The Discriminative stimulus effects of gamma-hydroxybutyrate and related compounds in rats discriminating baclofen or diazepam: The role of GABA(B) and GABA(A) receptors

The discriminative stimulus effects of gamma-hydroxybutyrate (GHB) can be mimicked by GABA(A) receptor-positive modulators (e.g., diazepam) and GABA(B) receptor agonists (e.g., baclofen). The purposes of this study were to see whether stimulus control could be established with baclofen and to further characterize the role of GABAergic mechanisms in the behavioral actions of GHB by evaluating GHB and related compounds in rats discriminating either diazepam or baclofen. Training criteria were satisfied with baclofen and diazepam after 69 and 44 sessions, respectively. GHB and its precursors gamma-butyrolactone and 1,4-butanediol occasioned >80% responding on the drug-associated lever in rats discriminating baclofen and <11% in rats discriminating diazepam. Diazepam and other GABA(A) receptor-positive modulators occasioned intermediate levels of responding on the baclofen lever, whereas baclofen occasioned less than 4% responding on the diazepam lever. The GABA(B) receptor antagonist CGP 35348 [(3-aminopropyl)(diethoxymethyl) phosphinic acid] partially antagonized the effects of baclofen as well as the baclofen-like effects of GHB, and flumazenil partially antagonized the effects of diazepam. This study established stimulus control with baclofen, and substitution data provided direct evidence for a role of GABAergic, especially GABA(B), mechanisms in the discriminative stimulus effects of GHB. The lack of substitution by GHB or its metabolic precursors for diazepam indicates a comparatively smaller role of GABA(A) mechanisms in these effects of GHB. The inability of CGP 35348 to completely attenuate the effects of baclofen and GHB suggests that multiple receptors could be involved in the discriminative stimulus effects of GHB.     

East meets West: integrating psychotherapy approaches for Muslim women

Psychotherapists' knowledge and understanding of Muslim women's culture is essential for them to effectively treat patients. Muslim women's culture is based on Islam, which permeates their thinking patterns, their interaction with themselves and others, and all activities of their daily lives. Western psychotherapy ineffectively treats Muslim women because its individualistic and fragmented method is contrary to the Muslim population's holistic spiritual approach to life. This article provides a theoretical integration of Eastern and Western therapeutic concepts for Muslim women, to promote a more effective therapeutic approach for this population residing in the United States.     

Immunosuppressive treatment of multiple sclerosis

Multiple sclerosis is thought, by many investigators, to be an immunologic disease. Therefore, a rationale exists for treating this disease by immunosuppressive therapy. In exacerbating-remitting multiple sclerosis, corticosteroids and adrenocorticotropic hormone are the most widely used drugs; high doses of intravenously administered methylprednisolone have recently gained favor. Chronic progressive multiple sclerosis has been treated with a number of immunosuppressive regimens, several of which have shown promise to date. Cyclophosphamide and azathioprine have been used most often and are reviewed in this report, as are other agents currently under investigation. No firm guidelines for the treatment of chronic progressive multiple sclerosis can be offered, but an approach to immunosuppressive therapy is suggested in this review.     

Circulating cardiac troponin-T in patients before and after renal transplantation

Background: The diagnostic and prognostic use of cardiac troponin T (cTnT) in patients with renal failure has been questioned. Raised serum concentrations of cTnT, with no apparent signs of cardiac damage using conventional methods of detection, have been reported. We aimed to relate circulating concentrations of cTnT to improved renal function following renal transplantation over a one-year period. Method: Plasma cTnT was analysed from patients with end stage renal disease before and after transplantation and subsequently at 1, 3, 6 and 12 months. Eight patients had diabetes, 14 had hyperlipidaemia, 8 were smokers and 4 were ex-smokers; all were hypersensitive. Results: At the time of transplantation, 3 of the 32 patients (9.4%) had plasma cTnT concentrations above 0.1 μg/l. In addition to these three patients, five others showed raised cTnT over the one-year period. Conclusions: The overall trend in circulating cTnT concentrations did not seem to be affected by improved renal function. However, all of the patients that had raised cTnT concentrations at any stage of the one-year period had explainable pathologies or were exposed to multiple cardiac risk factors.     

Cefamandole Therapy in Anaerobic Infections

Thirty-one adult patients with infections due to anaerobic bacteria were treated with cefamandole. Bacteroides fragilis group (17) and Bacteroides melaninogenicus (13) were the most frequent anaerobes isolated. Duration of therapy varied from 2 to 49 days. Results were judged satisfactory in 26 cases, and unsatisfactory in 1 case. Four cases could not be evaluated. Adverse reactions occurred in 16 patients and included positive direct Coombs' test without hemolysis, transient liver function abnormalities, phlebitis, reversible neutropenia, fever, eosinophilia, and toxic epidermal necrolysis. The more significant reactions were associated with prolonged therapy. None was lethal. These data suggest that cefamandole is effective in treatment of most anaerobic infections.     

Limitations of risk analysis in the determination of medical factors in road vehicle accidents

The purpose of risk analysis in the determination of medical factors in road vehicle accidents is to evaluate the risks that are associated with different strategies for accident reduction, so that the subsequent decision making process can be based on a best assessment of the likely benefits. However, it is vital to appreciate the limitations of such an approach, especially where the conclusions depend heavily on the accuracy of the assumptions made. In this paper the assumptions used in some recent analyses concerned with incapacitation, epilepsy, hypoglycaemia and psycho-active medication are explored, and the additional information required to reduce the uncertainty in the estimation of risk indicated. The conclusions from this analysis do not invalidate the use of risk assessment, but draw attention to its limitations and show how a sensitivity analysis can help to identify those areas where more precise information is needed before such an approach can be used confidently in a policy setting.     

A phase II,double-blind,randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies

tgAAVCF, an adeno-associated cystic fibrosis transmembrane conductance regulator (CFTR) viral vector/gene construct, was administered to 23 patients in a Phase II, double-blind, randomized, placebo-controlled clinical trial. For each patient, a dose of 100,000 replication units of tgAAVCF was administered to one maxillary sinus, while the contralateral maxillary sinus received a placebo treatment, thereby establishing an inpatient control. Neither the primary efficacy endpoint, defined as the rate of relapse of clinically defined, endoscopically diagnosed recurrent sinusitis, nor several secondary endpoints (sinus transepithelial potential difference [TEPD], histopathology, sinus fluid interleukin [IL]-8 measurements) achieved statistical significance when comparing treated to control sinuses within patients. One secondary endpoint, measurements of the anti-inflammatory cytokine IL-10 in sinus fluid, was significantly (p < 0.03) increased in the tgAAVCF-treated sinus relative to the placebo-treated sinus at day 90 after vector instillation. The tgAAVCF administration was well tolerated, without adverse respiratory events, and there was no evidence of enhanced inflammation in sinus histopathology or alterations in serum-neutralizing antibody titer to adeno-associated virus (AAV) capsid protein after vector administration. In summary, this Phase II trial confirms the safety of tgAAVCF but provides little support of its efficacy in the within-patient controlled sinus study. Various potentially confounding factors are discussed.