Venous thromboembolism prophylaxis for hospitalized medical patients, current status and strategies to improve. Venous thromboembolism (VTE), comprising life-threatening pulmonary embolism (PE) and its precursor deep-vein thrombosis (DVT), is commonly encountered problem. Although most patients survive DVT, they often develop serious and costly long-term complications. Both unfractionated heparin and low molecular weight heparins significantly reduce the incidence of VTE and its associated complications. Despite the evidence demonstrating significant benefit of VTE prophylaxis in acutely ill medical patients, several registries have shown significant underutilization. This underutilization indicates the need for educational and audit programs in order to increase the number of medical patients receiving appropriate prophylaxis. Many health advocacy groups and policy makers are paying more attention to VTE prophylaxis; the National Quality Forum and the Joint Commission recently endorsed strict VTE risk assessment evaluation for each patient upon admission and regularly thereafter. In the article, all major studies addressing this issue in medical patients have been reviewed from the PubMed. The current status of VTE prophylaxis in hospitalized medical patients is addressed and some improvement strategies are discussed.


Imaging lung manifestations of HIV/AIDS. Advances in our understanding of human immunodeficiency virus (HIV) infection have led to improved care and incremental increases in survival. However, the pulmonary manifestations of HIV/acquired immunodeficiency syndrome (AIDS) remain a major cause of morbidity and mortality. Respiratory complaints are not infrequent in patients who are HIV positive. The great majority of lung complications of HIV/AIDS are of infectious etiology but neoplasm, interstitial pneumonias, Kaposi sarcoma and lymphomas add significantly to patient morbidity and mortality. Imaging plays a vital role in the diagnosis and management of lung of complications associated with HIV. Accurate diagnosis is based on an understanding of the pathogenesis of the processes involved and their imaging findings. Imaging also plays an important role in selection of the most appropriate site for tissue sampling, staging of disease and follow-ups. We present images of lung manifestations of HIV/AIDS, describing the salient features and the differential diagnosis.


Asthma insights and reality in the United Arab Emirates. The burden of asthma in the United Arab Emirates (UAE) and the extent to which guidelines are being followed for optimum asthma control are largely unknown. This survey assessed the current level of asthma control, the burden of the disease, and adherence to asthma guidelines by patients. A face-to-face interview of 200 asthmatics in the UAE was conducted. In addition to the questionnaire administered by expert interviewers, each respondent self-completed an Asthma Control Test. The sample was stratified by region within the country and sampled proportionately. Sudden severe attacks of asthma were reported by 64% in the past year. Day time symptoms and night time symptoms were reported by 57.5% and 35.5%, respectively, in the past 4 weeks. Overall, 52.8% of the children and 17.1% of the adults missed school and work in the past year, respectively. The percentage of asthmatics that had emergency room visits within the past year was 27.5%, and 4% were hospitalized. Only 5.5% used inhaled corticosteroids in the past year and 47.5% were on short-acting beta-2 agonists. Only 17.8% ever owned a peak flow meter and only 30% ever had a lung function test. Only 17% had scheduled follow-up and 66% were followed-up by general practitioners. This survey shows that the current level of asthma control in the UAE is far from optimal. Therefore, it is necessary to increase the awareness among patients and update doctors about asthma control guidelines for attaining optimal asthma control, and thus reducing the burden of the disease.


Assessment of visual evoked potentials in stable COPD patients with no visual impairment. To assess whether patients having stable chronic obstructive pulmonary disease (COPD) with no clinical evidence of visual impairment or peripheral neuropathy have visual evoked potentials (VEP) abnormalities on electrophysiologic evaluation. In the present study, 80 male subjects with no clinical neuropathy or visual impairment were included; 40 COPD patients and 40 age-matched healthy volunteers. The characteristics of subjects including age, quantum of smoking, duration of illness (in COPD patients only), and spirometric indices {forced expiratory volume in first second (FEV₁), FEV₁/forced vital capacity (FVC) %, and peak expiratory flow rate (PEFR)} were assessed. The mental status was assessed using a questionnaire Mini-Mental State Examination (MMSE) Questionnaire. Electrophysiologic studies for the evaluation of VEP were carried out on computerized equipment. Latency and amplitude of P100 wave were analyzed from the VEP wave patterns obtained through a standardized protocol in both the groups to detect abnormalities in the COPD group. For the COPD group, correlations of P100 parameters with patient characteristics, spirometric indices, and MMSE scores were assessed. Significant abnormality was defined as a variation beyond healthy volunteer mean ± 3 standard deviation. We observed significantly prolonged latency and decreased amplitude of P100 in both eyes of the patients in COPD group compared with healthy volunteers. Twenty-two of the 40 COPD patients (55%) had significant abnormalities in P100 latency, and three COPD patients (7.5%) had abnormalities in P100 amplitude. The latency of P100 on the right side had statistically significant inverse correlation with FEV₁/FVC% and MMSE score. Twenty-three of the 40 stable COPD patients (compared with healthy volunteers) were observed to have significant VEP abnormality detected on electrophysiologic evaluation: 21/40 having prolonged P100 latency and only 2/40 with decreased P100 amplitude. The statistically significant correlations were observed only between P100 latency (right eye) and FEV1/FVC as well as MMSE scores. The rest of the correlations were not statistically significant.


Prophylactic use of laxative for constipation in critically ill patients. This study was designed to evaluate the use of laxative prophylaxis for constipation in intensive care unit (ICU) and the impact of early versus late bowel movement on patient's outcome. The study was a prospective, randomized controlled trial in critically ill ventilated adult patients, who were expected to stay on ventilator for >72 h. Control group did not receive any intervention for bowel movement for the first 72 h, whereas interventional group received prophylactic dose of lactulose 20 cc enterally every 12 h for the first 72 h. The parameters measured during the study were admission diagnosis, age, gender, comorbid conditions, admission Simplified Acute Physiologic Score (SAPS II), sedative and narcotic agents with doses and duration, timing and tolerance of nutrition, daily assessment of bowel movement, total use of prokinetic, doses of suppositories, and enema for first bowel movement, total number of days on ventilator, weaning failures, extubation or tracheostomy, ICU length of stay, and death or discharge. A total of 100 patients were enrolled, 50 patients in each control and interventional group. Mean age was 38.8 years, and both groups had male predominance. Mean SAPS II score for both was 35. Mean dose of Fentanyl (323.8 ± 108.89 mcg/h in control and 345.83 ± 94.43 mcg/h in interventional group) and mean dose of Midazolam (11.1 ± 4.04 mg/h in control and 12.4 ± 3.19 mg/h in interventional group). There were only two (4%) patients in control, while nine (18%) patients in interventional group who had bowel movement in <72 h (P < 0.05). Mean ventilator days were 16.19, and 17.36 days in control and interventional groups, respectively. Subgroup analysis showed that the patients who moved bowel in <5 days in both groups had mean ventilator days of 18.5, whereas it was 15.88 days for the patients who moved bowel after 5 days in both groups (P< 0.05). Mean ICU days for control was 21.15 ± 10.44 and 20.77 ± 8.33 days for interventional group. Forty-eight (96%) patients in each group were discharged from the ICU. Two (4%) patients died in ICU in each group. Laxative prophylaxis can be used successfully to prevent constipation in ICU patients. Late bowel movement >5 days is associated with less ventilator days, compared to early <5 days bowel movement.


Evaluation of a novel method to assess corticosteroid responsiveness in chronic obstructive pulmonary disease. Some patients with chronic obstructive pulmonary disease (COPD) may benefit from oral steroid therapy. These steroid-responsive patients are diagnosed based on laboratory spirometry. We hypothesize that daily, home-based spirometry is a better tool. Thirty patients with COPD underwent a single-blinded study, with a crossover design. They received 2 weeks of placebo followed by 2 weeks of prednisone therapy (40 mg/day). Laboratory spirometry was done at the beginning and end of the study and daily home-based spirometry was done twice a day. Analysis of variance model was used. The variability of the median day-to-day forced expiratory volume in 1 s (FEV₁) was 72.5 mL (25th percentile of 40 mL and 75th percentile of 130 mL). The daily FEV₁ variation was 70 mL (25th percentile of 50 mL and 75th percentile of 100 mL). The overall laboratory FEV₁ variability was larger after the steroid course (P < 0.001), but not clinically significant. The variability was not significant postplacebo treatment compared with the baseline values. For home-based spirometry, steroid treatment was not significantly different. The majority (97%) completed more than 80% of the measurements. Ninety percent of the performed tests were considered acceptable. Only 53% of the tests were considered accurate. Overall both laboratory and home-based measurements did not show significant association between airway responsiveness and dyspnea or exercise capacity. Twice-daily home measurements of FEV₁ might be better than the conventional approach to identify steroid responsive COPD patients. However, this finding was only statistically but not clinically significant. Therefore, we would not recommend this approach to identify COPD patients with steroid responsiveness.


A case-control study of bidi smoking and bronchogenic carcinoma. To evaluate the risks imposed by tobacco smoking, in particular, bidi smoking, in the development of lung cancer. Two hundred eighty-four histologically confirmed patients of bronchogenic carcinoma and 852 controls matched for age, sex, and socioeconomic status were interviewed according to a predesigned questionnaire. Effects of individual variables defining the various aspects of tobacco smoking, in particular, bidi smoking, were assessed using logistic regression models. 81.3% cases of bronchogenic carcinoma were ever smokers as compared with 42.2% among controls. The odd ratios for ever smoking, bidi smoking, and cigarette smoking were 5.9 (confidence interval [CI] 4.3, 8.4), 6.1 (CI 4.3, 8.7), and 5.3 (CI 2.7, 10.4), respectively. Bidi smoking poses a very high risk for lung cancer even more than that of cigarette smoking.


Endobronchial cryobiopsy or forceps biopsy for lung cancer diagnosis. Invasive procedures such as bronchoscopic biopsy, bronchial washing, and bronchial brushing are widely used in diagnosis of lung cancers. The mean diagnostic rate with bronchoscopic forceps biopsy is 74% in central tumors. This study was designed to evaluate the efficacy of cryobiopsies in histopathological diagnosis. Forty-one patients who had interventional bronchoscopy were included in this study. Three forceps biopsies and one cryobiopsy with cryorecanalization probe were obtained from each subject. Biopsies interpretations were done by one expert pathologist. Hemorrhage was the only complication in both procedures. There was no significant difference between these two procedures in the incidence of hemorrhage (P > 0.05). Mean diameters of samples taken with forceps biopsy and cryoprobe biopsy were 0.2 and 0.8 cm, respectively (P < 0.001). Thirty-two patients (78%) were diagnosed with forceps biopsies, and 38 patients (92.7%) were diagnosed with cryoprobe biopsies (P = 0.031). We concluded that cryoprobe biopsies were more successful than forceps biopsies in diagnosis. Nevertheless, further investigations are warranted to determine an efficacy of cryoprobe biopsy procedures and a rationale to use as a part of routine flexible bronchoscopy.


Nonresolving pleural effusion in an elderly woman: A case report.


H1N1 infection and thyroid storm.

H1N1 infection and thyroid storm.


Tobacco smoking by medical students: KAP study.


Influenza vaccination program for medical workers.


Large orthotopic reservoir stone burden: Role of open surgery. To present our experience in open poucholithotomy as a primary management of large orthotopic reservoir stone burden and discuss different management options. Records of men underwent radical cystectomy and orthotopic urinary diversion were retrospectively reviewed as regards pouch stone formation. Patients with large reservoir stone burden managed by open poucholithotomy were further selected. Large reservoir stone burden was encountered in 12 post radical cystectomy men. All underwent open poucholithotomy as a primary management of their reservoir stones. Median age at cystectomy was 46 (range: 32-55) years with a median total follow up period of 214.15 (range: 147-257) months and a median interval to stone detection of 99 (range: 63-132) months. The median stone burden was 5260 (range: 3179-20410) mm(2). All patients were continent during the day while 5 showed nocturnal enuresis; 2 of them became continent after removal of the stones. Post poucholithotomy, all patients had sterile urine cultures except one who showed occasional colonization. None of the 12 patients showed stone recurrence after poucholithotomy. Two patients underwent revision of a dessuscepted nipple valve in association with stone removal. Open poucholithotomy for large reservoir stone burden is a feasible and safe option. It saves the reservoir mesentery and adjacent bowel. It allows complete removal of the stone(s) leaving no residual fragments. Furthermore, it permits correction of concomitant reservoir abnormalities.


Assessment of angiogenic factor, vascular endothelial growth factor, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical Bacillus Calmette-Guerin. Bladder tumor is one of the most common genitourinary tumors. Management of non-muscle invasive (NMI) bladder tumors is primarily by transurethral resection (TURBT) followed by intravesical immunotherapy or chemotherapy. Bacillus Calmette-Guerin (BCG) is the most effective adjuvant therapy in NMI bladder tumor. Since angiogenesis is an essential factor in solid tumor progression and vascular endothelial growth factor (VEGF) is an important factor in angiogenesis, the aim of this study is the assessment of angiogenic factor, VEGF, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical BCG. A total of 23 patients with bladder transitional cell carcinoma (TCC) in stage Ta/T1 or carcinoma insitu (CIS), low or high grade, which passed a 2-4 week period from TURBT participated in this study. Blood and urine samples were obtained at first and sixth sessions before instillation of BCG. Enzyme-linked immunosorbent assay (ELISA) method was used to obtain VEGF level in samples. Urine and serum VEGF levels did not change significantly before and after BCG therapy. Changes in VEGF level were significantly different neither in low grade against high grade tumors nor in stage T1 against stage Ta tumors. A significant difference in VEGF level was seen between low grade and high grade tumors in serum after BCG therapy (P=0.007); but not in urine samples. Although intravesical BCG possesses anti-angiogenic activity, it seems that it exerts its effect through pathways other than VEGF, especially in low grade tumors.


Diagnostic significance of atypical category in the voided urine samples: A retrospective study in a tertiary care center. Voided urine samples continue to play an important role in the surveillance of urothelial malignancy and also as a screening mode for high risk patients. In some cases, it is difficult to reliably distinguish changes induced by inflammation, stone or other reactive condition from neoplasm, and these cases are categorized as atypical. The aim of our study is to evaluate the prevalence and the significance of atypical diagnosis in the voided urine samples and also to identify the cytomorphologic features that are seen more frequently in the atypical malignant urine samples. All voided urine cytology samples with a diagnosis of atypical urothelial cells, between the period of 2000 and 2009, were obtained from the cytology database. Only those cases with histologic follow-up were included in the study. The cytology and the histology slides were retrieved and reviewed. The following parameters were evaluated: cellularity, cell clusters, nuclear membrane irregularities, hyperchromasia and India-ink type nuclei, the presence of spindle cells and the cytoplasmic characteristics. Out of 72 voided urine samples included in the study, 49 cases (68%) had a positive histologic diagnosis of urothelial malignancy in the follow-up histology; of these (55%) were high-grade urothelial carcinoma. Increased cellularity, papillary cell clusters, nuclear membrane irregularity, hyperchromasia and India-ink type nuclei were observed more frequently in the atypical malignant urine samples, while cytoplasmic vacuolization were seen more in the negative reactive urine samples. The atypical category diagnosis is associated with a significant proportion of urothelial carcinoma. It should be used by the pathologist to convey concern to the clinician in difficult cases that may require close follow-up.


Continuous ambulatory peritoneal dialysis catheter placement: Is omentectomy necessary? There are different methods of continuous ambulatory peritoneal dialysis (CAPD) catheter placement. Open surgical technique is a widely followed method. The complication rate following catheter placement varies and catheter blockage due to omental plugging is one of the main reasons. To analyze the need for routine omentectomy during CAPD catheter placement. This was a retrospective analysis of 58 CAPD catheter placements performed between July 2002 and June 2007. Tenckhoff double cuffed catheter was used in all. The postoperative complications were analyzed. There were 44 males and 14 females. The mean age was 51 years ranging from 15 to 76 years. Of these, 40 (69%) patients underwent omentectomy (group A) and 18 (31%) did not (group B). Laparoscopic and open techniques were performed in 5 and 53 patients, respectively. Omentectomy was not performed in 13 patients with open technique and all the five in the laparoscopic group. One patient in group A developed hemoperitoneum which was treated conservatively. None from group A developed catheter blockage, whereas five (27.8%) from group B developed catheter blockage postoperatively. The median time interval between the primary procedure and development of catheter blockage was 45 days (ranged from 14 to 150 days). Omentectomy during CAPD catheter placement prevents catheter blockage and secondary interventions.


Urological manifestations of Chikungunya fever: A single centre experience. Chikungunya is a viral infection often associated with lower urinary tract dysfunction. This study evaluates the urological squeal of Chikungunya fever in a single centre after an epidemic in 2006-2007 in India. Retrospective analysis of medical records of 13 patients with lower urinary tract symptoms after Chikungunya fever was evaluated and outcome following intervention assessed. A total of 13 patients (M:F=9:4), with age ranging from 30 to 72 years, were included in the study. They presented with chronic urinary retention (n=9, 69.23%) of which two had paraparesis, voiding symptoms alone (n=7, 53.8%), storage symptoms alone (n=3, 23%), and acute urinary retention (n=1, 7.6%). Presentation with lower urinary tract symptoms after an episode of Chikungunya fever was after a mean period of 163 days (range 30-360 days). Mean serum creatinine on presentation was 1.8 mg/dl (0.6-6.5 mg/dl). Evaluation revealed dilated upper tract in four (30.7%) patients. Cystometrography showed acontractile detrusor (n=3, 37.5%), hypocontractile detrusor (n=3, 37.5%), overactive detrusor (n=1, 12.5%) and normal study (n=1, 12.5%). At the mean follow up of 11 months, 11 patients (84.6%) had satisfactory functional outcome after intervention, namely supra pubic diversion and bladder training (n=5, 38.4%), alpha blocker (n=3, 23%), timed frequent voiding (n=2, 15.3%), clean intermittent catheterization (n=2, 15.3%), trial void with alpha blocker (n=1, 7.6%) while two are on continuing supra pubic diversion due to persistent neurological deficit. Chikungunya fever is an uncommon entity in urological practice, often associated with urinary symptoms. An accurate assessment of the symptoms and timely intervention prevents upper tract deterioration and improves the quality of life.


Endoscopic placement of double-J ureteric stents in children as a treatment for primary obstructive megaureter. To determine the efficacy and potential complications of double-J ureteric stents in the treatment of persistent or progressive primary obstructive megaureter in pediatric patients within our institution. A retrospective case-note review of all patients with double-J ureteric stents, between 1997 and 2004, was performed. In all, 38 stents were inserted in 31 patients aged between 2 months and 15 years of age. Complications and results of follow-up investigations and the need for follow-up investigations were recorded. Patients were followed up clinically and radiologically for a minimum of 2 years following stent insertion. Endoscopic placement of double-J ureteric stents in childhood is straightforward and complications are uncommon (8/38 insertions). In non-resolving or progressive primary non-refluxing megaureter, double-J ureteric stenting alone is effective with resolution of primary non-refluxing megaureter in 66% of cases (25/38 insertions). Ureteric stenting provides an alternative to early surgery in patients with primary non-refluxing megaureter. The youngest patient in our series was 2 months old at the time of endoscopic ureteric double-J stent insertion. Endoscopic placement of ureteric double-J stents should be considered as a first-line treatment in the management of persistent or progressive non-refluxing megaureter leading to progressive hydronephrosis or pyonephrosis.


Subcapsular renal hematoma after ureterorenoscopy: An unknown complication of a known procedure. Renal subcapsular hematoma is not an uncommon complication after extracorporeal short wave lithotripsy, trauma, renal angiographic procedures and spontaneously in patients of malignancy and in patients on anticoagulation. We present a patient who developed renal subcapsular hematoma after ureterorenoscopy, which has not been mentioned in literature ever. Clinical spectrum varies from spontaneous resolution through acute renal failure to Page kidney. Page kidney is the external compression of a kidney usually caused by a subcapsular hematoma associated with high blood pressure and occasional renal failure. It is named after Dr. Irvin Page who first demonstrated in 1939 that wrapping cellophane tightly around animal kidneys could cause hypertension. Various management options are mentioned in literature and depend upon the severity of hematoma. Percutaneous drainage is a successful option for the management of subcapsular hematoma in hemodynamic stable patients.


Primary renal adenosquamous carcinoma.

Primary renal adenosquamous carcinoma. A case of renal adenosquamous carcinoma is presented. The fact that the urothelium has no glandular or squamous structures makes the pathogenesis of this tumor unique. The process is assumed to begin with urothelial metaplasia resulting from chronic irritation leading to dysplasia and subsequently squamous and glandular differentiation.


Xanthogranulomatous cystitis: A rare clinical entity. Xanthogranulomatous cystitis (XC) is a rare benign disease of unknown etiology. A case of XC in a 30-year-old male is presented due to sparcity of such case report in medical literature. Patient evaluation included clinical, biochemical and radiological studies before treatment. Histological study revealed the rare diagnosis. Patient was asymptomatic at eight weeks follow-up after treatment.


Upper gastro-intestinal bleeding - Rare presentation of renal cell carcinoma. Renal cell carcinoma (RCC) constitutes 2-3% of all adult malignancies and often diagnosed incidentally. Classical tried of RCC now rarely seen, it behaves unpredictably and having diverge range of clinical manifestation including paraneoplastic syndromes. Upper gastrointestinal (GI) bleeding due to stomach metastasis of RCC is uncommon and to the best of our knowledge, only few cases are reported in world literature and most of them were diagnosed during follow-up after complete treatment of RCC but in our case, it was the primary manifestation of disease. Our case also demonstrates the importance of imaging in undiagnosed cases of upper GI bleeding.


Giant adrenal myelolipoma: Incidentaloma with a rare incidental association. Adrenal myelolipoma is an unusual, benign and biochemically inactive tumor that is composed of mature adipose and hematopoietic tissue. It is usually diagnosed accidentally and nowadays much more frequently because of widespread use of ultrasonography, computed tomography (CT) and magnetic resonance imaging. Adrenal myelolipoma is usually unilateral and asymptomatic, though known to be associated with obesity, hypertension, endocrinological disorders and some malignancies. We report herein two cases of right-sided giant adrenal myelolipoma diagnosed by multidetector-row CT. One patient was symptomatic because of a large mass in the right upper abdomen, which on imaging with CT was seen to be right adrenal myelolipoma. Another patient had a large left side Bochdalek hernia and right adrenal myelolipoma was incidentally discovered on CT.


The role of serum pepsinogen in the detection of gastric cancer. The incidence of gastric cancer is very high in Japan, Korea, and China. Reducing the morbidity and mortality associated with gastric cancer requires early diagnosis, which can be facilitated by applying gastroscopy more frequently in high-risk groups. A strategy of population screening for gastric cancer is currently being adopted in Korea, Japan, and the Matsu region of Taiwan, but using different screening methods. In addition, the history of pepsinogen (PG) in research as a gastric cancer biomarker has varied, in that the use of serum levels of PGI and PGII and the PGI/PGII ratio as gastric cancer screening tools was introduced in Japan before 1990, but in Korea the first research results were only reported in 2008. This review first evaluates the physiology of PG, followed by the usefulness or limitations of serum PG testing with regard to the detection of gastric cancer. Finally, the factors affecting the efficacy of PG tests as a gastric cancer biomarker (i.e., Helicobacter pylori infection status, gender, histopathologic features, and cancer location and depth) are evaluated. It was found that the strategies used to increase the efficacy of PG tests should be individualized in each country according to the seroprevalence of H. pylori.


Halimeter ppb Levels as the Predictor of Erosive Gastroesophageal Reflux Disease. In a previous issue published in Gut and Liver, we found that erosive changes in the esophagogastroduodenal mucosa were strongly correlated with increased levels of volatile sulfur-containing compounds (VSC), suggesting that halitosis could be a symptom reflecting the erosive status of the upper gut mucosa. Together with other studies showing a possible association between halitosis and gastroesophageal reflux disease (GERD), under the premise that halitosis could be one of extraesophageal manifestations of erosive GERD (ERD), we investigated the significance of Halimeter ppb levels on ERD compared to non-erosive gastroesophageal reflux disease (NERD). Subjects were assigned to the NERD group if there was no evidence of esophageal erosive changes on endoscopy, despite reflux symptoms, and to the ERD group if they had GERD A, B, C, or D (according to the Los Angeles classification). The VSC levels were measured in all patients with either a Halimeter (before endoscopy) or by gas chromatography of the gastric juices aspirated during endoscopy. The VSC level differed significantly between the NERD and ERD groups (p<0.0001), suggesting that this can be used to discriminate between NERD and ERD. However, the VSC level did not differ significantly with the severity of GERD. Even though hiatal hernia and a body mass index of >24 kg/m(2) was significantly associated with ERD, there was no correlation with Halimeter ppb levels. Minimal-change lesions exhibited the highest VSC levels, signifying that minimal change lesions can be classified as ERD based on our finding that halimeter ppb levels were descrimitive of erosive change. Erosive changes in the esophageal mucosa were strongly associated with VSC levels, supporting the hypothesis that halitosis can be a potential biomarker for the discrimination between ERD and NERD, reflecting the presence of erosive change in the lower esophagogastric junction.


Is colonoscopy necessary in children suspected of having colonic polyps? The clinical spectrum, histology, and endoscopic features of colonic polyps in the pediatric age group were studied to evaluate the role of colonoscopy in children suspected of having colonic polyps. Seventy-six patients with colorectal polyps were studied. Investigations included barium enema (n=6), sigmoidoscopy (n=17), and colonoscopy (n=53) at the initial visit. Colonoscopy was also performed in 23 patients who received barium enema or sigmoidoscopy. Data related to age, gender, family history, signs, symptoms, size, location, polyp types, and associated diseases were collected and analyzed. Among the 76 patients, juvenile polyps were detected in 58 (76.3%), potentially premalignant polyposis in 17 (22.4%), familial adenomatous polyposis in 11 (14.5%), Peutz-Jegher syndrome in 4 (5.3%), and juvenile polyposis syndrome in 2 (2.6%). Twenty-two patients (28.9%) had polyps in the upper colon. All patients with potentially malignant polyps had polyps in both the upper colon and rectosigmoid colon. Although most of the children with colorectal polyps had juvenile polyps, a significant number of cases showed multiple premalignant and proximally located polyps. This finding emphasizes the need for a colonoscopy in such patients. Thus, the risk of malignant change, particularly in children with multiple polyps, makes surveillance colonoscopy necessary.


The role of bacteria in the pathogenesis of inflammatory bowel disease. Crohn's disease (CD) and ulcerative colitis (UC) have features that suggest bacterial involvement, and all genetic models of inflammatory bowel disease (IBD) require the presence of commensal bacteria. CD is associated with innate immune response genes such as NOD2/CARD15 and the autophagy genes ATG16L1 and IRGM. However, IBD responds to immunosuppression, suggesting that any bacteria involved are not acting as conventional pathogens. Molecular techniques are rapidly advancing our knowledge of the gut microbiota. In CD there is reduced diversity, and notably a reduction in the probiotic Faecalibacterium prausnitzii, the presence of which in the terminal ileum is associated with a reduced risk of recurrence following surgery. There is also a consistent increase in mucosa-associated Escherichia coli with an "adherent and invasive" phenotype, which allows them to replicate inside macrophages and induce granulomas. Speculation that CD could be caused by the Mycobacterium avium subspecies paratuberculosis (MAP) continues. The response to antitumor necrosis factor treatments suggests that, if relevant at all, MAP is not acting as a conventional pathogen. However, there is increased colonization by MAP in CD, and there is evidence that it could have an indirect effect mediated by the suppression of macrophage function. UC relapse is frequently associated with infection by pathogens, but there is less evidence for involvement of a specific bacterial species. Poor barrier integrity followed by an inflammatory reaction to bacterial components, with chronicity maintained by an autoimmune process, seems a plausible pathogenic model. Bacterial theories of pathogenesis are now becoming testable by targeted therapeutic interventions.


Risk Factors for Treatment Failure and Recurrence after Metronidazole Treatment for Clostridium difficile-associated Diarrhea. The incidence of treatment failure or recurrence of Clostridium difficile-associated diarrhea (CDAD) following metronidazole treatment has increased recently. We studied the treatment failure, recurrence rate, and risk factors predictive of treatment failure and recurrence after metronidazole treatment for CDAD. We retrospectively identified consecutive patients who were admitted and treated for CDAD at a single tertiary institution in Korea over a recent 10-year period (i.e., 1998-2008). Metronidazole was administered as the initial treatment to 111 of 117 patients (94.9%) with CDAD. Fourteen patients (12.6%) had no clinical response to the metronidazole treatment, and in 13 patients (13.4%) CDAD recurred after successful metronidazole treatment. Diabetes mellitus (p=0.014) and sepsis (p=0.002) were independent risk factors for metronidazole treatment failure. Patients who had received surgery within 1 month before CDAD developed were more likely to experience a recurrence after metronidazole treatment (p=0.032). Vancomycin exhibited a higher response rate after treatment failure, and metronidazole showed a reasonable response rate in the treatment of recurrence. Treatment failure and recurrence rates increased with time after metronidazole treatment for CDAD over the 10-year study period. Our data suggest that diabetes mellitus and sepsis are independent risk factors for metronidazole treatment failure, and that operation history within 1 month of development of CDAD is a predictor of a recurrence after metronidazole treatment.


Sacroiliitis is common in Crohn's disease patients with perianal or upper gastrointestinal involvement. Sacroiliitis (SI) is one of the most frequent extraintestinal manifestations in inflammatory bowel disease (IBD) patients, but the exact prevalence has not been evaluated in Asia. There are few data on the association between SI and other clinical features of IBD. The prevalence of SI was evaluated using computed tomography (CT) and the phenotypic parameters associated with SI in Korean IBD patients were determined. Eighty-two patients with ulcerative colitis (UC) and 81 patients with Crohn's disease (CD) were evaluated clinically. The presence of SI was evaluated using bone window setting of abdomino-pelvic CT images by two radiologists. The prevalence rates of SI were 12.2% and 21.0% in the UC and CD groups, respectively. There was no relationship between the localization or extent of intestinal inflammation and the presence of SI in the UC group. Multivariate analyses confirmed that perianal and upper-gastrointestinal (from the mouth through to the jejunum) diseases were associated with the occurrence of SI in the CD group (p=0.026 and p=0.047, respectively). SI was as common among Korean IBD patients as among Western patients. Perianal or upper-gastrointestinal involvement is associated with SI in CD patients.


Associations between the Plasticity Region Genes of Helicobacter pylori and Gastroduodenal Diseases in a High-Prevalence Area. Genes associated with the Helicobacter pylori (H. pylori) plasticity region may play a role in the pathogenesis of H. pylori. We compared the genes jhp0940, jhp0947, and jhp0986 in H. pylori isolates from patients with different gastroduodenal diseases and in different age groups. The H. pylori hyperplasticity region genes jhp0940, jhp0947, and jhp0986 were studied by PCR. We also evaluated whether these genes were related to the cytotoxin-associated gene (cagA) and histology findings. Of the patient cohort, 71 (62%) were positive for jhp0940, 67 (59%) for jhp0947, 12 (10%) for jhp0986, and 69 (60%) for cagA. jhp0940 (n=18, 67%) and jhp0947 (n=23, 85%) were found more frequently in duodenal ulcer (DU) patients than in gastritis patients (n=14, 39%; p=0.029 and p<0.001, respectively). Gastric ulcer (GU) was more frequently associated with jhp0940 (17 patients, 77%; p=0.003) than with gastritis (14 patients, 39%). Gastric carcinoma (GC) was more strongly associated with both jhp0940 (22 patients, 76%; p=0.003) and jhp0947 (22 patients, 76%; p=0.003) than was gastritis (14 patients, 39%). jhp0947 was more frequently associated with chronic active inflammation (58 patients, 87%; p=0.009) than with chronic inflammation (9 patients, 13%). Multivariate analysis demonstrated that jhp0947 was associated with DU (odds ratio, 6.1; 95% confidence interval, 1.87-20). The genes jhp0947 and jhp0940 were identified in H. pylori isolates from patients with GC and DU, while jhp0940 was also isolated from patients with GU. jhp0947 was independently associated with DU.


Secondary appendiceal tumors: a review of 139 cases. This study evaluated the clinicopathologic characteristics of patients with secondary appendiceal tumors (SATs). We performed a single-center, retrospective study of patients with pathologically confirmed SATs. Among 180 cases of appendiceal malignancies diagnosed between 2000 and 2007, 139 cases (77.2%, 46 male) were SATs. The median age at SAT diagnosis was 55 years. The most common primary origin was the ovary. The mode of appendiceal involvement was metastasis in 122 and invasion in 17 patients. Extra-appendiceal involvement was present in 134 patients. The only manifestation that could be attributed to the SAT itself was appendicitis (n=8). Serosal involvement was predominant. The median survival after diagnosis of SAT was 22.6 months. In the Cox regression analysis, chemotherapy included in the treatment was the only factor associated with prolonged survival (hazards ratio, 0.12; 95% confidence interval, 0.06-0.23; p<0.001). Complete resection of the SAT had no influence on survival. SATs accounted for 77.2% of all pathologically diagnosed appendiceal malignancies. The most common origin was the ovary. SATs were usually associated with widespread disease, and the median survival after SAT diagnosis was 22.6 months. Complete resection of the SAT had no influence on survival.


Efficacy of rifaximin compared with ciprofloxacin for the treatment of acute infectious diarrhea: a randomized controlled multicenter study. Ciprofloxacin has been widely prescribed for acute infectious diarrhea. However, the resistance to this drug is increasing. Rifaximin is a novel but poorly absorbed rifamycin derivative. This study evaluated and compared the efficacies of rifaximin and ciprofloxacin for the treatment of acute infectious diarrhea. We performed a randomized controlled multicenter study in Korea. Patients with acute diarrhea were enrolled and randomized to receive rifaximin or ciprofloxacin for 3 days. The primary efficacy endpoint was the time to last unformed stool (TLUS). Secondary endpoints were enteric wellness (reduction of at least 50% in the number of unformed stools during 24-hour postenrollment intervals), general wellness (subjective feeling of improvement), and proportion of patients with treatment failure. Intent-to-treat analysis (n=143) showed no significant difference between the rifaximin and ciprofloxacin groups in the mean TLUS (36.1 hours vs 43.6 hours, p=0.163), enteric wellness (49% vs 57%, p=0.428), general wellness (67% vs 78%, p=0.189), or treatment failure rate (9% vs 12%, p=0.841). The adverse events did not differ significantly between the two groups. These results suggest that rifaximin is as safe and effective as ciprofloxacin in the treatment of acute infectious diarrhea.


What are the risk factors for acute suppurative cholangitis caused by common bile duct stones? Acute suppurative cholangitis (ASC), a severe form of acute cholangitis, is a life-threatening condition that must be treated with appropriate and timely management. The purpose of this study was to identify the factors that predispose patients to ASC. We retrospectively investigated 181 patients (100 men, 81 women; age, 70.66±7.38 years, mean±SD) who were admitted to Wonkwang University Hospital between January 2005 and June 2007 for acute cholangitis with common bile duct (CBD) stones. All patients underwent endoscopic retrograde cholangiopancreatogram to remove the stones. Variables and factors that could be assessed upon admission were analyzed to identify the risk factors for the development of ASC. Of the 181 patients, 44 (24.3%) presented with ASC. On multivariate analysis, the followings were found to be independent risk factors for the development of ASC: impacted common bile duct stone (p=0.010), current smoker status (p=0.008), advanced age (>70 years; p=0.002), and gallstone (p=0.016). The most commonly isolated organisms in bile culture were Enterococcus species, Escherichia coli, and Klebsiella species. Impacted bile-duct stones, current smoking, advanced age, and gallstones were identified as independent risk factors for the development of ASC in patients with CBD stones. These results suggest that emergency biliary drainage is beneficial in patients with these risk factors.


Effect of transdermal fentanyl patches on the motility of the sphincter of oddi. Pain is one of the most troublesome symptoms of pancreatitis. Transdermal fentanyl patches (TFPs) are long-acting analgesics with a reduced risk of dependency. This prospective study evaluated the effect of TFPs on sphincter of Oddi (SO) motility for the management of pain in pancreatitis. SO manometry (SOM) was performed using triple-lumen catheters anterogradely inserted through the percutaneous transhepatic route during cholangioscopy in 16 patients. The basal pressure, amplitude, and frequency of the SO were assessed before and after applying a TFP at 24 hour at doses of 25 and 12.5µg/hr, respectively. Two of 16 patients receiving a 25µg/hr. TFP were excluded because of adverse side effects (headache and/or nausea). The mean basal pressure, amplitude, and frequency of SOM did not change significantly in the 25µg/hr TFP group (n=4 patients). Parameters of SO function also did not significantly change in the 12.5µg/hr TFP group (n=11 patients). TFPs below a dose of 25µg/hr may not affect the motility of the SO. Administration of TFPs at lower dosages seems to be a safe analgesic treatment for the pain control of patients with pancreatitis without affecting the function of the SO.


Efficacy and long-term outcome of endoscopic treatment of sporadic nonampullary duodenal adenoma. Endoscopic resection has proven to be a safe and effective alternative to surgery for duodenal adenomas. However, few data are available on the adequacy of resection and long-term outcomes. This study evaluated the efficacy and longterm endoscopic findings in a cohort of Korean patients who underwent endoscopic mucosal resection (EMR) of sporadic duodenal adenomas. Seventeen patients with nonampullary duodenal adenomas without familial polyposis syndrome and who were treated by EMR between January 2001 and December 2007 were evaluated retrospectively. Their management, follow-up, and outcomes were reviewed. In total, seventeen lesions were removed from EMR in 17 patients (mean age, 59.3 years; 6 women, 11 men). The mean size of the tumors was 15.1 mm (median, 13 mm, range, 8-27 mm). Of these 17 adenomas, 16 adenomas were tubulous and 1 was tubulovillous. The EMR was performed successfully in all 17 patients in a single session. After a median follow-up period of 29 months (range, 13-72 months), all patients remained in remission. One patient had bleeding at the site of the EMR. There were no perforations after the EMR. EMR for sporadic duodenal adenomas seemed to be a safe and effective treatment modality.


Serum uric Acid as a predictor for the development of nonalcoholic Fatty liver disease in apparently healthy subjects: a 5-year retrospective cohort study. This study evaluated the relationship between hyperuricemia and nonalcoholic fatty liver disease (NAFLD) by comparing the incidence rates of NAFLD in relation to serum uric acid levels in apparently healthy subjects during a 5-year period. Among 15,638 healthy Korean subjects who participated in a health-screening program in 2003 and 2008, respectively, 4954 subjects without other risk factors were enrolled in this study. We compared the incidence rates of NAFLD in 2008 with respect to baseline uric acid levels. In 2003, serum uric acid levels were categorized into the following quartiles: 0.6-3.9, 3.9-4.8, 4.8-5.9, and 5.9-12.6 mg/dL. The incidence of NAFLD in 2008 increased with the level of baseline uric acid (5.6%, 9.8%, 16.2%, and 20.9%, respectively; p<0.05). Multiple logistic regression analysis demonstrated that hyperuricemia was associated with the development of NAFLD. When compared to the subjects in quartile 1, the odds ratio (OR) for the incidence of NAFLD for quartiles 2, 3, and 4 were 1.53 (95% confidence interval [CI], 1.09-2.16; p=0.014], 1.69 (95% CI, 1.17-2.44; p=0.005), and 1.84 (95% CI, 1.25-2.71; p=0.002), respectively. High serum uric acid levels appear to be associated with an increased risk of the development of NAFLD.


Transcatheter arterial chemoembolization for hepatic recurrence after curative resection of pancreatic adenocarcinoma. Despite curative resection, hepatic recurrences cause a significant reduction in survival in patients with primary pancreatic adenocarcinoma. Transcatheter arterial chemoembolization (TACE) has recently been used successfully to treat primary and secondary hepatic malignancy. Between 2003 and 2008, 15 patients underwent TACE because of hepatic recurrence after curative resection of a pancreatic adenocarcinoma. The tumor response was evaluated based on computed tomography scans after TACE. The overall duration of patient survival was measured. After TACE, a radiographically evident response occurred in six patients whose tumors demonstrated a tumor blush on angiography. Four patients demonstrated stabilization of a hypovascular mass. The remaining five patients demonstrated continued progression of hypovascular hepatic lesions. The median survival periods from the time of diagnosis and from the time of initial TACE were 9.6 and 7.5 months, respectively. TACE may represent a viable therapeutic modality in patients with hepatic recurrence after curative resection of pancreatic adenocarcinoma.


A case of solitary rectal diverticulum presenting with a retrorectal mass. Colonic diverticula are common whereas but rectal diverticula are very rare, with only sporadic reports in the literature since 1911. Most patients with rectal diverticula are diagnosed incidentally, inflammatory processes may have developed at the time of the diagnosis. We report the case of a 42-year-old woman presenting with a retrorectal mass that was detected incidentally. She was suspected of having a rectal diverticulum by transrectal ultrasonography and magnetic resonance imaging. However, the colonoscopic findings were unremarkable. A rectal diverticulum was confirmed intraoperatively, and a transanal diverticulectomy was performed.


Fanconi's Syndrome Associated with Prolonged Adefovir Dipivoxil Therapy in a Hepatitis B Virus Patient. Adefovir dipivoxil (ADV) is commonly used as an antiviral agent in the treatment of chronic hepatitis B or human immunodeficiency virus infection. Nephrotoxicity has been shown to occur at daily dosages of 60-120 mg. Fanconi's syndrome is a generalized dysfunction of the renal proximal tubular cells, which is usually accompanied by complications. Here we report a case of Fanconi's syndrome in a chronic hepatitis B patient who had been treated with a prolonged regimen of ADV at 10 mg/day. A 47-year-old man complained of severe back and chest-wall pain. He had chronic hepatitis B and had been treated with ADV at a daily dose of 10 mg for 38 months. He was hospitalized because of severe bone pain, and laboratory and radiologic findings suggested a diagnosis of Fanconi's syndrome with osteomalacia. After discontinuation of the ADV, he recovered and was discharged from hospital. His laboratory findings had normalized within 2 weeks. This case indicates that Fanconi's syndrome can be acquired by a chronic hepatitis B patient taking ADV at a conventional dosage of 10 mg/day. Therefore, patients treated with long-term ADV should be checked regularly for the occurrence of ADV-induced Fanconi's syndrome.


Peroral direct cholangioscopic-guided biopsy and photodynamic therapy using an ultraslim upper endoscope for recurrent hepatocellular carcinoma with intraductal tiny nodular tumor growth. Bile-duct invasion is rare in patients with hepatocellular carcinoma (HCC). We report a case that received peroral direct cholangioscopy (PDCS)-guided endoscopic biopsy and photodynamic treatment (PDT) for recurrent HCC with intraductal tiny nodular tumor growth. A 64-year-old woman presented with recurrent right upper-quadrant pain. Six months previously she had been diagnosed with HCC with bile-duct invasion in the right anterior segment and had received right anterior segmentectomy. On pathological examination, the margin of resection was clear, but macroscopic bile-duct invasion was noted. On admission, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) revealed a 0.5-cm-sized polypoid mass at the hilar portion. ERCP-guided biopsy failed, and an ampullary stricture was noted. PDCS-guided endoscopic biopsy was thus performed, and histopathology of the retrieved specimen revealed HCC. The patient submitted to PDT. There was no procedure-related complication. After 1 month of PDT the polypoid lesion and scar change at the hilar lesion had disappeared.


Signet ring cell carcinoma of the extrahepatic bile duct. Most tumors affecting the extrahepatic bile duct are adenocarcinomas; the other histologic types occur only rarely. We herein report the extremely rare case of signet ring cell carcinoma (SRCC) originating from the extrahepatic bile duct. A 55-year-old man was hospitalized for jaundice and pruritus. Computed tomography and positron emission tomography suggested the presence of distal extrahepatic bile-duct cancer. He underwent a pylorus preserving pancreaticoduodenectomy. A histologic study confirmed a signet ring cell neoplasm of the distal common bile duct. Because the upper resection margin was invaded by the tumor, he received postoperative concurrent chemoradiotherapy and four cycles of chemotherapy. The patient has survived with no evidence of recurrence for 2 years. This is the second case of primary SRCC of the distal extrahepatic bile duct reported in the literature; further reports of cases are warranted to determine the nature of SRCC in the extrahepatic bile duct.


Tufting Enteropathy with EpCAM Mutations in Two Siblings. Tufting enteropathy is a rare autosomal recessive disorder presenting with early-onset severe intractable diarrhea. The epithelial cell adhesion molecule gene (EpCAM) has recently been identified as the gene responsible for tufting enteropathy. Based on histology, a diagnosis of tufting enteropathy was made in two Korean siblings. They developed chronic diarrhea and failure to thrive. They had a broad nasal bridge and micrognathia. Duodenal and colonic biopsies showed villous atrophy, disorganization of surface enterocytes, and focal crowding resembling tufts. Protracted diarrhea continued and so cyclic parenteral nutrition was supplied. The sister had juvenile rheumatoid arthritis. Mutation analysis of EpCAM identified two compound heterozygous mutations in these siblings: 1) a donor splicing site mutation in intron 5 (c.491+1G>A) and 2) a novel nonsense mutation in exon 3 (c.316A>T, Lys106X). Analysis of EpCAM will be useful for genetic counseling and prenatal diagnosis of tufting enteropathy.


Colonoscopic clipping as a treatment for appendiceal bleeding. Bleeding from the appendix has been reported very rarely in patients with lower-gastrointestinal-tract bleeding. In general, after a colonoscopic diagnosis of appendiceal bleeding, laparoscopic or surgical appendectomy would be recommended. Two patients with continuous bleeding from the appendix were treated with partial occlusion of the appendiceal orifice by colonoscopic clipping. In neither case was there evidence of further active bleeding over the following 12 months. This is the first report of such a treatment in the English literature.


A case of phlegmonous gastritis associated with marked gastric distension. Phlegmonous gastritis is an acute and severe infectious disease that is occasionally fatal if the diagnosis is delayed. Alcohol consumption, an immunocompromised state (e.g., due to HIV infection, rheumatoid arthritis, diabetes mellitus, or adult T-cell lymphoma), and mucosal injury of the stomach are reported to be predisposing factors. The main treatments for phlegmonous gastritis are antibiotics administration or surgery. In this case, the patient's stomach was markedly distended due to long-lasting gastric-outlet obstruction, which is thought to be the predisposing factor for phlegmonous gastritis. We inserted a metal stent at the obstructed site palliatively due to strong refusal by the patient for surgery. The patient recovered after stenting and antibiotic therapy.


An inflammatory myofibroblastic tumor of the ampulla of vater successfully managed with endoscopic papillectomy: report of a case. Inflammatory myofibroblastic tumors (IMTs) are solid neoplastic mesenchymal proliferations composed of myofibroblastic spindle cells admixed with inflammatory infiltrates. The documented sites in the gastrointestinal tract include the esophagus, small intestine, colon, appendix, rectum, pancreas, spleen, liver, and Meckel's diverticulum. Biliary IMTs are rare, and IMTs arising from the ampulla of Vater have not been reported previously. Herein we report the case of a 65-year-old woman with an extrahepatic biliary obstruction due to IMT of the ampulla of Vater, and a successful therapeutic approach using endoscopic ultrasonography and endoscopic papillectomy.


Treatment of hepatocellular carcinoma with portal vein thrombosis by sorafenib combined with hepatic arterial infusion chemotherapy. Treatment with sorafenib prolongs both the median survival and time to progression by nearly 3 months in patients with advanced hepatocellular carcinoma. Although the effects of combining sorafenib therapy with other anticancer treatment modalities have not been clarified, combination treatment is strongly expected to be beneficial. We report the case of a 50-year-old man who exhibited a partial response and portal vein thrombosis (PVT) revascularization after sorafenib combined with hepatic arterial infusion chemotherapy (HAIC). He exhibited a decrease in tumor size and PVT after 2 months of sorafenib monotherapy. However, no additional response was seen during the subsequent 2 months. To achieve a better tumor response, we combined HAIC with sorafenib. Daily cisplatin (7 mg/m(2) on days 1-5) and 5-fluorouracil (170 mg/m(2) on days 1-5) were infused repeatedly every 4 weeks, and the sorafenib prescription was modified. After four cycles of combined therapy, both the tumor size and PVT were much improved and exhibited partial response.


Frameshift Mutation of MARS Gene Encoding an Aminoacyl-tRNA Synthetase in Gastric and Colorectal Carcinomas with Microsatellite Instability.


Bile-Duct Stone Removal under Direct Transnasal Cholangioscopy Using an Ultraslim Upper Endoscope. The transnasal endoscopic examination using an ultraslim upper endoscope may be more comfortable and less stressful than the peroral approach. Transnasal endoscopic retrograde cholangiopancreatography (ERCP), endoscopic nasobiliary drainage, and direct peroral cholangioscopy using an ultraslim upper endoscope have recently been reported. An 82-year-old woman with a previous history of endoscopic sphincterotomy and stone removal was admitted with acute cholangitis. Instead of conventional ERCP, we performed direct transnasal cholangioscopy (TNC) using an ultraslim upper endoscope for biliary decompression and stone removal because of her unstable vital signs. Direct TNC using an ultraslim upper endoscope may be useful in selected patients with biliary disease.


Analysis of nucleotide variations in genes of iron management in patients of Parkinson's disease and other movement disorders. The capacity to act as an electron donor and acceptor makes iron an essential cofactor of many vital processes. Its balance in the body has to be tightly regulated since its excess can be harmful by favouring oxidative damage, while its deficiency can impair fundamental activities like erythropoiesis. In the brain, an accumulation of iron or an increase in its availability has been associated with the development and/or progression of different degenerative processes, including Parkinson's disease, while iron paucity seems to be associated with cognitive deficits, motor dysfunction, and restless legs syndrome. In the search of DNA sequence variations affecting the individual predisposition to develop movement disorders, we scanned by DHPLC the exons and intronic boundary regions of ceruloplasmin, iron regulatory protein 2, hemopexin, hepcidin and hemojuvelin genes in cohorts of subjects affected by Parkinson's disease and idiopathic neurodegeneration with brain iron accumulation (NBIA). Both novel and known sequence variations were identified in most of the genes, but none of them seemed to be significantly associated to the movement diseases of interest.


Gender dependence for a subset of the low-abundance signaling proteome in human platelets. The incidence of cardiovascular diseases is ten-times higher in males than females, although the biological basis for this gender disparity is not known. However, based on the fact that antiplatelet drugs are the mainstay for prevention and therapy, we hypothesized that the signaling proteomes in platelets from normal male donors might be more activated than platelets from normal female donors. We report here that platelets from male donors express significantly higher levels of signaling cascade proteins than platelets from female donors. In silico connectivity analysis shows that the 24 major hubs in platelets from male donors focus on pathways associated with megakaryocytic expansion and platelet activation. By contrast, the 11 major hubs in platelets from female donors were found to be either negative or neutral for platelet-relevant processes. The difference may suggest a biological mechanism for gender discrimination in cardiovascular disease.


Developmental pharmacogenetics in pediatric rheumatology: utilizing a new paradigm to effectively treat patients with juvenile idiopathic arthritis with methotrexate. Although methotrexate is widely used in clinical practice there remains significant lack of understanding of its mechanisms of action and the factors that contribute to the variability in toxicity and response seen clinically. In addition to differences in drug administration, factors that affect pharmacokinetics and pharmacodynamics such as genetic variation may explain individual differences in drug biotransformation. However, the pediatric population has an additional factor to consider, namely the ontogeny of gene expression which may result in variation throughout growth and development. We review the current understanding of methotrexate biotransformation and the concept of ontogeny, with further discussion of how to implement a developmental pharmacogenomics approach in future studies.


Pharmacogenomics of mood stabilizers in the treatment of bipolar disorder. Bipolar disorder (BD) is a chronic and often severe psychiatric illness characterized by manic and depressive episodes. Among the most effective treatments, mood stabilizers represent the keystone in acute mania, depression, and maintenance treatment of BD. However, treatment response is a highly heterogeneous trait, thus emphasizing the need for a structured informational framework of phenotypic and genetic predictors. In this paper, we present the current state of pharmacogenomic research on long-term treatment in BD, specifically focusing on mood stabilizers. While the results provided so far support the key role of genetic factors in modulating the response phenotype, strong evidence for genetic predictors is still lacking. In order to facilitate implementation of pharmacogenomics into clinical settings (i.e., the creation of personalized therapy), further research efforts are needed.


Pharmacogenetics of anticoagulants.

Pharmacogenetics of anticoagulants. Warfarin, acenocoumarol, and phenprocoumon are among the major anticoagulant drugs worldwide. Because of their low therapeutic index and serious adverse reactions (ADRs), their wide use, and their varying kinetics and pharmacogenetic dependence, it is of great importance to explore further possibilities to forecast the dose beyond conventional INR measurements. Here, we describe particulars of the relative pharmacogenetic influence on the kinetics of these agents, the population distribution of genetics risk groups, and novel data on clinical features with influence on dose requirement and ADR risk. The usefulness of genetic information prior to and soon after start of therapy is also discussed. The current renewed focus on these issues is caused not only because of new genetic knowledge and genotyping facilities but also because of the high rate of serious ADRs. Application of these measures in the care of patients with anticoagulant therapy is important awaiting new therapeutic principles to be introduced, which may take long time still.


Genome-wide linkage and association scans for quantitative trait Loci of serum lactate dehydrogenase-the framingham heart study. Serum lactate dehydrogenase (LDH) is used in diagnosing many diseases and is significantly determined by genetic factors. Three genes coding for LDH isoenzymes were mapped to chromosome 11q15 and 12p12. We used 330 Framingham Heart Study largest families for microsatellite linkage scan and 100K SNPs association scan to determine quantitative trait loci of LDH level. We estimated the heritability at 41%. Our genome-wide linkage analysis yielded several chromosomal regions, other than 11q and 12p, with LOD scores between 1 and 2.5. None of the 100K SNPs with a P-value <10(-4) in our genome-wide association study was close to the chromosomal regions where the LDH genes reside. Our study demonstrated a strong genetic effect on the variation of LDH levels. There may not be a single gene with a large effect, instead may be several genes with small effects in controlling the variation of serum LDH. Those genes may be located on chromosomal regions that differ from where the genes encoding LDH isoenzymes reside.


Thermal mixing of two miscible fluids in a T-shaped microchannel. In this paper, thermal mixing characteristics of two miscible fluids in a T-shaped microchannel are investigated theoretically, experimentally, and numerically. Thermal mixing processes in a T-shaped microchannel are divided into two zones, consisting of a T-junction and a mixing channel. An analytical two-dimensional model was first built to describe the heat transfer processes in the mixing channel. In the experiments, de-ionized water was employed as the working fluid. Laser induced fluorescence method was used to measure the fluid temperature field in the microchannel. Different combinations of flow rate ratios were studied to investigate the thermal mixing characteristics in the microchannel. At the T-junction, thermal diffusion is found to be dominant in this area due to the striation in the temperature contours. In the mixing channel, heat transfer processes are found to be controlled by thermal diffusion and convection. Measured temperature profiles at the T-junction and mixing channel are compared with analytical model and numerical simulation, respectively.


Genetic variations in human glutathione transferase enzymes: significance for pharmacology and toxicology. Glutathione transferase enzymes (GSTs) catalyze reactions in which electrophiles are conjugated to the tripeptide thiol glutathione. While many GST-catalyzed transformations result in the detoxication of xenobiotics, a few substrates, such as dihaloalkanes, undergo bioactivation to reactive intermediates. Many molecular epidemiological studies have tested associations between polymorphisms (especially, deletions) of human GST genes and disease susceptibility or response to therapy. This review presents a discussion of the biochemistry of GSTs, the sources-both genetic and environmental-of interindividual variation in GST activities, and their implications for pharmaco- and toxicogenetics; particular attention is paid to the Theta class GSTs.


Integrated electrical concentration and lysis of cells in a microfluidic chip. Lysing cells is an important step in the analysis of intracellular contents. Concentrating cells is often required in order to acquire adequate cells for lysis. This work presents an integrated concentration and lysis of mammalian cells in a constriction microchannel using dc-biased ac electric fields. By adjusting the dc component, the electrokinetic cell motion can be precisely controlled, leading to an easy switch between concentration and lysis of red blood cells in the channel constriction. These two operations are also used in conjunction to demonstrate a continuous concentration and separation of leukemia cells from red blood cells in the same microchannel. The observed cell behaviors agree reasonably with the simulation results.


Successful treatment of early endometrial carcinoma by local delivery of levonorgestrel: a case report. We describe a case of a 67-year-old Caucasian woman with an early, moderately-differentiated adenocarcinoma of the endometrium. A levonorgestrel-releasing intrauterine system was inserted, which she tolerated well. A full D&C, following removal of the device, was performed after 9 months, confirming absence of tumoral tissue. Examination after 24 months showed a very thin endometrium, indicating complete remission.


Lipid mediators in skin inflammation: updates and current views.


Mixed deterministic and probabilistic networks. The paper introduces mixed networks, a new graphical model framework for expressing and reasoning with probabilistic and deterministic information. The motivation to develop mixed networks stems from the desire to fully exploit the deterministic information (constraints) that is often present in graphical models. Several concepts and algorithms specific to belief networks and constraint networks are combined, achieving computational efficiency, semantic coherence and user-interface convenience. We define the semantics and graphical representation of mixed networks, and discuss the two main types of algorithms for processing them: inference-based and search-based. A preliminary experimental evaluation shows the benefits of the new model.


Toll-like receptor signaling pathways--therapeutic opportunities. Toll-like receptors (TLRs) are transmembrane proteins acting mainly as sensors of microbial components. Triggering TLRs results in increased expression of multiple inflammatory genes, which then play a protective role against infection. However, aberrant activation of TLR signaling has a significant impact on the onset of cancer, allergy, sepsis and autoimmunity. Various adaptor proteins, including MyD88, IRAKs, TIRAP, TRIF, and TRAM, are involved in specific TLR signaling pathways. This article reviews the role of these molecules in TLR signaling, and discusses the impact of this pathway on various disease scenarios. Given their important role in infectious and non-infectious disease settings, TLRs and their signaling pathways emerge as attractive targets for therapeutics.


Order-free co-regionalized areal data models with application to multiple-disease mapping. With the ready availability of spatial databases and geographical information system software, statisticians are increasingly encountering multivariate modelling settings featuring associations of more than one type: spatial associations between data locations and associations between the variables within the locations. Although flexible modelling of multivariate point-referenced data has recently been addressed by using a linear model of co-regionalization, existing methods for multivariate areal data typically suffer from unnecessary restrictions on the covariance structure or undesirable dependence on the conditioning order of the variables. We propose a class of Bayesian hierarchical models for multivariate areal data that avoids these restrictions, permitting flexible and order-free modelling of correlations both between variables and across areal units. Our framework encompasses a rich class of multivariate conditionally autoregressive models that are computationally feasible via modern Markov chain Monte Carlo methods. We illustrate the strengths of our approach over existing models by using simulation studies and also offer a real data application involving annual lung, larynx and oesophageal cancer death-rates in Minnesota counties between 1990 and 2000.


Enumerating the junction trees of a decomposable graph. We derive methods for enumerating the distinct junction tree representations for any given decomposable graph. We discuss the relevance of the method to estimating conditional independence graphs of graphical models and give an algorithm that, given a junction tree, will generate uniformly at random a tree from the set of those that represent the same graph. Programs implementing these methods are included as supplemental material.


Curvilinear Immersed Boundary Method for Simulating Fluid Structure Interaction with Complex 3D Rigid Bodies. The sharp-interface CURVIB approach of Ge and Sotiropoulos [L. Ge, F. Sotiropoulos, A Numerical Method for Solving the 3D Unsteady Incompressible Navier-Stokes Equations in Curvilinear Domains with Complex Immersed Boundaries, Journal of Computational Physics 225 (2007) 1782-1809] is extended to simulate fluid structure interaction (FSI) problems involving complex 3D rigid bodies undergoing large structural displacements. The FSI solver adopts the partitioned FSI solution approach and both loose and strong coupling strategies are implemented. The interfaces between immersed bodies and the fluid are discretized with a Lagrangian grid and tracked with an explicit front-tracking approach. An efficient ray-tracing algorithm is developed to quickly identify the relationship between the background grid and the moving bodies. Numerical experiments are carried out for two FSI problems: vortex induced vibration of elastically mounted cylinders and flow through a bileaflet mechanical heart valve at physiologic conditions. For both cases the computed results are in excellent agreement with benchmark simulations and experimental measurements. The numerical experiments suggest that both the properties of the structure (mass, geometry) and the local flow conditions can play an important role in determining the stability of the FSI algorithm. Under certain conditions unconditionally unstable iteration schemes result even when strong coupling FSI is employed. For such cases, however, combining the strong-coupling iteration with under-relaxation in conjunction with the Aitken's acceleration technique is shown to effectively resolve the stability problems. A theoretical analysis is presented to explain the findings of the numerical experiments. It is shown that the ratio of the added mass to the mass of the structure as well as the sign of the local time rate of change of the force or moment imparted on the structure by the fluid determine the stability and convergence of the FSI algorithm. The stabilizing role of under-relaxation is also clarified and an upper bound of the required for stability under-relaxation coefficient is derived.


Use of preputial skin as cutaneous graft after nevus excision. We report a four-year-old boy with a nevus covering all the plantar side of his second finger on the left foot. He was also affected by congenital phimosis. Surgical excision of the nevus was indicated, but the skin defect would have been too large to be directly closed. The foreskin was taken as a full-thickness skin graft to cover the cutaneous defect of the finger. The graft intake was favourable and provided a functional repair with good aesthetic characteristic.


A Summary of the Endocrine Society Clinical Practice Guidelines on Congenital Adrenal Hyperplasia due to Steroid 21-Hydroxylase Deficiency. Steroid 21-hydroxylase deficiency accounts for about 95% of cases of congenital adrenal hyperplasia (CAH). Newborns are currently being screened for the classical forms of this disease throughout the United States and in 12 other countries. As such, it seems important to develop the best practice guidelines for treating not only infants and children, but affected adults as well. This report gives a brief overview of the most recent expert opinion and clinical practice guidelines for CAH as formulated by The Endocrine Society Task Force.


Biosorption of Lanthanides from Aqueous Solutions Using Pretreated Buccinum tenuissimum Shell Biomass. Biosorption experiment from aqueous solutions containing known amount of rare earth elements (REEs) using pre-treated Buccinum tenuissimum shell was explored to evaluate the efficiency of shell biomass as sorbent for REEs. In this work, four kinds of sieved shell samples: (a) "Ground original sample", (b) "Heat-treatment (480°C, 6 hours) sample", (c) "Heat-treatment (950°C, 6 hours) sample" and (d) "Heat-treatment (950°C, 6 hours) and water added sample" were used. Furthermore, to confirm the characteristics of the shell biomass, the crystal structure, the surface morphology, and the specific surface area of these shell samples were determined. Consequently, the following matters have been mainly clarified. (1) The crystal structure of the shell biomass was transformed from aragonite (CaCO(3)) into calcite (CaCO(3)) phase by heat-treatment (480°C, 6 hours); then mainly transformed into calcium oxide (CaO) by heat-treatment (950°C, 6 hours), and calcium hydroxide (Ca(OH)(2)) by heat-treatment (950°C, 6 hours) and adding water. (2) The shell biomass showed excellent sorption capacity for lanthanides. (3) Adsorption isotherms using the shell biomass can be described by Langmuir and Freundlich isotherms satisfactorily for lanthanides except "heat-treatment (950°C, 6 hours) sample". (4) Shell biomass (usually treated as waste material) can be an efficient sorbent for lanthanides in future.


Struggling with a Gastric Volvulus Secondary to a Type IV Hiatal Hernia. Type IV hiatal hernias are characterized by herniation of the stomach along with associated viscera such as the spleen, colon, small bowel, and pancreas through the esophageal hiatus. They are relatively rare, representing only about 5%-7% of all hernias, and can be associated with severe complications. We report a 71-year-old veteran wrestler who presented to our department with a type IV paraesophageal hernia containing a gastric volvulus and treated successfully with emergency operation.


The SSX family of cancer-testis antigens as target proteins for tumor therapy. Cancer-testis antigens (CTAs) represent an expanding class of tumor-associated proteins defined on the basis of their tissue-restricted expression to testis or ovary germline cells and frequent ectopic expression in tumor tissue. The expression of CTA in MHC class I-deficient germline cells makes these proteins particularly attractive as immunotherapeutic targets because they serve as essentially tumor-specific antigens for MHC class I-restricted CD8+ T cells. Moreover, because CTAs are expressed in many types of cancer, any therapeutic developed to target these antigens might have efficacy for multiple cancer types. Of particular interest among CTAs is the synovial sarcoma X chromosome breakpoint (SSX) family of proteins, which includes ten highly homologous family members. Expression of SSX proteins in tumor tissues has been associated with advanced stages of disease and worse patient prognosis. Additionally, both humoral and cell-mediated immune responses to SSX proteins have been demonstrated in patients with tumors of varying histological origin, which indicates that natural immune responses can be spontaneously generated to these antigens in cancer patients. The current review will describe the history and identification of this family of proteins, as well as what is known of their function, expression in normal and malignant tissues, and immunogenicity.


A metabonomic comparison of urinary changes in Zucker and GK rats. To further investigate pathogenesis and pathogenic process of type 2 diabetes mellitus (T2DM), we compared the urinary metabolic profiling of Zucker obese and Goto-kakizaki (GK) rats by NMR-based metabonomics. Principal component analysis (PCA) on urine samples of both models rats indicates markedly elevated levels of creatine/creatinine, dimethylamine, and acetoacetate, with concomitantly declined levels of citrate, 2-ketoglurarate, lactate, hippurate, and succinate compared with control rats, respectively. Simultaneously, compared with Zucker obese rats, the GK rats show decreased levels of trimethylamine, acetate, and choline, as well as increased levels of creatine/creatinine, acetoacetate, alanine, citrate, 2-ketoglutarate, succinate, lactate, and hippurate. This study demonstrates metabolic similarities between the two stages of T2DM, including reduced tricarboxylic acid (TCA) cycle and increased ketone bodies production. In addition, compared with Zucker obese rats, the GK rats have enhanced concentration of energy metabolites, which indicates energy metabolic changes produced in hyperglycemia stage more than in insulin resistance stage.


A hypothesis test for equality of bayesian network models. Bayesian network models are commonly used to model gene expression data. Some applications require a comparison of the network structure of a set of genes between varying phenotypes. In principle, separately fit models can be directly compared, but it is difficult to assign statistical significance to any observed differences. There would therefore be an advantage to the development of a rigorous hypothesis test for homogeneity of network structure. In this paper, a generalized likelihood ratio test based on Bayesian network models is developed, with significance level estimated using permutation replications. In order to be computationally feasible, a number of algorithms are introduced. First, a method for approximating multivariate distributions due to Chow and Liu (1968) is adapted, permitting the polynomial-time calculation of a maximum likelihood Bayesian network with maximum indegree of one. Second, sequential testing principles are applied to the permutation test, allowing significant reduction of computation time while preserving reported error rates used in multiple testing. The method is applied to gene-set analysis, using two sets of experimental data, and some advantage to a pathway modelling approach to this problem is reported.


Does valproic acid induce neuroendocrine differentiation in prostate cancer? Valproic Acid (VPA) is a histone deacetylase inhibitor that holds promise for cancer therapy. Here, we investigate whether VPA treatment induces neuroendocrine differentiation of Prostate Cancer (PCa). A tissue microarray of VPA-treated and untreated tumor xenografts and cell lines of human PCa (LNCaP, C4-2, DU145, and PC-3) were generated and were analyzed by immunohistochemical analysis (IHC) for NE markers chromogranin A (CgA), synaptophysin, and NCAM (neural cell adhesion molecule). Western blot analysis for CgA was performed to confirm the results of the TMA. IHC analysis did not reveal any induction of CgA, synaptophysin, or NCAM in any xenograft after VPA treatment in vivo. In vitro, VPA treatment induced little synaptophysin expression in C4-2 and PC-3 cells and NCAM expression in LNCaP and PC-3 cells. In the case of CgA, VPA treatment decreased its expression in vitro in a dose-dependent manner, as determined by western blot analysis. Thus our data demonstrates that VPA does not induce NE differentiation of PCa cells in the physiologically relevant in vivo setting.


The add-on effect of solifenacin for patients with remaining overactive bladder after treatment with tamsulosin for lower urinary tract symptoms suggestive of benign prostatic obstruction. To investigate the add-on effect of solifenacin for Japanese men with remaining overactive bladder (OAB) symptoms after tamsulosin monotherapy for lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) in real-life clinical practice. Patients aged ≥ 50 having remaining OAB symptoms (≥ 3 of OAB symptom score (OABSS) with ≥2 of urgency score) after at least 4 weeks treatment by 0.2 mg of tamsulosin for BPO/LUTS received 2.5 or 5.0 mg of solifenacin for 12 weeks. The International Prostate Symptom Score (IPSS), QOL index and OABSS, maximum flow rate (Qmax) and postvoid residual urine volume (PVR) were determined. A total of 48 patients (mean age 72.5 years) completed the study. There were significant improvement in IPSS (15.1 to 11.2) and QOL index (4.2 to 3.0) by add-on of solifenacin. Although the IPSS storage symptom score was significantly improved, there were no changes observed in the IPSS voiding symptom score. The OABSS showed significant improvement (8.0 to 4.8). No changes were observed in Qmax and PVR. Under the supervision of an experienced urologist, the additional administration of solifenacin to patients with BPO/LUTS treated with tamsulosin, is effective in controlling remaining OAB symptoms.


Influence of Hsp90 and HDAC inhibition and tubulin acetylation on perinuclear protein aggregation in human retinal pigment epithelial cells. Retinal pigment epithelial (RPE) cells are continually exposed to oxidative stress that contributes to protein misfolding, aggregation and functional abnormalities during aging. The protein aggregates formed at the cell periphery are delivered along the microtubulus network by dynein-dependent retrograde trafficking to a juxtanuclear location. We demonstrate that Hsp90 inhibition by geldanamycin can effectively suppress proteasome inhibitor, MG-132-induced protein aggregation in a way that is independent of HDAC inhibition or the tubulin acetylation levels in ARPE-19 cells. However, the tubulin acetylation and polymerization state affects the localization of the proteasome-inhibitor-induced aggregation. These findings open new perspectives for understanding the pathogenesis of protein aggregation in retinal cells and can be useful for the development of therapeutic treatments to prevent retinal cell deterioration.


Direct vasocontractile activities of bupivacaine enantiomers on the isolated rat thoracic aorta. Background. In vitro studies with isolated arteries have shown direct vasoactivity of racemic bupivacaine. However, there is little information on the direct vasoactivities of bupivacaine enantiomers, S(-)- and R(+)-bupivacaine. Methods. We performed functional examinations using isolated intact thoracic aortic rings from male Wistar rats. Changes in ring tension produced by S(-)-, R(+)-, or racemic bupivacaine were measured in Krebs solution. Results. S(-)-bupivacaine produced the strongest contraction of the three agents. R(+)-bupivacaine showed limited vasoconstriction. The effects of racemic bupivacaine were located between these two. Conclusion. Each bupivacaine enantiomer showed specific vasocontractile activity, which affects the activity of racemic bupivacaine.


Studies of complex biological systems with applications to molecular medicine: the need to integrate transcriptomic and proteomic approaches. Omics approaches to the study of complex biological systems with potential applications to molecular medicine are attracting great interest in clinical as well as in basic biological research. Genomics, transcriptomics and proteomics are characterized by the lack of an a priori definition of scope, and this gives sufficient leeway for investigators (a) to discern all at once a globally altered pattern of gene/protein expression and (b) to examine the complex interactions that regulate entire biological processes. Two popular platforms in "omics" are DNA microarrays, which measure messenger RNA transcript levels, and proteomic analyses, which identify and quantify proteins. Because of their intrinsic strengths and weaknesses, no single approach can fully unravel the complexities of fundamental biological events. However, an appropriate combination of different tools could lead to integrative analyses that would furnish new insights not accessible through one-dimensional datasets. In this review, we will outline some of the challenges associated with integrative analyses relating to the changes in metabolic pathways that occur in complex pathophysiological conditions (viz. ageing and altered thyroid state) in relevant metabolically active tissues. In addition, we discuss several new applications of proteomic analysis to the investigation of mitochondrial activity.


Successful endoscopic management of fish bone embedded into the bladder wall. We report a case of a pyogenous vesical abscess resulting from an ingested fish bone embedded in the bladder wall that was treated endoscopically in an asymptomatic man. Computed tomography of the abdomen showed a linear radiopaque structure in the thickened left anterolateral wall of the bladder. Cystoscopy revealed a protruding mass, covered with normal-appearing mucosa, with outflow of pus from a shallow recess. Histopathological findings indicated that the transurethrally removed linear structure, located in the submucosa, was compatible with fish bone. A high index of suspicion should be maintained for the correct diagnosis to be made.


Does gender impact intensity of care provided to older medical intensive care unit patients? Introduction. Women receive less aggressive critical care than men based on prior studies. No documented studies evaluate whether men and women are treated equally in the medical intensive care unit (MICU). The Therapeutic Intervention Scoring System-28 (TISS-28) has been used to examine gender differences in mixed ICU studies. However, it has not been used to evaluate equivalence of care in older MICU patients. We hypothesize that given nonsignificant, baseline health differences between genders at MICU admission, the level of care provided would be equivalent. Methods. Prospective cohort of 309 patients ≥60 years old in the MICU of an urban university teaching hospital. Explanatory variables were demographic data and baseline measures. Primary outcomes were TISS-28 scores and MICU interventions. We compare TISS-28 scores by gender using a statistical test of equivalence. Results. Women were older and had more chronic respiratory failure at MICU admission. Using equivalence limits of ±15% on gender-based scores of TISS-28, MICU interventions were equivalent. Supplementary analysis showed no statistically significant association between gender and mortality. Conclusions. In contrast with other reports from the cardiac critical care literature, as measured by the TISS-28, gender-based care delivered to older MICU patients in this cohort was equivalent.


Changing trends of breast cancer survival in sultanate of oman. Breast cancer is the leading cause of cancer-associated mortality in women, with elevated incidence in developing countries. This retrospective study included all 122 patients diagnosed with breast cancer from January 2003 to December 2008 in the Sultanate of Oman. Age at presentation was 47.41 years (SD±12.88), with one-third of patients younger than 40 years. The majority of patients presented with stage III (41.2%) and IV (18.2%) breast cancer. T size (P = .023), skin involvement (P = .003), and stage at presentation (P = .004) were significantly associated with overall survival. Skin involvement at presentation (P = .003), T size (P = .09), lymph node status (P = .013), and stage (P = .003) were strong predictors of relapse-free survival. Patients had a 5-year survival of 78%, compared to 64% of breast cancer patients diagnosed between 1996 and 2002 identified in our previously published study. Thus, despite Omani breast cancer patients continuing to present with advanced breast cancer, survival rates have significantly improved.


Gender-Specific Neuroimmunoendocrine Response to Treadmill Exercise in 3xTg-AD Mice. The 3xTg-AD mouse develops a progressive Alzheimer's disease- (AD-) like brain pathology that causes cognitive- and neuropsychiatric-like symptoms of dementia. Since its neuroimmunoendocrine axis is likewise impaired, this mouse is also useful for modelling complex age-related neurodegeneration. This study analyzed behavioral, physiological, neurochemical, pathological and immunoendocrine alterations in male and female 3xTg-AD mice and assayed the effects of a short therapy of forced physical exercise at the moderate pathology stage of 6 months of age. Gender effects were observed in most AD-related pathology and dysfunctions. Five weeks of treadmill training produced beneficial effects, such as the reduction of brain oxidative stress and GABA-A receptor dysfunction in males and improvement of sensorimotor function in females. In both sexes, exercise decreased the brain amyloid β 42/40 ratio levels. The results highlight the importance of analyzing experimental therapies in both mouse model genders in order to improve our understanding of the disease and develop more appropriate therapies.


Analysis of the pathogenesis of experimental autoimmune optic neuritis. Optic neuritis associated with multiple sclerosis has a strong association with organ-specific autoimmune disease. The goal of our research is to establish an optimal organ-specific animal model to elucidate the pathogenetic mechanisms of the disease and to develop therapeutic strategies using the model. This paper is divided into five sections: (1) clinical picture of optic neuritis associated with multiple sclerosis, (2) elucidation of pathogenesis using animal models with inflammation in optic nerve and spinal cord, (3) clinical relevance of concurrent encephalomyelitis in optic neuritis model, (4) retinal damage in a concurrent multiple sclerosis and optic neuritis model, and (5) development of novel therapies using mouse optic neuritis model. Advanced therapies using biologicals have succeeded to control intractable optic neuritis in animal models. This may ultimately lead to prevention of vision loss within a short period from acute onset of optic neuritis in human. By conducting research flexibly, ready to switch from the bench to the bedside and from the bedside to the bench as the opportunity arises, this strategy may help to guide the research of optic neuritis in the right direction.


Incarcerated femoral hernia containing ipsilateral fallopian tube. Femoral hernias are more common in women and lead to a substantial higher rate for an emergency operation, due to strangulation. Incarcerated femoral hernia with fallopian tube as a content is an extremely rare condition. A 20-year-old woman presented to the emergency department complaining of a 6-day right groin swelling, which became painful and tender to palpation during the last 48 hours. Preoperative ultrasonography detected an oedematous hernia sac, above the femoral vessels, suggesting the presence of an incarcerated femoral hernia. The patient eventually underwent emergency surgery and the diagnosis of a strangulated femoral hernia sac, containing fallopian tube, was established. No resection of the uterine tube was performed and the hernia was repaired with polypropylene plug. The postoperative period was uneventful and the woman was discharged on the second postoperative day.


Rationale for possible targeting of histone deacetylase signaling in cancer diseases with a special reference to pancreatic cancer. There is ongoing interest to identify signaling pathways and genes that play a key role in carcinogenesis and the development of resistance to antitumoral drugs. Given that histone deacetylases (HDACs) interact with various partners through complex molecular mechanims leading to the control of gene expression, they have captured the attention of a large number of researchers. As a family of transcriptional corepressors, they have emerged as important regulators of cell differentiation, cell cycle progression, and apoptosis. Several HDAC inhibitors (HDACis) have been shown to efficiently protect against the growth of tumor cells in vitro as well as in vivo. The pancreatic cancer which represents one of the most aggressive cancer still suffers from inefficient therapy. Recent data, although using in vitro tumor cell cultures and in vivo chimeric mouse model, have shown that some of the HDACi do express antipancreatic tumor activity. This provides hope that some of the HDACi could be potential efficient anti-pancreatic cancer drugs. The purpose of this review is to analyze some of the current data of HDACi as possible targets of drug development and to provide some insight into the current problems with pancreatic cancer and points of interest for further study of HDACi as potential molecules for pancreatic cancer adjuvant therapy.


An Allergen Portrait Gallery: Representative Structures and an Overview of IgE Binding Surfaces. Recent progress in the biochemical classification and structural determination of allergens and allergen-antibody complexes has enhanced our understanding of the molecular determinants of allergenicity. Databases of allergens and their epitopes have facilitated the clustering of allergens according to their sequences and, more recently, their structures. Groups of similar sequences are identified for allergenic proteins from diverse sources, and all allergens are classified into a limited number of protein structural families. A gallery of experimental structures selected from the protein classes with the largest number of allergens demonstrate the structural diversity of the allergen universe. Further comparison of these structures and identification of areas that are different from innocuous proteins within the same protein family can be used to identify features specific to known allergens. Experimental and computational results related to the determination of IgE binding surfaces and methods to define allergen-specific motifs are highlighted.


Candidate single nucleotide polymorphism markers for arsenic responsiveness of protein targets. Arsenic is a toxic metalloid that causes skin cancer and binds to cysteine residues-a property that could be used to infer arsenic responsiveness of a target protein. Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) result in amino acid substitutions and may alter arsenic binding with cysteine residues. Thus, the objective of this investigation was to identify and analyze nsSNPs that lead to substitutions to or from cysteine residues as an indication of increased or decreased arsenic responsiveness. We hypothesize that integration of data on molecular impacts of nsSNPs and arsenic-gene relationships will identify nsSNPs that could serve as arsenic responsiveness markers. We have analyzed functional and structural impacts data for 5,811 nsSNPs linked to 1,224 arsenic-annotated genes. In addition to the identified candidate nsSNPs for increased or reduced arsenic responsiveness, we observed i) a nsSNP that results in the breakage of a disulfide bond, as candidate marker for reduced arsenic responsiveness of KLK7, a secreted serine protease participate in normal shedding of the skin; and ii) 6 pairs of vicinal cysteines in KLK7 protein that could be binding sites for arsenic. In summary, our analysis identified non-synonymous SNPs that could be used to evaluate responsiveness of a protein target to arsenic. In particular, an epidermal expressed serine protease with crucial function in normal skin physiology was prioritized on the basis of abundance of vicinal cysteines for further research on arsenic-induced keratinocyte carcinogenesis.