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Biomedical subjects

T Roth

Publications and source records attributed to T Roth.

At least 19 recordsLinked to original sources
PubMed1992

Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime performance.

Pravastatin and lovastatin, two HMG-CoA reductase inhibitors with similar cholesterol-lowering effects, differ in their lipid solubility. The hydrophilic characteristics of pravastatin may explain why the drug has not been detected in cerebrospinal fluid. On the other hand, lovastatin, a lipophilic compound, has been detected in the cerebrospinal fluid. Previous reports have suggested that lovastatin administration may be associated with insomnia, which reflects an action in the central nervous system. The effects of the two drugs on nocturnal sleep and day-time performance in young, healthy men have been assessed in randomized, double-blind, placebo-controlled studies. Computer-based performance tests were administered on two consecutive days before drug administration and at the end of a 3-week active drug or placebo treatment period. Results from both sites were combined for analysis. Neither pravastatin nor lovastatin significantly affected nocturnal sleep or daytime sleepiness in this study population, but lovastatin significantly affected daytime performance. In subjects treated with lovastatin, the results showed that two measures of performance, divided attention (p less than 0.05) and vigilance (p less than 0.01), worsened significantly from baseline as did global performance (p less than 0.01). Performance was not affected in the pravastatin and placebo groups. These results provide preliminary evidence of an adverse effect of lovastatin on daytime performance.

Adolescent↗
PubMed1992

Rebound insomnia and hypnotic self administration.

Twenty-one (three groups of seven), men and women, 25-50 years of age were studied to determine whether or not rebound insomnia would increase the likelihood of self administering a benzodiazepine (triazolam 0.25 mg) hypnotic. The groups compared were patients with insomnia and disturbed sleep, insomnia and normal sleep, and healthy normals. Rebound insomnia, by both subjective and polysomnographic assessment, was induced. The experience of rebound insomnia did not increase the likelihood of self administering a benzodiazepine hypnotic in any of the groups. There were clear group differences in pill self administration with normals rarely and insomnia patients frequently, but not differentially (placebo versus active drug) self administering pills.

Adult↗
PubMed1992

Rebound insomnia in normals and patients with insomnia after abrupt and tapered discontinuation.

Rebound insomnia was studied in subjects, aged 25-50 years, with insomnia complaints and normal sleep, insomnia complaints and disturbed sleep, and normal sleep with no complaints (N = 21, n = 7 per group). Standard sleep recordings were collected on a baseline night and after abrupt discontinuation of 6 nights of 0.50 mg triazolam, tapered discontinuation (3 nights of 0.50 mg, 2 nights of 0.25 mg, and 1 night of 0.125 mg triazolam) and 6 nights of placebo. Significantly disturbed sleep on the discontinuation night compared to the baseline night was found. The relative degree of rebound insomnia was greater in the abrupt condition than in either the tapered or placebo conditions. The tapered condition reduced sleep time by half that of the abrupt condition which was twice the reduction found in the placebo condition. An overall (regardless of group or condition) difference in baseline versus discontinuation sleep was found, suggesting that pill discontinuation itself leads to sleep disturbance. Subjects did not differ in rebound insomnia as a function of pre-existing sleep disturbance.

Adult↗
PubMed1992

Biperiden administration during REM sleep deprivation diminished the frequency of REM sleep attempts.

Sixteen subjects were assigned to a group using either placebo or biperiden, with eight subjects in each group. Both groups were studied for one acclimatization night, one baseline night, four nights of rapid eye movement (REM) sleep deprivation and two recovery nights. All the subjects received either placebo or 4 mg biperiden 1 hour before sleep during the four nights of REM sleep deprivation. During the baseline and the recovery nights both groups received placebo capsules. The results showed that REM sleep time during the REM sleep deprivation was reduced by 70-75% below the baseline night in both groups. The number of attempts to enter REM sleep was significantly reduced by biperiden as compared to placebo for each of the four REM sleep deprivation nights. Because the total sleep time in the biperiden group was reduced, the number of REM sleep attempts was corrected by the total sleep time. The adjusted number of REM sleep attempts was also significantly reduced in the biperiden group. REM sleep latency showed a reduction in the placebo group, whereas in the biperiden group REM sleep latency was unchanged throughout the deprivation nights. In the recovery night REM sleep time was increased in both groups, with no differences between the groups. The REM sleep latency showed a reduction in the first recovery night in both groups that persisted through the second recovery night. The above findings support the role of biperiden as a REM sleep suppressive drug.

Adult↗
PubMed1992

Sedating effects of ethanol and time of drinking.

Ethanol (0.5 g/kg) was administered to 12 healthy, normal-sleeping men, aged 21 to 45, at two different times of the day (0900 and 1700 hr). The Multiple Sleep Latency Test (MSLT) was conducted at 1000, 1200, 1400, and 1600 hr in the day drinking condition and at 1800, 2000, 2200, and 2400 hr in the evening drinking condition. On placebo, sleepiness was greater in the daytime testing hours than in the evening, replicating findings on the circadian rhythm of sleepiness/alertness. There was a time of drinking (day versus evening) by ethanol interaction. An ethanol effect on sleep latency was found in the daytime hours, when alertness was relatively low. Ethanol failed to have a significant effect on sleep latency during the evening hours when alertness levels were increasing. Performance on a divided attention task, administered 1 hr postconsumption, was impaired by ethanol consumption, but did not vary as a function of time of drinking (day versus evening). However, at 5 hr postconsumption, mean reaction time on the first 20 min of a 40-min auditory vigilance task was slowed by ethanol to a greater extent after day drinking then after evening drinking.

Adult↗
PubMed1992

Long-term study of the sleep of insomnia patients with sleep state misperception and other insomnia patients.

OBJECTIVE: The objectives were 1) to investigate differences among patients with subjective insomnia (sleep state misperception), patients with objective findings of insomnia, and normal volunteers and 2) to assess the consistency of the sleep findings during a 2-month period. METHOD: Twenty-one subjects were studied. Subjects with sleep state misperception (N = 7) had insomnia complaints for more than 1 year, no objective sleep disturbance, and sleep efficiency of 90% or greater (on the diagnostic screening sleep recording), while subjectively estimating that sleep time was less than 6.5 hours. Subjects with objective insomnia (N = 7) met the same subjective criteria, but objectively sleep efficiency was 85% or less. Normal subjects (N = 7) had no insomnia complaints and objective sleep efficiency of 90% or greater. All subjects were recorded on 2 consecutive nights three times with a 3-week period between each pair of nights (6 standard all-night polysomnographic sessions of 8 hours). A subjective sleep questionnaire was administered after each sleep recording night. RESULTS: Sleep stage variables (percentages) were similar between the two insomnia groups, and both were different from the normal subjects. Sleep continuity variables were disturbed in the objective insomnia group, but they were similar in the sleep state misperception and normal groups. Both insomnia groups rated their sleep as inadequate on the questionnaires and differed from the normal subjects. The distinct sleep patterns of each of the three groups did not vary over the 6 nights of assessment. CONCLUSIONS: Sleep state misperception may be a prodromic or transitional state of sleep dysfunction between normal sleep and the sleep pattern of objective insomnia.

Adult↗
PubMed1992

Pap smear histories in a medical clinic: accuracy of patients' self-reports.

Women using the medical clinic of a public hospital were interviewed about their Pap smear histories to assess the accuracy of self-reported smears and to identify groups in need of further screening. Interview data from 263 women were compared with cytology files and hospital records. In spite of considerable agreement between patient report and record, patients reported significantly more recent smears than were documented. Accuracy of recall was not dependent on age or birthplace, but on the length of time since the last smear. About half the women had been screened within the past two years, whereas one tenth had never been screened. Women aged 65 years or older had fewer recent smears than younger women, while foreign born women were more likely never to have had a Pap smear than were United States born women. We conclude that self-reported information is useful in assessing Pap smear histories, but the screening rates that result should be treated as high estimates. Significant opportunities for screening exist in ambulatory care sites in low-income communities.

Age Factors↗
PubMed1992

Multiple Sleep Latency Test: technical aspects and normal values.

Excessive daytime sleepiness is now recognized as an important medical problem. This paper describes the Multiple Sleep Latency Test (MSLT), a direct, objective method of measuring daytime sleepiness. The standard methodology of the MSLT is outlined, including a description of possible and sources of error in conducting an MSLT. Data regarding the reliability and validity of the MSLT are presented. Finally, normal values are offered, and clinical MSLT results in patients with disorders of excessive daytime sleepiness are interpreted.

Cerebral Cortex↗
PubMed1992

Issues in the use of benzodiazepine therapy.

In selecting a hypnotic for the symptomatic management of insomnia, clinicians should look for those that most favorably balance sleep induction and sleep maintenance with potential adverse side effects. While all benzodiazepines have demonstrated efficacy in nocturnal sedation, the side effects of different compounds--and different doses of the same compound--vary greatly. The most common adverse effects associated with benzodiazepines are residual sedation, anterograde amnesia, and rebound insomnia, which are also related to the insomnia complaint itself. Therefore, careful evaluation of the dose of a benzodiazepine hypnotic is the key to effective treatment of insomnia without inducement of adverse effects. The most common side effects of hypnotics and their relation to drug dose are reviewed.

Amnesia↗
PubMed1991

HLA DR2 in narcolepsy with sleep-onset REM periods but not cataplexy.

To determine the association of HLA DR2 in patients with narcolepsy without cataplexy, a case-control study was performed. Patients receiving the diagnosis of narcolepsy without cataplexy had excessive daytime sleepiness (EDS) and polysomnographic findings consistent with narcolepsy but no clinical evidence of cataplexy. Of 28 patients identified, 12 agreed to return for HLA typing. Respondents did not differ from nonrespondents in demographic, clinical, or sleep laboratory data. The comparison group was 503 individuals, those 30 years and older, on the Michigan Kidney Transplant Registry. The odds ratio obtained from logistic regression indicated a strong association between narcolepsy without cataplexy and HLA DR2. To control for potential confounding variables, multivariate models were constructed to explore the joint effects of HLA DR2 and each one of the covariates (age, sex, and race), their possible combinations, and the effect of all three covariates. The odds ratios decreased minimally and the association between the disease and HLA DR2 remained significant.

Adult↗
PubMed1991

Expression of genes related to the extracellular matrix in human endothelial cells. Differential modulation by elevated glucose concentrations, phorbol esters, and cAMP.

To identify agents and mechanisms responsible for the thickened basement membranes characteristic of diabetic angiopathy we examined the effects of high glucose (30 mM) on the expression of genes related to extracellular matrix composition and turnover and investigated whether the changes induced by high glucose were mimicked and sustained by activation of protein kinase C or A. In human umbilical vein endothelial cells high glucose increased fibronectin, collagen IV, tissue plasminogen activator (tPA), and plasminogen activator-inhibitor 1 (PAI-1) mRNA levels 2-fold but did not affect type IV and interstitial collagenase expression. Acute treatment with phorbol esters resulted in increased collagen IV, tPA, PAI-1, and interstitial collagenase mRNAs; the type IV collagenase mRNA levels were instead suppressed to 50% of control. Upon longer exposure to phorbol esters (48 h) suppression of fibronectin and PAI-1 mRNAs also occurred. Intracellular elevation of cAMP led to over-expression of fibronectin and type IV collagenase and potentiated the effects of phorbol esters on collagen IV, tPA, and interstitial collagenase expression. The mRNA changes induced by high glucose occurred in the absence of protein kinase C activation or cAMP elevation. These studies indicate that events other than activation of protein kinase C or A bridge high ambient glucose to changes in endothelial cell gene expression that may contribute to diabetic angiopathy.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Development of non-Hodgkin's lymphoma of the colon after radiation therapy for Hodgkin's disease.

Developments in the therapeutic approach to Hodgkin's disease have resulted in excellent long-term survival statistics. However, these patients are at risk for second malignancies, most commonly acute myelogenous leukemia and non-Hodgkin's lymphoma. We present a patient who developed non-Hodgkin's lymphoma of the colon simulating adenocarcinoma 14 years after successful radiation therapy for Hodgkin's disease.

Colonic Neoplasms↗
PubMed1991

Enforced 24-hour recovery following sleep deprivation.

The pattern of recovery sleep after sleep deprivation was investigated in healthy young adults. Six subjects experienced three experimental conditions (0, 24, and 48 hr sleep deprivation) in a Latin Square design. The recovery period consisted of a 24-hr enforced time in bed during which subjects were polysomnographically recorded beginning at 0800. To assess the differential effects of the deprivation conditions, the total sleep time on the 24-hr recordings was submitted to a six (4-hr block) by three (deprivation condition) multivariate analysis of variance. Subjects slept more following the 24- and 48-hr conditions when compared to the 0-hr condition. Across conditions, subjects slept more during the first 4 hr when compared to the remaining five blocks. Importantly, there was a significant interaction of sleep deprivation by 4-hr block. In block 1 sleep was differentially recovered between each condition with more sleep being recorded following longer hours of deprivation. In block 2 subjects in the 24- and 48-hr conditions slept comparable amounts and significantly more than those in the 0-hr condition. In blocks 3 and 4 only the 48-hr condition exhibited significantly more sleep than the 0-hr condition. However, significantly less sleep was found in block 6 following the 48-hr condition. Overall, subjects recovered 72% and 42% of the total amount of sleep lost during the 24- and 48-hr conditions, respectively.

Adult↗
PubMed1991

Characteristics and mechanisms of high-glucose-induced overexpression of basement membrane components in cultured human endothelial cells.

Growing evidence that high glucose may be a causative agent of the thickened vascular basement membranes that characterize diabetic microangiopathy prompted this investigation of the underlying mechanisms. When exposed to 30 mM glucose, 70% of 52 primary cultures of human endothelial cells, each derived from a single umbilical vein, showed increased levels of fibronectin (median 181% of control, range 104-549%) and collagen IV mRNA (175% of control, range 101-807%). The response of the two transcripts to high glucose was concordant in 77% of the 52 cultures studied (P = 0.01), required 5 days of exposure, and was accompanied by proportionally increased synthesis of the respective protein. Laminin B1 expression was also upregulated by high glucose, concordantly with that of fibronectin and collagen IV. Increased fibronectin and collagen IV mRNA levels resulted from increased gene transcription (median 183 and 236% of control, respectively) without evidence of translational regulation, were not triggered by hypertonicity or signals originating from the matrix, and were also induced by hexoses with limited (D-galactose) or no (L-glucose) access to metabolic pathways but capable of inducing nonenzymatic glycosylation. There was no amplification of the overexpressed genes. Thus, high glucose upregulates in a coordinated fashion the transcription of genes coding for basement membrane components through effects exerted intracellularly or at the cell-matrix boundary and modulated by individual characteristics of the target cells.

Basement Membrane↗
PubMed1991

A review of the safety profiles of benzodiazepine hypnotics.

Although over 20 years of clinical experience with benzodiazepine hypnotics have demonstrated their relative safety, flurazepam, temazepam, triazolam, and quazepam do not have identical safety profiles. Dose-related central nervous system (CNS) depression such as daytime sedation and psychomotor impairment may be expected because they are an extension of the therapeutic action of these agents. Therefore, drug dose is an important factor in determining the expected frequency and severity of these side effects. Also, it is important for a clinician not to assume that these unwanted CNS effects relate only to the length of a drug's half-life. Half-life does appear to be an important determinant of the presence or absence of rebound insomnia.

Aged↗
PubMed1991

Rebound insomnia: duration of use and individual differences.

This study assessed consistency, duration of use, and individual difference in rebound insomnia. Eleven healthy men, 20-30 years old, with normal sleep by both subjective and polysomnographic criteria, received each of four treatments in a double-blind Latin Square design (triazolam 0.50 mg for 1, 6, and 12 nights and placebo for 12 nights), followed by two placebo discontinuation nights. Triazolam increased sleep compared with placebo without differences in effects between the first and last nights of treatment. On discontinuation following active drug, sleep efficiency was reduced compared with placebo, but duration of administration did not alter the likelihood or intensity of rebound insomnia. Those subjects (5) showing poorer sleep on discontinuation from the 12-night treatment also had poorer sleep in the 1- and 6-night treatment. Subjects with rebound insomnia had poorer baseline sleep and a greater drug effect than did subjects without.

Adult↗
PubMed1991

Alerting effects of caffeine after normal and restricted sleep.

To assess the alerting effects of caffeine after normal and restricted nocturnal sleep, 36 healthy, nonsmoking men, 19 to 35 years old, who reported normal sleep and daytime alertness received 0, 75, or 150 mg caffeine twice daily after 8 and 5 hours in bed the previous night. Sleep restriction reduced average daily sleep latency measured by the Multiple Sleep Latency Test (MSLT) and slowed auditory vigilance reaction time in the latter half of the 40-minute task. Caffeine (75 and 150 mg) increased average daily sleep latency and improved vigilance reaction time. However, sleep restriction did not alter the alerting effects of caffeine. The data show that, unlike ethanol, basal level of sleepiness/alertness does not interact with the effects of caffeine.

Adult↗