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Transfusional iron overload is a potentially fatal complication of the treatment of thalassaemia. We aimed to investigate short-term efficacy, pharmacokinetic/pharma- codynamic (PK/PD) relations, and safety of ICL670, a novel, tridentate, orally active iron chelator.We enrolled 24 patients and divided them into three cohorts consisting of a minimum of seven individuals. Patients were admitted to a metabolic unit and consumed a diet with a defined content of iron. Two patients in each cohort were randomly allocated placebo. Five or more patients received one daily dose of ICL670 at 10, 20, or 40 mg x kg(-1) x day(-1), from day 1 to 12. Net iron excretion (NIE) was measured between days 1 and 12. Primary objectives included assessment of safety and tolerability (measured by adverse events and clinical laboratory monitoring), pharmacokinetics (measured as drug and drug-iron complex), and cumulative net iron excretion (measured by faecal and urine output minus food input). Analysis was for efficacy.ICL670 was absorbed promptly and was detectable in the blood for 24 h. Exposure (area under the curve of plasma concentration) to ICL670 at pharmacokinetic steady state was proportional to dose. All three doses resulted in positive NIE. The NIE achieved at 20mg x kg(-1) day(-1) would prevent net iron accumulation in most patients transfused with 12-15 mL packed red-blood-cells kg(-1) month(-1), equivalent to 0.3-0.5 mg iron kg(-1) x day(-1). A linear relation (PK/PD) was recorded between exposure to ICL670 and total iron excretion, by contrast with placebo (r2=0.54, p0.0001). Skin rashes were noted in four patients treated at 20 and 40 mg x kg(-1) x day(-1), and one patient also developed grade 2 transaminitis.ICL670 given once daily at 20 mg/kg seems to be an effective orally active iron chelator and is reasonably well tolerated. Long-term studies are now necessary to establish the practical contribution of this drug.

Components of the Structured Interview in employed women and the overlap between these components and those identified by self-report measures of Type A behavior were investigated. The sample consisted of 177 employed, white females 26 to 52 years old; 48% were classified as Type A. Principal components factor analysis yielded five factors: Clinical Rating, Hurried-Drive, Impatience, Pressured-Competitiveness, and Expression of Anger. Some differences in the factor structure were noted for this sample of employed women, compared with previous studies of employed men, particularly with respect to anger and impatience. The behavioral components of the Structured Interview did not correlate with self-report measures of Type A behavior (Framingham Type A scale and the Jenkins Activity Scale). Implications for future studies of employed women are discussed.

This study addresses the hypothesis that electrocardiographic T-wave amplitude is influenced by beta-adrenergic stimulation of the heart. Beta-adrenergic activity was manipulated both pharmacologically and through behavioral challenge. Under resting conditions, 12 healthy men underwent infusion of placebo and then the beta-agonist, isoproterenol, and the beta-blocker, propranolol, in a counterbalanced, crossover design. During infusion of placebo, subjects also underwent two behavioral challenges, a structured interview and mental arithmetic. Analysis of the resting data indicated that propranolol produced a significant increase in T-wave amplitude, and isoproterenol produced significant T-wave amplitude attenuation. As previously reported, drug effects were also in evidence for heart rate. Behaviorally-induced reduction of T-wave amplitude was observed for mental arithmetic but not structured interview, which again paralleled heart rate data. Both pharmacological and behavioral data reported in this study support the hypothesis that the T-wave is significantly affected by beta-sympathetic influence on the heart. However, a nonspecific effect of heart rate change on T-wave amplitude would also account for these results. The findings are discussed in terms of their implications for the utility of T-wave amplitude in psychophysiological research.

To ascertain the incidence of infections in intravenous users of illicit drugs, we performed a retrospective study of 270 intravenous drug users (IVDUs) and 562 controls who did not use drugs over a seven-year period from 1978-1985. IVDUs had an increased overall incidence of infections (P less than 0.001) compared to controls, which was explained to a large degree by an increased incidence of hepatitis. Endocarditis and disseminated gonococcal infection were seen with increased frequency in IVDUs (P less than 0.05), but abscess and cellulitis were not. Neither acquired immunodeficiency syndrome (AIDS), tuberculosis, Pneumocystis pneumonia, nor disseminated viral or fungal infection were seen in IVDUs or controls. Heroin users, but not other IVDUs, had an increased incidence of infections not thought to be associated with needle use, suggesting impaired immunity. This study demonstrates that IVDUs have an increased incidence of infection compared to control subjects, but the kinds of infections have changed substantially over the past two decades. The presence of opportunistic pathogens in these patients should suggest concurrent infection with human immunodeficiency virus (HIV).