Changes in cholesterol and triglyceride concentrations in the Vanguard population of the Carotene and Retinol Efficacy Trial (CARET).

BACKGROUND: The Beta-Carotene and Retinol Efficacy Trial (CARET) was terminated 21 months ahead of schedule due to an excess of lung cancers. Deaths from cardiovascular disease also increased (relative risk=1.26 (95% confidence interval (CI) 0.99-1.61)) in the group assigned to a combination of 30 mg beta-carotene and 25 000 IU retinyl palmitate (vitamin A) daily. The basis for increased cardiovascular mortality is unexplained. DESIGN: We analyzed data on serum lipids, available for 1474 CARET Vanguard participants who were enrolled in the two CARET pilot studies and transitioned to the Vanguard study. Total cholesterol and triglycerides were measured 2 months prior to, 4 and 12 months following randomization, and annually thereafter for up to 7 y. INTERVENTION: In the asbestos-exposed pilot (N = 816), participants were assigned to beta-carotene and retinol or to placebo; in the smokers pilot (N = 1029), participants were assigned to beta-carotene, retinol, a combination, or placebo. RESULTS: Serum cholesterol showed a decline over time in both arms; serum triglycerides had a continuous decline over time in the placebo arm, but an initial increase that persisted in the active arm. Both serum cholesterol concentrations (P < 0.0003) and serum triglycerides (P < 0.0001) were significantly higher in the participants receiving vitamin A and/or a combination of vitamin A and beta-carotene (n = 863) as compared to the placebo group (n = 611). Those in this active intervention group had an average cholesterol concentration 5.3 mg/dl (0.137 mmol/l) higher than those in the placebo arm. CONCLUSION: The differences in cholesterol and triglyceride concentrations between the groups following randomization may account in part for the unexpected excess in cardiovascular deaths seen in the active intervention arm of CARET.

Seasonal variation in neuroendocrine and mood responses to i.v. L-tryptophan in depressed patients and healthy subjects.

Seasonality of mood disorders might involve alterations in the rhythmicity of serotonin [5-HT] function. We examined seasonal effects on the neuroendocrine and mood responses to L-tryptophan (L-TRP) in depressed patients and healthy subjects. In this study, 126 drug-free patients with DSM-III-R major depression and 58 healthy subjects received in i.v. infusion of L-TRP. Serum prolactin (PRL) and plasma tryptophan levels were measured. Mood was assessed with visual analogue scales. Cosinor analysis revealed seasonal variation in peak change (delta) PRL and baseline tryptophan levels in the combined depressed and in unipolar, nonmelancholic, and nonpsychotic patients. Peak delta PRL and tryptophan levels were inversely correlated in combined depressed and unipolar patients. Seasonality was more evident in female than in male patients. These data support previous evidence that 5-HT function is abnormal in depression and further suggest a seasonal variability of such abnormalities that is absent in healthy subjects.

Interactive effects of subanesthetic ketamine and haloperidol in healthy humans.

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist with prominent psychoactive effects in humans. This study evaluated whether the oral administration of haloperidol 5 mg would block the effects of an intravenous ketamine infusion (bolus of 0.26 mg/kg followed by 0.65 mg/kg per hour). Twenty healthy subjects completed 4 test days involving the oral administration of haloperidol or matched placebo 2 h prior to the intravenous infusion of ketamine or saline. Ketamine produced cognitive, behavioral, neuroendocrine, and physiologic effects in the healthy subjects that were similar to previous reports. Haloperidol pretreatment reduced impairments in executive cognitive functions produced by ketamine as measured by proverb interpretations and the Wisconsin Card Sorting Test. However, it failed to block the capacity of ketamine to produce psychosis, perceptual changes, negative symptoms, or euphoria in healthy subjects. These data outline an important, but functionally delineated modulation of ketamine effects by dopamine2 receptors and other sites of haloperidol action.

Global functioning of inpatients with obsessive-compulsive disorder, schizophrenia, and major depression.

A chart review was conducted to compare the social, occupational, and daily functioning of 17 inpatients with obsessive-compulsive disorder, 17 with major depression, and 17 with schizophrenia. Current Global Assessment of Functioning (GAF) scores of patients with schizophrenia were significantly lower than those of patients with depression and with obsessive-compulsive disorder. However, on work performance, daily living skills, and past-year GAF scores, patients with obsessive-compulsive disorder and those with schizophrenia did not differ significantly, and both groups were significantly more impaired than patients with depression. Results show that inpatients with obsessive-compulsive disorder may exhibit severe and chronic functional impairments requiring extensive supportive and rehabilitative services.

Extended work hours and risk of acute occupational injury: A case-crossover study of workers in manufacturing.

OBJECTIVE: This study was designed to determine whether injury risk among manufacturing workers was related to hours worked during the previous week. METHODS: A case-crossover design was utilized to contrast hours worked prior to an injury shift with those worked prior to a non-injury shift for hourly workers. Paired t-tests were used to determine significance of the difference. Conditional logistic regression was used to assess dose-response. RESULTS: Hours worked prior to injury significantly exceeded hours during the control week. Workers who worked more than 64 hr in the week before the shift had an 88% excess risk compared to those who worked 40 hr or fewer, P < 0.05. CONCLUSION: The study provides evidence that injury risk is related to time worked during the previous week. Control of overtime in manufacturing may reduce risk of worker injury.

Family accommodation of obsessive-compulsive symptoms: instrument development and assessment of family behavior.

Relatives frequently accommodate patients' obsessive-compulsive symptoms and clinicians hypothesize that such accommodations adversely affect patient outcome. This study's purpose was to develop a valid and reliable measure, the Family Accommodation Scale for Obsessive-Compulsive Disorder (FAS), and to investigate the family accommodation construct. We administered the FAS and additional family and patient measures to 36 adult obsessive-compulsive patients and their primary caregivers. The FAS demonstrated excellent interrater reliability and good internal consistency and performed well on assessment of its convergent and discriminant validity. Family accommodation was significantly associated with patient symptom severity and functioning, and with relatives' own obsessive-compulsive symptoms. Although most relatives accommodated patient symptoms, many did not believe that such accommodations improved the patient's clinical status. The FAS will provide researchers and clinicians with a useful tool for assessing family accommodation and for identifying families who may benefit from interventions aimed at developing more adaptive coping strategies.