Intra-abdominal dilation of artificial bowel sphincter pressure-regulating balloon: a case report

# The Author(s) 2011. This article is published with open access at Springerlink.com Introduction Fecal incontinence is a debilitating condition with considerable impact on quality of life. The artificial bowel sphincter may be used as a treatment option in severe cases in which no less invasive form of therapy is sufficient

A ‘quiet revolution’? The impact of Training Schools on initial teacher training partnerships

This paper discusses the impact on initial teacher training of a new policy initiative in England: the introduction of Training Schools. First, the Training School project is set in context by exploring the evolution of a partnership approach to initial teacher training in England. Ways in which Training Schools represent a break with established practice are considered together with their implications for the dominant mode of partnership led by higher education institutions (HEIs). The capacity of Training Schools to achieve their own policy objectives is examined, especially their efficacy as a strategy for managing innovation and the dissemination of innovation. The paper ends by focusing on a particular Training School project which has adopted an unusual approach to its work and enquires whether this alternative approach could offer a more profitable way forward. During the course of the paper, five different models of partnership are considered: collaborative, complementary, HEI-led, school-led and partnership within a partnership

Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients

Background: Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated. Methods: We assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D ,75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks. Results: Clinical characteristics of 26 patients were: age 50614 (mean61SD) years, eGFR 41611 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43616 to 84629 nmol/L, p,0.001 and 2.3760.09 to 2.4260.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.868.6 to 7.464.4; p = 0.001). FMD improved from 3.163.3% to 6.163.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 566662123 to 525662058 pg/mL; p = 0.032, ICAM-1, 3.4560.01 to 3.1061.04 ng/mL; p = 0.038 and VCAM-1, 54633 to 42633 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. Conclusion: This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23. Trial Registration: ClinicalTrials.gov NCT0200571

Comparison of a new transcutaneous bilirubinometer (Bilimed®) with serum bilirubin measurements in preterm and full-term infants

<p>Abstract</p> <p>Background</p> <p>The gold standard to assess hyperbilirubinemia in neonates remains the serum bilirubin measurement. Unfortunately, this is invasive, painful, and costly. Bilimed^®, a new transcutaneous bilirubinometer, suggests more accuracy compared to the existing non-invasive bilirubinometers because of its new technology. It furthermore takes into account different skin colours. No contact with the skin is needed during measurement, no additional material costs occur. Our aim was to assess the agreement between the Bilimed^®and serum bilirubin in preterm and term infants of different skin colours.</p> <p>Methods</p> <p>The transcutaneous bilirubin measurements were performed on the infant's sternum and serum bilirubin was determined simultaneously. The agreement between both methods was assessed by Pearson's correlation and by Bland-Altman analysis.</p> <p>Results</p> <p>A total of 117 measurement cycles were performed in 99 term infants (group1), further 47 measurements in 38 preterm infants born between 34 - 36 6/7 gestational weeks (group 2), and finally 21 measurements in 13 preterm infants born between 28 - 33 6/7 gestational weeks (group 3). The mean deviation and variability (+/- 2SD) of the transcutaneous from serum bilirubin were: -14 (+/- 144) μmol/l; -0.82 (+/- 8.4) mg/dl in group 1, +16 (+/- 91) μmol/l;+0.93(+/- 5.3) mg/dl in group 2 and -8 (+/- 76) μmol/l; -0.47 (+/- 4.4) mg/dl in group 3. These limits of agreement are too wide to be acceptable in a clinical setting. Moreover, there was to be a trend towards less good agreement with increasing bilirubin values.</p> <p>Conclusion</p> <p>Despite its new technology the Bilimed^®has no advantages, and more specifically no better agreement not only in term and near-term Caucasian infants, but also in non-Caucasian and more premature infants.</p

ProCOC: The prostate cancer outcomes cohort study

BACKGROUND: Despite intensive research over the last several decades on prostate cancer, many questions particularly those concerning early diagnosis and the choice of optimal treatment for each individual patient, still remain unanswered. The goal of treating patients with localized prostate cancer is a curative one and includes minimizing adverse effects to preserve an adequate quality of life. Better understanding on how the quality of life is affected depending on the treatment modality would assist patients in deciding which treatment to choose; furthermore, the development of prognostic biomarkers that indicate the future course of the illness is a promising approach with potential and the focus of much attention. These questions can be addressed in the context of a cohort study. METHODS/DESIGN: This is a prospective, multi-center cohort study within the canton of Zurich, Switzerland. We will include patients with newly diagnosed localized prostate cancer independently of treatment finally chosen. We will acquire clinical data including quality of life and lifestyle, prostate tissue specimen as well as further biological samples (blood and urine) before, during and after treatment for setup of a bio-bank. Assessment of these data and samples in the follow up will be done during routine controls. Study duration will be at least ten years. Influence of treatment on morbidity and mortality, including changes in quality of life, will be identified and an evaluation of biomarkers will be performed. Further we intend to set up a bio-bank containing blood and urine samples providing research of various natures around prostate cancer in the future. DISCUSSION: We presume that this study will provide answers to pertinent questions concerning prognosis and outcomes of men with localised prostate cancer

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

Incidence and Risk Factors of Recurrence after Surgery for Pathology-proven Diverticular Disease

Contains fulltext : 69776.pdf (publisher's version ) (Closed access)BACKGROUND: Diverticular disease is a common problem in Western countries. Rationale for elective surgery is to prevent recurrent complicated diverticulitis and to reduce emergency procedures. Recurrent diverticulitis occurs in about 10% after resection. The pathogenesis for recurrence is not completely understood. We studied the incidence and risk factors for recurrence and the overall morbidity and mortality of surgical therapy for diverticular disease. METHODS: Medical records of 183 consecutive patients with pathology-proven diverticulitis were eligible for evaluation. Mean duration of follow-up was 7.2 years. Number of preoperative episodes, emergency or elective surgeries, type of operation, level of anastomosis, postoperative complications, persistent postoperative pain, complications associated with colostomy reversal, and recurrent diverticulitis were noted. The Kaplan-Meier method was used to calculate the cumulative probability of recurrence. Cox regression was used to identify possible risk factors for recurrence. RESULTS: The incidence of recurrence was 8.7%, with an estimated risk of recurrence over a 15-year period of 16%. Risk factors associated with recurrence were (younger) age (p < 0.02) and the persistence of postoperative pain (p < 0.005). Persistent abdominal pain after surgery was present in 22%. Eighty percent of patients who needed emergency surgery for acute diverticulitis had no manifestation of diverticular disease prior to surgery. In addition, recurrent diverticulitis was not associated with a higher percentage of emergency procedures. CONCLUSION: Estimated risk of recurrence is high and abdominal complaints after surgical therapy for diverticulitis are frequent. Younger age and persistence of postoperative symptoms predict recurrent diverticulitis after resection. The clinical implication of these findings needs further investigation. The results of this study support the careful selection of patients for surgery for diverticulitis

Glucocorticoid-Treated Mice Are an Inappropriate Positive Control for Long-Term Preclinical Studies in the mdx Mouse

Dmd(mdx) (mdx) mice are used as a genetic and biochemical model of dystrophin deficiency. The long-term consequences of glucocorticoid (GC) treatment on dystrophin-deficient skeletal and heart muscle are not yet known. Here we used systematic phenotyping to assess the long-term consequences of GC treatment in mdx mice. Our investigation addressed not only the effects of GC on the disease phenotype but also the question of whether GCs can be used as a positive control for preclinical drug evaluations.We performed nine pre-clinical efficacy trials (treated N = 129, untreated N = 106) of different durations in 9-to-50-week-old dystrophic mdx mice over a 3-year time period using standardized methods. In all these trials, we used either 1 mg/kg body weight of prednisone or 5 mg/kg body weight of prednisolone as positive controls to compare the efficacy of various test drugs. Data from untreated controls and GC-treated mice in the various trials have been pooled and analyzed to assess the effects of GCs on dystrophin-deficient skeletal and cardiac muscles of mdx mice. Our results indicate that continuous GC treatment results in early (e.g., at 50 days) improvements in normalized parameters such as grip strength, motor coordination and maximal in vitro force contractions on isolated EDL muscle, but these initial benefits are followed by a progressive loss of muscle strength after 100 days. We also found a significant increase in heart fibrosis that is reflected in a significant deterioration in cardiac systolic function after 100 days of treatment.Continuous administration of prednisone to mdx mice initially improves skeletal muscle strength, but further therapy result in deterioration of muscle strength and cardiac function associated with enhanced cardiac fibrosis. These results suggest that GCs may not serve as an appropriate positive control for long-term mdx mouse preclinical trials