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Biomedical subjects

D F Kripke

Publications and source records attributed to D F Kripke.

At least 19 recordsLinked to original sources

Dietary calcium blocks lithium toxicity in hamsters without affecting circadian rhythms.

Lithium can be toxic to rodents at plasma concentrations (0.6-1.2 mmol/L) that also phase delay circadian rhythms. In hamsters, raising the concentration of calcium in the diet from 0.1%-3% reduced weight loss and polydipsia caused by 0.4% lithium carbonate. Calcium ingestion did not affect plasma lithium concentration or the phase of the circadian wheel-running rhythm in lithium-treated animals. Calcium ingestion did not alter weight gain, salt or water intake, or circadian rhythms in hamsters not receiving lithium. Dietary calcium supplementation may prevent some toxic effects of lithium without interfering with other central nervous system actions.

Animals

Controlled trial of bright light for nonseasonal major depressive disorders.

Psychotropic drug-free hospitalized veterans with nonseasonal major depressive disorders or depressed forms of bipolar disorder were treated with light for 1 week. Twenty-five patients were randomly assigned to bright white light treatment (2000-3000 lux), and 26 patients were randomized to dim red light placebo control treatment. Unlike those treated with dim red light, those treated with bright white light showed declines in three measures of depression during treatment. Partial relapse appeared within 2 days. A global depression score showed a statistically significant (p = 0.02) difference favoring bright white light treatment. Two bright-light-treated patients became mildly hypomanic, but side effects were mild. Improvement was not correlated with patient expectations; indeed, patients expected somewhat greater benefit from the placebo. Patients treated in summer responded as well as those treated in winter. Baseline electroencephalogram (EEG) sleep stage data (e.g., rapid eye movement; REM latency) did not predict treatment responses. These 1-week treatment results suggest that bright light might produce benefits for patients with nonseasonal depression. Bright light should not be recommended for routine clinical application before additional assessments with longer treatment durations are done.

Adult

Automatic sleep/wake identification from wrist activity.

The purpose of this study was to develop and validate automatic scoring methods to distinguish sleep from wakefulness based on wrist activity. Forty-one subjects (18 normals and 23 with sleep or psychiatric disorders) wore a wrist actigraph during overnight polysomnography. In a randomly selected subsample of 20 subjects, candidate sleep/wake prediction algorithms were iteratively optimized against standard sleep/wake scores. The optimal algorithms obtained for various data collection epoch lengths were then prospectively tested on the remaining 21 subjects. The final algorithms correctly distinguished sleep from wakefulness approximately 88% of the time. Actigraphic sleep percentage and sleep latency estimates correlated 0.82 and 0.90, respectively, with corresponding parameters scored from the polysomnogram (p < 0.0001). Automatic scoring of wrist activity provides valuable information about sleep and wakefulness that could be useful in both clinical and research applications.

Adult

Peripheral vision suppression of melatonin.

The suppression of melatonin by bright light is probably mediated by the suprachiasmatic nucleus (SCN) in humans. In animals, SCN cells have broad visual receptive fields, suggesting that peripheral bright light could be effective for melatonin suppression. Twelve healthy subjects were subjected to 1000 lux illumination for 2 hr from 0100 to 0300 on two occasions: once lighting the central visual field 5 degrees from the center of gaze and once lighting the peripheral visual field 60 degrees lateral to the direction of gaze. Six subjects were observed on a third occasion in dim light. The three conditions differed significantly, with less melatonin secreted in 1000 lux, but melatonin levels with central and peripheral illumination did not differ. This suggests that phototherapy using bright light in the visual periphery may be effective.

Adult

Fatigue, sleep disturbance, disability, and indices of progression of HIV infection.

OBJECTIVE: The authors' objective was to test the hypothesis that fatigue affects the activities and employment of subjects with HIV infection and that indices of immunosuppression and inflammation may have statistical utility in predicting fatigue and sleep disturbance. METHOD: The authors prospectively asked 112 homosexual men (62 HIV-seropositive subjects and 50 HIV-seronegative comparison subjects) to complete a questionnaire on fatigue and sleep disturbance. In addition, hematocrit, WBC count, CD4+ cell number, lactate dehydrogenase, albumin, and total globulin were measured. RESULTS: For HIV-seropositive patients fatigue was significantly more of a problem and interfered more with important activities such as employment and driving than with seronegative comparison subjects. The HIV-infected patients were significantly more likely to be unemployed, to feel fatigued through more hours of the day, to sleep more, to nap more, and to have diminished midmorning alertness. The medical variables could be used to statistically predict fatigue, its interference with daily activities, and employment. CONCLUSIONS: Fatigue and sleep disturbances contribute to morbidity and disability in HIV-infected homosexual men, especially those in CDC stage IV (AIDS-related complex or AIDS). Correlation with measures of immunosuppression and inflammation and comparison between fatigued versus nonfatigued groups suggest the possibility of statistical prediction of fatigue by using these measures. Further study is needed to examine the possibility of eventual specific intervention to clinically treat HIV-related fatigue, sleepiness, and sleep disturbance.

AIDS-Related Complex

Daily light exposure among psychiatric inpatients.

1. The light environment is a key element in the restoration and maintenance of health. 2. People need exposure to bright light (greater than 2,000 lux) to synchronize their circadian rhythms. 3. The affective state of people is related to their light exposure. 4. Bright light among psychiatric inpatients is low. Interventions to increase light exposure in therapeutic environments and individual care plans are recommended.

Adult

Prevalent sleep problems in the aged.

Quality of sleep influences the level of daytime functioning, including stress levels, psychosomatic complaints, general health, and overall well-being. As people age, they complain more about disturbed sleep, insomnia, increased time in bed, and sleep fragmentation. These complaints can be related to circadian rhythm desynchronization, hypnotic or other medication use, chronic bedrest, napping, dementia, or to sleep apnea, a disorder of respiratory cessation which is quite prevalent in the elderly. We review here the results of 12 years of research on sleep in the elderly. In studies of three populations of elderly, it was found that between 24% and 42% had five or more apneas per hour of sleep and 4%-14% had 20 or more apneas per hour of sleep. Since apnea is related to dementia and even to mortality, this high prevalence of apnea is of extreme importance.

Aged

The effects of depression and age on the Horne-Ostberg morningness-eveningness score.

Effects of depression and age on the Horne-Ostberg morningness-eveningness scale in human volunteers were assessed. Thirty-nine healthy outpatients with current DSM-IIIR depression, free of recent substance abuse or confounding medications, were compared to 39 age- and sex-matched controls. Patients reported greater 'eveningness' than controls (P = 0.014, Wilcoxon signed-ranks test). There was multimodality in the distribution of Horne-Ostberg scale scores in the depressed group, but a normal distribution in controls. Pearson's correlation of age vs. Horne-Ostberg score was positive (r = 0.42-0.55). Depression and age influence the Horne-Ostberg score. Potential multimodality of circadian phase in the depressed group deserves further study.

Adult

Sleep-disordered breathing in community-dwelling elderly.

These are the final results of a survey of sleep-disordered breathing, which examined objective and subjective information from a large randomly selected elderly sample. We randomly selected 427 elderly people aged 65 yr and over in the city of San Diego, California. Twenty-four percent had an apnea index, AI, greater than or equal to 5 and 62% had a respiratory disturbance index, RDI, greater than or equal to 10. Correlates of sleep-disordered breathing included high relative weight and reports of snoring, breathing cessation at night, nocturnal wandering or confusion, daytime sleepiness and depression. Body mass index, falling asleep at inappropriate times, male gender, no alcohol within 2 hr of bedtime and napping were the best predictors of sleep-disordered breathing. Despite statistical significance, all of the associations between interview variables and apnea indices were small. No combination of demographic variables and symptoms allowed highly reliable prediction of AI or RDI.

Aged

Periodic limb movements in sleep in community-dwelling elderly.

The prevalence of periodic limb movements in sleep (PLMS) in a randomly selected elderly sample is reported. In San Diego, 427 elderly volunteers aged 65 yr and over were recorded in their homes. Forty-five percent had a myoclonus index, MI greater than or equal to 5. Correlates of PLMS included dissatisfaction with sleep, sleeping alone and reported kicking at night. Although statistically significant, the strengths of the associations between interview variables and myoclonus indices were all small. No combination of demographic variables and symptoms allowed highly reliable prediction of PLMS.

Aged

Short and long sleep and sleeping pills. Is increased mortality associated?

Prospective epidemiologic data of the American Cancer Society disclosed that reported usual sleep durations among groups who complained of insomnia and sleeping pill use "often" overlapped with those of groups who had no complaints. Reports of insomnia were not consistently associated with increased mortality when several factors were controlled; however, men who reported usually sleeping less than four hours were 2.80 times as likely to have died within six years as men who reported 7.0 to 7.9 hours of sleep. The ratio for women was 1.48. Men and women who reported sleeping ten hours or more had about 1.8 times the mortality of those who reported 7.0 to 7.9 hours of sleep. Those who reported using sleeping pills "often" had 1.5 times the mortality of those who "never" used sleeping pills. These results do not prove that mortality could be reduced by altering sleep durations or by reducing hypnotic prescribing. Rather, studies are needed to determine the causes of these mortality risk factors.

Adult

Polygraphic evaluation of ethchlorvynol (14 days).

Ethchlorvynol 500 mg was administered to four young insomniacs for 14 days as part of a standard 22-day sleep laboratory protocol. Subjects slept more while receiving drug, but these benefits were not statistically significant. Ethchlorvynol impaired mood during both drug and withdrawal periods as compared to baseline, and serious side effects were reported. Stage REM and stage 1 were suppressed by ethchlorvynol, and stage 1 (but not stage REM) showed withdrawal rebound.

Adult

Circadian rhythm of lithium toxicity in mice.

The existence of cyclical (circadian) variations in lithium toxicity in mice was determined. Mice, standardized to a light-dark cycle, were injected with lithium chloride (940 mg/kg) at one of six times (20:00, 24:00, 4:00, 8:00, 12:00, and 16:00) and subsequently observed for mortality over 28 h. A significant (P less than 0.01) time-of-day effect was found for lithium-induced lethality, with highest lethality following injection at 12:00.

Animals

Wrist actigraphic measures of sleep and rhythms.

With a piezo-electric activity transducer, wrist activity recordings were made simultaneously with EEG, EOG and EMG recordings. Wrist activity alone was used to estimate Total Sleep Time and blind independent scoring of sleep and wakefulness by EEG-EOG-EMG was done. Correlations between the two methods were termined for minutes of Sleep (r = 0.98), Total Sleep Period (r = 0.95) and minutes of Wake Time Within Sleep (r = 0.85). Continuous wrist activity recordings may thus provide inexpensive but very accurate estimates of Sleep Time.

Electroencephalography