Calcineurin Inhibitor Withdrawal from Sirolimus-Based Therapy in Kidney Transplantation: A Systematic Review of Randomized Trials

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function, however, it also carries risk of acute rejection. We conducted a systematic review of randomized trials that involved CNI withdrawal from a sirolimus-based immunosuppressive regimen. The search strategy yielded six trials (n = 1047 patients) reported in eight publications. CNI withdrawal from sirolimus-based therapy, was associated with an increased risk of acute rejection (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87; 95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p = 0.76) were similar in both groups at 1 year. Hypertension was significantly reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p = 0.0006). CNI withdrawal from sirolimus-based therapy is associated with an increased risk of acute rejection in the short term with a significant improvement in renal function and a reduction in hypertension. Longer follow-up is needed to determine if these changes will result in a significant improvement in patient and graft survival.     

The interleukin-5 messenger RNA expression in a patient with idiopathic hypereosinophilic syndrome

Interleukin-5 has a specific role in various eosinophilic activities. It is the predominant cytokine produces by activated T-lymphocytes isolated from patients with idiopathic hypereosinophilic syndrome. We studied a young patient suffering from idiopathic hypereosinophilic syndrome who presented with Horner's syndrome, peripheral neuropathy and skin ulcers. The IL-5 gene expression by CD4⁺ T-lymphocytes and the peripheral eosinophil count were raised. The skin ulcers continued to deteriorate despite a swift reduction of the IL-5 gene expression and peripheral eosinophil count following systemic corticosteroid treatment. We suggest that peripheral eosinophilia may not be responsible for the damage in skin lesions and more aggressive treatment may be required.     

Randomised controlled trial of ondansetron in smoking cessation

A double-blind, placebo controlled trial was undertaken to examine the effect of the 5-HT₃ antagonist, ondansetron .25 mg bd on cigarette withdrawal symptoms and on proportion of individuals maintaining continuous abstinence for 4 weeks in a smoking treatment programme. A total of 111 smokers were allocated to active or placebo conditions and began taking their study medication 2 weeks before the quit date. They attended the smokers clinic for weekly group treatment sessions. The results showed no evidence for less severe withdrawal symptoms or improved abstinence rates in the active medication group. They suggest that inhibiting 5-HT₃ activity is not an effective method of controlling nicotine withdrawal or helping smokers to stop.     

Heterogeneity of FeNO response to inhaled steroid in asthmatic children

Background Nitric oxide in exhaled air is regarded as an inflammation marker, and may be used to monitor the anti‐inflammatory control from inhaled corticosteroids (ICSs). However, this response to ICSs exhibits a heterogeneous pattern. Objective The study aimed to describe the independent variables associated with the heterogeneity in the response of exhaled nitric oxide to ICSs. Methods Exhaled nitric oxide (FeNO), lung function, bronchial hyper‐responsiveness (BHR), specific IgE to common inhalant allergens, blood eosinophils, other atopic manifestations and variants in nitric oxide synthethase 1 (NOS1) gene were studied in a double‐blind, placebo‐controlled crossover comparison of budesonide (BUD) Turbohaler 1600 mcg daily vs. placebo in asthmatic schoolchildren. Results Forty children were included in the study from a screening of 184 asthmatic children with moderately persistent asthma, well controlled on regular BUD 400 mcg daily: 20 children with normal FeNO and 20 with raised FeNO. FeNO, BHR and forced expiratory volume in 1 s improved significantly after BUD 1600 mcg (BUD1600). However, FeNO after ICS treatment exhibited a Gaussian distribution and FeNO was significantly raised in 15 children. Allergy and BHR, but none of the other independent variables under study were significantly related to FeNO after BUD1600. Conclusion Exhaled nitric oxide exhibited a heterogeneous response to ICS in asthmatic schoolchildren. Allergy and BHR were driving FeNO level independently of high‐dose steroid treatment. This should be considered when using FeNO for steroid dose titration and monitoring of ICS anti‐inflammatory control in asthmatic children.     

儿童退缩和同伴关系的相关

目的：用元分析方法对近20年关于儿童退缩和同伴关系相关的研究结果进行总结。方法：用多水平分析技术对儿童退缩和同伴接受的相关、退缩和同伴拒绝相关的研究结果进行总结分析。结果：儿童退缩和同伴接受之间有显著的负相关关系，退缩和同伴拒绝之间有低度的非负相关关系，各研究结果之间的变异显著。结论：退缩导致儿童不良的同伴关系。     

Recent developments in molecular action of antihormones

 Antihormones are by definition antagonists of steroid hormone action. They interact with the ligand binding domains of steroid hormone receptors and competitively inhibit the action of the receptors by mechanisms that are not quite understood. In certain cases antihormones also exhibit agonistic activity especially in connection with certain naturally occurring receptor mutants. These observations together with findings of indiscriminate interaction of antihormones with several classes of steroid receptors have necessitated a search of more effective and reliable antihormones. Recent advances in the resolution of the crystal structure of the ligand binding domains of certain members of the steroid receptor family and identification of non-liganded activation of steroid receptors have produced considerable information that can be harnessed into a fruitful search for a new generation of antihormones. Received: 19 June 1997 / Accepted: 10 October 1997     

Renal metabolism of corticosteroid hormones

Summary IK and STF from male and female rats have been used to study in vitro the renal metabolism of B. in male rat tissue four lipid soluble metabolites (I–IV) have been found, I+II being more polar and III+IV being less polar than B. I and II have been identified as 11-dehydro-20-hydroxy-B and 20-hydroxy-B. The structure of III and IV remains to be determined. Renal tissue from female rats produced predominantly III indicating sexual variations of steroid metabolism in kidneys. — The literature has been reviewed which documents that the kidneys in addition to B metabolize A, cortisol, progesterone and other corticosteroids.

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Abbreviations A Aldosterone - B Corticosterone - Alb Albumin - CS Corticosteroids - MCS/GCS Mineralo-/gluco-CS - IK Isolated (perfused) kidney - STF Suspended tubular fragments Supported by Deutsche Forschungsgemeinschaft Hi 97/16     

Expert opinion on the management and follow-up of uveitis patients during SARS-CoV-2 outbreak

ABSTRACT

Introduction

Routine medical and ophthalmic care is being drastically curtailed in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Uveitis patients require particular attention because of their theoretical risk of viral infection, in the context of therapeutic immunosuppression.