Living Without Temporal Cues: A Case Study.

Isolation from external time cues allows endogenous circadian rhythmicity to be demonstrated. In this study, also filmed as a television documentary, we assessed rhythmic changes in a healthy man time isolated in a bunker for 9 days/nights. During this period the lighting conditions were varied between: (1) self-selected light/dark cycle, (2) constant dim light, and (3) light/dark cycle with early wake up. A range of variables was assessed and related to the sleep-wake cycle, psychomotor and physical performance and clock-time estimation. This case study using modern non-invasive monitoring techniques emphasizes how different physiological circadian rhythms persist in temporal isolation under constant dim light conditions with different waveforms, free-running with a period (τ) between 24 and 25 h. In addition, a significant correlation between time estimation and mid-sleep time, a proxy for circadian phase, was demonstrated.

Impact of neurohormonal blockade on association between body mass index and mortality.

BACKGROUND: The prognostic impact of body mass index (BMI) in patients following acute myocardial infarction (AMI) may be altered by neurohormonal blockade. METHODS: The impact of neurohormonal blockade on the association between BMI and mortality was examined in 5548 patients following AMI (CONSENSUS II), 50% receiving enalapril and 7% beta-blockade, and in 4367 patients with coronary artery disease (CAD) (4S), 79% with prior AMI, 12% receiving ACEi and 67% beta-blockade. Median follow-up was 0.4 and 5.2 years, respectively. Patients were categorized into 4 BMI groups: Underweight, < 22.00; normal-weight, 22.00-24.99; overweight, 25.00-29.99; obese, > or = 30.00 kg/m2. Multivariable analysis adjusted for demographics, patient history, physical examination, biochemistry and medication. RESULTS: CONSENSUS II: Overall, adjusted mortality (n=301) risk was similar across BMI groups. Comparing overweight with normal-weight patients, the hazard ratios (HRs) for mortality differed significantly (P=0.028) between patients randomized to placebo (HR 1.41) and enalapril (HR 0.75). 4S: Overall, adjusted mortality (n=421) risk was similar for normal-weight, overweight and obese patients. In a time-dependent analysis for drug use, comparing obese with normal-weight patients, the HRs for mortality differed significantly (P=0.047) between patients without (HR 1.86) and those with (HR 0.97) neurohormonal blockade. CONCLUSION: In patients after AMI or with CAD, high BMI was associated with increased mortality risk among patients not receiving neurohormonal blockade, but with decreased or neutral mortality risk among those receiving neurohormonal blockade. Tests for interaction indicate that neurohormonal blockade may attenuate the relationship between high BMI and increased mortality risk. Neurohormonal blockade may thus partly explain the so-called obesity paradox.