The intelligent use of systemic glucocorticoids in rheumatoid arthritis

Glucocorticoids (GC) have potent anti-inflammatory and immunomodulatory effects and are widely used in the management of rheumatoid arthritis in combination with other disease-modifying anti-rheumatoid drugs. Concern about the risk of adverse effects may be to some extent misplaced as low to moderate doses of GC have different mechanisms of action and risk profiles compared with high doses. This review discusses the current understanding about the different modes of action of GC, their strong disease-modifying properties and the efforts at improving the therapeutic ratio of GC through the development of new drugs which promise greater safety such as selective GC receptor agonists, liposomal GC and modified-release (MR) prednisone.     

The clinical use of films in psychotherapy

This article discusses the ways in which client attitudes about mental illness, psychotherapy, and therapists are shaped by contemporary films. Five common myths about mental illness that are promulgated by films are discussed, and the potential applications of films in psychotherapy are reviewed. Numerous examples of films relevant to psychotherapy are presented, and a clinical vignette is used to demonstrate how films can enrich and expand psychotherapy.     

Endangerment of the brain by glucocorticoids: Experimental and clinical evidence

In this paper, we review studies suggesting that elevated glucocorticoids increase the susceptibility of the brain to adverse events. The events themselves can be varied, and their effects on the brain can also differ. The common feature is that glucocorticoids may modulate the likelihood (risk) of damage or malfunction following adversity. In the first part of our paper, we describe experimental studies on the brain's cellular response to neurotoxins that support this thesis; in the second, we survey clinical evidence that indicate that glucocorticoids may endanger the brain's response to adverse social events. We suggest that there may be common features in the experimental and clinical findings. To begin, however, we draw attention to some of the properties of the hypothalamic-pituitary-adrenal (HPA) axis that seem relevant to our discussion.     

The clinical use of the MSLT and MWT

The studies examined in this review indicate that the MSL is sensitive to conditions expected to increase sleepiness. MSL are generally lower following sleep loss, following use of sedating medications, during wakefulness in the late night or early morning hours, and among patients with sleep disorders associated with excessive sleepiness such as narcolepsy or obstructive sleep apnea. However, the wide range in MSL makes it difficult to establish a specific threshold value for excessive sleepiness or to discriminate patients with sleep disorders from non-patients. Some of this variation may be attributable to methodological differences and some may be attributable to individual differences in sleep tendency (e.g., related to age). The studies analyzed in this review indicate that the MSL on both the MSLT and MWT does not discriminate well between patients with sleep disorders and normal populations. This is due to large SD as well as floor or ceiling effects in the tests. However, the MSL shows appropriate change from initial testing to subsequent testing following treatment or manipulations intended to alter sleepiness or alertness. Additionally the presence of two or more SOREMPs on the MSLT is a common finding in narcolepsy patients. However, SOREMPs are not exclusive to narcolepsy patients but are frequent in untreated sleep apnea     

The use of microarray technologies in clinical oncology

Purpose

Based on previous studies that demonstrated the safety profile and preliminary clinical activity of prostate specific antigen (PSA) targeted therapeutic vaccines, as well as recent laboratory data supporting the value of the addition of co-stimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM?) to these vaccines, we conducted a Phase I study to evaluate the safety and immunogenicity of a novel vaccinia and fowlpox vaccine incorporating the PSA gene sequence and TRICOM.

Methods

In this study, ten patients with androgen independent prostate cancer with or without metastatic disease were enrolled. Patients were treated with 2 × l0⁸ pfu of a recombinant vaccinia virus vaccine (PROSTVAC-V) followed by 1 × 10⁹ pfu of the booster recombinant fowlpox virus (PROSTVAC-F) both with gene sequences for PSA and TRICOM. The mean age of patients enrolled in the study was 70 (range 63 to 79). The mean PSA at baseline was 434 (range 9 – 1424).

Results

There were no deaths, and no Grade 3 or 4 adverse events. The most commonly reported adverse events, regardless of causality, were injection site reactions and fatigue. One serious adverse event (SAE) occurred that was unrelated to vaccine; this patient developed progressive disease with a new sphenoid metastasis. PSA was measured at week 4 and week 8. Four patients had stable disease (with less than 25% increase in PSA) through the week 8 study period. Anti-PSA antibodies were not induced with therapy: however, anti-vaccinia titers increased in all patients.

Conclusion

This study demonstrated that vaccination with PROSTVAC-V and PROSTVAC-F combined with TRICOM is well-tolerated and generated an immune response to vaccinia. Therefore, PROSTVAC-VF/TRICOM represents a feasible therapeutic approach for further phase II and III study in patients with prostate cancer.     

The clinical use of gabapentin in bipolar spectrum disorders

BACKGROUND: with increasing awareness of lithium's limitations, several new anticonvulsants had been tested for their mood stabilisation during recent years. Among the innovative third generation mood stabilizing anticonvulsants, gabapentin (GBP) seems to have a broad spectrum of efficacy, although no certain data are available as to its efficacy and use in clinical practice. Accordingly, an extensive review on this subject has been carried out. METHODS: A computer-generated search of the biomedical literature and abstract books of the more important scientific psychiatric congresses until June 2000 was undertaken to identify all pertinent case reports, case series and studies of GBP as monotherapy or adjunctive therapy in mood disorders. We identified 40 open-label studies on the use of GBP in at least 600 patients with bipolar disorder (BP), manic, depressed, or mixed episodes and unipolar depression and four controlled studies. RESULTS: The 40 open-label studies and two of the controlled trials suggested that GBP may have a role as adjunctive agent in the treatment of patients with bipolar disorders particularly when complicated by co-morbid anxiety disorder or substance abuse. GBP is usually very well tolerated and has no pharmacological interference with other mood stabilisers. However, in the other two double-blind studies GBP has not been found to be efficacious in the treatment of refractory mania or refractory bipolar depression. CONCLUSIONS: Although failing to show clear antimanic efficacy in randomized trials, gabapentin still remains a clinically useful agent when it comes to combination treatment in refractory and co-morbid patients.     

The use of computers in teaching clinical laboratory science

The Transfusion Medicine Tutor (TMT) has been designed to study the use of computers in teaching concepts and problem- solving skills important in the field of clinical laboratory science. This system provides students with an opportunity to gain experience by solving a wide range of actual cases, and coaches these students when they are having difficulties. This system is designed specifically to detect and respond to a variety of errors that students may make while solving cases, and to suggest more advanced problem-solving methods when appropriate. This article describes the concepts behind the design of TMT.     

糖皮质激素治疗胎粪吸入综合征疗效和安全性的Meta分析

目的评价糖皮质激素治疗胎粪吸入综合征（MAS）的疗效及安全性。方法检索PubMed、MEDLINE、EMBASE、EBSCOhost、Cochrane图书馆、Cochrane临床对照试验库（CENTRAL）、Ovid、中国生物医学文献数据库、万方数据库和维普中文科技期刊数据库,检索时间均从建库至2010年12月,并辅以手工检索,获得糖皮质激素治疗MAS的RCT文献。依据随机方法、分配隐藏、盲法、结果数据的完整性、选择性报告研究结果和其他偏倚来源进行文献偏倚评价。采用RevMan5.0.23软件进行Meta分析,根据异质性结果选择相应的效应模式分析;无法进行Meta分析时采用描述性分析。结果共检索到1012篇文献,符合纳入标准的5篇RCT文献（n=295）进入Meta分析。文献偏倚评价结果显示,存在低度和高度偏倚风险的文献各1篇,3篇文献存在中度偏倚风险。Meta分析结果显示,糖皮质激素能显著缩短住院时间（MD=-5.42,95%CI：-7.38～-3.45,P〈0.0001）,减少败血症发生率（OR=0.33,95%CI：0.12～0.78,P=0.01）。亚组分析结果显示,布地奈德混悬液雾化吸入可显著缩短住院时间（MD=-6.11,95%CI：-8.88～-3.34,P〈0.0001）、呼吸窘迫持续时间（SMD=-1.56,95%CI：-2.12～-1.00,P〈0.00001）和氧疗时间（SMD=-1.22,95%CI：-1.96～-0.48,P=0.001）,减少败血症发生率（OR=0.25,95%CI：0.07～0.95,P=0.04）。②糖皮质激素组住院期间病死率、胸部X线片恢复正常的时间与对照组差异均无统计学意义。③糖皮质激素组持续性肺动脉高压、鹅口疮及其他浅表部位真菌感染、脑膜炎、高血糖、高血压、慢性肺疾病和生长发育延迟发生率与对照组差异均无统计学意义。结论出生后48h内雾化吸入布地奈德混悬液可显著缩短MAS患儿住院时间、呼吸窘迫及氧疗时间。糖皮质激素治疗不能改善MAS患儿最终结局,亦不会增加糖皮质激素相关感染的发生。鉴于纳入的RCT文献较少,研究间异质性较大,故结论应谨慎对待。