The discriminative stimulus and subjective effects of d-amphetamine,phenmetrazine and fenfluramine in humans

The discriminative stimulus (DS) and subjective effects of d-amphetamine (AMP), phenmetrazine (PMT) and fenfluramine (FFL) were studied in a group of normal healthy adults. Subjects (N=27) were trained to discriminate between placebo and 10 mg AMP (PO). Fourteen of the subjects (discriminators) reliably learned the discrimination, whereas the other 13 did not. Nearly all discriminators labelled AMP as a stimulant, and AMP, relative to placebo, increased ratings of drug liking and general activity level, and produced typical stimulant-like subjective effects, as measured by the Profile of Mood States, the Addiction Research Center Inventory, and a series of visual analog scales. The discrimination accuracy of discriminators increased as a function of hour after drug ingestion, as did analog ratings of how certain subjects were that their discrimination responses were correct. Discriminators were tested with doses of PMT (25 and 50 mg) and FFL (20 and 40 mg) to determine whether the DS properties of these drugs would substitute for those of AMP. Both doses of PMT consistently substituted for AMP, and PMT produced subjective effects very similar to those of AMP. Conversely, neither dose of FFL consistently substituted for AMP, and FFL produced essentially no subjective effects. These findings are consistent with results from discrimination studies with other species, and provide further evidence of the validity of this procedure for studying the DS properties of drugs in humans. Offprint requests to: L.D. Chait     

A pilot study exploring the effect of discharging cancer survivors from hospital follow-up on the workload of general practitioners.

BACKGROUND: The tradition of routine, long-term follow-up of cancer patients in the outpatient clinic has led to busy clinics and long waiting times. Many cancer patients are anxious and have become dependent on the specialist clinic for reassurance. General practitioners (GPs) have been shown to be willing to assume greater responsibility for the routine follow-up of breast cancer patients, but patients have demonstrated a preference for hospital follow-up. If patients are discharged unwillingly, their rehabilitation may be at the cost of an increased demand on GP practices. AIM: To determine the consequences for GPs of discharging long-term cancer patients from a hospital outpatient follow-up clinic. METHOD: A consecutive sample of 65 patients under annual review in a hospital oncology clinic were offered a planned discharge in which their return to the clinic, if necessary, was guaranteed. The 41 patients who accepted discharge were monitored. Anxiety and depression rates were assessed using the Hospital Anxiety and Depression Scale (HADS) at the time of discharge and four months later at a home interview. The GPs of all patients who were discharged were sent questionnaires four and twelve months after discharge to evaluate consultation rates and change in psychological morbidity. RESULTS: The results showed no significant increase in the consultation rates during the 12 months after discharge compared with the previous 12 months. There was no significant change in the level of patients' anxiety or depression at four months after discharge. The great majority of GPs (71%) reported no change in their perception of patients' levels of anxiety or depression. GPs thought there was a need for more specialist Macmillan nurses working in the community and highlighted the importance of fast-track specialist referral. CONCLUSION: Discharging this group of long-term cancer survivors did not increase the workload of GPs. However, GPs' concern over the lack of availability of Macmillan nurses in the community suggests that primary care services may find it difficult to cope adequately with the special requirements involved in cancer patient care. Finally, there is a need to address the further training requirements of GPs in the routine follow-up of cancer patients.     

Working conditions and health behavior as causes of educational inequalities in self-rated health: an inverse odds weighting approach

Objective:Using a novel mediation method that presents unbiased results even in the presence of exposure–mediator interactions, this study estimated the extent to which working conditions and health behaviors contribute to educational inequalities in self-rated health in the workforce.Methods:Respondents of the longitudinal Survey of Health, Ageing, and Retirement in Europe (SHARE) in 16 countries were selected, aged 50–64 years, in paid employment at baseline and with information on education and self-rated health (N=15 028). Education, health behaviors [including body mass index (BMI)] and working conditions were measured at baseline and self-rated health at baseline and two-year follow-up. Causal mediation analysis with inverse odds weighting was used to estimate the total effect of education on self-rated health, decomposed into a natural direct effect (NDE) and natural indirect effect (NIE).Results:Lower educated workers were more likely to perceive their health as poor than higher educated workers [relative risk (RR) 1.48, 95% confidence interval (CI) 1.37–1.60]. They were also more likely to have unfavorable working conditions and unhealthy behaviors, except for alcohol consumption. When all working conditions were included, the remaining NDE was RR 1.30 (95% CI 1.15–1.44). When BMI and health behaviors were included, the remaining NDE was RR 1.40 (95% CI 1.27–1.54). Working conditions explained 38% and health behaviors and BMI explained 16% of educational inequalities in health. Including all mediators explained 64% of educational inequalities in self-rated health.Conclusions:Working conditions and health behaviors explain over half of the educational inequalities in self-rated health. To reduce health inequalities, improving working conditions seems to be more important than introducing health promotion programs in the workforce.     

An alternative approach: antegrade catheter-directed thrombolysis in a case of phlegmasia cerulea dolens

Phlegmasia cerulea dolens is an uncommon sequela of severe deep venous thrombosis of the lower extremities. Characterized by massive edema, arterial and venous compromise, and threats to limb and life, this clinical entity is a clear indication for thrombolytic therapy. We report an innovative approach to conventional thrombolysis via a lesser saphenous vein cut-down. This simple technique is a safe, reliable alternative to present methods of achieving deep venous access. Hence, it should be considered as an addition to the treatment armamentarium for massive deep venous thrombosis of the lower extremity.     

Effects of chronic Δ9-tetrahyrocannabinol administration on schedule-controlled behavior of pigeons: Cross-tolerance to pentobarbital and barbital

Pigeons responding under a variable-interval (VI) 75-s schedule of food presentation were used to study cross-tolerance from ⁹-tetrahyrocannabinol (⁹-THC) to pentobarbital and barbital. After initial dose-effect functions for pentobarbital and barbital were determined, the birds received ⁹-THC injections for 6 weeks. This chronic administration regimen resulted in a greater than 100-fold tolerance to ⁹-THC. Redetermination of the pentobarbital and barbital dose-effect functions during the chronic ⁹-THC regimen revealed statistically significant shifts to the right for the pentobarbital (0.191 log unit) and barbital (0.078 log unit) dose-effect curves. All six birds showed tolerance to pentobarbital, while four of the six showed tolerance to barbital. Blood barbital levels before and after chronic ⁹-THC administration did not differ significantly. Tolerance to ⁹-THC was more prolonged and of much greater magnitude than the cross-tolerance to pentobarbital or barbital. The results demonstrate that cross-tolerance can develop from ⁹-THC to a barbiturate that normally undergoes little metabolism.     

Effect of dietary fructose on triglyceride transport and glucoregulatory hormones in hypertriglyceridemic men.

Effects of dietary fructose on triglyceride metabolism and on basal levels and meal responses of glucose, insulin, and glucagon were studied in six hypertriglyceridemic men, two of whom were also diabetic. Constant composition, weight-maintaining formula diets were used with substitution of fructose for 20% of the carbohydrate calories in both fat-containing (45% carbohydrate) and fat-free (85% carbohydrate) periods; each of the four dietary periods was at least 2 weeks long in every subject. No effect of fructose on fasting levels of triglycerides could be seen in any of the diets. No alterations of triglyceride transport occurred with fructose substitution in the fat-containing diets, but significant reductions of triglyceride transport rates were seen with fructose substitution in the 85% carbohydrate diets using both the heparin infusion lipolytic rate method and the 3H-glycerol methods of assessment of tryglyceride turnover (- 16 and - 21%, respectively). Dietary fructose induced no significant changes in either basal levels or responses during a "formula tolerance test" of glucose, insulin, or glucagon. Thus, dietary fructose given for several weeks does not appear to cause further elevations of plasma triglyceride levels in hypertriglyceridemic men.