending colon and detected the diverticular bleeding point , which was then clipped colonoscopically ( fig . 1 , fig . she was prohibited from eating , and was given high - calorie intravenous hyperalimentation for 3 weeks , which is estimated to be long enough for elimination of bevacizumab . in breast cancer patients treated with bevacizumab and paclitaxel , the incidence of all - grade hemorrhage is 79.2% . [ 2 , 811 ] . to our knowledge , this is the first report of colonic diverticular bleeding associated with bevacizumab . hemorrhage may result from the anti - vegf action of bevacizumab . as a neutralizing antibody against vegf , bevacizumab may damage vascular integrity by inhibition of endothelial survival and proliferation , particularly in tissues with a high vegf dependence , such as injured mucosal membranes of the airway or peptic ulcers . in addition , bevacizumab may inhibit the coagulation cascade regulated by tissue factor , whose expression on endothelial cells is induced by vegf . epidemiological data show that in industrialized nations , the prevalence of diverticular disease is 65% in the population older than 65 years . diverticula may develop at sites of weakness in the colonic wall , where the vasa recta penetrate the circular muscle layer . diverticular bleeding occurs when a nutrient artery ruptures into the colon lumen , commonly involving local mucosal ulceration in the absence of inflammation . regular use of aspirin , non - steroidal anti - inflammatory drugs ( nsaids ) , and opioid analgesics is associated with an increased risk of diverticular bleeding . nsaids , including aspirin , likely promote blood loss from existing lesions via inhibition of platelet aggregation . in addition , nsaids , including aspirin , are thought to damage the colon via direct topical injury and/or impaired prostaglandin synthesis , which compromise mucosal integrity , increase permeability , and enable the influx of bacteria and other toxins . constipation increases colonic pressure and may reduce the integrity of the colonic wall , which may increase the occurrence of multiple diverticula . moreover , regular use of bevacizumab and nsaids could be associated with an increased risk of diverticular bleeding in patients who have multiple diverticula . we need to carefully review anamneses for a history of diverticulitis , prior abdominal surgeries , peritoneal carcinomatosis , and regular use of certain drugs .

backgroundbevacizumab has been increasingly used in combination chemotherapy with paclitaxel for treatment of metastatic or recurrent breast cancer . the aim of this report is to underline possible risks associated with the new combination chemotherapy.case presentationa 39-year - old woman with recurrent breast cancer was treated with bevacizumab and paclitaxel . positron emission tomography revealed breast cancer metastasis to the left supraclavicular lymph nodes and right axillary lymph nodes , with no distant metastasis.resultsafter the third cycle of bevacizumab and paclitaxel , the patient developed a bloody bowel discharge . emergent colonoscopy demonstrated diverticular bleeding on one of the multiple diverticula in the ascending colon . the bleeding point was successfully clipped colonoscopically.conclusionthe factors for diverticular bleeding are believed to be non - steroidal anti - inflammatory drugs , constipation , and bevacizumab . we recommend reviewing anamneses for diverticulitis , multiple prior abdominal surgeries , peritoneal carcinomatosis , and regular use of certain drugs .

whole blood viscosity ( wbv ) is one of virchow 's triad , which is an established concept of three phenomena including stasis , endothelial dysfunction and atherothrombosis that ultimately lead to , and/or result from cardiovascular complications[14 ] . each phenomenon represents a subclinical vascular process , which in turn is indicated by a clinical pathology index . specifically , wbv is an intrinsic resistance of blood flow in the vascular system , and index for stasis . increase in wbv is a potential risk factor for future cardiovascular disease . in current clinical practice considering the implication of stasis in metabolic diseases , its clinical management with antiplatelet and the controversies regarding antiplatelet and its bleeding complications[79 ] , such usage is under - utility . international normalized ratio ( inr ) is used to determine the clotting tendency of blood and the need for anticoagulant ( especially warfarin ) therapy . normal range is about 1.0 for a healthy person , and 2.0 - 3.5 for people who are on anticoagulant therapy . a higher inr level indicates a high tendency of bleeding complications , whereas lower inr level is indication of high risk of having a thrombotic event in patients who are on anticoagulant therapy . thus , while anticoagulant and antiplatelet are used interchangeably , there is an established laboratory index ( inr ) being employed for routine monitoring to assess contraindication to and/or need for anticoagulant ; but none for antiplatelet . the objective of this work is to establish whether difference in wbv level is associated with different levels of inr and platelet count . it would be expected , and thus hypothesized that a patient with low inr requiring anticoagulant therapy should present with higher wbv . the findings from this study would provide evidence to suggest wbv as a potential laboratory index to assess for contraindication to antiplatelet therapy synonymous to how inr is being used for anticoagulants . it is supported materially by the albury south west pathology a unit of western pathology cluster of nsw health australia . one year of de - identified archived clinical pathology data for the period of january to december 2008 was audited . 7387 cases ( female - male ratio = 3528 - 3859 ) for international normalizing ratio , which were concomitantly tested from one phlebotomy collection point for full blood count ( fbc ) haematocrit and total proteins , were extracted . haematocrit results from the fbc were used in conjunction with total protein to extrapolate wbv values based on previously published algorithm . whether whole blood viscosity differs between normal vs. high international normalizing ratio and thrombocytopenia vs. thrombocytosis were evaluated . inr level was commonly determined arithmetically from the result of prothrombin time using the formula inr = ptpatient / ptnormal inr data for this study were determined with this formula included in a standard operational procedure ( sop ) . the sop included measurement of prothrombin time ( pt ) by quantitative analysis using the sysmex ca540 method and inr calibration curve , which is plotted for every new lot of pt reagent . results of inr were reported with the following interpretative consideration to risk of bleeding normal patients no therapy = 1.0anitcoagulated patient = 2.0 3.5 including prophylaxis for prosthetic heart valves = 2.5 3.5all other indications = 2.0 3.0 critical results for anticoagulated patients = < 1.5 or > 4.5 normal patients no therapy = 1.0 anitcoagulated patient = 2.0 3.5 including prophylaxis for prosthetic heart valves = 2.5 3.5all other indications = 2.0 3.0 prophylaxis for prosthetic heart valves = 2.5 3.5 all other indications = 2.0 3.0 critical results for anticoagulated patients = < 1.5 or > 4.5 in this study , numerical levels of inr results have been used as reported . it was assumed on the premise of the hypothesis that a pathology that impacts on inr should also impact on platelet count and wbv . the data were sorted by wbv results and categorized into three groups of low , normal or high wbv levels based on the continuum of 15.00 , 15.01 - 19.01 and 19.02 respectively . high , normal and low wbv were named groups i , 2 and 3 respectively . in the statistical analysis , it was considered to avoid errors due to unequal sample size such as exaggerating the effects of inequality of variance . the high wbv ( group 1 ) had the least number ( n = 173 ) and was used as the base sample size for the sub - groups . the discretional criterion for selection of [ n = 173 ] from the other two groups was to make the comparison be between the lowest - median - highest intervals in ranking ( fig . 1 ) . therefore , the lowest [ n = 173 ] in the low wbv rank and the median [ n = 173 ] in the wbv groups were selected . to determine association of high , normal or low wbv with inr and platelet count , multivariable analysis of variance ( manova ) indication of selections from the ranks of wbv - groups . 1 - 173 , 2102 - 2274 , 7215 - 7387 , 173 , g1 , g2 & g3 : hyperviscosity , normoviscosity and hypoviscosity groups respectively , r : ranking , s : selection for statistical analysis . the complete data set were further re - analyzed thrice to observe for consistency in result . first , data were sorted by , and selection of ( n = 173 ) from groups 2 and 3 were repeated to match for age and gender . second , data were sorted by inr . the top ( n = 120 ) vs. the bottom ( n = 120 ) were selected to represent high vs. low inr sub - groups respectively and wbv level was compared between the sub - groups . the top ( n = 120 ) vs. the bottom ( n = 120 ) were selected to represent thrombocytosis vs. thrombocytopenia sub - groups respectively and wbv level was compared between the sub - groups . the statistics of the groups for the complete data set are presented in table 1 . the result shows that platelet count increases with whole blood viscosity or vise versa , whereas low viscosity is associated with high inr ( table 1).manova show that levels of international normalizing ratio and platelet counts statistically significantly differs between different ranges of whole blood viscosity levels ( p<0.001 ) . platelet count is statistically significantly lower in low whole blood viscosity compared to hyperviscosity and normoviscosity ( p<0.001 ) . conversely , international normalized ratio is statistically significantly higher in low whole blood viscosity compared to hyperviscosity ( p<0.001 ) and normoviscosity ( p<0.002 ) . no difference was observed between hyperviscosity and normoviscosity in platelet count or international normalized ratio ( fig . 2 ) . comparison of inr & plt between wbv - groups . 1 - 3 : hyperviscosity , normoviscosity and hypoviscosity groups respectively , inr : international normalized ratio , plt : platelet count x10/l , wbv : whole blood viscosity . in the repeat analyses for observation of consistency , manova on the age and gender matched data set also showed statistical significance ( p<0.005 ) . wbv was observed to statistically significantly differ between high vs. low inr ( p<0.001 ) , as well as between thrombocytopenia vs. thrombocytosis ( p<0.005 ) ( fig . inr : international normalized ratio , plt : platelet count x10/l , wbv : whole blood viscosity . this study reports observation of significantly higher level of inr associated with lower level of wbv . this observation is in consonance with the study 's hypothesis and has relevant applicability in clinical practice . on one hand , it affirms that the use of anticoagulant therapy is in tandem with relative high wbv level . more importantly on the other hand , low wbv being associated with relative high inr , whereby the latter indicates risk of bleeding , suggests that blood viscosity can be utilized as a laboratory index of contraindication / indication to anticoagulant and/or antiplatelet therapies . the issue is that inr is mainly used to assess the status of extrinsic ( clotting ) pathway in order to determine indication / contraindication for anticoagulant therapy . neither is wbv assessed on the chronic patients , nor is the risk of bleeding complication of less concern . therefore , if the latter is assessed to determine possible risk of bleeding complication anticoagulant , chronic disease patients who are not qualified for inr assessment , but who are to be treated with antiplatelet would benefit from assessment of wbv . a recommended guideline is not to prescribe antiplatelet if contraindicated[1720 ] . yet , lack of laboratory assessment of compliance is an acknowledged major issue . the report provides insight to assessment of hypoviscosity as part of antiplatelet drug monitoring and in compliance to guidelines and good evidence - based clinical practice . further , this study reports observation of significantly higher and lower level of platelet count associated with high and low wbv respectively . it is known that antiplatelet therapy is employed in the management of hyperviscosity / stasis through modulation of platelet hyperreactivity . therefore , it is not out of place that relative high platelet count is associated with high blood viscosity . this logic is not in line with the fact that several studies have reported an association between platelet hyperreactivity after antiplatelet therapy . nevertheless , platelet function can be measured by different methods and platelet counting has been in use , except that the usage to monitor antiplatelet drugs is not common . factors that increase wbv include haematocrit , total plasma protein , erythrocyte aggregation , erythrocyte deformability and oxidative stress . in current clinical practice , a low platelet count is a factor that determines temporary stopping chemotherapy , but not antiplatelet therapy . this observation of thrombocytopenia associated with low blood viscosity provides evidence to suggest that low platelet count is also occasion to consider stopping any antiplatelet therapy . a review has reported gender - specific differences in platelet function and response to antiplatelet therapy . the report further acknowledged role for laboratory monitoring of antiplatelet medications in predicting individual responsiveness . the results from this study show that age and gender differences may not impact on the association between wbv and inr or platelet count . in corroboration with previous observation of infrequent prevalence of hyperviscosity in thromboembolic state ( whole blood viscosity issues ii on this series ) , it surmises that platelet count should necessarily be used as adjunct laboratory index to determine indication or contraindication for antiplatelet therapy . it is known that thrombocytopenia is associated with bleeding complications[2628 ] . what this article contributes is that inr , platelet count and wbv are laboratory indices to consider in constituting antiplatelet monitoring panel . the observations also corroborate with previous report to suggest putting into perspective the specificity of wbv relative to stasis . in addition , the result indicates that wbv identify individuals in whom anticoagulant and antiplatelet therapies may be contraindicated that is , from the association and clinical utility of inr . perhaps , one question is : will hypoviscosity be associated with gastrointestinal bleeding to prove evidence of being a possible contraindication index ? this report presents that higher level of inr is associated with lower level of wbv and vise versa , whereas thrombocytopenia is associated with hypoviscosity . the results indicate that wbv identifies individuals in whom anticoagulant and antiplatelet therapies are indicated or contraindicated . the findings suggest that inr , platelet count and wbv are laboratory indices to consider in constituting antiplatelet monitoring panel .

background : anticoagulant and antiplatelet therapies are being used interchangeably or in combination . while international normalized ratio is assessed to determine anticoagulant 's contraindication / need , whole blood viscosity is not assessed to determine the need for antiplatelet.aims:the objective of this study is to investigate whether whole blood viscosity value is associated with levels of international normalized ratio and platelet count.materials and methods : de - identified archived clinical pathology data for the year 2008 were audited . all cases of international normalized ratio , which were concomitantly tested for haematocrit and total proteins , were extracted ( n=7,387 ) . whole blood viscosity levels were extrapolated . whether differences are associated with normal vs. high international normalized ratio and thrombocytopenia vs. thrombocytosis were evaluated.results:multivariate analysis show that whole blood viscosity levels statistically significantly differs between international normalized ratio and platelet counts ( p<0.001 ) . platelet count is statistically significantly lower in low blood viscosity when compared with hyperviscosity and normoviscosity ( p<0.001 ) . conversely , international normalized ratio is statistically significantly higher in low blood viscosity relative to hyperviscosity ( p<0.001 ) and normoviscosity ( p<0.002 ) . no difference was observed between hyperviscosity and normoviscosity in platelet count or international normalized ratio.conclusion:the observation corroborates with previous reports to suggest putting into perspective the specificity of whole blood viscosity relative to stasis , against which antiplatelet is employed . it indicates that low whole blood viscosity is synonymous to high international normalized ratio whereby anticoagulant and antiplatelet therapies are contraindicated . international normalized ratio , platelet count and blood viscosity are laboratory indices to consider in constituting antiplatelet monitoring panel .

a 30-year - old female patient reported to the outpatient department of vasantdada patil dental college and hospital , sangli with a chief complaint of gingival swelling on the right maxillary posterior region . the patient noticed a painless swelling 6 months ago , which was small in size initially , started growing gradually and reached the present size . the patient revealed a history of similar swelling in the same region 2 years ago . surgical removal of the mass had been attempted , however it had been unsuccessful due to heavy bleeding from the site . the patient showed unilateral port - wine stain on the right side of her face extending from the superior border of the upper lip to the bridge of the nose superoinferiorly and from the midline to the preauricular region anteroposteriorly since her birth . on clinical examination , the patient revealed about 33 cm sized solitary extraoral swelling on the right maxilla extending from the midline to the midpupilary line anteroposteriorly and from the superior border of the upper lip to the base of the nose superoinferiorly . intraorally , about 36 cm sized solitary swelling , reddish pink in color was found extending from the right central incisor to the third molar on the buccal and palatal gingivae of the maxilla . the swelling involved marginal , papillary , and attached gingivae , and had smooth surface . it was soft in consistency , non - tender on palpation , compressible , pulsatile and blanched on pressure . no bleeding on palpation was noted . the right maxillary first and second premolars showed grade ii mobility . 1 ) . a provisional diagnosis of vascular lesion was given and the patient was subjected to radiographic examination . intraoral periapical radiographs showed coarse bony trabeculae and enlarged marrow spaces on the right maxillary anterior and posterior regions . widening of periodontal ligament space was seen with lateral incisor , first and second premolar and the first molar was supraerupted ( figs . panoramic radiograph showed ill - defined , irregular area of bone destruction extending from the mesial surface of the left maxillary central incisor upto the mesial surface of the right maxillary canine . admission laboratory tests showed hemoglobin ( hb ) of 7.3 g / dl , a platelet count of 63,000 per mm , prothrombin time of 17 seconds , activated partial thromboplastin time of 35 sec , and international normalized ratio of 1.3 . the patient was then given blood and platelet transfusions after which the blood investigations showed hemoglobin of 13.3 g / dl , platelet count of 1,96,000 , prothrombin time 15 seconds , activated partial thromboplastin time of 28 seconds and international normalized ratio of 1.1 . the diagnostic angiogram showed a high - flow vascular malformation supplied principally by the alveolar branch of the internal maxillary artery . surgical treatment of such lesion required extensive resection of the maxilla and might result in the dysfunction and disfigurement . ligation of the external carotid artery was not advisable , since many anastomoses promoted the rapid appearance of a collateral circulation . therefore , embolization which consisted of occlusion of the vessels which contributed to the lesion was considered . one year follow - up revealed a significant reduction of clinical symptoms and signs of the lesion without any further complications . avms are extremely rare conditions that can be fatal if left untreated.6 they are caused by disturbances in the late stages of angiogenesis , mainly abnormal differentiation of vascular system.10 vascular malformations can be subdivided further into high - flow and low - flow lesions.1,2 in the present case , angiography was performed which demonstrated a high - flow avm . most avms have a history that includes the presence of a vascular blush in the overlying skin in the childhood , which begins to expand more rapidly as the patient enters puberty or undergoes other hormonal changes . they may also reveal a history of trauma to the involved area prior to the notification of the lesion . bleeding , pain , and tissue destruction are often subsequent signs in avm.1,6 on physical examination , early avms may have an overlying vascular blush in the skin similar to an early port - wine stain . the teeth may be loose or may exhibit pumping movement when pressure is applied and released.1,3,4,6 avms can invade the skin where ulcerations and bleeding are common.1,11 some " high - flow " lesions may result in consumption coagulopathy , requiring transfusion therapy.12,13 multiple imaging modalities should be used to evaluate characteristics of avms such as size , flow velocity , flow direction , relation to the surrounding structures and lesion contents.2 there are no pathognomonic radiographic features to distinguish avms on plain radiographs . they may appear as bone erosion , sclerotic change , periosteal reaction or a cyst like radiolucent lesion . a sunburst effect , created by spicules radiating from the center , is often present.2,14 the lesions most often have a multiloculated appearance due to residual bone trapped around vessels . small radiolucent locules may resemble enlarged marrow spaces surrounded by coarse , dense , and well defined trabeculae . they may have a honey comb or soap - bubble pattern that is well demarcated from adjacent bone . the roots of the teeth in proximity of the lesion may show displacement or resorption . high - flow lesions tend to result in more destructive skeletal changes , appearing as moth - eaten and poorly defined areas of radiolucency.12 the radiographic differential diagnosis of these lesions include ameloblastoma , ameloblastic fiboma , odontogenic myxoma , central giant cell granuloma and metastatic malignant tumors.6 color doppler ultrasound examination can provide information about the flow velocity . the drawbacks of ct are considerable exposure to ionizing radiation and limited information about blood flow.2 angiography and mr imaging are the preferred imaging modalities.2,6,10,15 mri depicts the anatomic relation of the vascular lesion with adjacent organs and the flow velocity of lesions . it is useful for evaluating the lesions postoperatively.2 angiography is currently the gold standard for the determination of location and flow characteristics of vascular lesions . angiography is useful to determine blood vessels supplying blood to the lesion , and the relative venous out - flow characteristics , and the presence or absence of arteriovenous shunts.3 according to orbach , the angiographic features of avms include dilatation and lengthening of afferent arteries , early and preferential filling of shunts , delayed filling of associated normal arteries , early opacification of draining veins and rapid flow to collateral vessels.16 intentional transarterial embolization was originally described in 1969 by lalli and coworkers.17 treatment of vascular malformation with selective embolization procedure is currently highly recommended and often used . the purpose of the selective embolization is to abruptly cut off the blood supply of the lesion , reducing the risk of potentially massive and lethal blood loss after its rupture , enabling a more focused and selective surgical procedure with less morbidity and with maximal preservation of important structures.18 various materials can be used for embolization . permanent agents include silicone spheres , lyophilized dura , pva , isobutyl cyanoacrylate and stainless steel or platinum coils . pva was used in present case as it is nonabsorbable and denser than gelfoam.9 to conclude , vascular malformations represent some of the most difficult lesions to diagnose and treat . interventional radiography plays an essential role in diagnosis and management of such lesions . with the use of this technique , extensive surgical procedures can be avoided so as to avoid facial disfigurement and functional compromise .

arteriovenous malformations are extremely rare conditions in that can result from abnormalities in the structure of blood vessels , which may be potentially fatal . a 30-year - old female patient visited our hospital with a complaint of swelling on the right maxillary posterior gingiva along with the large port - wine stain on right side of face . on clinical examination , the swelling was compressible and pulsatile . radiographic examination revealed a lytic lesion of maxilla . diagnostic angiography revealed a high - flow arteriovenous malformation of maxilla which was treated by selective transarterial embolization of maxillary artery using polyvinyl alcohol particles .

elastosis perforans serpiginosa ( eps ) , characterized by transepidermal elimination of fragmented elastic fibres , clinically presents as hyperkeratotic papules . it 's rare association with pseudoxanthoma elasticum ( pxe ) has been documented in the literature . we report a case of pxe with associated lesions that were histopathologically compatible with eps . pxe is due to the mutations in the mrp6/abcc6 gene , which is a member of the atp - binding cassette ( abc ) family and acts as a transmembrane transporter primarily in the liver and the kidney , primary defect of which results in the accumulation of certain metabolic compounds with secondary calcification of elastic fibers . we also highlight the importance of the clinical finding of an exaggerated mental crease , which has been shown to be a sensitive and highly specific finding in patients under the age of 30 years with pxe . a 22-year - old female , third of four siblings born of first - degree consanguinity presented with a three - year history of excess folds of the skin on the sides of the neck and a six months history of asymptomatic eruption on the neck . there was no history of intermittent claudication , chest pain , seizures , or melena . physical examination revealed numerous small yellow brown non follicular papules about 12 mm in size arranged in a linear fashion on the sides of the neck . skin of the neck was soft , lax and was hanging in folds on the sides of neck and in both the axillae [ figures 1 and 2 ] . a few brown to black distinctive hyperkeratotic nonfollicular papules about 5 mm in diameter arranged in a serpiginous fashion with a central plug , revealing a crateriform pit on dislodgment were seen on the sides of the neck [ figure 3 ] . electrocardiogram ( ecg ) , 2d echo , and radiography of the chest were normal . the ophthalmologic examination revealed the presence of angioid streaks in the fundus , which were clinically asymptomatic [ figure 5 ] . lax skin demonstrated on the sides of neck lax skin hanging in folds in both the axillae hyperkeratotic nonfollicular papules and atrophic scars arranged in a serpiginous seen on the sides of the neck a single prominent mental crease angioid streaks in the fundus demonstrated on ophthalmoscopy histopathology of the biopsy specimen from a hyperkeratotic papule revealed hyperplastic epidermis . there were numerous fragmented , stringy , and curled elastic fibers giving the appearance of revealed wool in the upper- and mid - reticular dermis [ figure 6 ] . special staining with von kossa stain revealed calcification of the elastic fibers in the reticular dermis and in the disrupted follicular infundibular wall . with the above clinical and histopathological evidence , we diagnosed the case as pxe with associated eps . histopathology revealing numerous fragmented , stringy , and curled elastic fibers giving the appearance of raveled wool in the upper- and mid - reticular dermis [ h and e , 10 ] higher magnification revealing disrupted follicle surrounded by foreign body type granulomatous inflammation with several foreign body giant cells and neutrophils with small fragments of elastic fibers in the infundibular wall [ h and e , 40 ] pxe ( mim 264800 ) , also known as systematized elastorrhexis or gronblad strandberg syndrome is an autosomal recessive disease of the connective tissue , which primarily affects the dermis , retina , and the cardiovascular system . the prevalence is currently estimated to be 1 in 25,000 - 70,000 live births . the diagnosis of pxe is most often made late in the second or third decade of life . genetic studies have identified mutations in the mrp6/abcc6 gene on chromosome 16p13.1 , which is a member of the abc family and acts as a transmembrane transporter primarily in the liver and the kidney , primary defect of which results in the accumulation of certain metabolic compounds with secondary calcification of elastic fibers . characteristic skin lesions include yellow papules in a linear or reticulate pattern with soft , lax , wrinkled skin hanging in folds by the sides of the neck , below the clavicles , the axillae , abdomen , groins , perineum , and thighs described as eye involvement results from breaks in bruch 's membrane at the posterior aspect of the retina ( angioid streaks ) , which is symptomless but may be complicated by retinal neovessels , recurrent hemorrhage , disciform scarring , and eventual loss of central vision . most of the cardiovascular manifestations are related to early arteriosclerosis as a consequence of degenerated elastic laminae , which manifest as disappearance of peripheral pulses , intermittent claudication , angina pectoris , rarely myocardial infarction , cerebral stroke , and visceral hemorrhage . early diagnosis is important if the ocular and cardiovascular complications are to be prevented . to facilitate and unify the clinical diagnosis for pxe , three major diagnostic criteria ( characteristic yellow skin lesions in flexural sites , elastic fiber calcification in lesional skin , and ocular disease ) and two minor criteria ( histopathologic features in nonlesional skin and family history of pxe in a first - degree relative ) have been adopted . the presence of exaggerated mental crease has been shown to be asensitive and highly specific finding in patients under the age of 30 years with pxe . it may be the result of deterioration of elastic tissue in the lip and chin , or blood vessels supplying the jaw . the clinical finding of a horizontal chin crease in the presence of central loss of vision , arterial occlusive disease , or acute gastrointestinal hemorrhage should prompt the physicians to examine their patients for other features of pxe . a rare association of pxe with eps such as lesions characterized by spontaneous perforating lesions with transepidermal elimination of fragmented elastic fibers , clinically presenting as hyperkeratotic papules has been reported . eps is classified into three types : ( 1 ) idiopathic ; ( 2 ) reactive , associated in 25% of cases with connective tissue diseases ; ( 3 ) induced by d - penicillamine . confusion exists whether these perforating lesions should be considered as eps associated with pxe or simply as perforating pxe . the first group includes patients previously diagnosed with generalized hereditary pxe , who in the course of their disease progression develop clinical lesions that are histopathologically indistinguishable from eps . the second group is characterized by transepidermal elimination of altered elastic fibers occurring in a localized , acquired form of pxe usually in the periumbilical region , who do not develop other ocular , vascular , and visceral manifestations of hereditary pxe . the term periumbilical perforating pxe was first proposed by hicks et al . , in 1979 , for the second entity . localized acquired cutaneous pseudoxanthoma elasticum , as they believed that the process was acquired and was lacking differentiating the above conditions is important as the prognosis differs and a close follow up is needed in the hereditary form of pxe to rule out the systemic involvement . we categorize our patient into the hereditary form with systemic involvement such as angioid streaks and having associated eps lesions . we also highlight the importance of prominent mental crease , which when identified in an individual less than 30 years should prompt a search for pxe , which is often diagnosed as in our patient .

elastosis perforans serpiginosa ( eps ) , characterized by transepidermal elimination of fragmented elastic fibers , clinically presents as hyperkeratotic papules . eps is classified into three types : ( 1 ) idiopathic ; ( 2 ) reactive , with associated connective tissue diseases such as pseudoxanthoma elasticum ( pxe ) , ehlers danlos syndrome , cutis laxa , marfan syndrome , osteogenesis imperfecta , down 's syndrome ; ( 3 ) the one that is induced by d - penicillamine . a rare association of eps with pxe , which is primarily a defect of transmembrane transporter protein with accumulation of certain metabolic compounds and secondary calcification of elastic fibers has been documented in the literature . we report a case of pxe with associated lesions that were histopathologically compatible with eps .

according to the most recent report from the seer database , an estimated 46,420 new cases of pancreatic cancer will be diagnosed in the united states in 2014 , with 39,590 related deaths . despite recent advances in neoadjuvant and adjuvant treatment modalities , the prognosis is still dismal , with an estimated 5-year survival rate of 6.7% . unlike tumors that arise in the head of the pancreas , which present with obstructive jaundice , those that arise in the body and tail usually present late and are typically unresectable [ 24 ] . the nccn guidelines still consider tumors with celiac axis invasion to be unresectable ; nonetheless , there has been a relatively recent trend towards a more aggressive surgical approach in the management of locally advanced pancreatic cancer [ 58 ] . in the 1950s , lyon appleby first described the feasibility of celiac axis resection for locally advanced gastric cancer , which relied on the presence of an effective superior mesenteric artery ( sma ) collateral circulation to the common hepatic artery ( cha ) through the gastroduodenal artery ( gda ) or on the presence of aberrant anatomy . in 1976 , nimura et al . adopted appleby 's understanding of the utility of the collateral sma circulation and applied the technique to the surgical treatment of locally advanced pancreatic body carcinoma with celiac axis or branch invasion this technique was further modified in the 1990s to preserve the stomach via sparing of the gda and the right gastroepiploic artery , known as the modified appleby resection [ 11 , 12 ] . given that the feasibility of this advanced surgical technique is entirely based on the presence of collateral circulation or aberrant anatomy , it is crucial to objectively confirm the presence of an anatomical and functional collateral system . the original description by appleby included an intraoperative assessment of collateral flow through the gda after manually occluding ( clamping ) the cha proximal to the takeoff of the gda . this technique has been adopted by many surgeons and is by far the most commonly used method . others have described assessment by intraoperative doppler ultrasonography to complement manual digital assessment as a more objective method . the drawback of both techniques is the necessity of performing an exploratory laparotomy in order to do the assessment . preoperative assessment of vascular anatomy and collateral circulation could provide crucial information to help with decision making . snapshot of the arterial anatomical system to illustrate the patient 's vascular anatomy , including aberrant variants . an angiogram , on the other hand , not only provides more of a real - time demonstration of the patient 's vascular anatomy , but is also the only reliable way to conclusively demonstrate , preoperatively , the presence or absence of collateral flow in the case of celiac trunk occlusion . the use of an angiogram to reliably assess sufficient visceral flow through collateral vessels has been tested and described during the endovascular repair of thoracoabdominal aneurysms , where occasionally coverage of the celiac artery ( ca ) is necessary and has been shown to be feasible and safe [ 15 , 16 ] . we here describe a novel technique used in two cases of pancreatic cancer at our institution that were candidates for appleby resection . both patients had a preoperative angiogram for assessment of anatomical circulation and placement of an endovascular stent to cover the ca once confirmation of adequate collateral flow was obtained . this procedure not only helps enhance collateral circulation but , theoretically , it may help to minimize intraoperative blood loss when transecting the ca at its takeoff . moreover , extra length on the ca margin may be gained as the artery can be transected at its origin without the need for vascular clamp placement . the first case is a 63-year - old woman with diabetes mellitus and no surgical history , who was found to have pancreatic adenocarcinoma during an investigation of her epigastric pain . her preoperative ct scan showed a pancreatic body and tail mass , measuring 3.4 3.2 3.5 cm ( figure 1 ) . the primary mass encircled the splenic artery circumferentially , focally abutting the stomach , as well as the anterosuperior aspect of the left renal vein . an ultrasound - guided biopsy of the mass confirmed an adenocarcinoma compatible with a pancreatic origin . the patient underwent neoadjuvant treatment ( folfirinox followed by radiation therapy and gemcitabine ) . a follow - up ct scan of the chest , abdomen , and pelvis after her neoadjuvant treatment showed stable disease . three weeks later , in november 2014 , she underwent an angiogram with an endovascular stent placement . filling of the small bowel mesentery after the ca angiogram confirmed the presence of collateral circulation to the sma . an endovascular stent ( 24 mm/42 mm proximal extension graft [ renu stent graft , cook medical ] ) was placed to cover the ca , as illustrated in figure 2 . three weeks later , the patient underwent a subtotal pancreatectomy with en bloc celiac axis resection ( modified appleby resection ) with splenectomy , en bloc left adrenalectomy , and partial gastrectomy . during the exploration , it was noted that good collateral system development was evident from the size of the gastroepiploic vessels . demonstration of continued flow to the proper hepatic artery after clamping the cha proximal to the gda takeoff was accomplished by using intraoperative doppler ultrasonography . the ca was clamped and suture ligated with a 3.0 prolene suture . the patient 's postoperative course was unremarkable and she was discharged home on postoperative day 4 . her final pathology report showed residual ductal adenocarcinoma moderately to poorly differentiated in the tumor bed measuring 3 cm with estimated viable tumor cell cellularity of 15% . all margins were negative and there was no evidence of lymph node involvement ( 0/14 lymph nodes ) . his original diagnosis of pancreatic cancer was in 2007 in an outside institution , after which he underwent a distal pancreatectomy . he was seen postoperatively at our institution for adjuvant treatment and surveillance , during which time he was found to have a local recurrence on imaging . his annual ct scan showed a soft tissue mass , located between the hepatic artery and the portal vein , which encased the former vessel . its maximal diameter was measured at 2.5 2 cm , with an adjacent necrotic node measuring 1.2 1.5 cm ( figure 3 ) . on positron emission tomography , only focal mild hypermetabolism was noted at the site of the suspected recurrence with no evidence of metastatic disease , which was confirmed on a ct chest . the patient underwent neoadjuvant therapy ( gemcitabine with radiation therapy followed by gemcitabine - oxaliplatin ) . a ct scan to assess response showed stable disease . in april 2013 , the patient underwent an angiogram that detected a replaced right hepatic artery originating from the sma ( figure 4 ) . an endovascular stent ( 32 mm proximal extension graft [ renu stent graft , cook medical ] ) was placed to cover the ca . three weeks later , the patient underwent an exploratory laparotomy , which revealed the mass in the surgical bed , where the cha was completely engrossed by the tumor with a margin of less than 1 cm before the takeoff of the gda . confirmation of effective collateral flow after clamping the cha was demonstrated and further confirmed with intraoperative doppler sonography . the mass was resected en bloc after clamping the cha and transecting it just proximal to the gda . in this patient 's case , we were required to resect the ca flush with the aorta to ensure gross negative margins ; this was made less complicated because of the presence of the endovascular stent . the patient did well postoperatively with no complications and was discharged home on postoperative day 5 . his final pathology report showed moderately differentiated adenocarcinoma measuring 2.5 cm with focal involvement of resection margin . this patient was seen recently for his 18-month follow - up and was doing very well with no clinical or radiological evidence of recurrence of his disease . with this report , we introduce a novel technique in candidates for a modified appleby resection . the use of a preoperative angiogram offers real - time visualization of the patient 's circulation with reliable assessment of collateral circulation . this can be demonstrated by viewing hepatic flow during a selective sma angiogram or by viewing mesenteric flow during a selective ca angiogram . another technique that could also be used ( but was not used in our cases ) is the balloon occlusion test , in which the ca can be temporarily occluded and then collateral flow demonstrated during a selective sma angiogram . in certain patients , such as in our second case , aberrant hepatic artery anatomy can be demonstrated during the angiogram . in the event of demonstration of inadequate collateral circulation , a more aggressive combined and technically demanding resection with hepatic artery reconstruction could be discussed with the patient [ 1719 ] . preoperative ca obstruction not only confirms the adequacy of the collateral circulation prior to performing a major resection but may also allow for the patient to improve his / her collateral flow preoperatively and potentially decrease the risk of postoperative ischemic complications , a well - recognized risk with this procedure . keskitalo and colleagues demonstrated in animal lab that experimental acute ca occlusion in dogs increased the collateral blood flow to 30% immediately and to 50% after three hours . this occlusion - induced increase of pressure within the preexisting collateral system triggers arteriogenesis ( defined as the growth of functional collateral arteries from preexisting arterioarteriolar anastomoses ) and is mediated by the proliferation of vascular smooth muscle cells [ 22 , 23 ] . this neocollateral network was found in animal labs to have partial flow detectable as early as few days with the bulk of network development occurring by 3 weeks [ 24 , 25 ] . the presence of the stent also allows the resection of the ca as close as possible to its takeoff without the need to place a vascular clamp . this is a major advantage as compared to the technique of coiling the common hepatic artery preoperatively as described by takasaka et al . . thus , this will improve the ability to safely obtain negative margins and limit intraoperative blood loss during this part of the procedure . it is true that an angiogram with endovascular stent placement is on its own an invasive procedure with potential complications ; however , if done by experts in the field in properly selected patients , it can be deemed safe [ 2729 ] . we therefore propose this novel technique in the preoperative management of patients undergoing a modified appleby procedure . while further experience is required , we believe that it confers significant advantages to the current standard of care .

background . pancreatic adenocarcinoma of the body and tail usually presents late and is typically unresectable . the modified appleby procedure allows resection of pancreatic body carcinoma with celiac axis ( ca ) invasion . given that the feasibility of this technique is based on the presence of collateral circulation , it is crucial to confirm the presence of an anatomical and functional collateral system . methods . we here describe a novel technique used in two patients who were candidates for appleby resection . we present their clinical scenario , imaging , operative findings , and postoperative course . results . both patients had a preoperative angiogram for assessment of anatomical circulation and placement of an endovascular stent to cover the ca . we hypothesize that this new technique allows enhancement of collateral circulation and helps minimize intraoperative blood loss when transecting the ca at its takeoff . moreover , extra length on the ca margin may be gained , as the artery can be transected at its origin without the need for vascular clamp placement . conclusion . we propose this novel technique in the preoperative management of patients who are undergoing a modified appleby procedure . while further experience with this technique is required , we believe that it confers significant advantages to the current standard of care .

phytophotodermatitis connotes phototoxic reactions consisting of erythema ( with or without blistering ) and delayed hyperpigmentation . it is entirely independent of the immune system ; that is , phytophotodermatitis can occurs in any individual and does not require prior sensitization . the ingredients needed to produce phytophotodermatitis include temporal exposure to both a photosensitizing substance ( such as furocoumarins ) and the appropriate wavelength of ultraviolet radiation ( uvr ) . herein , we first report two cases of phytophotodermatitis after contact with chinese herbal medicine ( chm ) decoction . on june 28 2009 , a chinese 24-year - old female presented to the clinic with a 7-day history of linear hyperpigmentation on her legs . physical examination showed sharply demarcated hyperpigmented lines and curves on the extensor aspects of thighs and legs [ figure 1 ] , bizarre fuscescent patches on the dorsal aspects of laps [ figure 2 ] . the patient complained of mild burning erythema on these sizes before 4 days , without any treatment , the preceding inflammatory reaction disappeared and left behind these rebarbative brown lines . she remembered that , before the onset of the rash , she had prepared the decoction of chm ( including atractylodes macrocephala , cicada slough , pheretima asiatica , liquorice root , astragalus mongholicus , chinese angelica , sinensis , pricklyash peel , common selfheal fruit - spike ) for her son ( case 2 ) . during the process , inadvertent splash of chm decoction onto the skin happened to her and her son . at that time , she was in a skirt ; the decoction was sprayed onto the dorsal aspects of laps and trickled down the legs to the ankles . one day thereafter , she developed mild erythema with slight and transient burning sensation on the sites of contact with the chm decoction . ultimately , a final diagnosis of phytophotodermatitis was established . the patient was prescribed with topical complex arbutin cream twice daily and vitamin c by mouth . the hyperpigmentation over the affected areas was slightly lightened 2 months after the initial clinical presentation . sharply demarcated hyperpigmented lines and curves on the extensor aspects of thighs and legs bizarre fuscescent patches on the dorsal aspects of laps an 11-month - old boy , the son of case 1 , was referred to for evaluation of alutaceous maculae and patches on his right neck and upper chest [ figure 3 ] for 7 days . the boy suffered from fever cough and was prescribed with the chm decoction ( above mentioned ) peros . frequently , the boy struggled and refused to drink this decoction because of its bitter in taste . the physic liquor was sporadically sprinkle on his perioral areas and run down onto neck and upper chest , even splashed onto his mother 's legs in one time . the child was exposed to sunlight . during the subsequent 24 h , a burning erythema developed on these sites , disappeared within 34 days , and remained brown patches . alutaceous maculae and patches on right neck and upper chest of the boy physical examination showed bizarre hyperpigmented maculae and patches with blurry borders on his right neck and upper chest . the skin covered by his suit was spared . without any treatment , the light tan maculae and patches resolved during the 2-month follow - up on june 28 2009 , a chinese 24-year - old female presented to the clinic with a 7-day history of linear hyperpigmentation on her legs . physical examination showed sharply demarcated hyperpigmented lines and curves on the extensor aspects of thighs and legs [ figure 1 ] , bizarre fuscescent patches on the dorsal aspects of laps [ figure 2 ] . the patient complained of mild burning erythema on these sizes before 4 days , without any treatment , the preceding inflammatory reaction disappeared and left behind these rebarbative brown lines . she remembered that , before the onset of the rash , she had prepared the decoction of chm ( including atractylodes macrocephala , cicada slough , pheretima asiatica , liquorice root , astragalus mongholicus , chinese angelica , sinensis , pricklyash peel , common selfheal fruit - spike ) for her son ( case 2 ) . during the process , inadvertent splash of chm decoction onto the skin happened to her and her son . at that time , she was in a skirt ; the decoction was sprayed onto the dorsal aspects of laps and trickled down the legs to the ankles . one day thereafter , she developed mild erythema with slight and transient burning sensation on the sites of contact with the chm decoction . ultimately , a final diagnosis of phytophotodermatitis was established . the patient was prescribed with topical complex arbutin cream twice daily and vitamin c by mouth . the hyperpigmentation over the affected areas was slightly lightened 2 months after the initial clinical presentation . sharply demarcated hyperpigmented lines and curves on the extensor aspects of thighs and legs bizarre fuscescent patches on the dorsal aspects of laps an 11-month - old boy , the son of case 1 , was referred to for evaluation of alutaceous maculae and patches on his right neck and upper chest [ figure 3 ] for 7 days . the boy suffered from fever cough and was prescribed with the chm decoction ( above mentioned ) peros . frequently , the boy struggled and refused to drink this decoction because of its bitter in taste . the physic liquor was sporadically sprinkle on his perioral areas and run down onto neck and upper chest , even splashed onto his mother 's legs in one time . the child was exposed to sunlight . during the subsequent 24 h , a burning erythema developed on these sites , disappeared within 34 days , and remained brown patches . alutaceous maculae and patches on right neck and upper chest of the boy physical examination showed bizarre hyperpigmented maculae and patches with blurry borders on his right neck and upper chest . the skin covered by his suit was spared . without any treatment , the light tan maculae and patches resolved during the 2-month follow - up on june 28 2009 , a chinese 24-year - old female presented to the clinic with a 7-day history of linear hyperpigmentation on her legs . physical examination showed sharply demarcated hyperpigmented lines and curves on the extensor aspects of thighs and legs [ figure 1 ] , bizarre fuscescent patches on the dorsal aspects of laps [ figure 2 ] . the patient complained of mild burning erythema on these sizes before 4 days , without any treatment , the preceding inflammatory reaction disappeared and left behind these rebarbative brown lines . she remembered that , before the onset of the rash , she had prepared the decoction of chm ( including atractylodes macrocephala , cicada slough , pheretima asiatica , liquorice root , astragalus mongholicus , chinese angelica , sinensis , pricklyash peel , common selfheal fruit - spike ) for her son ( case 2 ) . during the process , inadvertent splash of chm decoction onto the skin happened to her and her son . at that time , she was in a skirt ; the decoction was sprayed onto the dorsal aspects of laps and trickled down the legs to the ankles . one day thereafter , she developed mild erythema with slight and transient burning sensation on the sites of contact with the chm decoction . ultimately , a final diagnosis of phytophotodermatitis was established . the patient was prescribed with topical complex arbutin cream twice daily and vitamin c by mouth . the hyperpigmentation over the affected areas was slightly lightened 2 months after the initial clinical presentation . sharply demarcated hyperpigmented lines and curves on the extensor aspects of thighs and legs bizarre fuscescent patches on the dorsal aspects of laps an 11-month - old boy , the son of case 1 , was referred to for evaluation of alutaceous maculae and patches on his right neck and upper chest [ figure 3 ] for 7 days . the boy suffered from fever cough and was prescribed with the chm decoction ( above mentioned ) peros . frequently , the boy struggled and refused to drink this decoction because of its bitter in taste . the physic liquor was sporadically sprinkle on his perioral areas and run down onto neck and upper chest , even splashed onto his mother 's legs in one time . the child was exposed to sunlight . during the subsequent 24 h , a burning erythema developed on these sites , disappeared within 34 days , and remained brown patches . alutaceous maculae and patches on right neck and upper chest of the boy physical examination showed bizarre hyperpigmented maculae and patches with blurry borders on his right neck and upper chest . the skin covered by his suit was spared . without any treatment , the light tan maculae and patches resolved during the 2-month follow - up contact with plant - derived phototoxic substances ( frequently found in umbilliferae , moracea , rutaceae , and leguminous ) followed by sunlight exposure produces the clinical lesions . furocoumarins , which are frequently found in limes , lemons , oranges , celery , fig , parsnip , parsley , carrots , dill , and perfumes , are photosensitizing chemical components and consist of psoralens , 5-methoxypsoralens , 8-methoxypsoralens , angelicin , bergaptol , and xanthotal.[24 ] the wavelengths of ultraviolet light that most efficiently produce phytophotodermatitis lie within the uv - a range and have peak activity at 335 nm . a type i reaction occurs in the absence of oxygen , whereas a type ii reaction occurs in the presence of oxygen . these photochemical reactions damage cell membranes and dna and result in dna interstrand cross - linking between the psoralen furan ring and the thymines or the cytosines of dna . this results in activation of arachidonic acid metabolic pathways and in cell death ( sunburn cells and apoptotic keratinocytes ) . first , melanin , which is normally found in the epidermis , falls into the dermis and is ingested by melanophages . second , an increased number of functional melanocytes and melanosomes are distributed in the epidermis following phytophotodermatitis and also account for the hyperpigmentation . clinically , this corresponds with irregular hyperpigmentation seen as the end stage of the phototoxic reaction . phytophotodermatitis most commonly occurs in the spring and the summer when furocoumarins are at their highest concentration in plants and when uv exposure is greatest for patients . it is frequently found in people who spend a lot of time participating in outdoor activities , beach - goers , and children playing outdoors . therefore , phytophotodermatitis is most commonly found on skin sites exposed to plants and sunlight , such as arm and leg , but it may occur anywhere . lesions may or appear as hyperpigmented patches without a preceding erythematous phase , as happened in case 1 . . these patterns often result from brushing against a plant 's stems or leaves while outdoors or from the liquid spread of lime juice over the hand or down the forearm . reproduce phytophotodermatitis in animal models by spraying peel juice of tahiti lemon onto the skin of epilated albino rats and observe its serial pathological changes . after 24 h spongiosis , vacuolization and keratinocyte necrosis are observed , clinically there are no changes . almeida et al . examined the epidermis in induced phytophotodermatitis using transmission electron microscopy in order to detect histological changes even before lesions are visible by light microscopy , they found vacuolization in keratinocytes immediately after induction . free desmosomes and membrane ruptures were also seen . at 2 h after induction , similar changes were found , and granular degeneration of keratin was also observed . a history of contact with one of the offending plants and subsequent sunlight exposure should be sought . most commonly , it is a localized cutaneous phenomenon resulting initially in a burning sensation . in severe cases , first , our patients lesions were caused by inadvertent splash of chm decoction onto the skin , did not result from exposure to fresh fluid of plants . the boiled chm included eight kinds of plant in which chinese angelica and pricklyash peel containing furocoumarins that can induce phytophotodermatitis . second , the lesions in case 1 mainly presented bizarre hyperpigmented lines and curves depending on how the decoction drip over the skin surface without obviously acute inflammatory reaction such as erythema and blister .

a 24-year - old female presented to the clinic complaining of bizarre patterns and linear streaks of hyperpigmentation on her legs and bizarre alutaceous patches on the neck and upper breast of her son for 7 days . physical examination showed sharply demarcated hyperpigmented streaks on the extensor aspects of legs and bizarre brown maculae and patches on the right neck and upper chest of her son . considering the history of chinese herbal medicine decoction had been splashed onto these sites , phytophotodermatitis was definitely diagnosed .

the most significant and debilitating complication of herpes zoster is herpetic neuralgia that accompanies and may persist in 10 - 15% of all zoster patients , particularly those over 60 years of age . herpes zoster ( hz ) , a sporadic infection with an estimated lifetime risk of 10 - 20% , occurs in all age groups , especially among individuals who have had varicella any time in the past , but its prevalence almost doubles in each decade past the age of 50 years . the most significant and debilitating complication of hz is herpetic neuralgia that accompanies and may persist in 10 - 15% of all zoster patients , particularly those over 60 years of age . cranial and peripheral nerve palsies , encephalitis , pneumonitis , acute retinal necrosis , encephalitis , myelitis , and secondary bacterial infection are other well - known complications of hz . the described cases had an uncommon complication of spontaneous tooth exfoliation after trigeminal hz , of which only about 30 cases have been reported before 2006 in the english literature.[138 ] this 80-year - old hiv - negative male had spontaneous loss of teeth from right upper jaw about 10 days after severe tooth pain , gingival swelling / ulceration , and cutaneous vesicular eruptions over right cheek , suggestive of hz , for which he took analgesics only . he had few loose or missing teeth previously but not in the right upper quadrant . the skin and gingival lesions had healed in about 2 weeks , but he still had paresthesia over the right cheek . oro - cutaneous examination [ figure 1a and b ] showed hyperesthesia , scarring , and milia over right facial skin innervated by maxillary division of right trigeminal nerve , slight deviation of upper lip , and edentulous right upper alveolar ridge due total loss of teeth . there was minimal periodontitis and few missing teeth in lower jaw , but no oral lesions , gingival ulceration / necrosis , blood , purulent exudates , granulation or loose teeth were noted . x - ray of the jaw and orthopantograph ( opg ) showed complete loss of teeth in right upper quadrant and no necrosis or other abnormality of the alveolar bone [ figure 1c and d ] . systemic examination , complete blood counts , serum biochemistry , urinalysis , and chest x - ray were essentially normal , and he had no other predisposing factors for immune suppression . the oral prophylaxis performed , and the patient was provided with artificial removable dentures later . ( a ) post - herpes zoster scarring and milia formation over the skin innervated by maxillary branch of right trigeminal nerve . ( b ) unilateral exfoliated right upper incisors , canine , premolar , and molar teeth leaving him edentulous in right upper quadrant . no alveolar bone necrosis is noted this 55-year - old hiv - negative female was hospitalized for painful vesicular lesions over right cheek , right half of tongue and buccal mucosa innervated by right mandibular nerve , and corresponding gingival swelling . although she had toothache 2 days prior to onset of skin lesions , there was no blood , purulent exudates , granulation , or loose teeth . she had mild generalized periodontitis and few missing teeth , but teeth in right lower quadrant were intact . systemic examination , complete blood counts , serum biochemistry , urinalysis , and chest x - ray showed no abnormality , and there were no predisposing factors for immune suppression . clinical diagnosis of hz was made , and she was treated with intravenous acyclovir ( 500 mg 8 hourly / d ) for initial 2 days , followed by oral acyclovir ( 800 mg 5 times / d ) for the next 1 week and was sent home . oro - cutaneous examination on return visit 2 weeks later showed hyperesthesia and hyperpigmentation of facial skin over right mandibular area , slight hypo-/hyperpigmentation of lower lip , and edentulous right lower alveolar ridge due total loss of teeth [ figure 2a and b ] . orthopantograph showed complete loss of teeth in right lower quadrant and no necrosis or other abnormality of the alveolar bone [ figure 2c ] . the oral prophylaxis performed . ( a ) post - herpes zoster hypopigmentation and hyperpigmentation over the skin innervated by mandibular branch of right trigeminal nerve . ( b ) edentulous alveolus showing healing after exfoliation of all teeth in right lower quadrant . ( c ) orthopantograph shows total loss of right mandibular teeth but no alveolar bone necrosis this 45-year - old hiv - negative male presented with spontaneous loss of few teeth from right lower jaw about 3 weeks after severe gingival / tooth pain and vesiculo - ulcerative eruptions over tongue and skin over right mandibular region , suggestive of hz . the skin and gingival lesions had healed in about 2 weeks , but he still felt abnormal sensations over the healed skin eruption area . there was hyperpigmentation and hyperesthesia over right facial skin innervated by mandibular division of right trigeminal nerve , loss of right lower incisors , canine , premolar teeth , exposed portions of the empty tooth sockets in the alveolar bone , and root surfaces of the exfoliated teeth , but no loose teeth were found [ figure 3 ] . x - ray of the jaw showed empty sockets corresponding to lost teeth and no necrosis or other abnormality of the alveolar bone . systemic examination , laboratory work - up , and chest x - ray were essentially normal , and there were no predisposing factors for immune suppression . ( a ) post - herpes zoster hyperpigmentation ending abruptly in the midline over the skin innervated by mandibular branch of right trigeminal nerve . ( b ) unilateral empty tooth sockets from the exfoliated right lower incisors , canine , and premolar teeth ending abruptly in the midline are clearly visible . this 80-year - old hiv - negative male had spontaneous loss of teeth from right upper jaw about 10 days after severe tooth pain , gingival swelling / ulceration , and cutaneous vesicular eruptions over right cheek , suggestive of hz , for which he took analgesics only . he had few loose or missing teeth previously but not in the right upper quadrant . the skin and gingival lesions had healed in about 2 weeks , but he still had paresthesia over the right cheek . oro - cutaneous examination [ figure 1a and b ] showed hyperesthesia , scarring , and milia over right facial skin innervated by maxillary division of right trigeminal nerve , slight deviation of upper lip , and edentulous right upper alveolar ridge due total loss of teeth . there was minimal periodontitis and few missing teeth in lower jaw , but no oral lesions , gingival ulceration / necrosis , blood , purulent exudates , granulation or loose teeth were noted . x - ray of the jaw and orthopantograph ( opg ) showed complete loss of teeth in right upper quadrant and no necrosis or other abnormality of the alveolar bone [ figure 1c and d ] . systemic examination , complete blood counts , serum biochemistry , urinalysis , and chest x - ray were essentially normal , and he had no other predisposing factors for immune suppression . the oral prophylaxis performed , and the patient was provided with artificial removable dentures later . ( a ) post - herpes zoster scarring and milia formation over the skin innervated by maxillary branch of right trigeminal nerve . ( b ) unilateral exfoliated right upper incisors , canine , premolar , and molar teeth leaving him edentulous in right upper quadrant . this 55-year - old hiv - negative female was hospitalized for painful vesicular lesions over right cheek , right half of tongue and buccal mucosa innervated by right mandibular nerve , and corresponding gingival swelling . although she had toothache 2 days prior to onset of skin lesions , there was no blood , purulent exudates , granulation , or loose teeth . she had mild generalized periodontitis and few missing teeth , but teeth in right lower quadrant were intact . systemic examination , complete blood counts , serum biochemistry , urinalysis , and chest x - ray showed no abnormality , and there were no predisposing factors for immune suppression . clinical diagnosis of hz was made , and she was treated with intravenous acyclovir ( 500 mg 8 hourly / d ) for initial 2 days , followed by oral acyclovir ( 800 mg 5 times / d ) for the next 1 week and was sent home . oro - cutaneous examination on return visit 2 weeks later showed hyperesthesia and hyperpigmentation of facial skin over right mandibular area , slight hypo-/hyperpigmentation of lower lip , and edentulous right lower alveolar ridge due total loss of teeth [ figure 2a and b ] . orthopantograph showed complete loss of teeth in right lower quadrant and no necrosis or other abnormality of the alveolar bone [ figure 2c ] . the oral prophylaxis performed . ( a ) post - herpes zoster hypopigmentation and hyperpigmentation over the skin innervated by mandibular branch of right trigeminal nerve . ( b ) edentulous alveolus showing healing after exfoliation of all teeth in right lower quadrant . ( c ) orthopantograph shows total loss of right mandibular teeth but no alveolar bone necrosis this 45-year - old hiv - negative male presented with spontaneous loss of few teeth from right lower jaw about 3 weeks after severe gingival / tooth pain and vesiculo - ulcerative eruptions over tongue and skin over right mandibular region , suggestive of hz . the skin and gingival lesions had healed in about 2 weeks , but he still felt abnormal sensations over the healed skin eruption area . there was hyperpigmentation and hyperesthesia over right facial skin innervated by mandibular division of right trigeminal nerve , loss of right lower incisors , canine , premolar teeth , exposed portions of the empty tooth sockets in the alveolar bone , and root surfaces of the exfoliated teeth , but no loose teeth were found [ figure 3 ] . x - ray of the jaw showed empty sockets corresponding to lost teeth and no necrosis or other abnormality of the alveolar bone . systemic examination , laboratory work - up , and chest x - ray were essentially normal , and there were no predisposing factors for immune suppression . ( a ) post - herpes zoster hyperpigmentation ending abruptly in the midline over the skin innervated by mandibular branch of right trigeminal nerve . ( b ) unilateral empty tooth sockets from the exfoliated right lower incisors , canine , and premolar teeth ending abruptly in the midline are clearly visible . hz of trigeminal nerve manifests as painful vesicular eruptions of the skin and mucosa innervated by the affected nerve division . its major complications vary from temporary prodromal odontalgia to permanent tooth nerve damage , devitalized teeth , abnormal development of permanent teeth , root resorption , muscle paralysis , multiple ocular and ear complications , prolonged neuralgia , trigeminal trophic syndrome , and occasionally encephalitis . the pain of trigeminal zoster frequently simulates toothache , not uncommonly leading to tooth extraction . other oral complications like exfoliation of teeth and alveolar bone necrosis or osteomyelitis of maxilla or mandible have been rarely described in dermatology literature . osteonecrosis following hz often presents as painless exfoliation of teeth in the involved area approximately 6 weeks after the vesicular eruptions when the acute phase has subsided . the precise pathomechanism(s ) of these oral complications eventually leading to tooth loss and necrosis of the alveolar bone , periodontal tissue membrane , nerve supply , and adjacent gingival tissue remain largely uncertain . the pre - existing local periodontal disease does not appear to influence the tooth loss . although the majority of the described cases are aged over 50 years , had severe hz , were suffering from lymphoproliferative or other malignancies , hiv infection , receiving corticosteroids or chemo-/radiotherapy , the conditions well - known for increased incidence and severity of hz , few of the reported cases have been young , immunocompetent , and otherwise healthy individuals suggesting that factors like old age , pre - existing systemic illnesses too seem not to precipitate this rare complication . it has been also postulated that it could result from intense vasoconstriction , endarteritis , or vasculitis with ischemia of the blood supply that may be caused by the virus migrating along the trigeminal neurovascular bundle . it is possible that the varicella zoster virus invades the sympathetic nerves that accompanying the blood vessels to the alveolar bone causing vasoconstriction and hampered blood supply or that systemic viral infection perhaps injures odontoblasts and cause degenerative tissue changes / pulp necrosis . another plausible explanation is that by direct extension of neural inflammation and edema , the adjacent alveolar artery may get compressed in the narrow bony channels and resultant poor tissue perfusion . the postulation of local vasculitis caused by varicella zoster virus leading to infarction and ischemia of the periodontal tissue and alveolar bone has limited evidence despite well - documented vascular damage it causes in the central nervous system . interestingly , early anti - viral medication too does not appear to prevent this complication as is evident in our case-2 . our patients were immunocompetent , never used tobacco , and had only minimal pre - existing local periodontal disease , suggesting that the hz infection perhaps remains the primary determinant for exfoliation of teeth / bone necrosis . we feel that the described cases will make dermatologists aware of this rather unusual trigeminal hz complication described mainly in the literature on oro - dental diseases . spontaneous tooth exfoliation after trigeminal herpes zoster is a rare complication that rarely finds mention in dermatology literature .

the most significant and debilitating complication of herpes zoster ( hz ) is herpetic neuralgia that accompanies and may persist in 10 - 15% of all zoster patients , particularly those over 60 years of age . the described 3 cases had an uncommon complication of spontaneous tooth exfoliation after trigeminal hz that rarely finds mention in dermatology literature .

a 22-year - old woman was exposed to severe acute carbon monoxide poisoning at 29 gestational weeks after an accidental home fire . she felt diminished fetal movements , and the cardiotocographic monitoring showed a micro oscillating and unresponsive fetal heart rate . fetal cerebral magnetic resonance imaging at 31 gestational weeks exhibited bilateral basal ganglia , thalami , posterior brain stem , and corticospinal tract injuries ( figure 1 , images 1 - 3 ) . frontal periventricular cysts revealed white matter injuries and a hyposignal of the posterior limb of the internal capsule was also observed ( figure 1 , images 2 and 3 ) . transcerebellar diameter measured at 38 mm , below the fifth percentile for equivalent gestational week reflected cerebellar atrophy . a female infant was born ( birth weight : 2.340 kg [ 75th percentile ] , head circumference : 31 cm [ 50th percentile ] , height : 46 cm [ 75th percentile ] ) . the chest was hypoplasic , and the face was amimic with a severe swallowing impairment . neurologic examination displayed a diffuse arthrogryposis affecting all joints of the superior and inferior limbs leading to severe wrist and elbow contractures and hips dislocation . antenatal brain imaging ( 1 - 3 ) t2-weighted sequences ( 1 ) sagittal view , hyposignal of the posterior brainstem ( arrow ) ; ( 2 ) coronal view : bilateral periventricular cysts ( arrow ) ; ( 3 ) axial view : bilateral hyposignal of the posterior limb of the internal capsule ( arrows ) . 4 , coronal t1-weighted sequence , bilateral hypersignal of the corticospinal tracts and putamen ( arrow ) ; ( 5 ) coronal t2-weighted sequence , bilateral periventricular cysts ( arrow a ) , hypersignal of the putamen ( arrow b ) , hyposignal of the cortical ribbon ( arrow c ) ; ( 6 ) axial t1-weighted sequence , bilateral hypersignal of the lentiform nuclei and thalami ( arrows ) . basal ganglia , thalami , posterior limb of the internal capsule , and corticospinal tracts should also be closely analyzed for all patients with arthrogryposis multiplex congenita , even in less severe cases , requiring some expertise on fetal radiology . severity of arthrogryposis multiplex congenita is related to its etiology and its time of occurrence ; the second trimester causes are the severest . however , in this observation , the fetus developed extensive arthrogryposis multiplex congenita over 5 weeks only , suggesting that the severity of brain damage plays a key role . charollais et al described a fetus with normal vitality and brain morphology on ultrasound investigations up to 32 gestational weeks . at 36 gestational weeks , active movements diminished and finally the infant was born at 37 gestational weeks with a severe arthrogryposis multiplex congenita related to multicystic encephalopathy due to an acute ischemic event . multiple etiologies of arthrogryposis multiplex congenita have been reported . neurological diseases ( central or peripheral ) are the most frequent ( 70%-80% ) and have the poorest outcome . central disorders account for one - third of arthrogryposis multiplex congenita causes , including migration disorders , olivopontocerebellar - corticospinal tracts degeneration , and encephaloclastic process . peripheral disorders include peripheral neuropathy due to hypomyelinative process , anterior horn diseases , neuromuscular junction disorders , and disease of the muscle . deep gray matter and corticospinal lesions are rare . in a cohort of 83 patients , a patient presented pyramidal tract degeneration and 2 other patients evidenced acquired brain ischemic injuries with no further details . in another report of a cohort of 68 cases , 2 patients with arthrogryposis multiplex congenita had a history of intrauterine ischemia , with a gestation marked by a severe maternal hemorrhagic shock occurring the second trimester for the first patient , and a twin - to - twin transfusion syndrome at 25 gestational weeks leading to a fetal death of the twin . the mechanism of brain lesions in our observation can be interesting to discuss with the questionable respective part of carbon monoxide poisoning and circulatory impairment in the generation of the fetal injury . carbon monoxide binds to hemoglobin with an affinity estimated 200 times superior than oxygen , leading to hypoxia . moreover , carbon monoxide has 2.5 times more affinity for fetal hemoglobin than adult hemoglobin . the fetus accumulates carbon monoxide , exposed to higher rates of carbon monoxide hemoglobin for a longer period of time than his or her mother . fetal neurological consequences of the carbon monoxide poisoning depend on the severity of maternal intoxication and the gestational age occurrence of this insult . fetal and postnatal magnetic resonance imaging in the present observation showed mostly deep gray matter mimicking severe term hypoxic ischemic magnetic resonance imaging patterns . in this observation , 2 intricate mechanisms leaded to fetal hypoxia , namely , direct carbon monoxide toxicity and maternal hemodynamic compromise . deep gray matter is the most vulnerable region requiring the highest energy resources and has the highest concentration of excitatory amino acid receptors in fetus and neonates . during gestation , thalami and brain stem the magnetic resonance imaging appearances of brain lesions after acute carbon monoxide intoxication were reviewed in 19 adult patients . globus pallidus was reported as the commonest site of injuries . in our case report , ischemia was also responsible for decreased cerebellar growth without evidence of cortical atrophy , demonstrating the peculiar cerebellar vulnerability during the third trimester of pregnancy . in another cohort , 2 infants exposed to intrauterine ischemic event presented microcephaly and cerebral atrophy . in conclusion , acquired in utero ischemic corticospinal tracts and basal ganglia injuries can be a cause to consider in infants with arthrogryposis multiplex congenita , requiring a focused reading of magnetic resonance imaging .

arthrogryposis multiplex congenita is a syndromic condition defined by contracture of 2 or more joints . a large range of etiologies has been reported such as neuromuscular disorders ( peripheral dysfunction ) , chromosomal abnormalities , or cerebral malformations ( central dysfunction ) leading to fetal immobility . severity of arthrogryposis depends on the etiology and duration of fetal immobility . the authors report a 34 gestational weeks infant presenting with severe diffuse arthrogryposis symptoms and respiratory failure at birth . her mother experienced cardiac arrest at 29 gestational weeks due to carbon monoxide intoxication . fetal magnetic resonance imaging revealed extensive corticospinal tract lesions . antenatal ischemia of the deep gray matter needs to be considered as a possible arthrogryposis cause .

chorioangiomas are the most common benign tumors of the placenta originating from primitive angioblastic tissues . the newborn are rare and usually associated with tumors greater than 5 cm in diameter and consist of polyhydramnios , fetal anemia , massive edema with pleural effusion , ascites and intrauterine growth retardation . we present a case with large chorioangioma as the cause of non - immunologic hydrops fetalis with a successful outcome . the patient was a female newborn with history of polyhydramnios , symptoms of congestive heart failure and associated anemia , thrombocytopenia and coagulopathy . chorioangioma of the placenta has potentially serious perinatal risks and so the pregnancy needs to have regular surveillance . the term non - immunologic hydrops fetalis ( nihf ) defins an edematous fetus with fluid collections in some or all serous cavities that does not have erythroblastosis fetalis from isoimmunization . in 1943 dr edith potter published the first description of nihf ; now over 80 conditions are known to be associated with hydrops with very high perinatal mortality ranging from structural heart disease , fetal arrhythmias , chromosomal anomalies , intrauterine infections and larger chorioangiomas of the placenta[25 ] . in most countries with low rhesus - negative rates in the population , nonimmune causes are more prevalent ; the incidence depends on the region and also varies seasonally in relation to parvovirus b19 epidemics . we describe a newborn in whom cardiac enlargement and congestive heart failure were caused by a vascular shunt through a large placental chorioangioma , emphasizing the importance of the anatomical study of the placenta for the correct diagnosis , managing the neonatal care and evolution of the newborn . a 2.120 g preterm female newborn , product of a non consanguineous marriage was born from a primigravida by emergency cesarean section at 32 weeks of gestation because ultrasound examination revealed cardiomegaly with abnormal umbilical flow and signs of vascular fetal insufficiency . physical examination at birth revealed 1 minute apgar score 8 , anasarca , poor respiratory effort with bilateral wet rales , hepatosplenomegaly with ascites and no reflexes . the initial chest radiograph obtained 2 hours after birth showed soft tissue edema , cardiomegaly and pleural effusion compatible with congestive heart failure . laboratory data included hypoproteinemia and hypoalbuminemia , anemia ( hematocrit 31% ; hemoglobin 10.3mg / dl ) and hyponatremia ( na 125 meq / l ) , thrombocytopenia ( platelets 4110/l ) and deranged coagulation profile ( prothrombin time 19 seconds , activated partial thromboplastin time 120 seconds ) . the infant 's cardiorespiratory status gradually improved with water restriction , conventional respiratory assistance and inotropic drugs which resulted in 29 percent decrease in weight compared to her birth weight . pathology of the placenta showed edema without signs of placental infarction and a big tumoral mass measuring 1043 cm ( fig . microscopic examination revealed large fusiform vessels in a fibrotic stroma with focal edema and clusters of myxoid cells ( fig . 2 and 3 ) . placental chorioangioma : tumoral mass measuring 1043 cm placental chorioangioma : large fusiform vessels in a fibrotic stroma with focal edema and clusters of myxoid cells placental chorioangioma is a benign vascular tumor detected in 1 percent of placentas after systematic examination . most of these tumors are small and discovered only by microscopic examination and have no adverse impact on the fetus . larger tumors are rare and when above 5 cm in diameter , they are associated with serious complications . these tumors are found accidentally by ultrasound examination . in our case , the placental tumor measured more than 10 cm and led to cardiomegaly with abnormalities in the umbilical flow and signs of vascular fetal insufficiency . where the tumor is avascular , no specific complications should be expected . when the tumor is vascularized , and in particular if it contains numerous large vessels , serial ultrasound and doppler examinations are warranted to detect early features of fetal congestive heart failure . two hypotheses are proposed for formation of congestive heart failure in this condition : the left to right shunt as a result of intra tumoral arteriovenous shunting and chronic fetal hypoxia secondary to insufficient placental function or anemia and thrombocytopenia[8 , 9 ] . the detection of ultrasound findings of heart failure or suggestive signs of anemia as cardiomegaly , enlargement of the liver and abnormal umbilical vein . large placental chorioangiomas are rare and the prognosis is bad when a big tumor causes fetal hemodynamic changes with nihf , but treatment of heart failure may be promising in these newborns and complete recovery is achieved in some cases . chorioangioma of the placenta has potentially serious perinatal risks and so the pregnancy needs to have regular surveillance .

backgroundchorioangiomas are the most common benign tumors of the placenta originating from primitive angioblastic tissues . it comprises near 1 percent of placental tumors . clinical manifestations in the newborn are rare and usually associated with tumors greater than 5 cm in diameter and consist of polyhydramnios , fetal anemia , massive edema with pleural effusion , ascites and intrauterine growth retardation . we present a case with large chorioangioma as the cause of non - immunologic hydrops fetalis with a successful outcome.case presentationthe patient was a female newborn with history of polyhydramnios , symptoms of congestive heart failure and associated anemia , thrombocytopenia and coagulopathy . the pathophysiology and management of the complications of hydrops fetalis with chorioangioma are discussedconclusionchorioangioma of the placenta has potentially serious perinatal risks and so the pregnancy needs to have regular surveillance . the chance of developing complications is directly related with the tumor size .

a 55-year - old man , presented to our hospital , complained of a large pelvic mass , which was found incidentally during a routine ultrasonography . the patient had no history of abdominal or pelvic discomfort , nor any abdominal or pelvic surgery . in addition , the patient had no relevant medical or family history except for diabetes mellitus . upon a digital rectal examination , a large mass with a stone - like hardness was palpated at 5 - 6 cm above the anal verge . a single - phase helical ct ( lightspeed ultra ; ge healthcare , milwaukee , wi ) , spanning the whole abdominopelvic cavity , was performed . the ct scanning parameters included a beam collimation of 8 1.25 mm , a reconstruction interval of 1.25 mm , a pitch of 1.35 , a rotation time of 0.8 seconds , a table speed of 13.5 mm / rotation , 120 kv and 160 mas . transverse ct images were obtained 70 seconds after the intravenous injection of non - ionic contrast material ( 120 ml ) at a rate of 3 ml / sec ( ultravist 300 ; bayer schering pharma , berlin , germany ) . the ct images revealed a large , well - defined mass in the presacral space of the pelvic cavity , which seemed to have a long stalk arising from the left gluteus medius muscle ( fig . the stalk traversed along the surface of the left iliac bone , and proceeded through the left sciatic foramen , and ended up connecting with the mass . the ct attenuation generated an easily recognizable mass , which was mainly composed of fatty tissue and calcification , with most of the stalk becoming calcified . some focal areas of intermediate attenuation were identified as a mixture between fatty tissue and calcification , and occupied only a limited portion of the mass . mr imaging ( horizon 1.5 t ; ge healthcare , milwaukee , wi ) was also performed with the use of a torso coil . on both the t1-weighted ( 366/8 , echo train length of zero , 5-mm slice thickness , 2-mm gap , 256192 matrix , 24-cm field of view , 2 signal acquired , and sequence duration of 3 - 4 minutes ) and t2-weighted ( 4300/84 , echo train length of ten , 5-mm slice thickness , 2-mm gap , 512256 matrix , 24-cm field of view , 2 signal acquired , and sequence duration of 3 - 4 minutes ) mr images , the mass was revealed to mainly consist of the hyperintense and signal void areas that represent fatty tissue and calcification , respectively ( fig . 1c - e ) . also seen are the focal areas of intermediate signal intensity , as shown on the ct images . the gadolinium - enhanced t1-weighted mr images obtained 30 seconds , 60 seconds , and 3 minutes after the intravenous injection of contrast material ( gadovist ; bayer schering pharma , berlin , germany ) , and the focal areas of the intermediate signal intensity around the calcifications observed at 30 and 60 seconds post - injection , became isointense as the surrounding fat tissue at 3 minutes post - injection . the main mass was resected using a transabdominal approach , whereas the stalk was removed through the sciatic foramen . the surgical specimen consisted of a 13 cm , well - circumscribed , hard mass , with a severely calcified external surface . the cut surface of the resected specimen revealed a mass mixed with fatty tissue and calcification ( fig . a histopathological examination revealed that the mass was composed of lipoma with chondroid metaplasia ( fig . the term mesenchymoma was originally defined by stout ( 7 ) in 1948 to describe tumors containing at least two mesenchymal tissues not normally found together . the tumors can be classified as benign or malignant , and most of the benign varieties have been called angiomyolipomas , angiolipomas , chondrolipomas , osteolipomas , and other names depending on the predominant tissue form in the tumor . however , fibrous tissue is found in all mesenchymal tumors , and is not counted as one of the elements ( 6 ) . conversely , if a mesenchymal tumor is well - defined or encapsulated and composed predominantly of one type of mesenchymal tissue , along with one or more minor element , the diagnosis should reflect the predominant mesenchymal tissue ( 6 ) . in our case , the diagnosis of a chondrolipoma was appropriate , since the mass was composed of a sufficiently high proportion of both fatty tissue and extensively calcified chondroid tissue , though it was well - defined and encapsulated . two possible explanations for the pathogenesis of cartilage and bone formation in benign mesenchymomas have been proposed ( 5 , 6 , 8 , 9 ) . the first is that cartilage arises from chondro - osseous metaplasias of adipose tissue , presumably as a result of mechanical stress or trophic disturbance . the close proximity or contact with bone and a large joint , myxoid background , or a lipodystrophy - like change , which are often associated with these tumors , suggest a metaplastic process caused by a trophic disturbance or mechanical stress ( 8 - 10 ) . a previous immunohistochemical study supported the explanation that the pattern of expression for growth factor- , latent transforming growth factor- binding protein-1 transforming , and bone morphogenetic protein might play an important role in the transformation of multipotential cells into the chondrolipoma ( 11 ) . considering the proximity of the identified chondrolipoma to the iliac bone of our case study , we agree with the first explanation of chondroid - osseous metaplasia , which states that the mass may be a result of a micro - trauma . our mass occupied both the inside and outside of the pelvic cavity ; however , we could not clarify whether its primary site was the pelvic cavity or the left buttock . according to previously reported cases the only reported case of an abdominal chondrolipoma in a human occurred in the small bowel ( 8) , whereas a chondrolipoma was once documented in the pelvic cavity of a dog ( 12 ) . considering these reports , we thought that in our case , a chondrolipoma in the buttock might be extended to the pelvic cavity through the sciatic foramen , though the proportion of the mass in the pelvis was greater than in the buttock . there are few reports pertaining to the imaging features of chondrolipomas of various organs , with most cases describing their mr features ( 5 , 9 , 13 , 14 ) . for these reports , chondroid and fatty tissues were described as intermediate and high signal intensity areas on t1-weighted images , respectively . both chondroid and fatty tissues were identified as having a higher signal intensity area than the surrounding muscle , whereas chondroid tissue was depicted as having a higher signal intensity area than fatty tissue on t2-weighted images . signal void areas corresponding to calcifications were only found in a small portion of these reported cases . for the ct images , fatty tissue was depicted as a low attenuation area ( less than -30 hounsfield units ) , whereas chondroid tissue was depicted as an intermediate attenuation area . in our case , the mass was depicted to be primarily composed of fatty tissue and calcification , which matched the ct attenuation and mr signal intensity . also , we found that additional focal areas of intermediate attenuation or signal intensity corresponded to chondroid tissue . these findings were different from those described in previously reported cases whereby , in our case , the calcification was much more extensive , and the signal intensity of chondroid tissue on the t2-weighted images was intermediate . moreover , we found extensive calcification located peripherally in a linear and rosary pattern . a previous report also cited the observation of chondroid tissue in a rosary pattern ( 9 ) . despite the very limited number of reported cases , we propose that the rosary pattern of either the chondroid tissue or calcification could be a characteristic finding of chondrolipomas , and in our case , the calcification in a rosary pattern was likely a consequence of the dystrophic change involving the chondroid tissue . moreover , the signal intensity of chondroid tissue was intermediate on the t2-weighted images , and could be explained by the presence of fibrous tissue within the chondroid tissue ( fig . 1i ) , which reduced the signal intensity of chondroid tissue below the fatty tissue . it is interesting that the focal areas of intermediate signal intensity around the calcifications showed delayed enhancement on the gadolinium - enhanced mr images . ( 9 ) described the presence of enhancing foci between the fatty tissue and chondroid tissue in a chondrolipoma , without clarifying the histopathological findings . also , there have been no reports of chondrolipomas with delayed enhancement . in our case , however , keeping in mind that the location of these focal areas corresponded to chondroid tissue , and that chondroid tissue is usually not enhanced , even on the delayed phase , the delayed enhancement of these focal areas may be attributed due to sufficient fibrous tissue within the chondroid tissue . despite the characteristic imaging findings of chondrolipomas , fatty tumors such as lipomas or liposarcomas , which contain chondro - osseous differentiation , the treatment of choice for chondrolipomas is surgical excision ( 5 , 8 , 14 ) . conclusively , we experienced the only reported human case of a chondrolipoma in the pelvic cavity , and found that it had characteristic imaging features consistent with fatty tissue and calcification , as well as the areas corresponding to cartilage .

a chondrolipoma is an extremely rare form of a benign mesenchymal tumor containing mature cartilage and fatty tissue . chondrolipomas may be found in almost any part of the body , particularly in the connective tissue of the breast , head and neck area , as well as in the skeletal muscle . however , to the best of our knowledge , chondrolipomas located in the pelvic cavity have not been reported . in this case report , we describe a case of a chondrolipoma in the pelvis , and show that it has its own characteristic imaging findings , which included the composition of fatty tissue and calcification in most parts , as well as some focal areas of chondroid tissue based on the ct and mr findings .

atypical antipsychotics are believed to reduce the risk of extrapyramidal syndrome , including tardive dyskinesia ( td ) . quetiapine is reported to be less likely to induce td side effects and , in fact , has been shown to relieve symptoms of severe td1 ) and reduce td risk.2 ) quetiapine 's low affinity and fast dissociation from postsynaptic dopamine d2 receptors should contribute to low td symptom production.3 ) additionally , quetiapine reduces td side effects from clozapine , a drug already associated with very low td risk.4 ) however , since the first case report of quetiapine - related td side effects was published in 1999,5 ) quetiapine 's safety has been questioned . this case report describes severe , late - onset td side effects after long - term quetiapine use in a patient with psychotic depression . since td onset , the patient has had no significant findings based on comprehensive neurological examinations , brain magnetic resonance imaging , and electroencephalogram . the patient was a female homemaker who has suffered with psychotic depression for 3 years . her symptoms included depressed mood , lack of interest , lack of energy , suicidal ideation , insomnia , feelings of worthlessness , auditory hallucinations ( voices commenting around her ears and commanding her to die ) , and delusions of poverty . diagnosis was based on criteria of the diagnostic and statistical manual of mental disorders iv text revision ( dsm - iv - tr ) and the structured clinical interview for dsm - iv - tr . symptom severity was as follows : brief psychiatric rating scale-18 items ( bprs-18 ) score=31 , especially for hallucinatory behaviors ( 5 points ) , and hamilton rating scales for depression ( hrsd ) score=27 . quetiapine and duloxetine were delivered using gradual titration to relieve symptoms , and the final stable medication doses were quetiapine 600 mg / day and duloxetine 90 mg / day across 2.5 years . the patient 's depressive and psychotic symptoms responded to psychotropic medication and reached partial remission status ( bprs score=9 ; hrsd score=12 ) . she did not have extrapyramidal symptoms during the first two years after initiating the above medications . however , she began to experience severe perioral tremors with involuntary , repetitive , and irregular movements of tongue starting in the third year of quetiapine treatment . the protruding tongue with irregular movements was a significant detriment to her quality of life , as irregular movements occurred all day and were not relieved by anticholinergic medications . quetiapine - related td was suspected , and the quetiapine dose was tapered to 150 mg / day . however , after 3 months , td severity remained the same and seemed unresponsive to interventions , including switching to other atypical antipsychotics such as aripiprazole or ziprasidone . no significant exacerbations of psychotic or mood symptoms were observed after td onset and antipsychotic switch . the patient also received concurrent comprehensive neurological examinations , brain magnetic resonance imaging , and electroencephalograms . no significant alterations in brain anatomy or function were observed , and according to the neurological report , no organic etiology could be found to explain the presence of td . in this case , we observed unique , late - onset , and irreversible td side effects after long - term quetiapine use . late - onset td after 3 years might suggest independent factors . however , comprehensive neurological examinations and imaging studies could not pinpoint organic evidence to suggest that this patient 's td was independent of quetiapine use . late - onset td side effects in this patient appear irreversible even after decreasing quetiapine dose and switching antipsychotics . however , case reports of late - onset td have not been included in previous reports . rather , these reports mention the long - term safety of quetiapine in adolescent6 ) and adult patients.3 ) sacchetti and valsecchi7 ) showed that quetiapine has the lowest risk for td side effects when compared with olanzapine and clozapine in their long - term trial ( 154 weeks ) . quetiapine - related td was noted and described in an early case report about 15 years ago.5 ) however , some reports also mention contrary findings of quetiapine 's ability to relieve td.1,2,8,9,10,11,12,13 ) emsley et al.14 ) found that quetiapine could effectively reduce td severity in patients with established td , but the mechanism of this action is unclear . quetiapine is the atypical antipsychotic most similar to clozapine ( without its hematologic side effects ) based on receptor and pharmacologic profile , which may explain its treatment effects for td.11 ) quetiapine is believed to express lower affinity for d2 receptors in striatal and extrastriatal regions of brain,15 ) which could explain the mechanisms by which it can treat or relieve td side effects . the presence of mood disorders may be a possible reason for quetiapine - related td in this patient . sharma16 ) reported that patients with mood disorders were more prone to treatment - emergent td with quetiapine . recently , reports reveal quetiapine 's td side effects and suggest precautionary attention to td risk characteristics.17 ) a recent dopamine receptor imaging study showed that quetiapine occupies dopamine d2 receptors extensively in striatal regions , which likely contributes to td side effects.18 ) furthermore , low - dose quetiapine also seems to induce early - onset td in the neuroleptic - nave patient.19 ) recent reports provide evidence of quetiapine 's td risk as well as possible mechanisms . previously , it was suggested that quetiapine - related td could be relieved by tapering the dose or switching to another atypical antipsychotic such as aripiprazole.15 ) however , in this case study , td was not abated with quetiapine dose tapering or with a switch to other atypical antipsychotics . therefore , use of quetiapine should be approached with caution , with close attention paid to td risk factors .

the atypical antipsychotics were believed to induce less extrapyramidal syndrome , including tardive dyskinesia ( td ) . since the introduction of the quetiapine , it is also reported with less td side effects . it even can relieve the symptoms of severe td and reduce the risk of td . the quetiapine 's low affinity and fast dissociation from postsynaptic dopamine d2 receptors should give the least risk of producing the symptoms of td . the quetiapine even can reduce the td side effects related to clozapine , which has the lowest risk for td . however , since the first case report of td side effects related to quetiapine published on 1999 , the safety of quetiapine in td aspect has been questioned . therefore , we want to share this case report , which was written to describe the severe late - onset td side effects after long - term use of quetiapine in a patient with psychotic depression . the patient had no significant findings after concurrent comprehensive neurological examinations , magnetic resonance imaging of brain and electroencephalogram since the onset of td .

the sequential deletion method and other biological and biochemical experiments are generally used to locate the functional domain of a protein . for example , a previous study ( 1 ) used the sequential deletion method accompanied by manual pcr primers design to generate the n - terminal truncated mutants of different lengths ( figure 1 ) , which in turn were used in further biological experiments to decipher the functional domain of the 5s rna - protein complex ( 5s rrnp ) . the 5s rrnp is believed to be formed by a co - translation event leading to the binding of the 5s rrna to the nascent ribosomal protein l5 . lin et al . ( 1 ) used an in vitro translation system to investigate how and when 5s rrna triggers the formation of the eukaryotic 5s rrnp . the l5 and truncated l5 mutant mrnas were prepared on a large scale for their investigation and a great amount of time was needed to manually modify the in - frame pattern of atg start codon for conventional pcr and truncated mutant translation experiments . the illustration of the produced n - terminal truncated mutants . in order to save time and money needed in the traditional sequential deletion method , this web - based application system ntmg is proposed to automatically do the multiplex pcr assays design in order to generate the various n - terminal truncated mutants . given a protein cdna sequence , the ntmg will first find those atg - like codons that are suitable to act as the starting positions of truncated mutants . then , the ntmg will design the forward primers for all possible truncated mutants . finally , with all these primers , the ntmg will choose those primers that can be divided into the least number of groups such that each group constitutes a multiplex pcr assay . in this section , we describe the input to the ntmg , the methodology of the ntmg and the output of the ntmg . since the primer design and the multiplex pcr primer design are two important parts of the ntmg , some factors concerning the primer design such as the primer length and the melting temperature are input as parameters . there are also some factors that may affect the multiplex pcr amplification with multiple primers in the same tube ( 2,3 ) . these factors include the cross - dimerization , the melting temperature , the products co - existence and others . figure 2 gives the input screen of the ntmg . on the top of the screen , the cdna sequence , the start codon address and the stop codon address are input . then comes four classes of parameters : primer criteria ( 47)these include the forward primer length ( default 2030 bp ) , the reverse primer length ( default 1428 bp ) and the gc content ( default 40 - 60%).temperature criteria ( 5,810)these include melting temperature ( default 5160c ) , the melting temperature range for each group ( default 5c ) , the molar concentration of monovalent cation ( default 50 mmol / l ) , the molar concentration of mg ( default 1.25 mmol / l ) and the dntps concentration ( default 0.02 mmol / l).complementary criteria ( 4,8,1012)these include the terminal repeated sequence ( default 3 bp ) , the intra self - complementary sequence ( default 3 bp ) , the specificity ( default 65% ) , the cross - dimer distance ( default 10 bp ) , the cross - dimer total similarity ( default 50% ) and the cross - dimer terminal similarity ( default 3 bp).grouping criteriathese include the product length difference ( default 80 bp ) and the maximum number of primers in each group ( default 16 ) . figure 2.the input screen of the ntmg . primer criteria ( 47 ) these include the forward primer length ( default 2030 bp ) , the reverse primer length ( default 1428 bp ) and the gc content ( default 40 - 60% ) . temperature criteria ( 5,810 ) these include melting temperature ( default 5160c ) , the melting temperature range for each group ( default 5c ) , the molar concentration of monovalent cation ( default 50 mmol / l ) , the molar concentration of mg ( default 1.25 mmol / l ) and the dntps concentration ( default 0.02 mmol / l ) . complementary criteria ( 4,8,1012 ) these include the terminal repeated sequence ( default 3 bp ) , the intra self - complementary sequence ( default 3 bp ) , the specificity ( default 65% ) , the cross - dimer distance ( default 10 bp ) , the cross - dimer total similarity ( default 50% ) and the cross - dimer terminal similarity ( default 3 bp ) . these include the product length difference ( default 80 bp ) and the maximum number of primers in each group ( default 16 ) . first , a cdna sequence is input , then the ntmg searches the sequence with in - frame criterion in order to find all the atg - like codons . an atg - like codon is a xtg , an axg or an atx with x representing a , t , c or g. for each atg - like codon , the ntmg generates candidate primers using the sliding window . the ntmg also modifies the atg - like codon into the atg codon in each candidate primer . hence , each candidate primer contains the atg start codon with in - frame criterion that can translate correctly to truncated mutants . after that , the ntmg applies the primary criteria and the secondary criteria to check if the candidate primers satisfy all the criteria . those candidate primers that pass the criteria checking are then divided into classes according to the melting temperature . each class contains primers whose melting temperatures are within the same range ( default 5c ) . so the primers chosen from the same class may be used in the same pcr experiment . for candidate primers in the same class , the ntmg does the cross - dimer check and the co - existence check and builds the cross - dimer matrix and the co - existence matrix . these two matrices are then anded to produce a new matrix which acts as an adjacency matrix of a graph . previous studies ( 13,14 ) proposed the transformation of minimizing the number of primers into the finding of the maximum clique in a graph . next , each class is further divided into subclasses according to the positions of the atg - like codons . the proposed genetic algorithm is then applied for each class in order to choose a set of primers , one from each subclass and the objective is to divide these primers into as few groups as possible such that each group of primers can be put in a tube in the pcr experiment . that is , the genetic algorithm tries to find a good multiplex pcr assay design . a heuristic maximum clique algorithm is proposed to calculate the fitness of a chromosome in the genetic algorithm . this heuristic algorithm tries to find the maximum clique in the graph previously mentioned and the maximum clique corresponds to the minimum number of grouping . the ntmg is written in java using java 2 platform standard edition 5.0 development kit ( j2sdk ) and employs the java server page ( jsp ) on the apache tomcat server ( http://tomcat.apache.org/ ) . the ntmg outputs the number of primer groups , the number of forward primers , the number of reverse primers and the primers in each group ( figure 4 shows a solution report ) . figure 2 gives the input screen of the ntmg . on the top of the screen , the cdna sequence , the start codon address and the stop codon address are input . then comes four classes of parameters : primer criteria ( 47)these include the forward primer length ( default 2030 bp ) , the reverse primer length ( default 1428 bp ) and the gc content ( default 40 - 60%).temperature criteria ( 5,810)these include melting temperature ( default 5160c ) , the melting temperature range for each group ( default 5c ) , the molar concentration of monovalent cation ( default 50 mmol / l ) , the molar concentration of mg ( default 1.25 mmol / l ) and the dntps concentration ( default 0.02 mmol / l).complementary criteria ( 4,8,1012)these include the terminal repeated sequence ( default 3 bp ) , the intra self - complementary sequence ( default 3 bp ) , the specificity ( default 65% ) , the cross - dimer distance ( default 10 bp ) , the cross - dimer total similarity ( default 50% ) and the cross - dimer terminal similarity ( default 3 bp).grouping criteriathese include the product length difference ( default 80 bp ) and the maximum number of primers in each group ( default 16 ) . figure 2.the input screen of the ntmg . primer criteria ( 47 ) these include the forward primer length ( default 2030 bp ) , the reverse primer length ( default 1428 bp ) and the gc content ( default 40 - 60% ) . temperature criteria ( 5,810 ) these include melting temperature ( default 5160c ) , the melting temperature range for each group ( default 5c ) , the molar concentration of monovalent cation ( default 50 mmol / l ) , the molar concentration of mg ( default 1.25 mmol / l ) and the dntps concentration ( default 0.02 mmol / l ) . complementary criteria ( 4,8,1012 ) these include the terminal repeated sequence ( default 3 bp ) , the intra self - complementary sequence ( default 3 bp ) , the specificity ( default 65% ) , the cross - dimer distance ( default 10 bp ) , the cross - dimer total similarity ( default 50% ) and the cross - dimer terminal similarity ( default 3 bp ) . these include the product length difference ( default 80 bp ) and the maximum number of primers in each group ( default 16 ) . the input screen of the ntmg . first , a cdna sequence is input , then the ntmg searches the sequence with in - frame criterion in order to find all the atg - like codons . an atg - like codon is a xtg , an axg or an atx with x representing a , t , c or g. for each atg - like codon , the ntmg generates candidate primers using the sliding window . the ntmg also modifies the atg - like codon into the atg codon in each candidate primer . hence , each candidate primer contains the atg start codon with in - frame criterion that can translate correctly to truncated mutants . after that , the ntmg applies the primary criteria and the secondary criteria to check if the candidate primers satisfy all the criteria . those candidate primers that pass the criteria checking are then divided into classes according to the melting temperature . each class contains primers whose melting temperatures are within the same range ( default 5c ) . so the primers chosen from the same class may be used in the same pcr experiment . for candidate primers in the same class , the ntmg does the cross - dimer check and the co - existence check and builds the cross - dimer matrix and the co - existence matrix . these two matrices are then anded to produce a new matrix which acts as an adjacency matrix of a graph . previous studies ( 13,14 ) proposed the transformation of minimizing the number of primers into the finding of the maximum clique in a graph . next , each class is further divided into subclasses according to the positions of the atg - like codons . the proposed genetic algorithm is then applied for each class in order to choose a set of primers , one from each subclass and the objective is to divide these primers into as few groups as possible such that each group of primers can be put in a tube in the pcr experiment . that is , the genetic algorithm tries to find a good multiplex pcr assay design . a heuristic maximum clique algorithm is proposed to calculate the fitness of a chromosome in the genetic algorithm . this heuristic algorithm tries to find the maximum clique in the graph previously mentioned and the maximum clique corresponds to the minimum number of grouping . the ntmg is written in java using java 2 platform standard edition 5.0 development kit ( j2sdk ) and employs the java server page ( jsp ) on the apache tomcat server ( http://tomcat.apache.org/ ) . the ntmg outputs the number of primer groups , the number of forward primers , the number of reverse primers and the primers in each group ( figure 4 shows a solution report ) . a web - based application system called the ntmg is provided for researches who need to apply the sequential deletion method to locate the functional domain of a protein . each group of primers can be put in a tube and all tubes can be accommodated in a single batch of the multiplex pcr amplification under the same condition . we conducted a wet laboratory experiment on the multiplex pcr assay design proposed by the ntmg on input hl5 cdna . the ntmg found 48 forward primers and one reverse primer and it divided them into 8 groups . in the wet pcr experiment , 44 pcr products had been found and the success rate is 91.7% ( see supplementary data ) . hence , the ntmg is of practical use to researchers who need to apply the sequential deletion method . as a future work , we plan to develop the more general multiplex pcr assay design . given a set of pcr experiment requirements , we plan to develop a system that can automatically find the primers and try to divide the primers into as few groups as possible such that the primers in each group can be put in a tube and all tubes can be accommodated in a single batch of the multiplex pcr experiment .

the sequential deletion method is generally used to locate the functional domain of a protein . with this method , in order to find the various n - terminal truncated mutants , researchers have to investigate the atg - like codons , to design various multiplex polymerase chain reaction ( pcr ) forward primers and to do several pcr experiments . this web server ( n - terminal truncated mutants generator for cdna ) will automatically generate groups of forward pcr primers and the corresponding reverse pcr primers that can be used in a single batch of a multiplex pcr experiment to extract the various n - terminal truncated mutants . this saves much time and money for those who use the sequential deletion method in their research . this server is available at http://oblab.cs.nchu.edu.tw:8080/websdl/.

hermansky and pudlak reported in 1959 two cases of unrelated albinos with lifelong bleeding tendency and peculiar pigmented reticular cells in the bone marrow as well as in lymph nodes and liver biopsies . one albino was female and the other was male , both were 33 years old . after her death , autopsy revealed horseshoe kidney with large amount of pigment in reticuloendothelial cells and in the walls of small blood vessels . hermansky - pudlak syndrome ( hps ) is an autosomal recessive disorder that is caused by different genetic mutations . this syndrome is characterized by oculocutaneous albinism , platelets storage - pool deficiency , and lysosomal accumulation of ceroid lipofuscin . these patients have decreased skin and hair pigmentation and transillumination of the iris with markedly decreased visual acuity . patients with hps have easy bruisability , secondary to the absence of platelet dense bodies , which trigger platelet aggregation . ceroid lipofuscin is an amorphous lipid protein complex , and its accumulation in tissues is believed to be responsible for pulmonary fibrosis and granulomatous colitis . this ceroid lipofuscin also accumulates in the kidney , giving it a dark appearance when examined during an autopsy or kidney biopsy [ 4 , 5 ] . although no specific renal disease has been attributed to hps , compromised renal function in these patients has been reported [ 1 , 4 ] . renal insufficiency has been thought to occur due to the ceroid lipofuscin deposition in the kidney . gahl et al . reported a series of 49 patients with hsp , of which 9 had ckd ; however , no kidney biopsies where performed and there is no information about the proteinuria and hypertension in any of the above reports . to our knowledge , we report the first pediatric renal pathology case of hps associated with ckd , tubular pathology , focal segmental glomerulosclerosis ( fsgs ) , and hypertension . the patient is a 15-year - old male born in puerto rico to nonconsanguineous parents of puerto rican descent . he moved to the usa when he was 2 years old at which time the diagnosis of hps was made by hematologist who saw him because of easy bruisability and prolonged bleeding time . genetic testing was done , and he was found to be homozygous for the 16 bp duplication in the hps1 gene , which is denoted c.1472_87dup 16 on the cdna level . he had no known family history in parents , grandparents , and immediate relatives of renal failure , albinism , or known hps , although paternal grandmother had hypertension . our service was consulted secondary to persistent hypertension detected during a hospitalization for asthma - like symptoms , when he was 8 years old . physical examination at that time showed an active child , with global developmental delay , albino , obese ( with body mass index > 95th for age ) with normal cardiovascular and respiratory exam . he had no fever , heart rate was 96 beats per minute , and blood pressure in the right arm was 149/93 mmhg , left arm 127/78 mmhg , right leg 154/64 mmhg , and left leg 151/77 mmhg in sitting position . serum chemistries showed sodium of 135 mg / dl , potassium of 3.8 mg / dl , blood urea nitrogen of 16 mg / dl , and creatinine of 1 mg / dl . renal ultrasound showed both kidneys to be normal in position and without evidence of hydronephrosis . the right kidney measured 8.4 cm , and left kidney measured 9.7 cm . doppler examination demonstrated patency of renal veins , with resistance indices 0.5 ( right renal artery ) and 0.6 ( left renal artery ) . his hypertension workup included normal serum / urine catecholamines , thyroid function tests , and normal brain imaging ( mri head ) . to control hypertension , , patient 's blood pressure was < 90 percentile for age , gender , and height . lvh subsequently resolved as documented on follow - up echo at age of 9 years . at 12 years of age , calcium channel blocker was stopped , secondary to gingival hyperplasia , and an angiotensin receptor blocker ( arb ) was started . at that time , patient did not have proteinuria . his serum creatinine remained stable ( ranged from 1 to 1.3 mg / dl ) , and serum potassium ranged from 3.8 to 4.6 mg / dl . in this time period , , he had a gastric , duodenum , and colonic biopsies done , which showed mild acute - chronic inflammation ( there were no bleeding complications ) . during his routine follow - up visit at age 14 years , 30 mg / dl of protein without hematuria was noted on the dipstix , but measured urine protein / creatinine ratio ( upc ) of this sample was 0.2 . he was seen in the renal clinic every 36 months , and since then his first morning upc ranged from 0.2 to 0.38 . a reliable 24-hour urine collection was not possible to obtain due to his developmental delay . when he was 15 years old , his blood pressure was still controlled with arb , his serum creatinine was elevated at 1.4 mg / dl , and proteinuria became fixed , that is , 1st morning upc was 0.38 and 0.5 . first morning urinalysis showed ph of 6 , yellow color , specific gravity 1.020 , 100 mg / dl protein , no blood , and no glucose , and microscopic examination showed 03 red blood cells per high - power field and 05 white blood cells per high - power field , without casts , indicative of functional renal concentrating and acidifying abilities . he had no edema and no hematuria , and his serum albumin was 4.2 g / dl . his serologies for hepatitis b / c and lupus ; complement 3 and 4 , antinuclear antibodies , and vasculitis ; antineutrophil cytoplasmic antibodies ( anca ) were all negative . kidney biopsy was performed due to persistent proteinuria and compromised renal function , with estimated gfr 70 ml / min/1.73 m by schwartz formula . the hematology service was consulted prior to biopsy and coagulation studies : prothrombin time ( pt ) was 10.5 seconds ( normal 9.512 seconds ) and partial thromboplastin time was 26.9 seconds ( normal 26.233.8 seconds ) . immediately after the kidney biopsy , a small perinephric hematoma was observed by ultrasonographic evaluation but no gross hematuria was seen and there were no other complications during and after the procedure . tissue for light microscopy was evaluated at 10 section levels with h&e , pas , and trichrome staining . there were total 19 glomeruli in two renal biopsy cores of tan - red cylindrical tissue each core up to 1.2 cm and 1.9 cm . there were three sclerotic glomeruli , including one with segmental hyalinosis ; one of the four additional enlarged glomeruli per level of section had perihilar segmental sclerosis . mild interstitial fibrosis with associated tubular atrophy , and no significant interstitial inflammation was present . acute tubular injury with variable tubular ectasia , variable hypertrophic tubular epithelial cells with marked cytoplasmic vacuolization , fuchsinophilic and pas - negative waxy dull brown - yellow spherule cytoplasmic inclusions were present . no arteriosclerosis was present , and no vascular inflammatory lesions were present , figures 1(a)1(c ) . on immunofluorescent examination , up to 3 enlarged glomeruli per level of section had irregular coarse granular capillary wall and mesangial staining with antisera specific for c3 . the glomeruli had no staining with antisera specific for igg , iga , igm , c1q , kappa light chains , or lambda light chains . electron microscopy ( figure 2 ) revealed no capillary wall or mesangial immune complex - type electron - dense deposits . although original description of hps originated in prague , the majority of literature reports describing this syndrome have come from puerto rico . when hermansky and pudlak reported for the first time in 1959 two cases of albinism and prolonged bleeding time , renal insufficiency was described in one patient with horseshoe kidney . tagboto et al . reported a patient with hps with iga nephropathy and anca - positive glomerulonephritis . the kidney tissue showed a dark - brown pigmentation , and the tubular injury was similar to what we found in our case . ceroid - like lipofuscin material has been found in the urine of hps patients with renal involvement , and the deposition of this material in other tissues ( lungs , colon ) has been blamed for cellular dysfunction and subsequently fibrosis , although , if this is the cause , the exact mechanism has not been described . the mechanism of injury of renal tubular cells by lipofuscin accumulation is not completely understood . hps is a rare , autosomal recessive disorder which affects multiple cytoplasmic organelles : melanosomes , platelet dense granules , and lysosomes . hps can be caused by mutation in several genes : hps1 ( common among population of the northwestern part of puerto rico ) , hps3 , hps4 , hps5 , and hps6 . hps2 , which includes immunodeficiency in its phenotype , is caused by a mutation in the ap3b1 gene . hps is characterized by defect in the coat - protein complexes resulting in abnormal function of lysosomes , melanosomes , and platelet dense granules as hps - gene products are part of distinct protein complexes : the adaptor complex ap-3 and various blocs ( biogenesis of lysosome - related organelles complex ) [ 1416 ] . although there is no data to support it , it is plausible to hypothesize that podocytes of hps subjects may demonstrate molecular defects in proteins analogous to dysbindin ( part of bloc-1 , found in axonal synapses ) involved in lysosomal trafficking . the hps phenotype is heterogenic , and it was reported that hps observed in an isolated swiss alps village [ 17 , 18 ] usually shows a relatively mild clinical course with normal life expectancy and the lack of clinical manifestations of ceroid storage . our patient presents yet another phenotype with htn and constellation of renal lesions that include evidence of tubular injury and fsgs . patients with hps have mild prolonged bleeding time secondary to functionally impaired platelets , but platelet numbers are normal . our patient had had a gastric and colonic biopsy in the past , as well as a tooth removal without significant bleeding . slow rise in serum creatinine from 1 mg / dl at age 8 y to 1.4 mg / dl at age 16 y might be clinically important in our case description , indicative of slow progression despite multiple risk factors : obesity , htn , fsgs , and presence of tubular fuchsinophilic cytoplasmic inclusions with mild interstitial fibrosis on renal biopsy . to the best of our knowledge , there are no previous reports of pediatric hps patients with described renal pathology . the animal model of hps is the fawn - hooded rat ( fh ) and pale ear mouse [ 19 , 20 ] . the fh rat has an inherited platelet storage - pool deficiency and a widespread impairment of serotonin storage , susceptibility to systemic and pulmonary hypertension , but does not have mutations in the gene homologous to hps1 . the fh rat has a genetic predisposition to develop chronic renal failure , fsgs , htn , and proteinuria . the progression of sclerosis results in premature death from end - stage kidney disease in these rats . but the precise cause of the spontaneous development of systemic hypertension in fh rats is not well understood . hps1 is homologous with the pale ear mouse ( ep mutation ) . in that mouse , there is lysosomal accumulation of beta - galactosidase and em showed large multilamellar granules in proximal tubules with the accumulation of lipofuscin material in the tubules . in the last decade , verani reported 14 biopsies of obese adults with fsgs . in that report , glomerulomegaly was reported in patients with fsgs associated with obesity , as well as lack or hyperplasia of glomerular epithelial cells . in that report , patients with fsgs associated with obesity had higher cholesterol and atherosclerosis . our patient had normal cholesterol and no atherosclerosis on biopsy . no tubular lesions , as in the case of our patient , had been reported in fsgs associated with obesity . in a previous case of hps , tubular atrophy and accumulation of a ceroid - like material in tubular epithelial cells were reported . our patient had increased bmi and hypertension with lvh since initial presentation at age 8 years . we can speculate that htn was secondary to obesity at 8 years of age but it would be uncommon clinical scenario to encounter the child at this age with htn significant enough to cause lvh due to obesity alone . our patient did not have evidence of renal artery stenosis or endocrine causes of hypertension , and his blood pressure was controlled with monotherapy . the effects on the kidney secondary to obesity in animals and humans include structural and functional changes , such as increased gfr , increased renal blood flow , and renal hypertrophy [ 21 , 22 ] . some of the changes in the renal tissue of our patient might be consistent with fsgs associated with obesity , and the tubular changes may contribute to the renal insufficiency . although it is not our intention to draw any association between hps and fsgs , we can speculate that obese patients with hps and hypertension may be at risk of unrecognized fsgs . however , it is possible that the sclerosis of the glomeruli observed in our case is secondary to the tubular damage . to the best of our knowledge , this is the first pediatric case of hps associated with ckd and defined renal pathology . further studies are needed to determine the cause of renal insufficiency in patients with hps .

we report a child with hermansky - pudlak syndrome ( hps ) and chronic kidney disease ( stage ii ) with histological diagnosis of focal segmental glomerulosclerosis ( fsgs ) . a 15-year - old male of puerto rico ancestry with history of hps , hypertension ( htn ) , asthma , obesity , and chronic kidney disease ( ckd ) stage ii presented with new - onset proteinuria without edema . his blood pressure had been controlled , serum creatinine had been 0.91.4 mg / dl , and first morning urine protein / creatinine ratio ( upc ) ranged from 0.2 to 0.38 . due to persistent nonorthostatic proteinuria with ckd , renal biopsy was performed and fsgs ( not otherwise specified ) with chronic diffuse tubulopathy ( tubular cytoplasmic droplets ) and acute tubular injury was reported . ceroid - like material is known to infiltrate tissues ( i.e. , lungs , colon , and kidney ) in hps , but the reason for the renal insufficiency is unknown . nonspecific kidney disease and in one adult case iga nephropathy with anca - positive glomerulonephritis have previously been reported in patients with hermansky - pudlak syndrome . to our knowledge , we report the first pediatric renal pathology case of hps associated with ckd . this paper discusses presentation and management of renal disease in hps .

limb load asymmetry ( lla ) is common in clinical conditions related to the lower limbs such as degenerative joint disease , soft - tissue injuries , joint replacements , amputations , and stroke1 , 2 . lla is defined as an uneven distribution of body weight on one lower extremity when compared with the other extremity2 . lla may occur due to pain , reduced muscle strength , and/or impaired joint mobility1 . eventually , lla may cause degeneration of the joint and osteopenia1 . hence , lla may be an important clinical variable for investigation of impairments and the need for further rehabilitation . a variety of equipment is available to measure lla , including biofeedback systems , ambulatory devices with sensors , the tekscan matscan system , and force platforms3 . however , they are rarely available in practice due to their high costs and are confined to laboratory settings . in addition , these pieces of equipment also require ample space and specialized training to handle them in clinical settings . the aforementioned limitations of these pieces of equipment highlight the need for a simple , inexpensive device to measure lla in daily practice . recent studies have utilized a visual simulation gaming tool , such as the nintendo wii ( wii ) , to measure lla3 , 4 . the wii provides reliable and valid lla measurements when compared with the gold standard force platform ( icc = 0.770.89)5 . nevertheless , the wii requires a television for data capture , and it is less mobile . recent literature has proposed measurement of lla using 2 pieces of digital weight scale ( dws ) equipment4 . the dws is inexpensive , portable , and easy to utilize in the clinical setting3 , 4 . , accuracy refers to the closeness of agreement between the limb loading measurement values from the dws to the measurement values from the wii . hence , this study focuses on the accuracy of the dws by comparison with the wii . this experimental study was conducted in the human movements and health research unit of a public university teaching hospital . the study samples comprised 12 osteoarthritis kellgren- lawrence grade 2 and 3 and 12 healthy participants . participants were recruited if they could understand commands and stand independently and were without any neurological disorders . lla was measured using two beurer dwss ( beu - gs27 - 0007 , beurer , ulm , germany ) , each with a precision of 0.01 kg . prior to data collection , the accuracy of the two dwss was tested with dead weights to ensure zero errors2 . the two dwss were placed on flat , hard flooring at a distance equivalent to the participant s shoulder width6 . participants were instructed to stand in a relaxed posture while facing forward with their bare feet centrally placed on each dws7 . three trials of measurement were noted and averaged for data analysis . the nintendo wii fit system ( nintendo of america inc . , redmond , wa , usa ) consists of a balance board , console , remote , and television for data acquisition . the wii console was used to synchronize the data from the balance board to a television . the measurement procedure used for the dws the loading measurements from both lower limbs were computed for lla analysis using the symmetry index ( si)8 . the si is derived from a mathematical formula that provides lla values in percentages . accuracy was analyzed using the statistical package for the social sciences ( version 20 ) . a receiver operating characteristic ( roc ) curve was utilized to compare the measurement data obtained from the wii and dws . two- sample kolmogorov - smirnov ( k - s ) tests were utilized in conjunction with the roc , as this test is sensitive to differences in measurement values , for both the location and shape of the empirical cumulative distribution functions of the dws and wii . the study group consisted of 24 participants , 12 osteoarthritis ( oa ) participants ( 8 female , 4 male ) and 12 healthy participants ( 8 female , 4 male ) . the mean age of the osteoarthritis participants was 61.25 6.68 yrs , mean body mass index ( bmi ) was 27.263.36 kg / m and mean visual analogue scale ( vas ) score was 4.831.59 . the mean age of the healthy participants was 61.83 7.86 yrs , and their mean bmi was 26.71 4.76 the roc curve was used to test the accuracy of the dws relative to the wii . the area under the curve was 0.67 with a 95% confidence interval ( p=0.06 ) . the standard error of measurement was 0.08% of change between the symmetry indexes of the dws and wii . comparison of si values from the dws and wii using the two - sample kolmogorov - smirnov ( k - s ) testmean sd95% cihighlowsi ( dws)4.16 2.73.02 5.300.101.33si ( wii)4.16 2.92.93 5.390.112.38 . in practice , existence of asymmetry in lower limb loading among healthy populations is a controversial issue . measurement of limb loading during while standing is crucial in various orthopedic and neurological conditions1 , 8 , 9 . however , the current measurement tools are not readily available in clinical practice . hence , the present study proposed the use of two dwss for measurement of lla and tested the accuracy relative to the nintendo wii . the results of the present study demonstrate the measurement accuracy of the dws relative to the wii . the area under the roc curve was found to be 0.65 , which is between 0.5 to 1.0 , indicating a best fit between the two pieces of equipment . in addition , the logistic regression line indicates that the results are not by chance . hence , the dws and wii produce similar lla measurements during a standing task . according to the k - s test , the maximum difference between the cumulative distributions of the si obtained from the dws and wii is given by a d value of 0.16 , which is greater than the critical value ( p = 0.86 ) . this proves that the symmetry index scores obtained from the dws and wii are comparable . the study findings could be ascribed to the technical configurations of the two pieces of equipment , as the dws and nintendo wii balance board uses strain gauge sensors to sense load shifts5 . they could also be attributed to the calibration and zero error checking conducted for the two dwss prior to data collection . the two dwss used in this study had a precision of 0.01 kg , which indicates that the closeness of agreement between independent measurements might have reduced the chance of uncertainty . also , this study used three trails , and the measurements were averaged for computation , which might have reduced the random error , as supported by the central limit theorem10 . finally , the standard procedure and instructions given to the participants during the measurements might have been responsible for the similarities in measurements between the devices . the dws could fill the gap with regard to tools for measurement of lla based on its advantages in terms of portability , ease of operation , instant readings , and proven accuracy . the findings of the present study could indicate opportunities for clinicians and researchers to decide on the usefulness of the dws as a clinical and research tool for measurement of lla in the field of rehabilitation .

[ purpose ] the aim of the present study was to investigate the accuracy of a digital weight scale relative to the wii in limb loading measurement during static standing . [ methods ] this was a cross - sectional study conducted at a public university teaching hospital . the sample consisted of 24 participants ( 12 with osteoarthritis and 12 healthy ) recruited through convenient sampling . limb loading measurements were obtained using a digital weight scale and the nintendo wii in static standing with three trials under an eyes - open condition . the limb load asymmetry was computed as the symmetry index . [ results ] the accuracy of measurement with the digital weight scale relative to the nintendo wii was analyzed using the receiver operating characteristic ( roc ) curve and kolmogorov - smirnov test ( k - s test ) . the area under the roc curve was found to be 0.67 . logistic regression confirmed the validity of digital weight scale relative to the nintendo wii . the d statistics value from the k - s test was found to be 0.16 , which confirmed that there was no significant difference in measurement between the equipment . [ conclusion ] the digital weight scale is an accurate tool for measuring limb load asymmetry . the low price , easy availability , and maneuverability make it a good potential tool in clinical settings for measuring limb load asymmetry .

the most important causes of death in western industrialized countries are cardio- and cerebrovascular diseases and malignancies . for instance , in germany in 2008 , 68.6% of all women and 65.9% of all men died from these diseases . in contrast , the third most frequent cause of death are respiratory diseases which cause less than 10% of deaths each year ( table 1 ) . important risk factors for cardio- and cerebrovascular diseases include smoking , arterial hypertension , obesity , diabetes mellitus , and dyslipidemia along with atrial fibrillation for ischemic strokes [ 1 , 2 ] . regular physical activity reduces the risk of and/or improves many diseases and conditions including arterial hypertension , diabetes mellitus type 2 , dyslipidemia , obesity , coronary heart disease , chronic heart failure [ 3 , 4 ] , and chronic obstructive pulmonary disease . in addition , the risk of colon [ 3 , 5 ] , breast [ 4 , 5 ] , and possibly endometrial , lung , and pancreatic cancer is reduced ( table 2 ) . the relative risk of death is approximately 20% to 35% lower in physically active and fit persons compared to that in inactive and unfit persons [ 6 , 7 ] . physical inactivity represents a major independent risk factor for mortality accounting for up to 10% of all deaths in the european region . hence , because a 40% lower mortality rate corresponds to an approximately 5-year higher life expectancy , one would expect an approximately 3.5- to 4.0-year higher life expectancy in physically active persons compared to that in inactive persons . the purpose of this review was to synthesize the literature on life expectancy in relation to physical activity . specifically , cohort studies on physically active and inactive subjects were reviewed to detect a possible difference in life expectancy between these subject groups . in addition , cohort studies on athletes and non - athletes were reviewed to detect a possible difference in life expectancy between these subject groups . to identify all relevant articles about cohort studies investigating the life expectancy of physically active versus inactive persons , a systematic literature search was conducted in the electronic bibliographical database pubmed ( http://www.ncbi.nlm.nih.gov/pubmed/ ) . we only searched for english - language peer - reviewed journal articles using the search terms ( life expectancy or longevity ) and ( physical activity or exercise or sport ) ( last update january 3 , 2012 ) . a total of 1,932 articles were found . using the abstracts and/or titles , forty - one of these articles were identified as cohort studies comparing mortality and/or life expectancy of physically active and inactive persons . however , of these , only 13 articles presented detailed data on life expectancy for both groups . subsequently , a search was performed using the terms ( life expectancy or longevity ) and athlete to find articles on life expectancy in ( former ) athletes . ( life expectancy or longevity ) and ( physical activity or exercise or sport ) . of all these articles , 21 articles investigated mortality and/or life expectancy of ( former ) athletes . eleven of these articles presented detailed data on life expectancy of athletes compared to that of a control group . the remaining life expectancy for physically active and inactive individuals or the difference in remaining life expectancy between the two groups , respectively , were reported in the articles . however , the attained ages of subject groups differed between studies . because the differences of remaining life expectancies can not be assumed to be independent from the attained age , we report the results stratified for attained age . within each stratum of attained age , only five articles [ 1620 ] reported confidence intervals for the difference in remaining life expectancies between groups . in four articles [ 16 , 1820 ] , a parametric bootstrap procedure was used , and in one publication a nonparametric maximum likelihood approach was used . because a meta - analysis model was not appropriate , all data found in the literature search were reported despite some overlaps between the cohort studies . [ 2124 ] used data from the harvard alumni cohort . while most studies reported results based on multivariate life - table analysis , the studies by menotti et al . and pekkanen et al . only reported the results of gained life expectancies for the cohorts based on classical survival analysis . additionally , the study of pekkanen et al . reported the survival rate of men aged 40 to 65 years in the following 20 years and not the total life expectancy . thirteen cohort studies presented data on life expectancy in physically active individuals compared to that in physically inactive control subjects ( table 3 ) . all studies reported a higher life expectancy in physically active subjects , ranging from 0.43 to 6.9 additional years ( mean one standard deviation , men : 2.9 1.3 years , women : 3.9 1.8 years ) . eleven studies considered confounding factors that could affect life expectancy , such as body mass index , blood pressure , diabetes mellitus , dyslipidemia , cardiovascular and lung diseases , cancer , smoking , or alcohol consumption [ 1625 , 27 ] . the additional life expectancy in physically active compared to inactive persons in these studies ranged between 0.43 and 4.21 years ( 2.7 1.1 years ) . the physically most active groups , included in the estimations of life expectancy , participated in moderate to high leisure time [ 16 , 2729 ] or leisure time and all - day activities [ 1725 ] . the median increase of life expectancy of men and women in the eight studies presenting data on both sexes amounted to 3.7 years each . physical activity during leisure time seems to increase life expectancy more effectively than total physical activity ( all - day , professional , or leisure time activity altogether ; professional physical activity alone has not been studied ) : 3.4 added years due to total activities and 4.7 added years ( median values ) due to leisure time activities in women , 1.9 and 3.9 added years , respectively , in men . furthermore , the description of the amount of physical activity in the active and inactive groups are too heterogeneous for any statistical correlation between the amount of activity and the added years of life . the eleven case control studies on life expectancy of athletes , mostly elite athletes ( table 4 ) , reported a mean life expectancy that was between 5.0 years lower and 8.0 years higher than that of the nonathlete control groups . aerobic endurance sports resulted on average in a 4.3 to 8.0 years higher life expectancy and team sports activities on average in a 5.0 years lower to about 5 years higher life expectancy compared to that for normal physical activity . only one study presented data on strength sports and reported a slightly higher life expectancy compared to that for normal physical activity . none of these studies considered any confounding factor that could affect life expectancy the purpose of this review was to synthesize the literature on life expectancy in relation to physical activity . reported a mean reduction of mortality of 31% to 35% in persons who participate in regular leisure - time or daily life physical activity compared to that in inactive persons . assuming a 40% lower mortality corresponding to a 5-year higher life expectancy , regular physical activity should increase mean life expectancy by approximately ( 31% to 35%)/40% 5 years or by 3.9 to 4.4 years indeed , the few articles that presented data on life expectancy in physically active individuals reported a 0.43- to 6.9-year higher life expectancy . high - quality studies considering confounding factors that could affect mortality reported a 0.43- to 4.21-years higher life expectancy in physically active compared to inactive persons . the wide range of years added can not be explained based on the published data . the studies that standardized extended life estimates for confounding factors [ 16 , 1825 , 27 ] virtually calculated a net gain in life expectancy by being physically active . however , the actual increase in life expectancy should be much higher because of favorable effects of physical activity on other risk factors for mortality such as arterial hypertension , glucose and lipid metabolism , coronary heart disease , stroke , or malignancies ( table 1 ) . in fact , nonsmoking , normal weight , and physically fit men live on average 12 years ( 95% confidence interval , 8.6 to 14.6 years ) longer than smoking , overweight , and physically unfit control subjects . subjects who never smoked , follow a healthy diet , are adequately physically active , and consume only moderate alcohol have a mean life expectancy that is 11.1 years longer than those who practice none of these healthy life behaviors . the mechanisms underlying the net effect of physical activity are speculative and include reduction of triglyceride and apolipoprotein b concentrations , increase of high - density lipoproteins and tissue plasminogen activator activity , and reduction of coronary artery calcium resulting in reduced risks of vascular diseases , which carry the strongest mortality risk . in addition , regular physical activity increases the endurance of cells and tissues to oxidative stress , vascularization , and energy metabolism . according to the results of the meta - analysis on all - cause mortality in relation to physical activity performed by samitz et al . , vigorous physical activity ( > 6 metabolic equivalents ( met ) ) reduces mortality slightly , but this reduction is significantly more pronounced than that for moderate activity ( 36 met ) . a greater life expectancy is not associated with more years of being frail and depending on assistance . in contrary , nusselder et al . reported a gain of disability - free years of life with a higher life expectancy . the few data available on life expectancy in athletes who were much more physically active than the average individual are inconclusive . all studies proved an increased life expectancy in endurance athletes ranging between 2.8 to 8.0 added years . this gain is probably higher than that found for persons performing vigorous physical activity in the cohort studies . in team sports and other sports disciplines however , data on health behaviors of these athletes other than their physical activity during their active sports career such as smoking , food , and alcohol consumption are not available . thus , the effect of elite sports activities on life expectancy warrants further investigation . in summary , as expected from numerous prospective cohort studies on all - cause mortality in physically active and physically inactive persons , estimates on life expectancy in relation to physical activity indicate additional years of life in active subjects : the conservative estimate of the net increase in life expectancy with physical activity is about 24 years but presumably even greater because of the positive influence of physical activity on major risk factors for mortality .

physical activity reduces many major mortality risk factors including arterial hypertension , diabetes mellitus type 2 , dyslipidemia , coronary heart disease , stroke , and cancer . all - cause mortality is decreased by about 30% to 35% in physically active as compared to inactive subjects . the purpose of this paper was to synthesize the literature on life expectancy in relation to physical activity . a systematic pubmed search on life expectancy in physically active and inactive individuals was performed . in addition , articles comparing life expectancy of athletes compared to that of nonathletes were reviewed . results of 13 studies describing eight different cohorts suggest that regular physical activity is associated with an increase of life expectancy by 0.4 to 6.9 years . eleven studies included confounding risk factors for mortality and revealed an increase in life expectancy by 0.4 to 4.2 years with regular physical activity . eleven case control studies on life expectancy in former athletes revealed consistently greater life expectancy in aerobic endurance athletes but inconsistent results for other athletes . none of these studies considered confounding risk factors for mortality . in conclusion , while regular physical activity increases life expectancy , it remains unclear if high - intensity sports activities further increase life expectancy .

for years many physicians firmly believed that a hemoglobin of 10 g / dl and a hematocrit of 30% represented desirable goals in anemic patients , especially those undergoing surgical procedures and those with cardiac disease . despite the paucity of objective data to support this contention , the so - called ' 10/30 rule ' persisted until recently . most authorities attribute this bias to a 1942 report by adams and lundy in which they recommended a hemoglobin of 10 g / dl and a hematocrit of 30% in the perioperative setting based on their clinical experience . recent studies [ 3 - 7 ] have provided compelling evidence against the 10/30 rule in critically ill patients as well as in the perioperative period . despite these data , many clinicians continue to provide transfusion using a hematocrit of 30% as a ' transfusion trigger ' . however , current practice and available evidence is gradually shifting from transfusing to an arbitrary hemoglobin ( 10/30 ) to achieving a level of hemoglobin necessary to meet the patient 's tissue oxygen demands . the optimal hemoglobin level is more closely approximated by physiologic measurements . in patients who are not critically ill , most studies have demonstrated that a substantially lower hemoglobin level ( 7 g / dl ) can be tolerated if normovolemia is maintained . experience in jehovah 's witness patients has allowed an assessment of human tolerance of severe acute anemia and demonstrated the feasibility of survival in the case of very low hematocrit [ 12 - 18 ] . in a review of 61 medical and surgical reports published from 1970 to 1993 , viele and weiskopf identified 50 deaths attributed to anemia in untransfused jehovah 's witnesses with hemoglobin concentrations of 8 g / dl or less , or hematocrit of 24% or less . of the 50 deaths , 23 except for three patients who died after cardiac surgery , all patients whose deaths were attributed to anemia died with hemoglobin concentrations of 5 g / dl or less . recently , weiskopf and coworkers conducted an interventional study to determine whether acute , severe isovolemic reduction in hemoglobin levels to 5 g / dl in healthy , resting individuals would result in inadequate cardiac compensatory mechanisms , and therefore compromise oxygen delivery . no evidence of inadequate oxygenation , as assessed by lack of change in oxygen consumption and plasma lactate concentration , was noted in the 11 preoperative patients and 21 nonsurgical volunteers with hemoglobin levels as low as 5 g / dl . anemia in the setting of critical illness is quite prevalent , with 3744% of patients receiving at least one blood transfusion during their intensive care unit ( icu ) stay . in one representative study , 85% of patients with an icu length of stay greater than 1 week received at least one blood transfusion . in more than two thirds of these cases blood transfusion concerns over the deleterious effects of anemia are increasingly being balanced by an increased awareness of the serious , well documented consequences of packed red blood cell ( rbc ) transfusion . in a pivotal study published in 1999 , hebert and coworkers prospectively randomized 838 critically ill icu patients with hemoglobin under 9 g / dl to one of two transfusion strategies . the control group ( ' liberal strategy ' ) received transfusion of packed rbcs when the hemoglobin fell below 10 g / dl . the study group ( ' restrictive strategy ' ) received transfusion of packed rbcs when hemoglobin fell below 7 g / dl . the 30-day mortality rate was not significantly different between groups but was significantly lower with the restrictive strategy in patients who were less ill ( acute physiology and chronic health evaluation ii score 20 ) and those who were younger ( age < 55 years ) . . a restrictive strategy of rbc transfusion is at least as effective and possibly superior to a liberal transfusion strategy in critically ill patients , with the possible exception of patients with acute myocardial infarction and unstable angina . current evidence suggests that clinicians are reconsidering more conservative transfusion practices in light of these and similar data . vincent and coworkers conducted a cross - sectional study intended to evaluate transfusion practices in 146 european icus . they reported that pretransfusion hemoglobin concentrations ( 8.4 g / dl ) are currently lower than those previously cited . data from a prospective , multi - center , observational trial suggest a similar trend toward more restrictive transfusion practices in the usa . this shift toward restrictive transfusion policies may in part be related to the work published by the canadian critical care trials group . the hemoglobin concentration at which risk for death or serious morbidity occurs was investigated by carson and colleagues using a retrospective cohort of 1958 patients who underwent surgery and declined blood transfusion . cardiovascular disease was defined as a history of angina , myocardial infarction , congestive heart failure , or peripheral vascular disease . in patients with preoperative hemoglobin levels of 12 g / dl or greater the mortality rate was 1.3% , whereas patients with preoperative hemoglobin levels of less than 6 g / dl had a mortality rate of 33.3% . the authors concluded that low preoperative hemoglobin substantially increases the risk for death and serious morbidity . the threshold for transfusion in the critically ill or perioperative patient with known coronary artery disease is still debated . the traditional belief is that anemic patients with coronary artery disease are at high risk for myocardial ischemia or infarction because they can not increase oxygen extraction or augment coronary arterial flow . retrospective studies to date in this population , including the study by carson and colleagues , suggest that critically ill patients with cardiac disease had higher mortality when hemoglobin levels dropped from approximately 10 g / dl perioperatively to 6.06.9 g / dl . in fact , the adjusted odds of death in patients with cardiovascular disease increased five - fold ( from 2.3 to 12.3 ) . there is little available evidence supporting the use of blood transfusions in the setting of acute myocardial infarction , excluding retrospective work based on a large administrative discharge database done by wu and colleagues . ignoring the significant limitations of the study design and methods , wu and coworkers reported that patients with lower hematocrit values on admission had higher 30-day mortality rates . at least one randomized controlled trial has suggested that lowering the hemoglobin threshold for transfusion in aortocoronary bypass grafting procedures to 8 g / dl postoperatively does not adversely affect outcome . there is some suggestion that cardiac bypass patients with higher hematocrit levels postoperatively are more likely to sustain a postoperative myocardial infarction . in this setting , both study groups consisted of patients whose surgical lesions were corrected , and as such , they may have behaved differently from patients with fixed cardiac disease . there is substantial evidence on the beneficial effect of -blockade in patients who have or are at risk for coronary artery disease in reducing mortality as well as the incidence of cardiovascular complications . however , of the recent studies investigating anemia in cardiac disease , all have failed to control for confounding variables such as -blockade and heart rate . the investigators in the transfusion requirements in critical care ( tricc ) trial performed a subgroup analysis of the main study to include patients who were thought to be at increased risk for complications associated with anemia because of a diagnosis related to coronary artery disease . those investigators analyzed 357 patients and found no significant difference in 30-day mortality between the restrictive and the liberal transfusion strategies . other outcome measurements including multiorgan dysfunction scores , icu and in - hospital length of stay were superior in the restrictive strategy group . furthermore , there was a greater incidence of pulmonary edema , a common complication of blood transfusion , in the liberal transfusion strategy group ( 10.7% versus 5.3% ) than in the restrictive group . intuitively , transfusion in the asymptomatic patient with ischemic heart disease and left ventricular dysfunction may actually be detrimental by precipitating pulmonary edema . in a subgroup with severe ischemic heart disease ( n = 257 ) , the absolute survival rate was lower in the restrictive strategy group than in the liberal strategy group , but this difference was not statistically significant . the authors concluded that a restrictive transfusion strategy appeared to be safe in most critically ill patients with cardiovascular disease , with the possible exception of patients with acute myocardial infarction and unstable angina . because this conclusion was derived from a subgroup analysis , caution is warranted in the interpretation of these results . the critically ill patient with active ischemic cardiac disease continues to represent a ' gray area ' in the literature . under these circumstances , it is prudent to recommend individualizing transfusion decisions to meet the patient 's specific myocardial oxygen supply / demand , which may change during the course of their illness . arbitrary application of the 10/30 rule may result in avoidable adverse outcomes and as such can no longer be advocated as a transfusion trigger in any patient population . based on the available data , it appears appropriate and safe to withhold transfusion based on the hemoglobin or hematocrit level until the patient 's hemoglobin is 7 g / dl or less . regarding patients with cardiac disease but without acute myocardial infarction or unstable angina , evidence from the tricc study suggests that this approach is safe in this group as well , provided euvolemia is maintained . there is still controversy about this group of patients , however , and more trials addressing transfusion triggers in patients with coronary artery disease are needed . given the well documented risks associated with blood transfusion , these data strengthen the contention that blood transfusion should be carefully considered and that the decision to transfuse rbcs can not be justified by the 10/30 rule .

despite the increasing availability of data supporting more restrictive transfusion practices , the risks and benefits of transfusing critically ill patients continue to evoke controversy . past retrospective and observational studies suggested that liberal transfusion strategies were more beneficial in patients whose hematocrit levels fell below 30% . an expanding body of literature suggests that an arbitrary trigger for transfusion ( the ' 10/30 rule ' ) is ill advised . a recent randomized controlled trial provided compelling evidence that similar , and in some cases better , outcomes result if a restrictive transfusion strategy is maintained . the impact of this accumulating evidence on clinical practice is evident in large reports , which show that the average transfusion trigger in critically ill patients was a hemoglobin level in the range 88.5 g / dl . based on the available evidence , transfusion in the critically ill patient without active ischemic heart disease should generally be withheld until the hemoglobin level falls to 7 g / dl . transfusions should be administered as clinically indicated for patients with acute , ongoing blood loss and those who have objective signs and symptoms of anemia despite maintenance of euvolemia . the hemoglobin level at which serious morbidity or mortality occurs in critically ill patients with active ischemic heart disease is a subject of continued debate but it is likely that a set transfusion trigger will not provide an optimal risk benefit profile in this population .

the collective arrangement of the teeth in function is quite important and has been subjected to a great deal of analysis and discussion over the years . as the mandible moves laterally , the lower posterior teeth leave their centric contact with the upper teeth and travel sideways down a path dictated by the condyles in the back and by the lateral anterior guidance in the front . in the diversified literature on occlusion and its role for functional patterns of the masticatory system , two concepts stand out : ( 1 ) canine protection as described by damico is said to favor a vertical chewing pattern and to prevent wear of teeth , as in lateral occlusion where the canine guides the mandibular movement directly through contact or indirectly through periodontal receptors . ( 2 ) group function as described by beyron following his observations on australian aborigines implies contact and stress on several teeth in lateral occlusion and indicates abrasion as a positive and inevitable adjustment . the reason for bringing any teeth into lateral function is to distribute stress and wear over more teeth . group function occlusion , which is also commonly known as unilateral balanced occlusion , is a widely accepted and used method of tooth arrangement in restorative dental procedures today . , the contacting inclines must be perfectly harmonized to border movements of the condyles and the anterior guidance . kleinberg has pointed out the importance of the feedback mechanism between mechanoreceptors in the temporomandibular joint and the functional mandibular movement pattern . in addition , a probable change in the input signals from the periodontal receptors after occlusal adjustment seems to affect the functional movement of the mandible . ingervall recorded tooth contact patterns in laterotrusion , protrusion of the mandible , and in the retruded position in young men with varying types of occlusion . contact on the nonfunctional side was found in half of the subjects in a 1.5-mm laterotrusive position and in one third of them in a 3-mm laterotrusive position . yaffe & ehrlich recorded the dynamic contact pattern of teeth in lateral glide movement in 72 individuals , 19 to 35 years of age , with normal tooth alignment and angle s class i molar and canine relationship . the lateral glide movement was divided into three stages to simulate the total range of events in lateral glide movement naturally demonstrated by the patient . this study has shown that lateral glide movement is a complex movement in which the nature of tooth contact is altering in location , direction , and number of teeth participating . consequently the restoration of an occlusion in accordance with a given concept does not always apply to all patients . the present study was designed to evaluate the incidence of occlusal patterns in a group of dental students . fifty subjects ( male : 27 , female : 23 ) aged 2029 years ( mean , 24.1 years ) were included in the study . they were selected from a group of 225 undergraduate students of the faculty of dentistry , tabriz university of medical sciences . the research and ethics committee approved the study protocol and informed consent was obtained from the subjects after they were provided an explanation of the general nature of the study . the criteria for selection were as follow : all subjects ( i ) were in their twenties ; ( ii ) had normal occlusal alignment , no temporomandibluar signs and symptoms with angle s class i relationship ; ( iii ) had full dentition except for third molars ; ( iv ) had no history of orthodontic therapy ; and ( v ) had no restorations involving a cusp . the occlusal contacts were recorded with occlusion foil ( 8 m thick , occlusions pruf - folie , ghm , germany ) in three lateral excursions , after laterally sliding the mandibular incisal point on both sides , 1 , 2 and 3 mm from the maximum intercuspation ( mi ) . when recording the occlusal contacts , each patient was instructed to close in the intercuspal position and to slide the mandible laterally to the right and left side performing the three lateral excursive movements designed as lateral 1 ( 1 mm from mi ) , lateral 2 ( 2 mm from mi ) , and lateral 3 ( 3 mm from mi ) on each side . each subject was required to sit upright in a dental chair with the frankfort plane almost horizontal . marks were made on the upper central incisors with a sharp black water - resistant pencil from the mandibular midline . three lines were marked on the maxillary incisor . in case of deviation of mandibular midline , a reference line was traced at the labial surface of the mandibular incisor in the intercuspal position to serve as a guide for the measurement . the blue occlusion foil was placed on the occlusal surface of the left - side most posterior mandibular molar , and the subject was requested to close his / her mandible to the mi . while a constant pulling force was maintained on the occlusion foil , red occlusion foil was put and the subject was requested to perform gliding movement to the right with the teeth in light contact . when the subject s mandible moved 1 mm right from the intercuspal position , the presence or absence of an occlusal contact was examined . only the red marks on teeth were considered to indicate occlusal contact . to prevent movement with mandibular opening or movement without occlusal contact and lateral - protrusive excursion , the movement was observed closely , and occasionally the subject was instructed to correct the movement . when the subject could not perform the movement voluntarily , he or she was asked to practice with the use of a hand mirror . the examination was continued from the left - side most posterior molar to the left - side central incisor sequentially . for examination of the molars , the occlusion foil was placed on both the mesial and distal sides of the occlusal surface . the same procedure was performed for the 1 , 2 and 3 mm right positions and also for the 1 , 2 and 3 mm left positions . in addition , the working - side occlusal contacts were recorded in the same manner . all recordings were performed by the same examiner and were repeated . in the case of differing results , all recordings were made between 10 oclock in the morning and 4 oclock in the afternoon to avoid possible diurnal variations . working - side occlusal contact patterns were determined for the total range of lateral positions and classified into three groups : canine protection , group function or others ( occlusal patterns other than those described ) . canine protection was defined as the contact of only working - side maxillary and mandibular canines in the total range of lateral positions from 1 to 3 mm . group function was defined as the contacts of two or more working - side teeth in at least one lateral position , and/or as single tooth contacts on the working - side in different lateral positions , e.g. the contact of only first molars in the 1 mm position followed by the contact of only canines in the 2 and 3 mm positions . the others type was identified when a contact pattern other than those described above was observed , e.g. contact of only first premolars throughout the lateral positions or contact patterns with no working - side contacts . figure 1 shows the number of working occlusal contacts recorded for each dental unit on right and left sides . the working - side occlusal contacts were mostly on the first premolar in r1 ( right 1 mm ) followed by canine ; but in l1 ( left 1 mm ) , the percentage of contacts on canine and first premolar were the same . the frequency of contact on premolars decreased gradually from the 1 to 3 on both sides . in all lateral positions , the frequency of contact decreased from the canine to the first molar as the tooth type became located posteriorly . however , the contact on the first molar almost was as prevalent as that on the second premolar . the frequency of the working - side canine contact increased from the 1 to the 3 mm position . figure 2 presents the number of non - working occlusal contacts recorded for each dental unit on right and left sides . the non - working - side contacts primarily involved the first and second molars , most frequently the second molar . the prevalence of non - working - side contacts decreased as the mandible moved from the 1 to 3 mm position on the premolars and molars . table 1 shows the percentage of occlusal patterns in mandibular lateral movement on the right and left sides . most of working - side contact patterns were classified as group function ( 60% ) ; canine protection was rare ( 17.3% ) , and contact patterns other than canine protection and group function were found in 23.7% of the contact patterns on the right side . on the left side , group function was found in 51.3% , canine protection in 20.7% and others in 28% of the contact patterns . most of the subjects ( 66% ) had the same pattern on both sides : 42% group function , 8% canine protection , and 16% others . this study demonstrated that the occlusal contact pattern during lateral movement differs between 1 mm , 2 mm and 3 mm . in the position close to the maximum intercuspation the occlusal contact pattern varying with lateral positions should be a critical factor on diagnosis and treatment of occlusal disharmonies . the marked difference in the pattern of occlusal contacts between the 1 , 2 and 3 mm positions , suggests that the contact pattern in the 1 mm position reflects a pattern of occlusal contact distinct from that commonly observed during lateral excursion . in a study analyzing two working - side inter - occlusal contacts , a large number of subjects presented unclassified patterns of articulations . more individuals had canine guidance on the left side , whereas the most frequent pattern on the right side was group function . another study on occlusal contact areas using a 3-d digitization measurement system found that , at intercuspal position , estimated occlusal contact areas were 12.6 mm . however , after 3.0 mm of lateral excursion , their areas were sharply reduced to 2.2 mm . ogawa et al10 - 12 found most contact patterns belonged to group function and a few to canine protection . they also found the presence of occlusal contacts in different lateral positions may have different effects on biomechanics of the related teeth . for instance , the force on individual teeth may be more traumatic in the more lateral positions because of the increased vector of the force . occlusal force is transmitted to the teeth during four functional and parafunctional stages : mastication , swallowing , clenching and grinding . the occlusal contact during mastication and swallowing is suggested to occur mainly in lateral positions close to the mi , i.e. within 1 mm of the mi.10 - 1 in addition , forces during these two functional movements are relatively low and their durations are short . taking into consideration these various factors , the biomechanical significance of non - working - side occlusal contact may increase over the non - functional range of lateral movement corresponding to the 3 mm position . in the present study , incidence of non - working - side occlusal contact decreased from 1 to 3 mm ; so it does not seem appropriate to deduce that contact in this position produces harmful force to the teeth or periodontal structures . however , this does not exclude the possibility that the non - working - side contacts in the position close to the mi may be important in masticatory function . contact patterns other than canine protection and group function were found in 23% of the contact patterns on the right side . on the left side , group function was seen in 51% , canine protection in 21% and others patterns in 28% of the studied subjects . on laterotrusion , most subjects had group function on the working side but canine protection was rare .

background and aims this study observed occlusal contacts and their area on the teeth during lateral mandibular movements . the percentage of each occlusal pattern was determined . materials and methods fifty subjects ( male : 27 , female : 23 ) , aged 20 - 29 years , were included in the study . the criteria for selection were as follow : all subjects ( i ) were in their twenties ; ( ii ) had normal occlusal alignment , no temporomandibular signs and symptoms with angle s class i relationship ; ( iii ) had full dentition except for third molars ; ( iv ) had no history of orthodontic therapy ; and ( v ) had no restorations involving a cusp . the occlusal contacts were recorded with occlusion foil in three lateral excursions : 1 , 2 and 3 mm from the maximum intercuspation . data were analyzed with chi - square test . results most of working - side contact patterns were classified as group function ( 60% ) . canine protection was rare ( 17% ) . contact patterns other than canine protection and group function were found in 23% of the contact patterns on the right side . on the left side , group function was seen in 51% , canine protection in 21% and others patterns in 28% of the studied subjects . conclusion on laterotrusion , most subjects had group function on the working side but canine protection was rare .

respiratory syncytial virus ( rsv ) is a negative sense single - stranded rna virus belonging to pneumovirus genus , subfamily pneumovirinae . rsv is considered a major cause of severe lower respiratory tract infections in children less than two years of age worldwide . therefore , early detection of the virus is a critical step in the initiation of proper care , and the prevention of further spread of the virus in public places such as schools and health care facilities . direct fluorescence assay ( dfa ) is a conventional method that is frequently used in the clinical setting for the detection of respiratory viruses including rsv . however , nucleic acid detection methods have proven to be more sensitive for rsv detection . some countries , particularly developing countries , can not afford to use nucleic acid detection methods within hospital laboratories due to high cost and lack of technical expertise . in this study , we compared the sensitivity and specificity of the dfa against real - time reverse transcriptase polymerase chain reaction ( rt - rt - pcr ) as a point - of - care method for rsv detection . comparison was also made between both assays in relation to the days after onset of symptoms . four hundred and fifty one specimens were collected between december , 2006 and november , 2007 from patients presenting to abou el rish pediatric hospital , cairo , egypt , with acute lower respiratory tract infection ( alrti ) as per the who case definition ( who / cds/2004.25 ) . for each patient that met the criteria , a nasopharyngeal aspirate ( npa ) was collected using the infant mucous extractor ( argyle delee , kendall , usa ) . virus transport media was added to each npa and was split into two aliquots , one for direct fluorescent assay ( dfa ) and the second for nucleic acid extraction . for dfa , an epithelial cell suspension in phosphate buffered the respiratory panel 1 dfa kit ( light diagnostics millipore , calif , usa ) was used for dfa . total nucleic extraction was performed using magmax express96 ( applied biosystems ) and the total nucleic acid isolation kit ( ambion ) per manufacturer 's instructions . rt - rt - pcr was performed as per centers for disease control and prevention ( cdc ) , atlanta , ga , usa using cdc 's primers . a sample was considered positive for rsv if its cycle threshold ( ct ) was 38 . statistical significance was determined by chi - square and fisher 's exact t - test using epiinfo software , version 6.04 in this study , rt - rt - pcr served as the standard test , and sensitivity and specificity of dfa were calculated on the basis the pcr results . sensitivity of dfa was calculated by dividing the number of samples positive for rsv by both dfa and rt - rt - pcr by the total number of samples positive by rt - rt - pcr . specificity of dfa was calculated by dividing the number of samples negative by both dfa and rt - rt - pcr by the total number of samples negative by rt - rt - pcr . positive predictive value ( ppv ) of dfa was calculated by dividing the number of samples positive by both dfa and rt - rt - pcr by the total number of dfa positive samples . negative predictive value ( npv ) was calculated by dividing the number of samples negative by both dfa and rt - rt - pcr by the total number of dfa negative samples . the age range of patients was 060 months , 41.5% were between 0 and 6 months of age . the prevalence rate of rsv in this study population by the two assays was 23.7% ( 107/451 ) . patients aged 06 months had a statistically significant higher rate of rsv infection compared to in the other age groups ( figure 1 ) . we examined the effect of sample collection date in relation to date of onset of symptoms on the dfa sensitivity for detection of rsv . the dfa was 86% sensitive and 99% specific between 0 and 3 days after onset of symptoms . the sensitivity of dfa dropped to 75.8% when samples were collected 47 days after onset of symptoms and was 100% specific . dfa was only 65% sensitive when samples were collected 8 days and more after symptom onset , and the specificity remained at 100% , indicating that the assay is still reliable ( figure 2 ) . the rate of rsv infection was significantly higher among children aged 06 months old , which is in accordance with other studies . both assays are very specific and have good predictive value for diagnosis . in general , the downfall of this technique is the expense and that it is not currently available in many clinical settings , especially in developing countries . therefore , we also examined the commonly used dfa assay for the detection of rsv in a clinical setting . dfa still offers a reliable option for the detection of rsv especially for patients tested with the first 3 days after onset of symptoms . successful rsv testing during the first days of illness enables the physician to make the best decision regarding treatment for the child and prevent the spread of infection especially within health care facilities .

respiratory syncytial virus ( rsv ) is the major cause of lower respiratory tract infections in children worldwide . early detection of rsv is critical to initiate proper care . two methods , the direct fluorescence assay ( dfa ) and the real - time reverse - transcription polymerase chain reaction ( rt - rt - pcr ) , that are used for rsv detection were compared . a total of 451 nasopharyngeal aspirates from children 5 years of age or less were tested for rsv using both methods . the overall prevalence rate of the rsv among the children was 23.7% with a significantly higher prevalence among children under the age of 6 months of age when compared to other age groups . the sensitivity of dfa in comparison to rt - rt - pcr was highest ( 86% ) during the first 3 days of symptoms onset and decreased gradually till it reached 65% after the first week . the specificity of dfa in comparison to rt - rt - pcr ranged between 99 and 100% irrespective of the date of collection . we concluded that , although the rt - rt - pcr is more sensitive for rsv detection , the dfa offers a reliable point - of - care alternative detection method especially during the first few days of illness .

acute pulmonary embolism ( pe ) is a common life - threatening condition and represents the most serious manifestation of venous thromboembolic disease . acute pe interferes with both the circulation and gas exchange and right ventricular ( rv ) failure due to pressure overload is considered as the primary cause of death in severe pe . the standard treatment is anticoagulation and systemic thrombolysis , while the latter is usually indicated in massive acute pe with improvement in cardiopulmonary hemodynamics . although systemic thrombolysis is indicated for the treatment of acute pe with hypotension or shock , many patients can not undergo systemic thrombolysis due to contraindications , and even though patients with acute pe are prescreened for absolute contraindications , the rate of major hemorrhage from systemic thrombolytic administration is approximately 10%20% . another category of acute pe patients without hypotension or shock but with signs of rv dysfunction with elevated cardiac biomarkers can also be considered for systemic thrombolysis . catheter - directed thrombolysis ( cdt ) can be considered as an alternative life - saving procedure in such patients as it is associated with much lower risk of bleeding . mechanical methods such as thrombus fragmentation , rheolytic thrombectomy , suction thrombectomy , and rotational thrombectomy are indicated for patients with absolute contraindications to thrombolysis whereas , conventional pharmacological cdt and pharmacomechanical thrombolysis with ultrasound enhancement as well as rheolytic thrombectomy are indicated for patients without absolute contraindications to thrombolysis . these methods have improved the outcomes compared to systemic thrombolysis as well as anticoagulation alone with lesser risk of bleeding . however , the mechanical and pharmacomechanical methods require specialized catheters , expertise and are expensive . on the other hand , conventional pharmacological cdt is done in catheterization laboratories under fluoroscopic guidance with repeated pulmonary angiographies adding to cost , radiation exposure , and risk of contrast - induced nephropathy . a bedside method of pharmacological cdt using pulmonary artery catheter with no radiation exposure and real time monitoring of pulmonary artery pressures ( paps ) as an end - point of thrombolysis has been reported in the present study . a 60-year - old male with no comorbid illness underwent cervical laminectomy for compression myelopathy 3 months back . there was prolonged immobilization for 2 weeks of postsurgery and patient was put on thromboprophylaxis with low molecular weight heparin . after resuming daily routine activities the patient has presented with complaints of acute onset of breathlessness , palpitation , syncopal attacks , and bilateral lower limb swelling for 10 days . on physical examination , the patient had an arterial blood pressure ( bp ) of 120/80 mmhg , a heart rate ( hr ) of 136 beats / min , respiratory rate ( rr ) of 28 breaths / min and oxygen saturation ( sao2 ) of 88% on room air . the arterial blood gas on room air showed a pao2 of 45.7 mmhg , paco2 of 36.4 mmhg , hco3 of 30.2 mmol , and ph of 7.53 with wide alveolar - arterial gradient 60.3 mmhg ( respiratory alkalosis with metabolic alkalosis with hypoxemic respiratory failure ) . chest skiagram showed obliteration of pulmonary bay with bilateral prominent pulmonary arteries and hyperlucent left lung [ figure 1 ] . two - dimensional echocardiography revealed dilated right atrium and right ventricle , hypokinetic rv wall , dilated inferior vena cava , moderate tricuspid regurgitation ( estimated mean pap = 44 mmhg ) , and left ventricular ejection fraction of 55% . contrast - enhanced computed tomography ( ct ) thorax showed multifocal filling defects noted in the right and left branch of pulmonary artery extending into the descending branch of the left pulmonary artery as well as the bifurcation of right and left pulmonary artery [ figure 2 ] . quantitative troponin - i was raised ( 0.2 pg / ml ) and serum n - terminal brain natriuretic peptide level was also raised ( 5871 pg / ml ) . ultrasound doppler venography showed subacute thrombus in the right distal superficial femoral and right popliteal vein . the diagnosis of intermediate - high risk acute pe was established on the basis of calculated simplified pe severity index score of > 1 along with signs of rv dysfunction on echocardiography and elevated cardiac biomarkers in the absence of shock or hypotension . the patient was prepared and draped in standard sterile fashion while supine on the procedure table . swan - ganz catheter ( edwards lifesciences llc irvine , usa ) was introduced through the right internal jugular vein . cdt using the flow directed technique , which is a form of pharmacologic thrombolysis in which the fibrinolytic drug infusion is administered through a catheter positioned in the pulmonary artery proximal to the location of pulmonary artery thrombus , was then pursued . the catheter was positioned in the pulmonary artery guided by the pressure readings , and alteplase was administered with nonbolus continuous infusion at 0.51 mg / h with initial higher infusion doses with a slower rate of taper ( 50 mg of alteplase reconstituted in 50 ml of sterile water and diluted with 500 ml of 0.9% normal saline solution to a concentration of 0.10.2 mg / ml ) . systemic intravenous ( iv ) heparin was also administered through continuous infusion with an initial dosing rate of 1000 units / h to prevent thrombus propagation and was further titrated to achieve a partial thromboplastin time of 6080 s by performing coagulation profile every six hourly . the patient was continuously monitored for any evidence of bleeding in an icu setting during the thrombolytic therapy . the clinical progress of cdt was assessed by evaluating patient 's hemodynamic status , sao2 and mean pap . daily chest radiography was performed to ensure catheter positional stability and to enable catheter repositioning as needed . thrombolysis was continued until mean pap was normalized ( < 18 mmhg ) or the maximum dose of alteplase ( 100 mg ) was reached . after 3 days of thrombolysis with total dose of alteplase 50 mg , there was a reduction of pap to 18 mmhg . the patient became hemodynamically stable as vital parameters returned to normal ( hr 94/min , bp 130/80 mmhg and rr 20/min ) . there was also an improvement in oxygenation parameter with pao2 of 74.4 mmhg as well as sao2 of 97% on room air and normalization of alveolar - arterial gradient to 21.5 mmhg as shown in table 1 . serial two - dimensional ( 2d ) echocardiogram after thrombolysis revealed normal right atrium and right ventricle and serum n - terminal pro - b - type natriuretic peptide decreased to 562 pg / ml . after completion of thrombolytic therapy , the pulmonary artery catheter was removed , and hemostasis was achieved at the venous site with manual compression . ct - pulmonary angiography ( ctpa ) was not performed immediately at the completion of thrombolysis to avoid harmful radiation exposure and contrast - induced nephropathy . the patient was on continuous infusion of heparin for 3 days during thrombolysis followed by intermittent dosing of iv 5000 units three times daily for next 2 days and then switched to oral anticoagulation dabigatran 150 mg twice daily on 6 day of admission and further maintained on a 6-month course of oral anticoagulation after completion of cdt . he was discharged on the 10 day of admission under regular follow - up at three and 6 months of oral anti - coagulation therapy . the findings of serial 2d echocardiogram at each follow - up remained unremarkable after thrombolysis . follow - up ctpa was also advised after 3 months that revealed near resolution of thrombus at bifurcation of right and left pulmonary artery as shown in figure 3 . frontal radiograph of chest shows obliteration of pulmonary bay with bilateral prominent pulmonary arteries pretreatment axial contrast enhanced computed tomography image of thorax shows prominent main pulmonary artery ( transverse diameter measures 3 cm ) with hypodense filling defects in right and left main pulmonary artery suggestive of thrombus serial hemodynamic and gas exchange parameters in our patient undergoing catheter guided thrombolytic therapy post intrapulmonary arterial instillation of alteplase axial contrast enhanced computed tomography image of thorax shows dissolution of the thrombus seen within the right and left pulmonary artery previously the objective of cdt is to remove obstructing thrombi from the main pulmonary arteries to facilitate rapid reperfusion leading to rv recovery and improve symptoms and survival . the indication for application of thrombolytic therapy in treatment of patients with intermediate high risk pe is currently considered as controversial . in the current case , doctors were successfully able to normalize pap and achieve complete resolution of pa clot using alteplase infusion without any bleeding or other complication . the time required for normalization of pa pressures and the dose required for clot dissolution was comparable to that reported in previous studies . however , the dose was half of that required with systemic thrombolysis , probably due to high local concentration of alteplase in the pulmonary circulation . another advantage of local instillation of alteplase through pulmonary artery is real time measurement of paps throughout the period of thrombolysis with a measurable endpoint of normalisation of pa pressures . . the major limitations of cdt were the risk of catheter related blood stream infection and prolonged period of thrombolytic therapy ( 50 h for the infusion ) . however , there was no evidence of bloodstream infections in the patient . mechanical and pharmacomechanical cdt are associated with several demerits such as periprocedural hemodynamic deterioration , distal embolization , pulmonary artery perforation , systemic bleeding complications , lung hemorrhage , pericardial tamponade , transient heart block or bradycardia , contrast - induced nephropathy , and access - related complications , including hematoma , pseudoaneurysm , or arteriovenous fistula . patients with preexisting renal failure can also be considered for pulmonary artery cdt as no iv contrast is used . the safety and efficacy should be validated by conducting large - scale studies for comparing efficacy and safety of pulmonary artery cdt to other methods of cdt , which would be necessary before its inclusion in the existing guidelines .

a case of 60-year - old male with acute pulmonary embolism without hypotension but signs of right ventricular dysfunction and elevated cardiac biomarkers is reported in this study . the patient comes under intermediate high - risk category and was successfully thrombolysed with alteplase infused through pulmonary artery catheter . catheter - directed thrombolysis ( cdt ) can be considered as much safer and effective alternative to systemic thrombolysis in such patients with lower risk of bleeding . this novel bedside method of pulmonary artery cdt with the advantage of no radiation exposure and real time monitoring of pulmonary artery pressures as an end - point of thrombolysis can be utilized in the near future .

ingestion of some amino acids has presumable roles in performance improvement in athletes.[13 ] among them , -alanine supplementation has been suggested to improve performance during high - intensity exercises . on the other hand , it has been shown that large amounts of h are produced in the muscles during high - intensity exercise and result in ph reduction . there are many cellular ph buffers defend against exercise - induced acidosis , which include phosphocreatine , inorganic phosphates and histidine - containing dipeptides . carnosine ( -alanyl - l - histidine ) is the main histidine - containing dipeptide in humans . additionally , hill et al . and harris et al . , showed that 28 days of -alanine supplementation increased intramuscular levels of carnosine by nearly 60% . antioxidant function , muscle contractility regulation , and ph buffering , are the possible physiological roles of carnosine in skeletal muscle . thus , the possible role of carnosine could be prevention of skeletal muscle acidity in improving exercise performance . prolonged exercise can result in oxidative stress and muscle fatigue , which may be prevented by carnosine due to its antioxidative properties . on the other hand , -alanine administration could increase carnosine content of skeletal muscles by 4080%.[1719 ] increase of carnosine concentrations in muscle results in altered buffering capacity,[1819 ] and thus affects performance . furthermore , some studies have shown that carnosine acts as a ca sensitizer for the sarcomeres in muscles[2021 ] and thus could prevent fatigue . however , synthesis of carnosine in muscle is limited by the availability rate of -alanine , which can be overcome by -alanine supplementation . although it has been estimated that carnosine is responsible for nearly 10% of the total buffering capacity in human muscle there are few studies on -alanine supplementation and its possible effects on endurance exercise ; therefore , the purpose of this study is to assess the effects of -alanine administration on vo2 max , time to exhaustion and lactate concentrations in male physical education students . these students were fit ( bmi<25 ) and active ( physical activity2 hr / d ) , but not involved in professional sports . participants age , weight and height were 21.10.7 years , 71.88.8 kg and 1787 cm , respectively , for -alanine ( n=20 ) group and 21.91.5 years , 74.98.3 kg and 1805 cm for placebo group ( n=19 ) , respectively ( ns ) . before initiating the study , all participants were informed of all procedures of the study and signed an informed consent . none of the participants had ingested -alanine , or any other nutritional supplements , for a minimum of 3 months before the initiation of the study . participants were asked to abstain from exercise 24 h before trial initiation and to maintain their current physical activity and dietary patterns . after pre - testing , the participants were randomly assigned to one of the two groups : a ) -alanine ( 2 g / day ) , b ) placebo ( 2 g dextrose per day).the supplements had the same appearance , and ingested four times per day for 42 consecutive days before post - testing . all participants completed all experiments , and there were no complaints of side effects of the supplements . participants were supplemented orally for 6 weeks with either -alanine ( ajinomoto , usa , inc ) or placebo ( dextrose ) . the study was approved by the ethics committee ( esfahan sport medicine association , iran ) . supplements were provided in capsules of 400 mg and were administered each day as five divided single doses , with at least 2 h in between ingestions . venous blood samples were obtained from all participants between 5:00 and 6:00 p.m , after intensive endurance exercising , at the baseline and after intervention . all measurements were done before the start of the supplementation ( pre ) and after the intervention ( post ) . prior to and following the supplementation protocol , participants performed a continuous graded exercise test ( gxt ) on an electronically braked cycle ergometer ( lode , the netherlands ) to determine vo2 max and time to exhaustion ( tte ) . for each gxt , the primary power output was set at 30 w and elevated 30 w every 2 min until the participant could not maintain the required power output at a pedaling rate of 70 rpm due to fatigue . plasma samples were obtained for the determination of plasma lactate and glucose concentrations immediately prior to each gxt and 2 min post - exercise . glucose and lactate were analyzed using ysi auto - analyzer ( yellow springs , oh ) . statistical analyses were conducted using the statistical program for the social sciences ( spss version 13 , inc , chicago , il ) computer software package . paired t test was used to analyze before and after test data for each group differences . table 1 shows the mean sd values of exercise performance indices for the pre - and post - supplementation . supplementation with -alanine demonstrated a significant increase in vo2 max ( p<0.05 ) . on the other hand , tte and lactate concentrations decreased after 6 weeks of supplementation with -alanine ( p<0.05 ) . the placebo group showed a significant increase in lactate concentrations ( p<0.05 ) , but a non significant increase in tte . comparison of exercise performance indices , pre - and post - supplementation ( mean sd ) the post - exercise concentrations of plasma lactate were significantly higher ( p<0.05 ) than baseline in two groups . however , the post - exercise concentrations of lactate were significantly lower ( p<0.05 ) during the alanine supplementation compared to the placebo group . dietary intake before each trial was similar for energy and macronutrients [ table 2 ] . the findings of our study suggest that supplementation with -alanine may improve the endurance exercise performance as measured by the vo2 max , tte and plasma lactate concentrations . , showed that supplementation with creatine + -alanine resulted in significant increases ( p<0.01 ) in muscle carnosine content . the increased muscle carnosine content was accompanied with an improvement in vo2 max and tte in response to a maximal graded exercise test performed on a cycle ergometer . another study demonstrated that supplementation with both -alanine and creatine improved cycling performance ( tte ) . they concluded that this was due to h buffering by carnosine during this transitional period . our data demonstrate that the significant improvements in the performance indices with -alanine supplementation were due to ph reduction . the improvement in tte seen in the placebo group participants might be due to the encouragement provided by our staff and also the participants psychological status . also , the findings of the present study might have been influenced by the fluctuations in the skeletal muscle response to oral supplementation with -alanine . our data suggest that supplementation with -alanine may delay the onset of fatigue and thus improve performance during incremental cycle exercise in men . the glucose concentrations did not change significantly in our study , due to different individual response and insufficient dose or duration . the participants in this study , however , were male physical education students rather than untrained participants . however , according to the hypothesis , -alanine supplementation would prevent the drop in intracellular ph during high - intensity contractions and result in less circulating acidosis finally due to elevation of myocellular carnosine content . furthermore , several studies have shown the importance of ph regulation on performance during endurance exercise , by a pre - exercise alkalosis intervention . this suggests that the difference between groups is related to the presumable enhancement of muscle carnosine content . future studies should examine muscle carnosine levels along with vo2 max and plasma lactate concentration during strenuous exercise with variable quantities of -alanine supplementation also , further investigations are necessary to determine the effects of -alanine supplementation during more prolonged and submaximal exercise . it can be concluded from this study that -alanine administration can reduce acidosis during high - intensity exercise and thus can improve exercise performance in endurance athletes . also it is found that six weeks of supplementation with -alanine at the mentioned prescribed dose did not result in significant changes in glucose concentrations .

objectives : supplementation with -alanine has been proposed to improve performance in some exercises such as cycling and running . also , it has been demonstrated that great deals of proton ions are produced in the skeletal muscles during exercise that result in acidosis , whereas -alanine may reduce this effect . therefore , the aim of this study is to assess the effects of alanine supplementation on vo2 max , time to exhaustion and lactate concentrations in physical education male students.methods:thirty-nine male physical education students volunteered for this study . participants were supplemented orally for 6 week with either -alanine ( 5 * 400 mg / d ) or placebo ( 5 * 400 mg dextrose / d ) , randomly . vo2 max and time to exhaustion ( tte ) with a continuous graded exercise test ( gxt ) on an electronically braked cycle ergometer ; and serum lactate and glucose concentrations were measured before and after supplementation.results:supplementation with -alanine showed a significant increase in vo2 max ( p<0.05 ) and a significant decrease in tte and lactate concentrations ( p<0.05 ) . a significant elevation in lactate concentrations and a non significant increase in tte were observed in placebo group . plasma glucose concentrations did not change significantly in two groups after intervention.conclusion:it can be concluded that -alanine supplementation can reduce lactate concentrations during exercise and thus can improve exercise performance in endurance athletes .

enhanced surveillance involved the collection of a minimum dataset for each possible case , including demographic data , clinical symptoms , travel and contact history , and results of testing for respiratory pathogens ( 6 ) . nose and throat swab specimens and , when possible , lower respiratory tract specimens , were tested at 1 of 4 regional laboratories . although the testing guidelines recommended mers - cov testing after exclusion of alternative etiologies , other tests were conducted in parallel with mers - cov testing for most suspected cases . during the first few days of surveillance , a pan - coronavirus assay conducted at the phe national reference laboratory was used as a screening test ; then the viral genome was fully sequenced . after the generation of mers - cov specific assays , a first - line screening assay targeting the viral genomic area upstream of the e gene ( 7 ) was conducted , followed by confirmatory testing at the hpa / phe national reference laboratory . results of mers - cov testing are reported regularly in the hpa / phe weekly influenza report ( 8) . a descriptive analysis included the number of persons tested and proportion positive for mers - cov by key demographic , epidemiologic , and clinical characteristics . the positive predictive value of different combinations of signs and symptoms was calculated as the proportion of persons who had signs and symptoms of mers and tested positive for mers - cov and showed exact ( clopper - pearson ) binomial 95% confidence intervals . during september 24 , 2012october 15 , 2013 , 77 travelers from the middle east that met the possible case definition were tested for mers - cov . seventy - five travelers tested negative on the screening assay , and 2 tested positive . positive results on the screening assay were confirmed by positive results at the hpa / phe national reference laboratory . in addition to testing the 77 persons who met all of the possible case criteria , mers - cov testing was conducted on 13 patients who had severe acute respiratory disease but did not meet the travel requirements : 2 had a travel history outside the middle east , 4 had no travel history in the relevant exposure period , and travel histories of the remaining 7 were unknown . the clinical and epidemiologic characteristics of the 77 persons tested and their mers - cov test results are shown in table 1 . those tested ranged in age from 3 months to 90 years ; 34 ( 44% ) had signs of pulmonary parenchymal involvement . the 2 confirmed cases were in male patients , 45 and 60 years of age ; both had severe acute respiratory symptoms requiring treatment by extracorporeal membrane oxygenation ; both subsequently died . mers - cov pcr testing was conducted on 53 contacts of the 2 confirmed case - patients in england ; 2 of these contacts tested mers - cov positive ( 9,10 ) . * exposure period was 10 days until june 2013 , when it was increased to 14 days . the positive predictive value for mers - cov infection of different combinations of signs and symptoms is shown in table 2 . no case - patients who did not have pulmonary parenchymal involvement tested positive for mers - cov , and the positive predictive value of the clinical manifestations increased as the severity of disease increased . of the 77 patients tested , 22 had positive results for alternative respiratory pathogens , including 10 with influenza ( 7 influenza a and 3 influenza b ) ; 1 of the influenza a infected case - patients was later confirmed to also be infected with mers - cov . two case - patients tested positive for legionella pneumophila , 4 for rhinovirus , 3 for adenovirus , 1 for respiratory syncytial virus , and 1 for human metapneumovirus . unlike surveillance for established organisms , surveillance for a novel pathogen requires analysis of information collected from all patients tested , even from those that test negative , to build knowledge of the predictive value of different epidemiologic and clinical manifestations . this report on the characteristics of patients traveling to england from the middle east and tested for mers - cov enables a first crude estimation of the positive predictive value of different signs and symptoms during the first year following the emergence of this pathogen . because this study is based on a cohort of 77 suspected case - patients , of whom only 2 laboratory - confirmed cases were identified during the surveillance period , estimates on the basis of identified symptoms are very imprecise ( table 2 ) . however , in the context of an emerging pathogen , reporting such data progressively helps optimize case detection and surveillance systems . during the 12-month surveillance period , no patients who had respiratory symptoms but no pulmonary parenchymal involvement were positive for mers - cov by pcr , and the positive predictive value of signs and symptoms increased with the severity of clinical manifestation . this suggests that the case definitions that were in use during this period ( which recommended mers - cov testing only for patients who met the epidemiologic criteria and had a severe respiratory illness ) were appropriate . a range of respiratory pathogens were found in those patients that were mers - cov negative , highlighting the importance of looking for alternative diagnoses . however , the diagnosis of 1 of the mers - cov case - patients was delayed because of an initial diagnosis of influenza . the testing algorithm was subsequently changed to ensure that patients meeting the possible case definition were tested for mers - cov if they had an alternative etiology which did not fully explain their clinical manifestation . the predictive value of the possible case definition depends on the incidence of infection and would be expected to vary across different population groups and change over time , especially in the context of an emerging pathogen . we encourage other countries to similarly report the characteristics of all patients tested for mers - cov to improve understanding of the predictive value of different clinical and epidemiologic manifestations in various populations at different times .

during the first year of enhanced mers coronavirus surveillance in england , 77 persons traveling from the middle east had acute respiratory illness and were tested for the virus . infection was confirmed in 2 travelers with acute respiratory distress syndrome and 2 of their contacts . patients with less severe manifestations tested negative .

the developing nervous system in utero is exposed to myriad influences with potentially far reaching consequences . most of the research in this area is directed towards understanding the adverse influences and their structural or functional pathogenesis . however , it is also attractive to investigate if foetal neurodevelopment can be positively influenced or enhanced in an analogous manner . there is evidence that appropriate vibroacoustic stimulation by exposure to music alters foetal behaviour and is carried forward to the newborn period [ 2 , 3 ] . music is a noninvasive , culturally acceptable intervention with multiple putative direct and indirect beneficial effects on mother and foetus through the pregnancy and perinatal period . in animals , prenatal music exposure has been shown to improve postnatal spatial learning and memory ; to reduce isolation stress . music has been found to beneficially affect stress response and recovery from critical illness or surgery [ 5 , 6 ] . using optical topography and salivary cortisol as a marker of stress , music has been documented to simulate pleasure and happiness . on a molecular level , music has been shown to alter dominergic neurotransmission and have direct effect on neurotrophic growth factors including brain derived neurotrophic factor and tyrosine kinase receptor b [ 5 , 8 ] . besides direct influence on emotions , behavior , and neurotransmitter systems , there are multiple endocrine effects of music exposure including altered levels of adrenal and gonadal steroids . these changes in a pregnant woman can influence neuroblast proliferation , axonogenesis , synaptogenesis , and neuronal organization with effects on cognitive performance and behavioural gestalt . the present study was carried out to test the hypothesis that music exposure to mother during pregnancy can affect the neonatal behaviour . this was a single - centre , open - label , randomized controlled trial ( rct ) conducted at a teaching hospital from january 2003 to december 2005 . the study was approved by institutional ethics committee and is registered with clinicaltrials.gov ( nct01278329 ) . all consecutive primigravida mothers of 19 to 29 years of age with singleton pregnancy attending the antenatal clinic of the study institution first time , at or before 20 weeks of gestation , were eligible for inclusion . mothers with significant coexisting medical diseases or severe to profound hearing loss were excluded ( figure 1 ) . mothers were then randomized to music and control groups using a printed random number table . allocation to the groups was concealed from the investigator ( ra ) performing outcome assessment . mothers randomized to music group were given a cassette player and a prerecorded music audio cassette and were demonstrated their use . garbh sanskar audio cassette ( times music inc . , mumbai , india ) with a running duration of approximately 50 minutes and a cassette player with headphones . this contains a medley of instrumental music , natural sounds , and chants from religious scriptures . they were asked to listen to the recorded music daily in the evening just before going to the bed with a minimum of ambient noise . they were also asked to maintain a record of their music listening activity by making a check mark on a printed calendar . criteria for protocol violation included noncompliance with music listening for more than 2 weeks , development of preeclampsia or eclampsia in the mother , delivery of the newborn at a gestation of less than 37 or more than 42 completed weeks , delivery of the baby by emergency caesarean section , requirement of general anaesthesia even in case of elective caesarean section , neonatal birth weight less than 2500 grams or more than 4000 grams , or presence of significant neonatal disease precluding application of outcome assessment . all healthy term appropriate for date neonates born of spontaneous vaginal delivery or elective caesarean section conducted under epidural anaesthesia were subjected to outcome assessment . outcome measures consisted of the performance on brazelton neonatal behavioral assessment scale ( bnbas ) . the bnbas is a means of scoring interactive behaviour for term and stable preterm infants . the scale consists of 27 behavioural items , each scored on a 9-point scale , and 20 elicited responses , each scored on a 3-point scale . in most cases , the infant 's score is based on the best performance , not an average performance . the bnbas was administered once to each infant in the study on day 2 or 3 of life . the assessment was performed by the investigator ( r.a . ) who has received prior training in its application , and the items were scored as recommended in the manual . infants were tested midway between feeds in a quiet , dimly lit room with an ambient temperature of 3234c . the items were grouped as recommended by lester into the following 7 clusters : habituation , orientation , motor performance , range of state , regulation of state , autonomic stability , and reflexes . sample size estimation for this study presented many challenges . a prior prospective study with similar design used a sample size of 20 believing it to capture significant differences in fetal behavior . a pilot study was not feasible because of long follow - up period from enrolment of the mother to delivery of the newborn ; lack of single primary outcome measure . hence , it was decided to conduct the study in an open - ended manner limited by time of enrolment ( january 2003 to march 2005 ) rather than number of mothers enrolled . the data was entered in a microsoft excel spreadsheet ( ms office version 2003 ) . a total of 352 primigravida females attending antenatal clinic for the first time at a gestation of 20 weeks or less were evaluated for participation . ten females were excluded because of chronic medical diseases including rheumatic heart disease , chronic hepatitis , uncontrolled type 1 diabetes , chronic obstructive pulmonary disease , and vesicoureteric reflux - associated chronic renal failure ( 1 each ) . two females were unwilling to participate , and 1 was found to have 90 db hearing loss on audiometric evaluation . the remaining 339 females were randomized to receive music exposure in addition to standard antenatal care ( intervention arm , n = 169 ) and standard care alone ( control arm , n = 170 ) . the primary analysis was per protocol , and bnbas assessment was applied to 126 newborns in the music exposure group and 134 newborns in the control group ( figure 1 ) . the infants born to mothers exposed to music during their pregnancy scored significantly higher on 5 of the 7 bnbas clusters including habituation , orientation , range of state , regulation of state , and autonomic stability . in all these clusters , the 95% confidence interval ( ci ) for effect size ( es ) remained on 1 side of the point of no difference ( table 2 ) . the maximal beneficial effect was seen in the clusters of orientation ( es 1.13 , 95% ci 0.821.44 , p < 0.0001 ) and habituation ( es 1.05 , 95% ci 0.531.57 , p = 0.0001 ) . the newborns of music exposure group also showed a significant trend towards better motor performance ( es 0.25 , 95% ci 0.00.5 , p = 0.0479 ) ; however , the lower bound 95% ci touched the point of no difference . there was no difference between the infants of intervention and control arms on the reflexes cluster . there were 43 ( 25.4% ) protocol violations in the mothers randomized to music group and 36 ( 21.2% ) in the control group ( z = 0.9292 , p = 0.3528 ) . the mean duration of music exposure in mothers of intervention arm was found to be 173.3 ( 18.9 ) hours . the present study supports the hypothesis that maternal exposure to music during pregnancy can beneficially influence neonatal behaviour . behavioral responses test the integrity of neonatal nervous system at several levels including perception , afferent conduction , integration , conscious decision , and efferent motor apparatus . the maximum effect of music exposure was seen in the orientation cluster ( mean difference 1.13 points ) ( table 2 ) . orientation items test the infants ' response to animate and inanimate , auditory , and visual stimuli presented separately or together and constitute the social interactive package of bnbas . the mean score of infants belonging to music group in this cluster was 6.5 which implies that the average infant was able to follow the visual stimulus with smooth coordinated movement of head and eyes in 3060 arcs horizontally and probably also vertically ; exhibited alerting and searching behaviour in response to sound stimulus . the habituation cluster also showed significantly better scores in infants born to mothers exposed to music during pregnancy ( mean difference 1.05 points ) ( table 2 ) . the habituation package of bnbas tests response decrement to repeated stimuli , including visual ( light ) , auditory ( rattle and bell ) , and tactile ( pin prick to foot ) stimuli . the average infant in the intervention arm scored 5.7 in this cluster which implies shutdown of body movements and some diminution of blinks and respiratory changes after few repetitions of visual or auditory stimuli . for the tactile stimulation item , this score implies a response localized to stimulated leg or foot after 5 trials with no movement in rest of the body . such motor behaviour belongs to the volpe 's category of high level responses which depend on intact integration function in central nervous system ( cns ) . the infants of the mothers of music group also showed significantly better performance than the control group with respect of range and regulation of behavioural states and autonomic stability ( table 2 ) . the neonatal infant displays a rich repertoire of behavioural states ; the interplay of these states , their transition , and variety presented by the newborn is akin to examining the higher mental functions of the adult . there was also a trend towards better motor performance in the infants belonging to intervention arm , but it failed to reach statistical significance . the effects of maternal experiences on foetal or neonatal behaviour have been studied previously and explored for the possibility of modifying this behaviour . a prospective rct studied the effect of music played to 10 foetuses ( median gestation 38 weeks ) with a headphone on the maternal abdomen . the exposed foetuses showed higher mean heart rates ( fhr ) and higher fhr variation in the first hour itself , with significantly more state transitions by fourth hour . these newborns also showed more state transitions and spent a higher proportion of time in awake state , when exposed to same music stimulus after birth . the authors concluded that this suggests the occurrence of a simple form of foetal programming or learning . another study has been conducted to examine whether foetal response to music differs from that to human voice . ten healthy term foetuses were exposed to music , voice , and sham in random order for three 15 second intervals . foetuses were found to respond by increased fhr and motor response to both music and voice which was significantly different from sham exposure but not different between themselves . it has also been demonstrated that foetal repertoire of responses to music exhibits a pattern of maturation with the gestation . in response to piano recordings , younger foetuses ( 2832 weeks gestation ) responded by transient increase or decrease in heart rate depending on sonic intensity , probably indicating selective attention to stimulus ; whereas the more mature foetuses displayed sustained elevation in heart rate ( > 33 weeks ) and change in body movements ( 35 weeks ) . the authors concluded that processing of complex sounds changes at 33 weeks of gestation . experience in the present study agrees with published literature that music exposure in utero does influence neonatal behaviour this study enrolled mothers in first half of pregnancy and the foetus was exposed to a mean duration of 173 hours of music before birth , whereas other studies have exposed the foetus only for a few hours prior to birth . also , the present study used conventional headphones worn by the mother over her ears instead of the one taped to her abdomen as in other studies . although this would likely have resulted in less direct sonic stimulation of the foetus , the practical implications of this approach are more because of its better adaptability to routine clinical practice . a limitation of the present study was no standardization of the intensity of music stimulus . however , this might be relevant in case of directly applied stimulus over maternal abdomen where it conveys both vibratory and acoustic sensations , but not in present circumstances where it was better to let individual mothers decide about the volume of music as per their convenience . the onset of foetal hearing occurs at about 24 weeks of gestation . in the present study it is not known when the favourable effect of maternal music exposure started , and hence optimal timing for such stimulation in clinical practice can not be ascertained . it is improbable in the present study that music directly had any auditory effects on the foetus . the effects are more likely to be mediated via endocrine changes produced in the mother . music is known to have multiple endocrine effects including increased growth hormone which modulates the production of certain cytokines , increased ovarian steroid secretion , changes in the biorhythms and levels of cortisol , testosterone , and estrogen [ 5 , 16 ] . corticosteroids have several regulatory effects on growth of neuroblasts , myelination , and metabolism in developing brain . they have been demonstrated to influence important enzymes , for example , sodium - potassium atpase , and growth factors , for example , basic fibroblast growth factor ( bfgf-2 ) in developing cerebrum in animals . over 200 steroid responsive genes have been identified in the rat hippocampus involved in axonogenesis , synaptogenesis , cell adhesion , and signal transduction . thus , music exposure in the mother might influence neurogenesis and cerebral plasticity in the foetus through mechanisms mediated by steroids . in conclusion , this study provides preliminary evidence that maternal music exposure beneficially affects neonatal behaviour . a trained clinician can utilize the behavioural organization of the newborn infant to gain insights into the intrauterine experience and the perinatal events which may have influenced the neonate 's cns organization . the present clinical trial was not designed to study these aspects and provides no information regarding the mechanism behind the observed effect . further studies should confirm this observation with a more rigorous design and try to elucidate the direct and endocrine - mediated mechanisms of the effect of music on foetus and newborn .

objective . this study evaluated the effect of antenatal music exposure to primigravida healthy mothers on the behaviour of their term appropriate - for - date newborns assessed using brazelton neonatal behavioral assessment scale ( bnbas ) . methods . this was a single - centre , randomized , open - label controlled trial . primigravida mothers aged 1929 years , free of chronic medical diseases or significant deafness , with singleton pregnancy , with a gestation of 20 weeks or less , were randomized to listen to a pre - recorded music cassette for approximately 1 hour / day in addition to standard antenatal care ( intervention arm ) or standard care only ( control arm ) . perinatal factors with adverse effect on neonatal behaviour were deemed as protocol violations . outcome measure included scores on 7 clusters of bnbas . primary analysis was per protocol . the trial is registered with clinicaltrials.gov ( nct01278329 ) . results . one hundred and twenty - six newborns in the music group and 134 in the control group were subjected to bnbas assessment . the infants of mothers exposed to music during pregnancy performed significantly better on 5 of the 7 bnbas clusters . the maximal beneficial effect was seen with respect to orientation ( es 1.13 , 95% ci 0.821.44 , p < 0.0001 ) and habituation ( es 1.05 , 95% ci 0.531.57 , p = 0.0001 ) . conclusion . prenatal music exposure to mother significantly and favourably influences neonatal behaviour .

there are various analgesic options like systemic opioids , neuraxial blocks , non steroidal anti inflammatory drugs ( nsaids ) , local infiltration , and so on ; however , in renal transplant patients systemic opioids are used with caution because of altered pharmacodynamics and opioid - related side effects . hence , we decided to explore an alternative technique for postoperative analgesia in the form of continuous transversus abdominis plane ( tap ) block . it is more suitable for operations where parietal pain is a major cause of pain . renal transplant recipients are ideally suited to gain maximum benefit from tap blocks as the incision involves the lower abdomen which is usually covered by this block without any intraperitoneal extension eliminating the visceral pain component . results of various trials suggest that the effect of single shot tap block lasts for variable duration of time hence , we decided to insert catheter in tap plane under direct vision to increase the duration of analgesia . after obtaining approval by the hospital ethical committee and written informed consent , 43 american society of anesthesiologists risk iii patients scheduled for open iliac fossa renal transplantation were enrolled in a prospective , randomized , double - blind , controlled study . patients allergic to local anesthetics drugs , opioid addicts , hepatic disease and psychiatric disorders were excluded from our study . patients were randomly allocated to group s ( study group ) and group c ( control group ) by sealed envelope method . the patients , observer , and staff providing postoperative care were blinded to group assigned . pulse , electrocardiogram , noninvasive blood pressure , peripheral oxygen saturation ( spo2 ) , end - tidal co2 ( etco2 ) , central venous pressure were monitored throughout the procedure and urine output was measured after clamp release . a multiorifice epidural catheter was placed above the approximated transversus abdominis , through an epidural needle . about 5 - 6 cm of catheter was positioned between the ta and internal oblique muscles ( ioms ) . [ figures 1 and 2 ] after closure of wound , before reversal 1 mg / kg of 0.25% bupivacaine for group s or normal saline for group c was given as a bolus . this was followed by an infusion of 0.125% bupivaciane at 0.25 mg / kg / h for group s and an infusion of normal saline for group c in postoperative room by the infusion pump . insertion of epidural needle in transversus abdominis plane placement of epidural catheter visual analogue score ( vas ) at rest and movement was noted at the interval of 2,4,6,12 and 24 h. postoperatively . when vas score was more than 3 , inj . time for the first request of rescue analgesic and total pentazocine consumption in 24 h. was noted . sedation scores were assigned by the investigator using a sedation scale ( awake and alert= 0 , asleep but easily aroused = 2 , deep sleep = 3 ) . antiemetics , that is , inj ondansetron 8 mg were given to any patient who complained of nausea or vomiting and to all patients who received pentazocine . the primary outcome measure in this study was 24 h opioid ( pentazocine ) consumption . secondary outcome measures included time to first request for analgesic , vas score , and side effects associated with pentazocine consumption like nausea and sedation score . the sample size was calculated on the basis of 24 h pentazocine consumption for the patients undergoing open renal transplantation . we conducted a pilot study which showed 24 h pentazocine consumption of 39 13.4 mg in control group versus 18 16.4 mg in study group . based on this pilot study , we calculated 16 patients per group would be required to get a power of 95% and error of 0.05 . statistical analysis was performed using statistical package of social sciences , that is , spss version 12 . data are expressed as mean standard deviation for continuous variables and number ( % ) for categorical variables . fisher 's exact test and chi - square analysis was used for comparing categorical data . statistical analysis was performed using statistical package of social sciences , that is , spss version 12 . data are expressed as mean standard deviation for continuous variables and number ( % ) for categorical variables . fisher 's exact test and chi - square analysis was used for comparing categorical data . the catheter was blocked in one patient in each group and there was accidental removal of catheter in one patient of group s. so they were excluded from the study . there was no significant difference in demographic profile as well as duration of anesthesia and surgery between the two groups [ table 1 ] . vas pain scores were significantly high in group c compared to group s at rest and on movement [ figures 3 and 4 and tables 4 and 5 ] . patients in group s had significantly longer time for first analgesia ( tfa ) request than those in group c. total consumption of pentazocine was higher in group c ( 56.42 12.46 mg ) as compared with group s ( 9.75 13.95 mg ) . total number of patients requiring rescue analgesia in group s was only 9 as compared with group c where all patients required rescue analgesia [ table 2 ] . graph depicting visual analogue score score at rest graph depicting visual analogue score score on movement postoperative analgesic requirement in 24 h postoperative sedation score visual analogue score at rest visual analogue score scores on movement postoperative sedation score was higher in group c [ table 3 ] . there were no signs of systemic toxicity of local anesthetic in any of our patients . preexisting pain , anxiety , fear of graft rejection , and emotional stress increase the risk of significant postoperative pain in renal transplant patients . main principle of tap block is to deposit local anesthetic in plane between iom and transversus abdominis muscle to block the sensorimotor innervations of the anterior abdominal wall which is supplied by anterior rami of the spinal segmental t7-t11 . it can be single shot or continuous via catheter to prolong its analgesic effect . we kept epidural catheter in tap plane by open technique for 24 h as there is significant decline in the use of analgesics in renal transplant recipients from the 2 day after surgery and usually they are switched over to oral analgesics . vas scores were significantly higher in group c compared with group s both at rest and on movement all throughout 24 h. in study by mukhtar and khattakm pain scores up to 12 h were similar to our study ; however , there was no difference in pain at 24 h in two groups probably because they gave a single shot block in their study . the first dose of rescue analgesia was required after about 270 347.96 min and total consumption of pentazocine ( opioid ) in 24 h was higher in group c. in a study by jankovic et al . , where they gave continuous tap block in seven patients for renal transplant . there was 80% reduction in morphine requirement during the first 24 h. our result regarding opioid consumption in first 24 h is not similar to the result shown by wong et al . , where unilateral tap block was given prior to general anesthesia in renal transplant patients . in their study , median fentanyl consumption was lower at 2 , 4 , and 6 postoperatively in tap block group but did not reach statistical significance . no significant postoperative nausea vomiting ( ponv ) was observed in both the groups as prophylactic ondansetron was given . sedation score was higher in control group which is similar to study done by mukhtar et al . there was minimal chance of hematoma as catheter was placed under direct vision minimizing chances of inadvertent vascular injury . these patients are more prone to infection as they are immunocompromised . to prevent tap catheter - related infection , the catheter was removed after 24 h and patients were switched over to oral analgesics as it is an extraperitoneal surgery . we preferred open technique as tap plane in renal transplant is accessed without any major dissection . it is not a blind technique with minimal probability of injury to surrounding structures or inadvertent intravascular injection . open technique allows anatomically accurate placement of the tap catheter and prolongs the analgesic effect of the tap block . from this study , it seems that tap block holds considerable promise for patients undergoing renal transplant ; however , further large well - controlled studies are required in terms of its safety , optimal dose , and volume of local anesthetic before it can be implemented in routine clinical practice . the transversus abdominis plane catheter technique for postoperative control after renal transplant has proved to be of equal efficacy in relieving the postoperative pain after renal transplant .

background and aims : transversus abdominis plane ( tap ) block is suitable for operations where parietal pain is a major cause of pain . renal transplant recipients are ideally suited to gain maximum benefit from tap block as the incision classically involves the lower abdomen . this study was conducted to evaluate the analgesic efficacy of continuous tap block in transplant recipients.material and methods : in a prospective double - blind study , 40 chronic renal failure patients undergoing open renal transplant were randomly divided into two groups . at the end of surgery during closure , a multiorifice epidural catheter was placed in tap plane . study group ( group s ) received inj bupivacaine bolus 1 mg / kg ( 0.25% ) followed by infusion 0.25 mg / kg ( 0.125% ) through the catheter , whereas control group ( group c ) received normal saline through the catheter . inj pentazocine ( 0.3 mg / kg ) was given as rescue analgesic at visual analogue score ( vas ) > 3 in any group at rest or on movement . the analgesic efficacy was judged by vas , time of first rescue analgesic , and total analgesic consumption in 24 h.results:patients in group s had significant lower vas scores , longer time to first rescue analgesic ( 270 347.96 vs. 42.85 32.27 min ) and lower pentazocine consumption ( 9.75 13.95 vs. 56.42 12.46 mg ) in 24 h. there was significant sedation in group c.conclusion:the tap catheter technique for postoperative pain control after renal transplant has proved to be effective in relieving the postoperative pain after renal transplant with less pentazocine requirement and less sedation .

paget 's disease of bone is a chronic bone remodeling disorder featuring one or more areas of aggressive osteoclast - mediated bone resorption , followed by imperfect osteoblast - mediated bone repair . the disease is frequently recognized because of elevation in serum alkaline phosphatase levels , which reflects both the extent and the activity of the disease . however , alkaline phosphatase levels can be normal when there is only a small focus of paget 's disease or after successful medical treatment . we report one such case that was incidentally detected during evaluation of nephrolithiasis and polyarthralgia and had normal radiographs and normal serum alkaline phosphatase levels . a 46-year - old man , driver by occupation , presented with a history of sudden onset pain abdomen , which was colicky in nature and localized to the right lumbar region . there was no history of dysurea , hematuria , fever , loose stools , or vomiting . he also had a history of multiple joint pains for the last 4 months , aggravated for the past 1 week . there was no history of fever , weight loss , skin rash , loss of appetite , or backache . there was no past history of diabetes , hypertension , tuberculosis , polyarthritis , or any other significant illness . his blood urea , creatinine , lft , electrolytes , and sugar levels were normal . abdominal ultrasound revealed bilateral renal calculi with gross pelvicalyceal dilatation of right kidney and right hydroureter . renal pyelogram showed non - functioning right kidney with multiple left - sided renal calculi . tc99 m diethylene triamine pentaacetic acid ( dtpa ) renogram revealed normal functioning and draining left kidney with a gfr of 55 ml / min and poorly functioning right kidney with a gfr of 10 ml / min . the patient underwent ureteroscopy with intra - corporeal lithotripsy of right kidney and bilateral dj stenting . he had normal esr , negative crp , negative rheumatoid factor , serum ionised calcium 4.4 mg / dl , and serum alkaline phosphatase 86 iu / ml . whole - body bone scan done revealed extremely hot focus involving the right humerus ( head and proximal shaft ) and left hemipelvis - features , suggestive of paget 's disease [ figure 1 ] . x - rays of right humerus and pelvis did not reveal any abnormality [ figure 2 ] . magnetic resonance imaging ( mri ) showed thickened cortex with altered signal intensity involving the right humerus head and proximal shaft and left iliac bone , commensurate with the bone scan findings [ figures 3 and 4 ] . a bone biopsy from left iliac crest was done , which showed irregular bony trabeculae lined by plump osteoblasts , with multinucleate osteoclasts and increase in cement lines [ figure 5 ] . serum calcium was 9 mg / dl and pth level was 12 pg / ml , both normal . hence , a diagnosis of paget 's disease was made and the patient was started on biphosphonate therapy . bone scan done using tc-99 m labeled mdp - showing extremely high osteoblastic activity in the right humerus and left pelvic bone ( as marked ) x - rays of right arm and pelvis showing no abnormality in bones mri right arm showing thickened cortex with altered signal intensity involving the right humerus head and proximal shaft mri pelvis showing thickened cortex with altered signal intensity involving left iliac bone bone biopsy from left iliac crest shows plump osteoblasts ( black arrow ) and increase in cement lines ( white arrow ) bone expansion may also cause various neurological compression syndromes , but most patients with paget 's disease are discovered because of an increased alkaline phosphatase level or an incidental x - ray finding and are asymptomatic . in our case , bone scan was done for polyarthralgia that showed the typical pattern of paget 's later confirmed by bone biopsy . paget 's disease is known to be associated with aortic valve , endocardial , and arterial calcification . the patient was also found to have depression and was started on treatment for the same . skeletal scintigraphy has had a major impact in diagnosis of paget 's disease because of the high sensitivity of the technique for detection of both increased vascularity and increased osteoblastic activity characteristic of the disorder . radiography has much inferior sensitivity and bony pagetic changes may be missed by it , as in our case . lesions become visible on x - rays when more than 30 - 50% of the bone has been resorbed . , in his study found that 73% of patients with positive bone scan and normal radiographs were symptomatic . the scintigraphic appearances are fairly characteristic , showing intense accumulation of radiopharmaceutical throughout the affected part with uniform distribution . pagetic lesions in long bones appear at the articular margin , progressing along the shaft , and producing a sharp v - shaped advancing edge like a flame , as was seen in our case in the humerus . however , scintigraphy is not totally specific , as the differential diagnosis can be metastasis , metabolic bone disease , and even fibrous dysplasia if detected in later age group . preservation or enhancement of normal bony anatomy is typical and differentiates paget 's from other scan abnormalities . also , there is a clear distinction between normal and abnormal bone differentiating it from metabolic bone disease . in fibrous dysplasia , there is a lack of preservation of bony outline unlike paget 's . metastatic prostate cancer and rarely breast cancer can mimic paget 's disease . the pelvis and the spine clinical manifestations of paget 's disease in which pharmacologic therapy is recommended are symptoms resulting from active bone lesions like bone pain , headache with skull involvement , back pain due to pagetic radiculopathy or arthropathy , other neurologic syndromes , and fissure fractures . follow - up of these cases and monitoring the treatment response can be done by serum levels of biochemical markers like alkaline phosphatase . patients with mono - ostotic disease and limited polyostotic disease may have normal levels of these markers . in such patients , scintigraphy is advocated to monitor disease status and treatment response . in our case , despite polyostotic form , the biochemical markers were normal and hence bone scan will be utilized to follow - up the patient . in fact , it has been suggested that scintigraphy may better assess long - term response , since scintigraphic activity may persist after biochemical normalization . this case highlights the role of bone scintigraphy in detecting an unusual presentation of paget 's disease in the form of nephrolithiasis , polyarthralgia , normal radiographs , and normal biochemical markers despite being in the polyostotic form .

paget 's disease of bone is a chronic bone remodeling disorder . although most patients are asymptomatic , a variety of symptoms and complications may develop directly from bone involvement or secondarily due to compression by the expanded bone . it is usually diagnosed from radiological and biochemical abnormalities or in advanced cases it becomes clinically evident due to the expanded bone . we report a case of paget 's disease which was detected incidentally during evaluation of nephrolithiasis and polyarthritis but had normal radiographs and normal biochemical markers .

intracranial intraparenchymal schwannomas , which are unrelated to the cranial nerves , are very rare . since gibson et al.7 ) reported the first case of an intracerebral schwannoma located at the temporal lobe in 1966 , about 70 cases have been reported in the english - language literature . although some general characteristics of these tumors have been described , preoperative diagnosis is very challenging due to its rarity in the central nervous system and because of the absence of pathognomonic signs on radiologic images . often , these challenges lead to delay in proper treatment of the patient . to our knowledge , this is the first case of a supratentorial intracerebral schwannoma reported in korea . the patient had an exceptionally long preoperative observational period ( 9 years ) which allowed us to clarify the clinical and radiological course of this rare tumor . based on our observations and a review of the relevant literature a 25-year - old man presented with recent aggravation of focal seizure activities on the right arm was referred to our clinic . his first seizure attack took place 9 years ago which started with involuntary right arm tremors followed by a loss of consciousness and generalized tonic - clonic convulsions . when he first visited the neurology clinic at that time , a neurologic examination revealed no abnormalities . he had no relevant medical history , no stigmata of neurofibromatosis and no family history of this disorder . his magnetic resonance images ( mri ) of the brain revealed a small mass measuring 1.51.01.1 cm at the left precentral gyrus . the mass was predominantly hypointense to gray matter on the t1 weighted images , heterogeneously hyperintense on the t2 weighted images and showed intense enhancement on gadolinium injection ( fig . initial radiologic differential diagnoses were a pleomorphic xanthoastrocytoma , ganglioglioma , and dysembryoplastic neuroepithelial tumor . since he was free of symptoms between seizure attacks and well tolerated his condition after taking anti - epileptic medication , he refused to undergo surgical treatment . during the 9 years of follow - up he complained of only intermittent focal seizures presented as right arm tremors and transient weakness , and these seizure attacks mostly occurred under stress conditions like sleep deprivation and heavy alcohol consumption combined with poor drug compliance . a brain mri which was taken two years after the initial image work - up , revealed no interval change . because the patient 's symptom was stable , nine years later , he complained of sudden prolonged seizure duration with right arm weakness , which became progressively worse over the past month prior to his visit . the size of the enhancing portion had increased to 2.31.91.6 cm , and a large peritumoral cyst measuring about 5.5 cm in diameter had newly appeared ( fig . since the mass was located at the precentral gyrus , awake craniotomy was performed to minimize postoperative motor and sensory deficit . a rectangular fronto - parietal craniotomy was done to expose the enhancing mass with the help of a neuronavigation system . sonography was used to identify the mass located just beneath the cortical surface which appeared to have a bluish discoloration ( fig . , we confirmed that the motor cortex of the right wrist and hand were located just on the posteromedial side of the mass . it was well circumscribed from adjacent brain tissue and could be removed in an en bloc fashion . during removal , slight yellowish but cerebrospinal fluid like clear fluid gushed out from the cyst . the patient 's postoperative course was uneventful and his right forearm and hand weakness improved . one month after the operation , he had a postoperative mri which revealed no residual enhancing mass , but the cyst remained although its size was somewhat decreased ( fig . , he has remained seizure free since the operation and his right hand and arm weakness has recovered to near normal status , with no difficulty in his daily living . the specimen consisted of several fragments of soft tissues , measuring 2.01.0 cm in the largest dimension . grossly , the cut surfaces showed a gray yellow myxoid appearance . under light microscopy , the tumor was composed of alternating antoni a and b areas , i.e. , cellular and less cellular areas ( fig . there was few mitoses ( 1/10 hpf ) and the mib-1 ( ki67 ) labeling index was low ( 1.03% ) . electron microscopic examination was consistent with schwannoma , which showed elongated cells surrounded by a continuous external lamina and scattered luse bodies ( long space collagen ) . a 25-year - old man presented with recent aggravation of focal seizure activities on the right arm was referred to our clinic . his first seizure attack took place 9 years ago which started with involuntary right arm tremors followed by a loss of consciousness and generalized tonic - clonic convulsions . when he first visited the neurology clinic at that time , a neurologic examination revealed no abnormalities . he had no relevant medical history , no stigmata of neurofibromatosis and no family history of this disorder . his magnetic resonance images ( mri ) of the brain revealed a small mass measuring 1.51.01.1 cm at the left precentral gyrus . the mass was predominantly hypointense to gray matter on the t1 weighted images , heterogeneously hyperintense on the t2 weighted images and showed intense enhancement on gadolinium injection ( fig . initial radiologic differential diagnoses were a pleomorphic xanthoastrocytoma , ganglioglioma , and dysembryoplastic neuroepithelial tumor . since he was free of symptoms between seizure attacks and well tolerated his condition after taking anti - epileptic medication , he refused to undergo surgical treatment . during the 9 years of follow - up he complained of only intermittent focal seizures presented as right arm tremors and transient weakness , and these seizure attacks mostly occurred under stress conditions like sleep deprivation and heavy alcohol consumption combined with poor drug compliance . a brain mri which was taken two years after the initial image work - up , revealed no interval change . because the patient 's symptom was stable , nine years later , he complained of sudden prolonged seizure duration with right arm weakness , which became progressively worse over the past month prior to his visit . the size of the enhancing portion had increased to 2.31.91.6 cm , and a large peritumoral cyst measuring about 5.5 cm in diameter had newly appeared ( fig . since the mass was located at the precentral gyrus , awake craniotomy was performed to minimize postoperative motor and sensory deficit . a rectangular fronto - parietal craniotomy was done to expose the enhancing mass with the help of a neuronavigation system . sonography was used to identify the mass located just beneath the cortical surface which appeared to have a bluish discoloration ( fig . , we confirmed that the motor cortex of the right wrist and hand were located just on the posteromedial side of the mass . it was well circumscribed from adjacent brain tissue and could be removed in an en bloc fashion . during removal , slight yellowish but cerebrospinal fluid like clear fluid gushed out from the cyst . the patient 's postoperative course was uneventful and his right forearm and hand weakness improved . one month after the operation , he had a postoperative mri which revealed no residual enhancing mass , but the cyst remained although its size was somewhat decreased ( fig . , he has remained seizure free since the operation and his right hand and arm weakness has recovered to near normal status , with no difficulty in his daily living . the specimen consisted of several fragments of soft tissues , measuring 2.01.0 cm in the largest dimension . grossly , the cut surfaces showed a gray yellow myxoid appearance . under light microscopy , the tumor was composed of alternating antoni a and b areas , i.e. , cellular and less cellular areas ( fig . there was few mitoses ( 1/10 hpf ) and the mib-1 ( ki67 ) labeling index was low ( 1.03% ) . electron microscopic examination was consistent with schwannoma , which showed elongated cells surrounded by a continuous external lamina and scattered luse bodies ( long space collagen ) . although intracranial intraparenchymal schwannomas are rare , we have developed knowledge of these tumors thanks to the case reports that have accumulated since 1966 . excluding 9 malignant cases1,10,12 ) , we found 59 published case reports and series in the english - language literature . these tumors were reported within various age groups , but most commonly are reported in pediatric and young adult populations . unlike intracranial schwannomas affecting cranial nerves , the intraparenchymal type shows no sexual predominance15 ) , and has a low association with neurofibromatosis ( only 4 of 66 cases were reported to have neurofibromatosis3,5,13 ) ) . schwannomas can arise in any part of the brain parenchyma but 70% of them are supratentorial lesions , thus showing a predilection for the superficial cerebral cortex or a periventricular location15 ) . symptoms and clinical indications are usually related to the tumor location and size . in cases involving the superficial cerebral cortex , such as the one reported herein , eventually , such lesions may be more than 5 cm in diameter , and they present symptoms related to increased intracranial pressure , such as headache , vomiting , visual disturbance , hemiparesis , and change of mental status . certain radiographic characteristics of intracranial intraparenchymal schwannoma have been commonly reported , including intratumoral calcification ( 25% ) , cyst formation ( > 60% ) , mild to moderate peritumoral edema ( > 50% ) , and varying degrees of gadolinium enhancement of the solid tumor component8,15 ) . however , many authors have indicated that there is no pathognomonic sign for intraparenchymal schwannoma , and that it is impossible to distinguish them from other tumors , such as pilocytic astrocytoma , ganglioglioma , pleomorphic xanthoastrocytoma , and dysembryoplastic neuroepithelial tumor , with radiographic evidence only . our case appears to share many of the previously described typical features of intracerebral schwannoma . young age , no known history of neurofibromatosis , seizure as an initial symptom presentation , small size mass located at the supratentorial cerebral cortex , peritumoral edema , and cyst are features that are commonly reported for intracerebral schwannoma . preoperatively , we presumed the diagnosis of our case as pilocytic astrocytoma or pleomorphic xanthoastrocytoma because these tumors share the characteristics described above , and they have a higher incidence of occurrence . however , pathologic examination revealed that the tumor was a typical schwannoma , indicating our expectation was erroneous . thus , we suggest that demographic , clinical , and radiologic findings are insufficient to derive an accurate diagnosis . we emphasize the importance of obtaining a surgical specimen in order to make proper diagnosis . intracerebral schwannoma is mostly benign and can be readily cured by surgery2,8,14,15 ) . typically , the tumor is well demarcated and can be easily dissected from brain parenchyme in most cases2 ) . if the tumor is located at the superficial cerebral cortex , which is a common location for intracerebral schwannomas including our case , it can be removed completely without resulting in any neurological deficit . based on the 9 years of observations present for this case we suggest that this tumor type grows slowly , but even though the tumor may be small , it can produce a mass effect resulting in neurological symptoms through cyst formation . this may occur frequently because cyst formation near the tumor mass is a relatively common feature of schwannomas . thus , considering the necessity of obtaining a correct diagnosis and a favorable surgical outcome , and because of patient deterioration that may result from simple observation - based diagnosis , early curative surgery is highly recommended when treating these tumors . intracerebral schwannomas are rare benign tumors that can be cured with complete surgical excision . despite their rarity and the lack of pathognomonic radiologic findings , there are several demographic , clinical , and radiologic characteristics that can be helpful , but not definitive , when diagnosing intracerebral schwannoma . considering the excellent surgical outcome and the risk of neurologic deterioration in the patient 's near future , early curative surgery

intracerebral schwannomas are rare and there have been none reported in korea . we present the case of a 25-year - old man with newly developed right - side weakness and recent seizure aggravation . his seizures started approximately 9 years prior to admission . at that time , a 1 cm diameter intra - axial enhancing mass at the left precentral gyrus was found on magnetic resonance image ( mri ) . after 9 years of observation and treatment with antiepileptic medication , an mri taken due to symptom aggravation revealed peri - tumoral cyst formation with tumor enlargement . the tumor was surgically removed . subsequently , right - side weakness diminished and there was good seizure control . pathologic diagnosis was schwannoma . schwannoma is a very rare tumor and there are no pathognomonic findings on radiologic images ; thus , it is challenging to make a correct diagnosis . however , considering the natural course and excellent prognosis after surgical treatment of this kind of intra - axial mass with benign features , early surgery for diagnosis and proper treatment is highly recommended .

we ascertained subjects with lada and type 2 diabetes from the lada china multicenter study ( 46 hospitals throughout china contributed ) ; type 1 diabetes , defined by who criteria ( 4 ) , from the type 1 diabetes collaboration net ( 18 hospitals in hunan province ) ; and normal subjects were screened by 75-g oral glucose tolerance test from 5,000 chinese in a population - based study . definition of lada ( 57 ) was 1 ) gad antibody ( gada ) positive , 2 ) age > 30 years at diagnosis , 3 ) independence from insulin treatment 6 months postdiagnosis , and 4 ) without ketoacidosis . subjects with hs - crp > 10 mg / l or taking anti - inflammatory drugs within 3 months were excluded . metabolic syndrome was defined by national cholesterol education program - adult treatment panel iii criteria ( 8) . this study was approved by ethics committees at second xiangya hospital of central south university and at each center and conducted according to the declaration of helsinki . height , weight , waist circumference , hip circumference , and blood pressure were recorded locally , and fasting sera samples were processed centrally . elisa determined high - sensitivity il-6 ( il-6 hs ; r&d systems , minneapolis , mn ) , 7% intraassay and 5% interassay coefficient of variation ( cv ) ; lcn2 ( 10 ) , 3.86.0% intraassay and 3.15.2% interassay cv ; adiponectin ( 11 ) 56% intraassay and 68% interassay cv . hs - crp was measured by immunoturbidometric assay ( orine diagnostica ) with 2.13.3% intraassay and 3.44.6% interassay cv . we used spss ( version 13 ; spss , chicago , il ) for statistical analysis . data are expressed when normally distributed as means sd and when skewed as median ( 25th75th percentiles ) . we used a general linear model of univariate analysis adjusted for age , sex , and bmi ; log - transformed cytokine value was the dependent variable , different diabetes groups were fixed , and age , sex , and bmi were covariates ( fig . multivariate regression models investigated differences in log - transformed cytokine concentrations ( dependent variables ) , with increasing number of variables ( model 1 : unadjusted ; model 2 : sex and age adjusted ; model 3 : age , sex , and bmi [ independent variables ] adjusted ) ( supplementary table 2 ) . linear relationships were evaluated by partial correlations test adjusted age , sex , and bmi . data were not corrected for multiple comparisons and are descriptive ; p < 0.01 was considered significant . univariate of general linear model adjusted according to age , sex , and bmi between groups . * p < 0.05 , * * p < 0.01 , * * * p < 0.001 . ngt , normal glucose tolerance subjects ; t1d , type 1 diabetic subjects ; t2d , type 2 diabetic subjects . we used spss ( version 13 ; spss , chicago , il ) for statistical analysis . data are expressed when normally distributed as means sd and when skewed as median ( 25th75th percentiles ) . we used a general linear model of univariate analysis adjusted for age , sex , and bmi ; log - transformed cytokine value was the dependent variable , different diabetes groups were fixed , and age , sex , and bmi were covariates ( fig . multivariate regression models investigated differences in log - transformed cytokine concentrations ( dependent variables ) , with increasing number of variables ( model 1 : unadjusted ; model 2 : sex and age adjusted ; model 3 : age , sex , and bmi [ independent variables ] adjusted ) ( supplementary table 2 ) . linear relationships were evaluated by partial correlations test adjusted age , sex , and bmi . data were not corrected for multiple comparisons and are descriptive ; p < 0.01 was considered significant . univariate of general linear model adjusted according to age , sex , and bmi between groups . * p < 0.05 , * * p < 0.01 , * * * p < 0.001 . ngt , normal glucose tolerance subjects ; t1d , type 1 diabetic subjects ; t2d , type 2 diabetic subjects . of 784 subjects , patients with both lada and type 2 diabetes were significantly older than subjects with normal glucose tolerance or type 1 diabetic patients . as expected , lada patients had lower insulin secretion than type 2 diabetic patients , while in type 1 diabetic patients , insulin secretion was lower than in both lada and type 2 diabetic patients . metabolic syndrome in type 1 diabetic and control subjects was less frequent than in both lada and type 2 diabetic subjects . we used univariate and multivariate regression models to adjust age , sex , and bmi differences ( fig . 1 and supplementary table 2 ) . after adjustment , all three types of diabetes ( type 1 diabetes , lada , and type 2 diabetes ) showed increased il-6 and lcn2 . all four cytokines were increased in lada . in type 1 diabetes , adiponectin but not hs - crp was increased . in type 2 diabetes , hs - crp but not adiponectin was increased , and adiponectin was decreased after adjustment . gada titer was positively correlated with adiponectin ( r = 0.14 , p < 0.01 ) and negatively correlated with hs - crp ( r = 0.15 , p < 0.001 ) ( supplementary tables 3 and 4 ) . in lada subjects , hs - crp was strongly related to bmi ( r = 0.363 , p < 0.001 ) . some inflammatory markers were increased in diabetes ( i.e. , il-6 and lcn2 ) irrespective of diabetes type , implying that cytokine changes are secondary features of the disease independent of obesity , and consistent with a proinflammatory effect in diabetes in general . nevertheless , obesity ( waist - to - hip ratio ) was associated with all four cytokines assayed , and the pattern of cytokine changes differed according to diabetes type . cytokines ( il-6 , tnf , and il-1 receptor antagonist ) in europeans with these same major diabetes types were also positively associated with bmi , which was higher in diabetic patients than in control subjects and highest in type 2 diabetes but similar in lada and type 1 diabetes ; after correction , only tnf in lada and type 1 diabetes was no longer different from that in control subjects ( 5 ) . in both the european study and this chinese study , il-6 showed remarkably similar increases in major diabetes types ; il-6 , as well as lcn2 , levels were higher than in control subjects and highest in type 2 diabetes ( 5 ) . however , hs - crp was increased in both lada and type 2 diabetes , but not type 1 diabetes , while adiponectin was only increased in lada and type 1 diabetes . despite adiponectin being positively correlated with gada titer , it has no established role in autoimmune diabetes and certainly can not predict it ( 12 ) . however , low - grade inflammation could be important in autoimmunity , potentially explaining any benefit of rosiglitazone ( 13 ) . indeed , each cytokine ( il-6 , lcn2 , hs - crp , and adiponectin ) was increased in chinese lada , though probably for different reasons ( 14 ) . given the relative lack of obesity in china , comparative chinese and european studies could delineate the relative roles of obesity , diabetes , and autoimmunity on cytokines . surprisingly , therefore , metabolic syndrome was prevalent in this large lada cohort , in contrast to european studies ( 5,6 ) . these results point toward a complex relationship between diabetes types and altered cytokine levels .

objectiveto determine the relationship between selected cytokines and diabetes in chinese subjects.research design and methodsadult patients with recent - onset type 1 diabetes ( n = 53 ) , latent autoimmune diabetes in adults ( lada ) ( n = 250 ) , and type 2 diabetes ( n = 285 ) from multiple centers were compared with normal subjects ( n = 196 ) . we centrally tested serum gad antibodies ( gadas ) , interleukin-6 ( il-6 ) , lipocalin 2 ( lcn2 ) , high - sensitivity c - reactive protein ( hs - crp ) , and adiponectin.resultsafter adjustment for age , sex , and bmi , all diabetes types had increased il-6 and lcn2 ( p < 0.01 ) , and all four cytokines were increased in lada ( p < 0.01 ) . in type 1 diabetes , adiponectin but not hs - crp was increased ( p < 0.01 ) , whereas in type 2 diabetes , hs - crp but not adiponectin was increased ( p < 0.01 ) . adiponectin was correlated positively with gada titer and negatively with hs - crp ( p < 0.01 for both).conclusionsin china , inflammatory markers are increased in all three major types of diabetes , but probably for different reasons , even in autoimmune diabetes .

torsion of uterine adnexa is an important cause of acute abdominal pain reported in the literature.1 however , isolated torsion of fimbrial cysts has rarely been described as a cause for acute abdomen.23 we report a rare case of isolated torsion of fimbrial cysts leading to acute abdomen . a 22-yr - old female presented to the hospital with acute abdomen , amenorrhea for a half month and a half , and spotting on and off . the patient provided written consent to reproduce information or photographs . on physical examination , the patient s vital signs were found to be normal . laboratory investigations including hemoglobin , total leucocyte count , differential leucocyte count , and routine and microscopic examination of the urine were found to be normal . therefore , a serum beta human chorionic gonadotropin ( hcg ) test was done to confirm pregnancy . however , serum beta hcg levels were within normal range . the ultrasound report showed a tubo - ovarian mass in the right adnexa along with fluid in the pouch of douglas , suggestive of fimbrial cysts or ectopic pregnancy ( fig . on laprotomy , multiple cystic structures attached to the fimbriae were seen , which were twisted at their pedicle . many of them had ruptured leading to collection of about 200 ml of straw colored fluid . however , the fallopian tubes and ovaries were normal on both the sides , so a cystectomy was done . multiple cystic structures varying in size from 3 3 cm to 2 2 cm were seen . the cystic structures were filled with yellow colored fluid and were twisted at the pedicle ( fig . 2 ) . histopathology showed ciliated , columnar cells with underlying stroma and few chronic inflammatory cells , and a diagnosis of fimbrial cysts was made ( fig . paraovarian cysts represent approximately 10% of adnexal masses.4 they are more common in childbearing women.5 paratubal cysts arise from mllerian or wolffian structures and are common in adult females . these are hormone sensitive and are generally asymptomatic.6 malignant neoplasms arising from paratubal cysts are very rare.7 rarely , they can be associated with torsion of fallopian tubes.7 other complications include hemorrhage , rupture , and infection.3 paratubal cysts are difficult to diagnose preoperatively , and even transvaginal ultrasound in older women has detected only about 44% of paratubal cysts preoperatively.8 in only 1 of 15 patients is the diagnosis of fimbrial cyst suspected before surgery.4 thus , acute abodomen is a rare presentation of fimbrial cysts , which needs to be considered in a female of reproductive age group . timely diagnosis and excision of these cysts may prevent the rare complications of torsion and rupture that are associated with them .

we present a case of a 22-year - old female who presented with acute abdomen and amenorrhea . emergency laprotomy was done with a clinical diagnosis of ectopic pregnancy . on laprotomy , twisted fimbrial cysts were found . thus , although fimbrial cysts are rarely twisted , they should be considered as a cause of acute abdomen in a female of reproductive age group .

congenital diaphragmatic hernia ( cdh ) is a congenital malformation of diaphragm , characterized by a defect in the diaphragm along with herniation of gastro - intestinal loops and other abdominal viscera into the thoracic cavity . in case of extreme maldevelopment of diaphragm , there might be a complete agenesis of diaphragm , usually involving one side , but , sometimes both sides . to repair a defect like that is a management dilemma . various techniques have been put forward for repairing such defects including use of prosthetic material , abdominal or intercostals muscle flaps and so on . we are reporting the index case on the basis of extreme rarity of the congenital hemidiaphragmatic agenesis ( chda ) and its successful repair without the need of a prosthetic material . a 45-day old male infant was referred to the surgical emergency of our institution with complaints of fever , cough and respiratory distress for 1 week . the baby was born to a primigravida 22-year old mother in a village setting , as spontaneous vaginal delivery . the baby was alright for more than a month when he developed respiratory distress associated with fever and few episodes of non - bilious and non - projectile emesis . the parents took the baby to local hospital where the baby was given steam nebulization and intra - muscular antibiotics along with oxygen therapy . the baby did not improve , and was thus referred to our hospital . during the admission , the weight of the baby was 3.2 kg and a general physical examination revealed mild pyrexia ( 100f ) and tachypnea ( respiratory rate > 50/min ) . pulse was 120/min and blood pressure within normal age range . on respiratory system examination there were overt signs of respiratory distress including nasal flaring , intercostal and subcostal retractions and tachypnea . on auscultation the air entry was absent on lower right chest and reduced on the upper right chest . a chest radiograph was requested that revealed intestinal gas shadows in the right hemi - thorax . a diagnosis of right - sided cdh was made and patient optimized for elective surgical intervention . his preoperative laboratory parameters were normal except for the wbc count which was in upper normal limits . the fever was settled in two days and an elective operation was planned on the 10 day of admission . the entire liver and most of small and large intestine were found herniating into the right hemi - thorax . the diaphragm was absent on anterior and lateral aspects of the right hemi - thorax and only a small rim of diaphragm was present on posterior aspects [ figure 1 ] . the diaphragm was absent on anterior and lateral aspects whereas a small rim of diaphragm can be appreciated posteriorly and lifted up by taking stay sutures the lung was looking hypoplastic . the part of diaphragm present on posterior aspects was mobilized and sutured to the intercostal muscles ( an incision was given on inferior aspects of the intercostal space to get some mobilization ) and ribs using interrupted stitches of silk 0 sutures [ figure 2 ] . the abdominal wound was closed by only skin closure , as we were not able to oppose the abdominal wall muscles . diaphragmatic defect was repaired by apposing the residual diaphragm with the intercostal muscles and ribs using a 0 silk suture the postoperative recovery was uneventful . we were anticipating a need of ventilator assistance but the patient did not require mechanical ventilation postoperatively . the nasogastric tube was removed on the fourth postoperative day ; and started orally on the next day and discharged on the ninth postoperative day . patient has a symptom - free follow up of three months and we advised a definitive closure of the ventral hernia after one year of age . classical cdh is characterized by a left - sided postero - lateral defect in the diaphragm , and named after bochdalek who was the first to identify the defect in 1848 . the right - sided bochdalek 's cdh are very rare and reported to be 815% . chda is considered as one of the rare congenital malformations of diaphragm and reported to be in 6% of all cdh . unilateral diaphragmatic agenesis is common on left side as compared to the right side.[24 ] however , in our case the hemidiaphragmatic agenesis was on right side showing rare side of occurrence of a very rare lesion . the etiology of chda is largely based on assumptions and speculation , and not well defined to date . a failure of pleuroperitoneal membrane to close the pleuroperitoneal canal on the involved side is considered the probable etiology ; however , others proposed a failure of all the precursors components of diaphragm to develop . environmental factors and various drugs have been proposed to play a key role in development of the cdh in animal modules.[24 ] the classical presentation of cdh is within first 24 hours of life with clinical features dependent upon the severity of pulmonary hypoplasia and pulmonary hypertension . more severe the lung hypoplasia and pulmonary hypertension , early will be the presentation and worse will be the outcome , and vice versa . about 10% of patients with mild to modest lung hypoplasia and pulmonary hypertension may escape the early presentation , as happened in our case . in our case the patient escaped the early newborn - period - presentation , thus , reflecting a less severe grade of pulmonary hypoplasia and pulmonary hypertension . the patients with cdh may present in infantile age or thereafter ; nascent presentation of cdh in adults and even senile persons have frequently been reported in literature . the presentation of chda is somewhat similar to the cdh and is considered , by many authors , as an extreme variety of bochdalek cdh . similarly as for cdh , chda may also appear in adults but the overall incidence is very low.[14 ] chest radiograph can not specifically diagnose the chda but is a modality of choice in case of cdh . ct scan and mri are important diagnostic modalities for the delineation of the diaphragm and its abnormalities.[23 ] in our case our diagnosis of cdh was straight - forward as depicted by the chest radiograph , thus , precluding us to opt for the sophisticated diagnostic modalities . the configuration of the defect , in a case of a bochdalek 's cdh , is a well - defined anterior part of diaphragm followed by a postero - lateral defect through which gastro - intestinal loops and other viscera herniated into the thoracic cavity , and a retroperitoneal - buried posterior rim of diaphragm on the affected side . in our case the defect was absent on anterior and lateral sides of right chest cavity and a small rim of diaphragm was present posteriorly . chda may be differentiated into partial and complete agenesis with regard to the defect . in case of partial diaphragmatic agenesis a small rim of diaphragm may be present especially on posterior aspects , whereas , in case of complete hemidiaphragmatic agenesis , no diaphragmatic remnant is present . the findings of remnant of diaphragm on posterior aspect led us to place our case in partial variety of chda . the surgical repair of the lesion is very difficult owing to completely absent diaphragmatic tissue or if present not suffice to accomplish the repair . various authors used different treatment options including , prosthesis , abdominal wall and chest wall muscle flaps , suturing the chest margins with liver , use of pre - renal fascia and some advocated no repair at all . about 3050% of cases with cdh , treated with mesh incorporation in the defect , showed prosthesis related complications and even recurrence of the herniation.[1245 ] in our case , we had a small rim of diaphragm that became sufficient after mobilization from retroperitoneum ; and suturing it with the intercostal muscles ( an incision was given on the inferior aspect of intercostal space to get mobilization of intercostal muscles ) and ribs served the purpose well . after reduction of entire liver and most of small and large intestine from the chest cavity to the abdominal cavity , there was a risk of abdominal compartment syndrome if a repair would have been done under tension . it is inferred that congenital right hemidiaphragmatic agenesis is a rare malformation of the diaphragm . it may remain asymptomatic for decades ; however , in case of symptomatic presentation , an early surgical intervention may prove boon for the patient . partial variety of chda can be repaired by mobilizing and suturing diaphragmatic remnant with intercostal muscles and ribs .

congenital diaphragmatic hernia is a congenital defect of the diaphragm through which intestine and other viscera herniate into the chest . in extreme form of diaphragmatic maldevelopment , there might be a complete agenesis of diaphragm . a 45-day old male infant was presented with fever , cough and respiratory distress for a week . chest radiograph showed right - sided congenital diaphragmatic hernia . the patient underwent surgical exploration and found to have an unusual and large defect of right hemidiaphragm . the diaphragm was absent on anterior and lateral aspects of the chest wall and only a small rim of diaphragm was present on posterior aspect . the defect was identified as agenesis of right hemidiaphragm and successfully managed by suturing the posterior rim of diaphragm to the intercostal muscles and ribs . this report describes successful management of hemidiaphragmatic agenesis without incorporating a prosthetic material .

levetiracetam ( lev ) is an antiepileptic drug that is approved for use as adjunct treatment for partial epilepsy in patients aged 4 years and older , as well as for juvenile myoclonic epilepsy in patients aged 12 years and older . irritability and agitation are known behavioral side effects of lev , and it is reported in almost 13% of patients across all age groups . levetiracetam use can be associated with insomnia , agitation , anxiety , emotional lability , and hyperactivity . some of these adverse events , however , are reported in patients with preexisting behavioral issues . furthermore , these adverse effects can lead to lev discontinuation in a small percentage of patients . previous case series from children and adolescents have indicated that pyridoxine ( vitamin b6 ) can alleviate behavioral side effects related to the use of lev . , we sought to explore the potential benefits of pyridoxine supplementation for the treatment of behavioral side effects induced by lev in our patients attending the epilepsy clinic . we retrospectively reviewed our electronic medical records to identify all patients attending our epilepsy clinic and being treated with both lev and pyridoxine . fifty - one adult patients were identified using pyridoxine supplementation for the management of either irritability or agitation following the introduction of lev . age , gender , epilepsy classification , duration of seizures , dosages of lev and pyridoxine , and the effect of the addition of pyridoxine on behavioral symptoms were carefully analyzed . the epilepsy was classified as idiopathic in 15 patients ( 29.5% ) and as partial in 36 ( 70.5% ) . levetiracetam monotherapy was used for 26 patients ; the others were taking an average of two additional antiepileptic drugs . pyridoxine was started at 50 mg / day , and if no or partial benefit was noted , the dose was increased to 100 mg / day . however , the average dose to control the behavioral symptoms in our study was 54.5 mg / day ( sd = 18.2 ) . most patients had reported behavioral problems within the first weeks after the addition of lev . none of our patients , however , had preexisting behavioral issues prior to the use of lev . none of the patients who did not receive pyridoxine supplementation reported any significant improvement in behavioral symptoms throughout the course of treatment with lev . on average , the effects of pyridoxine supplementation were reported during the first 2 weeks . on a separate note , none of the patients who received pyridoxine supplementation reported any significant improvement in seizure frequency throughout the course of treatment with lev . to our knowledge , this is the first study that suggests a possible benefit of pyridoxine supplementation in the treatment of lev - induced behavioral side effects in the adult population . previous reports in the pediatric population have demonstrated the potential beneficial effect of pyridoxine to control the lev - induced behavioral symptoms . miller was able to control the behavioral disturbances caused by lev completely , in 5 of 6 children aged between 2 and 10 years , by supplementing pyridoxine at an average dose of 7 mg / kg / day . in another study to examine the use of pyridoxine , major et al . twenty - two patients started pyridoxine after being on lev , due to behavioral side effects , and significant behavioral improvement was observed in nine ( 41% ) , no effect in eight ( 36% ) , deterioration in four ( 18% ) , and an uncertain effect in one . the effects of pyridoxine supplementation , similar to our study , were observed during the first week of its introduction . our study used a retrospective , chart review method and lacked a placebo - controlled approach . our results demonstrated that 66% of patients who started pyridoxine after being on lev had a significant behavioral improvement , and in the remaining one - third , pyridoxine was not helpful in preventing lev - related behavioral side effects . interestingly , and similar to previous reports in pediatric populations , the improvement occurred during the first few weeks after pyridoxine supplementation , probably supporting its potential effect . pyridoxine is a water - soluble cofactor in more than 100 enzyme - catalyzed reactions in the body , including many involved in the synthesis or catabolism of neurotransmitters . there is no known pharmacokinetic or pharmacodynamic interaction between lev and pyridoxine that could explain its potential clinical benefit . on that note , it can be said that the underlying mechanism(s ) that would explain its efficacy in controlling the behavioral adverse effects of lev is largely unknown , and its recommended use to control these symptoms is empirical at best . similarly , pyridoxine , based on empirical grounds , has been used to treat other medical conditions such as premenstrual depression . on the other hand , pyridoxine has been tried based on our current understanding for treatment of other underlying metabolic disorders . for example , pyridoxine - dependent epilepsy , a rare autosomal recessive error of metabolism characterized by neonatal seizures , responds to pyridoxine . intravenous administration of 50100 mg of pyridoxine promptly controls the seizures , but lifelong supplementation is required ( 5300 mg / kg / day ) . the average dose to control the behavioral symptoms in our study was less than 100 mg / day . toxicity of this supplementation tends to occur at a dose higher than 1000 mg / day . we realize the limitation of our study , being retrospective and from a single center . however , this preliminary study suggests that pyridoxine might be used safely to control lev- induced behavioral side effects in adults . whether vitamin b6 has the same efficacy in controlling behavioral symptoms in patients with epilepsy in general or it shows the same efficacy in those patients who are treated with other aeds remains to be carefully examined . a prospective , placebo - controlled study is needed to confirm our finding and to address these unanswered questions .

behavioral symptoms are known side effects of levetiracetam . previous case series in children and adolescents have demonstrated the potential effect of pyridoxine in ameliorating these symptoms . we retrospectively reviewed the charts of 51 patients treated with pyridoxine to control agitation and irritability following the introduction of levetiracetam . these symptoms were relieved in 34 patients ( 66.6% ) . seventeen patients did not appear to benefit from this supplementation . this preliminary study suggests that pyridoxine might be an effective option across all ages for patients suffering from levetiracetam - induced behavioral side effects .

we use density functional theory ( dft ) to compute the effects of substitutional al , b , cu , mn , and si solutes , and octahedral interstitial c and n solutes on the lattice parameters and elastic stiffness coefficients cij of bcc fe . the purefe.csv file contains the computed lattice parameter , magnetic moment , cij , and the derivatives of the cij with respect to lattice parameter for pure fe . the computational methodology we developed in ref . calculates a strain - misfit tensor for each solute which determines changes in the lattice parameter and volumetric contributions to the derivatives of the cij with respect to solute concentration . we also compute chemical contributions from each solute to the derivatives of the cij with respect to solute concentration . the sum of the volumetric and the chemical contributions gives the total derivatives of the cij with respect to solute concentration . the soluteeffects.csv file contains the diagonal components of the solute strain - misfit tensors and their average values , the volumetric and chemical contributions to the cij derivatives , the sum of the two contributions , and direct calculations of the total derivatives that encompass both contributions . we compute the solute data using 222 ( 16 atoms ) , 333 ( 54 atoms ) , and 444 ( 128-atom ) supercells . the calculation details , including the exchange - correlation functional , pseudopotentials , and all numerical convergence parameters used in generating the data , are given in ref . . the vasp input files incar and kpoints , and output files contcar , outcar , and oszicar for all the calculations are stored in the nist dspace repository ( http://hdl.handle.net/11256/67 ) , along with the analyzed data stored in the purefe.csv and soluteeffects.csv files . the repository also stores unix shell scripts we developed for calculating the data in the csv files from the raw vasp output files . the fundamental quantities necessary for computing strain misfit tensors and elastic stiffness coefficients are the numbers of atoms in the computational supercells , lattice parameters , applied strain magnitudes , and stresses . the scripts compute the elastic stiffness coefficients from derivatives of stress with respect to strain , approximated using a standard four - point central finite - difference formula . table 1 , table 2 list the properties contained in the purefe.csv and soluteeffects.csv files , respectively , along with identifying tags that label the properties in the files and their units .

we present computed datasets on changes in the lattice parameter and elastic stiffness coefficients of bcc fe due to substitutional al , b , cu , mn , and si solutes , and octahedral interstitial c and n solutes . the data is calculated using the methodology based on density functional theory ( dft ) presented in ref . ( m.r . fellinger , l.g . hector jr . , d.r . trinkle , 2017 ) [ 1 ] . all the dft calculations were performed using the vienna ab initio simulations package ( vasp ) ( g. kresse , j. furthmller , 1996 ) [ 2 ] . the data is stored in the nist dspace repository ( http://hdl.handle.net/11256/671 ) .

one serious intraoperative complication of cataract surgery occurs if the posterior capsule is damaged during phacoemulsification of the lens and the nucleus drops into the vitreous cavity . in such cases , a vitreous cutter or fragmatome must be used to extirpate the fragments of nucleus that have dropped into the vitreous cavity [ 1 , 2 ] . the popularization of microincision vitreous surgery ( mivs ) has led to the use of 25- , 23- , and even 27-gauge systems for vitreous surgery that would formerly have been performed with a 20-gauge system . this means that even when the nucleus drops as a complication of cataract surgery , the dropped lens is also often extirpated by mivs [ 4 , 5 ] . however , with the decrease in vitreous cutter diameter , the suction aperture in the vitreous cutters used in mivs has also decreased , making it difficult to deal with hard fragments of nucleus that have dropped into the vitreous cavity . in addition , when a vitreous cutter is used at high speed , the cutter aperture opens and the time for which suction is engaged ( the duty cycle ) shortens , reducing suction flow volume . the twin duty cycle ( tdc ) vitreous cutter developed by the dutch ophthalmic research center ( dorc , zuidland , the netherlands ) also has an aperture in the inner shaft cutting blade that opens for suction and extirpation , a design that prevents a drop in suction efficiency even when the cutter speed is increased . in this study , we describe the use of a 27-gauge tdc cutter , which maintains suction power even when the vitreous cutter is driven at high speed , to deal with dropped nucleus as a complication of cataract surgery . to treat 3 cases of dropped nucleus due to posterior capsule damage during cataract surgery ( emery - little grade 3 in 2 cases , grade 2 in 1 case ) , we used a 27-gauge tdc vitreous cutter to remove the nucleus . a 78-year - old woman underwent simultaneous vitreous and cataract surgery for proliferative diabetic retinopathy and cataract . part of the remaining nucleus was seen to have dropped into the vitreous cavity ( fig . as the original intention was to perform vitreous surgery with a 27-gauge system , an attempt was made to remove the nucleus using a 27-gauge tdc vitreous cutter . a chandelier fiber with a xenon light source ( xenon brightstar illumination system ; dorc ) was used for intraocular illumination . a 27-gauge tdc vitreous cutter was inserted via a 27-gauge cannula , and the vitreous body behind the lens and the anterior portion of the vitreous membrane were extirpated from the vitreous body side . the nucleus that remained within the capsule was then extirpated from the vitreous body side with the 27-gauge tdc cutter . the vitreous cutter settings were : cut rate , 6,000 cuts per min ( cpm ) ; suction , 600 mm hg , and perfusion pressure , 30 mm hg . the 27-gauge vitreous cutter was pressed against the remaining fragments of nucleus while suction was applied from the vitreous body side , cutting into and extirpating the nucleus without repelling it ( fig . 1b ) . as portions were extirpated and size decreased , the nucleus dropped onto the retina . after the vitreous body had been removed with the vitreous cutter using the same settings , the nucleus that had dropped onto the retina was also removed . the fragments of nucleus that had dropped onto the retina were picked up from the retinal surface by suction with the vitreous cutter ( fig . extirpation of the nucleus fragments was attempted with the following cutter settings : cut rate , 6,000 cpm ; suction , 600 mm hg , and perfusion pressure , 30 mm hg . nucleus fragments that had been picked up by the suction power of the 27-gauge tdc vitreous cutter were retained because suction power was maintained even while the inner shaft cutting blade was being driven ( fig . pieces of dropped nucleus were also successfully extirpated with the vitreous cutter while they were skewered with the 27-gauge light pipe . all dropped lens fragments were extirpated successfully with the 27-gauge tdc vitreous cutter alone , with no intraoperative complications . at the end of the operation , the trocar cannula was removed without any leakage from the scleral incision , and no suturing was required . a 78-year - old woman underwent simultaneous vitreous and cataract surgery for proliferative diabetic retinopathy and cataract . part of the remaining nucleus was seen to have dropped into the vitreous cavity ( fig . as the original intention was to perform vitreous surgery with a 27-gauge system , an attempt was made to remove the nucleus using a 27-gauge tdc vitreous cutter . a chandelier fiber with a xenon light source ( xenon brightstar illumination system ; dorc ) was used for intraocular illumination . a 27-gauge tdc vitreous cutter was inserted via a 27-gauge cannula , and the vitreous body behind the lens and the anterior portion of the vitreous membrane were extirpated from the vitreous body side . the nucleus that remained within the capsule was then extirpated from the vitreous body side with the 27-gauge tdc cutter . the vitreous cutter settings were : cut rate , 6,000 cuts per min ( cpm ) ; suction , 600 mm hg , and perfusion pressure , 30 mm hg . the 27-gauge vitreous cutter was pressed against the remaining fragments of nucleus while suction was applied from the vitreous body side , cutting into and extirpating the nucleus without repelling it ( fig . 1b ) . as portions were extirpated and size decreased , the nucleus dropped onto the retina . after the vitreous body had been removed with the vitreous cutter using the same settings , the nucleus that had dropped onto the retina was also removed . the fragments of nucleus that had dropped onto the retina were picked up from the retinal surface by suction with the vitreous cutter ( fig . extirpation of the nucleus fragments was attempted with the following cutter settings : cut rate , 6,000 cpm ; suction , 600 mm hg , and perfusion pressure , 30 mm hg . nucleus fragments that had been picked up by the suction power of the 27-gauge tdc vitreous cutter were retained because suction power was maintained even while the inner shaft cutting blade was being driven ( fig . pieces of dropped nucleus were also successfully extirpated with the vitreous cutter while they were skewered with the 27-gauge light pipe . all dropped lens fragments were extirpated successfully with the 27-gauge tdc vitreous cutter alone , with no intraoperative complications . at the end of the operation , the trocar cannula was removed without any leakage from the scleral incision , and no suturing was required . to treat 3 cases of dropped nucleus due to posterior capsule damage during cataract surgery ( emery - little grade 3 in 2 cases , grade 2 in 1 case ) , we used a 27-gauge tdc vitreous cutter to remove the nucleus . in all 3 cases , the nucleus that had dropped into the vitreous cavity was successfully dealt with using the 27-gauge tdc vitreous cutter alone , with no intraoperative complications . no patient required suturing because of postoperative leakage of intraocular fluid from the scleral incision , nor did any patient develop ocular hypotension or other postoperative complications . dropped nucleus as a result of posterior capsule damage represents a serious complication that may occur during cataract surgery . in the event that the nucleus drops into the vitreous cavity , it is important to deal with the dropped lens without causing further intra- or postoperative complications . however , problems include the fact that the cutter aperture is too small to easily deal with the dropped hard nucleus , fragmatomes adapted to mivs can not yet be used , and intraocular fluid leaks from the extended incision when the trocar pierces the sclera during port creation , causing a drop in intraocular pressure and making it difficult to insert the trocar . to avoid these problems , we have previously reported a transconjunctival vitreous surgery technique during anterior chamber irrigation , a vitreous cutter , and a light pipe through the cornea incision , with perfluorocarbon liquid to float the dropped nucleus to the surface of the iris , and using an ultrasound handpiece to emulsify and suction the fragments of nucleus while the anterior chamber is still perfused . this technique does not require creation of a scleral incision , and so prevents changes in intraocular pressure during scleral port creation , as well as retinal detachment , which contributes to postoperative incarceration of the vitreous body in the scleral incision . as this method entails the insertion of surgical instruments via a corneal incision , however , fundus visibility may decline during surgery as a result of changes in the shape of the cornea . in particular , the 27-gauge vitreous surgery system entails little risk of incarceration of the vitreous body in the incision , and as there is almost no leakage from the incision at the conclusion of the procedure , this system is also believed to decrease the risk of complications associated with port creation . the rate of postoperative intraocular fluid leakage from the incision is also extremely low and suturing is seldom required , alleviating the postoperative sensation of a foreign body in the eye felt by patients . taking reduced fundus visibility into consideration , if dropped nucleus could be extirpated with a 27-gauge vitreous cutter , 27-gauge trans pars plana vitreous surgery would be safer than transcorneal vitreous surgery for dealing with a dropped lens . normally , a finer diameter of the vitreous cutter corresponds to a smaller suction aperture and lower suction power . as the number of revolutions per second increases , the suction aperture is also closed for longer and the duty cycle decreases this means that the suction flow volume of a vitreous cutter declines when extirpation is being performed at a high speed . vitreous cutters use suction power to draw the vitreous body through the cutter aperture into the inner shaft of the cutter , and the inner shaft blade moves forward against the drawn - in vitreous body and extirpates it . in this process , the cutter aperture is closed by the guillotine blade of the inner shaft , causing a drop in suction power . to extirpate a nucleus with a vitreous cutter requires that a portion of the lens be drawn by suction power through the cutter aperture into the inner shaft , where it is finely shredded by the guillotine blade of the inner shaft . normally , driving the guillotine blade at a high speed lengthens the time for which the guillotine blade of the inner shaft closes the cutter aperture , causing a drop in suction power . to deal with a moderately hard or harder nucleus requires both that suction power be maintained and that the nucleus be finely shredded , but as the suction power of conventional vitreous cutters drops when they are driven at a high speed , the nucleus is repelled from the suction aperture , and extirpation has therefore previously been carried out by running the vitreous cutter at a lower speed . attempts to improve the shape of vitreous cutters to maintain and improve suction power have been reported . the tdc vitreous cutter reported here is designed with an aperture in the inner shaft cutting blade , which means that even when the cutting blade is driven forward and backward , the aperture in the outer shaft is not closed . with conventional cutters , extirpation only occurs when the inner shaft cutting blade moves forward like a guillotine , but opening an additional aperture in the inner shaft cutting blade enables extirpation to take place when the inner shaft is driven both forward and backward . this means that the cutter can be driven at a higher speed with almost no drop in suction power , as well as enabling efficient extirpation of the vitreous body . similarly , the 27-gauge tdc vitreous cutter is capable of extirpating a lens with a nucleus of around emery - little grade 3 hardness by retaining it with suction power and shredding it at a high speed . in addition , fewer postoperative complications are expected to occur when a 27-gauge vitreous system is used , meaning that fragments of dropped nucleus can be removed more efficiently and safely than with conventional cutters . however , a nucleus of emery - little grade 4 hardness or harder remains difficult to resect efficiently with a 27-gauge vitreous cutter and must be floated to the surface of the iris with perfluorocarbon liquid and emulsified and suctioned with an ultrasound handpiece . further studies are required to investigate procedures for cases of dropped nucleus harder than the present case . this study was approved by the ethics committee of the jikei university school of medicine and complied with the tenets of the declaration of helsinki .

we report herein a method for the treatment of dropped nucleus during cataract surgery with a 27-gauge twin duty cycle ( tdc ) vitreous cutter . when a tdc vitreous cutter is used , suction flow volume is maintained even when the cutter is driven at a high speed . this enables an emery - little grade 3 nucleus that had been difficult to treat with a conventional 27-gauge cutter to be successfully excised using only a vitreous cutter , with no intra- or postoperative complications . a dropped lens during cataract surgery of up to moderate hardness can be removed using a tdc cutter alone with a 27-gauge cutter system .

inflammatory myofibroblastic tumor ( imt ) occurring at intra - abdominal sites in children is a rare entity , which , because of its large size and location , may often be confused with malignancy . the treatment of imt is primarily surgical excision and re - excision of recurrent lesions . as these tumors are rare , correct diagnosis is important in order to avoid unnecessary wide surgical removal and aggressive chemotherapeutic regimens . we present here a brief outline of three such cases of imt presenting as abdominal mass in infants . the patient , a 5-month - old girl , weighing 6.9 kg , presented with a slow - growing abdominal mass , noted for one and half months . blood examination showed microcytic , hypochromic anemia with hemoglobin 9 g% . on exploration , a mass of size approximately 8 5 cm , attached to the mesenteric border of the ileum , 25 cm from the ileo - cecal junction was noted . mass attached with the mesenteric border of the ileum on gross examination , the mass was firm and grey - white in color . on light microscopic examination , the tumor was made up of loosely arranged spindle - shaped cells separated by abundant myxoid stroma sprinkled with inflammatory cells comprising mainly lymphocytes and plasma cells . on immunohistochemistry , the tumor expressed desmin , vimentin , and smooth muscle actin ; moreover , it was negative for anaplastic lymphoma kinase ( alk ) [ figure 3 ] . [ h and e , 100 ] micro section shows part of the ileum and a mass composed of spindle - shaped cells ; inset : [ h and e , 100 ] micro section shows spindle - shaped cells in the edematous stroma sprinkled with inflammatory cells ( 100 ) immunohistochemistry of the tumor showing positivity for smooth muscle actin , vimentin , and desmin and negativity for alk-1 a 7-month - old girl presented with fever , weight loss , and abdominal mass . computed tomography ( ct ) of the abdomen revealed a lobulated mass in the jejunum . she had anemia ( hb 8.5/dl ) , leukocytosis ( 18,500/mm ) , mild thrombocytosis ( 5 lakh / mm ) , and raised esr ( 85 mm in the first hour ) . the patient underwent laparotomy and the mass was excised . the cut - section was rubbery , firm , and tan - yellow in color . a one - year - old boy presented with a failure to thrive and recurrent intestinal obstruction . he had anemia ( hb 6.5 g / dl ) and multiple lumps in the abdomen . on opening , large masses in the mesentery were found , stretching across 20 cm of the length of ileum and compromising the lumen at many places . the masses were excised along with the adjoining gut , with the restoration of gut continuity where required . the patient , a 5-month - old girl , weighing 6.9 kg , presented with a slow - growing abdominal mass , noted for one and half months . blood examination showed microcytic , hypochromic anemia with hemoglobin 9 g% . on exploration , a mass of size approximately 8 5 cm , attached to the mesenteric border of the ileum , 25 cm from the ileo - cecal junction was noted . mass attached with the mesenteric border of the ileum on gross examination , the mass was firm and grey - white in color . on light microscopic examination , the tumor was made up of loosely arranged spindle - shaped cells separated by abundant myxoid stroma sprinkled with inflammatory cells comprising mainly lymphocytes and plasma cells . on immunohistochemistry , the tumor expressed desmin , vimentin , and smooth muscle actin ; moreover , it was negative for anaplastic lymphoma kinase ( alk ) [ figure 3 ] . [ h and e , 100 ] micro section shows part of the ileum and a mass composed of spindle - shaped cells ; inset : [ h and e , 100 ] micro section shows spindle - shaped cells in the edematous stroma sprinkled with inflammatory cells ( 100 ) immunohistochemistry of the tumor showing positivity for smooth muscle actin , vimentin , and desmin and negativity for alk-1 a 7-month - old girl presented with fever , weight loss , and abdominal mass . her medical history was not significant . computed tomography ( ct ) of the abdomen revealed a lobulated mass in the jejunum . she had anemia ( hb 8.5/dl ) , leukocytosis ( 18,500/mm ) , mild thrombocytosis ( 5 lakh / mm ) , and raised esr ( 85 mm in the first hour ) . the patient underwent laparotomy and the mass was excised . the cut - section was rubbery , firm , and tan - yellow in color . inflammatory cell infiltration , mainly lymphocytes and plasma cells , were conspicuous . however , mitosis was lacking . a one - year - old boy presented with a failure to thrive and recurrent intestinal obstruction . he had anemia ( hb 6.5 g / dl ) and multiple lumps in the abdomen . on opening , large masses in the mesentery were found , stretching across 20 cm of the length of ileum and compromising the lumen at many places . the masses were excised along with the adjoining gut , with the restoration of gut continuity where required . inflammatory myofibroblastic tumor is a rare entity found in various sites and across all age groups . it is known by many names such as pseudosarcoma , atypical myofibroblastic tumor , atypical fibromyxoid tumor , and plasma cell granuloma . however , among the extrapulmonary sites , similar tumors have been reported in multiple locations including the skin , orbit , gingiva , breast , thyroid , thymus , spleen , lymph nodes , tonsil , liver , gall bladder , pancreas , kidney , renal pelvis , urinary bladder , adrenal gland , uterus , ovary , brain , spinal cord , mesentery , appendix , and gastro - intestinal tract . the long list of differential diagnosis of intra - abdominal spindle cell lesions closely mimicking imt include gastro - intestinal stromal tumor , fibromatosis , retroperitoneal fibrosis , solitary fibrous tumor , leiomyosarcoma , and malignant peripheral nerve sheath tumor . in adult women most patients present with fever , anemia , thrombocytosis , and hyperglobulinemia and weight loss . all three of our patients came with anemia and the signs and symptoms of recurrent intestinal obstruction with failure to thrive . microscopically , the tumors are composed of an admixture of proliferating spindle cells and chronic inflammatory cells in a variably vascular stroma that ranges from being loosely myxoid to densely collagenous . these spindle cells were eventually recognized as myofibroblasts , and the tumor was renamed imt . immunohistochemical staining further supports the myofibroblastic nature of the spindle cells , with a positivity of smooth muscle actin and vimentin . alk positivity is related to clonal abnormalities involving the alk gene located on 2p23 , which encodes a tyrosine kinase receptor . ultrastructural studies of the spindle cells show features that are common to both smooth muscle cells and fibroblasts . there is a gradual transition in the concept of imt . although many of the previously reported pseudotumors of various organs pursued a benign clinical course , some lesions , particularly in the mesentery , retroperitoneum , and peritoneal surface of the abdominal cavity , show a remarkable propensity for recurrence and metastasis . it seems wise to interpret these lesions as more closely related to inflammatory fibrosarcoma than merely accepting them as a post - inflammatory process . the recent who classification of soft tissue tumors places them in the category of fibroblastic / myofibro - blastic tumors - intermediate ( rarely metastasizing ) . the involvement of alk gene and cytogenetic clonality also support the neoplastic nature of imt . further studies are essential to decide whether imt and inflammatory fibrosarcoma are closely related entities or not . designating these lesions as sarcoma does not necessarily mandate radical treatment . complete excision and close clinical follow - up accurate diagnosis of this rare tumor is important in the pediatric age group to avoid unnecessary aggressive treatment .

inflammatory myofibroblastic tumor occurring at intra - abdominal sites in children can be confused with malignancy because of its large size and location . it is a tumor classified as intermediate between benign and malignant , but usually benign , with a strong tendency for recurrence . treatment is surgical excision . here , we present a brief outline of three such cases presenting as abdominal mass in infants .

the lifetime risk of urolithiasis is estimated to be between 5% and 12% in europe and the united states . acute renal colic is commonly observed in emergency rooms and is usually described as an acute flank pain radiating to the groin . it is often caused by ureteral stones . because up to 98% of ureteral calculi of < 5 mm in diameter are likely to pass spontaneously , shock wave lithotripsy ( swl ) and ureteroscopy ( urs ) when drug therapy does not resolve symptoms , the next step involves the placement of a ureteral catheter or a nephrostomy tube . these simple procedures can provide prompt symptom relief , and they are usually followed by urs or swl , which are currently the main treatment options for symptomatic ureteral stones . although urs is a more invasive option than swl , it probably has a better success rate , especially for mid- and distal ureteral stones . today , consensus appears to favor the superiority of minimally invasive therapeutic procedures , but it is still debated whether swl or urs should be the first - line treatment option for patients with ureteral stones . the recent developments of small - caliber semi - rigid and flexible deflectable ureteroscopes and of diminutive intracorporeal lithotripsy probes have made retrograde access to urinary calculi throughout the entire ureter more feasible and of lower risk . however , few data are available regarding the emergency ureteroscopic management of ureteral colic caused by ureteral stones . in the present study , we describe our experiences with emergency ureteroscopic management of ureteral stones and compared these data with data obtained by the delayed ureteroscopic management of ureteral stones . from january 2009 to june 2011 , 760 patients visited the emergency department at sanggye paik hospital because of renal colic caused by ureteral stones . the study inclusion criteria were as follows : no evidence of urinary tract infection or acute renal failure . children , pregnant women , patients with radiolucent stones or a solitary kidney , and patients with a history of ureteral stricture or multiple ureteral stones were excluded . patients were divided into two groups according to the time when ureteroscopic management was performed . group a consisted of patients who were hospitalized immediately at their first visit to the emergency department and underwent urs within 48 hours ( n=67 ) , and group b consisted of patients who underwent urs more than 48 hours after their first visit ( n=159 ) . all patients underwent a radiologic examination ( plain x - ray , ultrasonography , non - enhanced computed tomography , or intravenous pyelography ) to evaluate stone location and size . proximal and distal ureteral stones were defined as above and below the pelvic brim , respectively , as suggested by hollenbeck et al . , and midureteral stones were defined as over the sacral bone . urs was performed under general or spinal anesthesia by use of an 8 fr semirigid ureteroscope ( wolf ) . when necessary , pneumatic intracorporeal lithotripsy was performed by using the swiss lithoclast ( ems medical , nyon , switzerland ) . attempts were made to remove stone fragments with an endoscopic grasper , but small fragments ( <3 mm ) were largely left to pass spontaneously . at the end of the procedure , a ureteral catheter was left in place in 158 patients ( 69.9% ) and was removed 24 hours later . in the other 68 remaining patients , a double - j stent was inserted because of significant tissue trauma ( n=11 , 16.2% ) and edema at the impaction site ( n=26 , 38.2% ) or suspected ureteral perforation ( n=5 , 7.4% ) , because of mild or severe dilation ( n=5 , 7.4% ) , because a large fragment was still in place ( n=10 , 14.7% ) , or because stones had been pushed back into the pyelocaliceal system ( n=11 , 16.2% ) . after treatment , all patients were evaluated by urinalysis , urine culture , and renal function tests . scheduled postoperative radiologic follow - ups included plain abdominal radiography on day 1 to assess the initial stone - free rate , and for those with a stent in place , to confirm the correct stent position . at 15 to 21 days postoperatively , plain abdominal radiography was repeated before scheduled stent removal . in a few selected cases , the production of fragments of <3 mm was considered successful fragmentation and overall stone - free status was defined as the complete absence of calculus at 1 month after urs . cost analysis was performed by analyzing preoperative evaluation , operative , office visit , emergency department visit , and auxiliary procedure costs . the chi - square , kruskal - wallis , and fisher 's exact test were used to compare group variables . the two - tailed t - test was used to assess the significance of differences between continuous variables . , chicago , il , usa ) , and statistical significance was accepted for p - values < 0.05 . mean patient age was 47.8611.51 years ( range , 22 to 72 years ) in group a and 51.2013.80 years ( range , 14 to 82 years ) in group b ( p=0.097 ) ( table 1 ) . mean stone size was 2.411.62 mm in group a and 4.112.64 mm in group b ( p<0.001 ) , and the mean number of visits to the emergency department was 1 in group a and 2.711.02 in group b ( p<0.001 ) . mean total hospital cost was 525,35031,250 korean won ( krw , the currency of south korea ) in group a and 762,36051,420 krw in group b. with respect to intraoperative complications , no significant difference was found between the two groups ( 4.48% and 9.43% , respectively : p>0.05 ) ( table 2 ) . mucosal injury was observed in 3 patients ( 4.48% ) in group a and in 9 patients ( 5.66% ) in group b. hematuria , which occurred in 6 patients in group b , was considered a minor intraoperative complication ( grade 1 complication according to the modified clavien classification system ) like mucosal injury . after ureteroscopic stone removal , swl was performed to manage the remaining fragments in 3 patients ( 4.48% ) in group a and in 6 patients ( 3.77% ) in group b. flexible urs was performed in 6 patients in group b. no significant difference was found between the two groups in terms of the need for additional procedures ( p>0.05 ) . stone - free rates were 89.55% ( 60 of 67 ) and 89.93% ( 143 of 159 ) in groups a and b , respectively . the procedure was unsuccessful in 2 patients ( 2.98% ) in group a and in 6 patients ( 3.77% ) in group b. residual fragments were present in 5 patients ( 7.46% ) in group a and in 10 patients ( 6.29% ) in group b , and all fragments were confirmed by non - contrast spiral computed tomography after suspicious plain abdominal radiographic findings after urs . in group a , the 2 patients ( 2.98% ) who underwent unsuccessful urs had stones located in the proximal ureter . in the 5 patients ( 7.46% ) with residual fragments ( > 3 mm ) , the stones were located in the proximal ureter in 3 and in the distal ureter in 2 . mean stone size was 8.4 mm ( range , 7 to 15 mm ) in the 7 patients who underwent an unsuccessful procedure or who had residual fragments of > 3 mm . in group b , evaluation of the 6 patients in whom the procedure was unsuccessful showed that stone migration into the renal pelvis and severe kinking with a relatively narrowed ureteral segment preventing stone access were underlying reasons for failure during lithotripsy . severe edema formation and bleeding due to large , impacted calculi and migration of disintegrated fragments into the renal pelvis during lithotripsy were the causes of the residual fragments in group b. obstructive ureteral calculi are the most common cause of severe colic pain evaluated and treated in an emergent manner . most ureteral stones can be reasonably expected to be uneventfully passed , and if successful , this strategy is less costly and less invasive than any other option . ureteral stones with a diameter of less than 5 mm will pass in up to 98% of cases , but for stones with a diameter of greater than 7 mm , the overall likelihood of spontaneous passage is low . when active ureteral stone treatment is warranted , the best procedure to choose depends on several factors , such as stone size and location , operator experience , patient preference , available equipment , and related costs . because of its noninvasive and practical nature , swl is the preferred therapeutic option and is performed after the onset of renal colic to relieve stones and related problems . however , swl is more successful for the management of proximal ureteral calculi and its success rates tend to decrease for distal stones and stones treated in an emergency setting . furthermore , published data demonstrate that urs could play a major role in these selected cases . urs represents a safe and minimally invasive procedure for the management of ureteral stones , and technologic advancements have made it a highly successful procedure with low complication rates . regarding the success rates of urs , the american urological association ureteral stones guidelines panel summary report found a stone - free rate of 56% for stones of < 1 cm and a stone - free rate of 44% for stones of > 1 cm in the proximal ureter as compared with rates of 89% and 73% for stones in the distal ureter , respectively . in the present study , the overall stone - free rate was 89.8% and increased to 97.6% when only stones in the distal ureter were considered . the overall complications rate was 7.96% , which decreased to 2.7% when only stones of < 10 mm were considered . these results are in accordance with published data for electively scheduled urs , which ranges from 86.6 to 94.6% for all ureteral stones and from 95.6 to 100% for distal stones . highly effective stone fragmentation and reasonably lower complication rates have resulted in the application of emergency urs in selected cases . the possible reasons for adopting this approach are the need for prolonged anti - inflammatory and analgesic medication to prevent additional colic attacks and an expected protracted hospitalization period . however , this approach has some limitations , which include decreasing the chance of conservative management and spontaneous passage of calculi without the use of interventions that require the patient being under anesthesia . thus , it seems that , depending on stone - related and patient - related factors , preferred treatment management , that is , medical , emergency urs , or elective urs , is a matter for joint decision making by the physician and the informed patient . the findings of the present study and published data demonstrate that the removal of ureteral calculi immediately after the first colic attack should significantly decrease readmission rates to emergency departments , and thus decrease analgesic medication and economic costs originating from prolonged hospitalization and loss of work . furthermore , our comparison of the complication rates in our two study groups showed that emergency urs can be ideal for relieving the colic pain and morbidity associated with spontaneous passage . in addition , cost analysis showed that total charges ( initial procedures , additional procedures , radiographs , postoperative office visits ) were less when urs was performed emergently . this study is limited by its retrospective nature and a relatively small cohort . however , in the absence of international guidelines regarding the ureteroscopic management of ureteral stones in an emergency setting , the results of this study suggest the need for emergency urs . emergency urs appears to be an effective and safe procedure for the treatment of obstructive ureteral stones that provides immediate relief from colic pain and allows ureteral stones to be fragmented . nonetheless , it should be borne in mind that this procedure requires specific technical expertise and dedicated facilities . we recommend that an additional large - scale study that includes other parameters be conducted to confirm our findings .

purposeto evaluate the efficacy and safety of the ureteroscopic management of ureteral stones immediately after a first colic attack.materials and methodswe retrospectively analyzed the data of 226 patients with obstructive ureteral stones who underwent ureteroscopy with stone retrieval . the 67 patients in group a underwent ureteroscopy within 48 hours of admission to our emergency department , whereas the 159 patients in group b underwent ureteroscopy more than 48 hours after admission . the chi - square test was used to evaluate and compare stone - free status , auxiliary procedures , and complications and the kruskal - wallis and fisher 's exact tests were used to analyze qualitative data.resultsmean stone sizes in groups a and b were 2.411.62 mm and 4.112.64 mm , respectively . no patient experienced a major complication during or after the procedure . stone - free rates were 89.55% and 89.93% , respectively.conclusionsemergency ureteroscopy in cases of obstructive ureteral stones is both safe and effective and offers the advantages of immediate stone fragmentation and the relief of acute - onset colic pain .

the achilles tendon attaches the plantaris , gastrocnemius , and soleus muscles to the heel1 . excessive stress or tight or fatigued gastrocnemius and soleus muscles can result in microtrauma , degeneration , or inflammation of the tendon a condition called achilles tendonitis / tendinosis1 . this condition can occur in the general population2 and is exacerbated by prolonged walking , excessive running , jumping , or walking hills . mountaineering and mountain - related activities are associated with significant risk of injury in the ankle joint and achilles tendon3 . the nomenclature for disorders of the achilles tendon is important , as the treatment is dependent on the underlying tendon pathology4 achilles tendon conditions such as tendinosis are often chronic and non - inflammatory , although the area can be painful to touch . based on the etiology , achilles tendinosis can be caused by a combination of factors such as failure of the normal healing mechanisms and repeated trauma5 . the achilles tendon serves to attach the plantaris , gastrocnemius , and soleus muscles to the calcaneus ( heel ) bone1.this study developed heel support banding ( hsb ) using an elastic band for flexible heel support and investigated its effect on chronic achilles tendon pain of a mountaineer . a 40-year - old male mountaineer with chronic achilles tendon pain participated in this study . the purpose and methods of the study were explained to the participant and informed consent was obtained according to the principles of the declaration of helsinki . the patient complained of chronic pain in the achilles tendon of the right leg . he developed severe pain during active plantar flexion and palpation of the pre - insertion area of the achilles tendon after mountain climbing , which he does three times per week . active dorsiflexion and active plantar flexion , measured with a goniometer , were 13 ( population normal angle , 20 ) and 28 ( population normal angle , 45 ) , respectively , due to pain . the visa - a questionnaire is a reliable and valid instrument for the evaluation of pain intensity and levels of function in patients with achilles tendon disorders . the visa - a questionnaire score was 56 ( normal population range > 95 ) , and the load - induced pain , assessed on a numeric rating scale from 0 to 10 , was 7 . the pressure - pain threshold , assessed with an algometer ( pain test - model fpk ; wagner instruments , greenwich , ct ) , was 2.0 kg . rompe et al.6 defined tenderness using a numeric rating scale following the application of 3 kg of pressure to the most tender area of the achilles tendon . the tenderness at 3 kg , assessed on a numeric rating scale from 0 to 10 , was 8 . hsb is an elastic band ( about 250 cm long ) , divided into four sections with the center piece binding together to form a figure x. to apply the band , the center of the band was placed above the knee approximately 5 cm from the patella . second , the other two pieces were placed longitudinally along the lower leg , while the third section of the band wraps around the lower leg , approximately 5 to 7 cm below the knee , and was bound to itself laterally . the third and fourth pieces of the band crossed each other at half of the distance between the foot and patella . finally , these pieces of the band were placed around the foot and support the heel and foot arch . an elastic band of proper strength for the patient was selected by a therapist for maximum support of the heel and foot arch . the range of elastic bands includes black , silver , blue , green , red , and yellow . the patient in the study applied a level silver band prior to mountain climbing and proceeded to climb three times a week for one month . after one month of applying the hsb , the dorsiflexion and plantar flexion angles increased to 18 and 37 , respectively , compared to the initial 13 and 28. the visa - a questionnaire score increased to 79 compared to the initial 56 . the load - induced pain assessment decreased to 4 compared to the initial 7 . the pain threshold increased to 5.2 kg compared to the initial 2.0 kg and tenderness at 3 kg , assessed on a numeric rating scale , decreased to 3 compared to the initial 8 . the function of this musculotendinous unit is to serve as the chief plantar flexor of the ankle joint during walking and running , providing the primary dynamic force for locomotion and jumping5 , 7 . based on the etiology , the achilles tendinosis was caused by a combination of failure of the normal healing mechanisms and repeated trauma5 . the severe pain may have occurred gradually as repetitive microtrauma was imposed on the achilles tendon . for this , this study developed hsb using an elastic band and investigated its effect on chronic achilles tendon pain of a mountaineer . the result showed that after one month after applying hsb , the dorsiflexion and plantar flexion angles increased , the visa - a questionnaire increased , the load - induced pain assessment decreased , the pain threshold increased and tenderness at 3 kg , assessed on a numeric rating scale , decreased . the tension of hsb created by increased stimulation during active ankle movement may have also created tension in the soft tissue structures . increased tension may facilitate a pain inhibitory mechanism by providing an afferent stimulus to large - diameter nerve fibers to mitigate nociception . as the patient s pain level reduced , the fear of pain during ankle movement might have reduced by proper sensory feedback , thus improving ankle range of motion . a thera - band , which provides varied resistance through the range of movement , has been used for rehabilitation in combination with therapeutic exercise8 . it is light and portable , has low resistance , and can be adjusted to accommodate various situations9 . in conclusion , one month of hsb for flexible heel support improved range of motion in the ankle and reduced pain . therefore , the hsb could provide a new approach for effective intervention and management of chronic achilles tendon pain .

[ purpose ] this study developed heel support banding ( hsb ) using an elastic band for flexible heel support and investigated its effect on chronic achilles tendon pain of a mountaineer . [ subject ] a 40-year - old male mountaineer with chronic achilles tendon pain [ methods ] ankle dorsiflexion and plantar flexion angles , visa - a questionnaire , load - induced pain , total pain threshold and tenderness at 3 kg of pressure were measured before and after applying hsb . [ results ] after one month of applying hsb , the dorsiflexion and plantar flexion angles increased ; the visa - a questionnaire score increased ; the load - induced pain assessment score decreased ; the pain threshold increased ; and tenderness at 3 kg decreased . [ conclusion ] these results indicate that hsb use improves ankle range of motion , decreases pressure and pain , and could provide a new approach for effective intervention and management of chronic achilles tendon pain .

the clinical presentation of these patients is varied , ranging from headache and focal neurological deficits to personality changes and/or mental deterioration , including memory loss , inattention , confusion , hallucination , and hyperphagia . as a result , these patients are often confused with encephalitis and its sequel , as happened in our patient . the role of surgery is limited , owing to the architectural complexity and depth of location of the lesion . an 8-year - old patient was referred to the pediatric emergency services with complaints of moderate- to high - grade fever for 10 days , 2 months back . on 5 day of fever , the patient developed choreoathetoid movements on right side of the body , which was more severe in the upper limb . few days later , he developed progressive loss of ambulation , cognition , and speech . on examination , he was in a state of altered consciousness ( e2v2m5 ) . however , his vitals were stable . the neurological assessment revealed , increased tone in all four limbs , with exaggerated deep tendon reflexes and bilateral extensor plantar reflex . fundoscopy revealed mild papilledema , pupils were of normal size and reacting to light . his complete hematological profile and serum chemistries were unremarkable . noncontrast computed tomography ( ct ) of the head revealed a bilateral thalamic iso- to hyperdense lesion with moderate hydrocephalus [ figure 1 ] . the mr examination of the brain showed significant swelling of thalamus with diffuse hypointense signal on t1-weighted ( t1w ) imaging and hyperintense signal on t2 and fluid - attenuated inversion recovery ( flair ) sequences [ figure 2 ] . hypointense signals on t1 and hyperintense signal changes on t2w and flair were also present in the basal ganglia , head of the caudate nuclei , and upper brainstem . findings were considered nonspecific and diagnosis of encephalitis was considered , however , bilateral thalamic glioma was the second possibility . noncontrast computed tomography of head reveals bilateral iso- to hyperdense thalamic masses with hydrocephalus and periventricular ooze t2-weighted magnetic resonance imaging reveals bilateral hyperintense thalamic masses with focal hypointensities t1-weighted axial post - contrast image reveals mild peripheral enhancement patient was managed on the lines of encephalitis and its sequelae . he was started on antiepileptic drugs and decongestants to decrease raised intracranial pressure and a low pressure ventricular shunt was inserted . histopathological examination of the biopsy specimen revealed a highly cellular tumor with foci of palisading necrosis [ figure 4a ] and microvascular proliferation [ figure 4b ] . the tumor cells showed marked nuclear pleomorphism and frequent mitotic figures [ figure 4b ] , including atypical forms . on immunohistochemistry , the tumor cells were immunopositive for p53 [ figure 4c ] and were negative for epidermal growth factor receptor ( egfr ) . mib - i labeling index was approximately 60% in the highest proliferating areas [ figure 4d ] . based on these features , a diagnosis of glioblastoma multiforme , world health organization ( who ) grade iv , was arrived at . photomicrographs showing ( a ) a highly cellular tumor with foci of palisading necrosis ( hematoxylin and eosin ( h and e ) , original magnification 400 ) and ( b ) microvascular proliferation ( h and e , original magnification 400 ) . ( b ) the tumor cells display marked nuclear pleomorphism and frequent mitotic figures ( h and e , original magnification 400 ) . ( c ) immunohistochemistry for p53 showed nuclear positivity ( immunohistochemistry ( ihc ) , original magnification 400 ) . ( d ) mib - i labeling index is 60% ( ihc , original magnification 400 ) tracheostomy was done in view of poor glasgow coma scale ( gcs ) considering the need of prolonged ventilatory support . although thalamic tumors constitute between 2 and 5% of all the pediatric intracranial tumors , it is only 1% in adult series . bilateral pediatric thalamic glioblastomas are extremely rare and only five cases are published in the english literature . the largest series on pure thalamic tumors to date is from the necker enfants malades hospital , paris , which reported 69 children treated over a 14-year period . lesions in the ventrolateral thalamus typically manifest with motor deficits , given their close proximity to the internal capsule . the visual signs and symptoms are present in as many as 50% of these patients and are due to involvement of the optic tracts and the lateral geniculate body . the oculomotor deficits are due to involvement of the retrolenticular segment of the internal capsule or the midbrain tegmentum . involvement of the mammillothalamic tracts or the fornices can lead to cognitive dysfunction and memory problems . bilateral thalamic lesions are associated with changes in personality , memory deficits , confusion , hallucinations , hyperphagia , and bradyphrenia . diffuse and bilateral involvement of thalamic nuclei by these tumors makes the surgical therapy very difficult . the role of surgery , hence , is limited and is performed for histological diagnosis as was done in our patient . the role of chemotherapy and radiotherapy is of questionable significance and are utilized as adjuvant therapies . bilateral thalamic tumors are typically treated with radiation therapy , regardless of whether they are histologically malignant . for bilateral thalamic tumors , the prognosis remains relatively poor regardless of tumor histology and treatment . in our patient , left thalamic tumor was biopsied under magnetic resonance imaging ( mri ) guidance . , documented p53 protein accumulation in 75% of high - grade childhood gliomas , and p53 mutation in 38% . pollack et al . , documented increased expression of p53 in about 35% of high - grade gliomas in children , which increased to 58% when only glioblastomas were considered . the authors determined that this feature was an adverse prognostic factor in a cohort of children who were treated uniformly with surgery , radiotherapy , and chemotherapy . on the other hand , egfr amplification is much less common in pediatric glioblastomas compared to adult primary glioblastomas and the reports on egfr protein expression have been quite varied . , who found only very small foci of tumor cells showing egfr immunopositivity in four of 13 glioblastomas . thalamic lesions continue to be a challenging entity to the neurosurgeons , particularly owing to their deep location and complex circuitry . unilateral tumors are increasingly being tackled by the neurosurgeons with an improved patient outcome . however , bilateral thalamic glioblastomas have a very poor prognosis , irrespective of the modality of treatment .

bilateral thalamic tumors are rare . pediatric bilateral thalamic glioblastomas are even rarer , only five cases reported in the english literature till date . the clinical presentation , natural history , and prognosis of pediatric thalamic tumors are still relatively obscure . in this article , we report an 8-year - old patient with large bilateral thalamic glioblastomas and briefly discuss its clinical presentation , possible modalities of management , and prognosis , in the light of available literature .

across a very broad taxonomic range animals frequently respond differentially to close kin , even if those kin were previously unfamiliar . logically , this differentiation between individuals according to kinship requires well - defined mechanisms to allow recognition . and whereas animals may learn the cues of familiar individual kin during rearing , recognition of unfamiliar kin must really be recognition of genetic similarity - either to self or to other known kin . a challenge in this area lies in discovering the cues that animals use for genetic recognition of kin , and the genetic encoding of such cues . in many vertebrates , odors are key to the recognition process , and have been widely implicated as cues that allow genetic kin recognition in many species of fish , reptiles and mammals ( figure 1 ) . however , vertebrate scents are generally complex , and there have been few attempts to identify the specific scent components used in kin recognition or their genetic basis . in work published recently in bmc evolutionary biology , boulet and colleagues have advanced this field by demonstrating a significant correlation between genetic similarity ( estimated from 11 - 14 microsatellite loci ) in a captive population of ring - tailed lemurs ( lemur catta ) and similarity of volatile chemicals in their genital gland secretions , as assessed by gas - chromatography mass - spectrometry . the genetic similarity of two individuals is thus manifest in the odor profile ( sometimes referred to as an ' odortype ' ) . even more intriguing , although the genital glands of the two sexes are anatomically distinct ( scrotal glands in the male , labial glands in the female ) , this covariance between genetic and chemical similarity is evident even between individuals of the opposite sex . while some components are expressed only by animals of one sex , more than half ( about 170 ) were expressed by individuals of both sexes . to provide a simple estimate of chemical distance between a pair of individuals , boulet et al . used the relative abundance of each of these shared compounds to calculate the euclidean distance between the pair ( derived from the pythagorean theorem , this sums the pairwise difference , , in abundance of all 170 compounds , such that chemical distance = sqrt(1 + 2 + 3 + .... 170 ) . while there was a broad spread of chemical distances between male - female dyads that had intermediate genetic distance , dyads with low genetic similarity had low chemical similarity whereas those with a high genetic similarity had a higher chemical similarity . this relationship is consistent with the hypothesis that odors from genital secretions can be used to assess genetic relatedness , and maybe close kinship . of particular interest , these relationships were significant both within and between the sexes during the breeding season , but were much weaker or nonsignificant during the non - breeding season . odortype may be particularly important during the competitive breeding season to prevent inbreeding and/or to direct nepotistic behavior towards more closely related individuals . however , this study is still only a first step in establishing whether such odor signals could offer a reliable means of recognizing kinship among ring - tailed lemurs and the genetic basis of the cues used . if lemurs used a measure of chemical distance based on all volatile compounds that are shared within or between the sexes , it would only be of very limited value in assessing kinship because of the considerable range in that measure between individuals of intermediate genetic relatedness . although very closely related animals have similar odortypes , so do many individuals that are much less closely related . if odortype were used to avoid inbreeding , for example , the consequence would be exclusion as mates of many individuals that are not closely related , reducing choice without gaining any genetic benefit . it is likely , therefore , that animals use more specific markers within the odortype to distinguish close relatives reliably ( figure 2 ) . chemical distance between pairs of animals based on all volatile compounds in a scent correlates with genetic distance ( a ) , but variance will be high for any particular genetic distance because some compounds are likely to be strongly influenced by non - genetic factors such as current hormone levels and bacterial flora . instead , selective assessment of specific semiochemicals within the scent that correlate strongly with genotype ( b ) will provide a much more reliable assessment of kinship . there has been surprisingly little progress in establishing the genetic and molecular markers used to recognize kin through scents in vertebrates . in part , this may be due to the molecular complexity of vertebrate scents , which are the product not only of an individual 's genes but also of hormonal and metabolic status , diet and microflora . for the past 30 years , the focus on genetic mechanisms underlying vertebrate kin recognition through odors has been on the major histocompatibility complex ( mhc ) , which is often held to be the major genetic component apparently determining an individual 's scent . inbred laboratory mice have been a key model organism for manipulating mhc genes on a constant genetic background as proof that animals can detect mhc type through scent . as mhc is so highly polymorphic in natural populations , those that share the same mhc type ( and mhc - based scent ) are very likely to be closely related - mhc odors could be used as a marker of genetic relatedness . yet , despite the precise genetic control offered by laboratory rodent strains , chemical analyses of volatile profiles have found correlations of some volatile components with mhc type but have not yet discovered consistent differences in compounds that are regulated by mhc type [ 3 - 6 ] . in reality , complex interactions are found with genetic background , microflora and diet , all of which alter the odor profile [ 3,5 - 7 ] . this plasticity of mhc - derived odortype creates a conundrum . to be useful in natural populations , kin markers must be stable and readily recognized against the variable genetic and environmental background of normal outbred animals . our own studies of wild - derived mice with normal genetic variation in semi - natural populations provided clear evidence that wild mice do not use mhc to avoid inbreeding . in fact , mice showed a very strong avoidance of inbreeding with those sharing another very highly polymorphic marker in mouse scent , the major urinary proteins ( mups ) , which have a strong influence on an individual 's scent profile regardless of other genetic and non - genetic variation . sharing of a single highly polymorphic marker , like mup or mhc type , can provide a reliable indicator of relatedness because only close relatives are likely to inherit both of the same alleles at a particular locus ( or both of the same haplotypes in the case of clusters of closely linked genes like mup or mhc ) . however , this type of mechanism can only be partially effective for kin recognition . for any single locus , the number of alleles shared between two relatives is a matter of chance ; even very close relatives such as full siblings are as likely to share no alleles as they are to share both alleles at a particular locus . modeling alternative genetic mechanisms that could be used to discriminate full sibs from unrelated animals reveals that reliance on a single genetic locus will either fail to identify many relatives ( if the requirement is that both alleles are shared ) or will mistake many unrelated animals as sibs ( if sharing of any allele is used ) . notwithstanding the theory , house mice do use sharing of mup type , encoded by a single tightly linked cluster of genes , to avoid inbreeding . this may be specific to house mice - there are insufficient data to assess whether such simple recognition systems are widespread . an alternative model is that instead of directly comparing the similarity of scents to self , imprinting on maternal scent encoded by several independent loci is employed to provide reliable recognition of all siblings and maternal half - sibs , because all offspring share with their mother one allele at every locus . laboratory cross - fostering studies in which newborn mouse pups were fostered onto a mother of different mhc type to their own have suggested that animals might imprint on the genotype of their mother and subsequently avoid ' inbreeding ' with those sharing the foster mother 's genotype rather than avoiding mates that match their own mhc type . however , maternal imprinting does not require recognition of the mother 's genotype for kin recognition ; instead animals must be able to recognize the separate haplotypes carried by the mother when these are combined with other unknown haplotypes . this recognition task is likely to be considerably more difficult given the complex effects that mhc type has on odors , particularly as the odors of mhc heterozygotes are not an additive combination of the two homozygous profiles . a key test would be whether mice ( or other animals ) can recognize the separate mhc haplotypes carried by a heterozygous animal when combined with other mhc haplotypes ( for example , animals imprinted on the mhchaplotype must be able to recognize mhcor mhc ) ; they also need to be able to do this on the randomly assorting genetic background of outbred animals . a recent study using inbred laboratory mice found that animals recognized non - genetic similarities in offspring from the same mother compared to those from another genetically identical female due to their shared maternal ( in utero and postnatal ) environment . the approach of relating genetic similarity to the global volatile profile of scent glands is a step towards the systems biology of complex behaviors . indeed , the application of global profiling methodologies to scents could be said to introduce the concept ( but preferably not the term ! ) of ' semiomics ' . as with many studies of this nature , the analyte mixtures are complex , and a major challenge is in unbundling the important semiochemicals from the entire volatile profile - although boulet and colleagues refer to a ' semiochemical profile ' , it is likely that many of the constituent compounds will be ' silent ' in kin recognition . an attractive way forward is to use the combined datasets to identify those chemicals that show the greatest correlation with relatedness , focusing on differences in relatedness that can be discriminated behaviorally . the candidates can be examined in ' kin - shifting ' experiments such that when they are spiked into a distant sample , they elicit a response more ' akin ' to a close relative . indeed , similar experiments could be conducted using humans to establish the extent to which we too can discriminate our own kin based on genetically determined scents . the development of these ideas was supported by research grants from bbsrc ( s19816 , bbc603897 ) and nerc ( neg018650 ) .

a recent study in bmc evolutionary biology has shown that genetically similar individual ring - tailed lemurs are also more similar in their scent composition , suggesting a possible mechanism of kin recognition . theoretical and experimental studies reveal challenges ahead in achieving a true systems - level understanding of this process and its outcomes.see research article http://www.biomedcentral.com/1471-2148/9/281 .

lymphoid neoplasms of the conjunctiva may appear as an isolated tumor or as part of systemic disease.15 generally , conjunctival lymphoma presents as a mass lesion on the superficial ocular surface . these lymphomas are classically described as salmon - colored patches , and may present bilaterally in up to 20% of patients.4,5 lesions have a fleshy appearance and may develop rapidly . b cell lymphoma is the most common type of conjunctival lymphoma , whereas the t cell form is very rare.25 in this report , we document the clinical and histopathological findings in a patient with conjunctival lymphoma that was the first presentation of systemic malignant lymphomatous t cell proliferation . on march 15 , 2006 , a 67-year - old male patient came to our attention complaining of pain and hyperemia in his left eye . anterior segment slit - lamp biomicroscopy of the left eye showed a pink - yellow colored mass infiltrating the bulbar conjunctiva in the lower fornix of the eyelid and a corneal ulcer at the 9 oclock position with perilimbal congestion and chemosis ( figure 1a and b ) . the left eye was treated with topical steroid / antibiotic medication with an ocular bandage for one week . a control visit showed disappearance of corneal ulcer , and a diagnostic punch biopsy of the conjunctival mass was taken for immunohistochemical examination . the conjunctiva was infiltrated by a diffuse proliferation of small- to medium - sized lymphoid cells which were partly necrotic . focal effacement of the serous glands of the conjunctiva was observed ( figure 2 ) . the neoplastic cells were homogeneously cd3 + , cd5 , cd20 , and cd43(mt1)+/. a high proliferation rate reaching 80% of the neoplastic population was observed , as detected by ki67/mib1 immunoreactivity ( figure 3a and b ) . over the next two weeks slit - lamp biomicroscopy revealed was followed carefully by the oncology service for staging that was classified as ivb . he was receiving a regimen of chemotherapy comprising cyclophosphamide 750 mg / mq , epidoxorubicin 50 mg / mq , vincristine 1.4 mg / mq , and prednisone 50 mg / mq on days 1 and 5 . simultaneously , the patient underwent locoregional radiotherapy with a total of 20 gy to the retro - orbital region . ocular involvement of t cell lymphoma may include orbital , conjunctival , eyelid , uveal , and vitreous localization.1 malignant ocular t cell lymphoma can be associated with systemic involvement.25 despite a typical appearance , the differential diagnosis includes scleritis and several other benign tumors of the ocular surface , including squamous papilloma , pyogenic granuloma , and lymphangiectasis.4 there are two important aspects concerning this case report . firstly , the initial manifestation of this tumor was at the lower fornix of the left conjunctiva that was easy accessible to diagnostic punch biopsy , which enabled early diagnosis of t cell lymphoma . secondly , general examination showed systemic involvement with ethmoidal , maxillary and sphenoidal sinus masses , and pancreatic infiltration . lymphoid tumors of the conjunctiva are associated with systemic lymphoma in about 31% of patients.4 they may not be symptomatic for many months or years.15 in this case , we could not identify the primary site of the lymphoid tumor because ocular involvement was found to be associated with extraocular systemic lymphomatous proliferation . t cell lymphoma of the conjunctiva as a primary manifestation of systemic cancer is an extremely rare entity . punch conjunctival biopsy may be the first diagnostic pathway useful to initiate a search for systemic involvement of a malignant lymphoid tumor of the t cell variety .

this report documents a case of t cell lymphoma manifesting only with a conjunctival mass . a 67-year - old man underwent a diagnostic punch biopsy , histopathological examination , and immunohistochemical study for a pink - yellow colored mass infiltrating the bulbar conjunctiva in the lower fornix of the eyelid . a biopsy specimen of the conjunctival mass was found histopathologically to be a malignant t cell lymphoma . systemic involvement was diagnosed within four weeks after the initial diagnosis by computed tomography , showing evidence of extension at the level of the ethmoidal cells , optic nerve , periorbital tissue , and pancreas . t cell lymphoma of the conjunctiva as a primary manifestation of systemic cancer is an uncommon entity . punch biopsy may be the first diagnostic pathway useful to initiate a search for systemic involvement of a malignant lymphoid tumor of t cell lineage .

pemphigus vulgaris ( pv ) is a chronic autoimmune mucocutaneous disease that usually manifests first in the oral cavity and may later spread to the skin or other mucous membranes . apart from ulcers , vesicles , bullae and pustular lesions , it can present solely as mucosal erosions . herein we report a case of intraoral pv presenting as intense erythema and erosions involving the gingiva . a 52-year - old female presented to the department of periodontics , al - badar dental college and hospital , gulbarga with complaints of bright red gingivae and discomfort in her normal oral function . the site most severely affected was her upper front buccal gingivae . the considerable pain and discomfort that the patient felt hindered her from carrying out effective oral hygiene measures and this in turn exacerbated the gingival symptoms . she had essential hypertension , diabetes mellitus and hyperlipidemia and her daily medications included insulin , antihypertensive drugs and statins . on intraoral examination , there were multiple large irregular erosions and areas of intense erythema involving particularly the gingivae of both upper and lower arch , buccally and palatally / lingually [ figures 1 and 2 ] . orthopentamogram showed a combination of horizontal and vertical bone loss . the nikolky 's sign ( loss of epithelium occasioned by rubbing apparently unaffected skin ) that is a feature of pv was positive . the patient had no cutaneous involvement and other mucosal sites such as conjunctiva , nasal passages and oesophagus were free of lesions . intensely erythematous gingivae with multiple erosions erosive lesions on the gingiva palatally based on the history , multiple erosions and the apparent fragility of the gingivae experienced during examination , a vesiculobullous disorder was suspected . is usually seen in the elderly , the former was thought to be more likely . the other common conditions that can present with similar manifestations are oral lichen planus , drug hypersensitivity or idiopathic . histopathological examination revealed suprabasal blister formation associated with extensive acantholysis of keratinocytes , suggestive of pv [ figure 3 ] . photomicrograph showing suprabasilar split and acantholytic cells since the patient only had isolated gingival involvement , she was started on systemic corticosteroids ( prednisolone 0.5 mg / kg / day ) . this initial dose was stepped up to 1mg / kg / day , which gave marked improvement in two weeks . the patient was instructed to apply twice daily topical steroid oral paste ( triamcinolone acetonide 0.1% ) along with local anesthetic gel . sometime after commencement of corticosteroid therapy , scaling and root planing was performed . over the past 1 year currently , the patient is on this daily low - dose systemic corticosteroid therapy ( prednisolone ) , topical steroid oral paste ( triamcinolone acetonide 0.1% ) and supplementary medications . till date , no other sites are involved . pemphigus is a group of potentially life - threatening autoimmune mucocutaneous diseases characterized by epithelial blistering affecting cuteneous and/or mucosal surfaces , the term being derived from the greek word pemphix ( bubble or blister ) . although vulgaris means common in latin , the worldwide incidence of pv is low and has been reported to be 0.10.5 per 100,000 persons per year . pv is the most common variant of pemphigus , comprising of 80% of the disease entity . pv frequently involves the mouth and has a fairly strong genetic background ; ethnic groups such as ashkenazi jews and people of mediterranean and indian origin are particularly susceptible and there is a link to hla class ii alleles . clinically , pv appears to occur in males and females in an equal ratio , and is most frequently reported in patients between the fourth and sixth decades of life . mortality from pv before the development of effective therapies was as high as 90% , mainly due to dehydration and secondary systemic infection . oral lesions are common and early manifestations of pv , seen typically in adults ( rarely in childhood ) . one recent multicenter study in several countries showed that bulgarian patients less frequently had oral mucous membrane lesions ( 66% ) compared with italian ( 83% ) and israeli ( 92% ) patients . initially vesiculobullous , the oral lesions readily rupture and as the older ones rupture and ulcerate , new bullae develop . gingival lesions are less common and usually comprise severe desquamative or erosive gingivitis , characterized by red erosions or deep ulcerative craters . in the present case , gingiva was the only site involved ; the gingiva was intensely erythematous and erosive involving both attached and marginal gingiva . however , the patient 's oral hygiene was very poor and this in turn contributed further to gingival inflammation , leading to generalized periodontitis . the classic signs of oral or gingival pv are multiple erosions or desquamation and a positive nikolsky sign which both of which were present in our case . histologically , there is an intraepithelial blister associated with acantholytic cells , features which were evident in this patient . systemic corticosteroids are the treatment of choice in patients with pv ; topical steroid therapy alone is insufficient for sustained control of the disease because of the systemic autoimmune nature of pv . in the present case , systemic and topical corticosteroid treatment and adjuvant therapy of antifungal mouthwash , use of soft brush and vitamin supplementation were instituted . pv is a chronic autoimmune mucocutaneous disease that often primarily involves the oral cavity . as it is a life - threatening disease condition , it is important for the clinician to be able to recognize oral manifestations of pv at an early stage and treat or refer appropriately . dental professionals can thus play an important and significant role in the early diagnosis and management of pv .

pemphigus vulgaris ( pv ) is an autoimmune blistering disease affecting the mucous membrane and skin . typically , oral lesions appear before skin lesions , and in a majority of the cases only oral lesions are present . the dentist may then be the first to recognize and diagnose this disease . it is unusual for pv to present over the gingiva as a primary site of involvement . diagnosis is based on clinical presentation and confirmed by histopathological study . early diagnosis and management can prevent the uneven life- threatening effects of this potentially chronic mucocutaneous disorder . the case serves to enhance our awareness of the gingiva as a site at which systemic disease can manifest itself .

blood samples were obtained from 66 of the 67 factory workers , including the administrative employees . serologic testing was carried out at 2 time points ( december 2006 and december 2007 ) by using a commercial elisa ( serion , wrzburg , germany ) based on plates coated with purified anthrax protective antigen ( pa ) ( technical appendix ) . the first year , 3 workers had immunoglobulin ( ig ) g titers above the threshold recommended by the manufacturer for vaccine protection ( > 15 iu / ml ) , and titers for another worker were considered borderline ( 1015 iu / ml ) . all 4 workers had positive results by western blot or dot blot analysis with pure recombinant anthrax pa and lethal factor ( lf ) . the second round of testing gave similar results , except for 3 additional borderline cases which could also be confirmed by western blot / dot blot analysis ( table ) . lymphocyte proliferation assays were performed concurrently by using fresh , heparinized , whole blood samples to evaluate the cell - mediated immunity of the workers ( 9 ) . this technique measures the ability of lymphocytes placed in short - term tissue culture to undergo clonal proliferation when stimulated in vitro by a foreign antigen . cell proliferation was determined by measuring the incorporation of h - thymidine into chromosomal dna . the release of interferon - gamma ( ifn- ) in the course of lymphocyte stimulation was also measured to assess antigen - specific , cell - mediated reactivity . the antigens used here were pure recombinant pa and lf , along with positive control ( concanavalin a ) and negative control ( phosphate buffer ) stimulants . of these 2 cultures , 1 reacted with pa and lf , and 1 reacted with pa only . when added together , pa and lf suppressed the proliferative effect of the individual antigens , consecutive to the probable cytotoxicity induced by the 2 assembled antigens ( porin + toxin ) . the lymphocyte cultures found to be responsive to pure anthrax antigens originated from workers who had little circulating anti - pa igg ( < 15 iu / ml ) , as tested by elisa ( figure 2 ) . however , their serum tested positive by western blot analysis ( table ) . moreover , supernatants of pa - stimulated lymphocyte cultures derived from the blood of these workers with positive results by determining counts per minute , were confirmed by ifn- release assay . * pa , protective antigen ; lt , lymphocyte ; ag , antigen ; lf , lethal factor ; cona , concanavalin a. performed on serum samples according to the manufacturer s instructions and thresholds ( serion , wrzburg , germany ) . note : 1 worker who tested positive at year 1 was not enrolled at year 2 , and 3 workers tested negative at year 1 seroconverted to borderline at year 2 . conducted only on serum samples found positive or borderline by anti - pa elisa together with negative controls ( n = 25 ) . dot blots were spotted with 1,000 , 100 , 10 , and 1 ng of each purified pa and lf ag purchased from quadratech ltd . western blot antigens consisted in supernatant proteins derived from the culture of a reference b. anthracis strain . assayed on blood samples from year 2 as described earlier ( 9 ) by using a proliferative index threshold set to 3 the index of a negative control stimulant ( phosphate buffer ) . stimulating ag was used at a final concentration of 4 mg / ml ( pa , lf , cona ) . lymphocyte cultures found activatable by pa were confirmed by quantifying ifn- release by elisa , according to the manufacturer s instructions ( pierce , rockford , il , usa ) . serum samples from these workers tested positive by both western blot and dot blot analysis . proliferation was assayed by measuring h - thymidine incorporation ( counts per minute [ cpm ] ) of culture lymphocytes stimulated with different antigens and by determining the respective proliferative indexes . the latter were calculated by dividing the cpm induced by a given antigen by the cpm induced by a negative control antigen ( phosphate - buffered saline ( pbs ) , white boxes ) . the proliferative index is a parameter that reflects the reactivity of a lymphocyte culture toward a given antigen . the figure shows 3 representative culture profiles that react either with protective antigen ( pa ) and lethal factor ( lf ) ( 1 sample , t2 ) , with pa only ( 1 sample , t9 ) , or with none of them ( 41 samples , exemplified by t56 ) . each value is the mean of 3 independent experiments and is shown with the standard deviation ( error bar ) . cona , concanavalin a. graph showing anti protective antigen ( pa ) immunoglobulin g ( igg ) titers plotted against h - thymidine counts per minute ( cpm ) derived from pa - stimulated blood cell cultures conducted in year 2 . the vertical lines define the elisa borderline and upper thresholds ( 10 iu / ml and 15 iu / ml , respectively ) , which were defined as pa titers by the elisa kit manufacturer , i.e. , titers supposed to confer protection after vaccination . samples testing below the borderline threshold are considered negative . t29 and t2 refer to workers whose samples had a remarkably high antibody titer or lymphocyte proliferation count , respectively . although some progress made in improving the biologic safety of the industrial processing of wool and goat hair ( for example , systematic disinfection , air filtering , and protective gear for employees working in closed areas ) , this study shows that b. anthracis still poses a health risk to modern wool workers . handling nondisinfected , raw animal fibers from areas where anthrax is endemic , such as the southern caucasus region and the middle east , has been and remains an at - risk activity . the presence of circulating antibodies and t lymphocytes that react with antigens expressed only by vegetative cells of b. anthracis in unvaccinated wool workers confirms several previous findings . first , these findings support the conclusions that anthrax spores are able to germinate into vegetative cells at the sites of exposure ( skin , mucosa , respiratory tract ) and cause asymptomatic infection ( 10,11 ) . second , the extent to which the human immune system responds to exposure to anthrax spores from the surrounding environment as well as the nature of this response varies tremendously from person to person . results from 1 worker ( t29 ) displayed a high igg titer ( > 100 u / ml ) but little or no cell - mediated reactivity . results from the other worker ( t2 ) showed significant lymphocyte reactivity ( h - thymidine counts > 700 counts per minute , which corresponds to a proliferative index of 6 , p>0.01 ) , but a low igg titer ( figure 2 ) , which reflects reciprocal t- and b - cell responses . none of the persons whose samples tested positive by elisa reported a past episode of anthrax ( according to face - to - face interviews conducted when blood was sampled ) . hence , their seroconversion most likely resulted from asymptomatic b. anthracis infection . one worker reported having had a skin lesion possibly compatible with cutaneous anthrax 4 years before the study . that worker s samples tested positive by lymphocyte proliferation assay , western blot , and dot blot , but not by anti - pa elisa . notably , samples from many workers from the same factory , who had been exposed to goat hair for years in similar conditions , did not display positive serologic results when tested by elisa . during our study , however , we noticed that serum samples from 3 workers had seroconverted from negative to partially protective ( borderline ) igg titers at some point between the 2 blood samplings as determined by anti - pa elisa . given the long history of these workers at the company , the apparent lack of anti - pa antibodies at the first blood sampling may have been misestimated due to the high threshold defined for seropositivity by the commercial elisa used in the study . this commercial kit is indeed primarily aimed at evaluating the efficacy of anthrax vaccination rather than at detecting antibody responses after exposure to subinfectious doses of anthrax spores ( 12 ) . accordingly , we noticed that of the 3 workers who seroconverted , 2 tested positive by western blot , and 1 tested positive by dot blot when tested retrospectively at year 1 . blotting techniques seem thus more sensitive than the presently used elisa seropositivity threshold for detecting low anti - pa antibody titers . the low sensitivity of the method used in this work to assess cell - mediated immunity ( whole blood proliferation assay ) may have also underestimated the actual number of workers who exhibited cell - mediated immunity against b. anthracis , and the results should be regarded as indicative rather than representative . pa - based anthrax vaccines are available to protect professionally exposed people , such as the us anthrax vaccine adsorbed or the uk anthrax vaccine . these vaccines are efficient and elicit humoral responses that protect the vaccinees against toxin - associated death ( 13 ) . they do require long clinical protocols and yearly boosters ( 14 ) and are not officially licensed in european union member states ( except the united kingdom ) . according to some authors , these vaccines might not protect wool - workers efficiently against subclinical infection , spore germination , or bacteremia ( 13,15 ) . anthrax vaccines that confer long - term immunity of both the humoral and cellular type are not yet available for the general public . vaccines with such characteristics would be highly desirable to better protect persons who work with animal products that are possibly contaminated with anthrax spores .

to determine immunologic reactivity to bacillus anthrax antigens , we conducted serologic testing of workers in a factory that performed scouring of wool and goat hair . of 66 workers , 10% had circulating antibodies or t lymphocytes that reacted with anthrax protective antigen . individual immunity varied from undetectable to high .

vitiligo can progress in some patients with or without medical treatment to involve a major part of the body surface area . depigmentation is the only treatment option possible in such patients who develop vitiligo on more than 90% body surface area , for which the term the residual pigmentation , seen in these patients , causes a lot of disfigurement as the sites most commonly involved are the face and other exposed parts of the body . moreover , this residual pigment tends to come again and again with the approach of summer months even after successful depigmentation therapy . the first - line treatment options used for depigmentation treatment in universal vitiligo include topical treatment with monobenzyl ether of hydroquinone ( mbeh),[57 ] phenol peels , cryotherapy , and lasers.[1214 ] topical treatments used for this indication are associated with certain limitations like local irritation of the skin , incomplete depigmentation and most importantly , a really long time to achieve a clinical response . in usual cases , it takes about 1 year for the topical treatment to act in this condition . lasers overcome many of these limitations as they are much more rapidly acting , relatively safer and usually do not require months of treatment . in addition , they have also been shown to help those patients who do not respond to topical treatments alone . lasers are claimed to be more effective in those vitiligo patients who show a positive koebner s phenomenon . for a patient who requires treatment of a cosmetically important area like the face urgently lasers that have been used for depigmentation therapy in vitiligo till date include the q - switched ruby laser and q - switched alexandrite laser.[1214 ] q - switched ruby laser uses a wavelength of 694 nm at nanosecond pulses to destroy the melanocytes present in the pigmented areas . a larger area can be treated in a single session and the treatment can be combined with topical mbeh treatment to accelerate the depigmenting process . q - switched alexandrite laser , which uses a wavelength of 755 nm , has also been reported to be useful in treating the residual pigmentation present in vitiligo . for treating pigmented lesions , q - switched nd : yag laser is the one that is most commonly used in india.[1517 ] the popularity of this laser system in india is because of its safer wavelength at 1064 nm as it is less likely to cause a postinflammatory pigmentation in dark skin . q - switched nd : yag laser can deliver energy at two different wavelengths of 1064 nm and 532 nm in nanosecond pulses to cause both a photothermolytic and photoacoustic damage to melanosomes and even melanocytes . while the former wavelength is useful for its deeper penetration and is thus used to treat dermal pigmentation , the 532-nm wavelength is commonly used to target the epidermal pigment.[2022 ] fifteen patients of vitiligo universalis , in whom the residual pigmentation had not responded satisfactorily to topical application of mbeh for at least 3 months , were enrolled for this prospective open - label study . all the patients had more than 80% body surface area involved with vitiligo and had residual pigmentation on cosmetically important areas like the face , hands , forearms , and feet . pregnant females , patients with keloidal tendency , and children less than 15 years of age were excluded from the study . the patients enrolled for the study were photographed at the initial visit and an informed consent was obtained from each one of them . the areas with residual pigment were noted down and a management plan was chalked out depending on the patient s preferences . in all enrolled patients only one area of the body was treated in a single session . the area that was the most troublesome for the patient was treated first ( in all cases the face ) followed by the other areas involved . before each laser session , topical treatment with mbeh was discontinued for about 57 days on the area to be treated . treatment was carried out with a frequency - doubled q - switched nd : yag laser at 532-nm wavelength . the fluence used was in the range of 12 j / cm with a spot size of 23 mm . no topical anaesthesia was used in any patient and after the laser session the patients were advised to use a mid - potent topical steroid with an antibacterial cream for 23 days and to limit their sun exposure . a broad - spectrum sunscreen lotion was also mandatorily used in every patient . in patient requiring further laser sessions at an already treated site a minimum gap of 6 weeks was kept in between the sessions . topical treatment with mbeh was continued at bedtime along with the laser sessions on all the treated areas . patients were called for follow - up at 1 and 2 weeks after each laser session and the response to treatment was noted down . at this follow - up visit , any other untreated area of the body any change in the residual pigment was assessed clinically as well as with repeat photography at the follow - up visits after 1 , 2 and 6 weeks . any need for further laser sessions was assessed at the 6-week follow - up visit . results to treatment offered were termed as excellent if there was more than 90% resolution of pigment . a 5090% resolution of pigment was termed as a partial response and anything less than 50% pigment resolution was termed as a poor response . adverse events noted down were pain and burning at the time of laser treatment and any post - treatment sequalae . all the patients were also followed for a period of 3 months to look for any relapse of pigmentation on the treated areas . the age of our patients ranged from 15 to 42 years with a mean of 27 years . the youngest patient in our study was a 15-year - old male student while the eldest one was a female aged 42 years . the duration of vitiligo ranged from 2 to 25 years with a mean of 10.6 years . face was the commonest area involved with the residual pigmentation and was thus the commonest site treated . in fact , face was treated in all the 15 enrolled patients [ table 1 ] . however , the type and degree of involvement of face varied among the enrolled patients , being patchy and limited to malar area and forehead [ figure 1a and b ] in majority ( 11 patients ) and residual pigmentation on hands in four patients [ figure 2a and b ] . various sites treated with depigmentation therapy ( a ) patchy residual pigmentation on face , ( b ) after treatment with q - switched nd : yag laser ( a ) residual pigmentation on hands and ( b ) after 2 sessions of q - switched nd : yag laser the next commonest site treated was the hands ( six patients ) followed by the forearms ( three patients ) and the feet ( two patients ) . thus , a total of 26 sites were treated in the 15 patients enrolled [ table 1 ] . most of the patients responded well to treatment and excellent results with more than 90% resolution of pigment were seen in 13 out of the 15 patients enrolled . both of these partially responding patients had a diffuse involvement of the face and these patients refused treatment at other body sites involved . all the body sites responded almost equally to the treatment offered and there was no site - specific difference in the results achieved . majority of the sites treated responded with just one or two laser sessions but in three cases , the treatment had to be repeated thrice on the face to achieve a satisfactory response . however , no patient was given more than three sessions of laser treatment at any site . no significant adverse effects were noted in any patient and the procedure was termed as similarly , there were no serious post - treatment sequalae in any patient . on follow - up no patient was seen to experience a relapse over 3 months . however , the follow - up period was too short to comment on the long - term efficacy of the treatment offered . topical depigmenting treatments in vitiligo have two main inherent limitations ; first , they are too slow to act and second , they too often cause an irritant reaction on the skin . patients of universal vitiligo who have residual pigment on the cosmetically important areas demand a treatment that is quick to act and is devoid of side effects . lasers are of help in such situations as their therapeutic effect is visible in days and the treatment is devoid of any serious adverse effects in usual circumstances . first , they target the melanosomes in the residual melanocytes by means of a selective photothermolysis and photoacoustic effect . in addition they are also believed to stimulate koebnerisation of the vitiligo process and this adds to the depigmenting effect . among the different lasers used to cause further depigmentation in vitiligo , q - switched ruby laser has been the most commonly used and reported till date . this laser has been used in patients after tanning to cause a permanent depigmenting effect . tanning in such cases is thought to activate melanocytes and these activated melanocytes can then be more easily targeted by laser light . in addition to q - switched ruby laser the other laser that has been reported to be useful in causing depigmentation in vitiligo patients is the q - switched alexandrite laser . this laser system has been used in combination with mbeh to cause a long - lasting depigmenting effect in patient who did not respond to q - switched ruby laser . the investigators used 10 sessions of laser treatment and within 22 months , they were able to achieve a permanent depigmenting effect in their patient . in the present study , we used the 532-nm wavelength of q - switched nd : yag laser as the target was the epidermal pigment only and we wanted some inflammation and thus a koebnerisation of the vitiligo process to take place . we were able to achieve a total or near - total depigmentation with just one or two sessions in combination with the use of a topical depigmenting agent mbeh in majority of our patients . we did not advise our patient to get tanned but we did stop the topical depigmenting agent for a few days before each laser session to have some active melanocytes to work on . the main advantage that we found with this combination was that the therapeutic effect was very rapid in onset and the patients could notice some pigment loss within just days after the laser treatment . it is noteworthy that all these patients had already been using topical depigmenting creams with no or minimal effect on the residual pigment . we did follow - up with our patients for 3 months and we did not encounter any relapses over the follow - up period . however , the follow - up of 3 months is too short to really comment upon the stability of the therapeutic effect achieved with the laser treatment .

background : any residual pigment left in patients of universal vitiligo is managed with topical treatments , cryotherapy , and lasers.aim:the study aims to assess the efficacy and safety of q - switched nd : yag laser in treating the residual pigmentation in patients with universal vitiligo.materials and methods : fifteen patients of universal vitiligo with residual pigmentation on the face , hands , or feet , resistant to topical treatments , were treated with single or multiple sessions of q - switched nd : yag laser treatment . topical treatments were continued in between the laser sessions and the depigmentation achieved was monitored by clinical examination and repeat digital photographs . response to the treatment was labelled as excellent if the residual pigment could be reduced by at least 90% while 5090% resolution of pigmentation was labelled as a partial response . adverse effects to the treatment offered were also monitored.results:thirteen of the 15 patients enrolled for the study showed an excellent response to the treatment offered . two other patients showed a poor response with less than 50% resolution of pigmentation . the number of laser sessions needed at a particular site ranged from 1 to 3 and no patient was offered more than three sessions of laser treatment at any site . no significant adverse events were reported by any patient.conclusions:residual pigmentation in patients with universal vitiligo that does not respond to topical treatment options alone can be managed quite effectively with q - switched nd : yag laser without any significant adverse effects .

type i and type ii , based on histology , which differs in molecular as well as in clinical and histopathological profiles . type ii is nonestrogen dependent , nonendometrioid , with higher grade histologies , more aggressive and carries an adverse prognosis . although type ii cancers contribute only about 10% of ec incidence , they present at advanced age and cause approximately 50% recurrence and deaths with a low 5-year , overall survival rate of 35% . type ii cancers typically arise in an atrophic endometrial background , and often have deep myometrial penetration and demonstrate lymph node spread . type ii ec is also characterized by genetic alterations in p53 , human epidermal growth factor ( her)-2/neu , p16 and e - cadherin . endometrial carcinomas diagnosed from endometrial biopsies and hysterectomy specimens received in the department of pathology , kasturba medical college , mangalore , from january 2007 to june 2012 were included in the study . all specimens were fixed in 10% neutral buffered formalin and paraffin embedded for histological examination with hematoxylin and eosin staining . p53 immunostaining was performed in two cases of serous carcinoma ; using mouse monoclonal antibody . p53 immunoreactivity was regarded as positive when brown staining was localized to the tumor cell nuclei . during the study period , a total of 84 cases of ec were reported . of these , ten cases were classified as type ii ec ( 11.9% ) as per histology . out of which , eight were serous carcinoma ( 9.5% ) and two clear cell ( 2.4% ) . the age of the patients ranged from 45 to 75 years , with mean age being 62 years . grossly , the type ii ec frequently appeared bulky on a background of an atrophic endometrium , with tumor filling almost the entire cavity [ figure 1 ] . p53 immunostain was performed in two of the serous papillary carcinomas which showed strongly positive ( > 75% of tumor cells nuclei ) staining in the nuclei . the tumor , node , metastasis staging and figo staging ( 2008 ) was done for all the cases , with four cases of stage iii disease [ table 1 ] . endometrial serous carcinoma gross specimen : uterus with fleshy tumor filling the endometrial cavity with papillary excrescences clinical profile and pathological features of type ii endometrial cancers treatment was surgical hysterectomy in all cases , with one case being followed with aggressive chemotherapy due to metastases in the liver . these generally occur in women a decade later than type i carcinoma , and in contrast to type i carcinoma they usually arise in the setting of endometrial atrophy . of the type ii ec , endometrial serous carcinomas ( escs ) constitute only 10% of ecs but have a substantially higher case - fatality rate than their more common endometrioid counterparts . this is attributable , at least in part , to the advanced stage at which many patients with esc present . the patient s age at the time of diagnosis is often a critical factor in determining the prognosis of a patient with endometrial carcinoma . generally , endometrial carcinoma in younger women , particularly before the menopause , is associated with a 5-year survival approaching 100% . one study found a 5-year survival of 96% for women aged 4049 years compared with only 53% for women of 7079 years . increasing age is associated with a higher grade and stage of endometrioid tumors and the likelihood of a nonendometrioid type tumor , but this accounts for only part of the difference in survival . an additional factor may be that a relative lack of immunocompetence is more prevalent in older patients . in our series too , the mean age was 62 years , and the histomorphological features were of high grade ( poorly differentiated ) . out of the 84 cases of ec reported during the study period , eight were serous carcinoma and two were clear cell carcinoma . escs are morphologically characterized by a complex pattern of papillae with cellular budding , cytologic pleomorphism , frequent lymphovascular and/or myometrial invasion , and not infrequently containing psammoma bodies . histologically , clear , glycogen - filled cells and hobnail cells that project individually into lumens and papillary spaces , and large , highly pleomorphic nuclei characterize the typical clear cell adenocarcinoma . in our study , esc showed complex , branching papillae with fibrovascular core [ figure 2 ] . the papillae are covered by a stratified epithelium with a prominent and characteristic tufting or budding pattern . marked nuclear pleomorphism and large macronucleoli along with occasional bizarre and hyperchromatic giant nuclei was seen . lymphovascular invasion and deep myometrial invasion was also present . in the clear cell carcinoma , the cells had clear cytoplasm with regular cell outline . the enlarged and pleomorphic nuclei were appearing to protrude into the lumens , presenting a complex branching papillae ( h and e ; 10 ) the precursor of serous carcinoma , endometrial intraepithelial carcinoma , consists of cells identical to those of serous carcinoma but lacks identifiable stromal invasion . mutations in p53 are found in approximately 75% of these lesions , suggesting that mutation of p53 is an early event in serous endometrial carcinoma . thus , serous carcinoma presumably begins as a surface epithelial neoplasm that extends into adjacent gland structures and later invades endometrial stroma . their generally poorer prognosis is thought to be a consequence of a propensity to exfoliate , undergo transtubal spread , and implant on peritoneal surfaces like their ovarian counterparts . myoinvasion is described by the presence of a constellation of features , including irregular , jagged contours of the neoplastic glands , single tumor cells or clusters in the myometrium , desmoplastic stroma , haphazard distribution of neoplastic glands in myometrium , etc . once the presence of myoinvasion is established , the depth of invasion is measured using the deepest undulation of endomyometrial junction . patients with more than 50% myometrial thickness invasion are at increased risk for extrauterine metastases , including pelvic and para - aortic lymph node metastases . these patients often require more aggressive surgical staging , which may include pelvic and para - aortic lymphadenectomy , as well as postoperative adjunctive therapy . in our findings , seven of the cases ( 70% ) had more than half of myometrial thickness invasion . the molecular changes of p53 mutation in 8090% of serous carcinomas is reflected in p53 immunohistochemistry , which typically shows a diffuse and intense nuclear staining pattern involving almost all tumor cells . in our study too , intense p53 staining was seen in 2 of the cases diagnosed as esc and progesterone receptor marker was negative [ figure 3 ] . our case series shows that the incidence of type ii ec is less than that of type i. among the type ii ec , serous carcinomas are higher in number . the aggressiveness and the poorer survival rates of type ii ec makes the diagnosis of this type very crucial for the histopathologist and the clinician .

introduction : endometrial carcinoma ranks 3rd in india among gynecological malignancies . endometrial cancer ( ec ) can be classified into two distinct groups type i and type ii , based on histology , which differs in molecular , clinical and histopathological profiles . type ii is nonestrogen dependent , nonendometrioid , more aggressive and carries poor prognosis . although type ii cancers contribute only about 10% of ec incidence , they present at advanced age and cause approximately 50% recurrence and deaths with a low 5-year , overall survival rate . type ii ec are also characterized by genetic alterations in p53 , human epidermal growth factor-2/neu , p16 and e-cadherin.materials and methods : endometrial carcinomas diagnosed from endometrial biopsies and hysterectomy specimens received in the department of pathology , kasturba medical college , mangalore , from january 2007 to june 2012 were included in the study . clinicopathological analysis of the 84 cases of ec was done with emphasis on morphology . p53 immunostaining was performed in two cases of serous carcinoma.results:out of a total of 84 cases of ec , ten cases were of type ii ( 11.9% ) . out of which , eight were serous carcinoma ( 9.5% ) and two clear cell ( 2.4% ) . p53 immunostain was strongly positive in the serous papillary carcinomas . the age of the patients ranged from 45 to 75 years . myometrial invasion was more than half . treatment was hysterectomy followed by aggressive chemotherapy.conclusion:of the type ii ec , serous carcinoma is the most common type . clinical presentation and prognosis differs in comparison to type i ec , thus the recognition of this type of ec is pivotal .

protein structures are stabilized by numerous non - covalent interactions , e.g. hydrophobic , hydrogen bonding , electrostatic and van der waals interactions ( 1,2 ) . hydrophobic interactions are believed to be the driving force behind protein folding and stability ( 3 ) . the cooperative , non - covalent and long - range interactions between residues provide stability for resisting the local tendency to unfold ( 4,5 ) . it has also been reported that the stabilizing residues ( srs ) show high conservations among protein sequences . these aspects suggest that by combining ( i ) surrounding hydrophobicity ( 6 ) , ( ii ) a quantitative measure of the number of long - range residue residue contacts [ quantified by means of long - range order ( lro ) ] ( 7 ) , ( iii ) stabilization centers ( 8,9 ) and ( iv ) conservation score ( 10 ) , the srs in protein structures could be predicted . we , therefore , developed a consensus approach for locating them in tim - barrel proteins ( 11 ) . as thermodynamic and kinetic experiments show ( 12,13 ) , srs identified by our algorithm have a significant role in the stabilization of protein structures . thus , we believe that our definition of srs can be a useful tool for scientists in the exploration of structural stability of proteins . for example , our tim - barrel study suggested that the structure of most tim - barrel proteins is stabilized by srs , which appear in the inner core of -strands and act as a skeleton of the protein . most of the tim - barrel proteins are enzymes or have functions that need a high level of flexibility for biochemical reactions , but at the same time they have high stability to ensure a long lifetime . by making a stable and rigid inner core and a flexible outer region of the barrel , this topology can satisfy both requirements . in this paper , we extend this approach to all globular protein structures . we have computed surrounding hydrophobicity , lro and involvement in stabilization center directly from 3d structures of proteins deposited in protein data bank ( 14 ) and conservation score from the alignment of sequences available in swiss - prot database ( 15 ) . users can also select their own threshold values for each parameter to identify srs . using the default values , the results obtained for tim - barrel proteins may slightly differ from the published ( 11 ) results . first , in the sride server , we use more accurate values for the van der waals atom radii ( 16 ) . second , the conservation scores calculated with our server differs slightly from the scores calculated with the consurf server . this could be probably due to the fact that we use a more current version of the clustalw alignment program ( 17 ) . we checked that the four criteria mentioned above were satisfied according to the definitions given and justified in our earlier papers ( 711 ) . surrounding hydrophobicity of a residue i [ hp(i ) ] is calculated as the sum of hydrophobic indices , obtained from thermodynamic transfer experiments , of residues whose c atoms are within the distance of 8 from the c atom of residue i : hp(i)=j=120nijhj where nij is the total number of surrounding residues of type j around residue i of the protein , and hj is the hydrophobic index of residue type j , in kcal / mol listed in ( 18 ) . the lro of a residue i is the number of long - range contacts of this residue counted in the following way : lroi=j=1nnij / n ; nij=1 , if |ij|>12 ; nij=0 otherwise , where i and j are two residues , in which the c distance between them is 8 , and n is the total number of residues in the protein . two residues are in contact if there is at least one pair of heavy atoms with a distance less than the sum of the van der waals radii of the two atoms plus 1.0 . a contact is considered long - range if it is between residues that are separated by at least 10 residues in the amino acid sequence . two residues are sc elements if they are involved in long - range contacts and if at least one supporting residue can be found in each of the flanking tetra - peptides of these residues , in such a way that at least seven out of the possible nine interactions are formed between the two triplets ( 8) . these can also be obtained using the public server scide ( ) ( 9 ) . if a residue is involved in a stabilization center , its sc value becomes 1 , and 0 otherwise . conservation of residues is identified by comparing the sequence of pdb ( 14 ) entries with sequences deposited in swiss - prot ( 15 ) using a local implementation of the public server consurf ( 10 ) ( ) . the clustalw ( 17 ) aligned homologous sequences found by psi - blast ( 19 ) are used to calculate the measure of conservation by the rate4site algorithm ( 20 ) . a score of 1 represents the most variable residues and a score of 9 represents the most conservative ones . surrounding hydrophobicity of a residue i [ hp(i ) ] is calculated as the sum of hydrophobic indices , obtained from thermodynamic transfer experiments , of residues whose c atoms are within the distance of 8 from the c atom of residue i : hp(i)=j=120nijhj where nij is the total number of surrounding residues of type j around residue i of the protein , and hj is the hydrophobic index of residue type j , in kcal / mol listed in ( 18 ) . the lro of a residue i is the number of long - range contacts of this residue counted in the following way : lroi=j=1nnij / n ; nij=1 , if |ij|>12 ; nij=0 otherwise , where i and j are two residues , in which the c distance between them is 8 , and n is the total number of residues in the protein . two residues are in contact if there is at least one pair of heavy atoms with a distance less than the sum of the van der waals radii of the two atoms plus 1.0 . a contact is considered long - range if it is between residues that are separated by at least 10 residues in the amino acid sequence . two residues are sc elements if they are involved in long - range contacts and if at least one supporting residue can be found in each of the flanking tetra - peptides of these residues , in such a way that at least seven out of the possible nine interactions are formed between the two triplets ( 8) . these can also be obtained using the public server scide ( ) ( 9 ) . if a residue is involved in a stabilization center , its sc value becomes 1 , and 0 otherwise . conservation of residues is identified by comparing the sequence of pdb ( 14 ) entries with sequences deposited in swiss - prot ( 15 ) using a local implementation of the public server consurf ( 10 ) ( ) . the clustalw ( 17 ) aligned homologous sequences found by psi - blast ( 19 ) are used to calculate the measure of conservation by the rate4site algorithm ( 20 ) . a score of 1 represents the most variable residues and a score of 9 represents the most conservative ones . the srs in the 3d structure of a protein are delineated with certain threshold values for each term ( i.e. sr is the one in which the values for all these four parameters are equal to or greater than the specified threshold values ) . in our study of tim - barrel proteins ( 11 ) , we have used the following conditions to predict the srs : ( i ) hp 20 kcal / mol ; ( ii ) lro 0.02 ; ( iii ) sc 1 ; and ( iv ) conservation score 6 . for example , our recent survey showed that in 63 tim - barrel proteins , only 4.0% of the residues ( i.e. 957 residues out of 23 968 ) were identified as stabilizing residues. users who prefer to apply stricter or more relaxed conditions in the definition of srs can adjust the thresholds in the server accordingly . the input of the sride server is the atomic coordinate file of the protein to be analyzed . alternatively , it can be any other atomic coordinate file in pdb format uploaded directly by the user . this second option is mainly for those who want to analyze structures obtained by homology modeling or other computational approaches . calculations are carried out on the selected protein chain , and inter - chain interactions are not taken into account to calculate lro , hp and sc properties . the output of the server is a list of the sequences used to calculate the conservation score and the list of the srs , together with the hp , lro and conservation score values . the output is sent to the user via email because calculating the conservation score is rather time consuming ( it can take several minutes ) . to avoid submissions with non - existent email addresses , the user must complete a simple registration procedure . in this registration procedure , only one email address must be given and this is the address to which a registration code is sent . when the registration code is copied back into the proper field of the registration page , the email address will be enabled to place submissions .

residues expected to play key roles in the stabilization of proteins [ stabilizing residues ( srs ) ] are selected by combining several methods based mainly on the interactions of a given residue with its spatial , rather than its sequential neighborhood and by considering the evolutionary conservation of the residues . a residue is selected as a stabilizing residue if it has high surrounding hydrophobicity , high long - range order , high conservation score and if it belongs to a stabilization center . the definition of all these parameters and the thresholds used to identify the srs are discussed in detail . the algorithm for identifying srs was originally developed for tim - barrel proteins [ m. m. gromiha , g. pujadas , c. magyar , s. selvaraj , and i. simon ( 2004 ) , proteins , 55 , 316329 ] and is now generalized for all proteins of known 3d structure . srs could be applied in protein engineering and homology modeling and could also help to explain certain folds with significant stability . the sride server is located at .

in this issue of critical care , yildiz and colleagues reported the first randomized , controlled trial on the efficacy and safety of physiologic doses of steroids in severe sepsis . during the past 5 years , five phase ii trials and a phase iii placebo - controlled trial on cortisol replacement , i.e. prolonged treatment with physiologic doses of steroids , have been completed in patients with vasopressor - dependent septic shock ( table 1 ) . two of them have already been published in peer - reviewed journals , three have been published in abstract form and will be published shortly in peer reviewed journals , and the results of a phase ii trial that has just been completed will be available very soon ( oppert and colleagues , personal communication ) . these trials have consistently shown beneficial effects of cortisol replacement on the amount of vasopressors , on the duration of shock , on the duration and intensity of organ dysfunction , and on the intensity of the systemic inflammatory response . the survival benefit observed with cortisol replacement in several phase ii trials was recently confirmed by the phase iii trial . in all these trials , cortisol replacement was never associated with even a trend toward serious side effects . a confirmatory phase iii , multinational , placebo - controlled trial ( the corticus study ) is under way , and results should be available within the next 3 years . in the meantime , given the consistency of the results across available trials , cortisol replacement should be considered as a standard of care for patients with vasopressor - dependent septic shock . yildiz and colleagues found that , in patients with severe sepsis , irrespective of the need for vasopressors , treatment for 10 days with prednisolone given intravenously twice daily ( 5 mg at 6 a.m. and 2.5 mg at 6 p.m. ) was associated with a 20% absolute reduction in mortality within 28 days . these findings are very challenging , because they suggest that cortisol replacement might be introduced in severe sepsis as well as in vasopressor - dependent septic shock , and that the mechanisms underlying the favorable effects of the treatment might not be limited to a reduction of the need for vasopressors . obviously , a phase iii trial must be set up to confirm the potential survival benefit of cortisol replacement in patients with severe sepsis who are not vasopressor - dependent . recently completed randomized , controlled trials of cortisol replacement in septic shock the study by yildiz and colleagues addressed another important issue , i.e. the need for an adrenocorticotropic hormone ( acth ) test to identify patients with severe sepsis or septic shock who will benefit from cortisol replacement . in this small trial , the effects of steroids were not significantly altered by the results of a short acth test . however , there were only 14 nonresponders ( 5 in the steroid group and 9 in the placebo group ) to the test , i.e. a cortisol increment after a 250-g intravenous bolus of acth of less than 9 g / dl , as previously defined . subsequently , in this subset of patients with occult adrenal insufficiency , the 15.6% absolute reduction in 28-day mortality in favor of the steroid group was not statistically significant . among the six completed trials of cortisol replacement in septic shock , only two reported separate data according to the results of a short corticotropin test , and only one trial was adequately powered to assess the survival benefit of cortisol replacement in patients with occult adrenal insufficiency . in fact , in this trial , cortisol replacement dramatically improved rates of survival for 28 days in the intensive care unit or elsewhere in the hospital in the nonresponders to the acth test but not in those having an increase in cortisol levels of more than 9 g / dl after acth . however , this trial was not adequately powered to allow definite conclusions regarding patients deemed to have normal cortisol response to acth and we therefore need to wait for the results of the corticus study . in the meantime , cortisol replacement should be considered only in vasopressor - dependent septic shock with occult adrenal insufficiency . as the results of the acth test might not be available everywhere at all times , it is recommended that cortisol replacement be started immediately after the acth test is performed , and that in the light of the results of the test , treatment could be continued for up to 7 days in nonresponders and stopped in patients with normal cortisol response to acth .

based on several recently completed randomized controlled trials , cortisol replacement is likely to become a standard of care for vasopressor dependent septic shock . further studies are needed in order to accomplish whether this treatment should be limited to patients with a blunted cortisol response to corticotrophin . similarly , in patients with severe sepsis who do not need vasopressors , the benefit / risk ratio of cortisol replacement remains to be assessed .

in the previous issue of critical care , huang and colleagues try to answer the unresolved question of the prognostic value of sepsis - related cardiomyopathy . since margaret parker and colleagues originally reported in 1984 that 65% of patients had significant left ventricular ( lv ) systolic dysfunction in the early phase of sepsis associated with acute lv dilatation ( > 100% increase in size ! ) and that such patients had a better prognosis , various groups have failed to replicate these results , leading to confusion and controversy . the article by huang and colleagues is interesting because it reports a large meta - analysis including more than 700 septic patients available for lv analysis . the meta - analysis failed to find any evidence for a protective effect of a decreased lv ejection fraction ( ef ) . nevertheless , the nonindexed lv dimension was moderately higher among survivors than nonsurvivors . these results have to be interpreted with caution since in most studies included in the meta - analysis patients with lv systolic dysfunction received inotropic drugs . in the study by cariou and colleagues in 10 patients , most patients were infused with epinephrine or dobutamine . in the study performed by our group in 68 patients , bouferrache and colleagues reported recently that dobutamine significantly improves the macrocirculation in patients with a low flow state who show a 40% increase in cardiac output despite normal venous oxygen saturation . de backer and colleagues demonstrated that the proportion of functional capillaries was decreased in septic patients compared with volunteers and that dobutamine , by inducing a 21% increase in cardiac output , led to a nearly complete reversal of such alterations . in the study by rivers and colleagues , demonstrating a better prognosis in the early goal - directed therapy group , close to 14% of patients received dobutamine in the first 6 hours in the interventional group versus 0.8% in the control group . finally , rhodes and colleagues , kumar and colleagues , and vallet and colleagues reported similar results - a huge decrease in mortality in septic patients who respond to dobutamine in terms of cardiac output [ 9 - 11 ] . more interestingly , however , the article by huang and colleagues allows us to try to clarify the meaning of lv function in septic shock patients . a lot of confusion exists . in all experimental models of septic shock , lv contractility impairment - called septic cardiomyopathy - has been reported to be constant . in these studies , as in the study by barraud and colleagues , intrinsic contractility is assessed using a parameter that is not dependent on load conditions ; that is , systolic elastance . unfortunately , this assessment requires the generation of pressure / volume loops , something difficult to achieve in human subjects at the bedside . this difficulty is why in clinical practice most intensivists use lv systolic function parameters that are for the most part dependent on load conditions . more than 20 years ago , robotham and colleagues nicely reiterated that lvef reflects the coupling between lv contractility and lv afterload . in other words , a normal lvef may be observed when the arterial tone is severely depressed , despite seriously impaired intrinsic lv contractility . everyone understands that it is crucial to remember this in septic shock , in which arterial tone is initially severely decreased . lv systolic function , evaluated using an echocardiograph or another device , is more a reflection of arterial tone ( and its correction ) than of intrinsic lv contractility . in a 1990 study , jardin and colleagues elegantly showed that patients with a normal lvef had a significantly lower systemic vascular resistance than patients with a low lvef in whom resistance was corrected . as shown in figure 1 , it is then easy to understand that the incidence of lv systolic dysfunction greatly depends on the time of the evaluation . this dependence only reflects the fact that , during resuscitation and treatment , vasoplegia and then lv afterload are corrected , thus unmasking septic cardiomyopathy . h6 , h12 , h24 , h72 , the time ( hours ) between admission and echocardiographic evaluation . with these points in mind , we can revisit the results of margaret parker and colleagues ' study : it is not that the patients with a low ef survived better , but rather that the other patients had an increased mortality due to persistent profound vasoplegia . this was suggested by our group in a study where 100% of patients with a hyperkinetic state ( lvef 67 7% ) finally died , compared with ' only ' 43% of patients with a hypokinetic state ( lvef 34 10% ) . weng and colleagues showed recently that high peak systolic velocity measured at the mitral annulus by tissue doppler imaging might be associated with mortality in patients with septic shock , suggesting that profound vasoplegia inducing high contractility is linked to poor prognosis . in conclusion , it will be very difficult to demonstrate that lv systolic dysfunction is associated with prognosis . septic cardiomyopathy is constant and lv systolic function is more a reflection of the status of lv afterload . rather , we have now to demonstrate what the best mortality - reducing strategy is when there is lv systolic dysfunction . persistence of a hyperkinetic state is a warning signal suggesting that the septic process is not under control and that the patient has a high probability of dying .

the meta - analysis of huang and coworkers failed to find any evidence for a protective effect of a decreased left ventricular ( lv ) ejection fraction ( ef ) . these results have to be interpreted with caution since in most studies included in the meta - analysis patients with lv systolic dysfunction received inotropic drugs . we have some arguments suggesting that such a treatment may improve macrocirculation and microcirculation and finally prognosis . this paper allows us to clarify the meaning of lv function in septic shock patients . in all experimental models of septic shock using the load - independent parameter of lv systolic function , lv contractility impairment , called septic cardiomyopathy , has been reported to be constant . however , lvef reflects the coupling between lv contractility and lv afterload . a normal lvef may be observed when the arterial tone is severely depressed , as in septic shock , despite seriously impaired intrinsic lv contractility . lv systolic function , evaluated using an echocardiograph or another device , is then more a reflection of arterial tone ( and its correction ) than of intrinsic lv contractility . as a consequence , the incidence of lv systolic dysfunction greatly depends on the time of the evaluation , reflecting the fact that , during resuscitation and treatment , vasoplegia and then lv afterload are corrected , thus unmasking septic cardiomyopathy . with these points in mind , we can revisit the results of margaret parker 's original study : it is not that the patients with a low ef survived better , but rather that the other patients had an increased mortality due to persistent profound vasoplegia .

adenoid cystic carcinoma ( acc ) of the breast is a rare condition , and cases in male patients are even less common . we describe a case of acc of the breast with axillary lymph node metastasis , disseminated osteolytic bone metastasis and bone marrow involvement in a 41-year - old man . male breast acc is an extremely rare malignancy ; there can be difficulty in obtaining a final diagnosis . breast cancer in men is very rare , and the majority of male breast cancers show pathological findings similar to breast cancer in females . guidelines for diagnosis and treatment are based on those for female breast cancer due to the extremely low incidence of male breast cancer , i.e. < 1% of the rate in females . male breast cancer usually presents as a firm , painless mass , along with palpable axillary nodes , nipple retraction and ulceration of the skin at presentation . the mass is usually located in the subareolar region , but can also be seen in the upper outer quadrant . adenoid cystic carcinoma ( acc ) of the breast is a rare subtype of breast cancer , usually originating from the salivary gland . acc of the breast has very favorable biological characteristics for treatment and patients usually have an excellent prognosis . axillary lymph node dissection is not helpful for clinical management due to the rarity of metastasis . acc of the breast is a rare subtype of breast cancer , and cases in males are even less common . we report a rare case of advanced acc of the breast in a 41-year - old man , along with a review of the relevant literature . the patient was a 41-year - old male who presented at the department of rehabilitation with symptoms of cervical back pain that had been occurring for 2 months . he was healthy , with an unremarkable medical history and a 20-pack per year smoking history . a cervical spine ct scan showed osteolytic changes with bony fragmentations in the c3 , c5 and c6 transverse processes and vertebral bodies . these findings are suggestive of pathological fracture related to the presence of a tumor , such as metastatic carcinoma or multiple myeloma , rather than trauma ( fig . to differentiate between metastatic bone lesions and the presence of a solid tumor , we examined the bone scan labeled with tc , and the results showed only osteolytic bone lesions , with the exception of a small number of fractures . we did a serum and urine protein electrophoresis evaluation and immunofixation , but there was no evidence of monoclonal gammopathy . in the bone marrow examination for excluding hematologic malignancies such as multiple myeloma and lymphoma , the findings showed that the hematopoietic cells were almost replaced by neoplastic cells with a glandular pattern . neoplastic cells were stained with ck pan ( ae1/ae3 ) and were positive ( fig . metastatic carcinoma was suspected , but there were no abnormal findings in the esophagogastroduodenoscopy or colonoscopy . a pet - ct scan showed a disseminated hypermetabolic lesion ( maxsuv = 7.4 ) in the axial skeleton , multiple , small - sized lung nodules and a multifocal hypermetabolic lung lesion ( maxsuv = 2.6 ) as well as focal hypermetabolic lesions in the left axillary lymph nodes ( maxsuv = 2.3 ) ( fig . an ultrasound - guided core biopsy of the two 1.7-cm , low - echoic , pathological lymph nodes in the left level i axilla area was performed . otorhinolaryngology and head and neck screening were performed to attempt to ascertain the location of the primary tumor in the salivary gland , as most acc tumors in men are of salivary gland origin . however , this screening failed to identify specific lesions . to identify the primary origin of the cancer this revealed palpable and movable small nodular lesions in the periareolar area of the left breast , which had escaped interpretation on the pet - ct scan because the lesion was obscured ( fig . there were clustered small nodules at the 1 o'clock and 2 o'clock locations around the left nipple upon physical examination . in a breast ultrasound , an irregularly - shaped solid lesion , 1.7 cm in size , the margin of the lesion was irregular and the internal area was relatively homogeneous and hypoechoic and was suggestive of a bi - rads category 4c lesion . a core biopsy was performed and the pathology result was acc , the same as that of the auxiliary lymph node biopsy ( fig . 2i , j ) . immunohistochemical staining was performed and the sample was negative for estrogen receptor ( er ) , progesterone receptor ( pr ) and c - erbb2 , and positive for ck5/6 and p53 . we finally diagnosed acc of the breast with multiple lung and bone metastases and bone marrow involvement . the authors submitted a waiver from their institutional review board ( irb ) stating that this case report does not require irb approval or oversight . the overall incidence of acc of the breast is 0.050.1% [ 3 , 4 ] , and is exceedingly rare in men . acc commonly occurs at the following sites : the minor or major salivary glands , oral mucosa , larynx , lung and maxillary sinus . the incidence of all types of pathology of breast cancer in men is < 1% in western countries , but the exact incidence in korea is not known due to the rarity of this disease in men . according to a subsequent review of the relevant literature of acc of the breast , this cancer generally affects older female patients , with a median age range of 5864 years . the median age of male breast acc patients is not clear because few reports exist ; however , of the cases published [ 6 , 7 , 8 ] , 2 patients were diagnosed during adolescence and another at the age of 82 years . in our report , the case of a 41-year - old , relatively young man with a nontender , movable , left - breast lesion is described . acc of the male breast can develop at a relatively younger age than the common male breast cancer pathological type . the published tumor sizes of male breast accs range from 1.8 to 3.7 cm , and in this case , the maximum tumor diameter was 1.7 cm . acc of the breast is not associated with a bloody nipple discharge , even though it is present near the nipple areola region . our case also had no subjective symptoms , with the exception of the small palpable nodularity in the periareolar area . one hundred and fifty cases of female acc of the breast have been reported in the literature , only two of which had axillary lymph node metastasis [ 10 , 11 , 12 ] . however , our case showed pathologically confirmed left axillary lymph node metastasis and bone marrow involvement . this finding suggests the possibility of the long - term duration of the disease prior to the diagnosis , due to the small - sized primary tumor and lack of symptoms or signs except for the presence of aggressive multiple bone and lung metastasis . this case displays an extraordinary pattern of bone metastasis findings compared to other solid tumors : ct and pet - ct scans showed osteolytic bone lesions , but the findings of bone scans labeled with tc were negative . this reflects almost all lesions as having osteolytic activity without compensatory osteoblastic activity , like in multiple myeloma . the majority of breast accs are triple - negative ( i.e. er- , pr- and her2-negative ) , according to previous studies and reports . in this case , male breast acc is rare , and only a few cases have been reported [ 6 , 7 , 8 ] . it is difficult to trace the cancer 's origin to the male breast when initial pathological findings reveal acc in metastatic lymph nodes , as in this case . salivary - gland origin tumors are suspected first because acc with this site of origin is common in men . furthermore , it was difficult to identify the primary site as breast cancer in this case because there was no skin retraction or nipple discharge , unlike common types of breast cancer . in contrast to triple - negative breast carcinomas , acc of the breast has an excellent prognosis for female patients , as the incidence of lymph node metastasis is lower and distant metastasis is uncommon . acc of head or neck origin is also known to have a slow progression and thus a good prognosis for patients . however , male breast acc could be overlooked by the patient , and this , coupled with the difficulty of diagnosis , can lead to extended periods of time , with possible aggressive metastasis , until a diagnosis is made .

introductionadenoid cystic carcinoma ( acc ) of the breast is a rare condition , and cases in male patients are even less common.casewe describe a case of acc of the breast with axillary lymph node metastasis , disseminated osteolytic bone metastasis and bone marrow involvement in a 41-year - old man.conclusionmale breast acc is an extremely rare malignancy ; there can be difficulty in obtaining a final diagnosis . we report this case because of its rarity .

influenza a and b cause highly contagious , acute respiratory illness , associated with high morbidity and mortality among persons with underlying diseases . the causes of death in the more severe forms of influenza are ( a ) severe pneumonia with respiratory distress , ( b ) neurological complications , and ( c ) secondary bacterial pneumonia . outbreaks in children units , senior facilities , cancer centers , neonatal units , pulmonary rehabilitation centers , emergency departments , and others have been described . large nosocomial outbreaks in large tertiary referral hospitals that provide care to large numbers of patients with advanced aids have not been frequently described . roosevelt hospital is a large teaching , university tertiary referral hospital in guatemala city , with 850 beds capacity . more than 3,500 aids patients were in followups , and 1561 treated with antiretroviral drugs at the time when the outbreak was detected in march 2006 ; all of whom were at potential risk to develop severe forms of influenza . 35% of the patients have less than 50 cd4 cells / mm and 68% less than 200 cd4 cells / mm , at the time the hiv infection diagnosis is made at roosevelt hospital . the main admission diagnosis in the internal medicine department in the men wards is aids ( on average 25/66 beds are occupied by patients with aids ) . throughout the country mortality rate at the time of the first hospital admission in these advanced aids patients has decreased from 85% to 89% in the pre - haart era ( 19902000 ) , to 18%21% after the year 2000 . rapid dissemination of influenza virus is more likey in closed areas with poor ventilation ( air exchanges less than 6 per hour ) , no policies for health care worker vaccination and suboptimal awareness about the clinical presentation of severe influenza in immunocompromised persons may contribute to the magnitude of the outbreaks . the mortality rates in immunocompromised patient can be high , as we observed in this group of patients , with fulminant pneumonia and respiratory distress as the final cause of death . during the months of february to april 2006 , a large outbreak of influenza a was detected at roosevelt hospital ; health care workers and hospitalized patients were affected in this large teaching hospital in guatemala city . during the first 5 days of the initial suspicion of a possible respiratory outbreak , after 3 consecutive deaths in aids patients who were stabilized for different opportunistic infections , the first results of nasopharyngeal swabs were positive for influenza a virus , with no other pathogens found . the patients had been hospitalized for diagnosis and treatment , developed acute respiratory failure , and died within 1836 hours from the beginning of symptoms ; testing for legionella , rapid antigen test for influenza a , influenza b , and parainfluenza virus in regional or national labs , and cultures for common bacterial causes for nosocomial pneumonia in our microbiology laboratory were negative . an extensive triage and surveillance program in health care workers ( hcws ) was initiated . we could establish that the medical students and the internal medicine residents in the ward had a clinical diagnosis of influenza . we began to test hcw and patients in all internal medicine wards and 3 days after in all wards of the hospital . influenza diagnosis was established by clinical case definition and rapid test for influenza a ; viral cultures and histopathological examination of tissues from dead patients were also instituted . patients were considered as having nosocomially acquired infection if they had been admitted at least 72 hours before the onset of the symptoms . clinical triage was established in the emergency room for the early detection of new influenza cases from the community . interventions to interrupt the transmission were implemented and includedbarrier methods ( n95 masks , respiratory isolation measures , etc . ) and strengthening of hand hygiene , vaccination of healthy health care workers ( hcws ) and furloughing of sick hcw for 3 to 5 days , antiviral use for treatment or prophylaxis of hospitalized immunosuppressed patients , initially with amantadine , and after several failures , and the results of susceptibility tests obtained from collaboration with the us cdc , with oseltamivir , daily active surveillance for early detection of influenza cases in patients and hcw , daily active surveillance for early detection of influenza a cases in new patients before admission from the emergency rooms , no family visits to the internal medicines wards were permitted for 3 weeks , no elective surgery was permitted during the last 10 days of the outbreak . barrier methods ( n95 masks , respiratory isolation measures , etc . ) and strengthening of hand hygiene , vaccination of healthy health care workers ( hcws ) and furloughing of sick hcw for 3 to 5 days , antiviral use for treatment or prophylaxis of hospitalized immunosuppressed patients , initially with amantadine , and after several failures , and the results of susceptibility tests obtained from collaboration with the us cdc , with oseltamivir , daily active surveillance for early detection of influenza cases in patients and hcw , daily active surveillance for early detection of influenza a cases in new patients before admission from the emergency rooms , no family visits to the internal medicines wards were permitted for 3 weeks , no elective surgery was permitted during the last 10 days of the outbreak . patient 1 presented during the first week in march with acute respiratory failure and died within 24 hours . his diagnosis prompted a reevaluation of three recent deaths ; all of whom tested positive in histopathology , resulting in the recognition of the outbreak . in the period from february to april 2006 , 59 hospitalized patients were diagnosed with influenza a ; 19 of them were aids patients ( mortality rate : 71% ) while 5/40 ( 12.5% ) had other underlying diseases including cancer ( 3 ) , severe cardiac failure ( 1 ) , and severe malnutrition ( 1 ) . the final attack rate at one month was 21% in doctors and medical students and 10.5% in other hcws ( figures 3 and 4).a selective emergency vaccination plan was instituted in 5 days : 1,720 of 3,100 hcws ( 56% ) were reached ( figure 1).a daily active surveillance plan for early detection of influenza cases in hospitalized patients and hcw was implemented.after 3 weeks of the implementation of the control plan , deaths were stopped , and after 3 more weeks no more cases were detected in hcw ( figure 2 ) . a selective emergency vaccination plan was instituted in 5 days : 1,720 of 3,100 hcws ( 56% ) were reached ( figure 1 ) . a daily active surveillance plan for early detection of influenza cases in hospitalized patients and hcw after 3 weeks of the implementation of the control plan , deaths were stopped , and after 3 more weeks no more cases were detected in hcw ( figure 2 ) . influenza a can cause a very severe disease , with a high mortality rate in advanced aids patients . the clinical presentation was characterized by the accelerated evolution to death from the beginning of symptoms ( average 50 hours ) and affected mainly the more advanced aids cases , with a mortality rate among this group of 74% , compared with the 12.5% mortality in the non - aids patients . it is important to consider the possibility of influenza in the differential diagnosis in advanced cases of aids that are admitted to the general internal medicine wards , who are under treatment for opportunistic infections and develop acute respiratory distress . the rapid evolution to death and the risk of transmission to other immunosuppressed patients can be stopped , if we implement general isolation measures and use antiviral drugs like oseltamivir as prophylaxis or therapy early in the course of the disease . the protection conferred by the available vaccines is uncertain , and the information in the aids population is limited . all patients had concomitant severe opportunistic infections , but the histopathological findings showed in more than 90% of the patients in whom an autopsy was performed the typical pathology caused by influenza virus in the respiratory epithelium previously described . amantadine failed to protect patients exposed to influenza in the hospital , due to the resistance that was documented during the evolution of the outbreak . the influenza a virus in advanced aids patient could be considered an acute and severe opportunistic infection , that requires rapid actions to limit the negative impact in morbidity and mortality in this population . in addition to these points , several aspects of this outbreak are unique , and they deserved a discussion / comment . few outbreaks of severe influenza have been described in tropical or subtropical regions ; the fact that this one follows the seasonal pattern of the northern hemisphere season is worthy of a comment . this is one of the largest outbreaks in hospitalized patients with advanced aids and highlights the high risk of severe disease and mortality in these patients . several aspects of the control plan instituted have been described as potential control measures for the control of outbreaks . respirators , respiratory precautions , hand hygiene , and early diagnosis and furloughing of health care workers have been described . this plan shows that institution of all the measures may be necessary to control outbreaks . vaccination of health care workers has been advocated but only mandatory programs have achieved 100% compliance . it would be good to know what the rate of vaccination in health care workers in the years after the outbreak has been . it is very urgent to investigate about the role of vaccination in the control of this outbreak , since it takes a few weeks to develop immunity after vaccination . the role of oseltamivir treatment and prophylaxis in the control of this outbreak also deserves some comment . a rapid , comprehensive plan for the control of nosocomial epidemic influenza a outbreaks is essential to limit severe morbidity and mortality in hospitals who attend large immunocompromised populations , including aids patients . a multidisciplinary approach is important to prevent possible future outbreaks , especially with increasing reports of human infection with highly pathogenic avian influenza viruses or other novel viruses that could become pandemic in the near future .

objective . to describe the characteristics and interventions to control a large epidemiological influenza a outbreak . methods . during the months of february to april 2006 , a large outbreak of influenza a was detected , which affected health care workers and hospitalized patients in a large teaching hospital in guatemala city . interventions to interrupt transmission were implemented and included barrier methods ( n95 masks , respiratory isolation measures , etc . ) and enhanced hand hygiene , vaccination of healthy health care workers ( hcw ) , restrictions for patient visits . results . from february to april 2006 , 59 hospitalized patients diagnosed with influenza a. 19 aids patients ( mortality : 71% ) and 5/40 ( 12.5% ) in other diseases : cancer ( 3 ) , severe cardiac failure ( 1 ) and severe malnutrition ( 1 ) . the attack rate at day 20 in doctors and medical students was 21% while in other hcw it was 10.5% . within 3 weeks of the beginning of the plan , deaths were stopped and no more cases in hcw were detected after 3 additional weeks . conclusion . a rapid , comprehensive plan for the control of nosocomial epidemic influenza a outbreaks is essential to limit severe morbidity and mortality in hospitals who attend large immunocompromised populations , including aids patients . hcw regular vaccinations programs are mandatory .

neuroferritinopathy is an autosomal dominant neurodegenerative disorder characterized by the deposition of iron and ferritin in the brain and a decreased level of serum ferritin . seven different pathogenic mutations of the ferritin light chain gene have been identified [ 17 ] . these mutations are predicted to affect the tertiary structure and stability of the ferritin light chain polypeptide and may cause inappropriate iron release from ferritin polymers [ 8 , 9 ] . it is supposed that the excess iron induces free toxic radical production , which leads to tissue oxidative stress and neuronal cell death [ 1012 ] . the clinical features of neuroferritinopathy are characterized by the adult onset of extrapyramidal motor symptoms : dystonia , chorea , choreoathetosis , parkinsonism , and tremor . some patients may present cerebellar ataxia , cognitive decline , and pyramidal signs [ 2 , 3 , 57 ] . the phenotypic signs of the disease are variable , even among members of the same family [ 1 , 3 ] . generally , there are no nonneurological symptoms , different from in other neurodegenerative brain iron accumulation diseases . the clinical features of neuroferritinopathy are not specific , and they overlap with those of common extrapyramidal disorders . brain mr imaging in the disease is quite characteristic and it may facilitate differential diagnosis of neuroferritinopathy from other extrapyramidal disorders . we will review the findings in neuroferritinopathy with conventional mri methods , t1-weighted imaging , t2-weighted imaging , and t2 * -weighted imaging . on t1wi , there is a sharp contrast between the parenchyma and ventricles , and it is adequate for evaluating brain atrophy and cystic changes . t2wi is suitable for detecting the pathological processes with an increase in water content , such as gliosis , edema and axonal / neuronal loss , as hyperintense signals . on t2*wi with a gradient echo sequence , signal abnormalities on brain mr imaging were observed in all affected individuals previously reported except for one case [ 1315 ] . despite the clinical differences , the findings are usually bilateral and symmetric but sometimes asymmetric [ 3 , 17 ] . radiological findings in patients with neuroferritinopathy have been shown to correlate with the observed pathology . the abnormalities observed on mri reflect four pathological changes : iron deposition , edema and gliosis , cystic changes , and cortical atrophy [ 13 ] . iron is essential for normal neuronal metabolism , but excessive iron may be harmful [ 19 , 20 ] . it is known that iron overload can cause free - radical formation and neuronal damage . physiologically , brain iron appears to be found predominantly in the extrapyramidal system , in particular the globus pallidus , substantia nigra , red nucleus , and putamen . it has been shown that moderate levels of iron occur in the striatum , thalamus , cerebral cortex , cerebellar cortex , and deep white matter . the brain histopathology of affected individuals with neuroferritinopathy involves excess iron and ferritin deposits throughout the forebrain and cerebellum , notably in the basal ganglia [ 13 ] . however , these regions still exhibit the general distribution pattern for iron in the normal aging brain . on fast spin echo t2wi , iron deposits are demonstrated as low - intensity areas and as signal loss on gradient echo t2*wi [ 13 , 22 ] . comparison of t2wi and t2*wi sequences suggests that the t2 * one is more sensitive for the detection of iron , while the t2 fast spin echo t2wi sequence is more frequently used in routine clinical practice . in particular , the cortical iron deposition in neuroferritinopathy is hardly detectable on t2wi but is easily observed on t2*wi . t2 hyperintense abnormalities are seen in the pallidum , putamen , caudate nucleus [ 1 , 3 ] , thalamus and dentate nucleus , and sometimes in the red nucleus and substantia nigra [ 16 , 24 ] in patients with neuroferritinopathy . the border of a lesion has a tendency to be unclear and the signal is unequal . because of the increased water content , the lesions are detected as hyperintense signals on t2wi . around these hyperintense areas , cavities are demonstrated as low - intensity signals on t1wi and high - intensity signals on t2wi , compared with the csf signal . in the region adjacent to a cystic lesion , severe loss of nerve cells and neuropil is observed pathologically . in one case , vidal et al . reported that microcavities measuring up to 1.5 mm in diameter were seen in the putamen anatomically and that these cavities were consistent with small hypointense areas on t1wi and to hyperintense ones on t2wi on mri . mcneill et al . analyzed the mri findings in 21 patients with neuroferritinopathy . in 52% ( 11/21 patients ) , they found that the globus pallidus and/or putamen coincided with a confluent area of hyperintensity and that this hyperintense area was likely to be due to fluid within an area of cystic degeneration . the presence of large cysts is thought to be a finding observed at an advanced stage . on brain mri in neuroferritinopathy , atrophy is sometimes noted in the cerebellar cortices and cerebral cortices , notably in the frontal lobe . regarding on clinicoradiologic correlation , patients having cerebellar atrophy present ataxia [ 2 , 3 , 26 ] , and ones having cerebral atrophy present cognitive decline [ 23 , 26 ] . the first mri change is loss of the t2 * signal due to iron deposits . in an early symptomatic stage , and even in an asymptomatic carrier , there is obvious signal loss on t2 * imaging in the basal ganglia , especially in the globus pallidus , at considerable frequency . in conventional spin echo mr sequences , . there has only been one report of that brain mr t2wi was normal without evidence of iron deposition ; however , it was obtained six years after the onset of neuroferritinopathy symptoms . in this case , the t2 * sequence was not examined at that time . the follow - up mri performed 16 years after the onset , however , showed typical abnormalities . with disease progression , the t2 hypointense signal and t2 * signal loss become more pronounced . the changes eventually extend to the thalamus , dentate nucleus , substantia nigra , red nucleus , and cerebral cortex . in the middle stage of the disorder , t2 hyperintense abnormalities reflecting tissue edema and gliosis are observed . in the basal ganglia , this change is thought to represent precystic degeneration . the combination of hyperintense and hypointense abnormalities is found in the pallidum , putamen , thalamus , and dentate nucleus frequently and sometimes in the red nucleus and substantia nigra [ 17 , 27 ] . the characteristic finding on brain mri at the advanced stage is symmetrical cystic degeneration of the basal ganglia [ 16 , 28 ] . pathologically , many microcavities due to the loss of neurophils and neurons are observed , which are consistent with hypointense areas on t1wi and with hyperintense ones on t2wi on mri . it is supposed that small cavities merge to form larger cavities with progression of the disease . brain mr images of our case are presented in figures 1 , 2 , 3 , and 4 . our patient is a 42-year - old japanese man who first developed hand tremor in his middle teens . he noticed his right foot dragging at age 35 , and generalized hypotonia , hyperextensibility , aphonia , micrographia , hyperreflexia , dystonia of his face , and cognitive impairment at age 42 . he was tested by means of the molecular technique and diagnosed as having neuroferritinopathy because a mutation of the ferritin light chain gene was detected . all images presented here were taken with a 1.5 tesla mr system . t1-weighted , t2-weighted , and t2 * -weighted sequences were collected in the transverse plane . a t1-weighted image is useful for evaluating the atrophy and size of a cyst . as compared with the image at 35 years ( figure 1 ) , that at 42 years demonstrates progression of the cystic formation and deterioration of the cortical atrophy in the frontal lobes ( figures 2(c ) and 3(c ) ) . a t2-weighted image is valuable for detecting the combination of degenerative change and iron accumulation . a clear hyperintense lesion with a hypointense signal was found in the center of the dentate nucleus ( figure 3(a ) ) . foggy high signal changes were found in the inner part of the thalamus bilaterally ( figure 3(c ) ) . iron deposits were indicated as signal loss in the dentate nuclei ( figure 4(a ) ) , red nuclei ( figure 4(b ) ) , thalamus ( figure 4(c ) ) , at the periphery of the cysts ( figure 4(c ) ) , and in the cerebral cortex ( figure 4(e ) ) in t2 * -weighted images . in this section , we provide an overview of the mri findings in three other subtypes of neurodegeneration with brain iron accumulation ( nbia ) : pantothenate kinase-2 associated neurodegeneration ( pkan , formerly known as hallervorden - spatz syndrome ) , aceruloplasminemia , and infantile neuroaxonal dystrophy ( inad ) for the differential diagnosis of iron deposition in the basal ganglia . over the last decade , iron deposition in the adult brain is being increasingly recognized as an indicator of neurodegenerative processes in many chronic neurologic disorders including parkinson disease and alzheimer disease . pkan is a childhood - onset extrapyramidal disorder with aberrant iron metabolism caused by a mutation of the pantothenate kinase-2 ( pank2 ) gene . brian mri findings in patients with the pank2 mutation include hypointensity with an area of central hyperintensity in the globus pallidi on t2- and t2 * -imaging , this characteristic sign being called the eye - of - the - tiger sign [ 14 , 3032 ] . mcneill et al . reported that two of 21 cases of neuroferritinopathy presented the eye - of - the - tiger he emphasized the importance of repeat imaging for a more accurate clinical diagnosis . in the majority of pkan cases , abnormalities are restricted to the globus pallidus and substantia nigra . in neuroferritinopathy , lesions in the globus pallidus , putamen , and dentate nuclei are consistently accompanied by ones in the caudate nuclei or thalami in a subset . the widespread location of lesions throughout the central nervous system is one of the characteristic mr findings in neuroferritinopathy patients . aceruloplasminemia is an adult onset extrapyramidal disorder with iron deposition in the brain , liver , and reticuloendothelial system . the iron deposition in the central nervous system in aceruloplasminemia exhibits a distribution comparable to that in neuroferritinopathy , but in aceruloplasminemia , all basal ganglia nuclei and thalami are simultaneously involved as seen in t2-weighted and t2 * -weighted images . a further distinguishing feature is the lack of the combination of hyperintense and hypointense abnormalities that is often observed in neuroferritinopathy . the cystic changes of the basal ganglia observed in neuroferritinopathy are rarely seen in aceruloplasminemia [ 13 , 14 , 33 ] . inad is an autosomal recessive disorder with motor and mental deterioration , appearing within the first two years of life . the characteristic mri finding in inad patients is cerebeller atrophy , which is often accompanied by signal hyperintensity in the diffuse cerebellar cortex . in inad , abnormal iron accumulation , detected as hypointense lesions on t2wi and t2*wi , is mainly observed in the globus pallidus , sometimes in the substantia nigra , and occasionally in the dentate nuclei . even in advanced cases of inad , there has been no report of iron accumulation in other structures . it is different from the frequent involvement of the putamen , caudate and thalami in neuroferritinopathy . it has been observed in two inad families with pla2g6 mutations that no iron accumulation was detectable on mri despite severe clinical symptoms . patients with parkinson disease ( pd ) may show t2 hypointensity in many anatomic areas compared to normal controls including the substantia nigra pars compacta , dentate nucleus , subthalamic nucleus , and basal ganglia , probably reflecting an excess iron content . quantitative studies have shown a 25% to 100% increase in substantia nigra iron levels in patients with pd compared to in normal controls . the correlation between t2 hypointensity of the substantia nigra and clinical severity has been demonstrated . in patients with alzheimer disease ( ad ) , iron deposition in neurons , neurofibrillary tangles , and plaques has been reported pathologically . to detect brain iron accumulation using mri in ad , investigators tried the high - solution 4.7 t mri or field - dependent - rate - increase ( fdri ) technique . in these studies , increased iron levels were found in the basal ganglia . the signal change on mri reflecting an excess iron content observed in patients with chronic neurologic disorders such as pd and ad is usually slight as compared with that in patients with nbia including neuroferritinopathy . for exact measurement of brain iron or mineralization as a major risk factor for neurodegenerative diseases , multimodal and advanced mri techniques the variety of mri findings including cystic degeneration of the basal ganglia , the combination of hyperintense and hypointense abnormalities , t2 hypointense lesions reflecting iron deposits , and cortical atrophy are specific to neuroferritinopathy . in cases of suspected neuroferritinopathy , mri may be useful for the detection and confirmation of such findings . at an early stage , since the abnormal iron deposits might be not detectable on t2-weighted imaging , t2 * -weighted imaging is recommended . in most cases , there are clear distinguishing features for neuroferritinopathy and other iron accumulative disorders , including pkan , inad , and aceruloplasminemia . however , there is a degree of radiological overlap between neuroferritinopathy and these other iron accumulative disorders . the multimodal and advanced mri techniques being developed to more sensitively and specifically quantify brain iron will be important for correct diagnosis and better understanding of the neurodegenerative processes in the pathological brain .

neuroferritinopathy is a neurodegenerative disease which demonstrates brain iron accumulation caused by the mutations in the ferritin light chain gene . on brain mri in neuroferritinopathy , iron deposits are observed as low - intensity areas on t2wi and as signal loss on t2wi . on t2wi , hyperintense abnormalities reflecting tissue edema and gliosis are also seen . another characteristic finding is the presence of symmetrical cystic changes in the basal ganglia , which are seen in the advanced stages of this disorder . atrophy is sometimes noted in the cerebellar and cerebral cortices . the variety in the mri findings is specific to neuroferritinopathy . based on observations of an excessive iron content in patients with chronic neurologic disorders , such as parkinson disease and alzheimer disease , the presence of excess iron is therefore recognized as a major risk factor for neurodegenerative diseases . the future development of multimodal and advanced mri techniques is thus expected to play an important role in accurately measuring the brain iron content and thereby further elucidating the neurodegenerative process .

controversial issues in the management of inguinal hernia in premature infants , include timing of repair , the need for contralateral inguinal exploration and the minimum postconceptional age ( pca ) for day surgery repair . optimal timing for inguinal hernia repair ( hr ) in a premature infant in the neonatal intensive care unit ( nicu ) is still debated . although some authors recommend early hr to prevent the risk of incarceration , others prefer delaying surgery until infants are ready to be discharged home . optimal timing must represent a balance of complications , including hernia incarceration against the risk of intraoperative and postoperative respiratory and surgical complications . there is still no clear consensus as to routine contralateral inguinal exploration in the premature infant without clinical evidence of a hernia . routine admission of former premature infants after general anesthesia for hr has been recommended because of postoperative respiratory complications , however , the minimum pca for day surgery remains uncertain . the aim of this study is to review our experience in the management of premature infants with inguinal hernia at king abdulaziz medical city - riyadh ( kamc - r ) . after obtaining approval from the scientific research committee at kamc - r , a retrospective chart review was undertaken of premature infants ( gestational age ( ga ) < 37 weeks ) diagnosed with inguinal hernia from january 1999 to december 2009 . the practice at our institution is hr in premature infants just before discharge from nicu . the discharge criteria include : ability to feed orally and gaining weight , out of incubator and able to maintain vital parameters , including body temperature independently , weight > 1750 g at discharge andno apnea for 7 consecutive days while off theophylline and oxygen > 72 h. ability to feed orally and gaining weight , out of incubator and able to maintain vital parameters , including body temperature independently , weight > 1750 g at discharge and no apnea for 7 consecutive days while off theophylline and oxygen > 72 h. there were two groups of premature infants : group 1 had hr in the nicu just before discharge , and group 2 were former premature infants who had hr after discharge . the hospital practice is to admit a former premature infant whose pca is < 50 weeks for hr and 24 h apnea monitoring . the data extracted from the charts included gender , ga , birth weight ( bw ) , comorbidities , site(s ) of inguinal hernia , age , and pca at diagnosis of inguinal hernia . the age , pca and body weight at hr , and postoperative complications were also obtained . unpaired t - test and fisher 's exact analysis were performed and p < 0.05 was considered as significant . a total of 84 premature infants charts were reviewed : 74 ( 88% ) males and 10 females ( male to female ratio , 7.4:1 ) , 23 ( group 1 ) and 61 ( group 2 ) [ table 1 ] . hernias were 33 ( 39% ) right - sided , 26 ( 31% ) left - sided , and 25 ( 30% ) bilateral . comorbidities were small for ga , bronchopulmonary dysplasia , necrotizing enterocolitis , intraventricular hemorrhage , and patent ductus arteriosus as shown in tables 1 and 2 . five ( 5.9% ) infants presented with metachronous contralateral inguinal hernia within 10 - 1022 days ( mean 266.6 days ) . recurrent hernias were seen in 5 ( 5.9% ) infants within a range of 47715 days ( mean 302 days ) . other procedures performed included circumcision ( n = 35 ) , orchiopexy ( n = 1 ) , and repair of esophageal atresia and tracheoesophageal fistula ( n = 1 ) . demographic data and comorbidities of both groups comparison of demographic data and comorbidities of premature infants operated after initial discharge of 29 infants diagnosed with inguinal hernia in the nicu , 23 ( 79% ) including one female had repair just before discharge . the hernia sites were nine right - sided , seven left - sided , and seven bilateral . surgical complications included 3 ( 13% ) infants with hernia recurrence and one with scrotal hematoma . sixty - one former premature infants included six infants with inguinal hernia diagnosed in the nicu ; 47 ( 77% ) had day surgery hr and 14 admitted for repair [ table 2 ] . surgical complications included two infants with hernia recurrence , one infant with urinary bladder injury and another infant with surgical site infection . comparing the body weight of former premature infants admitted for repair to day surgery infants showed statistical significance ( p = 0.0039 ) . of 29 infants diagnosed with inguinal hernia in the nicu , 23 ( 79% ) including one female had repair just before discharge . the hernia sites were nine right - sided , seven left - sided , and seven bilateral . surgical complications included 3 ( 13% ) infants with hernia recurrence and one with scrotal hematoma . sixty - one former premature infants included six infants with inguinal hernia diagnosed in the nicu ; 47 ( 77% ) had day surgery hr and 14 admitted for repair [ table 2 ] . surgical complications included two infants with hernia recurrence , one infant with urinary bladder injury and another infant with surgical site infection . comparing the body weight of former premature infants admitted for repair to day surgery infants showed statistical significance ( p = 0.0039 ) . the risk for postoperative complications in premature infants undergoing hr is higher because of the technical difficulties from extreme friability of hernial sac and an increased frequency of concurrent medical problems . optimal timing for hr in premature infants must represent a balance of complications including hernia incarceration against the risk of intraoperative and postoperative respiratory and surgical complications . delaying hr until the infant is clinically stable for discharge allows for these medical conditions to be stabilized or resolved . in this study , 79% of premature infants with inguinal hernia in the nicu had repair just before discharge . at repair , the mean pca and mean body weight were 39.5 weeks and 2214 g , respectively . authors who recommend early hr are concerned about the risk of hernia incarceration before repair . the incidence of incarcerated hernia in the premature infant waiting for hr is reported between 29.8% and 39% . however , in this series no infant in the nicu had episodes of incarceration before hr , which supports the conclusions of a study by gonzlez santacruz et al . therefore , delaying hr until discharge allows the premature infant to be operated on closer to term , which decreases the risk of postoperative apnea without increasing the risk of incarceration . postoperative apnea in premature infants is inversely related to ga and pca and the incidence is less than 5% when the pca is > 60 weeks . if there is no history of apnea or chronic lung disease , lee et al . , propose that former premature infants with pca between 41 and 46 weeks can safely undergo outpatient herniorrhaphy . our hospital policy requires all former premature infants with pca < 50 weeks to be admitted for hr and 24-h postoperative apnea monitoring . a recent meta - analysis recommended that former premature infants undergoing general anesthesia with pca < 46 weeks should be observed for at least 12 h postoperatively , but individualized patient care should be based on associated comorbidities for those between 46 and 60 weeks pca . laituri et al . , had reported overnight observation after hr for premature infants < 50 weeks pca . a high percentage of these premature infants had a postoperative event related to apnea in the recovery room , but not overnight . due to the evolution of anesthetic practice , and the use of newer less soluble volatile anesthetic agents , infants have faster awakening in the recovery room . therefore , the incidence of apnea may have changed over the past decade as new agents are being used for general anesthesia . murphy et al . , believe that the risk of apnea is much lower in the current anesthetic practice . lee et al . , have questioned routine hospital admission because of the minimal risk of postoperative apnea in former premature infants undergoing elective hr . in this study , the mean pca for former premature infants admitted for hr and day surgery infants is 47 weeks and 66.5 weeks respectively ; and no infant had a postoperative apneic episode . a study by ozdemir and arikan showed the rate of postoperative apnea in a former premature infant older than 45 weeks as 0.8% . they concluded that infants with pca > 45 weeks and without comorbidities may undergo day surgery hr . despite the flaws in retrospective studies and a small number of patients in this study , with the current general anesthetic agents , former premature infants with pca > 47 weeks may undergo day surgery hr without increasing the risk of postoperative apnea . in our study , the incidence of metachronous inguinal hernia in premature infants has been reported between 7% and 14.8% . exploration of an asymptomatic inguinal side is to detect a patent processus vaginalis or a hernia , so as to avoid the chance of a contralateral inguinal hernia incarceration and second anesthesia . however , the presence of patent processus vaginalis does not mean that the infant will develop an inguinal hernia . in a prospective study of 264 premature and term infants who developed metachronous inguinal hernias , marulaiah et al . , concluded that routine contralateral exploration is not indicated because of the risk of spermatic cord injury and low occurrence . the hernia recurrence rate of 5.9% in our series is within the reported range of 2.6 - 8.6% . vaos et al . , had reported a hernia recurrence rate of 12.1% and 14.1% if hr is early or delayed , respectively . they suggested that repair of incarcerated inguinal hernia is associated with a high likelihood of recurrence because of technical difficulties from edematous and friable sac . , found a recurrence of 62.5% in premature boys who underwent hr and concluded that large hernial sacs , inadvertent opening of sacs , low gestation , and specific comorbidities such as the presence of ventriculoperitoneal shunt or connective tissue disease are associated with a higher likelihood of recurrence . laparoscopic hr in premature infants has been reported recently with postoperative complications similar to those reported by open technique . in a retrospective analysis of 67 infants weighing 3 kg or less ( 64 premature ) , who underwent laparoscopic hr , hernia recurrence was 4.4% . one disadvantage of laparoscopy in the premature is the need for endotracheal intubation and assisted respiratory ventilation . however , in laparoscopic repair there is no difference in the access for either unilateral or bilateral hernia . although laparoscopic hr is considered as a safe , procedure a structured training program is required for trainees to ensure satisfactory outcome . the limitations with this retrospective study include inadequate data collection from medical charts because of poor documentation , undetected or unreported episodes of apnea , and small number of infants . delaying hr in a premature infant in the nicu to just before discharge allows for repair closer to term without increasing the risk of incarceration . because of low occurrence of metachronous inguinal hernia contralateral inguinal exploration a former premature infant may undergo day surgery hr as day surgery if the pca is > 47 weeks without increased risk of postoperative apnea . however , a multicentered prospective study is required to establish the minimum pca for former premature infants to undergo day surgery hr .

aim : debatable issues in the management of inguinal hernia in premature infants remain unresolved . this study reviews our experience in the management of inguinal hernia in premature infants.materials and methods : retrospective chart review of premature infants with inguinal hernia from 1999 to 2009 . infants were grouped into 2 : group 1 had repair ( hr ) just before discharge from the neonatal intensive care unit ( nicu ) and group 2 after discharge.results:eighty four premature infants were identified . none of 23 infants in group 1 developed incarcerated hernia while waiting for repair . of the 61 infants in group 2 , 47 ( 77% ) underwent day surgery repair and 14 were admitted for repair . at repair mean postconceptional age ( pca ) in group1 was 39.5 3.05 weeks . mean pca in group 2 was 66.5 42.73 weeks for day surgery infants and 47.03 8.87 weeks for admitted infants . none of the 84 infants had an episode of postoperative apnea . five ( 5.9% ) infants presented subsequently with metachronous contralateral hernia and the same number of infants had hernia recurrence.conclusions:delaying hr in premature infants until ready for discharge from the nicu allows for repair closer to term without increasing the risk of incarceration . because of low occurrence of metachronous hernia contralateral inguinal exploration is not justified . day surgery hr can be performed in former premature infant if pca is > 47 weeks without increasing postoperative complications .

the patient was a 68-year - old man with a history of type ii diabetes mellitus , peripheral neuropathy , hypertension , chronic obstructive pulmonary disease on home oxygen , bipolar depression , and gastroesophageal reflux who presented with shortness of breath and cough for 2 weeks . he had noted a decrease in exercise tolerance and intermittent diarrhea over this time . in the emergency department , he was treated with vancomycin and piperacillin / tazobactam and transferred to the medical intensive care unit where dopamine was started for hypotension and presumed sepsis . his condition stabilized and he was transferred to a medical floor where the hospital course was complicated by a pulmonary embolus , colonic distension and profuse watery diarrhea . the patient was diagnosed with colonic pseudo - obstruction ( ogilvie 's syndrome ) , and nasogastric and rectal tubes were placed . the renal service was consulted for hypokalemia that was difficult to control with potassium supplementation . medications at the time of consultation included : aspirin 81 mg daily , atorvastatin 80 mg daily , budesonide / formoterol , levalbuterol , tiotroprium , insulin , pantoprazole 40 mg daily , piperacillin / tazobactam and a total of 100 meq of potassium chloride daily . his blood pressure was 103/50 mm hg , his pulse was 102 beats per minute , and the respiratory rate was 24 breaths per minute . on physical examination , the patient was tachypneic and was using accessory muscles . trace lower extremity edema was noted . a foley catheter and rectal tube were in place . laboratory evaluation revealed a serum sodium concentration of 146 mmol / l , chloride 118 mmol / l , potassium 2.7 mmol / l , and bicarbonate 19.9 concentrations were 6.1 mmol / l and 110 mol / l , respectively . of note , arterial blood gases showed a ph of 7.27 , pco2 of 36.9 mm hg and bicarbonate of 17.1 meq / l , compatible with a simple metabolic acidosis . urine electrolytes : sodium 49 mmol / l , potassium 20 mmol / l , and chloride 90 mmol / l with a urine anion gap of minus 21 . stool electrolytes revealed a sodium concentration of < 10 mmol / l and a potassium concentration of 139.7 mmol / l . marked colonic distension ( 13 cm ) was seen on a radiographic examination of the abdomen ( fig . 1 ) . a diagnosis of severe gastrointestinal potassium wasting as a result of colonic pseudo - obstruction ( ogilvie 's syndrome ) was made . the patient received large doses of potassium chloride ( > 100 mmol / day ) with serum potassium concentrations maintained in the 3.54.0 mmol / l range . hypokalemia may be the result of one or more basic processes including : inadequate oral intake , a shift of potassium from the extracellular fluid to the intracellular fluid , renal losses or gastrointestinal losses . inadequate intake alone is rarely a cause of hypokalemia given the kidney 's ability to reduce potassium excretion to about 10 mmol / day . renal and gastrointestinal losses are associated with a normal or low blood pressure . with renal losses , the urinary potassium excretion generally exceeds 2030 mmol per day , whereas with gastrointestinal losses , there is renal potassium conservation , and urinary potassium excretion is generally less than 20 mmol / day . gastrointestinal losses from the upper tract , such as with vomiting or nasogastric drainage , are associated with metabolic alkalosis , whereas metabolic acidosis is seen with diarrhea and laxative abuse . our patient had hypokalemia , metabolic acidosis , and a low 24-hour urinary potassium excretion as a result of diarrheal losses . stool electrolyte studies showed a very low sodium ( < 10 mmol / l ) and very high potassium concentration ( 139.7 this pattern is typical in patients with colonic pseudo - obstruction also known as ogilvie 's syndrome . colonic pseudo - obstruction or ogilvie 's syndrome was first described in 1948 by sir william ogilvie . as its name implies , it is characterized by a functional and not mechanical obstruction of the colon for reasons that are poorly understood . it has been speculated that the syndrome results from an imbalance in autonomic nervous system input in the colon with a stimulation of sympathetic and a suppression of parasympathetic activity . in the 2 patients originally reported by ogilvie patients presented with symptoms typical of bowel obstruction including abdominal distension , nausea and vomiting . the majority had diarrhea , but constipation was described in a subset of patients . the diagnosis was most often made on plain film of the abdomen , which was most commonly suggestive of a distal colonic obstruction that ultimately was found to be functional in nature . the distal colon receives its parasympathetic innervation from spinal segments s2s4 , and the disruption of this input ( which normally stimulates intestinal contraction ) can result in a functional obstruction . binder 's group carefully examined a 78-year - old woman that presented 1 week after surgery for a hip fracture with colonic pseudo - obstruction . fecal potassium concentrations ranged from 130 to 170 mmol / l , and fecal sodium concentrations were between 4 and 15 mmol / l . they concluded that colonic pseudo - obstruction was a unique form of secretory diarrhea that is mediated by excessive potassium and not the sodium losses in stool . up until this time , secretory diarrhea was recognized to result from either the inhibition of sodium reabsorption or active chloride secretion , followed by the passive movement of sodium to maintain electroneutrality . the accumulation of sodium salts in the intestinal lumen obligates the isotonic loss of water resulting in sodium and water losses in stool along with some potassium . in patients with ogilvie 's syndrome , it is the active secretion of potassium that drives the secretory diarrhea and stool potassium losses are high , while stool sodium losses are low . this is reflected in stool electrolytes that reveal a very high potassium concentration , > 130 mmol / l , and a very low sodium concentration , < 15 mmol / l . this same pattern of stool electrolytes was subsequently confirmed in a case series of 5 patients with colonic pseudo - obstruction . binder speculated that 3 mechanisms could be responsible for the stimulation of active colonic potassium secretion including hyperaldosteronism resulting from diarrhea - induced volume depletion , the activation of -adrenergic receptors by catecholamines as well as colonic distension . an imbalance in autonomic stimulation was postulated to be responsible for the potassium secretion that occurs in the setting of catecholamine - stimulated sodium reabsorption . this results in hypokalemia as a result of fecal potassium losses and hypernatremia due to fecal water losses in the setting of low sodium losses . simon et al . described a patient with colonic pseudo - obstruction after hemorrhagic shock . stool electrolytes showed the typical pattern of a low sodium concentration ( 11 mmol / l ) and a high potassium concentration ( 143 mmol / l ) . the diarrhea did not resolve after ileostomy , and the patient eventually underwent a colectomy with the resolution of hypokalemia . immunostaining showed a marked overexpression of the large conductance maxik or bk channel in both surface and crypt colonocytes far beyond that seen in end - stage renal disease ( esrd ) . a cell model of a typical colonic epithelial cell potassium movement into the colonic epithelial cell across the basolateral membrane can occur on either the na / k atpase or the ncc1 isoform of the na / k/2cl cotransporter . potassium then exits the cell via a large conductance potassium channel known as maxik or bk . this is the same channel that is expressed in the connecting tubule and collecting ducts of the kidney that mediates flow - stimulated potassium secretion . it is regulated by camp and protein kinase a as is the chloride channel cftr , and it is inhibited by somatostatin , an effect that is mediated via tyrosine phosphorylation . somatostatin was shown as early as 1984 in a case report to reduce the stool volume dramatically in a patient with colonic pseudo - obstruction . the zero splice variant , which is missing the 58 amino acid exon 18 , is activated by camp . in vitro studies show that adrenaline binding to the receptor upregulates the zero splice variant , and this effect is blocked by propranolol . our patient was also receiving inhaled -2 agonists , and this may have contributed to the colonic potassium losses . the bk channel is the same channel that plays an important role in potassium homeostasis in later stages of chronic kidney disease and esrd . under normal circumstances however , as renal function declines , the colon plays an increasingly important role in potassium excretion . the distal colon becomes a potassium secretory organ , especially in patients with esrd . under basal conditions , potassium secretion is about threefold greater in esrd patients compared to those with normal renal function . this effect is lost in bk knockout mice , and the bk channel appears to be the sole exit pathway for potassium movement into the colonic lumen . in summary , the nephrologist should be aware of colonic pseudo - obstruction because it can cause profound hypokalemia that requires large amounts of potassium supplementation to maintain potassium balance . the diagnosis is established by demonstrating marked colonic dilation in the absence of a mechanical obstruction on imaging studies associated with a high stool potassium concentration and a low stool sodium concentration .

we report a case of hypokalemia resulting from colonic pseudo - obstruction or ogilvie 's syndrome . colonic pseudo - obstruction is characterized by profuse watery diarrhea that has a low sodium and high potassium concentration . it is seen in a variety of medical and surgical conditions , but its exact cause remains unknown . it is thought to result from an imbalance of sympathetic and parasympathetic input in the distal colon . the diarrhea is secretory and driven by potassium secretion rather than the inhibition of sodium reabsorption or chloride secretion , which are the most common pathophysiologic mechanisms of secretory diarrhea . affected patients often lose > 100 mmol of potassium daily . colonic pseudo - obstruction is associated with a dramatic upregulation of the maxik or bk potassium channel . this channel plays a prominent role in flow - mediated potassium secretion in the connecting tubule and collecting duct and is also upregulated in the distal colon in patients with advanced chronic kidney disease and end - stage renal disease . in vitro studies show that the channel is regulated by catecholamine binding to the receptor and cyclic amp upregulation , somatostatin and aldosterone , insights that can be used to help guide pharmacologic therapy . nephrologists should be aware of colonic pseudo - obstruction as a cause of extrarenal potassium loss .

numerous short and thick hairs set obliquely in the fibers of orbicularis oculi , corrugator and frontal part of occipito frontalis are inserted in the dermis of eye brows . the head of the eyebrows overlies the frontal sinus and the tail is usually in the region of zygomatiocofrontal suture . it is an appendage of the hair bearing scalp rather than an extension of facial tissue . the head of the eyebrows overlies the frontal sinus and the tail is in the region of the zygomaticofrontal suture . the female eye brow is more arched and rest slightly higher than male eyebrow , which usually rests at the level of superior orbital rim . male eye brows are more irregular . the natural direction of hair of the eyebrow is varied . inferoateral hair direction is found in the upper and lateral parts . in medial and lower eyebrows play an important function in facial identification and may be at least as important as the eyes . human beings have a single eye brow above each eye , but this article presents a case report of a child with double eye brows on the left side . the present case report is about a 6-year - old girl presented to department of pediatric and preventive dentistry , guru nanak institute of dental science and research , kolkata for routine dental check - up . there was no relevant medical history with normal built , gait and intelligence . on facial examination , there was no gross asymmetry of face or any abnormal swelling . dermatological examination revealed that the eyebrows on the both the sides were sparser on the medial sides when compared with the lateral sides . the eye brows were free from any pathology except a double layer of eyebrow was present above the left eye . second layer of eye brow was just present above the first layer [ figures 1 and 2 ] . family history revealed no systemic disease or any extra layer of eye brow in either of maternal or paternal individual . no cosmetic / aesthetic or therapeutic treatment has been received by the child for double eyebrow . routine laboratory tests ( complete blood count , liver function test , urine analysis , abdominal ultrasound ) were all normal . considering the clinical features , a diagnosis of double eyebrow was concluded . the eyebrow is a transverse elevation of hair , which starts medially just inferior to the orbital margin and ends laterally above the orbital margin . they are formed by the transverse elevation of the superciliary ridge of the frontal bone . the superficial muscles of the head develop as mesodermal laminae which begin at the second branchial arch . from infraorbital lamina orbicularis , oculi , corrugator , these laminae join above the eye and form the interdigitating muscular structure of the brow . at 8 - 10 week of fetal development formation of primitive hair starts as a focal crowding of basal cell nuclei in the fetal epidermis . when the basal cell germ enlarges it becomes asymmetric and extends obliquely downward as a solid column . contracting the orbital sections of orbicularis oculi lowers the eyebrows and contracting the corrugators supercilia muscle draws the eyebrows together medially . there are three types of hair found in the eyebrow : ( 1 ) fine vellus hair ; ( 2 ) slightly larger and lightly pigmented hair and ( 3 ) large terminal hair known as the supercilia . the fine hairs form an effective moisture barrier to keep sweat from running downward into the eye . main function of eyebrows is to protect eyes and prevent flowing of salty sweat to eyes . the position and curvature of the eyebrow allows it to shields the eyes from bright light and it is an effective barrier to liquids running from the forehead into the eye . abundant sensory innervations are present in the large hairs of the eyebrow , which are very sensitive to tactile stimulation . the eye brows also function to depict the expression of an individual , like the depression of the medial portion of the eyebrow depicts anger or concern . eye brows abnormalities have a close relation with genomic disorders . in facial esthetics , sexual dimorphism , emotional expression and nonverbal communication eyebrows recent research suggests that eyebrows play an important function in facial identification and may be at least as important as the eyes . main physical function is to prevent flowing of salty sweat to eyes ; henceforth protection of eyes is the main function of eyebrows . eyebrows variation found in various syndromes such as chr1p36.33 microdeletion syndrome , chr2q21 - 23 microdeletion , mowat - wilson syndrome , chr3q26.3-q27 microdeletion , with sparse and broad - based eyebrow , chr7p15.3 duplication : extreme sparseness of the lateral portion of the eyebrows , chr9q34.3 terminal deletion , arched eyebrows and synophrys , chr10q22.3 - 23.2 duplication , with medial flaring eyebrows etc . ip 36.33 microdelation has a close relationship with deep - set eyes and horizontal eyebrows . eye brows abnormalities are useful diagnostic aids of chromosomal phenotype syndrome along with syndromic learning disability and developmental delay . suggested are diagnostic sign of genomic disorder . according to them array based comparative genomic hybridization cause multisystemic developmental diseases in human beings along with learning disability and developmental delay along with learning disability and developmental delay are responsible for most genomic disorder along with craniofacial skeletal and behavioral changes . the study done by berkenstadt et al . observed partial duplication of the eyebrows with other anomalies in a 7-year - old son . there was excess hair on the forehead and long eyelashes as well as excessive wrinkling of the periorbital skin when the eyes were closed . he had bilateral syndactyly involving the second to the fourth fingers and the second and third toes . gross - kieselstein and har - even also observed the same disorder in brother and sister of north african jewish descent . we could not detect any systemic disorder in our case with physical and laboratory investigations . it is clear that , new reports are still needed to enhance our knowledge about this rare entity .

eye brows are essential for esthetic and functional purposes . various kinds of eye brows are found in human species . protective function is one of the important functions of eye brows . double eye brow is a very rare condition found in human . this case report describes one of the rare cases of double eye brow .

cryptococcosis is a life - threatening fungal infection , caused by cryptococcus ( c. ) neoformans , an encapsulated yeast . primary infection develops in the lungs by inhalation and remains asymptomatic in the majority of immunocompetent hosts . t cell - related immunodeficiency , most commonly in association with hiv infection is a major predisposing factor for cerebral cryptococcosis . disseminating disease may develop as an aids defining disease in hiv infected individuals - predominantly in patients with cd4 + t cell count less than 100/l - and presents in up to 80% as meningitis or meningoencephalitis . positive direct staining or culture of cerebrospinal fluid ( csf ) and/or antigen testing in csf ensures the diagnosis of cryptococcal meningitis ( cm ) and a positive serum cryptococcal antigen ( cra ) titer is suggestive for dissemination . in hiv infected individuals responding to active anti retroviral therapy ( haart ) and prior cryptococcal infection , cases of immune reconstitution inflammatory syndrome ( iris ) related cm have been described . in a recent prospective study poor prognosis has been associated with a number of risk factors in aids - related cm . a serum cra - titer 1:512 , a csf cra - titer 1:1024 , culture of cryptococcus from csf > 10cfu / ml , a csf leukocyte count 20 cells/l , and initial alteration in mental status [ 8,10 - 12 ] . after 2 weeks of therapy with amphotericin b plus flucytosine , csf culture results are negative in 60% to 75% . hiv infection was diagnosed in may 2008 , in a 33 year old homosexual man who presented to another hospital with fever and unproductive cough . chest x - ray and ct - scans revealed diffuse homogeneous ground glass opacity in both lungs and pneumocystis jiroveci could be de monstrated in bronchoalveolar lavage ( bal ) . standard therapy with trimethoprim - sulfamethoxazole ( tmp - smz ) and prednisolone was successful . replicative hiv infection could be proven by pcr ( 91.000 copies / ml ) and the cd4 cell - count of 59/l indicated a profound immunodeficiency . two months later the patient was admitted to our clinic with increasing headache , emesis , lethargy and focal seizures for the past 4 weeks . initially performed magnet resonance imaging ( mri ) scan showed bihemispheric mass right more than left in basal ganglia area , which was not present on a mri done 3 weeks before admission . there were no signs of elevated intracranial pressure ( icp ) on mri ( figure 1 ) . a ) cerebral mri 3 weeks prior to admission ; b ) mri on admission with bihemispheric mass right more than left in basal ganglia area ( arrow ) ; c ) cerebral ct after 3 weeks of antifungal combination therapy with loss of gray - white distinction and effacement of cerebral sulci . a lumbar punction performed on the same day revealed a csf leukocyte count of 10/l , positive csf cra ( 1:8192 ) with positive india ink test . encapsulated c. neoformans var grubii isolates growing on culture were sensitive to amphotericin b , fluconazole and flucytosine . culture of csf for bacteria , including mycobacteria remained negative , so did specific test for treponema pallidum , toxoplasma gondii and jc - virus . on admission the viral load was undetectable and the cd4 cell - count was still low ( 44/l ) . an intravenous antifungal drug combination with fluconazole 400 mg / d , flucytosine ( 150 mg / kg / d ) and liposomal amphotericin b ( 4 mg / kg / d ) was administered . due to a rapid virological response under haart , initially the patient improved mildly in mental status and serum cra - titer dropped by 3 titer steps to 1:4096 one week after initiating antifungal therapy . about two weeks after starting antifungal therapy he unexpectedly clinically worsened continually with increase in seizure frequency . another lumbar puncture performed revealed a 3 titer steps decrease of csf cra - titer ( 1:1024 ) . biopsy ( figure 2 ) showed accumulation of c. neoformans within brain parenchyma with little cellular immune reaction and without any evidence of granulomatous encephalitis . course of serum cryptococal antigen titer , antifungal antigen titer , antifungal combination therapy , icp controlling therapy and the course of disease . during biopsy , an increased opening pressure of 462 mm of water ( physiological pressure < 200 mm of water ) could be measured . brain ct - scan obtained showed brain edema but no hydrocephalus , a common cause for elevated intracerebral pressure in cm ( figure 1 ) . due to the risk of herniation , reduction of icp at that time point would have require trepanation , which was denied by health care directives from the patient and his relatives . hiv - associated cm is an aids defining disease , indicating an advanced immunodeficiency . without therapy death by cm usually occurs within 2 - 4 weeks of diagnosis . in a nationwide surveillance in france a significant decrease of average mortality rate in the haart era ( 15.3 per 100 person - years ) compared to the pre - haart era ( 63.8 per 100 person - years ) cm associated mortality in patients under antifungal therapy is determined to be over 20% in the first 3 months after diagnosis . in accordance with the described risk factors the presented case fulfils criteria for severe cryptococcal cerebral infection . he initially presented with mental alteration , had a high serum cra - titer of 1:32.768 and a csf cra - titer of 1:8.192 , a low csf leukocyte count of 10/l and positive culture for c. neoformans . a rapid establishment of antifungal activity within affected tissue should be the primary goal of any induction therapy . in germany a triple therapy with amphotericin b , flucytosine and fluconazole is recommended for meningitis . the rate for complete remission of meningitis , which is achieved in around 80% of patients , may be slightly higher than under dual therapy with amphotericin b and flucytosine as favored in the united states . elevated icp in the presented case was due to brain edema without any signs of hydrocephalus on imaging . according to the guidelines of idsa managing of icp by lumbar punctures or external drainage is indicated in icp caused by hydrocephalus . due to the risk of herniation reduction of icp at that time point would not allow lumbar puncture . trepanation as the treatment of choice was denied by relatives . as an option of conservative icp controlling therapy mannitol and sedatives however prognosis in cases with elevated icp remains poor also in cases with internal hydrocephalus . although invasive measures can reduce icp , a survival benefit over 2 or 10 weeks was absent in a prospective study . clinical progress occurred despite an appropriate combination therapy with fluconazole , flucytosine and liposomal amphotericin b and evidence of fungal susceptibility - guidelines defined by clsi 2008 - in the initial as in the follow up csf culture and indicates the limited clinical correlation of resistance tests and clinical efficacy in cm . progress of infection is suggested by a positive csf culture after two weeks as well by histological demonstration of c. neoformans with signs of reproducing by budding but a lack of significant inflammatory signs . predominance of iris - related cm is unlikely in this case due to : ( i ) persistent positive culture from csf ; ( ii ) histological demonstration of vital c. neoformans with signs of fungal growth ; ( iii ) absence of granulomatous inflammation , which would be the expected type of inflammation in hiv - negative patients and in iris - related cryptoccocal infections . in contrast to the clinical progression of the infection serological and csf - titers for cryptococcus decreased under therapy . although sequential monitoring of elevated cra in serum and csf suggests to reflect directly the burden of fungal pathogen , it is potentially misleading and therefore not recommended as a surrogate marker to follow - up aids - related cryptococcal infection during therapy [ 12,20 - 22 ] . in conclusion careful and close clinical observation , neuroimaging and direct confirmation of csf sterility by lumbar puncture or biopsy are crucial in the monitoring during the acute phase of cryptococcal disease . as shown in the presented case a decrease of cra in serum and csf is not a reliable parameter for the response to antifungal treatment in the presented case . the primary failure of treatment occurred despite initial use of three recommended elements of an antifungal combination therapy , and in the absence of evidence for primary resistance in vitro of the isolated cryptococci .

cryptococcus neoformans is the most common cause of life threatening meningoencephalitis in hiv - infected patients . diagnosis is based on tests for cryptoccocal antigen in serum and cerebrospinal fluid , and on culture of the organism . we present a case of aids - related cryptococcal meningoencephalitis unresponsive to antifungal combination therapy , despite of evidence of fungal susceptibility in vitro . significant decreases in cryptococcal antigen titers in serum and cerebrospinal fluid did not correlate with progress in disease and fatal outcome .

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

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

mexican population is estimated to be over 120 million of which 78% lives in urban areas [ 1 , 2 ] . this implies a significant burden to provide medical care where gdp is nearly $ 1,300 billion usd and average income per capita is fairly below $ 10 thousand usd . yet nearly a fourth of its citizens is deprived of adequate medical services . among the obstetrical population , this has derived in abuse of cesarean sections ( cs ) achieving 45.1% of the total births in mexico . according to the world health organization , this figure should be under 15% , our private and governmental institutions average 69.6% and 40.6% , respectively , well above the who recomendation . these ciphers resemble those in regions like brazil ( > 30% ) , chile ( 40% ) , and the united states of america ( 32.8% ) [ 5 , 6 ] . cs have an increased risk of intraoperative complications ( 18% ) , excess blood loss ( 9% ) , blood transfusions ( 1% ) , febrile morbidity ( 20% ) , wound infection ( 6% ) , urinary tract infection ( 6% ) , neonatal respiratory morbidity ( 3% ) , and other critical situations like venous thromboembolism [ 710 ] . this surgical procedure is effective in saving maternal and infant lives but only when they are required for adequate medical reasons . vaginal deliveries performed with safe practice of forceps and vacuum extraction techniques may help diminish the increased cs rates . in the usa only 3.4% of the births in 2012 were assisted by forceps or vacuum extraction , compared to 1990 where forceps and vacuum extraction deliveries represented 9.01% of all births . these ovds can safely assist a vaginal delivery during the second stage of labor ( time elapsed from full cervical dilation to neonate delivery , nulliparas beyond 3 hours and multiparas beyond 2 hours ) and are associated with lower maternal morbidity without increasing neonatal complications . a total of 5,375 deliveries performed at the abc medical center ( from january 2007 to december 2012 ) were reviewed . in 146 cases forceps was used at delivery , and were evaluated for parameters on maternal forceps indication , type of forceps utilized , gestational age , neonatal birth weight , previous gestations and c - sections , apgar scores , surgical bleeding , and reported maternal and neonatal complications . all providers are certified obstetricians by mexican boards and standards , with a minimum 5-year experience as obstetrical practitioners . from a total of 5,375 deliveries selected for this study , 66.3% were c - sections and 33.7% vaginal deliveries with a forceps rate of only 2.55% ( included in the vaginal delivery percentage ) . the average maternal age was 30.9 4.7 years and the average gestational age was 39 1 weeks ; 56% were in their first pregnancy and 26% in their second , although we did have a patient with 12 and 9 previous gestations . most common forceps indications were prophylactic ( 30.8% ) , extended expulsion period ( 30.8% ) , and persistent posterior - occipital presentation ( 18.5% ) ( see table 1 ) . as for the most favored forceps , simpson ( 46.2% ) , kielland ( 32% ) , and salas ( 11% ) specific types of forceps applied for the indications mentioned above are described in table 1 . neonatal outcomes had no serious complications , with median apgar scores at 1 min of 8 and 9 at 5 min . further findings were 7 ( 5.5% ) abrasions and 2 ( 1.4% ) facial lacerations . only one neonate was admitted to the neonatal intensive care unit ( nicu ) due to a gestational age of 34.3 weeks and low apgar scores ( not ovd related ) . the most common maternal complications associated with the use of forceps were third degree perineal lacerations ( 17.12% ) , fourth degree perineal lacerations ( 8.9% ) , and cervical lacerations ( 6.16% ) ( figure 1 ) ; 50% of the ovds were free of any maternal complication and no significant association was seen with neonatal birth weight , albeit a third degree laceration was present in the highest birth weight reported ( average : 3126 370 g ) . surgical hemorrhage was nonsignificant when associated with the type of forceps employed ( p > 0.05 ) , although fourth degree lacerations utilizing the simpson forceps had the largest blood loss average volume ( 480.8 80 ml ) . specific complication risk associated with particular types of forceps employed was evaluated , finding vaginal and perineal lacerations as a common complication in simpson forceps use ( p < 0.05 ) and cervical lacerations using salas forceps ( p = 0.006 ) ( see figure 2 ) . thirteen cases with prior cs were delivered through forceps application and no significant complications were reported ; only 9 had cervical lacerations and 6 had third degree perineal tears . the preferred forceps in these cases was simpson ( 46% ) with prophylaxis as indication due to the prior cs as risk factor ( see table 2 ) . the cs surgery was initially introduced as an emergency technique , alternative to vaginal delivery ; but increased cs rates are associated with higher postpartum use of antibiotics , severe maternal morbimortality , and higher fetal mortality rates , with an increasing number of neonates admitted to intensive care units [ 14 , 15 ] . worldwide , cs have an approximate cost of $ 2.32 billion us dollars , the estimated cost of actual required cs is $ 432 million us dollars , and only 54 countries had cs rates under 10% . cs fails to evidence benefits on maternal and neonatal morbidity and mortality rates when their incidence is above 15% [ 16 , 17 ] . various factors that influence an increase in c - section rates are as follows : ( a ) healthcare providers perceiving c - section as a safer procedure over vaginal delivery ; ( b ) limited ovd trained personnel available to attend the on - growing obstetric population ; ( c ) greater number of advanced maternal age cases ; ( d ) increased misinterpretations of cardiotocographic monitoring ; ( e ) social preference for c - sections over vaginal delivery ; and ( f ) economical incentives related to private insurance companies favor c - sections . there is enough evidence to support the notion that nonmedical factors related to obstetricians and pregnant women play an important role in the delivery modality selection . according to gei et al . [ 18 , 19 ] , the decision to employ a forceps or vacuum should take into consideration three things : ( 1 ) increase of expelling force ; ( 2 ) decrease of resistance of the birth ( maternal ) channel correcting mal - presentations , asynclitism , and deflections , and ( 3 ) decrease of resistance of the birthing channel , increasing the soft pelvis perimeter . these parameters are the basis for the prophylactic use in our study group ; most of these cases were extended 2nd labor stage , previous cs history , and maternal exhaustion . station classification is not used in mexico , and hodge planes are preferred due to their anatomical specificity , being that all forceps were applied on 2nd or 3rd hodge plane . obstructed labor is a major cause of maternal mortality in developing countries and the who has determined that 8% of maternal deaths are due to this complication . prophylactic use of forceps is quite frequent and is applied to cases including prolonged second stage of labor , suspected fetal jeopardy , and maternal benefits provided by a shortened second stage . our study supports this observation since prophylaxis was the most common indication , followed by extended expulsion period and persistent posterior - occipital presentation ; the suitability of the forceps under these conditions remains to be demonstrated . few studies have actually evaluated cases using forceps when no assistance was required and determine morbidity rates and attributable risk [ 19 , 21 , 22 ] . cardiotocography readings are a major factor in deciding for an ovd or a c - section . the fact remains that in most of these cases the preferred procedure is c - section . in our study 2% of the ovds forceps application may have various neonatal complications , the most serious ones being fetal death , neonatal brain damage , and maternal death . among the complications associated with forceps we only found 7 cases of abrasions and 2 lacerations ; other findings like neonatal ecchymosis , caput succedaneum , cephalohematoma , subarachnoid hemorrhage , brachial plexus lesion , facial paralysis , skull fracture , corneal compression injury , retinal hemorrhage , and subgaleal hematoma were reviewed , yet none of these were found in our study [ 23 , 24 ] . in order to avoid complications one must try to employ nonoperative interventions to reduce ovd rates although they must be kept in mind prior to moving on to a cs . risk factors for complications include older women , nulliparous women , heavier fetuses , some variety of dystocia , abnormal contractility patterns , and fetal mal - presentations [ 19 , 21 , 25 ] ; many of these factors were absent in this study , since most of our patients were primiparous and the average neonatal weight was 3126 370 g. the few newborns weighing over 3,200 g had no serious complications . maternal age is always a concern due to chromosomopathies , maternal near miss , preterm deliveries , stillbirths and neonatal complications ; still the risks tend to increase in patients after 35 years of age . in our study the average age was 30.9 4.7 years and the one complication was a preterm 34.3-week - old , admitted to the nicu due to low apgar scores . forceps has achieved greater acceptance in our region over vacuum , hence the low incidence and data availability with the latter . experience recommends simpson , salas , and tucker mclane as prophylactic forceps ; our study shows that kielland ( 30.8% ) was the most selected for this indication , followed by simpson ( 26% ) ( see table 1 ) ; we believe that the main reason here is the experience , familiarity , and preference the physicians at our hospital have with this particular instrument . for prolonged expulsive periods , the favored forceps was simpson ( 30.8% ) , as well as for posterior - occipital presentation ( 18.5% ) ( see figures 1 and 2 ) . kielland forceps is well known for asynclitism , deflection , and mal - rotation correction , together with other instruments as salinas and salas ( both designed and published in mexico ) . each case must be individualized and the physician 's experience should be taken into account when selecting the most adequate instrument [ 27 , 28 ] . instrumental deliveries are perceived with a high morbidity ; misinformation as well as the severity of the worst cases reported have undermined the usefulness of the ovd . perineal lacerations in various degrees were the most prevalent complications ( third and fourth degree ) together with cervical lacerations . although all forceps types were quite safe to use , most complications were associated with the simpson class , although it was the most employed ( 46.2% ) , and the only statistically significant lesion associated with it was vaginal channel lacerations ( p = 0.016 ) . a significant finding was the salas forceps association with cervical lacerations ( p = 0.005 ) , considering its most frequent indication being extended expulsion period ( only 18% of the cases ) ( see figure 2 ) . we believe that salas forceps extensive toes and unfenestrated design may have been responsible for these cervical lesions . we recognize the need of a larger sample to further evaluate the complication rates , proper use , and indications of forceps and other ovds . our hospital is a sample of what happens in our region and would definitively benefit from an increased utilization of forceps and ovd when properly indicated . although a small percentage of forceps applications are performed , complication rates are remarkably low and when present few are severe or life - threatening . forceps are an underused option prior to cs , which could properly solve various obstetric situations while contributing to diminishing cs increasing incidence rates .

objective . assessment of the frequency of complications observed with various forceps and operative vaginal delivery ( ovd ) techniques performed at the abc medical center ( mexico city ) to evaluate their safety , bearing in mind the importance of decreasing our country 's high cesarean section incidence . methods . we reviewed 5,375 deliveries performed between the years 2007 and 2012 , only 146 were delivered by ovd . results . only 1.0% of the cases had a serious , life - threatening situation ( uterine rupture ) . the simpson forceps was the most favored instrument ( 46% ) due to its simplicity of use , effectiveness , and familiarity . prophylactic use was the most common indication ( 30.8% ) and significant complications observed were vaginal lacerations ( p = 0.016 ) , relative risk ( rr ) of 3.4 ( 95% confidence interval [ ci ] : 1.1510.04 ) , and fourth degree perineal tear ( p = 0.016 ) , rr of 3.4 ( 95% ci : 1.1510.04 ) . conclusions . forceps use and other ovd techniques are a safe alternative to be considered , diminishing c - section incidence and its complications .

fabry disease is an x - linked deficiency of -galactosidase ( gla ) resulting in widespread lysosomal storage of -galactose lipid conjugates represented mainly by , in decreasing order , globotriaosylceramide , digalactosyl ceramide ( desnick et al . 2001 ) , and blood group b glycolipid ( ledvinova et al . 1997 ) . the cell types expressing maximum storage are vascular endothelium , smooth muscle , cardiomyocytes , and podocytes . storage , in varying degrees , has also been described in fibroblasts ( elleder 2010 ) . there has only been one report that showed dermal adipocyte storage in a single case of fabry disease ( le charpentier et al . we present results of analysis of biopsies and postmortem samples in a series of ten fabry patients that showed regular expression of storage in adipocytes . skin biopsies of seven male fabry patients and samples from three autopsies of fabry hemizygotes were examined . in all of them , diagnosis was verified biochemically ( gla deficiency ) and/or at the dna level ( mutation in the gla gene ) . four patients were treated with enzyme replacement therapy ( ert ) ( see table 1 ) . the samples were processed by the standard procedures for ultrastructural examination , i.e. , fixation in 4% paraformaldehyde , followed by osmification , dehydration , and embedding into a epon - araldite mixture . thin sections were cut with a diamond knife , double - contrasted with uranyl acetate and lead citrate and examined using tesla 500 and jem 1200 ex electron microscopes . autopsy samples were also embedded in paraffin and examined using autofluorescence in unstained sections or after staining with sudan black b and periodic acid - schiff ( pas ) for detection of ceroid - type lipopigment . cryostat sections of unfixed tissues were examined in parallel using pas in sections pre - extracted with anhydrous acetone [ removal of triacylglycerols ( tags ) ] and following total lipid extraction ( chloroform - methanol 2:1 v / v , 1 h , room temperature ) . in paraffin sections , the lysosomal storage compartment was demonstrated using an immunohistochemical detection of cathepsin d , as described elsewhere ( hulkova et al . samples from autopsies of patients who died between the ages of 30 and 60 years without diagnosis of a lysosomal storage disorder were used as age - matched controls for detection of lipofuscin - type lipopigment ( age pigment ) . nomenclature of the lipopigment type was used as recommended ( seehafer and pearce 2006 ) , i.e. , ceroid as disease - induced lipopigment ; lipofuscin as solely the age - related variant . all were of typical complex fabry phenotypepatientbiopsy ( age)storage in adipocytesenzyme activity in leukocytes mutationertfurther remarks1.skin biopsy ( 24)+1.2p.gln280lyssince age 45aliveheart biopsy+2.skin biopsy ( 25)+1.4p.ser65argfsx61 ( p.ser65fs)withoutdied aged 50 on renal failure3.skin biopsy ( 16)+0.3p.arg342glnwithoutalive4.skin biopsy ( 33)+0.9p.arg342glnwithoutalive5.skin biopsy ( 28)+2.8p.ala135valwithoutalive6.skin biopsy ( 33)+2.4p.leu268valfsx4since age 57aliveheart biopsy+7.heart biopsy+0.4p.his225leufsx5since age 57alive8.not done+ in autopsynot donep.asp93asnwithoutdied aged 47 ; brain embolisation ( heart thrombosis)9.skin biopsy ( 37)+ in both biopsy and autopsynot donep.leu268valfsx4withoutdied aged 44 ; brain embolisation ( heart thrombosis)10skin biopsy ( 41)+ in both biopsy and autopsy1p.leu294termsince age 43died after cardiosurgery aged 52controls n = 100 , mean standard deviation ( sd ) 53,8 11,4 , range 32,2 89 ert enzyme replacement therapy measured in peripheral leukocytes ( nmol / mg / h ) survey of patients examined . all were of typical complex fabry phenotype controls n = 100 , mean standard deviation ( sd ) 53,8 11,4 , range 32,2 89 ert enzyme replacement therapy measured in peripheral leukocytes ( nmol / mg / h ) it was represented by a perinuclear crescent - shaped line of storage lysosomes of varying thicknesses that had been pushed into the subplasmalemmal area by the physiological cytoplasmic lipid storage depot . the storage lysosomes were represented by concentric lipid membranes , modified to varying degrees , by amorphous deposits of ceroid type lipopigment ( fig . . the number of storage lysosomes was increased , and the lysosomes were more clustered in adipocytes with less voluminous lipid content ( fig . 1b ) . with optical microscopy , storage was best observed in paraffin sections due to the prominent yellow autofluorescence or by positive staining with sudan black b and by the signal from the cathepsin d luminal lysosomal marker ( fig . , there was positive staining with pas , abolished practically completely with total lipid pre - extraction . storage was seen in all regions examined ( subcutaneous , subepicardial , retroperitoneal , perirenal ) . often , there were fibroblast - like cells in the vicinity of adipocytes expressing a high degree lysosomal storage ( preadipocytes ? ) . lipofuscin - type lipopigment in adipocytes of age - matched controls was either absent , or present in questionable amounts . fig . 1 a , b skin biopsy of a male fabry patient : a detail of storage lysosomes in an adipocyte showing prevalence of lipid membranes . b two subcutaneous adipocytes ( marked by asterisks ) and a collapsed storing capillary ( sc ) in their neighborhood . the number of storage lysosomes is inversely proportional to the amount of cytosolic lipid . c , d paraffin sections of autopsy specimens of subepicardial adipose tissue : c strong subplasmalemmal signal for cathepsin d in adipocyte lysosomes ( controls are negative ; not shown ) . d strong autofluorescence of subplasmalemmal lysosomes in adipocytes , indicating significant participation of ceroid in the storage a , b skin biopsy of a male fabry patient : a detail of storage lysosomes in an adipocyte showing prevalence of lipid membranes . b two subcutaneous adipocytes ( marked by asterisks ) and a collapsed storing capillary ( sc ) in their neighborhood . the number of storage lysosomes is inversely proportional to the amount of cytosolic lipid . c , d paraffin sections of autopsy specimens of subepicardial adipose tissue : c strong subplasmalemmal signal for cathepsin d in adipocyte lysosomes ( controls are negative ; not shown ) . d strong autofluorescence of subplasmalemmal lysosomes in adipocytes , indicating significant participation of ceroid in the storage we found no correlation with the genotype of the patients . adipocyte storage was seen already in the initial skin biopsies before any signs of organ failure . it correlated only with profound enzyme deficiency responsible for classic fabry disease phenotype ( table 1 ) . adipocyte lysosomal storage was not influenced by long - standing ert , as could be inferred from the findings in all treated cases ( see table 1 ) . this is in accord with our published observations on relative resistance of lysosomal storage to ert in fabry disease ( keslova - veselikova et al . in terms of molecular cell biology , the findings indicate the presence of limited , albeit significant , spontaneous lysosomal turnover of -galactose lipid conjugates demasked by gla deficiency . some findings ( see above ) suggest there might be an inverse relationship between tag lipid depots and lysosomal storage . 1980 ) that showed that the lysosomal system was active in autophagocytosis , which in fabry disease could represent a source of lipid substrate . similar activation of the lysosomal system was described in the process of mouse l - cell adipocyte differentiation ( borisov 1982 ) . a similar relationship between physiological lipid storage deposits and the degree of lysosomal expansion in lysosomal storage disorders was described in ito cells ( elleder 1984 ; elleder 2010 ) . knowledge about adipocyte participation in other lysosomal storage disorders is restricted to neuronal ceroid lipofuscinosis type 2 ( rowan and lake 1995 ) and elleder m ( unpublished observations ) . our results extend the knowledge of the adipocyte lysosomal system that was directly shown to be active under experimental conditions ( borisov 1982 ; meshkinpour et al . 1996 ) . indirect evidence of its presence stems from several experimental studies ( hou et al . 2009 ; kobayashi et al . 1980 ; kovsan et al . 2007 ; lee and fried 2006 ; palacios et al . 2001 ; zvonic et al our unpublished results , limited to several skin biopsies of cholesteryl ester storage disease ( cesd ) , showed no presence of lysosomal storage ( unpublished observations ) . our observation involving a single case ( unpublished ) revealed no discernible lysosomal storage in adipocytes ( unpublished ) . this contrasts with the striking impact of acid lipase deficiency on adipose tissue in the mouse model , featured by progressive loss of white adipose tissue and monovacuolar transformation of brown adipose tissue ( du et al . our report extends the list of cells affected by lysosomal storage in gla deficiency , which may encourage evaluation of adipose tissue function in patients with fabry disease . from a more general point of view , it raises the question of whether the storage - compromised lysosomal system interferes with regulation of adipocyte differentiation , fat mobilization , and endocrine function of adipose tissue .

ultrastructural and histochemical studies of bioptic and postmortem tissue samples from ten fabry hemizygotes showed lysosomal storage in adipocytes as a constant feature of the classic phenotype of -galactosidase ( gla ) deficiency . the storage was represented by a crescent - shaped line of storage lysosomes of varying thicknesses restricted to the perinuclear subplasmalemmal area . the ultrastructure of the storage lysosomes was dominated by concentric lipid membranes modified by simultaneous deposition of autofluorescent ceroid . storage was widely expressed in adipose tissue . the number of storage lysosomes was increased , and the lysosomes were more clustered in adipocytes with less voluminous lipid content . the findings should attract interest to studies of adipose tissue biology in fabry disease , a topic that has not been studied so far . in terms of cell biology , the observations represent indirect evidence of significant lysosomal turnover of -galactose lipid conjugates in adipocytes demasked by gla deficiency . the results extend the thus far limited information on the adipocyte lysosomal system and its participation in lysosomal storage disorders .

it is personal , highly transportable , and widely used , particularly in the western countries ( 1 , 2 ) . however , text messaging coupled with specific management strategies has yet to be utilized effectively in developing countries with high prevalence of diabetes . several studies showed that mobile phone might offer a useful means of providing information between clinic visits and might increase adherence to diabetes therapy regimens ( 3 - 5 ) . the aim of this study was to evaluate the feasibility of short message service ( sms ) and its effect on glycemic control in adults with type 2 diabetes . a total of 100 patients with type 2 diabetes with disorder duration of more than one year and no end organ complications who were on oral hypoglycemic agents and were followed at the diabetes clinics , security forces hospital , were recruited . the following parameters were recorded before initiating sending sms : glycosylated hemoglobin ( hba1c ) , frequency of simple hypoglycemic attacks ( defined as blood glucose level < 2.22 mmol / l ) , frequency of severe hypoglycemic attacks ( hypoglycemia associated with seizure or come ) , frequency of hyperglycemic attacks ( defined as blood glucose of > 9.99 mmol / l ) , mean fasting blood sugar ( fbs ) level , mean postprandial blood glucose level , and frequency of blood glucose monitoring . twenty educational multiple - choice questions for assessing patients knowledge were distributed . after four month of sending sms , the above parameters were recorded again and ten scoring questions to assess the quality of sms were answered by the participants . the content of the sms program short messages prepared in simple , understandable , constructive arabic language . the educational messages covered general diabetes care knowledge that included diabetes symptoms , signs , pathophysiology , etiology , diagnosis , diet therapy , psychotherapy , press news concerning diabetes , etc . these messages were considered as reminding messages about blood glucose check - up and medications intake . the messages were written by specialist in diabetes and diabetic educators , and then reviewed by the authors . statistical analyses were performed using the wilcoxon signed rank test , to evaluate the differences in hba1c , fbs , postprandial blood glucose levels , incidence of hypoglycemic / hyperglycemic episodes , and other variables before and after the intervention . the tests were two tailed and p < 0.05 was considered as significant deviation from the null hypothesis . a written informed consent with the security forces hospital institutional board review approval was obtained from participants . the average number of submitted sms messages was six messages ( range , 5 - 7 ) per patient per week with the total number of approximately 9600 messages over four months for all patients . a total of 100 phone calls were primarily made to ensure that the patients had received the messages at the middle the trial . mmol / l , the median frequency of documented simple hypoglycemic and hyperglycemic attacks per week were respectively zero and two , the mean hba1c was 9.9% 1.8% , the median frequency of blood glucose monitoring per day was zero , and the median score at the patient 's knowledge testing was 17 ( the maximum score was 20 ) . post - sms delivery and during the last month of the tele - educational period were as follow : the mean fbs level , 8.60 3.16 mmol / l ; the mean postprandial blood glucose level , 10.65 3.20 mmol / l ; the median frequency of documented simple hypoglycemic and hyperglycemic attacks per week , zero and two , respectively ; the mean hba1c , 9.5% 1.7% , the median frequency of blood glucose monitoring per day , one ; and the median score at the patients ' knowledge testing , 19 . the mean score of sms quality , assessed by the parents , was 8.7 out 10 . data are presented as median ( interquartile range ) or mean sd . abbreviations : sms , short message service ; fbs , fasting blood sugar ; and hba1c , glycosylated hemoglobin . growing evidence suggests that utilizing mobile phones might improve diabetes self - management and clinical outcomes ( 6 - 10 ) . a meta - analysis examined the effectiveness of mobile phone technology in diabetes mellitus care by reviewing 15 english - language articles , published between january 2002 and march 2012 . studies that used mobile phone intervention and reported changes in diet , physical activity , and blood glucose and/or hba1c levels were retrieved . overall , significant improvements were observed in blood glucose and/or hba1c concentration , adherence to medication , healthy lifestyle , and self - efficacy ( 11 ) . our study is probably among the first ones to be conducted in the arab peninsula where diabetes prevalence is very high . in our study , the change in post prandial blood sugar was remarkable , which significantly decreased the level of hba1c . holtz et al . identified peer - reviewed articles published between 2000 and 2010 and analyzed 21 articles in a systematic literature review . overall , 71% of the studies had used a study - specific application , which had supplemental features in addition to text messaging . the outcomes varied considerably across studies , but some positive trends such as improved self - efficacy , hba1c , and self - management behaviors were noted ( 12 ) . in our cohort , sms positively modified patients behavior . although the frequency of blood glucose monitoring was not increased significantly , the rate of glycemic control was improved . a feasibility study was conducted to evaluate the utility of sms in supporting 42 iraqi adults with newly diagnosed type 2 diabetes over 29 weeks . hba1c decreased from 9.3% ( sd , 1.3% ) to 8.6% ( sd , 1.2 ) ( p = 0.001 ) . mean knowledge score rose from 8.6 ( sd , 1.5 ) at baseline to 9.9 ( sd , 1.4 ) six months after receipt of sms ( p = 0.002 ) . all patients were satisfied with the text messages and wished the service to be continued after the study ( 13 ) . the effect of distance education via mobile phone text messaging on knowledge , attitude , practice , and self - efficacy was evaluated in patients with type 2 diabetes mellitus in iran . the results in the experimental group showed significant improvement in hba1c ( p = 0.024 ) , low density lipoprotein ( p = 0.019 ) , cholesterol ( p = 0.002 ) , and micro albumin ( p 0.001 ) . the knowledge ( p 0.001 ) , practice ( p 0.001 ) , and self - efficacy ( p 0.001 ) were also improved ( 14 ) . in a randomized study in india , the acceptability and feasibility of using sms via cell phones to ensure adherence to management prescriptions was tested . we did not test medications adherence in our study ; however , the patients admitted that their compliance with drug intake was better . a one - way video message about diabetes self - care was sent to 65 patients with type 2 diabetes for one year . participants were randomized to receive the usual care or the self - care video messages from their diabetes nurse practitioner . participants who received the messages had a larger rate of decline in hba1c than people who received usual care had ( 0.2% difference over 12 months ) ( 16 ) . we believe that multimedia message service might have a better audiovisual effect in comparison to regular sms ; however , it should be tested in further studies . mobile phone text educational and interactive messaging service might provide benefit in supporting diabetes self - management . the results of this study might help to design future text message interventional support programs for other chronic illnesses .

background : mobile phone text messaging has rapidly become a socially popular form of communication . several studies showed that mobile phone might offer a useful means of providing information between clinic visits and might increase adherence to diabetes therapy regimens.objectives:we conducted a study to evaluate the effect of mobile phone short message service ( sms ) on glycemic control in saudi patients with type 2 diabetes.patients and methods : one hundred patients ( mean age , 41 9.5 years ) were selected at the security forces hospital , riyadh , saudi arabia , and provided with daily educational , reminding sms messages for four months . glycosylated hemoglobin ( hba1c ) level , frequency of hypoglycemic and hyperglycemic attacks , and compliance with blood glucose monitoring were recorded before and after the trial.results:in addition to significant improvement in patients knowledge , mean fasting blood glucose level improved from 8.60 3.16 to 7.77 3.11 mmol / l and mean hba1c decreased from 9.9% 1.8% to 9.5% 1.7%.conclusions : mobile phone text messaging increased adherence to diabetes therapy and improved the clinical outcome in saudi patients with type 2 diabetes .

neonatal hemochromatosis ( nh ) is defined by liver disease associated with siderosis of the extrahepatic tissues 1 . the most frequent cause of nh is a gestational alloimmune disorder called gestational alloimmune liver disease , which results from the transplacental transfer of maternal immunoglobulin g ( igg ) antibodies 2 . although about 80% of nh patients can survive without liver transplantation because of exchange transfusions and intravenous ig therapy , some of the patients with more serious disease require transplantation 3 . nh with rtd has been reported in only five cases , all of which were stillborn or resulted in early neonatal death 58 . we describe a case of surviving patient who had nh with rtd and underwent peritoneal dialysis and liver transplantation from her father . a 29-year - old woman was referred to our hospital at 35 weeks gestation in her second pregnancy with atypical genital bleeding . she had been diagnosed with poor fetal growth and oligohydramnios from 30 weeks of gestation . a female infant was born by spontaneous vaginal delivery at 35 weeks with a birth weight of 1544 g ( 2.8 standard deviations , sd ) , a birth length of 42 cm ( 1.6 sd ) , and a head circumference of 29 cm ( 1.8 sd ) . apgar scores were 1 ( 1 min ) and 6 ( 5 min ) . physical examination revealed calvarial bone hypoplasia with enlarged fontanels and hepatosplenomegaly , but with no other abnormalities . renal ultrasound showed hyperechogenicity of both kidneys , but the size and morphology were normal . anuria , skull ossification defects , and renal hyperechogenicity suggested renal tubular dysgenesis . because the anuria persisted longer than 48 h and serum creatinine had increased to 3.0 mg / dl , peritoneal dialysis was performed on day 3 ( fig.1 ) . spontaneous urination was first observed on day 6 , and it increased gradually ; therefore , peritoneal dialysis was discontinued on day 10 . finally , serum creatinine reached normal levels ( 0.5 mg / dl ) on day 30 . ivig , intravenous immunoglobulin ; d - bil , direct bilirubin ; pt - inr , prothrombin time / international normalized ratio . hepatic failure was suspected on day 9 because of hepatosplenomegaly , a poor coagulation profile ( pt - inr : 2.07 ) , jaundice ( direct - bilirubin : 9.1 mg / dl ) , thrombocytopenia ( platelets : 7.2 10/mm ) , and hypoglycemia . congenital infections and metabolic disorders were ruled out by blood examinations . on the basis of the clinical course of acute liver failure and the complication of rtd , nh was suspected . however , she had a normal iron level of 138 g / dl and a ferritin level of 280 ng / ml . moreover , magnetic resonance imaging of the abdomen did not reveal hepatic and extrahepatic siderosis on day 15 . to obtain a definitive diagnosis , a liver biopsy was performed on day 30 , concomitant with the surgical ligation of the ductus arteriosus . the liver biopsy revealed an increase in stainable iron within the hepatocytes , confirming our diagnosis of nh ( fig.2 ) . moreover , a marked loss of hepatocytes and cholestasis was detected and the remaining hepatocytes were multinucleated . ( b ) parenchymal fibrosis was extensive in most areas ( azan staining , original magnification 100 ) . iron staining was predominantly both inside and outside the hepatocytes ( berlin blue staining , original magnification 200 ) . vitamin e was administered starting at day 16 ( 25 iu / kg / day ) , whereas vitamin k was intravenously administered periodically after birth . she received continuous infusions of ffp and repeated transfusions of platelets because of her overwhelming liver dysfunction . her liver function did not improve ; however , she gained weight , reaching 2500 g , which indicated that she was able to accept a liver transplantation from an adult ( fig.1 ) . a living donor liver transplantation with segment 2 monosubsegment graft ( 130 g ) for her was performed on day 59 . the liver extracted from patient was replaced by small nodules and overall fibrosis was progressing . microscopically , the liver showed almost total distortion of the lobular architecture , loss of the hepatocytes , and a diffuse increase in fibrous tissue . a high degree of iron deposition in hepatocytes was observed , which was definitely findings in neonatal hemochromatosis . first , the infusion of ffp and peritoneal dialysis were effective in treating persistent hypotension and renal failure in rtd with nh . to the best of our knowledge , second , repeated exchange transfusions improved the jaundice and coagulopathy , facilitating the patient s growth for subsequent liver transplantation regardless of her status as a preterm infant . nh with rtd has only been reported in five cases , all of which were fatal or resulted in early neonatal death because of coagulopathy and liver failure 57 . in the case reported here , ffp infusion and peritoneal dialysis were effective in maintaining systemic blood pressure and organ perfusion . this is supported by a recent report on a neonatal case of inherited rtd with an angiotensinogen gene mutation ; this patient survived for more than 18 months with a treatment regimen that comprised ffp infusion and peritoneal dialysis 9,10 . because the diagnosis of rtd was made on the basis of the clinical symptoms and the hyperechogenicity of both kidneys in the present case , a kidney biopsy was required to confirm the diagnosis . however , the kidney biopsy was difficult to perform because of the presence of severe coagulopathy . liver failure did not improve regardless of a plurality of times of exchange transfusion and other medications . moreover , her liver biopsy showed the remaining hepatocytes were multinucleated . on basis of clinical course and biopsy observation , we determined surgical liver transplantation was essential in this case . most liver transplantations for children in japan are performed using the liver from one of the patient s parents . our patient was very young , because of which we had to wait until her body weight reached at least 2500 g to accept an adult liver , and we thus treated her jaundice and coagulopathy with exchange transfusions . fortunately , she developed no serious hemorrhage but instead showed weight gain , indicating growth . our case report indicates that even a premature infant of nh with rtd can survive with peritoneal dialysis and exchange transfusions .

key clinical messagewe report the first surviving case of neonatal hemochromatosis with renal tubular dysgenesis . renal failure was treated with peritoneal dialysis . although hepatic failure from neonatal hemochromatosis was progressive , repeated exchange transfusions improved jaundice and coagulopathy . the patient gained weight and received a liver transplantation from her father .

endophthalmitis is a rare postoperative complication which is potentially devastating to visual function and the structural integrity of the eye . in the postoperative once detected postoperatively , the condition is treated with intravitreal antibiotics and vitrectomy and/or tap as per the recommendations of the endophthalmitis vitrectomy study ( evs ) . in recent years , there has been an increase of the number of antibiotic - resistant bacterial strains and new strains which are normally not part of the traditional etiological spectrum of postoperative infection [ 3 , 4 ] . the following case report has the objective of describing the diagnosis , treatment , and unfavorable evolution of one case of postoperative endophthalmitis , secondary to streptococcus uberis . this environmental pathogen is commonly responsible for a high proportion of cases of clinical ( and subclinical ) mastitis in lactating cows . the organism is highly resistant to the majority of the latest generation antibiotics which are commonly employed in the treatment of endophthalmitis . a 52-year - old , hispanic male presented to the retina department of our hospital complaining of a three - month history of progressive visual loss in his left eye . his past medical history was remarkable for diabetes mellitus ( 18 years ) with poor metabolic control ( last glucose level was 167 mg / dl , with a hba1c of 14.7% ) , high blood pressure , chronic renal failure ( treated with peritoneal dialysis ) , and diabetic ischemic foot problems ( previous amputation of three toes ) . the patient also had history of previous abdominal surgeries ( 23 years ago ) . as for the ophthalmologic background , the patient had a previous diagnosis of proliferative diabetic retinopathy , which had been treated previously with bilateral panretinal photocoagulation , and vitrectomy od along with chronic open angle glaucoma ou . the best corrected visual acuity was 20/40 in od and counting fingers at 30 cm in os , and the anterior chamber examination was unremarkable . the lens in the left eye was cataractous ( c2n3p2 , according to locs iii classification ) , and intraocular pressure was 16 mmhg ou . ultrasound examination of the left eye confirmed the presence of low reflective mobile vitreous opacities , consistent with vitreous hemorrhage , despite not show , evidence of traction retinal detachment . based on the existing evidence , we decided to offer the patient phacoemulsification surgery combined with a 23 ga vitrectomy . the surgery was performed without complications shortly after the initial examination , leaving balanced saline solution in the vitreous cavity at the end of the procedure . although the vitrectomy ports were self - sealing , we decided to place a suture ( 8 - 0 vicryl , ethicon , san angelo tx , usa ) in all of them . we also placed a suture in the phacoemulsification incision ( 10 - 0 nylon , ethicon , san angelo tx , usa ) . twenty - four hours after surgery , the patient complained of severe ocular pain , along with significant reduction of visual acuity ( hand movements ) and tearing . on ocular examination , we found severe conjunctival hyperemia , ciliary injection , clear cornea , hypopyon in the anterior chamber ( 1.2 mm ) , and intraocular pressure of 30 mmhg . the ultrasound examination revealed images of increased echogenicity which correspond to cellularity in vitreous cavity , pseudomembranes formation , and choroidal thickening ( figure 1(a ) ) . the diagnosis of postoperative endophthalmitis was evident , and we proceeded to immediately obtain aqueous and vitreous cavity samples for staining , cultures , and sensitivity tests . intravitreal ceftazidime ( 2.25 mg/0.1 ml ) , vancomycin ( 1 mg/0.1 ml ) , and dexamethasone ( 0.4 mg/0.1 ml ) were injected . the patient was admitted to the hospital , and treatment was started with topical moxifloxacin every hour ( vigamox , alcon lab , dallas fort worth , tx ) and oral moxifloxacin ( 400 mg ) . the following day , the visual acuity decreased to no light perception and severe pain and hypopyon continued . at the same day , the microbiology department reported the presence of gram - positive cocci in the vitreous cavity sample ( which was classified as streptococcus uberis two days later ( figure 1(b ) ) . the sensitivity test documented resistance to cephalothin , cefotaxime , ceftazidime , cefuroxime , dicloxacillin , vancomycin , azithromycin , clarithromycin , erythromycin , amikacin , gentamicin , netilmicin , tobramycin , clindamycin polymyxin , ciprofloxacin , gatifloxacin , moxifloxacin , ofloxacin , perfloxacin , and tetracycline ( figures 1(c ) and 1(d ) ) . due to the lability of the patient and the possibility of systemic dissemination of the bacteria , we offered to the patient an air - fluid exchange , silicone oil as tamponade , anterior chamber washout , and intraocular lens removal after the failure of the first intravitreal antibiotics . however , the patient refused to sign the informed consent form for the second surgery , delaying treatment for three days . after knowing the specific sensitivity of the microorganism , we added an intravitreal injection of ampicillin sodium 5 mg/0.1 ml to the original plan . finally , after extensive and exhaustive explanation , the patient agreed to the procedure . the next day , the patient reported decreased pain , and on examination the vision remained no light perception , though there was no evidence of hypopyon and only mild conjunctival hyperemia . the patient remained hospitalized for the next three days , and during that time ampicillin sodium was administered intravenously , at adjusted doses of 1000 mg bid according to creatinine clearance . after discharge , the patient continued treatment with maintenance doses of intramuscular ampicillin sodium for two weeks . four weeks later , the integrity of the eye was preserved but the vision remained no light perception ( figure 2 ) . despite the advances in surgical techniques and the technology available to perform ocular surgery , the incidence of postoperative endophthalmitis in the last 10 years appears to be increasing [ 6 , 7 ] . what possibly play a role in this development has been the indiscriminate and inappropriate dosing of broad - spectrum antibiotics by doctors and the inadequate compliance to full treatment duration by the patients . this has led to the emergence of new resistant strains to the latest generations of drugs [ 3 , 4 , 6 ] . evidence of this has been seen in the results published by the ocular tracking resistance in the u.s . today ( trust ) program , which reported an increase of 12.1% of methicillin - resistant staphylococcus aureus ( mrsa ) strains , with more than 80% of mrsa being resistant to fluoroquinolones . however , despite the considerable increase of this numbers , it is also important to note that the study has the limitation that they based the bacterial susceptibility to antibiotics on systemic drug - exposure breakpoints and not in local concentration ( as in an intravitreal injection ) . streptococcus uberis is an environmental pathogen which is typically responsible for mastitis cases in lactating cows . it is also the predominant organism isolated from mammary glands during the nonlactating period in cows . although -lactams are the treatment of choice , the bacteria possess unique mechanism to generate resistance to antibiotics like the mph(b ) gene for resistance to macrolide and sos response - like dna repair mechanism which may induce sos - driven adaptive mutations [ 5 , 8 ] . the uncommon strong resistance to antibiotics found in the strain cultured from the patient 's vitreous samples could be the result of all these conditions . the reason and circumstances by which this microorganism was able to reach the eye remains hidden to all of us . since there was no improvement clinically of our patient after the first intravitreal injection , and the isolated organism was resistant to practically all the intravitreal antibiotics that are commonly employed , we decided to use the only antibiotic to which the organism appeared to be sensitive . our use of 5 mg/0.1 ml of intravitreal ampicillin sodium was based on two previous reports in which the intravitreal administration proved to be safe . those reports were based on unpublished data from g. a. peyman in which he established that the ampicillin sodium could be safely administered intraocularly up to a dose of 10 mg/0.1 ml . however , although the results were published in his book , the original study was never published [ 9 , 10 ] . the fact that almost all the traditional pathogens responsible for endophthalmitis cases are beta - lactamase producing strains limits the use of this antibiotic as part of the first choice drugs for the treatment of postoperative endophthalmitis . the possibility of toxicity - induced damage due to ampicillin sodium is also a factor to be considered , although this patient 's vision already showed no light perception prior to administration of the intravitreal ampicillin . in this case , the eye was anatomically salvaged with this treatment regimen , although without visual recovery .

purpose . to describe the clinical characteristics , diagnosis , and treatment with intravitreal ampicillin sodium of a postoperative endophthalmitis case due to streptococcus uberis ; an environmental pathogen commonly seen in mastitis cases of lactating cows . methods . case report . a 52-year - old , hispanic diabetic patient who suddenly developed severe pain and severe loss of vision , following vitrectomy . results . the patient was diagnosed with postoperative endophthalmitis secondary to a highly resistant strain of streptococcus uberis that did not respond to intravitreal antibiotics . he was treated with an air - fluid interchange , anterior chamber washout , intravitreal ampicillin sodium ( 5 mg/0.1 ml ) , and silicon oil tamponade ( 5000 ck ) . the eye was anatomically stabilized , though there was no functional recovery . conclusion . streptococcus uberis is an uncommon pathogen to the human eye , which has unique features that help the strain in developing resistance to antibiotics . while treatment with intravitreal ampicillin is feasible , there are still concerns about its possible toxicity .

from july 2005 through october 2006 , a survey was conducted on 194 isolates of m. tuberculosis obtained from 194 patients with pulmonary tuberculosis ( tb ) ( 1 isolate per patient ) ( 1 ) . patients were recruited from the national hospital for pneumology and phtisiology in cotonou , benin , where most tb patients from the area are treated . cotonou is the largest city in benin , with a population of 655,000 in 2002 and an area of 79 km . the study was approved by the national tuberculosis program board of benin . among these 194 isolates , 17 belonged to the beijing st1 family and exhibited the same 12-loci miru - vntr pattern ( 223325163533 ) . the median age of the patients infected with the m. tuberculosis strains belonging to the beijing genotype ( 28 years ) was similar to that of patients from the general survey ( 30 years ) . demographic data that included date of birth , age , sex , and places of residence and work were collected from each patient . geo - coordinates of each patient s residence and workplace were obtained by using the global positioning system ( gps ) and mapped with the arcview 3.2 software ( esri , redlands , ca , usa ) . seropositive samples were confirmed by a discriminatory hiv1/2 test ( genie ii hiv1/hiv2 ; bio - rad , marnes - la - coquette , france ) . one sputum sample from each patient was decontaminated by using the modified petroff method and cultured in manual mycobacteria growth indicator tube ( mgit ) ( 6 ) and on lwenstein - jensen ( lj ) medium . all isolates were identified as m. tuberculosis complex by the para - nitrobenzoic acid method and tested for drug susceptibility against rifampin , isoniazid , streptomycin , and ethambutol by using the proportion method on lj medium at the following respective concentrations : 40 g / ml , 0.2 g / ml , 4 g / ml , and 2 g / ml ( 7,8 ) . dna was extracted by boiling a suspension of 2 drops of mgit - positive cultures in 300 l of 10 mmol / l tris - hcl and 1 mmol / l edta , ph 8.0 ( 1 tris - edta ) for 5 minutes . miru - vntr typing was performed at genoscreen ( lille , france ) by amplifying each of the 24 independent loci , and results were combined into digit allelic profiles ( 5 ) . all patients discussed here were born in benin and had lived in the country since birth . however , because some inhabitants of cotonou are immigrants from the asian continent , this strain could have been brought into the country by migrant residents of the community . in total , 6 ( 35% ) of 17 patients were hiv-1 seropositive , and the remaining 11 patients ( 65% ) were hiv seronegative . in contrast with the results in the initial survey , the m. tuberculosis beijing strain was more likely to be isolated from hiv seropositive patients than from those who were hiv seronegative ( 21 [ 12% ] of 173 ( p = 0.024 ) . of the 17 m. tuberculosis isolates belonging to the beijing genotype , drug susceptibility testing results were available for 16 . all isolates from the 16 patients were resistant to streptomycin but susceptible to isoniazid , rifampin , and ethambutol . of the remaining 177 isolates from the same survey , drug susceptibility testing was available for 127 , of which only 13 ( 10.2% ) were resistant to streptomycin . the m. tuberculosis beijing strains in this survey were more likely to be resistant to streptomycin than were their non - beijing counterparts ( p<0.001 ) . other researchers have suggested that m. tuberculosis beijing strains may be associated with drug resistance ( 9 ) and that the rapid spread of beijing strains in some settings suggests an intrinsic virulence of this family ( 10 ) . the combination of double alleles in several miru - vntr loci of 1 isolate suggests a mixed infection ( 11 ) . the other 16 strains showed identical profiles in the 24 miru - vntr set : loci 154 , 424 , 577 , 580 , 802 , 960 , 1644 , 1955 , 2059 , 2163b , 2165 , 2347 , 2401 , 2461 , 2531 , 2687 , 2996 , 3007 , 3171 , 3192 , 3690 , 4052 , 4156 , and 4348 with the following profile : 244233342xx4425163353723 . no amplification was achieved for loci 2163b and 2165 , despite 2 rounds of pcr for all 16 isolates . this common failure to amplify loci 2163b and 2165 , which are close in the m. tuberculosis chromosome , might be explained by a chromosomal deletion in the strain responsible for this possible outbreak . having a chromosomal deletion supports the hypothesis that all patients were infected by the same strain . however , other possible explanations such as nucleotide polymorphisms in the sequence complementary to pcr primers could not be excluded . many studies have reported pseudo - outbreaks caused by laboratory cross - contamination ( 12,13 ) . this is not likely in the present study because almost all the specimens for primary culture were processed on different days over several months . mapping of patients residences and workplaces showed that many lived or worked ( or both ) in the xwlacodji area of cotonou ( figure ) . to further investigate this spatial cluster and a possible link between patients , we mapped a place they habitually frequented and found that most patronized the same drinking bar ( figure ) . ten of the patients either lived or worked near the bar ( < 300 m ) or regularly visited it . although no epidemiologic link was evident between these patients and the remaining 7 patients , most of the latter were motorcycle taxi drivers and regularly moved from place to place . maps showing residences and workplaces of mycobacterium tuberculosis patients in xwlacodji , cotonou , benin , 20052006 . without gps we could not have identified the geographic cluster of these patients with beijing strains in xwlacodji . the residents are poor , and overcrowding creates conditions favorable for transmission of diseases from person to person and rapid spread of the resistant m. tuberculosis beijing strain . we can not completely exclude the unlikely possibility that the patients were infected by different strains with the same miru - vntr pattern . however , the 17 strains identical 24-loci miru - vntr profile , with a probable deletion of the same 2 loci ; the identical drug susceptibility pattern ( monoresistant to streptomycin ) ; and the fact that most patients resided in the same community as determined by gis strongly suggest that these strains are part of an outbreak . generally , molecular tools are used to study tb transmission and to suggest possible outbreaks . gis has rarely been used in health systems , particularly in resource - poor countries such as benin ( 14 ) . gis tools might be dispensable in industrialized countries where streets and houses are properly mapped and pinpointing specific addresses is generally sufficient to localize an outbreak . in many low - income settings , however , streets and houses are not properly numbered and mapped , and using gps is necessary to gain access to accurate geo - coordinates and localize such outbreaks . in the absence of genetic methods , differentiating cases from the same route of transmission from others however , gis can help tb control practitioners identify areas with aggregate cases so they can institute appropriate measures to control the disease .

using geographic information system and molecular tools , we characterized a possible outbreak of tuberculosis caused by mycobacterium tuberculosis beijing strain in 17 patients in cotonou , benin , during july 2005october 2006 . most patients lived or worked in the same area and frequented the same local drinking bar . the isolates were streptomycin resistant .

using scanning electron microscopic and light microscopic techniques , adriaens et al1 demonstrated bacteria invading the radicular cementum and the dentinal tubules of the radicular dentin of periodontally diseased , caries - free human teeth . it has been reported that periodontal diseases , periodontal treatment , such as root planing or surgery and over - vigorous tooth brushing can cause gingival recession.2,3 many authors claimed that such recession may account for the high prevalence of cervical dentin sensitivity ( cds ) in periodontal patients.3,4 furthermore , it is not known if hypersensitivity in the periodontal patients is true cds or due to some underlying pathological process such as bacterial penetration into the dentinal tubules during the disease process.5 periodontal treatment often results in the removal of the cementum and it has been claimed to be a factor in the occurrence of hypersensitive dentin and bacterial invasion to dentinal tubules.68 it has been suggested that bacteria and bacterial toxins , which are present in the diseased periodontium , can reach the pulp by way of lateral and/or accessory canals8,9 and dentinal tubules.10,11 it has been demonstrated that bacteria can invade open dentinal tubules and reach the pulp12 and that bacterial products , when applied to exposed dentin are capable of initiating inflammatory reactions in the underlying pulp.13 most of recently developed desensitizers are considered to contribute to better clinical results by reducing the rate of the cervical dentin sensitivity.14,15 however , little is known about their antibacterial effects.14 this study assessed the antibacterial activity of various desensitizers available on the market against some bacteria found in dental plaque by muller hinton agar well method . in this study , a benzalconium containing product ( micro prime ) , a triclosan containing product ( seal & protect ) , a dentin bonding primer ( all bond ) , a fluoride containing prophylaxis paste ( sultan desensitizer ) and two fluoride containing varnishes ( cavity shealth and ultra ez ) were used ( table 1 ) . the antibacterial efficacy of each material was evaluated against the following bacteria : streptococcus mutans ( nctc 10449 ) ; streptococcus salivarious ( rskk 606 ) ; staphylococcus aureus ( atcc 6538 ) ; streptococcus faecalis ( rskk 97008 ) ; and pseudomonas aeruginoza ( atcc 27853 ) . the agar was evenly distributed over the surface of 15 cm - in - diameter petri dishes to a thickness of 5 mm . standard wells with a diameter of 6.0 mm were punched into the agar with the blunt end of a pasteur pipette . approximately 0.5 ml suspensions of bacteria were swabbed over the surface of the agar plates . the concentrations of bacterial suspensions ( cfu ) were 210 s. mutans , 610 s. salivarious , 510 s. aureus , 210 s. faecalis , and 1.610 p. aeruginoza bacteria / ml , respectively . each material was inserted into the wells with its own sterile applicator under a laminar flow . the agar plates were incubated at 37c for 48 h. the diameters of the inhibition zones around the materials were measured in millimeter ( mm ) ( figure 1 ) . the results of 12 measurements were averaged and these values were subjected to kruskal wallis one way anova and mann whitney test at a significance level of p<.05 for the comparison of the products . the results of 12 measurements were averaged and these values were subjected to kruskal wallis one way anova and mann whitney test at a significance level of p<.05 for the comparison of the products . table 2 shows the mean values of the inhibition zones produced by each material tested . micro prime ( mp ) produced varying degrees of inhibitory effectiveness on the test bacteria . s. mutans and p. aeruginosa displayed a significantly lower resistance to mp than s. salivarious , s. faecalis and s. aureus respectively ( p<.05 ) . antibacterial effectiveness of sp against s. faecalis , s. mutans , and s. salivarious was not statistically different ( p>.05 ) . all bond primer showed its highest antibacterial effectiveness against s. faecalis and p. aeruginosa ( p<.05 ) . sultan demonstrated significant antibacterial effectiveness against all test bacteria with s. mutans being the least inhibited ( p<.05 ) . among the materials tested , no inhibition zones were noted for cavity sheld and ultraez ( p>.05 ) . antibacterial effectiveness shown by the dental materials in some studies was related to either their ph or their chemical composition . for example , current desensitizers include antibacterial components such as fluoride , triclosan , benzalkonium chloride , ethylene dianinetetraacetic acid , and glutaraldehyde . a dentin primer incorporating methacryloyloxydodecylpyridinium bromide was potentially able to kill any bacteria.16,17 the agar well technique test is an accepted method for initially differentiating antibacterial activity between materials . accordingly , even if the material contains less diffusive antibacterial components the substantive antibacterial activity is available . it is difficult to evaluate the antibacterial effects of desensitizer by a single test and more than one method needs to be used for screening the materials . furthermore , in order to speculate on clinical effects , in situ tests which simulate the clinical situation are indispensable . dental plaque is a host - associated biofilm . in this study , some microorganisms of dental plaque were used to determine antibacterial effectiveness of several desensitizers . these organisms have a strong affinity for hard surfaces , and do not usually appear in the mouth until after tooth eruption . s salivarious is only a minor component of dental plaque and not considered a significant opportunistic pathogen . however , s. salivarious and s. mutans have been found to produce root caries.18 s. fecalis have been recovered in low numbers from several oral sites . some strains can include dental caries in gnotobiotic rats while others have been isolated from infected root canals and from periodontal pockets.19 p. aeruginosa and s. aureus were colonized in pocket of the refractory chronic periodontitis patients.20 p. aeruginosa is resistant to tetracycline , penicillin g and erythromycin.19 antibacterial effectiveness of the desensitizers except for ultraez and cavity sheath used in this study was obtained against the bacteria above . in a study by emilson and bergenholtz,21 it was suggested that the antibacterial nature of the gluma and denthesive cleanser might be related to the high content of ethylene dianinetetraacetic acid ( edta ) in the materials . the results of the present study also indicate that chemical composition of the desensitizers play an active role their antibacterial properties . micro prime ( mp ) desensitizer is used for desensitizing under dental cements or temporary , provisional , or final restorative materials , abrasions , cervical erosions , and preps . the antibacterial activity of mp desensitizer may be related to the chemical composition , which is benzalkonium chloride in nature . mp desensitizer had significant inhibitory effect on not only s. mutans and p. aeruginosa but also on s. salivarious , s. faecalis . and s. aureus . this data supports the results of duran and sengun,14 who reported antibacterial effect of benzalkonium chloride containing heath - dent desensitizer . seal & protect desensitizer exhibited antibacterial zones that comparable in size with those of mp desensitizer . the zones of bacterial inhibition produced with all bond may be attributed to its ingredients . fluoride release is a factor in a materials antibacterial effect;22 however , in this category of materials , ultraez and cavity sheath had no inhibition effect when compared with sultan desensitizer in this study . in a study by ekenback et al,23 no statistically significant difference over time was found in s. mutans , lactobacilli or total streptococci after treatment with the fluoride varnishes or tymol varnish . on the basis of the findings of vermeersch et al,24 it was assumed that , in the set materials , fluoride ions might be firmly encapsulated by the resin matrix and that consequently its fluoride release rate into an aqueous environment might be small and slow . however , this finding does not necessarily indicate that these materials have no antibacterial effectiveness . moreover , release of fluoride from varnishes slowly in small amounts may be beneficial at the long term . thus , relationship between release of fluoride and antibacterial effectiveness of varnishes should be an issue of future studies . micro prime desensitizer containing benzalkonium chloride had the highest antibacterial effectiveness when compared with others in this study . in addition , seal & protect which contains triclosan and all bond which contains acidic components showed very high antibacterial efficacy . however , a fluoride component in a paste ( sultan desensitizer ) showed very high bactericidal efficacy . this study has demonstrated that currently marketed desensitizers have greatly in their ability to inhibit on growth of a variety of oral bacterial organisms in vitro . these experimental findings , however , only provide data that are useful for assessment of initial antibacterial effect . in vivo models that will account for many of the variables should be sought .

objectivesdesensitizers contribute to better clinical results by reducing the rate of cervical dentin sensitivity . however , information on their antibacterial effect is limited . this study examined the antibacterial activities of a triclosan containing ( seal & protect ) , a benzalconium containing desensitizer ( micro prime ) , a fluoride containing prophilaxy paste ( sultan desensitizer ) , two fluoride containing varnishes ( cavity shealth and ultra ez ) , and a dentin bonding primer ( all bond).methodsthe test materials were inserted in the wells of muller hinton agar plates inoculated with streptococcus mutans , streptococcus salivarious , staphylococcus aureus , streptococcus faecalis and pseudomonas aeruginosa . the diameters of the inhibition zones produced around the materials were measured after 24 h of incubation . the results were analyzed by the kruskal wallis one way anova and the mann - whitney tests at a significance level of p<.05.resultsmicro prime desensitizer containing benzalkonium chloride had the highest antibacterial effectiveness compared to other desensitizers used in this study . in addition , triclosan containing seal & protect and acidic components containing all bond showed very high antibacterial efficacy . on the other hand , fluoride within both varnishes had little antibacterial effectiveness . however a fluoride component in a paste ( sultan desensitizer ) showed very high bactericidal effect.conclusionsall desensitizers except fluoride varnishes showed various degrees of antibacterial effect against the bacteria tested in this study . if antibacterial effect is also required from the desensitizers clinicians should avoid use of varnishes .

serum amyloid a ( saa ) and c - reactive protein ( crp ) are acute - phase proteins predominantly produced and secreted by hepatocytes . other cells including lymphocytes , monocytes , and macrophages can also produce these proteins . the induction of saa and crp synthesis is triggered by a number of cytokines , chiefly il-6 , which is released from a variety of cell types , but mainly from macrophages and monocytes at inflammatory sites . although several studies have investigated the serum levels of the acute - phase proteins crp and saa in diseases [ 48 ] , few have focused on the levels of these type of proteins in effusions , that is , transudates and exudates . serum crp is widely used as a marker of inflammation and tissue injury [ 9 , 10 ] . although crp is also found in exudates and it has been proposed for differentiating diseases , the diagnostic application of this finding has not been fully explored . for saa , information regarding its presence and possible diagnostic use in effusions is not available at all . effusions are commonly classified as transudate or exudate according the light 's criteria that is based in determinations of total protein and lactate dehydrogenase . however , as the distinction between exudates and transudates are very important in the patient management , there is a continuous interest in the evaluation of other biochemical parameters [ 1216 ] . plasma ligands of saa and crp are distinct ( for review see [ 17 , 18 ] ) , supporting that they can differently leakage through membranes . the purpose of this study was to evaluate the presence of saa in pleural and ascitic fluids , compare it with crp , and evaluate the possibility of using these acute - phase proteins to discriminate effusions . saa , pcr , and total protein ( tp ) were determined in pleural and ascitic effusions and corresponding serum samples taken from adult patients hospitalized in the hospital universitrio / universidade estadual de londrina ( paran , brazil ) and hospital universitrio , universidade de so paulo ( so paulo , brazil ) . pleural and ascitic effusions were classified as transudates or exudates according to the light 's criteria ; effusion to serum total protein ratio > 0.5 , an effusion lactate dehydrogenase ( ldh ) value > 200 u / l , or a fluid to serum ldh ratio > 0.6 . all of the patients gave their informed consent to participate in the study , which was approved by the ethics committee of the hospital universitrio of universidade estadual de londrina ( cep 111/01 ) and the ethics committee of the faculdade de cincias farmacuticas of universidade de so paulo ( ofcio cep no 64 ) . serum and exudate samples were taken from 36 hospitalized patients , 27 with pleural effusions and 9 with ascitic effusions . the pleural exudates were caused by pneumonia ( 18 cases ) , tuberculosis ( 7 cases ) , and neoplasia ( 2 cases ) . the ascitic exudates resulted from peritoneal tuberculosis ( 3 cases ) , peritonitis ( 1 case ) , neoplasia ( 2 cases ) , cirrhosis ( 2 cases ) , and chronic hepatitis ( 1 case ) . serum and transudate samples were taken from 12 patients , 9 with pleural effusions and 3 with ascitic effusions . the pleural transudates were caused by congestive cardiac failure ( 5 cases ) , hepatic cirrhosis ( 2 cases ) , and renal failure ( 2 cases ) . the ascitic transudates resulted from hepatic cirrhosis ( 2 cases ) and undefined ascite ( 1 case ) . the samples were centrifuged at 3000 rpm for 10 minutes and stored at 70c for up to 10 months . crp was measured by immunonephelometry , using a beringher nephelometer 100 analyzer and a dade behring kit ( marburg , germany ) . saa was measured by elisa , using a tridelta phase kit ( maynooth , co , kildare ) . total protein was measured by a modified biuret method in an automated dimension clinical chemistry system analyzer , using the dade behring kit . the statistical package for the social sciences ( spss version 9.0 ) program was used to carry out a distribution analysis by the kolmogorov - smirnov test , while the correlation coefficients were determined according to spearman 's rank - correlation test and by multiple - level regression analysis because the comparative analysis showed no differences in the serum and exudate concentrations of saa , crp , and tp with respect to the origin and location of the effusion , a collective descriptive analysis for saa , crp , tp , and their effusion / serum ratio was made for exudates ( table 1 ) and for transudates ( table 2 ) . the concentrations of serum and effusion saa and crp varied over a broad interval , especially in exudates . likewise , the effusion / serum ratio for crp and saa also varied over a broad interval , specially in exudates ( table 1 ) when compared with transudates ( table 2 ) . the exudate displayed , on average , 10% and 39% of saa and crp present in the serum , respectively . the correlation analysis of serum and effusion for saa , crp , and tp ( figure 1 ) using spearman 's test showed , in exudates , a stronger correlation for saa than for crp and tp ( note the log scale for saa ) . although saa and crp were highly correlated in serum , they were only slightly correlated in exudate ( compare figures 2(a ) and 2(b ) ) . albeit the concentration of saa in transudates was low , it was possible to identify a correlation between serum and transudate ( see the value of r in figure 1(a ) ) . curiously this correlation was observed only for saa and was not present for crp . there was a good correlation between crp and saa in serum but not in transudates ( figure 3 ) . the crp / saa ratio varied over a broad interval in both exudates and transudates ( table 3 ) . the analysis of the individual values of saa , crp and tp found in exudates , transudates , and respective serum showed that the simple measurement of saa in the effusion was able to discriminate transudate from exudate ( figure 4 ) . the concentration of a given plasma protein in an effusion will depend on its leakage through the pleural and peritoneal membranes , and for some of them , on local synthesis . alternatively , proteolysis and cell uptake will contribute to a decrease in protein concentration ( figure 5 ) . thus , although local synthesis of saa can not be excluded , the positive correlation between serum and effusion ( figure 1(a ) ) indicates a strong contribution of serum to the pool of saa present in the effusion . the proteolysis of saa in the exudate and the association of saa with cells is expected because : ( i ) fragments of saa are present in synovial fluid of arthritic patients , ( ii ) saa undergoes proteolysis by lysosomic enzymes of neutrophils , and ( iii ) there is a specific receptor for saa in macrophages and neutrophils . based on the correlations found for crp and saa in serum and in exudate ( figure 2 ) , we assume that these proteins cross the membrane and/or are fragmented to varying degrees , that is , the passage of crp through membranes occurs more readily than the passage of saa , or the proteolysis or uptake of saa by cells is greater than that of crp . it is important to note that the concentration of saa in exudates is only 10% of that present in serum . however , this concentration is sufficiently high to trigger the biological effects described for this protein , for instance , 1 g / ml of saa is sufficient to trigger the mrna expression and the release of tnf- and il-8 from human neutrophil cultures [ 2628 ] . besides the induction of cytokine synthesis and release [ 2629 ] , saa primes neutrophils and is involved in cell migration . the presence of crp and saa in exudates supports a key role of these proteins in the activation of immune responses and/or in the repair of host tissues . the broad range of concentrations for saa and crp in exudates observed in this study was expected and probably reflected different phases of the inflammatory disease . even though , this study suggests the potential value of saa in the characterization of exudates , as already proposed for crp [ 9 , 34 ] . although several molecular markers have been proposed for the discrimination of exudates and transudates [ 35 , 36 ] , a definitive marker has not yet been found . saa determinations are relatively simple , rapid , and inexpensive and in this study we find that saa can undoubtedly contribute to the discrimination of an exudate . correlation between effusion and serum for saa ( a ) , crp ( b ) , and tp ( c ) . exudates and transudates were from 36 and 12 patients , respectively . correlation between crp and saa for ( a ) serum ( r = 0.796 ; p < 0.0001 ) and ( b ) exudate ( r = 0.449 ; p = 0.007 ) in 36 patients . correlation between crp and saa for ( a ) serum ( r = 0.749 ; p = 0.005 ) and ( b ) transudate ( r = 0.247 ; p = 0.438 ) in 12 patients . individual values of ( a ) saa , ( b ) crp , and ( c ) tp in serum and effusions ( 36 exudates and 12 transudates ) . factors affecting the concentration of a given protein in an exudate . descriptive analysis of parameters determined in serum and exudate samples and their exudate / serum ratio ( e / s ) ( n = 36 ) . descriptive analysis of parameters determined in serum and transudate samples and their transudate / serum ratio ( t / s ) ( n = 12 ) . descriptive values for the crp / saa ratio in exudates ( n = 36 ) and transudates ( n = 12 ) and respective serum .

the distinction between exudates and transudates is very important in the patient management . here we evaluate whether the acute - phase protein serum amyloid a ( saa ) , in comparison with c reactive protein ( crp ) and total protein ( tp ) , can be useful in this discrimination . crp , saa , and tp were determined in 36 exudate samples ( 27 pleural and 9 ascitic ) and in 12 transudates ( 9 pleural and 3 ascitic ) . crp , saa , and tp were measured . saa present in the exudate corresponded to 10% of the amount found in serum , that is , the exudate / serum ratio ( e / s ) was 0.10 0.13 . for comparison , the exudate / serum ratio for crp and tp was 0.39 0.37 and 0.68 0.15 , respectively . there was a strong positive correlation between serum and exudate saa concentration ( r = 0.764;p < 0.0001 ) . the concentration of saa in transudates was low and did not overlap with that found in exudates ( 0.02 - 0.21 versus 0.8360.5 g / ml ) . saa in pleural and ascitic exudates results mainly from leakage of the serum protein via the inflamed membrane . a comparison of the e / s ratio of saa and crp points saa as a very good marker in discriminating between exudates and transudates .

all patients in this study had previously been published as cases of meier - gorlin syndrome or fulfilled diagnostic criteria for meier - gorlin syndrome ( microtia , absent / small patellae and short stature ) . no cytogenetic abnormalites were observed on routine karyotyping of these meier - gorlin syndrome cases ( n=10 patients ) . furthermore , no significant increase of either spontaneous , or radiation - induced chromosome breaks was observed ( 2 cases versus 2 control patients , 100 metaphases assessed per patient ; p 0.7 , x - test ) . informed consent was obtained from all participating families and the studies were approved by the scottish multicentre research ethics committee ( 04:mre00/19 ) , regional committee on research involving human subjects nijmegen - arnhem ( 0006 - 0119 ) ; or university of texas southwestern medical center at dallas ( irb # 032008 - 066 ) . coding exons and exon - intron boundaries of each gene were screened by bidirectional capillary sequencing on an abi 3730 gene sequencer . sequence analysis and mutation detection performed using mutation surveyor v. 2.61 ( softgenetics llc ) . amplicons were separated by capillary electrophoresis on an abi3730 sequencer , and allele sizes obtained using genemapper ( applied biosystems ) . all patients in this study had previously been published as cases of meier - gorlin syndrome or fulfilled diagnostic criteria for meier - gorlin syndrome ( microtia , absent / small patellae and short stature ) . no cytogenetic abnormalites were observed on routine karyotyping of these meier - gorlin syndrome cases ( n=10 patients ) . furthermore , no significant increase of either spontaneous , or radiation - induced chromosome breaks was observed ( 2 cases versus 2 control patients , 100 metaphases assessed per patient ; p 0.7 , x - test ) . informed consent was obtained from all participating families and the studies were approved by the scottish multicentre research ethics committee ( 04:mre00/19 ) , regional committee on research involving human subjects nijmegen - arnhem ( 0006 - 0119 ) ; or university of texas southwestern medical center at dallas ( irb # 032008 - 066 ) . primers were designed using exonprimer ( supplementary table 2 ) . coding exons and exon - intron boundaries of each gene sequence analysis and mutation detection performed using mutation surveyor v. 2.61 ( softgenetics llc ) . amplicons were separated by capillary electrophoresis on an abi3730 sequencer , and allele sizes obtained using genemapper ( applied biosystems ) .

meier - gorlin syndrome ( ear , patella , short stature syndrome ) is an autosomal recessive primordial dwarfism syndrome characterised by absent / hypoplastic patellae and markedly small ears1 - 3 . both pre and post - natal growth are impaired in this disorder and although microcephaly is often evident , intellect is usually normal . we report here that this disorder shows marked locus heterogeneity and we identify mutations in five separate genes : orc1 , orc4 , orc6 , cdt1 and cdc6 . all encode components of the pre - replication complex , implicating defects in replication licensing as the cause of a genetic syndrome with distinct developmental abnormalities .

treacher collins syndrome ( tcs ) is a severe congenital disorder of craniofacial development characterized by numerous developmental anomalies that are restricted to the head and face . hypoplasia of the facial bones , particularly the mandible and zygomatic complex , is an extremely common feature of tcs . although the condition was probably first described by thomson ( 1846 ) followed by toynbee ( 1847 ) and berry ( 1889 ) , it is named after e. treacher collins who described the essential components of the syndrome in 1900 . the first extensive review of the condition was done by franceschetti and klein in 1949 , who coined the term mandibulofacial dysostosis to describe the clinical features . in england and in the american continent this abnormality is described as the treacher collins syndrome and in the european continent as mandibulo - facial dysostosis or franceschetti syndrome . an 18-year - old female reported to the department of oral medicine and radiology with the chief complaint of forwardly placed teeth in the upper anterior region of jaw . family history revealed that her father and grandmother had typical signs of the treacher collins syndrome . on extra oral examination , she presented with antimongloid slanting of the palpebral fissures with sparse eyelashes on the lower eyelid . the maxillary incisors were proclined and there were spacing in the maxillary and mandibular anteriors . radiographs revealed prominent antigonial notch , short ramus [ figure 3 ] , hypoplasia of the mandible , proclined upper anteriors [ figure 4 ] , hypoplasia of zygomatic bone , and maxillary sinus [ figure 5 ] . front view of the patient showing hypoplasia of facial bones , downsloping palpabral fissures , with scanty lower eye lashes lateral view showing retruded mandible and prominent nose orthopantomogram showing prominent antigonial notch , short ramus lateral cephalogram showing hypoplastic mandible , prominent nose , and proclined upper anteriors pa water showing hypoplasia of zygomatic bone and maxillary sinus tcs or franceschetti syndrome is an autosomal dominant disorder of craniofacial development which has an incidence of approximately one in 50,000 live births . while 40% of cases have a previous family history , the remaining 60% appear to arise as a result of a de novo mutation . in our case , several hypotheses were proposed to explain the pathogenesis of tcs including abnormal patterns of neural crest cell migration , abnormal domains of cell death , improper cellular differentiation during development , or an abnormality of the extracellular matrix ; however , there was little experimental evidence to support any of these hypotheses . recently genetic , physical , and transcript mapping techniques have identified the gene mutated in tcs which is designated as tcof1 and mapped to human chromosome 5q32 - -33.2 locus . it was found to encode a low complexity , serine / alanine - rich , nucleolar phosphoprotein termed treacle.- valdez et al . suggested that haploinsufficiency of treacle in tcs patients might cause insufficient rrna production in the prefusion neural folds , resulting in abnormal craniofacial development . ( the cephalic neural crest cells probably require a higher threshold concentration of rrna for their survival and proper differentiation during early embryogenesis . ) the structures affected in tcs are derived from the first and second pharyngeal arch , groove , and pouch . franceschetti and klein ( 1949 ) reviewed the literature and described the typical characteristics of the syndrome as follows : ( 1 ) antimongoloid palpebral fissures with either a notch or coloboma of the outer third of the lower lid , and occasional absence or paucity of the lashes of the lower lid . ( 2 ) hypoplasia of the facial bones , especially the malar bones and mandible . ( 3 ) malformation of the external ear , and occasionally of the middle and inner ear , with low implantation of the auricle . ( 4 ) macrostomia , high palate , malocclusion , and abnormal position of the teeth . ( 5 ) atypical hair growth in the form of tongue - shaped processes of the hairline extending toward the cheeks in the preauricular region . ( 6 ) association at times with other anomalies , such as obliteration of the nasofrontal angle , pits , or clefts between the mouth and ear , and skeletal deformities . after this description was published , some of these features were regarded as being of lesser importance and some were emphasized in the diagnosis . ( 1963 ) named the following features as obligatory : ( 1 ) antimongoloid palpebral fissures , ( 2 ) anomaly of the lower lid : coloboma of the outer third , or deficient lashes , or both , ( 3 ) hypoplasia of the malar bones , ( 4 ) hypoplasia of the mandible . in our case , while the clinical features are generally bilaterally symmetrical , expression of the mutated gene is highly variable . at one extreme , the features can be so mild that it may be difficult to reach a diagnosis . at the other extreme , the facial complex may be so severely hypoplastic that prenatal death ensues as a result of compromisation of the airway . prenatal diagnosis of tcs has only been performed in families with a history of tcof1 using either fetoscopy or ultrasound imaging in the second trimester of pregnancy ( approximately 18 weeks ) when termination of pregnancy is a particularly traumatic procedure psychologically as it involves the induction of labor . however , the onset of tcs abnormalities occurs very early during human embryonic development , typically within the first 4 - -8 weeks . hence first trimester prenatal diagnosis would seem to be preferable , particularly if the family feel that termination of pregnancy is desirable in the event that the fetus is affected . phenotypic diagnosis at this stage ( first trimester ) even with the most sophisticated ultrasonography available today is not possible . although linkage analysis ( molecular analysis ) has been used to make first trimester diagnostic predictions in a pregnancy at high risk of producing an affected child , it is not possible to predict how severely affected a fetus might be using this approach alone ; consequently , ultrasonography is an invaluable aid to prenatal diagnosis , as this technique may provide information about the severity of affected pregnancies and can be used to evaluate fetal progression . nager syndrome has similar facial features to tcs , particularly in the region of the eyes ( downward slanting with a deficiency of eyelashes ) . however , the mandible is usually more hypoplastic , the lower lid colobomas are rare , and preaxial limb abnormalities ( hypoplastic , or aplastic thumbs , fused radius and ulna ) are a consistent feature of nager syndrome , unlike tcs . miller syndrome also has some similarity in the facial features to tcs ; in addition it has postaxial limb defects ( absence or incomplete development of the fifth digital ray of all four limbs ) and ectropion or outturning of the lower lids . also cleft lip , with or without cleft palate , is more common than in tcs and some patients may exhibit congenital heart defects . the development of speech and language skills depends on the child 's ability to hear during the first 3 years of life . as the great majority of these patients are of normal intelligence , early recognition of deafness and its correction with hearing aids or surgery , when possible , is of great importance for development . an affected parent of either sex will transmit the defect to 50% of his or her offspring in accordance with mendelian laws of genetics . it is shown that chemical and genetic inhibition of p53 function can repress the wave of neuroepithelial apoptosis associated with tcs and in doing so prevents the pathogenesis of craniofacial anomalies . however , p53 performs many critically important cellular functions and suppressing p53 function completely is a very risky approach given that loss - of - function mutations in p53 are the most common mutations associated with cancer and tumorigenesis . therefore appropriate titration of p53 function is key in preventing the pathogenesis of tcs without risking the onset of tumorigenesis . individuals diagnosed with severe tcs typically undergo , over several years , multiple major reconstructive surgeries that are rarely fully corrective . although stem cell therapy holds promise for treating degenerative diseases , it is unlikely to benefit the reconstructive repair of severe craniofacial malformations . consequently , prevention provides the best hope for improving the prognosis of at - risk or affected individuals .

franceschetti syndrome is an autosomal dominant disorder of craniofacial development with variable expressivity . it is commonly known as treacher collins syndrome ( tcs ) . it is named after e. treacher collins who described the essential components of the condition . it affects both genders equally . this article reports a case of tcs in an 18-year - old female .

in the gastrointestinal ( gi ) tract , 5-hydroxytryptamine ( serotonin , 5-ht ) is a major signaling molecule , which mediates gi functions ( motility and secretion ) , emesis , nausea and pain [ 1 , 2 ] . most of colonic 5-ht is synthesized and released from mucosal enterochromaffin ( ec ) cells ; therefore , alterations in the release of 5-ht from ec cells affect both physiological and pathophysiological colonic functions . irritable bowel syndrome ( ibs ) is a gi chronic disorder characterized by abdominal discomfort or pain associated with altered bowel habits . abnormal levels of chromogranin a ( a marker for all endocrine cells ) in the colon of ibs patients have been demonstrated , thus indicating a role of the colonic endocrine cells ( namely , 5-ht - containg ec cells or peptide yy ( pyy)-containing l cells ) , in the regulation of colonic function in ibs patients [ 4 - 6 ] . indeed , a recent human study suggests that the increased 5-ht release from colonic ec cells contributes to the development of abdominal pain in ibs patients . therefore , an improved understanding of endogenous modulator system for 5-ht release from ec cells may provide novel insights into the etiology and pharmacotherapy of functional bowel disorders such as ibs . our in vitro studies have demonstrated that isolated guinea - pig colon is a helpful in vitro - preparation for studying the mechanism modulating the release of 5-ht from ec cells [ 8 - 10 ] . experimental data from the in vitro - preparations indicate that melatonin , endogenous tachykinins ( tks ; neuropeptides such as substance p and neurokinin a ) and pyy play important roles in the modulation of the release of 5-ht from ec cells via a unique endogenous tachykinergic nk2/nk3 receptor cascade system [ 8 - 11 ] . this review focuses on the evidence establishing a potential role of the endogenous nk2/nk3 receptors cascade system controlling the release of 5-ht from ec cells , with special attention being paid to the pathophysiology of gut disorders including ibs . a selective tachykinin nk2 receptor agonist ala - nka-(4 - 10 ) ( 0.01 - 1 m ) evoked a long - lasting 5-ht release from isolated guinea - pig colon in a concentration - dependent manner [ 8 - 11 ] . the 5-ht - releasing action of ala - nka-(4 - 10 ) was unaffected by tetrodotoxin ( ttx ) , and was also seen in myenteric plexus - free mucosal preparations , thus suggesting that the nk2 agonist - evoked 5-ht release is mediated by activation of nk2 receptors located on non - neuronal cells in the mucosal layer . this agrees with a previous report which showed tachykinin nk2 receptor expression on the surfaces of enterocytes of guinea - pig colon . the l - type calcium channel blocker nicardipine or the syntaxin inhibitor botulinum toxin type c also reduced the long - lasting 5-ht release evoked by ala - nka-(4 - 10 ) , thus suggesting that the nk2 receptor - triggered 5-ht release is mediated via syntaxin - related exocytosis mechanisms . however , an involvement of tachykinin nk1 receptors in the evoked 5-ht release is unlikely because a selective tachykinin nk1 receptor agonist , [ sar , met ( o2)]-substance p ( 100 nm ) failed to affect basal 5-ht release . a selective tachykinin nk3 receptor agonist senktide also evoked a transient 5-ht release from the isolated guinea - pig colon implicating tachykinin nk3 receptors , in addition to nk2 receptors in modulating 5-ht release from colonic mucosa . 1 , the enhancing effect of senktide on 5-ht release was prevented by both ttx and the nk2 receptor - selective antagonist sr48968 , thus suggesting that senktide stimulates the release of neuronal tks , which in turn enhances 5-ht release via mucosal nk2 receptors . this agrees with previous findings in guinea - pig colon where nk3 receptor activation releases tks and 5-ht [ 13 , 14 ] . the 5-ht - releasing action of senktide was also inhibited by hexamethonium , and was not seen in myenteric plexus - free mucosal preparations , thus suggesting that myenteric cholinergic interneurons also participate in the mechanism for nk3 receptor - triggered 5-ht release . thus , these findings support the view that the cascade of neuronal nk3 receptors and mucosal nk2 receptors represents an endogenous modulator system for 5-ht release from ec cells . these results are also in line with previous findings ( 1 ) in human colon where nk3 receptors present predominantly on myenteric and submucosal plexus neurons , and nk3 receptors come into a play only in pathological conditions such as rescue responses or inflammation , and ( 2 ) in healthy volunteers where the stimulation of nk2 receptors appears to induce ibs - like symptoms . moreover , it has been shown that the 5-ht release from mucosal biopsy specimens of ibs patients is increased by 10-fold over controls , and the increased 5-ht release contributes to development of abdominal pain in ibs patients . therefore , the view that the endogenous tachykininergic nk2/nk3 receptor cascade system can regulate the release of 5-ht from colonic ec cells , has an important implication for the potential role of endogenous tks in the generation of the symptoms associated with ibs ; it can be speculated that endogenous tks acting through the nk2/nk3 receptor cascade system facilitate the release of 5-ht which in turn affects the colonic function of ibs patients through the activation of 5-ht receptor subtypes . a sensory nerve - derived neuropeptide , calcitonin gene - related peptide ( cgrp , 1 - 100 nm ) has been also shown to produce a ttx - sensitive but atropine - resistant 5-ht release via stimulation of myenteric plexus neurons in the isolated segments of guinea - pig colon . the enhancing effect of cgrp on 5-ht release was also prevented by both the nk2 receptor - selective antagonist sr48968 and the nk3 receptor - selective antagonist sr142801 , but not by the nk1 receptor - selective antagonist l703606 . thus , these findings support the view that cgrp stimulates the release of neuronal tks , which in turn enhances 5-ht release via the endogenous nk2/nk3 receptor cascade system . thus , it appears that cgrp - sensitive tks - releasing neurons play a role in activating the endogenous nk2/nk3 receptor cascade system . this conjecture is also supported by a previous report which showed that cgrp can stimulate intramural tachykinergic neurons in the guinea - pig colon . furthermore , the evidence for the elevation of the levels of endogenous cgrp and tks in human diseased colonic mucosa has also been demonstrated [ 18 , 19 ] ; irritants , immunological and inflammatory mediators can release tks and cgrp within the intestinal wall where these peptides may facilitate the release of 5-ht via the endogenous nk2/nk3 receptor cascade system . thus , these findings suggest a possible role of the endogenous nk2/nk3 receptor cascade system controlling the release of 5-ht from ec cells in pathophysiological conditions that are associated with an upregulation of cgrp or tks release . the 36 amino - acid long peptide , peptide yy ( pyy ) is known as a major peptide hormone , which regulates colonic functions ( motility and secretion ) and appetite by acting via different neuropeptide y receptor subtypes [ 20 , 21 ] . in the colon , pyy the blood pyy levels have been shown to increase rapidly in response to food ingestion , and the postprandial blood pyy levels remain elevated for several hours . abnormal levels of pyy in large intestinal endocrine cells have also been reported in patients with ibs [ 6 , 22 ] , indicating a possible role of pyy in the generation of the symptoms associated with ibs . the nk2 receptor agonist , ala - nka-(4 - 10 ) ( 10 - 100 nm ) also evoked a long - lasting and ttx - resistant pyy release from isolated guinea - pig colonic mucosa , thus suggesting that activation of nk2 receptors on the mucosal layer induces a long - lasting pyy release from l cells . 2 , pretreatment with the neuropeptide y1 receptor - selective antagonist bibo3304 attenuated the ala - nka-(4 - 10)-evoked 5-ht release . these findings support the hypothesis that activation of nk2 receptors on pyy - containing l cells provokes the release of pyy , which in turn activates mainly y1 receptors located on ec cells to induce 5-ht release ( fig . this hypothesis is further corroborated by findings that exogenously applied pyy ( 10 nm ) evoked a long - lasting and bibo3304-sensitive 5-ht release with a time course similar to that found for the nk2 agonist - evoked 5-ht release . overall , the above observations indicate that endogenously released pyy play a fundamental role in the nk2 receptor - triggered 5-ht release from ec cells ; pyy - containing l cells appears to control 5-ht release from ec cells ( fig . 3 ) . given that food intake is a major and physiologically significant factor stimulating the release of pyy from mucosal l cells and both pyy and 5-ht are well - known mediators of nausea and vomiting , it is hypothesized that the cascade of nk2 receptors on pyy - containing l cells and y1 receptors on ec cells ( fig . 3 ) might play a role in the generation of postprandial symptoms ( nausea and vomiting ) in patients with ibs ; in fact , a postprandial increase in plasma 5-ht levels have been shown to be related to the generation of postprandial symptoms in diarrhea - predominant ibs [ 24 , 25 ] . therefore , the nk2 receptor - triggered pyy release from colonic mucosa may be expected as a pharmacological target for postprandial symptoms in functional bowel disorders including ibs . activation of tachykinin nk3 receptors on enteric cholinergic neurons has also been shown to provoke the release of pyy from colonic mucosa . thus , to elucidate whether the endogenous tachykinergic nk2/nk3 receptor cascade system participates in the mechanism for food intake - induced pyy release , is an interesting topic for future study . the 5-ht - derived neurohormone , melatonin ( mt ) is mainly synthesized in the pineal gland as well as in 5-ht - rich ec cells of the intestinal mucosa . it has been shown that exogenous mt modulates colonic motility and pain in ibs patients [ 28 , 29 ] ; therefore , mt is considered as a possible therapeutic agent for ibs [ 29 , 30 ] . in the isolated guinea - pig colonic mucosa , mt has been shown to inhibit the nk2 receptor - triggered 5-ht release by acting through mt3 melatonin receptors located on the mucosal layer , thus suggesting a possible role of mt as a negative - regulator for the nk2 receptor - triggered 5-ht release from ec cells ( fig . it is not yet known whether or not endogenous mt participates in the pathogenesis of ibs , but oral mt has been shown to reduce abdominal pain and the sensation of bowel urgency in ibs patients . it is therefore to be expected that if low mt concentrations in the colonic mucosa facilitate 5-ht release from ec cells , the enhanced 5-ht release leads to abdominal pain in ibs patients . in fact , it has been shown that ibs patients have lower mt levels compared with healthy controls . thus , to elucidate whether the endogenous nk2/nk3 receptor cascade system participates in the modulatory effect of mt on colonic motility or pain , is an interesting topic for future study . the present review shows that the cascade pathway of nk3 receptors on cholinergic interneurons and nk2 receptors on pyy - containing endocrine l cells represents an endogenous modulator system for 5-ht release from colonic ec cells , and that melatonin , endogenous tks and pyy play important roles in the modulation of the release of 5-ht from ec cells via the endogenous nk2/nk3 receptor cascade system ( fig . 3 ) . given that tks , 5-ht - containing ec cells , pyy - containing l cells and melatonin play important roles in the pathophysiological regulation of colonic functions in the diseased gut including ibs , the potential role of the endogenous nk2/nk3 receptor cascade system controlling the release of 5-ht from ec cells , will undoubtedly be a focus of future investigations .

5-hydroxytryptamine ( 5-ht ) released from colonic mucosal enterochromaffin ( ec ) cells is a major signaling molecule , which participates in the pathophysiological regulation of colonic functions in gut disorder including irritable bowel syndrome ( ibs ) , but the endogenous modulator system for the 5-ht release is not yet well elucidated . our in vitro studies in guinea - pig colon have indicated that the cascade pathway of neuronal tachykinergic nk3 receptors and nk2 receptors on peptide yy ( pyy)-containing endocrine l cells represents an endogenous modulator system for 5-ht release from ec cells and that melatonin , endogenous tachykinins and pyy play important roles in modulation of the release of 5-ht from ec cells via the endogenous nk2/nk3 receptor cascade system . this review aims at examining the potential role of the endogenous tachykinergic nk2/nk3 receptor cascade system controlling the release of 5-ht from ec cells , with special attention being paid to the pathophysiology of gut disorders including ibs .

as a simple example , let us think about how to obtain a protein of interest . , they may be obtained from a patient 's cells or tissues , whereas for experimental use on the bench , the proteins may originate from microorganisms or from cell lines derived from insects , vertebrate animals , or plants . in any case , endogenous proteins that we do not want are present in a much greater quantity than the proteins we do want . regardless of the source , is not easy to isolate a specific protein for several reasons , some of which are presented below . first , no generalized property can be applied in protein purification . in the case of nucleic acids ( dna or rna ) , one can employ selective adsorption techniques using silica residues with positive charges , since nucleic acids have negative charges from their phosphodiester bonds . the development of specialized methods of nucleic acid purification , such as miniprep and midiprep , was made possible by the fact that all nucleic acid molecules are highly negatively charged . in contrast , the applicability of selective adsorption to proteins is limited for several reasons . hydrophobicity or specific electrostatic properties can be found in a diverse range of molecules , including lipids , nucleic acids , and sugars . however , some proteins may have strong surface charges or specialized functional groups that can be useful for purification . for example , a purification method with phosphocellulose has been used for dna - binding proteins that have many positively charged residues . nonetheless , this does not guarantee high purity or loss - free purification . unlike dna , protein purification requires multiple steps , rather than a simple one - step procedure . as will be described later , fractionation during the isolation process and use of the proper column type during the purification process enable successful purification . intracellular protein concentrations are known to be in the range of 300 mg / ml . however , this value refers to the total amount of proteins in a cell . since the number of active proteins in cells is in the tens of thousands , most proteins are present in negligible quantities except for some housekeeping gene products . in some cases proteins such as keratins can be used as biomarkers for cancer diagnosis because they are overexpressed proteins . spectroscopic or calorimetric methods usually require protein samples with concentrations ranging from 0.01 to 1 mm ( or to tens of mg / ml ) . therefore , most proteins directly derived from living organisms can not be analyzed using those methods . in mass spectrometry however , mass spectrometry is not a panacea , because the ionization efficiency may be not high enough to obtain a useful signal , depending on the nature of the peptide fragments . third , there is no way to amplify proteins . in the case of nucleic acids , amplification is possible , to the point that even a trace amount obtained in a biological sample can be used for further analysis . polymerase chain reaction ( pcr ) amplifies dna sequences , and rna sequences can also be amplified by reverse transcription pcr . in contrast , if a protein is not overproduced at the beginning of the experiment , it may be lost continuously during the experiment , to the point that it is not detectable at the final analytical stage . more specifically , certain proteins make up an exceptionally large share of the proteins present in cells . intermediate filament proteins and histones are proteins that appear as contaminants when analyzing trace proteins by mass spectrometry . these samples may be attached to blood vessels , or may be a mixture of lesions and healthy tissue . lipid molecules , blood cells , and/or blood plasma may already be present in excess . proteins that are classified as noise are present in much greater quantities than the target protein , which often makes data analysis difficult . fifth , proteins are unstable . it is well known that rna is quickly degraded , but proteins are also degraded by enzymes both in vivo and in vitro . it is not easy to block all proteolytic activity by adding protease inhibitors to a test tube . if the temperature , ph , or salt concentration is not suitable , proteins are likely to be denatured . if the experimental conditions of the buffer are not optimal , the proteins may aggregate before or after the analysis . in proteins with cysteine residues , the structure may be destroyed by undesired oxidation - reduction reactions . experts familiar with protein purification emphasize that researchers should not leave proteins in the refrigerator for a long time because proteins are unstable macromolecules . the simplest way to solve all the above problems for researchers is to use overexpression , or enrichment . the rule of thumb for protein experiments is to obtain as much protein as possible at the beginning of the experiment . as discussed above , proteins are inevitably lost over the course of the experiment because of their chemical and/or biological instability . given these practical limitations , it is important to obtain as much protein as possible at the beginning of the process . with this in mind , let us start our discussion of protein isolation by addressing methods for the high - efficiency isolation of proteins with little loss . choosing the best protein isolation method depends on the properties of the source sample ( e.g. , whether the sample is liquid or solid ) . supposing that a solid sample contains a large number of cells , a process must be used for homogenizing the tissues and lysing the cells . in the case of tissue samples , methods for lysing cells range from physical methods , such as heat treatment and sonication , to chemical methods , such as treatment with a detergent solution . detergents that increase the solubility of proteins can be used most effectively by taking into consideration the conditions of the experimental medium , especially the buffer . using appropriate detergents , proteins that are difficult to extract ( membrane proteins or nuclear proteins ) in addition , chaotropic reagents , such as urea and guanidine hydrochloride , can be used to increase the efficiency of extraction because they break down the structure of the protein and dissolve well in water . therefore , if not removed using membrane dialysis , the high salt concentration can cause problems in further steps of the experiment . one should consider both the advantages and disadvantages of using chaotropic reagents when designing an experimental procedure . in the case of liquid samples , a decision should be made about whether to obtain the dissolved protein or to extract it from the cells it is contained in . in order to extract the protein from the cells where it is present using media with different densities may be useful to isolate proteins expressed in specific cells . for example , to obtain only the immune cells from bodily fluids or to separate adipocytes or keratinocytes from skin tissue , centrifuging the liquid containing the cells in a high - density medium may precipitate the desired cells depending on the density of each constituent cell . density - gradient ultracentrifugation is additionally applicable for eliminating undesired cellular impurities or obtaining certain cell organelles . if a soluble protein is obtained from bodily fluids , it is treated similarly to a cell lysate from solid samples . thus , it is necessary to perform an enrichment process , such as concentration or precipitation . the traditional techniques of salting out and heat denaturation have the advantage of being very simple . in addition , the precipitated protein is very stable , meaning that this process may be used as a means of increasing the shelf life of a protein . salting out is a method of lowering the solubility of proteins through competing solubility in water using salts that are more soluble in water , such as ammonium sulfate . since proteins precipitate at a specific concentration of salt , this procedure also has the advantage that the desired proteins can be separated from other proteins and precipitated . instead of using salts , it may be desirable to use isoelectric precipitation by lowering the ph . isoelectric precipitation can be performed when the ph reaches at isoelectric point ( pi ) of the target protein . each protein has a different pi value , meaning that isoelectric precipitation can be used as a fractionation method as well . generally , this method is also very simple since a mineral acid or trichloroacetic acid ( tca ) is titrated until the target protein is obtained through precipitation . when changing the ph or salting out is not preferable , polymers such as polyethylene glycol or organic solvents such as methanol or acetone can be used to promote precipitation . if required , a cocktail of precipitating reagents ( e.g. , a mixture of acetone and tca ) can be developed . however , the isolation technique should be chosen with the method of analysis in mind , as the isolation step may cause denaturation of the protein or require additional steps such as salt removal . the centrifugal membrane concentration method is a useful single - step method of concentrating a protein . however , it is important to keep in mind that this method may exhibit problems involving clogging when used with highly concentrated proteins , and such problems decrease the efficiency of the concentration procedure and increase the loss of the protein . after enrichment , purification is necessary . proteins for analytic experiments must be pure enough to have a high signal - to - noise ratio . methods for purifying target proteins from dirty mixtures vary widely , but preparation - grade purification is most commonly achieved using chromatography . since , as discussed above , proteins do not have a generalized purification method ( unlike nucleic acids ) , the type of chromatography to be used depends entirely on the physical and chemical properties of the target protein . proteins are usually purified by liquid chromatography ( lc ) , and fast protein lc and high - performance lc can be chosen depending on whether the goal is preparation or quantitative analysis . for proteins , it is possible to use the following techniques either in a single step or sequentially : hydrophobic interaction column chromatography , size exclusion chromatography , ion exchange column chromatography , and affinity chromatography . if it is not necessary to prepare a large quantity of the target protein , electrophoresis is a possibility . if the molecular weight of the target protein is known , the approximate band position on the gel can be cut and be used for further analysis like mass spectrometry . in general , sodium dodecyl sulfate - polyacrylamide gel electrophoresis ( sds - page ) provides 1-dimensional ( 1d ) results when analyzing proteins by size . instead of directly loading the protein sample when performing sds - page , it is possible to perform 2-dimensional ( 2d ) electrophoresis by performing isoelectric focusing and loading the resultant gel tube with proteins separated according to their pi values . gels developed in 2d have much better resolution than gels developed in 1d , making this a favorite technique in proteomics . if the target protein is too small for the band ( 1d ) or spot ( 2d ) to be easily stained after electrophoresis , a western blot using antibodies can be performed . in order to perform western blotting , it is necessary to have an antibody specific to the target protein . in recent years , western blotting has become possible in most cases due to the commercial availability of a very wide range of antibodies . since antibody binding is specific , most of the final products are obtained only from the target protein of the antibody . either protein a - conjugated or protein g - conjugated agarose , which bind to most antibodies , can be used in most cases , meaning that virtually any kind of antibody can be applied to obtain a small amount of target protein through several rounds of centrifugation . the enzyme - linked immunosorbent assay ( elisa ) technique is a sensitive assay method using antibodies . elisa is an enzyme - amplified reaction for antigens present in trace amounts in bodily fluids . using elisa , both the presence of the target protein and quantitative information about it can be obtained without purification . of course , if enough antibodies are present , it is possible to identify the amount and location of proteins in tissues and cells in situ via immunohistochemistry or immunofluorescent labeling . if the antibody is obtained from camelids , a unique antibody protein known as a single - chain antibody or nanobody can be obtained . a typical antibody usually consists of four polypeptide chains per molecule , whereas a camelid antibody has two chains per antibody molecule . since the antigen - binding site of a camelid antibody is composed of a single chain , the cloning and the production process are simpler than those of regular antibodies . as antibody design studies evolve , the use of single - chain antibodies will become more common . instead of using antibodies aptamers can be obtained by screening rna or dna macromolecules for binding to target molecules ( usually through a method known as selex [ systematic evolution of ligands by exponential enrichment ] ) . aptamers are likely to replace antibodies because they are very easy to synthesize in vitro . in recent years , techniques for identifying target proteins in which mass spectrometry and lc are combined have become very common . metabolic labeling can be used for quantitative analyses , but only in controllable culture conditions in bench work . nevertheless , it is becoming an accurate and reliable protein analysis method since sequence information can be obtained even from trace amounts of target proteins . recently , mass spectrometry imaging ( also known as imaging mass spectrometry ) has been studied as a way of detecting and analyzing proteins directly in specific locations in cells or tissues by imaging mass profiles ( or maps ) on 2d samples . this technique is very similar to finding a neurotransmitter in a specific section of the brain using magnetic resonance imaging . if this technique is generalized , it will be possible to detect the presence or absence of a target protein in situ just by looking at the tissue or cell . in other words , it may become possible to determine the presence or absence of a desired biomarker quickly and accurately even in a complex situation ( e.g. , when no appropriate antibody exists or the sample is a mixture of normal tissue and lesion tissue ) . much work must still be done in collecting and analyzing proteins , requiring considerable research on the part of bench scientists . as long as proteins continue to be used as the major biomarkers for diagnosing diseases i am confident that communication both among bench scientists and between bench scientists and clinicians will be a major driving force in future protein research .

at the summer workshop of the korean endocrine society held in 2016 , some examples of protein experiments were discussed in the session entitled all about working with proteins . in contrast to what the title suggested , it was unrealistic to comprehensively discuss all protein analytical methods . therefore , the goal was to outline protein experimental techniques that are useful in research or in bench work . in conversations with clinicians , however , i have always felt that researchers who do not engage in bench science have different demands than those who do . protein research tools that are useful in bench science may not be very useful or effective in the diagnostic field . in this paper , i provide a general summary of the protein analytical methods that are used in basic scientific research , and describe how they can be applied in the diagnostic field .

leptomeningeal carcinomatosis ( lc ) , also called carcinomatous leptomeningitis , neoplastic ( lepto)meningitis , leptomeningeal metastasis , or more commonly leptomeningeal seeding , is the dissemination and growth of cancer cells within the leptomeningeal space ; it is one of the most serious complications that can occur in cancer patients1 ) . lc is frequently found in patients with leukemia , breast cancer , lymphoma , and lung cancer2 ) . gastric cancer ( gc ) is one of the most common causes of cancer related death in asian countries including korea . kim , et al3 ) reported that the incidence of lc with gc was 0.06% of all cases of gastric cancer . lc is a more frequent manifestation of advanced or metastatic carcinoma rather than associated with early disease . we report a rare case with lc as the presenting symptom and review the medical literature . a 49-year - old woman was admitted to our hospital with headache , dizziness , easy fatigability , and melena for 10 days . her vital signs were as follows : a blood pressure of 130/75 mmhg , a pulse rate of 95 beats / min and a respiration rate of 21 breaths / min . the mri of brain showed no abnormalities , but the esophagogastroduodenoscopy showed thickening of the gastric folds on the greater curvature of the stomach and on the posterior wall of the stomach compatible with a borrman type iv gastric cancer ( figure 1 ) . the ct scan of abdomen and pelvis showed an advanced gastric cancer involving the posterior wall of the lower body of the stomach ; in addition , the angle and the antrum had extensive metastatic lymphadenopathy . the patient complained of an intractable persistent headache as well as nausea and vomiting on admission day 6 . a lumbar puncture and analysis of the cerebrospinal fluid ( csf ) there were many mucin - secreting cells and signet ring cell types , which were strongly positive for mucicarmin and alcian blue in the csf ( figure 4 ) . since the first report of leptomeningeal carcinomatosis ( lc ) in 1870 , the incidence of lc has been increasing . gastric cancer is the most common cancer in korea ; however , lc associated with gastric cancer ( gc ) is relatively rare . in the korean medical literature , the incidence of lc with gc has been reported to be 0.06% of all gastric cancers3 ) . among cases with lc , gc is reported as the most frequent cause of cancer in korea4 , 5 ) . however , these results are based on the experience of one institution , so these findings may not be generalized to the entire korean population . the clinical manifestations of lc are very variable and depend on the site of involvement . many patients complain of headache , nausea , vomiting , ataxia , and have a variety of neurological deficits . lc is usually a manifestation of advanced cancer discovered during follow - up after a cancer diagnosis ; it is rarely the presenting symptom as it was in this case . the median time to the diagnosis of lc , from the initial cancer diagnosis , is very variable ; reports have found a 76 day5 ) to 17 month4 ) time interval .. diagnosis is based on cytology examination of the csf and imaging studies ( especially , magnetic resonance imaging with gadolinium enhancement)8 ) . the csf findings include an increased opening pressure , elevated protein , the presence of tumor markers ( for example , cea , ca19 - 9 in gastric cancer ) , decreased glucose , and pleiocytosis . however , the diagnosis is frequently missed on the first trial but the diagnosis rate increases by 30% on a second one . in our case , reported on patients with breast cancer metastasized to the central nervous system over 20 years . out of five lc patients , only one ( 20% ) patient was confirmed cytologically9 ) . pathologically , poorly differentiated adenocarcinoma with signet ring cell features is the most frequent type of lc associated with gc in japan10 ) and this is likely true for korea3 ) . lc was a more frequent finding in advanced disease with or without distant metastases ; it is rarely reported with early gastric cancer11 ) . imaging studies ( mri with gadolinium enhancement ) show abnormalities in 67% of lc patients12 ) . there are several treatment options for patients with lc including intrathecal ( it ) chemotherapy with or without radiotherapy ( rt ) . most chemotherapeutic agents do not penetrate the blood - brain barrier ( bbb ) , and are given by direct intrathecal administration . agents that can be used for it chemotherapy include methotrexate ( mtx ) , cytarabine , thiotepa , and steroids . the benefit ( i.e. the prolongation of survival ) achieved by it chemotherapy ( single or multiple regimens ) in lc patients continues to be debated . the median survival of lc is reported to be four to six months even with aggressive therapy . in one study , the objective response rate and median survival of it mtx were 20% and 11 weeks ; with sustainedrelease cytarabine they were 25% and 15 weeks . therefore , the results did not confirm a definite benefit with the it chemotherapy13 ) . however , in a korean study , there was a favorable outcome with combination it chemotherapy , compared to the single it chemotherapy14 ) . mtx , one of most useful agents for it chemotherapy , penetrates the blood brain barrier poorly in low doses , but can penetrate in the higher dose range . high dose intravenous mtx ( 3.5 g / m ) injection showed a 28% partial response and stable disease and 44% progressive disease . the median survival of patients with lc ( with or without parenchymal disease ) was 12.6 weeks ; shorter than with isolated parenchymal disease ( 25.4 weeks)15 ) . the clinical risk factors that influence the survival of patients with lc are performance status , underlying malignant disease and previous responsiveness to anticancer therapy . the patients with disease that is more advanced , poor performance status ( ps ) , chemoresistant tumors , pronounced neurological clinical findings , and a heavy pretreatment status have a poor prognosis and additional management should be with conservative treatment16 ) . in our case , the patient had a poor ps , pronounced abnormal neurological clinical findings and a very rapidly deteriorating clinical course .

leptomeningeal carcinomatosis occurs in approximately 5% of patients with cancer . the most common cancers involving the leptomeninges are breast , lung cancer and melanoma . however , gastric adenocarcinoma has been rarely reported with leptomeningeal carcinomatosis . the presenting manifestations are usually headache , visual disturbances and seizures . we report a case of leptomeningeal metastasis that presented as a gastric cancer . a 49-year - old woman was admitted to our hospital with the symptoms of headache and melena for 10 days . the endoscopy showed a thickening of the folds of the stomach compatible with the diagnosis of a borrman type iv gastric cancer . the biopsy revealed a signet ring cell carcinoma . the mri of brain showed no abnormal findings ; however , the patient complained of an intractable persistent headache , nausea and vomiting on admission day 6 . the cytology examination of the cerebrospinal fluid supported the diagnosis of metastatic signet ring cell carcinoma .

however , only 40% of patients are eligible for radical surgical procedures ( tis - t3 n0 - 1 m0 ) [ 1 , 2 ] . the methods of surgical treatment for escc in the thoracic region and the cardia include radical esophagectomy with subsequent reconstruction of the gastrointestinal tract using fragments of the stomach , colon , or ( significantly less often ) the small intestine [ 3 , 4 ] . the success of the procedure depends on many factors ; the most important include the grafting technique and the type of anastomosis [ 5 , 6 ] . the place of anastomosis between the esophageal stump and the organ used to reconstruct the digestive tract may be affected by complications such as leaks or stenoses . anastomotic leak is an early complication observed between the 6 and 9 postoperative day , whereas stenosis is a late complication occurring 4 - 6 weeks after surgery . the aim of this paper is to present the case of a patient who underwent radical resection of the esophagus and stomach , complicated by necrosis of the colonic graft . the 45-year - old patient was admitted to the clinic due to esophageal cancer resulting in grade 3 dysphagia ( swallowing liquids only ) and malnutrition ( nutritional risk score : 5 ) . radiological examination with oral contrast revealed a stenosis in the vicinity of the cardia and an irregular contour of the gastric fundus . gastroscopy demonstrated the presence of a neoplastic infiltrate starting 35 cm from the dental margin and extending into the gastric fundus . histopathological examination of the samples obtained during gastroscopy yielded the diagnosis of squamous cell carcinoma . computed tomography revealed a thickening of the distal part of the esophagus ( fig . 1b ) up to 5 cm , without signs of pathology in the perigastric or mediastinal lymph nodes ( uicc tnm : t2n0m0 ) . the patient was qualified for a surgical procedure consisting in esophageal resection using the akiyama method . during the 10 days before the procedure , only parenteral feeding was employed . a ) at the level of the cardia , b ) at the level of the gastric fundus ( the arrows indicate the location of the tumor ) the patient was lying in a supine position , and access to the left side of her neck was ensured . after opening the abdominal cavity , infiltration of the gastric fundus was revealed along with a massive adhesion with the left lobe of the liver , but the disease had not disseminated across the abdominal cavity . as the neoplasm involved a significant portion of the stomach , the operative strategy was changed to complete gastrectomy with partial resection of the left hepatic lobe and the thoracic segment of the esophagus . the abdominal stage of the procedure consisted in total gastrectomy with d2 lymphadenectomy with resection of segments 2 and 3 of the liver . skeletonization from the side of the lesser curvature was preceded by resection of hepatic segments 2 and 3 . next , after the ligation of the left gastric vessels , the whole stomach was removed along with the regional lymph nodes ( fig . the distal part of the stomach was excised , and the stump of the duodenum was closed with a linear stapler ; in turn , the proximal side of the stomach was excised in the area above the cardia after the diaphragmatic crura were transected . the right half of the colon was used to restore the continuity of the gastrointestinal tract between the esophagus and the isolated loop of the jejunum using the roux - y method . the continuity of the large intestine was restored by ileotransversostomy . in order to anastomose the colonic graft with the cervical esophagus , as the evaluation of heart rate in the distal part of the graft was impeded , intraoperative doppler examination was performed , revealing a disturbance in the blood supply to the ultimate fragment of the large intestine ; subsequently , a resection of the ischemic part of the large intestine was performed . after the cervical esophagus was excised from the thoracic part of the esophagus , anastomosis was performed with the previously prepared colonic graft , which was interposed through a tunnel created in the frontal mediastinum . the anastomosis between the esophageal stump and the large intestine was performed end - to - side using a circular stapler ( eea 21 , tyco , usa ) . the distal end of the colonic graft was anastomosed with the isolated roux - y loop . the remaining portion of the esophagus was removed by opening the right half of the chest . on the 8 day after the procedure , signs of wound infection and increasing subcutaneous emphysema were found on the patient 's neck . radiological examination using oral contrast confirmed the presence of a leak in the frontal part of the anastomosis . postoperative histopathological examination confirmed the diagnosis of esophageal squamous cell carcinoma ( uicc ptnm : t2n0m0 ) . macroscopic image of the removed stomach with the tumor of the cardia and part of the left hepatic lobe the second procedure was performed on the 13 postoperative day . during the surgery , a decision was made to revise the anastomosis between the esophagus and the large intestine . the location of the leak was sutured and the lines of anastomosis were covered with collagen tissue glue . however , on the 16 postoperative day , the patient 's general condition deteriorated ; she was diagnosed with sepsis with signs of systemic inflammatory response syndrome and increasing infection of the neck wound . the third surgical procedure consisted in revising the neck wound and reopening the abdominal cavity to remove the colonic graft . the stump of the roux - y loop was closed , and a salivary fistula was created out of the esophageal stump . after this procedure , the patient 's general condition gradually improved . on the 23 postoperative day , the patient was discharged home with the recommendation of enteral feeding using a feeding microfistula . the fourth procedure was performed 10 months after the initial surgery ; its purpose was the reconstruction of the digestive tract using the remaining left side of the colon . as part of the preparations for the surgery , a pet scan was performed , revealing no signs of locoregional recurrence or neoplastic diffusion . during the surgery , an isolated graft was created out of the left side of the colon ; its proximal end was anastomosed with the esophageal stump , while the distal end was anastomosed with the roux - y loop ( fig . the postoperative course was uneventful , and the patient was discharged on the 8 postoperative day . the time of follow - up since the last procedure is 3 months ; during this time , the patient 's body weight has increased , her nutrition has improved , and no early or late complications have been observed . intraoperative image ( taken immediately before the performance of anastomosis ) of the isolated graft created from the left side of the colon . the proper selection of the extent of surgery in the case of cancer of the cardia is challenging for surgical teams due to the tumor 's location on the margin between the abdominal cavity and the chest . in the present case , the patient was diagnosed with squamous carcinoma , which is less common in this location in comparison with adenocarcinoma . according to literature data , these two types of neoplasms require different operative strategies in order to achieve a radical resection . in the case of adenocarcinoma of the cardia , this requires gastrectomy with resection of the distal part of the esophagus and thoracic anastomosis . in view of the diagnosis of squamous carcinoma of the cardia , a decision was made to perform additional resection of the thoracic segment of the esophagus with cervical anastomosis due to the increased risk of skip metastases associated with this type of tumor and in order to perform two - field lymphadenectomy . a possible alternative to the akiyama procedure would have been to perform gastrectomy and partial esophageal resection with thoracic anastomosis , but the surgical team was concerned that this procedure would not have been radical enough and that it would be impossible to monitor the performed anastomosis . restoring the continuity of the gastrointestinal tract after esophageal resection is most commonly performed using stomach tissue ; less commonly , the colon is employed for this purpose . the anastomosis is most often created in the neck , which allows for better clinical supervision of the anastomosis location ; it is also associated with less severe side effects if a leak develops [ 3 , 4 ] . in the present patient , the anastomosis was cervical , which enabled the surgical team to open the wound early and apply drainage . notwithstanding , the method proved to be insufficient , forcing the surgeon to remove the whole colonic graft . another significant factor influencing the quality of an anastomosis is the technique of its performance . at present , there is currently no uniform optimal standard concerning the method of performing cervical esophagogastric anastomosis . in the present case , stapler anastomosis was performed during the first procedure , and manual one - layer anastomosis was used during the repair procedure . most authors agree that surgical treatment of esophageal cancer should be performed in centers that employ surgeons with excellent operative technique and sufficient experience with regard to the proper selection of patients for the procedure [ 1 , 9 ] . the authors of this report work at a clinic which has over 40 years of experience with treating esophageal cancer . in the present case , preoperative endoscopy and computed tomography indicated that it was feasible to perform esophageal resection using the akiyama method . however , the greater extent of the neoplastic infiltrate within the stomach and the presence of a massive adhesion with the left lobe of the liver resulted in a change of operative strategy . this report confirms that individualization of surgical management is a crucial factor in oncological surgery . the experience accumulated in our clinic by several generations of surgeons enabled us to reduce postoperative mortality to 7.8% and achieve 18% 5-year survival among esophageal cancer patients treated with radical surgery .

surgery is the treatment of choice for squamous cell esophageal cancer . complete resection of the esophagus with reconstruction of the digestive tract is performed for tumors located in the chest or cardia . the aim of the report is to present the case of a complete esophageal and gastric resection complicated by colon graft necrosis . the patient was a 45-year - old woman diagnosed with cancer of the cardia infiltrating the distal section of the esophagus and the body and fundus of the stomach . the initial surgical procedure included the opening of three body cavities followed by resection of the thoracic esophagus , stomach , and a portion of the left hepatic lobe . right colon interposition was performed to restore digestive tract continuity . on the 8th day , a leak was observed in the esophagointestinal anastomosis . management consisted in two surgical procedures , one of which ended in the removal of the colon patch . the fourth and final procedure was conducted after 10 months .

anaesthesia for pituitary tumours booked for non neurosurgical surgeries is a challenge to an anaesthesiologist with the risk of sudden change in intracranial dynamics during administration of spinal anaesthesia or during laryngoscopy , intubation and extubation . here we report anaesthetic management for elective lower segment caesarian section ( lscs ) with previous pituitary tumour resection one with residual tumour done under general anaesthesia . a 24-year - old female weighing 65 kg and height of 156 cm , with 38 weeks of gestation with history of complete transphenoidal resection of functioning pituitary macroadenoma ( growth hormone and prolactin secreting ) two years ago was posted for elective lscs . airway examination done two days prior to lscs suggested a difficult intubation with mallampati class iii , macroglossia , prominent neck fold in the nape and a protruding mandible . she had no history of snoring . all heamatological , biochemical and hormonal investigations were unremarkable . magnetic resonance imaging ( mri ) of the brain done at 30 weeks showed tumour encasing left internal carotid artery with no evidence of raised intra cranial pressure ( icp ) . monitors ( pulse - oximeter , electrocardiogram , capnometer and non invasive blood pressure ) were attached . rapid sequence induction was done using thiopentone sodium and rocuronium , intravenous lignocaine 1.5 mg / kg was used to suppress the stress response . laryngoscopy was done using macintosh blade size 4 to find cormacke lehane grade ii and cuffed endotracheal tube ( i d 7.0 mm ) was passed . intravenous lignocaine 1.5 mg / kg was used for smooth emergence and patient was extubated once fully awake . the pituitary gland is located at the base of the skull in the sella turcica . the hypothalamus regulates hormone release from the anterior pituitary through hypothalamic releasing and inhibiting factors that reach the anterior pituitary by a complex portal vascular system . the anterior pituitary secretes at least seven hormones while the posterior pituitary stores and secretes two hormones , antidiuretic hormone and oxytocin . functioning pituitary adenomas produce an excess of the anterior pituitary hormones . other less common pituitary tumours are growth hormone secreting lesions resulting in acromegaly ; adenocorticotropic hormone ( acth ) secreting tumours causing cushing 's disease and a very rare thyroid - stimulating hormone ( tsh ) secreting lesion resulting in hyperthyroidism . prolactinomas may produce the amenorrhea - galactorrhea syndrome in females . as the pituitary lesion compresses the pituitary tissue , the sequence in which hormonal function is lost is gonadotrophins ; growth hormone ; acth and tsh . patients with acromegaly exhibit a general overgrowth of skeletal , connective and soft tissues leading to enlargement of hands , prognathism and macroglossia . thickening of laryngeal and pharyngeal soft tissues and vocal cords , reduction in size of laryngeal aperture , hypertrophy of uvula , epiglottic fold and recurrent laryngeal nerve palsy also occur . all major organs increase in size , including the heart , lungs , liver , thyroid and kidneys . these patients require preoperative evaluation and management of coronary artery disease , cardiomyopathy with arrhythmias , hypertension ( 30% ) , diabetes ( 25% ) and electrolyte imbalances . upper airway obstruction with sleep apnoea is a major cause of laryngeal airway obstruction and central depression . therefore , the risk of death from respiratory failure is threefold greater in patients with acromegaly . as glucocorticoids are also necessary to facilitate renal excretion of a water load , diabetes insipidus is usually not observed in the patient with pituitary insufficiency until cortisol replacement therapy is instituted . preoperatively , the patient with panhypopituitarism will be receiving oral steroid and levothyroxine therapy and , when indicated , intranasal instillation of synthetic vasopressin . other signs and symptoms in prolactin secreting microadenoma include amenorrhea , galactorrhea , anovulation , decreased libido , gynaecomastia and osteoporosis . tumour cells in patients with prolactinomas and that with gh secreting tumours may exhibit symptomatic enlargement during pregnancy , probably due to the growth - promoting effect of estrogens . this may be because of an increase in either peritumoural edema secondary to increased sodium and water retention or blood volume in vascular tumours such as meningiomas . accelerated tumour growth during pregnancy is likely , owing in part to the high levels of circulating progesterone that occur with gestation . as pregnancy itself is an insulin - resistant state , the pregnant acromegalic patient is at greater risk for hyperglycemia . there is also an increased incidence of hypertension and coronary artery disease in acromegalic patients , which poses potential risks to the fetus . however , none of these potential complications of elevated gh have been shown to have a deleterious effect in pregnant acromegalic patients . active acromegaly during pregnancy does increase insulin resistance and thus increase the risk of gestational diabetes and hypertension . underlying cardiac disease , from metabolic syndrome , hypertension , or acromegaly - associated cardiomyopathy , may become symptomatic during pregnancy . pregnancy has not been found to alter the course of acromegaly other than in rare , reported cases of asymptomatic tumour enlargement . whether tumour enlargement is more common in lesions that co if left untreated for the duration of pregnancy , it is thought not to have any adverse effects on the course of acromegaly , which otherwise is a chronic disease that can be addressed after delivery . diabetes insipidus ( di ) can occur de novo during pregnancy or in the postpartum period , while pre - existing di may be exacerbated during pregnancy . in addition , a transient di may occur during pregnancy in the absence of a known defect in arginine vasopressin ( avp ) secretion . glucocorticoid dose does not usually need to be changed during pregnancy , although symptoms occasionally indicate that a mild increase is required . stress levels of cortisol or its equivalent are needed for labour and for any intercurrent major stress during the pregnancy . the blood supply to the already enlarged pituitary gland is seriously compromised in times of acute volume depletion compounded by vasospasm due to circulating vasoconstrictors . the enlarged gland and low pressure in the portal system cause susceptibility to tissue hypoperfusion and infarction and it leads to an atrophic , hypofunctioning and a scarred gland . it has been suggested that patients with sheehan syndrome have a small , rigid sella from the outset . the hyperplastic pituitary in this sella may be more likely to compress its blood supply , predisposing the gland to infarction if hypotension occurs . pregnant women with type 1 diabetes , especially those with preexisting vascular disease , seem to be particularly at risk . the pre - anaesthetic considerations are related to the endocrine and the tumour status . during the pre - anaesthetic evaluation , the size and location of the tumour and its effect on intracranial dynamics there are four grades of airway involvement described in acromegaly ; grade 1- no significant involvement ; grade 2- nasal and pharyngeal mucosa hypertrophy but normal cords and glottis ; grade 3- glottic involvement including glottic stenosis or vocal cord paresis ; grade 4- combination of grade 2 and grade 3 . for patients with difficult airway and glottic abnormalities , the intubating laryngeal mask airway is another alternative in a patient with acromegaly . raised icp can result in either reduction in perfusion pressure with concomitant ischaemic injury or herniation of brain tissue causing brain injury . the main aim of the anaesthesiologist is smooth induction of anaesthesia by avoiding coughing , straining by maintaining patient in deeper plane of anaesthesia , avoiding hypo or hypertension . it will produce a fall in icp by lowering the cerebral metabolic rate ( cmro2 ) and the cerebral blood flow ( cbf ) . it is essential for pregnant patients to undergo mri after four months gestation especially those who have undergone pituitary surgery in the past to look for any residual tumour which can increase in size . unlike computerized tomography ( ct ) , we suggest that any pregnant patient with history of pituitary tumour or resection of the same should undergo preoperative extensive evaluation and those with acromegaly for detailed airway assessment .

successful anaesthetic management for caesarean section in a case with previous pituitary tumour resection , with residual tumour , is reported . the pituitary gland undergoes global hyperplasia during pregnancy . functional pituitary tumours may exhibit symptomatic enlargement during pregnancy . growth hormone secreting tumour is associated with acromegaly which has associated anaesthetic implications of difficult airway , systemic hypertension , and diabetes and electrolyte imbalance . intracranial space occupying lesions can increase intra cranial pressure and compromise cerebral perfusion or cause herniation . we report management of this case .

hirayama disease , a rare neurological disease , is characterized by insidious unilateral or bilateral muscular atrophy and weakness of the forearms and hands , without sensory or pyramidal signs . the disease progresses initially , but spontaneous arrest is known to follow several years after the onset , unlike motor neuron disease with which it is commonly confused . hirayama disease is characterized by focal ischemic changes in the anterior horn cells of the lower cervical cord that result in amyotrophy , which is usually unilateral but may also be bilateral . we describe the characteristic findings of flexion magnetic resonance imaging ( mri ) suggestive of hirayama disease . a 17-year - old male reported in the medicine out patient clinic with a one year history of slowly progressive weakness and atrophy that started in the left hand and the forearm and gradually involved the right hand . the hand weakness limited several activities of his daily living and he could no longer play cricket because of the same . his past medical history was noncontributory ; he denied any allergic disease and none of his family members had similar symptoms . neurological examination revealed severely wasted and weak forearms and hands , tremors but no evidence of pyramidal , spinothalmic , posterior column lesions , polyminimyoclonus or autonomic disturbances . plain cervical spine radiographs showed no abnormalities , or misalignment of the vertebral bodies [ figure 1 ] . plain cervical spine ( lateral view ) radiograph shows no abnormality and no misalignment of the vertebral bodies mri was performed on magnetom concerto 2002b siemens 0.2 tesla mr unit . the following mr sequences were used : 1)precontrast axial , sagittal and coronal t1 and t2-weighted spin - echo.2)post gadolinium contrast axial and sagittal t1-weighted spin - echo.3)axial and sagittal gradient - refocused echo ( gre ) flexion cervical mr study . cervical mr images in the neutral position showed focal atrophy of the lower cervical cord at the c4 - 7 vertebral levels but no abnormal intramedullary high signal intensity [ figure 2 ] . when the neck was flexed , the posterior wall of the cervical dural sac between c4 and d1 vertebral levels was seen to shift anteriorly ; the markedly flattened and anteriorly displaced cervical cord was compressed over the posterior surface of the c4 to d1 vertebral bodies . an enhancing epidural space , isointense with the cord on t1-weighted images and hyperintense on t2-weighted images was noted at the posterior aspect of the lower cervical canal [ figures 3 and 4 ] . cervical t1w - sagittal mr image in the neutral position shows focal atrophy of the lower cervical cord at the c4 - 7 vertebral levels but no abnormal intramedullary high signal intensity cervical gre - sagittal mr image in the flexion position shows the posterior wall of the dural sac between c4 and d1 vertebral levels to shift anteriorly , and the anteriorly displaced cervical cord compressed over the posterior surface of the vertebral bodies cervical gre - axial mr image in the flexion position shows the markedly flattened , anteriorly displaced cervical cord due to the epidural lesion ( black arrow ) the patient was prescribed a cervical collar to prevent neck flexion . this disease was described first by , and named after , hirayama in 1959 and most cases of this disease have been reported from japan and india . this non - familial disorder mostly hits young men , progresses slowly and is often self - limited . researchers argue that wasting and weakness associated with this disease is because of imbalanced growth between the patient 's vertebral column and spinal canal contents . the imbalanced growth causes a tight dural sac and displaces posterior dural wall anteriorly when the neck is flexed . normally , the spinal dura mater is loosely anchored to the vertebral canal by the nerve roots and the periosteum at ( a ) the foramen magnum and the dorsal surfaces of c2 and c3 and ( b ) the other at the coccyx . the dura mater is slack enough to adjust to the increased length of cervical spine in flexion . in patients with hirayama disease , however , the tight dural sac separates the posterior dural sac from its subjacent lamina and on neck flexion , can not compensate for the increased length of the posterior wall . the posterior dural wall shifts anteriorly , and the cervical spinal cord gets compressed against the posterior margin of adjacent vertebral bodies . this compression affects the anterior spinal artery and causes microcirculatory disturbances in its territory in the lower cervical cord ; the anterior horn cells which are vulnerable to ischemia begin to degenerate , resulting in localized cord atrophy of the lower cervical region , weak and wasted hands and forearms . hirayama disease is also associated with raised levels of serum ige and several allergic disorders . blood often stagnates in the compressed lower cervical cord allowing platelets to aggregate and cause histamine to be released , factors that cause arterial spasm and microcirculatory disturbances . moreover , the finding that atopic disorders affect young people more than the elderly , men more than women , and asians more than non - asians may in part explain the distribution of hirayama disease . the key to diagnose this disease during mri scanning is to obtain images when the neck is flexed . mr studies in flexion not only show the anterior displacement of the posterior wall but also a well - enhanced crescent - shaped lesion in the posterior epidural space of the lower cervical canal . although hirayama disease is a self - limiting disorder , early diagnosis is necessary because a cervical collar , by preventing neck flexion , may arrest the progression of the disorder . in conclusion , this case showcases how cervical mri , with neck flexed , can pick up dynamic cord compression and contribute to the diagnosis of hirayama disease

a 17-year - old male , who gave up his favorite sport cricket and started playing football , presented with one - year history of slowly progressive atrophic weakness of forearms and hands . neurological examination showed weak and wasted arms , forearms and hand but no evidence of pyramidal tract , spinothalmic tract and posterior column lesions . plain cervical spine radiographs showed no abnormal findings . cervical magnetic resonance imaging ( mri ) showed asymmetric cord atrophy ; images obtained with neck flexed showed the anterior shifting of the posterior wall of the lower cervical dural sac resulting in cord compression . these findings suggest hirayama disease , a kind of cervical myelopathy related to the flexion movements of the neck .

thyroid cancer is the 10th commonest cause of cancer in russian women , and the age - specific incidence of thyroid cancer has been on the rise . while most thyroid cancers have a good prognosis , those that show tracheal invasion often show poor survival because of extensive resection or tumor recurrence . surgical intervention is the key point of treatment , and appropriate surgical planning is essential to get a promising prognosis , postsurgical quality of life , and social rehabilitation of a patient . despite an increasing role of nonadjuvant radiotherapy and/or chemotherapy in the treatment of thyroid cancer , the surgical approach is still used when recurrence is treated after radiotherapy / chemoradiotherapy or in the case of combined treatment of patients with thyroid papillary carcinoma invading the trachea . the extensive resection that may be necessary for locally invasive thyroid cancer has led some surgeons to attempt to conservatively approach these tumors using peeling or shaving techniques aiming at preserving function [ 2 , 3 ] . such conservative approaches rely on the administration of postoperative radioactive iodine with / without external beam radiotherapy to manage a microscopic disease . many patients with locally advanced thyroid cancer tend to be older patients with more poorly differentiated histologic variants . tumors in such patients can be nonradioactive iodine avid , and the response to radioactive iodine therapy can be disappointing . recently , the importance of sparing surgery has also increased in clinical head and neck oncology . it fully applies , for instance , to the treatment of patients with laryngeal cancer . better functional and cosmetic result for a patient should also be an objective . in this report , we present a patient with advanced thyroid papillary carcinoma involving the trachea , who has previously undergone total thyroidectomy followed by radioactive iodine therapy in 2012 . the first one was a window resection of the trachea followed by an open tracheostomy , and the formed knitted tini - based mesh endograft ( ktnme ) , as reported by muhamedov et al . the second stage was the reconstruction of the large tracheal defect with the harvested endograft and the skin draping over the wound . the patient presented here is a 54-year - old female who was referred and admitted to the hospital of the tomsk cancer research institute on april 2 , 2014 ( clinical case # b273xx ) . the patient underwent total thyroidectomy for papillary thyroid cancer ( type t4nxm0 ) in june 2012 when the cancer directly involved the tracheal wall , followed by radioactive iodine therapy in the vladivostok central clinical hospital in july 2012 . apparently , she was considered with no evidence of disease until december 2013 when the mass in her trachea that she noticed had been gradually increasing in size within the recent months , and the histological findings verified well - differentiated papillary carcinoma recurrence . there were objectively no remarkable signs except for a neck incisional scar and the subcutaneous , rounded , newly grown palpatory mass detected ( about 1.5 cm in diameter ) . she had other symptoms such as dyspnea at rest , hoarseness , and minor hemoptysis . fiberoptic endoscopy and magnetic resonance imaging ( mri ) revealed a circumferential stenosis on the right side below the vocal cord , invading the lumen of the trachea . a submucosal mass from the 2nd to the 5th tracheal ring with an irregular surface penetrating the mucosa with signs of ulceration and erosion was noted ( fig 1 ) . according to the above findings , the case was classified as t4n0m0 , and a double - stage surgical treatment was scheduled ( fig 2 ) . the first stage was performed on april 15 , 2014 . to involve the platysma muscle , the u - shaped incision was made alongside the postoperative scar ( fig 3a ) . subcutaneous fat was removed with electrocautery to aid in exposure and to prevent later fat necrosis . dissection proceeded through the platysma until the midline raphe between the strap muscles was identified ( fig 3b ) . the sternocleidomastoid muscle was thus separated , retracted laterally , and preserved . by tracing , the right recurrent laryngeal nerve was assessed to be intact and half of the trachea ( 5.5 2.3 cm ) was dissected including 5 cartilaginous rings together with the left recurrent laryngeal nerve . the tumor was removed together with the invaded paratracheal tissue bilaterally ( fig 3c ) . the medial edges of the sternocleidomastoid muscle were sutured to a rectangular tracheal opening . to avoid tracheal stenosis , the anterior side of the defect was open , and a stent tube was kept in place . for muscle - flap prefabrication , the prepared ktnme , as described by muhamedov et al . the cut edges of the tracheal opening were circumferentially overedged to the skin with a few absorbable sutures to facilitate cannulation . after the airway was confirmed intact based on co2 return and bilateral breath sounds , the tracheostomy tube was secured to the skin with 40 sutures ( fig 3e ) . to avoid the risk of subcutaneous emphysema and subsequent pneumomediastinum , the skin was not tightly closed . a sponge soaked with iodine between the skin and the flange was placed for 24 h to deflect infection and anxiety about minor oozing of the skin edge . the patient was extubated after 7 days , and there was no granulation tissue or stenosis of the tracheal lumen 3 weeks thereafter ( fig 4 ) . the reconstructive stage was performed on may 19 , 2014 . the o - shaped incision around the formed tracheotomy having the gap 1.5 cm from the right edge was made . a cellulocutaneous flap was separated and overturned so that the epidermis overlapped the tracheostomy lumen ( fig 5a ) . the harvested ktnme after prefabrication was separated with the pedicle flap of the medial edge of the sternocleidomastoid muscle ( fig 5b ) , placed over the trachea , and sutured to the trachea ( fig 5c ) . the remaining defect in the anterior part of trachea was closed without any special procedure . the sliding skin flap was swung over the wound followed by aesthetic wound closure to achieve optimal cosmetic results with minimal scarring ( fig 5d ) . postoperative bronchoscopy revealed a pink - coated part in the tracheal mucosa with no stenosis ( fig 5e ) . the patient was discharged on june 3 , 2014 , and referred back home to be supervised by a local hospital , where she was socially rehabilitated in full . the patient remains alive and without any evidence of recurrence or complaints well over 24 months after surgery . she continued her job 2 months after discharge and calls us every 6 months to confirm her health status and current matters . the possibility to perform a sparing surgery depends on several factors , including the availability of adequate material for the tracheal replacement after lesion [ 7 , 8 ] . however , functional outcomes of such a kind of the treatment do not always satisfy both patients and clinicians given that a large portion of the trachea is to be resected in locally advanced thyroid papillary carcinoma invading the trachea . some surgical methods , on account of the improvement , standardization , and more widespread use of reconstructive surgery with microvascular flaps , for the management of tracheal invasion by thyroid carcinoma have been reported in the literature , so far with no consensus on the best approach . the development of techniques and the selection of an optimal material for the tracheal reconstruction remains the urgent aim of modern head and neck surgical oncology . the brief overview of published articles on tracheal sparing surgery studies reflects , in fact , that there are no commercially produced implants for a wide clinical practice in cases of extensive lesions of the trachea . since it is a mobile organ when breathing , swallowing , speaking , eating etc . , it is critical to raise standards regarding the material selection for the replacement . to succeed , clinicians should make their unconventional choice of what approach to use and how to perform the correct reconstruction . as a rule , the structures involved in cases of invasive thyroid papillary carcinoma are mostly the trachea , larynx , laryngeal nerve , and other surrounding sites . since a regional spread , increased incidence of local recurrence and distant metastasis are common ways of invasion to the surrounding structures , it is crucial to control local invasion , which makes treatment relatively difficult . the management of locally invasive , well - differentiated papillary carcinoma of the thyroid is disputable . palliative surgery had been the most common surgical procedure used for the treatment of patients with thyroid carcinoma invading the trachea for many years . however , the shaving - off procedure was reported to be often inadequate , and the postoperative survival rate was much worse in patients undergoing partial resection than in those undergoing total resection . for adequate surgery , as in our case , accurate preoperative examination of the tracheal invasion including bronchoscopy , ct , and mri is required to clarify the involvement of adjacent organs . the generally accepted technique for the reconstruction of circular tracheal lesions is to form the end - to - end primary anastomosis between the proximal and distal margins of the defect . however , this is feasible for small ( less than 3 rings ) circular defects , and a larger area of invasion may limit the feasibility of partial tracheal resection because it may lead to kinking or stenosis of the trachea after repair . contraindications include extensive involvement of the trachea , such that 6 or more tracheal rings need to be resected or simultaneous invasion of the esophagus occurs . moreover , in cancer patients , the upward trend in postoperative complications is probable , including a failure of the anastomosis or scar stenosis due to a previous treatment and the weak reparative ability of the tissue . in case of extensive tracheal defects ( more than 5 cm ) , the most reliable method is reconstructive surgery , which involves a layerwise restoration of the tracheal wall . such an approach assumes a fusion of the framework and a thin flap , which adequately replaces the frame function of the trachea without narrowing the lumen . there are several similar studies that aimed at exploring tracheal reconstruction considering the frame function , but they are strictly experimental and still not applicable in cases of large defects of the trachea . it should be pointed out that applying the implant in large defects of the trachea has to be done without any contact with the lumen when there are signs of a primary inflammation . it is suggested to ensure strict adherence to the criteria , otherwise the inflammatory process that occurs in situ eventually affects the consistency of the graft and leads to granulation tissue growth and a failure of the whole reconstruction stage . in summary , in order to succeed in a complex sparing surgery , the obvious procedure is to use the prefabricated endograft covered with a thin - walled lining by the adjacent tissues , as we did . this technique implies 2 stages of reconstruction , which do not contravene the modern concept of sparing surgery as repeated corrective treatments to restore the lumen are necessary . a two - stage surgical treatment has been applied before in cases of large tracheal lesion defects : first , after resection of the tumor , the tracheal wall and skin are sutured for the development of a persistent tracheocutaneous fistula trough. second , delayed closure of the tracheal defect was performed . unfortunately , compared to our method , this technique involves long - term treatment and is also not always aesthetically satisfactory because of the need for harvesting a local flap . in the case described herein , we demonstrated that the prefabricated ktnme is a useful and simple technique of sparing surgery for the tracheal reconstruction after excessive window resection in a patient with advanced thyroid papillary carcinoma invading the trachea . the offered method of a two - stage sparing treatment leads a long palliative period associated with a good quality of life . besides the ktnme applied can adequately restore the frame function of the trachea without postoperative aggravation . as a consequence of the successful application , the ktnme is shown to provide a superior reconstruction and stability for the tracheal grafting during the implantation procedure and thereafter . the surgery was performed in accordance with the ethical principles outlined in the declaration of helsinki . its protocol was approved by the ethical committee of the tomsk cancer research institute , and informed consent was obtained from the patient before the upcoming intervention . the authors declare that there are no conflicts of interests regarding the publication of this paper .

published reports on salvage treatment for trachea reconstruction after total thyroidectomy or partial tracheotomy are available , some of them using structures of the trachea itself , auricular cartilage , a musculocutaneous flap , or other methods . in our report , we emphasize the importance of a search for a new material and approach for sparing surgery . the purpose of this article is to describe a case of a successful sparing surgery in a patient with advanced thyroid papillary carcinoma invading the trachea . after total thyroidectomy in 2012 , partial resection of the trachea was performed in 2014 . the lesion defect was 5.5 2.3 cm in size , located between 4 ( 2nd6th ) tracheal cartilaginous rings and involving about a semicircumference . it was reconstructed with the aid of the knitted tini - based mesh endograft , which has been prefabricated in the sternocleidomastoid muscle and further covered with the skin draped over the wound . the tracheostoma was fully closed 6 weeks after the surgery . there were neither side effects nor complications . this kind of tracheal surgery for extensive lesions demonstrates good functional and cosmetic outcomes .

nodular scleroderma is a rare variant of scleroderma which can occur in connection with systemic sclerosis or morphea . a biopsy from the lesion can demonstrate the scleroderma pattern , i.e. , keloid pattern or mixed type . we present a case of systemic sclerosis in a 50-year - old female who developed nodular scleroderma in the absence of deterioration of the scleroderma condition . although this condition is rare , it has been reported sporadically , and clinicians should be able to recognize this variant in cases of scleroderma presenting with firm nodules or plaques . a 50-year - old female presented with a 1-year history of systemic sclerosis and interstitial lung disease . her current medications were prednisolone 5 mg , cyclophosphamide 75 mg , amlodipine 20 mg , sildenafil 50 mg , and aspirin 80 mg daily . ten months later , she developed multiple asymptomatic papules on the neck , abdominal wall , and back ( fig 1 , fig 2 ) . the physical examinations demonstrated sclerotic skin changes on the face , trunk , and extremities with sclerodactyly , digital pitting scars , and raynaud 's phenomenon . there were multiple , nontender , firm skin - colored papules and plaques scattered on the neck , abdominal wall , and back . the laboratory tests revealed positive antinuclear antibody in a homogenous pattern ( titer 1 : 320 ) and positive anti - scl70 . the biopsy revealed thick sclerotic collagen fibers in the mid - dermis ( fig 3 ) . nodular or keloidal scleroderma is a rare variant of scleroderma [ 1 , 2 , 3 , 4 , 5 ] . the term nodular scleroderma is used when the pathological change resembles scleroderma , and the term keloidal scleroderma is used when the pathological change shows hyalinization of thick sclerotic collagens similar to keloid [ 1 , 6 , 7 ] . nodular or keloidal scleroderma have been reported in either systemic sclerosis or localized scleroderma , usually 6 months after the presentation of systemic sclerosis [ 1 , 2 , 3 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ] . however , also the presence of nodular scleroderma before the onset of systemic sclerosis has been reported . this condition can be found in systemic sclerosis patients either with or without active systemic involvements [ 1 , 2 , 8 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] . the characteristic clinical presentations were firm nodules or plaques resembling keloid , distributed predominantly on the proximal extremities , i.e. , on the chest , back , and neck . nodular or keloidal scleroderma usually occur in middle - aged females ( table 1 ) [ 1 , 4 , 8 , 11 , 12 , 13 , 14 , 16 , 17 , 18 ] . variable histopathologic changes have been reported to include characteristics of keloid or hypertrophic scars , of morphea , or of both morphea and keloid [ 1 , 19 ] . complex interactions between cytokines , matricellular proteins , and local factors ( minor trauma and vascular insufficiency ) should be determined [ 2 , 19 , 20 ] . a role of pathogens , including acid - fast bacteria or chronic hcv infection , has been reported [ 11 , 14 , 21 ] . yamamoto et al . mentioned the role of increasing connective tissue growth factor ( ctgf ) in tissue fibrosis . nonetheless , an increase in ctgf was identified both in the nodular lesions and in skin with scleroderma . consequently , the increase in ctgf alone may not be the sole contributor to the pathogenesis of fibrosis in the lesions . . demonstrated increasing cartilage oligomeric matrix protein ( comp ) , collagen xii , and fibrillin-1 in nodular scleroderma lesions compared to perilesional skin and healthy skin . comp is induced by tgf- , which is an important cytokine in stimulating fibrosis in scleroderma and is involved in modulating the dermal collagen network as well as in sustaining fibroblast activation . our case presented with multiple skin - colored papules and plaques , a differential diagnosis that should be considered was localized cutaneous mucinosis , which can be found as a coexisting condition with systemic sclerosis or morphea [ 24 , 25 , 26 , 27 , 28 ] . however , the diagnosis of localized cutaneous mucinosis should be confirmed by mucin deposition in a skin biopsy . several treatment modalities are mentioned in the literature , including topical or intralesional steroids , systemic steroids , topical calcipotriene , psoralen photochemotherapy , cyclosporine , d - penicillamine , methotrexate , extracorporeal photochemotherapy , and excision [ 1 , 2 , 4 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 29 , 30 ] . however , these treatment modalities have shown unsatisfying results . a review of the reports on nodular or keloidal scleroderma in the past 10 years ( table 1 ) revealed that 1 case demonstrated stable nodular scleroderma without any specific treatment . interestingly , immunosuppressive agents that have previously been received can not prevent the development of nodular or keloidal scleroderma [ 11 , 12 , 13 , 16 ] . the condition of systemic sclerosis in our case has been stable , and the patient was not concerned about its appearance . therefore , we decided to closely observe and monitor her for any progression of the lesions . after 4 months , although this condition is rare , it has been reported sporadically , and it should be considered in scleroderma patients clinically presenting with firm nodules or plaques . this research did not receive any specific grant from funding agencies in the public , commercial , or not - for - profit sectors .

backgroundnodular scleroderma is a rare variant of scleroderma which can occur in connection with systemic sclerosis or morphea . a biopsy from the lesion can demonstrate the scleroderma pattern , i.e. , keloid pattern or mixed type . treatment is challenging , and several treatments modalities have been reported with unsatisfactory results.main observationswe present a case of systemic sclerosis in a 50-year - old female who developed nodular scleroderma in the absence of deterioration of the scleroderma condition . although no additional treatment was given , the lesions remained stable without progression.conclusionsalthough this condition is rare , it has been reported sporadically , and clinicians should be able to recognize this variant in cases of scleroderma presenting with firm nodules or plaques .

recently , more and more genomes have been sequenced and annotated , and the data of proteins and gene interactions are accumulating . biological data are mostly digital and stored in a wide variety of formats in heterogeneous systems . biological data exist all over the world as various web services , which provide biologists with much useful information . however , when users actually make use of them , they need to access to web services ( databases ) one by one . if they want to compare many different kinds of data , they need to do cumbersome task . actually , a large part of the work of biologists today consists in distributing local data , querying multiple remote heterogeneous data source , and integrating retrieved data manually . therefore , distributing and integrating biological data is a very important task and has been recognized as a key component of today s genome biology research . many communities have devoted to a large amount of work on the exchange and integration of biological data ( 1 ) . the difficulties in dealing with the bioinformatics data exchange and integration come from the following technical issues:1)the volume of biological data grows at an exponential rate.2)data are disseminated in a myriad of different databases and managed by different database management system ( dbms).3)biological data from different sources have heterogeneous formats ( 2).4)the platforms or systems for distributing data are different , and the interaction and independence is lacked among these platforms or systems.5)hypertext markup language ( html ) , as a language used widely for database browsing , data publishing , gathering , submission and analysis , is not suitable for extracting and integrating data . data are disseminated in a myriad of different databases and managed by different database management system ( dbms ) . the platforms or systems for distributing data are different , and the interaction and independence is lacked among these platforms or systems . hypertext markup language ( html ) , as a language used widely for database browsing , data publishing , gathering , submission and analysis , is not suitable for extracting and integrating data . data integration consists in wrapping data sources and either loading retrieved data into a data warehouse or returning it to the user . nowadays , database federation is a main technology for solving data integration problem ( 3 ) . database federation offers the promise of a unified view of these disparate data and detailed query through a single easy - to - use interface available via the world wide web . there are two approaches for implementing database federation : concrete and virtual ( or loose ) federation . some systems such as entrez , srs , discoverylink , and dbget ( 4 ) , have been designed for the specific integration of biomolecular data . however , there are some shortcomings by using database federation technology for integrating data . first , the retrieved data by concrete federation are not always the latest and greatest . second , because the retrieved data by virtual federation are web pages ( html format ) , it is an arduous task to parse the result documents . third , a client of virtual federation must be tied to the upstream web service directly . web services , a kind of service - oriented architecture , have been used worldwide to exchange and integrate data in e - commerce . actually , the shortcomings described above are addressed in part by web services and xml ( extensible markup language ) technologies . the flat file format ( ff format ) however , it is very difficult to parse the ff format for extracting the interesting information . xml provided a generic way to represent structured and typed data , which makes it easy to write a script for parsing an xml document . a web service is a unit of business logic , located somewhere on the internet , which is accessible through standard - based internet protocols such as http or simple message transfer protocol ( smtp ) . the core of today s web services technology is made up by soap ( simple object access protocol ) , wsdl ( web service description language ) and uddi ( universal , description , and discovery integration ; figure 1 ) . web services have some features for solving the problems of information exchange , data integration and distributed application:1)web service is xml - based . all of web services use xml as the data representation layer.2)web service is loosely coupled . a client of a web service is not tied to the web service directly.3)web service is coarse - grained . the technology provides a natural way of defining coarse - grained services that access the right amount of business logic.4)web service supports remote procedure calls ( rpcs ) . it allows clients to invoke procedures , functions , and methods on remote object using xml - based protocol.5)web service supports a transparent exchange of documents to facilitate data and documents integration . the technology provides a natural way of defining coarse - grained services that access the right amount of business logic . it allows clients to invoke procedures , functions , and methods on remote object using xml - based protocol . xml is a markup language that specifies neither the tag set nor the grammar for that language , and is a meta language used to define other language . xml allows one to define his own markup language , which consists of his own tags . furthermore , the meaning of tags is essentially different between xml and html . unlike html , the tags defined in xml indicate the semantics of a document rather than display a document . the set of tags and grammar , or schema , for an xml language , describing admissible combinations of tags in a document , can be formalized and enforced by standard parsing tools . it is clear that xml has some interesting features addressing the problems of data exchange and integration introduced above . for one thing , xml makes it very advantageous to exchange data among data sources if all of them adopt the same standardization in xml documents . thirdly , it is convenient to extract interesting information from xml documents , which helps to data integration . in life science , many commercial and academic communities are now adopting xml as a standard for their genome biology data management ( http://scbi.scu.edu.cn/xml/ ) . a web service is a unit of business logic , located somewhere on the internet , which is accessible through standard - based internet protocols such as http or simple message transfer protocol ( smtp ) . the core of today s web services technology is made up by soap ( simple object access protocol ) , wsdl ( web service description language ) and uddi ( universal , description , and discovery integration ; figure 1 ) . web services have some features for solving the problems of information exchange , data integration and distributed application:1)web service is xml - based . all of web services use xml as the data representation layer.2)web service is loosely coupled . a client of a web service is not tied to the web service directly.3)web service is coarse - grained . the technology provides a natural way of defining coarse - grained services that access the right amount of business logic.4)web service supports remote procedure calls ( rpcs ) . it allows clients to invoke procedures , functions , and methods on remote object using xml - based protocol.5)web service supports a transparent exchange of documents to facilitate data and documents integration . the technology provides a natural way of defining coarse - grained services that access the right amount of business logic . it allows clients to invoke procedures , functions , and methods on remote object using xml - based protocol . xml is a markup language that specifies neither the tag set nor the grammar for that language , and is a meta language used to define other language . xml allows one to define his own markup language , which consists of his own tags . furthermore , the meaning of tags is essentially different between xml and html . unlike html , the tags defined in xml indicate the semantics of a document rather than display a document . the set of tags and grammar , or schema , for an xml language , describing admissible combinations of tags in a document , can be formalized and enforced by standard parsing tools . it is clear that xml has some interesting features addressing the problems of data exchange and integration introduced above . for one thing , xml provides an open framework for standard specifications in managing bioinformatics data . , xml makes it very advantageous to exchange data among data sources if all of them adopt the same standardization in xml documents . thirdly , it is convenient to extract interesting information from xml documents , which helps to data integration . in life science , many commercial and academic communities are now adopting xml as a standard for their genome biology data management ( http://scbi.scu.edu.cn/xml/ ) . using web services , soap and xml , a simple web service client was constructed to retrieve xml nucleotides data . the extensible stylesheet language ( xsl ) was used to transform xml data into html form . the web service client is available at http://scbi.scu.edu.cn / webservices/. the new and exciting web services and xml technologies are drastically changing the way people conduct business , vastly altering the competitive landscape of information technology industries , and significantly improving enterprise efficiency . the influences of the web services and xml technologies are becoming increasingly visible , and their momentum will greatly become more significant over the next several years . under the web services , a single application can tap into the services of millions of applications scattered throughout the internet . the promise of web services is to enable a distributed environment in which any number of applications , or application components , can interoperate seamlessly among and between organizations in a platform - neutral , language - neutral fashion . the interoperation brings heterogeneity to the world of distributed computing . nowadays , web services are revolutionizing the internet , and are used in e - commerce worldwide . as a promising standard , web services and xml technologies will undoubtedly be a chance to exchange and integrate biological data on the bioinformatics community . it supports an integrated view for managing remote or local heterogeneous biological data sources with advanced data accessing . we propose to replace the flat file format by xml and to distribute data by web services , which would provide the programmers a uniform access to the biological data and a standardized interface for interoperable applications . in this paper , the author examined only a simple application for integrating biological data using web service client and xml technologies , but an architecture of web services is obviously more complex than the application that makes the web service call directly ( figure 2 ) . our service client is implemented by the hardware of pentium iv 1.8 g with 512 mb memory and 18 g hard disk . the set of software is redhat linux 8.0 , jakarta tomcat 4.1.24 , java ( j2sdk1.4.1_02 ) , apache axis 1.1 , and apache 1.3.27 . apache axis ( apache extensible interaction system , http://ws.apache.org/axis/ ) is an open - source implementation of the soap submission to w3c . it is essentially a soap engine a framework for constructing soap processors such as clients , servers , gateways , etc . the current version of axis is written in java the server provides various servers , including blast , fasta , clustalw , and so on ( 6 ) . the getentry is one of the appropriate servers for getting entries by specifying accession number . using soap message , our service sends a request into the getentry server to call the method getxml_ddbjentry . the information of the getentry server is obtained from the wsdl document ( http://xml.nig.ac.jp/wsdl/getentry.wsdl ; fig . consider , for example , that the same xml document may need to be displayed in html , pdf , and postscript form respectively . without xsl , the xml document would have to be manually duplicated , and then converted into each of these three formats . instead , xsl provides a mechanism of defining stylesheets to accomplish these types of tasks . rather than having to change the data because of a different representation , xsl provides a complete separation of data , or content , and presentation . to transform xml documents into html form , an xsl file named it is a key advantage of xml to bioinformatics data integration that xml documents are parsed easily . sax ( the simple api of xml ) , dom ( the document object model ) and jaxp ( java api for xml parsing ) are three major apis ( application programming interface ) to parse xml documents . by parsing xml documents , data extracted from various xml documents can be dumped into a database , or integrated into an xml document , which is the major task of bioinformatics data integration ( figure 5 ) . moreover , application interoperability , standardizing the interfaces between stand - alone applications such as the data generated from one application flow as the input to another application , will be convenient . the server provides various servers , including blast , fasta , clustalw , and so on ( 6 ) . the getentry is one of the appropriate servers for getting entries by specifying accession number . using soap message , our service sends a request into the getentry server to call the method getxml_ddbjentry . the information of the getentry server is obtained from the wsdl document ( http://xml.nig.ac.jp/wsdl/getentry.wsdl ; fig . consider , for example , that the same xml document may need to be displayed in html , pdf , and postscript form respectively . without xsl , the xml document would have to be manually duplicated , and then converted into each of these three formats . instead , xsl provides a mechanism of defining stylesheets to accomplish these types of tasks . rather than having to change the data because of a different representation , xsl provides a complete separation of data , or content , and presentation . to transform xml documents into html form , an xsl file named it is a key advantage of xml to bioinformatics data integration that xml documents are parsed easily . sax ( the simple api of xml ) , dom ( the document object model ) and jaxp ( java api for xml parsing ) are three major apis ( application programming interface ) to parse xml documents . by parsing xml documents , data extracted from various xml documents can be dumped into a database , or integrated into an xml document , which is the major task of bioinformatics data integration ( figure 5 ) . moreover , application interoperability , standardizing the interfaces between stand - alone applications such as the data generated from one application flow as the input to another application , will be convenient .

it is widely recognized that exchange , distribution , and integration of biological data are the keys to improve bioinformatics and genome biology in post - genomic era . however , the problem of exchanging and integrating biological data is not solved satisfactorily . the extensible markup language ( xml ) is rapidly spreading as an emerging standard for structuring documents to exchange and integrate data on the world wide web ( www ) . web service is the next generation of www and is founded upon the open standards of w3c ( world wide web consortium ) and ietf ( internet engineering task force ) . this paper presents xml and web services technologies and their use for an appropriate solution to the problem of bioinformatics data exchange and integration .

the motor unit ( which contains a spinal motor neuron , its axon , and the muscle fibers it innervates ) is the final common pathway for neuromuscular control and provides a basic structure - function framework for neuromuscular system examination . motor unit plasticity refers to motor unit adaptation or the ability of motor unit physical and functional changes as a result of activity , neurologic injury , age , rehabilitation training , and other factors . motor unit plasticity can be assessed in different ways including by analyzing electromyogram ( emg ) and muscle force output . among various emg signal processing methods , emg decomposition provides a unique approach to observing the behavior of spinal motor neurons and its adaptation or alteration in human subjects by monitoring motor unit recruitment and firing rates . the primary challenges of surface emg decomposition arise from large number of active motor units , similar motor unit action potential ( muap ) waveforms for different motor units , and heavy muap superposition . with amplification technology developments , high density surface emg relying on electrode arrays ( comprised of up to hundreds of closely spaced tiny probes ) has greatly advanced surface emg decomposition . various signal processing techniques using high density surface electrode arrays have been proposed for the decomposition purpose [ 69 ] , among which the convolution kernel compensation ( ckc ) has achieved distinguished yield for high density surface emg decomposition [ 1012 ] . the ckc approach has been tested using both simulated and experimental surface emg signals [ 1315 ] , including the two - source validation with simultaneous intramuscular emg recordings . very recently , we have developed a progressive fastica peel - off ( pfp ) framework for high density surface emg decomposition and tested this novel framework with both simulated and experimental surface emg signals . given that both the ckc and pfp methods are designed for high density surface emg recordings , they can be applied to the same set of data . this provides a strategy to assess the decomposition performance for both methods by comparing the discharge instants of the common motor units from independent ckc and pfp decompositions . the objective of the current study was to use such a strategy to compare the decomposition yield from the two different methods . we hypothesized that when processing the same set of high density surface emg signals , high agreement can be achieved when comparing the decomposition results , thus providing supportive evidence of the decomposition performance for both ckc and pfp methods . different from most of the other blind source separation technologies in surface emg , both pfp and ckc use a shift - invariant model to describe multichannel surface emg signal [ 10 , 16 ] , which allows muap shapes of a specific motor unit that vary in different channels but share the same discharge instants . assuming n active motor units recorded by m surface electrodes : x = [ x1 , x2, ,xm ] , the signal on each channel can be described as(1)xit=j=1n =0l1aijsjt+nit;i=1,2, ,m , t=0,1, ,t . in ckc , ( 1 ) can also be viewed as a convolutive linear time - invariant multiple - input multiple - output ( mimo ) model , where ni(t ) represents the additive white , zero - mean gaussian noise in the ith channel . each model input sj(t ) = k(t tj(k ) ) is a sparse binary motor unit discharge pattern ( i.e. , its values are either 0 or 1 ) that indicates whether the jth motor unit discharges at a specific time t. tj(k ) is the kth discharge time of the jth motor unit , whereas represents dirac delta function . the channel response aij stands for the waveform of the jth motor unit in the ith channel ; l is the length of the waveform . it is assumed that tj(k + 1 ) tj(k ) > l for each k. the model in ( 1 ) can be rewritten in matrix form:(2)xt = ast+nt , where s - t = s1t , s1t-1, ,s1t - l+1, ,snt, ,snt - l+1 t stands for an extended form of a sample vector s(t ) and n(t ) = [ n1(t ) , n2(t), the unknown matrix a comprises all the muaps as detected by the different surface electrodes ( for details , please refer to [ 10 , 16 ] ) . the ckc method first blindly estimates the cross - correlation vector between the discharge pattern of one motor unit and the emg measurements . then the unknown mixing matrix a ( i.e. , the convolution kernel ) is partially compensated by calculating an estimation of the discharge patterns of this motor unit using the estimated cross - correlation vector and the correlation matrix of the emg signal . as the convolution kernel is compensated gradually a number of motor units can be estimated . the pfp framework can be viewed as a process of progressively expanding the set of spike trains . in the framework peel - off procedure is employed to estimate the muaps of all the identified motor units and subtract them from the original signal . such a procedure mitigates the effect of the already identified motor units on the fastica convergence , so more motor units can emerge when processing the residual signal . in order to ensure the reliability of the decomposition , a constrained fastica is applied to assess the newly extracted discharge patterns and correct possible erroneous or missed spikes . the surface emg signals used for testing the proposed framework were acquired from the first dorsal interosseous ( fdi ) muscle of nine healthy subjects . subjects were seated upright in a mobile biodex chair ( biodex , shirley , ny ) . apex , nc ) setup was used to accurately record the isometric contraction force of the fdi muscle during index finger abduction . standard procedures were followed to minimize spurious force contributions from unrecorded muscles as described in . surface emg signals were recorded using a flexible two - dimensional 64-channel ( 8 8 , individual recording probe 1.2 mm in diameter , center - to - center distance of 4 mm ) surface electrode array ( tms international bv , netherlands ) . the maximum voluntary contraction ( mvc ) was first measured ; after that , each subject was asked to generate an isometric contraction force of the fdi muscle at different contraction levels . the subject was asked to maintain the force as stable as possible for at least 3 s ( preferably more than 5 s ) . the actual percent mvc for each contraction was calculated afterwards by normalizing the force measurement ( averaged from the stable force period ) to each subject 's mvc . a refa128 amplifier ( tms international bv , netherlands ) was used to record surface emg signals . the signals were sampled at 2 khz per channel , with a bandpass filter setting at 10500 hz . totally 91 experimental surface emg signals ( 35 27% mvc , range : ~1% to ~100% mvc ) were decomposed by pfp and ckc , respectively . the two decomposition processes were independent of each other and they were operated by two different operators . the decomposition by ckc was first processed by an automatic program , and a manual motor unit selecting process was used to ensure the reliability of the results . in particular , recently introduced pulse - to - noise ratio ( pnr ) metrics has been employed to assess the accuracy of motor unit identification and only the motor units with pnr 30 db ( sensitivity in identification of motor unit discharges 90% ) were kept whereas all the other motor units were discarded . for the pfp , manual monitoring was used to guarantee the reliability when using constrained fastica to assess the identified spike trains . the matching rate ( mr ) was calculated to precisely measure the matching degree of the commonly identified motor units from the two decomposition methods . for each common motor unit , the matching rate between two decompositions was calculated as(3)mr=2ncomnckc+npfp100%,where ncom stands for the number of discharges of a motor unit that were identified by both decomposition techniques ( i.e. , the number of corresponding discharges within time tolerance of 1 ms ) . nckc and npfp are the total number of discharges which were identified by ckc and pfp , respectively . note that if either of the two spike trains is considered as the standard spike train , mr is actually an f1-score measure . in this study we consider a motor unit as a common one only when mr between the two decomposition methods is higher than 90% . a cross - correlation function method introduced in was used to facilitate the identification of coupling discharge spike trains from the two decomposition algorithms and calculate mr . the following parameters were calculated:(4)i=maxjmaxtrsc , i , sp , jtrsc , i , sc , i0rsp , j , sp , j0,ji=argmaxjmaxtrsc , i , sp , jtrsc , i , sc , i0rsp , j , sp , j0,ti=argmaxtrsc , i , sp , jitrsc , i , sc , i0rsp , ji,sp , ji0,where r,(t ) represents cross - correlation function , sc , i stands for the ith spike train identified from ckc , and sp , j is the jth spike train identified from pfp . i is the maximum cross - correlation coefficient between sc , i and sp , j . if i 0.3 , we accepted potential existence of a spike train coupling between sc , i and sp , j . for the identified coupling , ji was used as the indicator of the corresponding spike train and the value of mr was used to determine whether the two spike trains really correspond or not . for this purpose , the corresponding delay ti has been estimated and sc , i and sp , j aligned in time . after such a time shift , mr has been calculated as defined in ( 3 ) . figure 1 shows an example of discharge instants for motor units identified from an isometric contraction at the level of approximately 18% mvc . the red spike trains represent the results obtained by the ckc , and the blue ones are the results obtained by the pfp . in this example , 19 common motor units were identified , whose discharge patterns are aligned together in the figure . black dots represent few locations where the two methods generated inconsistent discharge instants . in addition , each method also identified two different motor units , respectively , as shown in the figure . ninety - one trials of 9 subjects were processed with signal duration ranged from 3.2 to 11.2 s ( 7.9 1.8 s ) , from which the matching rate was calculated . there were a total of 1477 motor units identified from the two methods , including 969 common motor units . on average , 10.6 4.3 common motor units were identified from each trial , which showed a very high matching rate of 97.85 1.85% . we did not observe a clear dependence of the number of common motor units and the matching rate on the contraction level . in addition to the common motor units which accounted for the majority of the decomposition yield , the two methods also identified a relatively small number of different motor units , such as those demonstrated in figure 1 , where 4 different motor units were identified from the two methods . across the 91 trials , there were 5.6 2.8 different motor units identified per trial from the two methods . both ckc and pfp methods are designed for high density surface emg decomposition , using blind source separation approaches based on a sparse shift - invariant model . the sparsity assumption for the motor unit discharge patterns ensures the algorithm can obtain sufficient information to separate the motor units . unlike most of other decomposition methods primarily relying on muap template matching , the two algorithms focus on the underlying discharge patterns ( i.e. , the sparse components ) in the emg signal . the key iterative rules of the two algorithms also have a similar structure . because of these similarities , the two methods achieved high agreement for high density surface emg decomposition , as demonstrated in this study . when comparing the decomposition yield from ckc and pfp methods , we only focused on the motor unit discharge instants , from which the muap waveforms can be estimated using spike triggered averaging ( actually , during the pfp decomposition , the muap waveforms already emerge ) . thus , if high agreement can be achieved in motor unit discharge instants between the two methods , high agreement in muap waveforms can also be expected . in addition to the majority of common motor units , the two methods also identified a relatively small portion of different motor units . this might be due to differences between the pfp and ckc methods , such as in cost function and motor unit searching strategy ( in dealing with the local convergence problem in gradient - based algorithm ) . for example , the ckc acts on original signal and each time the initial value is properly selected ( at motor unit discharge instants ) to ensure that the algorithm can converge to reliable results . furthermore , the ckc adopts a probabilistic strategy , by blindly running the algorithm multiple times ( e.g. , 100 runs ) and gram - schmidt orthogonalization of separation vectors to allow the algorithm to have sufficient probability to find those difficult convergent solutions and finally integrate all the results . when new solutions are obtained , the algorithm uses the information from discharge patterns of the already identified or validated motor units to estimate their muap trains and subtract them from the original signal and then applies fastica to the residual signal to search other motor units . such a deflation strategy mitigates the effect of the already identified motor units on the fastica convergence , so extra motor units can emerge . however , it may lead to a cumulative error problem ; that is , the early estimation error will be accumulated and magnified in the later process ( this is why the constrained fastica is used to ensure the accuracy of the identified spike trains ) . given that the ckc based surface emg decomposition has been extensively validated in different situations [ 1315 ] , the high degree of agreement of common motor units between the decomposition results to some extent supports the accuracy of the pfp decomposition ( and the accuracy of the ckc decomposition as well ) . to further confirm the accuracy of the pfp decomposition , simultaneous intramuscular emg recording is necessary so a two - source validation can be performed . finally , it is noteworthy that some components of one method can be combined with the other . for example , the pfp can use the probability strategy ( as used in the ckc ) during each iteration to achieve more solutions . the ckc can adopt the muap estimation and the motor unit spike train validation mechanism similar to the constrained fastica . such a combination of ckc and pfp methods needs further investigation and might have a potential to increase the decomposition yield .

decomposition of electromyograms ( emg ) is a key approach to investigating motor unit plasticity . various signal processing techniques have been developed for high density surface emg decomposition , among which the convolution kernel compensation ( ckc ) has achieved high decomposition yield with extensive validation . very recently , a progressive fastica peel - off ( pfp ) framework has also been developed for high density surface emg decomposition . in this study , the ckc and pfp methods were independently applied to decompose the same sets of high density surface emg signals . across 91 trials of 64-channel surface emg signals recorded from the first dorsal interosseous ( fdi ) muscle of 9 neurologically intact subjects , there were a total of 1477 motor units identified from the two methods , including 969 common motor units . on average , 10.6 4.3 common motor units were identified from each trial , which showed a very high matching rate of 97.85 1.85% in their discharge instants . the high degree of agreement of common motor units from the ckc and the pfp processing provides supportive evidence of the decomposition accuracy for both methods . the different motor units obtained from each method also suggest that combination of the two methods may have the potential to further increase the decomposition yield .

principal neurons of the ca1 region receive input from the entorhinal cortex ( ec ) via two pathways : ( i ) the direct temperoammonic ( ta ) pathway , which consists of afferents from layer iii of ec and forms synapses with ca1 neurons in the stratum lacunosum moleculare ; and ( ii ) the indirect pathway , which originates from layer ii of ec and forms part of the trisynaptic pathway that terminates in schaffer collateral ( sc ) synapses on ca1 neurons in the stratum radiatum . nmdars are heteromeric assemblies of two essential glun1 subunits and two glun2 or glun3 subunits . there are four glun2 subunits ( a d ) of which the glun2a and glun2b predominate in the forebrain . nmdars are generally thought to be minimally active during basal synaptic transmission , but they have a key role to play during the induction of synaptic plasticity . although classically regarded as relatively stationary at the synapse , nmda receptors undergo lateral diffusion and various forms of plasticity [ 5 - 8 ] . furthermore , the subunit composition of nmda receptors can vary with development [ 9 , 10 ] and following different forms of synaptic activity [ 11 , 12 ] . recently we have shown that ltd of nmda receptor - mediated synaptic transmission can be induced by theta frequency stimulation at sc but not ta synapses and involves activation of group i mglurs ( termed mglur - ltd ; ) . the reason for the lack of activity - dependent mglur - ltd at ta - ca1 synapses is not clear but could be due to the afferent stimulation patterns in ta - ca1 not being ideal to activate group i mglurs . therefore to overcome this issue we have now used pharmacological activation of group i mglurs to investigate whether ltd can be induced at ta - ca1 hippocampal synapses and furthermore to probe the role of glun2b subunits in dhpg - ltdnmda . here we demonstrate that pharmacological activation of group i mglurs induces synaptic plasticity of nmda receptors at the sc pathway but fails to induce ltd in the ta - ca1 pathway . in addition , the nr2b - selective antagonist ro25 - 6981 was used to show that the subunit composition of nmdars remains unchanged following group i mglur - induced ltd . p14 male wistar rats were killed by cervical dislocation in accordance with united kingdom animal ( scientific procedures ) legislation . brains were removed and placed in ice - cold acsf consisting of the following ( in mm ) : nacl 124 , kcl 3 , nahco3 26 , nah2po4 1.25 , cacl2 2 , mgso4 1,d - glucose 10 ( bubbled with 95% o2/5% co2 ) . standard techniques were used to record excitatory postsynaptic potentials ( epsc ) in response to stimulation ( 100 s , 310 v ) of the sc or ta pathways . in those experiments in which both sc - ca1 and ta - ca1 inputs were studied , alternate stimulation of both pathways was conducted in each slice . electrodes ( 4 7 m ) were filled with ( in mm ) : csmeso4 , 130 , nacl 8 , mg - atp 4 , na - gtp 0.3 , egta 0.5 , hepes 10 , qx-314 5 , ph adjusted to 7.27.3 using csoh and osmolarity to 275290 mosm with sucrose . picrotoxin ( 50 m ) and nbqx ( 5 m ) were applied to isolate epscnmda . ( rs)-dhpg ( 100 m ; tocris bioscience ) was used to activate group i mglurs and ro25 - 6981 (; 5 m ; tocris bioscience ) as an antagonist of glunb receptors . changes in synaptic strength were expressed relative to the normalized baseline ( mean sem ) and significance tested using student s t - tests 30 min after ltd induction or 50 min following application of ro25 - 6981 . the group ii mglur agonist dcg - iv was applied at the end of experiments to ensure selective stimulation of ta and sc inputs . after a baseline period of 10 minutes , the group i mglur agonist ( rs)-dhpg ( 100 m ; 10 minutes ) was applied . an initial depression of nmda receptor - mediated epscs ( epscnmda ) was observed in both pathways ( at the end of dhpg application responses were : sc 53.1 3.3% ; ta 33.5 4.4% below baseline ; p < 0.05 compared to baseline ; n = 18 ; fig . thirty minutes following washout of dhpg , ltd of epscnmda ( ltdnmda ) was observed at the sc pathway ( 34.9 2.7% depression ; p=0.0012 ; n=18 ) , which was consistent with published findings [ 14 , 18 , 19 ] . however , epscnmda evoked by ta pathway stimulation recovered to baseline levels following dhpg washout ( 15.2 4.2% below baseline ; p = 0.764 ; n = 18 ) . after a baseline period of 10 minutes , the group i mglur agonist ( rs)-dhpg ( 100 m ; 10 minutes ) was applied . an initial depression of nmda receptor - mediated epscs ( epscnmda ) was observed in both pathways ( at the end of dhpg application responses were : sc 53.1 3.3% ; ta 33.5 4.4% below baseline ; p < 0.05 compared to baseline ; n = 18 ; fig . thirty minutes following washout of dhpg , ltd of epscnmda ( ltdnmda ) was observed at the sc pathway ( 34.9 2.7% depression ; p=0.0012 ; n=18 ) , which was consistent with published findings [ 14 , 18 , 19 ] . however , epscnmda evoked by ta pathway stimulation recovered to baseline levels following dhpg washout ( 15.2 4.2% below baseline ; p = 0.764 ; n = 18 ) . the difference in ltdnmda between sc - ca1 and ta - ca1 might be due to differences in nmdar subunits at the different synapses . different nmda receptor subunits are associated with different epsc characteristics and the epsc decay time constant ( ) can therefore be used as an indication of receptor subunit population at the synapse . we have previously shown that the decay constant of epscnmda in ta and sc synapses is similar , indicating a similar population of nmda receptor subunits at the two synapses . in order to clarify this further , ro25 - 6981 ( ro ; a potent and selective glun2b receptor antagonist ) was applied ( 1 m ) and a depression of epscnmda was observed in both pathways ( fig . 2 ) . after a period of 1 hour , epscnmda at the sc and the ta pathways had reduced by similar amounts ( sc : 55.8 7.0% ; ta : 43.3 5.2% ; p = 0.18 , n = 6 ) , confirming our previous work suggesting that a similar population of nmda receptor subunits are expressed at these two synaptic populations . the above result suggests that it is unlikely that differences in nmdar subunit composition within the ta - ca1 and sc - ca1 synapses explain the difference in ltdnmda between the two inputs . however , the role of nmda receptor subunits in the induction of ltd was not clear . therefore , to examine directly whether the induction of ltd in the sc pathway was dependent on glun2b activation , dhpg was applied in the presence of ro ( after 1 hour ro application ) . dhpg again caused a depression of the sc pathway ( 30.5 9.6% ; fig . 3 ) that was not significantly different from dhpg - ltdnmda induced under control conditions ( p = 0.617 ) . this suggests that dhpg - ltdnmda in the sc pathway is independent of glun2b subunit activation . ro25 - 6981 causes a similar depression of both pathways following dhpg application to examine whether there was a change in nmdar subunit composition following ltd at the sc synapse , we compared the effect of ro before and following dhpg - ltd ; a change in efficacy of glun2b - selective antagonists is often taken as an indication of a change in subunit composition of nmdars ( i.e. an increase or decrease in the complement of glun2b receptors ; e.g. ) . thus , thirty minutes following dhpg application ( 100 m ; 10 minutes ) when ltd was stably expressed , ro25 - 6981 ( 1 m ; 1 hour ) was bath applied . application of dhpg caused ltdnmda ( 34.0 4.3% depression ) . following ro25 - 6981 application , a further depression of epscnmda was observed ( 63.5 4.2% of pre - dhpg level ; fig . 4 ) that was not significantly different to the depression caused by ro25 - 6981 under control conditions ( p = 0.589 ) , indicating that a change in glun2b subunit composition does not occur as a result of dhpg - ltdnmda . recently we have demonstrated a form of ltdnmda that can be induced by synaptic stimulation at sc but not ta synapses in the hippocampus , using a short theta frequency stimulation ( tfs ; ) . this form of ltd involves activation of group i mglurs and produces metaplasticity such that the induction of subsequent ltp at the sc input is inhibited . in the current study we have utilised pharmacological activation of group i mglurs using the agonist dhpg to elucidate whether the lack of mglur - ltd of epscnmda at the ta input to ca1 in p14 animals is due to insufficient activation of mglurs by tfs . we now show that even with agonist activation of group i mglurs , ltd of epscnmda is not seen at the ta input . instead , despite an initial transient depression , responses recover to baseline levels upon washout of the agonist . a previous study , using 4 - 6 week old animals , has shown that ltd can be induced by dhpg at ta - ca1 input ( although of smaller magnitude than at sc synapses ; ) . this raises the possibility that either developmental changes may impact on the ability to induce mglur - ltd of epscnmda at ta - ca1 synapses or that there is a difference in the ability to induce ltd of epscnmda versus ltd of epscampa at ta - ca1 synapses . however , it is not possible at this stage to be able to make conclusive statements as to the impact of development on mglur - ltd of epscnmda or differences between ltd of epscnmda versus ltd of epscampa at ta - ca1 synapses . plasticity of epscnmda may involve a subunit switch in nmdar subunits [ 11 , 21 ] . as such , the ability to induce such plasticity may be dependent on the subunit composition of nmdars in the basal state . use of glun2b subunit - selective antagonists , such as ifenprodil and ro25 - 6981 , readily allows comparison of subunit composition [ 11 , 21 ] . we found that ro25 - 6981 produced the same the magnitude of depression in sc and ta inputs . similar to our previous work where we found no difference in the decay time constant of epscnmda at the two inputs to ca1 , this suggests that the inability to induce ltdnmda at ta - ca1 synapses is not due to differences in glun2b nmda subunit composition . the sensitivity of epscnmda to ro25 - 6981 in the sc input was not altered following induction of ltdnmda by dhpg . thus , a change in relative glun2a / glun2b subunit expression , which is seen in some forms of plasticity , does not underlie ltd . mglur - ltd of epscampa has been extensively investigated although there is no consensus on the precise mechanism of ltd and multiple signalling cascades have been implicated . ltdnmda induced by tfs is expected to be postsynaptically expressed , as this form of ltd is specific for epscnmda vs epscampa ; postsynaptic expression of pharmacologically - induced ltdnmda has also been demonstrated [ 14 , 18 ] . however , it affects subsequent induction of long - term potentiation ( ltp ; ) and is therefore a form of metaplasticity that will regulate the acquisition of hippocampal - dependent spatial information . future work will aim to elucidate the precise signalling and expression mechanisms underlying this ltd as well as its role in learning and memory .

nmda receptors are composed of multiple subunits and are crucial in the induction of synaptic plasticity and learning and memory . in this study , application of the group i mglu receptor agonist , dhpg , caused ltd of nmda - epscs ( dhpg - ltdnmda ) of the schaffer collateral , but not of nmda - epscs of the temperoammonic pathway onto ca1 neurons of the hippocampus . dhpg - ltdnmda did not alter the sensitivity of nmda - epsc to the glun2b - antagonist , ro25 - 6981 , indicating that the postsynaptic nmda receptor subunit composition remained unchanged following dhpg - ltdnmda . furthermore , blockade of glun2b receptors did not affect the induction of dhpg - ltdnmda . these results demonstrate a difference in the plasticity of nmda receptors between two synapses onto the same ca1 neuron , but indicate that the subunit composition of nmda receptors does not account for this difference .

type ii diabetes mellitus associated with obesity is becoming a worldwide epidemic and in most patients , the control of the disease is suboptimal even with maximum medical therapy currently available . the evidence for surgical intervention of dm is emerging and the international federation of diabetes ( idf ) has formally laid down the recommendations recently . this has changed the whole concept and approach to this dreadful disease and opened the green light for the development of metabolic surgery . the culprit of developing dm and obesity are associated with the imbalance of foregut and hindgut alimentation ( hyperalimentation of foregut and hypoalimentation of hindgut ) due to over ingestion of high - calorie , high - glycaemic index diet in modern society . all current metabolic procedures such as gastric bypass , duodenal switch ( ds ) and ileum interposition address and reverse this imbalance and their principles are based on the foregut or hindgut theory or the combination of both . santoro et al . has recently reported his long - term data regarding sleeve gastrectomy with transit bipartition ( sg + tb ) , which is a similar operation to ds but without complete exclusion of duodenum in order to minimize nutritional complications . we modified the operation by performing a loop rather than roux - en - y bipartition reconstruction in santoro 's operation and we are reporting the first patient who underwent this operation , laparoscopic sleeve gastrectomy with loop bipartition ( sg + lb ) in the treatment of poorly controlled type ii diabetes mellitus associated with obesity . a 46-year - old gentleman with a 7-year history of type ii diabetes mellitus underwent laparoscopic sleeve gastrectomy with loop bipartition in a private hospital in november 2012 in hong kong . he weighted 98.5 kg with bmi 32.9 kg / m before the operation . he required 50 units of lantus injection ( insulin glargine , sanofi - aventis ) daily and was on multiple medications to control his blood pressure and lipid level . his baseline hba1c was 10.1% and c - peptide was 1.8 nmol / l . in view of his conditions , the patient was fully informed regarding the modification of this operation ( sleeve gastrectomy with loop bipartition ) from the current metabolic procedures and formal consent was obtained . the procedure was performed by minimally invasive approach in french position with five ports ( 12 mm at umbilicus , 1 mm 5 mm at right upper quadrant , 1 mm 10 mm and 1 mm 5 mm at left upper quadrant and 1 mm 5 mm ports at epigastrium for liver retraction ) as in our standard laparoscopic sleeve gastrectomy . the greater curvature of stomach including the posterior fundus was mobilized completely from pylorus to the angle of his exposing the left crus of diaphragm . the greater curvature of stomach was transected by a linear stapler ( echelon 60 endopath stapler and cutter . 60 mm , ethicon , cincinnati , oh ) from antrum ( 6 cm from pylorus ) to angle of his with 38 fr . a loop gastroileostomy 250 cm from the ilececal valve was created at the dependent part of the antrum with 2 layers of handsewn suture but without division of the 1st part of duodenum . the resultant stomach tube has two outlets , one to the first part of duodenum through the pylorus and one to the terminal ileum through the gastroileostomy ( fig . the staple line and anastomosis was tested with methylene blue test at the end of the procedure . oral contrast study was performed on day 7 , which revealed no leakage and preferential passage of contrast through the gastroileostomy . the patient was kept in the hospital for 10 days for diet education and blood glucose monitoring . upon discharge from the hospital , the patient did not require insulin injection and was put on oral hypoglycaemic agents and adjusted doses of anti - hypertensive medications . he was prescribed a high protein liquid diet for the first two weeks and soft diet from week 3 to 4 . he was evaluated monthly at the outpatient clinic by his endocrinologist and our surgical team . the patient reported a change of bowel habit with increased frequency of passing flatus and bowel motion 23 times / day after the operation . the patient had progressive weight loss throughout the follow - up period with no major complaint except for occasional mild itchiness of skin . at 1-year follow - up , his bw and bmi dropped from 98.5 to 69.8 kg and 32.9 to 23.3 kg / m , respectively . the excess bmi loss was 97.0% with reference to ideal body weight at bmi 23 for an asian population . there was a significant improvement of hba1c level from 10.1 at baseline to 4.8% at 1-year follow - up . the patient developed mild hypoalbuminaemia and anaemia with albumin level decreased from 41 to 31 g / l and haemoglobin level from 13.8 to 11.5 g / dl after operation as compared to the baseline . this new surgical procedure ( sleeve gastrectomy with loop bipartition ; sg + lb ) was evolved and derived from the combined concepts of sleeve gastrectomy with transit bipartition ( sg + tb ) , single anastomosis duodenal - ileostomy ( sadi ) , mini - gastric bypass ( mgb ) and duodenal we believe the outcome of this operation would be comparable to the above metabolic procedures but with less nutritional issue and a much safer and easier operation . our first patient had a remarkable early outcome with complete resolution of dm and obesity at 1-year follow - up . in hong kong , we are very satisfied with the results of sg and the majority of our patients can achieve excellent outcomes with the operation . intestinal bypass added to sg , primary or staged , is only reserved and offered to those with extreme obesity and poorly controlled dm . gastric bypass ( both roux - en - y and mgb ) were not well received in hong kong for some reasons , namely a relatively higher incidence of stomach cancer and common bile duct stones in our locality . on the other hand , ds is almost being abandoned in asia due to the nutritional consequences and complexity of surgery . as a result , djb or sadi , which is a complementary procedure to sg , is gaining popularity in asia countries recently . we modified the santoro 's operation ( sg + tb ) by creating a loop bipartition at antrum instead and the resultant reconstruction ( sg + lb ) in fact is a very similar operation to the sadi and loop djb but without division of the duodenum . as shown by santoro et al . , the majority of nutrients and food still preferentially pass through the gastroileostomy rather than through the physiological sphincter , the pylorus and this observation obviate the necessity for complete exclusion of duodenum in sadi or djb . there are a lot of apparent advantages of this procedure over the other current metabolic operations . first , sg + lb is very straightforward and simple to perform without the need for division of duodenum . it is a single step complementary to sg and can be accomplished easily by minimally invasive approach with a relatively short operation time . it can be offered to patients as a primary or staged operation for the treatment of obesity and dm . in addition , from the experience of gastric cancer and ulcer surgery , we anticipate that the gastroileostomy anastomosis fashioned at the dependent part of the antrum in sg + lb rarely develops leakage or serious morbidity . this anastomosis should be the most robust and safest as compared to other procedures with minimal tension . moreover , without division of duodenum , it completely eliminates the possibility of duodenal stump leakage , which can be troublesome in sadi , djb or ds . the alimentary limb length we chose ( 250 cm from ileal caecal valve ) was derived from the experience of sadi as popularized by sanchez et al . in sg + lb , the limb length can be adjusted and modified according to the patient 's bmi and dm status and the procedure can be reversed and converted to other procedure if needed at ease . there are no foreign bodies , blind loops or excluded segments involved and the whole gi tract and bile duct can be assessed by endoscopy if necessary after the operation . what is more important , the nutritional issue of this operation should be less prominent . one of the major problems of mgb and djb is that up to 5% of patients may develop severe iron deficiency anaemia , which is related to the length of bilipancreatic limb being bypassed . sg + lb preserves the foregut for iron absorption and potentially diminish the severity and possibility of this complication . last but not the least , there is a theoretical benefit by adding this step to sg to decrease the stomach tube pressure . it has been shown that mgb rarely develop staple line leakage at the angle of his and this may attribute to the omega loop created at the distal end of the stomach tube decreasing the tube pressure in mgb . at the moment of time , we think ls + lb appears to be close to the ideal metabolic surgery and exhibits a lot of advantages as compared to other procedures . as in mgb , we foresee that there will still be controversial issues and potential criticisms for this operation namely bile reflux and dumping syndrome in non - diabetic patients . the bottom - line is that sg + lb can be completely reversed for dumping or revised to braun 's reconstruction to eliminate bile reflux in case it happens in a minority of patients undergoing this procedure . sleeve gastrectomy with loop bipartition may be proven to be a very effective , safe and simple operation with numerous theoretical advantages over the current procedures for the treatment of obesity and diabetes . however , we need more experts to explore and investigate this operation before we can draw any solid conclusions . lam katherine kar yee is the anaesthetist for the case and for preparation for the surgery .

introductionwe report the first case of laparoscopic sleeve gastrectomy with loop bipartition ( a modified form of santoro 's operation ) in the treatment of type ii diabetes mellitus associated with obesity.presentation of casea 46-year - old gentleman ( baseline bmi 32.9 ; bw 98.5 kg ) with 7-year history of type ii diabetes mellitus ( dm ) underwent the procedure in hong kong . the control of dm was poor even with intensive medical therapy before the operation . standard laparoscopic sleeve gastrectomy ( sg ) was performed and a loop gastroileostomy was fashioned at the antrum 250 cm from the ilececal valve without division of the 1st part of duodenum after sg . the resultant gastric tube has two outlets , one to the first part of duodenum and the other to the ileum with preferential passage of food through the gastroileostomy as shown on subsequent contrast study . the patient 's recovery was uneventful . the excess bmi loss was 97% with complete normalization of all metabolic parameters at 1-year follow-up.discussionthis new surgical procedure ( sleeve gastrectomy with loop bipartition : sg+lb ) was evolved and derived from the combined concepts of sleeve gastrectomy with transit bipartition ( sg+tb ) , single anastomosis duodenal - ileostomy ( sadi ) , mini - gastric bypass ( mgb ) and duodenal - jejunal bypass ( djb ) with less nutritional and surgical complications.conclusionsleeve gastrectomy with loop bipartition may be a very effective and simple operation to treat uncontrolled dm associated with obesity with a lot of apparent advantages over most current metabolic procedures available at the moment .

larvae were collected opportunistically from tammany creek , nez perce co. , i d ( 46 21.51.51 n , 117 03.32.05 w ) , a perennial , undammed creek approximately 13 m in width and roughly 10 km in length . tammany creek drains into the snake river approximately 770 km from the confluence of the snake and columbia rivers . we surveyed the study area ( 1 km in length ) on foot and collected odonates by drag net from 15 february 2012 to 12 march 2012 . upon collection , larvae were transported to lewis - clark state college and housed in 50-ml plastic vials with a 3-mm - diameter dowel for perching . larvae were measured with a millimeter rule for total body length and head width and maintained on a photoperiod of 14:10 ( l : d ) h cycle at an ambient air temperature of 22c . vivida head 24.5 mm , body 619 mm ; a. palmata head 48 mm , body 2335 mm . behavior trials were conducted in 250-ml containers with filtered tap water and a singular 3-mm - diameter perch . one shrimp was placed in the container , as alternative prey , 1 min after simultaneously placing both odonates in the container . vivida head 34 mm , body 1117 mm ; a. palmata head 48 mm , body 2335 mm . to evaluate whether the observed behaviors were species specific , we tested a. palmata and ar . animals used in congeneric trials ( not diagrammed ) were matched for total body length as closely as possible ( 31 ar . vivida , a previously undescribed luring behavior was observed by either a. palmata or ar . that luring behavior was demonstrated , the a. palmata attempted , unsuccessfully , to capture the shrimp prior to the luring behavior . luring behavior was initiated only when the odonates had entered into the field of view of one another . once the a. palmata and ar . vivida had oriented toward each other , a brief period ( 3060 s ) of no visible movement ensued . in four of five trials d ) sequence of points in luring abdominal movement by a. palmata during a. palmata ( large ) versus ar . . abdominal movement to the side and exposure of the abdomen of a. palmata to ar . vivida changed position to place the abdomen of a. palmata directly in the field of view ( fig . this behavior consisted of 710 movements of the abdomen within approximately 2 s ( fig . ( a d ) sequence of points in luring abdominal movement by a. palmata during a. palmata ( large ) versus ar . . abdominal movement to the side and exposure of the abdomen of a. palmata to ar . ar . vivida changed position to place the abdomen of a. palmata directly in the field of view ( fig . this behavior consisted of 710 movements of the abdomen within approximately 2 s ( fig . vivida luring a. palmata was observed . the following sequence of events details that observation ( fig . 2a).the abdomen was then fully moved to the opposite side of the body in a slow motion ( 2 s ) and held on the other side of the body for approximately 8 s ( fig . 2b).step 2 was repeated to the initial side of luring . at this point , ar . vivida positioned its abdomen directly behind its head and slowly continued movement toward head of a. palmata . vivida attempted to capture a. palmata at its head.upon being struck , a. palmata slowly retreated.ar . vivida continued attempts at luring a. palmata , with rapid abdominal movements to the initial side for approximately 5 s. while luring , ar . vivida slowly approached the retreating a. palmata.the sequence was broken as a. palmata used abdominal thrusts to propel itself away and over ar . the abdomen was then fully moved to the opposite side of the body in a slow motion ( 2 s ) and held on the other side of the body for approximately 8 s ( fig . step 2 was repeated to the initial side of luring . at this point , ar . vivida positioned its abdomen directly behind its head and slowly continued movement toward head of a. palmata . vivida continued attempts at luring a. palmata , with rapid abdominal movements to the initial side for approximately 5 s. while luring , ar . the sequence was broken as a. palmata used abdominal thrusts to propel itself away and over ar . vivida . in the other 13 of 18 a. palmata versus ar . , a. palmata actively pursued the shrimp prey item , catching and consuming the prey without attacking the ar . vivida positioned itself at the bottom of the chamber and remained motionless for the entirety of the trial . vivida pursuing the prey . in all of these trials , the a. palmata captured and consumed vivida attempting to consume the prey item after the a. palmata had caught and began consumption . in this instance , the ar . vivida was consumed by the a. palmata following consumption of the prey . in one trial , ar . vivida actively attacked and consumed the prey , and a. palmata remained motionless in the chamber . in every congeneric trial vivida , 12 a. palmata versus a. palmata ) , there were no instances of attack , luring , or attempted consumption of the congeneric by either animal . in our trials , luring occurred only when a head - to - head orientation was present . this is the same orientation described in the well - known agonistic behavior of many larval odonates ( corbet 1999 ) . however , in contrast to previously described agonistic behaviors , predatory luring occurred between different odonate families with a different repertoire of movements ( figs . 1 and 2 ) and typically ended in consumption of the prey . in trials where luring was not displayed a caudal attack by either species typically resulted in one of two possible scenarios : 1 ) removal of lamellae of ar . vivida and subsequent retreat and avoidance of further attack by prey and 2 ) prey being grasped and subsequent retaliatory bites and aggression resulting in injury to the predator ( e.m . , personal observations ) . these two scenarios , we believe , are the reasons for the head - to - head orientation that has been demonstrated as critical for the luring to occur . the caudal luring by the predator caused the lured individual to change orientation slightly to ensure that a successful attack was achieved . the exaggerated slow swaying of the caudal region caused the lured individual to change orientation . the subsequent rapid movements of the caudal region resembled that of the preferred prey in this environment , the freshwater shrimp , which further provoked the lured individual to investigate . the movement of the lured individual from the head - to - head orientation to the more vulnerable position of focusing on the lure provided the predator an opportunity to strike at the prey . we believe that more instances of predatory luring would have been observed had the time duration of the trials been longer than 7 min . all animals used in the trials were nave , not having been involved in any trials previously . we can not comment on the experience of the animals in the field before capture ; however , all animals were housed individually for 3 weeks before trials were conducted . the luring demonstrated by ar . vivida , even though consumption was not achieved ( although a strike at the head of the much larger a. palmata did occur ) , may indicate that this behavior can be used in situations other than predation . vivida is similar to the agonistic behavior of other coenagrionidaen odonates ( rowe 1992 ) , several differences exist . 3 ) the behavior displayed by ar . vivida to physically lure the larger a. palmata close to the ar . vivida versus a. palmata with closely matched sizes will help elucidate whether this behavior is predatory or used to ward off potential predators . although there was no luring of a. palmata by other a. palmata , similarity of ar . the possibility of predation by a congeneric may induce the larger dragonfly to lure the smaller but morphologically similar damselfly to a position in which a fatal attack is much easier and much more likely . vivida and a. palmata at this locale creates the possibility that large larvae are likely to encounter smaller conspecifics .

organisms in the order odonata are highly predatory insects that have a wide distribution globally . to date , there has been zero evidence that odonates employ luring as a means of prey acquisition . however , in this study , we show that aeshna palmata larvae use abdominal movements to lure larval argia vivida , subsequently consuming the lured organism . we also present findings of a similar behavior from larval ar . vivida in an attempt to lure larval a. palmata within striking distance .