Early pharmacokinetics and clinical effects of oral D-amphetamine in normal subjects

Seven normal subjects received 0.25 mg/kg D-amphetamine orally, both after an overnight fast and again after a standard breakfast. Plasma levels, subjective and cardiovascular effects, and observer-rated activation were assessed hourly for 5 hr. Food did not affect amphetamine levels. Plasma levels peaked at 2-3 hr. Maximum cardiovascular effects generally occurred at 1 hr, whereas maximum behavioral and subjective effects occurred at 2 hr. Subjective and behavioral effects declined thereafter, in spite of substantial amphetamine levels. A separate group of 8 subjects received 0.5 mg/kg D-amphetamine orally. Plasma levels, subjective and cardiovascular effects, and activation ratings were assessed hourly for 4 hr. Maximum plasma levels were approximately twice those seen in the first group. In this case, plasma levels peaked at 3-4 hr; blood pressure and subjective and behavioral effects were all maximal at 2-3 hr and were declining by 4 hr, in spite of stable or rising plasma levels.     

Cathodes for fuel cells using proton-conducting Li2SO4–Al2O3 electrolyte

The performances of three widely different cathode materials (Pt, strontium-doped lanthanum manganite (LSM), and NiO) have been compared for use with proton conducting Li₂SO₄–Al₂O₃ composite electrolyte, using H₂S–air and H₂–air fuel cells operating at 600 °C. Surface analysis and electrochemical techniques were used to characterize fresh and used electrode materials. Pt or LSM cathodes each became covered with Li₂SO₄ and Al₂O₃ and, as a consequence, the fuel cells showed poor performance. In contrast, the NiO cathode catalyst did not become covered with Li₂SO₄ and good fuel cell performance was achieved. Exceptionally good current densities of over 100 mA/cm² and power densities of over 30 mW/cm² were obtained for H₂S–air fuel cells having Mo–Ni–S anode catalysts. Slight agglomeration of NiO particles during fuel cell operation had only a minor effect on performance.     

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 2: Ring-Substituted Derivatives

A range of 18 derivatives of flavone-8-acetic acid (FAA) with substituents on the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. There was no clear-cut relationship between in vitro and in vivo activity but the activity in each situation was found to be very sensitive to the precise substitution pattern with closely related isomers giving widely different activities. Some of the compounds, notably 10b,cj , and r , were active in vivo and these require further studies in order to evaluate their potential for development.     

Doctoral Education in Nursing for Practitioner Knowledge and for Academic Knowledge: The University of Adelaide, Australia

Australian nursing has undergone rapid academization in the past 10 years and this radical change has tended to meld the somewhat different academic traditions of North America and Britain. The introduction of doctoral education in nursing in 1987 has led to a massive increase in scholarly activity and to the preparation of talented leaders. We concur with the view expressed by Henry (1997), "I am convinced that the problems we face in the nursing services would be much more creatively solved if the majority of our doctoral programs prepared young, energetic nurses, early in their career, for clinical practice, not for research and teaching" (p. 162).     

Acute cardiac and pulmonary arrest after infusion of vancomycin with subsequent desensitization

J Allergy Clin Immunol 1997;100:853-4.     

High-Risk Drinking across the Transition from High School to College

Alcohol use and related problems were studied from the senior year in high school to the first autumn in college for 366 heavy drinking students. Four risk factors-subject sex, family history of drinking problems, prior conduct problems, and type of college residence-were evaluated as predictors of: (1) differential changes in drinking rates, (2) differential changes in alcohol-related problems, and (3) alcohol dependence symptoms during the first college term. Results suggest that both dispositional and environmental factors are associated with changes in drinking rates and the existence of dependence symptoms. Increases in the frequency of drinking were specifically and strongly associated with residence in a fraternity (men) or sorority (women). Three risk factors were associated with increased quantity of drinking: male gender, residence in a fraternity or sorority, and a history of conduct problems. Prior conduct problems were also consistently associated with dependence symptoms during the first term in college. A family history of alcohol problems was not consistently related to changes in use rates or problems, although some analyses suggest interactive effects. Early interventions on college campuses should target individuals using additive risk profiles.     

A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996     

Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level

Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA.