Effects of fenfluramine, m-CPP and triazolam on repeated-acquisition in squirrel monkeys before and after neurotoxic MDMA administration

RATIONALE: Establishing functional deficits as a result of neurotoxic dosing regimens of MDMA has been difficult. However, moderate success has been achieved when sensitive animal models and drug challenge have been used together. OBJECTIVE: The present study used a repeated-acquisition technique and dose-effect determinations before, during and after neurotoxic MDMA exposure to characterize the effects of serotonergic drugs on learning, and to determine if MDMA-induced serotonin (5-HT) neurotoxicity is associated with learning deficits as measured by changes in response rate or the percentage of errors. METHOD: The effects of various serotonergic drugs were characterized in six squirrel monkeys responding under a repeated-acquisition procedure before and after neurotoxic dose regimens of MDMA. Specifically, cumulative dose-effect curves for m-CPP (0.032-1 mg/kg), fenfluramine (0.1-3.2 mg/kg) and triazolam (0.0032-0.1 mg/kg) were obtained prior to MDMA administration, with the latter drug serving as a non-5-HT control. RESULTS: In general, all of the drugs tested decreased overall response rate as the cumulative dose increased, whereas only triazolam markedly increased the percentage of errors. MDMA treatment produced significant (80-99%) decreases in brain 5-HT and 5-HIAA axonal markers, but did not lead to changes in either dependent measure of responding or shifts in the dose-effect curves obtained during pharmacological challenges with m-CPP, fenfluramine or triazolam. CONCLUSIONS:Taken together, these results demonstrate that serotonergic drugs can disrupt learning in monkeys, but indicate that MDMA-induced 5-HT neurotoxicity does not lead to disruptions in this particular type of serial learning task.     

Family caregivers making life-sustaining treatment decisions: factors associated with role strain and ease

Although recent studies have focused on life-sustaining treatment (LST) decision-making by families, research has not examined such decision-making as an aspect of ongoing caregiving by family caregivers. This article focuses on factors associated with family caregiver role strain and ease in LST decision-making. Using content analysis, factors were derived from interview data gathered from 17 family caregivers who had made LST decisions for 16 elderly ill relatives. The factors are incorporated in a framework, The Family Caregiving Process in Making LST Decisions for Elderly Ill Relatives, and fall under four key roles--caregiver, elderly ill relative, other family members, and health care providers. Factors affecting the strain and ease felt by family caregivers exist not only during the actual decision-making period, but also arise during the days, months, and years prior to the event and continue on after the LST decisions have been made. Nurses' knowledge of these factors can help nurses decrease family caregiver strain and increase ease during the family caregiver LST decision-making process.     

Comorbidity and socioeconomic deprivation: an observational study of the prevalence of comorbidity in general practice

Although inequalities in health between the most affluent and most deprived individuals in our communities have been well documented, the underlying causes are still not completely understood. There has been recent interest in the contribution of multiple morbidity as one explanatory factor, although there is little evidence as yet regarding this. The few general practice based studies investigating the presence of comorbidity have highlighted its significance. However the relationship between multiple morbidity and deprivation is still relatively under-researched and under-reported in the literature. As a result, the full extent of comorbidity and its implications remains unknown. Some argue, however, that there is now recognition that comorbidity is the rule rather than the exception and that this ought to influence approaches to quality of care. If this is to take place there is an urgent need for a greater understanding of the nature and impact of comorbidity.     

A double-blind, randomized, 26-week study comparing the cognitive and psychomotor effects and efficacy of 75 mg (37.5 mg b.i.d.) venlafaxine and 75 mg (25 mg mane, 50 mg nocte) dothiepin in elderly patients with moderate major depression being treated in general practice

To investigate the efficacy and cognitive and psychomotor effects of venlafaxine and dothiepin in elderly patients with moderate major depression. A prospective, randomized, double-blind, parallel-group, active comparator controlled study was conducted. Eighty-eight patients (aged > or = 60 years) were enrolled. Each patient received either venlafaxine (immediate release formulation) 37.5 mg twice per day or dothiepin 25 mg mane followed by 50 mg nocte for 26 weeks. Efficacy was assessed with the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. A psychometric test battery to assess cognitive function, activities of daily living and sleep consisted of Critical Flicker Fusion (CFF), Short-term Memory--Kim's Game, Cognitive Failures Questionnaire, Milford Epworth Sleepiness Scale, Leeds Sleep Evaluation Questionnaire, and an Accident Scoring Questionnaire. Quality of Life Questionnaires (Short Form 36 and Quality of Life in Depression Scale) were also administered. Venlafaxine significantly (p < 0.05) raised CFF scores compared to baseline but had no effect on any other measure. Dothiepin significantly (p < 0.05) lowered CFF threshold, and increased ratings of both sedation and difficulty in waking. The results showed that venlafaxine at doses of 37.5 mg b.i.d. in elderly depressed patients is free from disruptive effects on cognitive function and psychomotor performance.