Wildlife sequences of islet amyloid polypeptide (IAPP) identify critical species variants for fibrillization

Amyloid can be detected in the islets of Langerhans in a majority of type 2 diabetic patients. These deposits have been associated with β-cell death, thereby furthering diabetes progression. Islet amyloid polypeptide (IAPP) amyloidogenicity is quite variable among animal species, and studying this variability could further our understanding of the mechanisms involved in the aggregation process. Thus, the general aim of this study was to identify IAPP isoforms in different animal species and characterize their propensity to form fibrillar aggregates. A library of 23 peptides (fragment 8–32) was designed to study the amyloid formation using in silico analysis and in vitro assays. Amyloid formation was impeded when the NFLVH motif found in segment 8–20 was substituted by DFLGR or KFLIR segments. A 29P, 14K and 18R substitution were often present in non-amyloidogenic sequences. Non-amyloidogenic sequences were obtained from Leontopithecus rosalia, Tursiops truncatus and Vicugna pacos. Fragment peptides from 34 species were amyloidogenic. To conclude, this project advances our knowledge on the comparative pathogenesis of amyloidosis in type II diabetes. It is conceivable that the additional information gained may help point towards new therapeutic strategies for diabetes patients.     

The systemic lupus erythematosus Tri-nation Study: absence of a link between health resource use and health outcome

OBJECTIVE: Health consumption and health status in SLE in three countries with different health funding structures were compared. METHODS: Seven hundred and fifteen SLE patients (Canada 231, USA 269, UK 215) were surveyed semi-annually over 4 yr for health resource utilization and health status. Cross-country comparisons of (i) cumulative health expenditure (calculated by applying 2002 Canadian prices to resources in all countries) and (ii) disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, SLICC/ACR DI) at study conclusion were performed after adjustment. Missing expenditure and damage data were managed through multiple imputation using best predictive regressions with all available data from all patients as potential covariates. RESULTS: Four hundred and eighty-five patients provided data at study entry and conclusion and at least four resource questionnaires (Canada 162, USA 157, UK 166); 41 died (Canada 13, USA 18, UK 10); 189 withdrew, were lost to follow-up or provided data at entry and conclusion but fewer than four resource questionnaires (Canada 56, USA 94, UK 39). At conclusion, after imputation, in Canada, the USA and the UK respectively, mean cumulative costs per patient over 4 yr [95% confidence interval (CI)] were $15,845 (13,509, 18,182), $20,244 (17,764, 22,724) and $17,647 (15,557, 19,737) and mean changes in SLICC/ACR DI were 0.49 (0.39, 0.60), 0.63 (0.52, 0.74) and 0.48 (0.39, 0.57). After adjustment for baseline differences, on average (95% CI), Canadian and British patients utilized 20% (8%, 32%) and 13% (1%, 24%) less resources than patients in the USA respectively, but experienced similar health outcomes. CONCLUSION: Despite patients in the USA incurring higher health expenditures, they did not experience superior health outcomes.     

Effects of insulin resistance and insulin secretion on the efficacy of interventions to retard development of type 2 diabetes mellitus: the DA Qing IGT and Diabetes Study

OBJECTIVE: To investigate the effects of insulin resistance (IR) and insulin secretion (IS) on the development of diabetes mellitus in individuals with impaired glucose tolerance (IGT) who underwent lifestyle interventions. METHODS: 284 out of 577 individuals with IGT identified by population-based screening in Da Qing, China, who were randomized to undergo diet change and/or increased physical activity had baseline fasting and 2 h post-load insulin determinations. They were followed for 6 years for the development of diabetes. IR and IS were assessed using calculated indices based on fasting plasma insulin and glucose. The interactions of IR, IS, obesity and plasma glucose and the effects of the lifestyle interventions were evaluated using Cox Proportional Hazards analysis. RESULTS: Both IR and IS were significantly associated with the development of diabetes. Lifestyle interventions were more effective in those with lower IT and higher IS at baseline. Diet plus exercise interventions resulted in significantly lower incidence of diabetes, even after controlling for IR, IS, BMI and 2hrPG. CONCLUSION: Both IR and beta-cell function were predictors of diabetes in Chinese with IGT. Lifestyle intervention reduced the incidence of DM and these interventions were more effective in those with less IR.     

The Fetal Safety of Hydrocortisone-Pramoxine (Proctofoam-HC) for the Treatment of Hemorrhoids in Late Pregnancy

ObjectiveFetal safety has never been studied for any drug used in the treatment of hemorrhoids. Proctofoam-HC is a combination of a corticosteroid and a local anaesthetic that is proven effective for the treatment of hemorrhoids. The objective of this study was to assess prospectively the fetal safety of third trimester exposure to Proctofoam-HC.MethodsIn a multicentre study, 240 women exposed to Proctofoam-HC in the third trimester and a similar number of control pregnant women were followed up postnatally.ResultsWhen compared to controls exposure to Proctofoam-HC was not associated with any adverse fetal effects on birth weight, gestational age, rates of prematurity, or pre- or postnatal complications.ConclusionProctofoam-HC is safe to use in the treatment of hemorrhoids in late pregnancy.     

Pacemaker Lead Fracture Due to Twiddler's Syndrome

The authors report a case of pacemaker twiddler's syndrome that led to lead fracture and loss of consciousness. The role of chest X rays in the diagnosis of pacemaker twiddler's syndrome as well as the management of the syndrome is discussed.     

血小板激活因子对大鼠脑损伤的实验研究

目的研究血小板激活因子(platelet-activatingfactor,PAF)在缺血性脑损伤中的致病作用。方法将PAF或含0.25%的牛血清白蛋白(BSA)生理盐水注入大鼠右侧颈总动脉,检测给药后即刻和40min的平均动脉压(MAP)和脑血流(CBF);用干湿重量法检测给药侧大鼠脑水含量变化;观察大鼠脑组织病理学改变。结果给药后即刻和40min对照组与PAF组MAP、CBF比较,两3者差异均显著(P<0.05)。两组脑组织水含量相比(P<0.01),差异也十分显著。对照组神经组织结构、毛细血管均未见异常改变。PAF组光镜下仅见小血管周围间隙扩张。电镜下皮层超微结构变化明显。结论PAF在诱发大鼠系统性低血压的同时降低脑血流,破坏血脑屏障,损伤神经细胞和其他神经组织。     

Urgent neurology out-patient referrals from primary health care physicians

We retrospectively analysed patients seen in a rapid referral clinic to identify those with abnormalities genuinely requiring urgent assessment, and to evaluate the impact of the clinic on routine services. After advertising the availability of the service, 25% of telephone referrals from primary-care physicians led to identification of patients considered suitable for urgent evaluation. We assessed 350 patients over an 18-month period. After neurological review, relevant abnormalities were identified in 73%, and 33% were considered to have warranted urgent assessment. In addition, 74% required radiological evaluation and 14% had a neurophysiological procedure; 19.4% were admitted on the same day, 13% underwent CSF analysis and 34% required some form of therapeutic intervention. In retrospect, patients with a clinical history of > 11 days rarely warranted urgent referral. Visual failure and diplopia provided the highest correlation with patients deemed to require urgent assessment, and syncope and headache the lowest. Despite the number of patients reviewed, no effect was demonstrated on waiting times for standard out-patient review.