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Biomedical subjects

C F Reynolds

Publications and source records attributed to C F Reynolds.

At least 361 records · Page 20Linked to original sources
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Slow-wave sleep and symptomatology in schizophrenia and related psychotic disorders.

Deficits in slow-wave sleep (SWS), or delta sleep, are frequently seen in schizophrenia, but their relationship with schizophrenic symptomatology remains unclear. We examined the association between visually scored and automated measures of SWS and positive and negative symptoms in a series of unmedicated patients with schizophrenia and related psychotic disorders. Total and average automated delta wave counts were significantly inversely associated with negative symptoms overall, and the psychomotor poverty syndrome in particular. Total delta counts were also inversely related to the disorganization syndrome. No relation was seen between reality distortion or the Brief Psychiatric Rating Scale (BPRS) positive symptoms and SWS. These findings support the view that SWS deficits may be related to negative symptoms of schizophrenia and may perhaps be mediated by impaired functioning of frontothalamic neural circuits.

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Assessment of sexual function, interest and activity in depressed men.

Sexual function, interest, and activity were assessed in drug-free outpatient depressed men (n = 26) and in age-matched healthy control men (n = 20) by means of the Derogatis Sexual Functioning Inventory (DSFI), a retrospective sexual function questionnaire (SFQ), and a prospective daily sexual function log. Good test-retest reliability over 1 month was demonstrated for the DSFI and the SFQ in depressives and controls. Compared to healthy controls, depressed men reported significantly lower sexual interest and satisfaction, but no less sexual activity, on both retrospective questionnaires and prospective daily logs. Depressed men also showed significantly more negative body image and less 'manly' sexual role function as measured by the DSFI. Significant partial correlations (controlling for the effects of anxiety) were found between severity of depression and sexual interest, satisfaction, and role.

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Daytime sleepiness and performance among healthy 80 and 20 year olds.

This study investigated the relationship of daytime sleepiness and performance on a vigilance test in a sample of 10 healthy men and 13 women in their 80s (mean age 83.0 +/- 3.1 years) and 18 men and 12 women in their 20s (25.0 +/- 3.1). We hypothesized that "successfully" aged healthy individuals would have more daytime sleepiness with differentially greater decrements in performance than a younger comparison group. Daytime sleepiness was measured physiologically by the Multiple Sleep Latency Test (MSLT) and through self-report by the Stanford Sleepiness Scale (SSS). Morning and evening performance was measured with the Mackworth Clock Test of vigilance. The major findings were the absence of correlation between either MSLT or SSS daytime sleepiness with performance measures, no difference in daytime sleepiness between the old and young groups and performance decrements among the healthy elderly on all parameters. Results suggest that the modest decrements in performance among the elderly cannot be attributed to daytime sleepiness.

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Sleep-disordered breathing in healthy and spousally bereaved elderly: a one-year follow-up study.

This study examined the progression of sleep-disordered breathing (SDB) over 1 year in two samples of elderly subjects: 45 healthy controls (20 men; 25 women mean age 74.8 years) and 27 recently spousally bereaved elders (9 men; 18 women, mean age 69.7 years). Although controls and bereaved subjects did not differ in the proportions with SDB, both groups showed a rise in the proportion of subjects with apnea hypopnea index > or = 5 and > or = 10 at 1-year follow-up and a small but statistically significant worsening in average maximum desaturation. The severity of SDB did not correlate with medical burden or with other clinical variables, such as severity of depressive symptoms. In summary, SDB increased longitudinally in both samples. This finding may have health implications for the aging population although at this time the implications are unclear.

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Inducing jet lag in older people: adjusting to a 6-hour phase advance in routine.

A 15-day simulated jet lag experiment was performed in a time isolation laboratory using 15 old women (79-91 years, mean 82.9 years) and 10 old men (71-86 years, mean 80.5 years). After five full days and nights on the subject's habitual routine, the waketime of night 6 was advanced by 6 h, truncating the sleep episode. All subsequent events occurred 6 h earlier than normal. Adjustment to the phase shift was evaluated by the circadian rhythm in rectal temperature (measured every minute), polysomnography of each sleep episode, and daily averages of mood, activation, and performance speed. While the circadian rhythm amplitude reduction consequent upon the phase shift showed a tendency to be longer lived in the old men, both old groups showed fairly rapid adjustment of the timing of their circadian temperature rhythm, comparable (if not better) to that observed earlier in a study of middle aged men. However, sleep disruption (and daytime sleepiness) appeared to be longer lived in the elderly, showing little of the recovery over time observed in younger subjects. Thus, there appeared to be some separation in the elderly of the sleep disruption and circadian rhythm disruption effects of jet lag.

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Inducing jet lag in an older person: directional asymmetry.

An 85-year-old woman experienced simulated jet-lag in phase advance and phase delay directions, in laboratory simulations (in temporal isolation) involving 6-h changes in routine. Circadian rhythm amplitude and sleep efficiency were less disrupted in the delay than in the advance condition, in contrast to circadian rhythm timing (phase), which appeared to show more rapid adjustment in the advance condition than in the delay condition.

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Circadian temperature rhythms of older people.

This collection of studies had the aim of exploring whether older (77+ years) men and women have circadian body temperature rhythms different from those of younger adults. A total of 20 older men and 28 older women were compared with either 22 young men or 14 middle-aged men in four protocols; all but the first protocol using a subset of the sample. The four protocols were: 1) 24 h, and 2) 72 h data collections on a normal laboratory routine (sleeping at night); 3) between 36 h and 153 h of field data collection at home; and 4) 36 h of a constant conditions routine (wakeful bedrest under temporal isolation) in the laboratory. There was some evidence for an age-related phase advance in temperature rhythm, especially for the older men on a normal routine, though this was not present in the constant conditions protocol, where 5 of the older subjects showed major delays in the timing of the body temperature trough (10:00 or later). There was no statistically significant evidence from any of the protocols that older subjects generally had lower temperature rhythm amplitudes than younger adults. Only when older men were compared with younger men in 24-h rhythm amplitude by simple t-test did any comparison involving amplitude achieve statistical significance (p < 0.05).

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Accounting for covariate measurement error in a Cox model analysis of recurrence of depression.

When a covariate measured with error is used as a predictor in a survival analysis using the Cox model, the parameter estimate is usually biased. In clinical research, covariates measured without error such as treatment procedure or sex are often used in conjunction with a covariate measured with error. In a randomized clinical trial of two types of treatments, we account for the measurement error in the covariate, log-transformed total rapid eye movement (REM) activity counts, in a Cox model analysis of the time to recurrence of major depression in an elderly population. Regression calibration and two variants of a likelihood-based approach are used to account for measurement error. The likelihood-based approach is extended to account for the correlation between replicate measures of the covariate. Using the replicate data decreases the standard error of the parameter estimate for log(total REM) counts while maintaining the bias reduction of the estimate. We conclude that covariate measurement error and the correlation between replicates can affect results in a Cox model analysis and should be accounted for. In the depression data, these methods render comparable results that have less bias than the results when measurement error is ignored.

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Intent-to-treat analysis for longitudinal clinical trials: coping with the challenge of missing values.

Drop-out is a common phenomenon in clinical trials of drug treatments involving longitudinal assessments for a fixed duration of follow-up. For these trials intent-to-treat (IT) analysis is usually preferred because time effects are seen in practice. The IT analysis mandates that all subjects randomized to a treatment arm should be included in the analysis. The purpose of the present paper is to acquaint both clinicians and statisticians with recent statistical methodological advances in handling drop-outs and their usage for IT analysis. We discuss a sensitivity analysis of 12-month outcome data to investigate the efficacy of drug therapy from a longitudinal double-blind placebo-controlled clinical trial in the maintenance therapy of geriatric major depressive illness. Outcome measures consist of monthly Hamilton depression scores. The sensitivity analysis includes endpoint analysis, last observation carried forward analysis, repeated measures models and imputation models. Imputation models are based on multiple imputations of missing responses deriving from an 'as-treated' model. The model used imputed doses from a plausible treatment scenario after drop-out and a 'propensity-adjusted' model where the imputations for the drop-outs were obtained from the adhering subjects with the same probability to remain on study (propensity) given the observed trajectory prior to withdrawal. Issues related to bias and efficiency of the estimates obtained by different analyses are discussed. We recommend a more widespread use of imputation models for the IT analysis.

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Sleep as a mediator of the stress-immune relationship.

OBJECTIVE: To evaluate the role of sleep in the relationship of intrusive thoughts/avoidance behaviors to natural killer cell (NKC) number and function. METHOD: Twenty-nine individuals seeking treatment for bereavement-related depression were studied in the sleep laboratory. Background and clinical variables, including the Impact of Event Scale (IES) and the Hamilton Rating Scale for Depression (HRSD), were administered during the week preceding a 3-night sleep study. Blood samples were collected upon awakening after the second or third night of sleep. RESULTS: Greater frequency of intrusive thoughts and avoidance behaviors was associated with more time spent awake during the first non-rapid eye movement period (NREM-1) and lower NKC number (p values < .01). Greater time spent awake during NREM-1 was associated with lower NKC numbers (p < .05). Regression analyses revealed that the significant relationship between symptoms of intrusion/avoidance and NKC number was no longer significant when time spent awake during NREM-1 was entered into the regression equation. Time spent awake during NREM-1 accounted for 12% of the variance in NKC number (p < .05), whereas intrusion/avoidance accounted for 7% of the variance in NKC number (NS). CONCLUSIONS: These results suggest that EEG-assessed sleep may be a significant correlate of the stress-immune relationship.

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Symptoms of stress and depression as correlates of sleep in primary insomnia.

OBJECTIVE: Previous studies have not evaluated the clinical correlates of the electroencephalographic spectral profile in patients with insomnia. In the preliminary study described here, we evaluated the extent to which symptoms of stress and depression are associated with subjective sleep complaints and quantitative measures of sleep in individuals with chronic insomnia. METHODS: Subjects were 14 healthy adults who met criteria for primary insomnia as specified in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. Measures of stress, depression, and subjective sleep quality were collected before subjects participated in a two-night laboratory sleep series. We hypothesized that elevated symptoms of stress and depression would be associated with subjective sleep complaints and electroencephalographic evidence of hyperarousal during sleep. Hyperarousal during sleep was defined as decreases in delta power and elevations in alpha and beta power throughout non-rapid eye movement sleep, and symptoms of stress were defined as the tendency to experience stress-related intrusive thoughts and the interaction between intrusion tendency and the number of recent stressful events (subjective stress burden). RESULTS: A stronger tendency to experience stress-related intrusive thoughts was associated with greater sleep complaints and a trend toward higher beta power, whereas increases in subjective stress burden were associated with decreases in delta power. In addition, elevations in subclinical symptoms of depression were associated with greater sleep complaints and elevations in alpha power. CONCLUSIONS: Observed relationships among symptoms of stress, depression, subjective sleep complaints, and electroencephalographic power may be relevant to the discrepancy between subjective and objective measures of sleep in patients with insomnia and may be more broadly applicable to sleep complaints in association with stressful life events and major depression.

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Evaluation of the adult with sleep apnea.

Twenty-seven cases of adult sleep apnea are reported. The patients were studied with all-night polysomnography. Seven (26%) had predominately obstructive sleep apnea, while another seven (26%) had predominantly central sleep apnea. Thirteen patients (48%) were found to have a mixed pattern. Obesity was not a reliable guideline for predicting differential etiology. We conclude that sleep studies with specific monitoring are essential in the evaluation of the adult with sleep apnea prior to therapeutic intervention.

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Shy-Drager syndrome presenting as a REM behavioral disorder.

Shy-Drager syndrome (SDS) is associated with a myriad of autonomic and neurologic impairments, including sleep disturbances. A review of the literature reveals that there are no reports of SDS presenting with an abnormality of sleep. The following case report describes a patient who was diagnosed with SDS approximately one decade after initially presenting with a progressive, polysomnographically confirmed disturbance of sleep--specifically, an REM behavioral disorder (RBD).

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Receiver operating characteristic analysis for validating EEG sleep discrimination of elderly depressed and demented patients.

Receiver operating characteristic analysis is a useful tool in validating a diagnostic marker. This technique was applied to a discriminant function model using selected electroencephalographic sleep measures (sleep maintenance, percentage of rapid-eye-movement sleep, and percentage of indeterminate non-rapid-eye-movement sleep) in elderly patients with major depression or dementia of the Alzheimer type. The diagnostic model correctly classified 79.8% of elderly depressed and demented patients. The area under the curve was 0.86, statistically different from 0.5, which would be expected by chance (P less than .0001) and indicating good predictive power of the model. A logistic regression analysis demonstrated the reliability and stability of the diagnostic equation.

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Longitudinal analysis of nortriptyline side effects in elderly depressed patients.

Forty-five depressed elderly patients were closely monitored in a research setting during treatment with nortriptyline and interpersonal psychotherapy for 7 consecutive months of acute and continuation treatment. Overall, nortriptyline was efficacious and well tolerated in this group. The frequency of somatic complaints measured by the Rating Scale for Side Effects declined by 50% during the acute phase of treatment, suggesting that many somatic complaints that may be attributed to side effects of nortriptyline are actually somatic symptoms of depression. The authors discuss the implications of these findings and offer practical advice for the treating clinician.

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Sleep in bereavement-related depression during and after pharmacotherapy with nortriptyline.

Our objective was to assess the effects of nortriptyline on electroencephalographic sleep and subjective sleep quality in spousally bereaved, depressed elders. Ten elderly volunteers with bereavement-related major depression had electroencephalographic sleep studies while depressed, after remission of depressive symptoms while still taking nortriptyline, and after nortriptyline discontinuation. Changes in sleep measures over time were compared both within bereaved subjects and with age- and sex-matched healthy controls. Remission of depressive symptoms while still on nortriptyline was associated with improvements in sleep quality (P < .002), rapid eye movement (REM) percent (P < .02), REM latency (P < .05), REM density (P < .05), and delta sleep ratio (P < .05). After discontinuation of nortriptyline, REM percent, REM latency, and delta ratio reverted to pretreatment levels, while sleep efficiency and sleep quality continued to show improvement coincident with sustained clinical remission. These data suggest that nortriptyline may be clinically useful in treating the sleep disturbance of elders with bereavement-related depression and that a double-blind, placebo-controlled, randomized clinical trial is warranted.

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Gender-specific response to depression treatment.

Gender-specific responses to pharmacotherapy or psychotherapy for depression are virtually unknown. Early studies rarely examined treatment response by gender, and the small number of males studied has led to inaccurate comparisons between male and female response. This article addresses conceptual issues and reviews what little can be ascertained from earlier studies of the relationship between gender and treatment outcome. It also presents data from a series of studies conducted over the last 15 years at the University of Pittsburgh School of Medicine.

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