Oxygen-dependent up-regulation of mucoid exopolysaccharide (alginate) production in Pseudomonas aeruginosa.

We previously showed substantial differences in Pseudomonas aeruginosa exopolysaccharide production in vitro at oxygen tensions reflective of the right versus left cardiac circuits in vivo (40 versus 80 mm Hg, respectively; A. S. Bayer, T. O'Brien, D. C. Norman, and C. C. Nast, J. Antimicrob. Chemother. 23:21-35, 1989). However, those studies did not specifically confirm this exopolysaccharide to be the characteristic P. aeruginosa mucoid alginate seen in patients with cystic fibrosis. With a murine monoclonal antibody prepared against P. aeruginosa alginate, strongly positive immunofluorescence (IF) staining of a nonmucoid P. aeruginosa strain (PA-96) was seen after its exposure in vitro to oxygen tensions (pO2) of approximately 80 mm Hg; the intensity of the IF staining under these conditions was similar to that observed with a phenotypically mucoid P. aeruginosa strain (C1712M) from a cystic fibrosis patient. In contrast, the same nonmucoid strain (PA-96), after exposure to pO2 of approximately 40 mm Hg, showed little IF staining for alginate. Following enzyme treatment with alginase, PA-96 cells previously exposed to the higher pO2 and exhibiting enhanced alginate production, as determined by IF staining, now showed no IF staining. Moreover, treatment of the oxygen-up-regulated PA-96 cells with alginase released amounts of unsaturated alginate breakdown products (uronic acids) quantitatively similar to those released by typically mucoid strains treated with the same enzyme. These data indicated that the P. aeruginosa exopolysaccharide in our studies was, indeed, mucoid alginate and that variations in oxygen tensions represent one of the trigger mechanisms for the up-regulation of mucoid exopolysaccharide production.     

Refining the Amsterdam Criteria and Bethesda Guidelines: testing algorithms for the prediction of mismatch repair mutation status in the familial cancer clinic.

PURPOSE: Hereditary nonpolyposis colon cancer (HNPCC) is a Mendelian dominant syndrome of bowel, endometrial, and other cancers and results from germline mutations in mismatch repair (MMR) genes. HNPCC is now best diagnosed on molecular grounds using MMR mutation screening, aided by microsatellite instability (MSI) and immunohistochemistry in tumors. Selection of families for molecular investigation of HNPCC is usually based on suboptimal methods (Amsterdam Criteria or Bethesda Guidelines), but these can be improved using additional clinical data (mean ages of affected persons and presence of endometrial cancer) in a quantitative model. METHODS: We have verified the performance of the Wijnen model and have shown that it remains valid when HNPCC is diagnosed using mutation screening, MSI, and immunohistochemistry. We have also set up and verified our own models (Amsterdam-plus and Alternative), which perform at least as well as the Wijnen model. RESULTS: The Amsterdam-plus model improves on the Amsterdam Criteria by using five extra variables (numbers of colorectal and endometrial cancers in the family, number of patients with five or more adenomas, number with more than one primary cancer of the colorectum or endometrium, and mean age of presentation) and performs better than the Wijnen model. The Alternative model avoids the need to evaluate the Amsterdam Criteria and performs nearly as well as the other models. CONCLUSION: We believe that a quantitative model, such as the Amsterdam-plus model, should be the first choice for selecting families or patients for evaluation of HNPCC using molecular tests. We present an algorithm for this process.     

Incidence rate of prostate cancer in men treated for erectile dysfunction with phosphodiesterase type 5 inhibitors: retrospective analysis

The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction (ED) treated with phosphodiesterase type 5 inhibitors (PDE-5i) over a 7-year period vs. men with ED of the same age and with similar risk factors who were not treated with PDE-5i. In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006, men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified. These individuals were divided into two groups: 2362 men who had treatment with PDE-5i, and 2612 men who did not have treatment. Demographic data in each group were compared. During the study period, 97 (4.1%) men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 (9.9%) men with ED in the non-treated group (P<00001). A higher percentage of African Americans were treated with PDE-5i vs. those who were not (10.5% vs. 7.1% P<0.0001). The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen (10.0% vs. 13.1% P=0.0008) and higher percentage of benign prostatic hyperplasia (38.4% vs. 35.1% P=0.0149). Men with ED treated with PDE-5i tended to have less chance (adjusted odds ratio: 0.4; 95% confidence intervals: 0.3–0.5; P<0.0001) of having prostate cancer. Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of being diagnosed with prostate cancer. Further research is warranted.     

Coeliac disease in Iranian type I diabetic patients

BACKGROUND: The association between coeliac disease and type I diabetes mellitus has been evaluated in some previous studies, but its prevalence in Iranian diabetic patients remains unknown. AIM: To evaluate the prevalence of coeliac disease in patients with type I diabetes mellitus in Iran. PATIENTS: A total of 250 consecutive patients (102 male and 148 female) with type I diabetes mellitus. METHODS: Total serum immunoglobulin A level and immunoglobulin A endomysial antibody was measured for all patients. Endoscopy and biopsy of the duodenum were performed for immunoglobulin A endomysial antibody-positive patients and pathologic evaluation was done according to modified Marsh classification. RESULT: The mean age of the patients was 18.7 years (range: 2-55 years). Total serum immunoglobulin A was in the normal range for all patients. Immunoglobulin A endomysial antibody was positive in six (2.4%) patients (all of them were females; P = 0.04). Duodenal biopsy samples revealed grade I in two patients, grade II in three patients and grade IIIb in one patient (modified Marsh classification). Patients with coeliac disease and diabetes mellitus were older than patients with diabetes mellitus alone (mean age: 29.5 years versus 18.4 years; P < 0.001). There was a trend for longer duration of diabetes mellitus in coeliac patients than in patients without it (mean age: 17.3 years versus 12.5 years; P = 0.16). CONCLUSION: The prevalence of coeliac disease in Iranian patients with type I diabetes mellitus is relatively high (2.4%). Since almost half of the patients with coeliac disease are asymptomatic, all patients with type I diabetes mellitus should be screened for coeliac disease regardless of the presence of symptoms, at diagnosis of diabetes mellitus and with regular intervals in the follow up.     

The safety of hand‐assisted laparoscopic living donor nephrectomy: The Ohio State University experience with 1500 cases

Hand‐assisted laparoscopic donor (HALD) nephrectomy has been performed at our institution since December 1999. Through May 2014, a total of 1500 HALD procedures have been performed. We have evaluated the outcomes of HALD. The HALD procedure consists of a hand‐port incision as well as two 12‐mm ports. Mean donor age was 40.8 ± 10.8 yr, BMI was 27.9 ± 5.0, there were 541 males, 1271 Caucasians, and the left kidney was removed in 1236 patients. All procedures were successfully completed. Four donors (0.27%) were converted to an open technique due to bleeding. Four donors required blood transfusions. 53 donors (3.5%) were readmitted in the first month post‐donation; almost half were due to gastrointestinal complaints. Six donors required reoperation; three for SBO and three for wound dehiscence. 27 patients (1.8%) developed incisional hernias. Seven donors (0.47%) developed bowel obstruction. All donors recovered well with a mean hospital stay after donation of 2.1 ± 0.3 d. All except one kidney were successfully implanted. Twenty‐one recipients (1.4%) experienced DGF. Ureter complications occurred in 17 (1.1%) recipients. Early graft loss occurred in 13 patients (0.9%). In conclusion, HALD is a safe procedure for the donor with good recipient outcomes.     

Islet transplantation to the renal subcapsular space in streptozotocin-diabetic rats: short-term effects on glucose-stimulated insulin secretion

The immediate and short-term effects of transplantation of freshly isolated islets on glucose-stimulated insulin secretion were studied in streptozotocin-diabetic rats. At 2 days after the intravenous injection of streptozotocin (70 mg/kg), either 400 or 1000 freshly isolated, hand-picked islets were transplanted to the left renal subcapsular space. Intravenous glucose infusion (10 mg/min) performed 1, 3, 6, and 10 days after transplantation revealed that already at day 3, rats transplanted with 1000 islets had a significant plasma insulin response to glucose, though the response was lower than in healthy controls. At 6 and 10 days after transplantation, the 1000 islet-transplanted group of rats had a near-normal plasma insulin response to glucose. Basal plasma glucose levels were, however, still slightly elevated. Rats transplanted with 400 islets had a significant plasma insulin response at 10 days after transplantation, though the response was lower than in those transplanted with 1000 islets. It is concluded that a near-normal in vivo insulin secretory response to glucose is already obtained 6 days after transplantation with 1000 freshly isolated islets to the left renal subcapsular space in streptozotocin-diabetic rats. However, a slight hyperglycemia persists.     

Role of fine-needle aspiration cytology in evaluating thyroid nodules: A retrospective study from a tertiary care center of Western region,Saudi Arabia

Objectives:To evaluate the accuracy and efficacy of fine-needle aspiration cytology (FNAC) in diagnosing thyroid nodules, correlating it with the histopathological findings.Methods:A retrospective evaluation of 314 patients was undertaken at a tertiary referral center of King Abdullah Medical City (KAMC), Makkah, Kingdom of Saudi Arabia, between 2010-2019. Patients who presented with thyroid swellings underwent ultrasonography and FNAC. If indicated, surgery was performed. The FNAC findings were compared to the final histopathological reports.Results:The findings for FNAC from our data set of 314 patients showed a sensitivity value of 79.8%, specificity of 82.1%, accuracy of 74.8%, positive predictive value of 74.8%, and negative predictive value of 85.9%.Conclusion:Our study showed that FNAC has high sensitivity and specificity in the initial evaluation of patients with thyroid nodules. When guided by ultrasonography, the accuracy can be markedly improved. Molecular markers once widely available can improve the diagnostic power of FNAC to be no less than the histopathologic evaluation of thyroid tissue.     

Oncology research in Saudi Arabia over a 10-year period: A synopsis

Objectives:To assess the quality and quantity of Saudi publications in oncology over a 10-year period.Methods:A systematic PubMed search was conducted between January 2008 and December 2017 to retrieve all Saudi oncology publications. Data about the articles was collected. The level of evidence (LOE) was independently assessed by 2 authors. Two 5-year periods (2008-2012 and 2013-2017) were compared using the relevant parameters. Clinicaltrials.gov was also searched for all oncology trials registered in Saudi Arabia.Results:A total of 839 publications met our inclusion criteria. The most common type of research was case series, totaling 32% of all publications. Clinical trials formed less than 2% of the total. The LOE was I, II, III, and IV in 0.3%, 2.1%, 58.4%, and 39.3% of the included publications, respectively. The LOE was the same in the 2 periods. There were more publications in international journals (p=0.004), more international collaborations (p=0.001), and higher journal impact factors (p=0.037) in 2013-2017 than in 2008-2012. Only 76 registered clinical trials were found in the Clinicaltrials.gov registry.Conclusion:Despite an increase in the number of Saudi publications in the field of oncology over time, the LOE did not change. There were, however, some improvements in the international collaboration and journal impact factor, as well as an increase in the number of studies published in international journals. These observations call for a national strategy to improve oncology research in Saudi Arabia.