Caffeine self-administration in humans: 1. Efficacy of cola vehicle

Eight exclusive cola drinkers in Experiment 1 (mean caffeine intake = 157 +/- 74 mg/day) and 16 drinkers of both cola and coffee in Experiment 2 (mean caffeine intake = 579 +/- 201 mg/day) underwent 6 independent, double-blind weekly trials. Each trial began with a randomized cross-over sampling period of 1 day of access to noncaffeinated cola and 1 day of access to caffeinated (33 mg/8 oz) cola. During the subsequent 1- or 2-day test period, participants had unlimited concurrent access to the 2 colas. Reliable caffeine self-administration occurred in 2 of 8 participants in Experiment 1 and in 4 of 16 participants in Experiment 2. Self-reported drowsiness, fatigue, and headache were higher when participants received only placebo colas in Experiment 2, but not Experiment 1. Caffeine self-administration via cola occurs both among people whose primary source of caffeine is cola and among those whose primary source of caffeine is coffee.     

Alloimmune neonatal neutropenia in Australian aboriginals: an unrecognized disorder?

Alloimmune neonatal neutropenia (ANN) is reported for the first time in two Australian aboriginals. Both infants displayed the typical clinical features of ANN with profound neutropenia which persisted for 7 weeks and only minor infectious episodes. However, management strategies differed for the two infants because in one case (complicated by uncertain paternity) serological confirmation of ANN was not obtained until after recovery of the infant's neutrophil count. The maternal antibodies could not be assigned to known neutrophil antigen specificities and a new antigen may be involved. The antibodies were reactive with > 99% of neutrophils in a Caucasian population. Aboriginals comprise 1% of the total population of Australia and 1-2% of the obstetric population at our institution. Thus, ANN may be an unrecognized disorder in this ethnic group and a possible cause of neonatal infection and mortality.     

Attenuation of alcohol consumption by a novel nontoxic ibogaine analogue (18-methoxycoronaridine) in alcohol-preferring rats

We previously reported that single administration of ibogaine, an indol alkaloid with antiaddictive properties, dose dependently reduced alcohol intake in three strains of alcohol-preferring rats. The present study examined the effect of different doses of a newly developed nontoxic ibogaine analogue, 18-methoxycoronaridine (18-MC), on alcohol intake. Selectively bred alcohol-preferring rats received a single intraperitoneal injection of vehicle or 5, 20 and 40 mg/kg of 18-MC at 9:30 AM, and their consumption of alcohol, water and food was measured for 24 h. Our results demonstrate that a single injection of 18-MC significantly and dose dependently attenuated alcohol consumption and preference and commensurately increased water intake. Only the highest dose of 18-MC significantly decreased food intake. Although the true mechanism of action of 18-MC in suppressing alcohol intake is not yet fully understood, it may, like ibogaine, exert its attenuating effects on alcohol consumption by modulating neurotransmitters believed to be involved in the regulation of alcohol intake.     

Lovastatin decreases de novo cholesterol synthesis and LDL Apo B-100 production rates in combined-hyperlipidemic males

The effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, on the kinetics of de novo cholesterol synthesis and apolipoprotein (apo) B in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) was investigated in five male patients with combined hyperlipidemia. Subjects were counseled to follow a Step 2 diet and were treated with lovastatin and placebo in randomly assigned order for 6-week periods. At the end of each experimental period, subjects were given deuterium oxide orally and de novo cholesterol synthesis was assessed from deuterium incorporation into cholesterol and expressed as fractional synthesis rate (C-FSR) and production rate (C-PR). Simultaneously, the kinetics of VLDL, IDL, and LDL apo B-100 were studied in the fed state using a primed-constant infusion of deuterated leucine to measure fractional catabolic rates (FCR) and production rates (PR). Drug treatment resulted in significant decreases in total cholesterol (-29%), VLDL cholesterol (-40%), LDL cholesterol (-27%), and apo B (-16%) levels and increases in HDL cholesterol (+13%) and apolipoprotein (apo) A-I (+11%) levels. Associated with these plasma lipoprotein responses was a significant reduction in both de novo C-FSR (-40%; P = .04) and C-PR (-42%; P = .03). Treatment with lovastain in these patients had no significant effect on the FCR of apoB-100 in VLDL, IDL, or LDL, but resulted in a significant decrease in the PR of apoB-100 in IDL and LDL. Comparing the kinetic data of these patients with those of 10 normolipidemic control subjects indicates that lovastatin treatment normalized apoB-100 IDL and LDL PR. The results of these studies suggest that the declines in plasma lipid levels observed after treatment of combined hyperlipidemic patients with lovastatin are attributable to reductions in the C-FSR and C-PR of de novo cholesterol synthesis and the PR of apoB-100 containing lipoproteins. The decline in de novo cholesterol synthesis, rather than an increase in direct uptake of VLDL and IDL, may have contributed to the decline in the PR observed.     

Consensus heart failure. Centraal Begeleidingsorgaan voor de Intercollegiale Toetsing

Consensus heart failure--On June 17th, 1994, a consensus meeting was organised to establish guidelines for the diagnosis and treatment of heart failure. Reason to do this were controversies, especially among general practitioners, cardiologists, internists and gerontologists, which arise as a consequence of new diagnostic modalities (such as echocardiography) and altered aims of the treatment (besides relief of symptoms reduction of morbidity and mortality). A number of starting points were formulated by a preparatory committee: Heart failure constitutes a major health problem. It is defined by cardiac dysfunction with accompanying symptoms. Diagnosis and treatment should focus first on causes or contributing factors. The extent of diagnostic procedures depends on possible doubts with regard to diagnosis and aetiology and therapeutic consequences. Treatment should include non-medical measures. Apart from relief of symptoms, the choice of drugs is also determined by their potential to reduce morbidity and mortality. The pharmacotherapeutic approach has to be tailored to the needs of the patient with a central role for the ACE inhibitors. Patients with concomitant arrhythmias and (very) old patients form separate risk groups. Further attention should be paid to the prevention of heart failure.