Corticosteroid cross-reactions: an alternative view

An alternative view of corticosteroid cross-reactivity is proposed, based on 2 immune recognition sites on the corticosteroid molecule, 1 influenced by C 6/9 substitution and 1 by C 16/17 substitution. A case report is adduced in support of such a hypothesis.     

吸入激素联合缓释茶碱与β_2-受体激动剂治疗儿童哮喘比较

目的比较吸入糖皮质激素(ICS)联合缓释茶碱(SRT)与ICS联合长效β2-受体激动剂(LABA)治疗中、重度儿童哮喘的疗效和安全性。方法141例4—14岁中、重度哮喘患者随机分成两组。A组73例,吸入丙酸氟替卡松气雾剂(FP),同时口服茶碱缓释片舒弗美。B组68例,沙美特罗/丙酸氟替卡松(SM／FP)干粉剂吸入治疗,疗程12周。比较A、B两组的临床疗效及安全性。结果治疗后两组患者晨间最大呼气峰流速(PEFam)与第1秒时间肺活量(FEV1)占预计值的百分比明显升高(P<0．01),两组间比较无显著性差异(P>0．05)。日、夜间症状评分较治疗前均显著降低(P<0．01),两组间比较无显著性差异(P> 0．05)。两组患者使用快速缓解药物(沙丁胺醇气雾剂)的揿数较治疗前均明湿减少(P<0．01),两组间比较无显著性差异(P>0．05)。结论ICS联合SRT治疗中、重度儿童哮喘,其疗效相似于ICS联合LABA,无严重不良反应。     

High single-dose alternate-day corticosteroid regimens in treatment of polymyositis

Summary High single-dose alternate-day prednisolone therapy (ADT) was compared with daily-dose prednisolone therapy (DDT) for treatment of polymyositis. Thirty patients with polymositis were treated with ADT for an average of 33.9 months. The combined number of improvements was 21 out of 30, a response rate of 70%. Side-effects were very rare and mild. On the other hand, 9 of 17 patients treated with DDT for an average 18.5 months improved, a response rate of 53%. The incidence of side-effects was strikingly higher than with ADT. ADT is therefore strongly advocated for treatment of polymyositis to avoid infectious complications and lessen cushingoid side-effects.     

A stochastic version of corticosteriod pharmacogenomic model

The purpose of this study was to develop a stochastic version of corticosteriod fifth generation pharmacogenomic model. The Gillespie algorithm was used to generate the independent time courses of the receptor messenger RNA (mRNA). Initial parameters for the stochastic simulation were adapted from the study by Jin et al. The result obtained from the proposed stochastic model showed an overall agreement with the deterministic fifth generation model. This study suggested that because the stochastic model takes into account the "noise" nature of gene regulation, it would have potential application in pharmacogenomic modeling.     

Inhaled and intravenous corticosteroids both attenuate chlorine gas-induced lung injury in pigs

BACKGROUND: The accidental release of chlorine gas is a constant threat in urban areas. The purpose of this randomized, blinded, controlled experiment was to examine the effects of post-injury administration of inhaled or intravenous corticosteroid in chlorine gas-injured pigs followed for 23 h. METHODS: Anaesthetized, ventilated pigs (n = 24) in the prone position were exposed to chlorine gas (400 parts per million in air) (1160 mg/m3) for 15 min, then randomly allocated to receive inhaled budesonide (BUD) and intravenous placebo, intravenous betamethasone (BETA) and inhaled placebo or inhaled and intravenous placebo. Haemodynamics, gas exchange and lung mechanics were evaluated for 23 h after exposure to chlorine gas. RESULTS: Airway and pulmonary artery pressures increased and arterial oxygenation fell sharply (from 13.5 +/- 0.8 to 6.7 +/- 0.9 kPa, P < 0.001) after chlorine gas exposure. These immediate changes were followed by a gradual improvement over 5-7 h to a stable level of dysfunction for the rest of the experiment in placebo animals. Arterial oxygen tension, pulmonary vascular resistance and airway pressure recovered faster and more completely in the budesonide and betamethasone groups than in the placebo group (P < 0.01). Lung wet weight to dry weight ratios were greater in the placebo group than in the budesonide and betamethasone groups (6.34 +/- 0.59 vs. 5.56 +/- 0.38 and 5.53 +/- 0.54, respectively, P < 0.05). There was a trend towards lower histological injury scores compared with placebo in animals that received budesonide (P = 0.05) or betamethasone (P = 0.07). CONCLUSION: Treatment of chlorine gas lung injury with nebulized budesonide or intravenous betamethasone had similar positive effects on recovery of lung function.     

Bone mineral density in women with sarcoidosis

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Almost any organs of the body, but mostly the lungs, are involved. Bone mineral density (BMD) can be affected directly or indirectly in chronic granulomatous systemic diseases such as sarcoidosis. The aim of our study was to evaluate BMD in premenopausal and postmenopausal sarcoidosis patients with or without prednisone treatment and to compare their BMD values with those of a control group having the same menopausal status. Thirty-five premenopausal women (18 untreated, 8 treated, and 9 controls) and 21 postmenopausal women (5 untreated, 5 treated, and 11 controls) were included in the study. All of the patients had a histologically proven diagnosis and were being followed-up at the Sarcoidosis Outpatient Clinic of our unit. BMD of the lumbar (L) spine and femoral neck was measured by dual-energy absorptiometry (DEXA). The subgroups of premenopausals and postmenopausals were compared separately. Comparison among the groups was performed by using analysis of variance. Age, duration of the disease, and body mass index were comparable in treated, untreated, and control subgroups of the pre- and postmenopausal groups, and the subgroups of postmenopausals had comparable durations since menopause. For premenopausals, BMD values at L1–4 were not significantly different among the subgroups (0.920 ± 0.08g/cm², 0.801 ± 0.09g/cm², and 0.910 ± 0.05g/cm², for untreated, treated, and controls, respectively). However, the BMD value at the femoral neck in treated patients (0.921 ± 0.1g/cm²) was significantly lower than the values in untreated patients (1.080 ± 0.2g/cm²; P 0.01) and in controls (1.028 ± 0.17g/cm²; P 0.05). For postmenopausals, the BMD value at L1–4 in controls (1.019 ± 0.07g/cm²) was significantly higher than the values in untreated patients (0.783 ± 0.01g/cm²) and in treated patients (0.751 ± 0.08g/cm²; P 0.001 for both). The BMD value at the femoral neck in controls (0.890 ± 0.1g/cm²) was higher than the values in untreated patients (0.745 ± 0.08g/cm²) and treated patients (0.747 ± 0.1g/cm²), but the difference was not statistically significant (P = 0.06). We concluded that sarcoidosis patients, especially postmenopausal patients with corticosteroid treatment, may have an increased risk of bone mineral loss. Large-scale studies are warranted in order to delineate the exact roles of the disease itself, menopausal status, and corticosteroid treatment in this bone mineral loss.     

The biology and management of subglottic hemangioma: past, present, future

OBJECTIVES/HYPOTHESIS: Objectives were 1) to review the presentation, natural history, and management of subglottic hemangioma; 2) to assess the affect of five variables (age, gender, degree of subglottic narrowing, location and extent of subglottic hemangioma, and lack or presence of other hemangioma) and the outcome of six different treatment modalities (conservative monitoring, corticosteroid, laser surgery, tracheotomy, laryngotracheoplasty, and interferon) in the management of subglottic hemangioma; and 3) to present specific guidelines to help determine the best possible treatment modality at the time of initial presentation. STUDY DESIGN: Retrospective review in the setting of three tertiary care pediatric medical centers. METHODS: Methods included 1) extensive review of the literature; 2) a systematic review with respect to age, gender, presentation, associated medical problems, location and degree of subglottic narrowing, initial treatment, need for subsequent treatments, outcome, complications, and prognosis; and 3) statistical analysis to determine the effect of five variables (age, gender, degree of subglottic narrowing, location and extent of subglottic hemangioma, and lack or presence of other hemangioma) and the outcome of six different treatment modalities (conservative monitoring, corticosteroid, laser surgery, tracheotomy, laryngotracheoplasty, and interferon). RESULTS: In all, 116 patients with a mean age of 4.7 months were treated. The most common location of subglottic hemangioma was the left side. The range of subglottic narrowing was 10% to 99% (mean percentage, 65%). Twenty-six patients (22%) were managed with a single treatment modality, which included conservative monitoring (n = 13), corticosteroid (n = 11), and tracheotomy (n = 2). Ninety patients (78%) required multimodality treatments. Overall, the treatments included conservative monitoring (n = 13), corticosteroid (n = 100), tracheotomy (n = 32), CO2 laser (n = 66), interferon (n = 5), and laryngotracheoplasty (n = 25). Complication rates included the following: conservative monitoring (none), corticosteroid (18%), tracheotomy (none), CO2 laser (12%), interferon (20%), and laryngotracheoplasty (20%). The following variables showed statistical significance in the outcome of different treatment modality: 1) degree of subglottic narrowing (P < .001), 2) location of subglottic hemangioma (P < .01), and 3) presence of hemangioma in other areas (P < .005). Gender (P > .05) and age at the time of presentation (P > .06) did not show any statistical significance on the outcome of the treatments. CONCLUSION: Each patient should be assessed comprehensively, and treatment should be individualized based on symptoms, clinical findings, and experience of the surgeon. The authors presented treatment guidelines in an attempt to rationalize the management of subglottic hemangioma and to help determine the best possible treatment modality at the time of initial presentation.