Rationale and design of the oral HEMe iron polypeptide Against Treatment with Oral Controlled Release Iron Tablets trial for the correction of anaemia in peritoneal dialysis patients (HEMATOCRIT trial)

Background: The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin (R) ES) administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA)-treated peritoneal dialysis (PD) patients than conventional oral iron supplementation (Ferrogradumet (R))

Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes

Copyright: © 2010 Stimpson et al.Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extrachromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.This work was supported by the Tumorzentrum Heidelberg/Mannheim grant (D.10026941)and by March of Dimes Research Foundation grant #1-FY06-377 and NIH R01 GM069514

Metformin and serious adverse effects

Metformin, a biguanide derivative, has been used in the treatment of type 2 diabetes for nearly 50 years. It acts as an insulin-sensitising agent, lowering fasting plasma insulin concentrations by inducing greater peripheral uptake of glucose, as well as decreasing hepatic glucose output. In 1998, the United Kingdom Prospective Diabetes Study reported that, in overweight patients with type 2 diabetes, treatment with metformin compared with diet alone resulted in statistically significant absolute risk reductions (ARRs) in all-cause mortality (ARR, 7%), diabetes-related deaths (ARR, 5%), any diabetes-related endpoint (ARR, 10%), and macrovascular disease (myocardial infarction, sudden death, angina, stroke, peripheral vascular disease).1 This was achieved without hypoglycaemia or weight gain. As a result, metformin is now regarded as the oral hypoglycaemic agent of choice in the treatment of overweight people with type 2 diabetes

Audit of ticarcillan/clavulanate usage in a large teaching hospital

Aim: To assess compliance with ticarcillin/clavulanate prescribing guidelines, appropriateness of prescribing and to identify any patterns of inappropriate use that may aid in improving prescribing. Method: Patients on ticarcillin/clavulanate were prospectively reviewed over an 8-week period. Data collected included: demographics, diagnosis, hospital or community-acquired infection, specific bacteriology, type of treatment, dose, dose quantity, appropriateness of treatment, and compliance with guidelines. Results: 100 patients on ticarcillin/clavulanate were reviewed and 65% were compliant with guidelines. Treatment was considered appropriate in 76% of patients. Non-compliant/inappropriate usage was most commonly observed in community-acquired pneumonia. Conclusion: This audit indicated widespread use of ticarcillin/clavulanate outside hospital prescribing guidelines, although in some cases, use was considered appropriate

Predictors of decline of residual renal function in new peritoneal dialysis patients

Objective: The aim of this study was to prospectively evaluate the risk factors for decline of residual renal function (RRF) in an incident peritoneal dialysis (PD) population

The effect of oral iron administration on mycophenolate mofetil absorption in renal transplant recipients: a randomized, controlled trial

Background. Oral iron supplements are frequently prescribed to renal transplant recipients in the early posttransplant period. A recent trial in seven healthy volunteers demonstrated a significant 91% reduction in mycophenolate mofetil (MMF) absorption when co-administered with oral iron. However, the effect of iron on MMF absorption in renal transplant patients has not been studied

N-of-1 Randomized Trials to Assess the Efficacy of Gabapentin for Chronic Neuropathic Pain

Objective. The objective of this study was to compare the efficacy of gabapentin with placebo for neuropathic pain at the individual and population levels. Design. This study used an n-of-1 trial methodology with three double-blind, randomized, crossover comparisons of gabapentin with placebo. Setting. This study was carried out at specialist outpatient clinics at two Australian hospitals. Patients. The patients are adults with chronic neuropathic pain. Interventions. Following a dose-finding period, participants underwent three comparisons of 2-week periods on gabapentin (600-1,800 mg per day) and placebo. The dose-finding period was commenced by 112 patients, of whom 39 had no response so they did not enroll, leaving 73 trial participants. Of these, 48 completed and 7 partially completed their trials, and 18 withdrew. Outcome Measures. The five outcome measures were the visual analog scale (0-10) of pain, sleep interference and functional limitation; frequency of adverse events and medication preference. The aggregate response was determined by weighting the response to each measure equally. Results. Of the 55 participants who completed at least one cycle, the aggregate response to gabapentin was better than placebo in 16 (29%), of whom 15 continued gabapentin posttrial. No difference was shown in 38 (69%), and 1 (2%) showed a better response to placebo. Fifteen of these 39 continued gabapentin posttrial. Meta-analysis of the mean scores showed lower mean (standard deviation) scores for gabapentin by 0.8 (0.2) for pain, 0.6 (0.2) for sleep interference, and 0.6 (0.2) for functional limitation. Conclusions. The response rate and mean reduction in symptoms with gabapentin were small. Gabapentin prescribing posttrial was significantly influenced by the trial results