Effects of alcohol dependence comorbidity and antipsychotic medication on volumes of the thalamus and pons in schizophrenia

OBJECTIVE: Postmortem and in vivo brain imaging studies have identified abnormalities in the thalamus and the pons in both schizophrenia and alcoholism. The authors sought to determine whether patients with both schizophrenia and alcohol dependence would manifest exaggerated volume deficits in either structure. METHOD: Volumetric measures of the left and right thalamus and the pons were derived from magnetic resonance imaging scans obtained from 27 patients with schizophrenia, 19 patients with schizophrenia and comorbid alcohol dependence, 25 patients with alcohol dependence without comorbid axis I disorders, and 51 healthy comparison subjects. RESULTS: The alcohol-dependent patients had significant volume deficits in both the thalamus and the pons. Among patients with schizophrenia, there were no differences in thalamus volumes between those with and without comorbid alcohol dependence. However, patients with schizophrenia who were taking atypical antipsychotic medications had bilateral thalamic deficits, whereas those taking typical neuroleptics did not. Patients with schizophrenia and comorbid alcohol dependence had deficits in the pons. CONCLUSIONS: Patients with schizophrenia and comorbid alcohol dependence are at risk for alcohol-related reduction of pontine structures that are not necessarily affected by schizophrenia per se. The effect of alcohol dependence on the thalamus in schizophrenic patients may be mitigated by the type of neuroleptic medication they receive.     

Lipopolysaccharide attenuates thrombolysis in batroxobin-induced lung vasculature fibrin deposition but not in ferrous chloride-induced carotid artery thrombus in rats: role of endogenous PAI-1

In this study, we investigated if elevation of endogenous plasminogen activator inhibitor type 1 (PAI-1) by lipopolysaccharide (LPS) can retard thrombolysis in both a rat model of lung vasculature fibrin deposition and a platelet-rich thrombus model induced by endothelial injury. By 3 h following an intravenous bolus injection of 0.5 mg/kg LPS, the plasma PAI-1 level had increased to 8 ng/ml. ¹²⁵I-labeled fibrinogen was injected intravenously followed by an injection of batroxobin. Batroxobin converts fibrinogen into insoluble fibrin, which was then deposited in the lungs within 5 min, followed by spontaneous fibrinolysis that completely cleared fibrin deposition in the lungs by 30 min. In rats pre-treated with LPS, spontaneous fibrinolysis was significantly retarded. In the endothelial injury model, topical application of FeCl₂ on the carotid artery induced an occlusive platelet-rich thrombus, which was not sensitive to endogenous thrombolysis. Exogenous tissue-type plasminogen activator (tPA) was required to recanalize the occlusive thrombus in a dose-dependent manner. Pre-treatment with LPS did not alter the dose–response curve of exogenous tPA-induced thrombolysis. These data indicate that batroxobin-induced lung vasculature fibrin deposition in rats, unlike the FeCl₂ model, is sensitive to the impact of endogenous PAI-1 on fibrinolysis.     

Comprehensive transposon mutant library of Pseudomonas aeruginosa

We have developed technologies for creating saturating libraries of sequence-defined transposon insertion mutants in which each strain is maintained. Phenotypic analysis of such libraries should provide a virtually complete identification of nonessential genes required for any process for which a suitable screen can be devised. The approach was applied to Pseudomonas aeruginosa, an opportunistic pathogen with a 6.3-Mbp genome. The library that was generated consists of 30,100 sequence-defined mutants, corresponding to an average of five insertions per gene. About 12% of the predicted genes of this organism lacked insertions; many of these genes are likely to be essential for growth on rich media. Based on statistical analyses and bioinformatic comparison to known essential genes in E. coli, we estimate that the actual number of essential genes is 300-400. Screening the collection for strains defective in two defined multigenic processes (twitching motility and prototrophic growth) identified mutants corresponding to nearly all genes expected from earlier studies. Thus, phenotypic analysis of the collection may produce essentially complete lists of genes required for diverse biological activities. The transposons used to generate the mutant collection have added features that should facilitate downstream studies of gene expression, protein localization, epistasis, and chromosome engineering.     

Effectiveness of substance abuse treatment programming for women: a review

Recent research has shown that women and men differ in substance abuse etiology, disease progression, and access to treatment for substance abuse. Substance abuse treatment specifically designed for women has been proposed as one way to meet women's distinctive needs and reduce barriers to their receiving and remaining in treatment. However, relatively few substance abuse treatment programs offer specialized services for women, and effectiveness has not been fully evaluated. This article reviews the literature on the extent and effectiveness of substance abuse treatment programming for women and provides an overview of what is known about the components of successful treatment programs for women. Thirty-eight studies of the effect on treatment outcomes of substance abuse treatment programming for women were reviewed. Seven were randomized, controlled trials, and 31 were nonrandomized studies. In our review, six components of substance abuse treatment programming for women were examined: child care, prenatal care, women-only programs, supplemental services and workshops that address women-focused topics, mental health programming, and comprehensive programming. The studies found positive associations between these six components and treatment completion, length of stay, decreased use of substances, reduced mental health symptoms, improved birth outcomes, employment, self-reported health status, and HIV risk reduction. These findings suggest that to improve the future health and well-being of women and their children, there is a continued need for well-designed studies of substance abuse treatment programming for women.     

How Important Are Brain Banks for Alcohol Research?

This article contains the proceedings of a symposium at the 2002 RSA/ISBRA Meeting in San Francisco, organized and chaired by Clive Harper and co-chaired by Izuru Matsumoto. The presentations were (1) Introduction, by Clive Harper; (2) The quality of tissue-a critical issue, by Therese Garrick; (3) The first systematic brain tissue donor program in Japan, by Izuru Matsumoto; (4) Brain scans after death-really! by Adolf Pfefferbaum, Elfar Adalsteinsson, and Edith Sullivan; (5) Capture that (genial) expression, by Joanne Lewohl and Peter Dodd; and (6) Neurochemical/pharmacological studies: experimental design and limitations, by Roger Butterworth.     

Quality of life in adolescents with mild asthma

The majority of individuals with asthma have mild disease, often in conjunction with allergic rhinitis and exercise-induced bronchoconstriction (EIB). Although health-related quality-of-life (HRQoL) is reduced in moderate to severe asthma and allergic rhinitis, little is known about the effect of mild asthma, mild allergic rhinitis, and EIB on HRQoL outcomes. The objective of this study was to determine the effect of mild asthma, allergic rhinitis, and EIB on HRQoL. A cross-sectional study was conducted of 160 adolescent athletes participating in a screening program to detect EIB. Generic HRQoL was assessed with the teen version of the pediatric quality-of-life inventory (PedsQL). Prior diagnoses of asthma, allergic rhinitis, and EIB, and current symptoms of dyspnea during exercise and asthma, were recorded. Lung function and the presence of EIB were determined by spirometry before and after an exercise challenge test. Adolescent athletes with a prior physician diagnosis of asthma had a lower HRQoL scale summary score (P<0.01) and lower physical functioning, emotional functioning, and school functioning domain scores (P values, 0.01-0.02) in comparison to adolescent athletes with no prior diagnosis of these disorders. Athletes with a prior diagnosis of asthma reported dyspnea during exercise more frequently than did those without asthma (P<0.001). Adolescent athletes with dyspnea during exercise had a lower scale summary score, and lower physical functioning, general well-being, and emotional functioning domain scores (P values, 0.02-0.03). These data show that mild asthma and dyspnea without asthma significantly affect HRQoL. Symptoms of dyspnea during exercise are common in asthma and are associated with lower HRQoL. The clinical significance of these differences in HRQoL is unclear.     

Optimal timing of the Ross procedure in the management of chronic aortic incompetence in the young

The appropriate timing of intervention in patients with chronic aortic incompetence allows recovery of ventricular function. We sought to determine the optimal timing of the Ross procedure for chronic aortic incompetence in young patients. We retrospectively analysed case notes, and measured pre- and postoperative echocardiographic indexes of left ventricular function, in patients who had undergone the Ross procedure for chronic aortic incompetence. METHODS AND RESULTS: We found 21 patients with preoperative and postoperative data suitable for analysis. Their age at operation ranged from 5.6 to 26 years, with a median of 13.8 years, and the duration of follow-up was from 0.5 to 6.8 years, with a median of 2.4 years. The preoperative left ventricular end-diastolic dimension was converted to a z-score, and this was used as a threshold to divide the population. Using the threshold of a preoperative left ventricular z-score of more than 3 to divide the population did not show any difference in postoperative parameters of left ventricular function. Significant differences were found postoperatively, however, in both the left ventricular z-score and the ratio of left ventricular end-diastolic radius to posterior wall thickness in diastole, with a cutoff preoperative threshold z-score greater than 4. CONCLUSION: The increase in the ratio of left ventricular end-diastolic radius to the thickness of the posterior wall in diastole would suggest that there is disruption of left ventricular short axis architecture and myocardial contractile function when intervention is postponed. The significantly larger left ventricular dimension at end-diastole, despite the reduction in volume loading post surgery, may also demonstrate irreversible structural changes. Our data would suggest that recovery of left ventricular function is less likely when the left ventricular z-score has reached the value of 4, and that, ideally, intervention should be performed when the z-score approaches or exceeds 3.     

Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study

Antagonizing the effect of interleukin (IL)-5 is a potential new treatment strategy in allergic disorders. We evaluated the safety, biological activity, and pharmacokinetics of SCH55700, a humanized anti-human IL-5 antibody, in subjects with severe persistent asthma treated with oral or high doses of inhaled steroids. In a double-blind, randomized, multicenter trial, a rising single dose of SCH55700 (0.03 mg/kg [n = 2], 0.1 mg/kg [n = 4], 0.3 mg/kg [n = 6], or 1.0 mg/kg [n = 12]) or placebo (n = 8) was administered intravenously. SCH55700 dose dependently reduced circulating eosinophil counts. At a dose of 1.0 mg/kg, the decrease remained significant up to Day 30 [(0.07 +/- 0.01) x 10(9)/L versus (0.23 +/- 0.04) x 10(9)/L at baseline] (mean +/- SEM) (p = 0.05). After administration of SCH55700 at 0.3 and 1.0 mg/kg, a trend toward improvement in baseline FEV1 was observed, which reached significance 24 hours after the 0.3-mg/kg dose (p = 0.019 versus placebo). No significant changes occurred in other clinical indices of disease activity. Adverse events were not different between active treatment and placebo. We conclude that SCH55700 is a biologically active anti-human IL-5 antibody that can be safely used in severe steroid-treated asthma. Its therapeutic potential needs to be addressed in specifically designed efficacy trials.