Skin microvascular vasodilatory capacity in offspring of two parents with Type 2 diabetes

Aims<br/> Microvascular dysfunction occurs in Type 2 diabetes and in subjects with fasting hyperglycaemia. It is unclear whether this dysfunction relates to dysglycaemia. This study investigated in normogylcaemic individuals whether a genetic predisposition to diabetes, or indices of insulin resistance including endothelial markers, were associated with impaired microvascular function.<br/> Methods<br/> Maximum microvascular hyperaemia to local heating of the skin was measured using laser Doppler flowmetry in 21 normoglycaemic subjects with no family history of diabetes (Group 1) and 21 normoglycaemic age, sex and body mass index-matched offspring of two parents with Type 2 diabetes (Group 2). <br/>Results<br/> Although Group 2 had normal fasting plasma glucose and glucose tolerance tests, the 120-min glucose values were significantly higher at 6.4 (5.3-6.6) mmol/l (median (25th-75th centile)) than the control group at 4.9 (4.6-5.9) mmol/l (P=0.005) and the insulinogenic index was lower at 97.1 (60.9-130.8) vs. 124.0 (97.2-177.7) (P=0.027). Skin maximum microvascular hyperaemia (Group 1: 1.56 (1.39- 1.80) vs. Group 2: 1.53 (1.30-1.98) V, P=0.99) and minimum microvascular resistance which normalizes the hyperaemia data for blood pressure (Group 1: 52.0 (43.2-67.4) vs. Group 2: 56.0 (43.7-69.6) mmHgN, P=0.70) did not differ in the two groups. Significant positive associations occurred between minimum microvascular resistance and indices of the insulin resistance syndrome; plasminogen activator inhibitor type 1 (R-s=0.46, P=0.003), t-PA (R-s=0.36, P=0.03), total cholesterol (R-s=0.35, P=0.02), and triglyceride concentration (R-s=0.35, P=0.02), and an inverse association with insulin sensitivity (R-s=-0.33, P=0.03).<br/> Conclusions<br/> In normoglycaemic adults cutaneous microvascular vasodilatory capacity is associated with features of insulin resistance syndrome, particularly with plasminogen activator inhibitor type 1. A strong family history of Type 2 diabetes alone does not result in impairment in the maximum hyperaemic response

Kinematically Complete Experiment on Transfer Excitation in Intermediate-Energy p + He Collisions

We have performed a kinematically complete experiment on transfer excitation in intermediate-energy proton-helium collisions. The differential cross sections were compared to double excitation data and a nonperturbative time-dependent calculation. This comparison reveals the importance of dynamic couplings between the motion of the heavy nuclei and electronic transitions and/or electron-electron correlation effects

What drives the 'August effect'?: an observational study of the effect of junior doctor changeover on out of hours work

Objective: To investigate whether measurements of junior doctor on-call workload and performance can clarify the mechanisms underlying the increase in morbidity and mortality seen after junior doctor changeover: the ‘August effect’. Design: Quantitative retrospective observational study of routinely collected data on junior doctor workload. Setting: Two large teaching hospitals in England. Participants: Task level data from a wireless out of hours system (n = 29,885 requests) used by medical staff, nurses, and allied health professionals. Main outcome measures: Number and type of tasks requested by nurses, time to completion of tasks by junior doctors. Results: There was no overall change in the number of tasks requested by nurses out of hours around the August changeover (median requests per hour 15 before and 14 after, p = 0.46). However, the number of tasks classified as urgent was greater (p = 0.016) equating to five more urgent tasks per day. After changeover, doctors took less time to complete tasks overall due to a reduction in time taken for routine tasks (median 74 vs. 66 min; p = 3.9 × 10−9). Conclusion: This study suggests that the ‘August effect’ is not due to new junior doctors completing tasks more slowly or having a greater workload. Further studies are required to investigate the causes of the increased number of urgent tasks seen, but likely factors are errors, omissions, and poor prioritization. Thus, improved training and quality control has the potential to address this increased duration of unresolved patient risk. The study also highlights the potential of newer technologies to facilitate quantitative study of clinical activity

Projectile Angular-Differential Cross Sections for Transfer and Transfer Excitation in Proton Collisions with Helium

Projectile angular-differential cross sections for single-transfer and transfer excitation have been calculated with the two-center extension of the nonperturbative basis generator method for 5-200 keV proton-helium collisions. The calculations are based on the independent electron model, and the eikonal approximation has been used to extract angular-differential cross sections from impact-parameter-dependent transition amplitudes. The present results are compared with experimental and previous theoretical data where available. In particular, we consider the ratio of transfer excitation to single capture versus double excitation to single excitation at intermediate energies. An experimentally observed structure in this ratio at a scattering angle about 0.5 mrad is qualitatively reproduced, while a previous classical evaluation failed in this respect. Therefore, we conclude that this structure is caused by quantum mechanical heavy-particle-electron couplings

Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases - a longitudinal study.

INTRODUCTION: Patients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects. METHODS: This observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4-8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients. RESULTS: Of 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30 %) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81 % of patients, and 87 % became seropositive. After 1 year, 67 % of vaccinated compared with 90 % of observed patients were seropositive (p < 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections. CONCLUSIONS: PPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections

Translating research into practice in Leeds and Bradford (TRiPLaB): a protocol for a programme of research

Background The National Institute for Health Research (NIHR) has funded nine Collaborations for Leadership in Applied Health Research and Care (CLAHRCs). Each CLAHRC is a partnership between higher education institutions (HEIs) and the NHS in nine UK regional health economies. The CLAHRC for Leeds, York, and Bradford comprises two 'research themes' and three 'implementation themes.' One of these implementation themes is Translating Research into Practice in Leeds and Bradford (TRiPLaB). TRiPLaB aims to develop, implement, and evaluate methods for inducing and sustaining the uptake of research knowledge into practice in order to improve the quality of health services for the people of Leeds and Bradford. Methods TRiPLaB is built around a three-stage, sequential, approach using separate, longitudinal case studies conducted with collaborating NHS organisations, TRiPLaB will select robust innovations to implement, conduct a theory-informed exploration of the local context using a variety of data collection and analytic methods, and synthesise the information collected to identify the key factors influencing the uptake and adoption of targeted innovations. This synthesis will inform the development of tailored, multifaceted, interventions designed to increase the translation of research findings into practice. Mixed research methods, including time series analysis, quasi-experimental comparison, and qualitative process evaluation, will be used to evaluate the impact of the implementation strategies deployed. Conclusion TRiPLaB is a theory-informed, systematic, mixed methods approach to developing and evaluating tailored implementation strategies aimed at increasing the translation of research-based findings into practice in one UK health economy. Through active collaboration with its local NHS, TRiPLaB aims to improve the quality of health services for the people of Leeds and Bradford and to contribute to research knowledge regarding the interaction between context and adoption behaviour in health services

Role of vasopressin in the treatment of anaphylactic shock in a child undergoing surgery for congenital heart disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>The incidence of anaphylactic reactions during anesthesia is between 1:5000 and 1:25000 and it is one of the few causes of mortality directly related to general anesthesia. The most important requirements in the treatment of this clinical condition are early diagnosis and maintenance of vital organ perfusion. Epinephrine administration is generally considered as the first line treatment of anaphylactic reactions. However, recently, new pharmacological approaches have been described in the treatment of different forms of vasoplegic shock.</p> <p>Case presentation</p> <p>We describe the case of a child who was undergoing surgery for ventricular septal defect, with an anaphylactic reaction to heparin that was refractory to epinephrine infusion and was effectively treated by low dose vasopressin infusion.</p> <p>Conclusion</p> <p>In case of anaphylactic shock, continuous infusion of low-dose vasopressin might be considered after inadequate response to epinephrine, fluid resuscitation and corticosteroid administration.</p

Alterations in Retinal Microvascular Geometry in Young Type 1 Diabetes

OBJECTIVE - To describe retinal microvascular geometric parameters in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Patients with type 1 diabetes (aged 12-20 years) had clinical assessments and retinal photography following standardized protocol at a tertiary-care hospital in Sydney. Retinal microvascular geometry, including arteriolar and venular tortuosity, branching angles, optimality deviation, and length-to-diameter ratio (LDR), were measured from digitized photographs. Associations of these geometric characteristics with diabetes duration, A1C level, systolic blood pressure (SBP), and other risk factors were assessed. RESULTS - Of 1,159 patients enrolled, 944 (81.4%) had gradable photographs and 170 (14.7%) had retinopathy. Older age was associated with decreased arteriolar (P = 0.024) and venular (P = 0.002) tortuosity, and female subjects had larger arteriolar branching angle than male subjects (P = 0.03). After adjusting for age and sex, longer diabetes duration was associated with larger arteriolar branching angle (P ≤ 0.001) and increased arteriolar optimality deviation (P = 0.018), higher A1C was associated with increased arteriolar tortuosity (>8.5 vs. ≤8.5%, P = 0.008), higher SBP was associated with decreased arteriolar LDR (P = 0.002), and higher total cholesterol levels were associated with increased arteriolar LDR (P = 0.044) and decreased venular optimality deviation (P = 0.044). These associations remained after controlling for A1C, retinal vessel caliber, and retinopathy status and were seen in subjects without retinopathy. CONCLUSIONS - Key diabetes-related factors affect retinal microvascular geometry in young type 1 diabetes, even in those without evidence of retinopathy. These early retinal alterations may be markers of diabetes microvascular complications. © 2010 by the American Diabetes Association.link_to_OA_fulltex