Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders.

Impulsive aggressive behavior is common in psychiatric disorders and accounts for significant morbidity and mortality. However, little systematic treatment data exist from placebo-controlled trials for this symptom domain. This was a multicenter, randomized, double-blind, placebo-controlled study in which outpatients with a score of > or =15 on the Aggression scale of the Overt Aggression Scale-Modified (OAS-M) and who fulfilled DSM-IV criteria for Cluster B personality disorder (n=96), intermittent explosive disorder (n=116), or post-traumatic stress disorder (n=34) were randomized to divalproex sodium or placebo for 12 weeks duration. Based on average OAS-M Aggression scores over the last 4 weeks of treatment, a treatment effect was not observed in the intent-to-treat data set (combined across the three psychiatric disorders), but was observed in both intent-to-treat and evaluable data sets for patients with Cluster B personality disorders. In the Cluster B evaluable data set, statistically significant treatment differences favoring divalproex were also observed for component items of the OAS-M Aggression score, including verbal assault and assault against objects, as well as OAS-M Irritability score, and Clinical Global Impression (CGI)-Severity at multiple time points throughout the study. No treatment group difference was noted for overall premature discontinuation rate; however, across psychiatric diagnoses, 21 (17%) patients in the divalproex group prematurely discontinued because of an adverse event, as compared to 4 (3%) patients in the placebo group (p <0.001). While a treatment effect was not observed when all diagnostic groups were combined, in a large subgroup of patients with Cluster B disorders, divalproex was superior to placebo in the treatment of impulsive aggression, irritability, and global severity.     

Severe esophageal strictures: indications for balloon catheter dilatation

Bougienage of esophageal strictures is a traditional method of therapy for patients who present with a stricture sufficiently large to permit passage of a mercury-weighted rubber bougie. However, when the residual lumen is smaller than 12 mm diameter, bougie dilatation acquires a prohibitively high risk of esophageal perforation. Twenty patients who had severe esophageal strictures have undergone surgical repair or Eder-Puestow dilatation assisted by guidewire. Fluoroscopic balloon catheter dilatation obviated surgery and allowed subsequent standard bougienage both in hospital and at home performed by the patient. We discuss indications, technique, results, and complications.     

美托洛尔酒石酸盐胃内滞留漂浮型控释片的制备及药代动力学研究

本文根据水动力学平衡药物控释系统的设计原理制备了美托洛尔胃内滞留漂浮型控释片剂(简称M-HBS)。实验表明,本品的体外溶出符合一级动力学过程(K′r=0.1651 h^-1);贮存期为两年;人体胃内γ-闪烁照相结果表明,本品在胃内滞留时间(5～6 h)明显比普通片剂(1.0～1.5 h)长;体内动力学过程符合表观一级吸收与一级消除的单室模型;ⅳ美托洛尔体内为双室模型;体内数据经NONLIN计算机程序处理,求得各项参数:Ka=0.1944 h^-1,K=0.1867 h^-1,Vd=2.813,t_max=5.247 h,C_max=125.1 ng/ml。本品的体内外数据具有显著的相关性(P<0.01)。     

Modeling studies of the concurrent growth and neutralization of sulfuric acid aerosols under conditions in the human airways

A kinetic model of coupled droplet growth, gas uptake, and chemical reaction has been used to examine the possible changes to sulfuric acid aerosols as a result of exposure to respiratory ammonia under the conditions in the human airways. Results for a wide range of initial droplet sizes and concentrations spanning the extremes of likely atmospheric conditions are presented. It is predicted that gas phase reactions of SO2 will not significantly affect the neutralizing capability of airways ammonia. The effects of physical and chemical parameters on aerosol neutralization and growth are discussed and in particular, predictions of neutralization in typical inhalation times for aerosols characteristic of severe persistent London fogs and modern urban conditions are compared. The analysis supports the suggestion that the London fog episodes were unique in the relationship of the acid droplets formed to the neutralizing capability of ammonia in the human airways and that simple extrapolation of mortality and morbidity data from such episodes to modern conditions is unlikely to be valid.     

Frequency and presentation of neuroleptic malignant syndrome in a large psychiatric hospital

Neuroleptic malignant syndrome, a dangerous but little-known complication of antipsychotic drugs, is often assumed to be rare. To assess the frequency of the syndrome in a large psychiatric hospital, the authors first reviewed the literature and developed operational diagnostic criteria. Using these criteria to survey nearly 500 neuroleptic-treated patients admitted during a 1-year period, they found that seven (1.4%) had experienced definite or probable neuroleptic malignant syndrome. In several cases, including one fatal case, the diagnosis of neuroleptic malignant syndrome was not immediately considered. The authors conclude that neuroleptic malignant syndrome may be more common than previously thought and may be underdiagnosed.     

The effects of fenfluramine and fluoxetine on the acquisition of a conditioned avoidance response in rats

This study tested a behavior-suppressing punishment system and how its activity may be altered by agents known to interrupt or enhance serotonergic (5-HT) transmission. Holtzman male albino rats were tested for shuttle box avoidance acquisition and intertrial responding either 1 or 8 h following daily injections of fenfluramine (FEN) or fluoxetine (FXT). When the drug-test interval was 1 h, a time when both drugs are presumably potentiating 5-HT activity, avoidance acquisition and intertrial responding were impaired. When testing occurred 8 h after drug treatment, a time when 5-HT levels are unaltered by FXT and are maximally reduced by FEN, these drugs had no effect on avoidance acquisition, but FEN produced an increase in intertrial responses whereas FXT did not. These results support the proposal of an inhibitory 5-HT system. Furthermore, these data demonstrate that FEN is capable of exerting a biphasic action on intertrial responding and suggest that the time interval between drug administration and behavioural testing is a crucial variable when investigating FEN.