Biomedical subjects

A Kales

Publications and source records attributed to A Kales.

At least 37 records · Page 2Linked to original sources

PubMed1997

Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity.

Excessive daytime sleepiness (EDS) and fatigue are frequent symptoms in the general population and the chief complaint of the majority of patients at Sleep Disorders Centers. There is evidence that the inflammatory cytokines tumor necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1beta), and IL-6 are involved in physiological sleep regulation and that their administration to humans is associated with sleepiness and fatigue. To explore whether plasma levels of TNF alpha, IL-1beta, and IL-6 are elevated in patients with EDS, we measured morning plasma levels of TNF alpha, IL-1beta, and IL-6 in 12 sleep apneics, 11 narcoleptics, 8 idiopathic hypersomniacs, and 10 normal controls. TNF alpha was significantly elevated in sleep apneics and narcoleptics compared to that in normal controls (P < 0.001 and P = 0.001, respectively). Plasma IL-1beta concentrations were not different between sleep disorder patients and controls, whereas IL-6 was markedly and significantly elevated in sleep apneics compared to that in normal controls (P = 0.028). The primary factor influencing TNF alpha values was the degree of nocturnal sleep disturbance, whereas the primary determinant for IL-6 levels was the body mass index. Our findings suggest that TNF alpha and IL-6 might play a significant role in mediating sleepiness and fatigue in disorders of EDS in humans.

Adult↗

PubMed1996

Relationship of sleep abnormalities to patient genotypes in Prader-Willi syndrome.

To assess whether sleep abnormalities are related to the genetic abnormalities in Prader-Willi Syndrome (PWS), we performed polysomnographic studies (nighttime and daytime) and determined the chromosome 15 genotypes in eight patients with PWS. Four patients demonstrated sleep onset REM periods (SOREM), and five met the objective polysomnographic criteria for severe or moderate excessive daytime sleepiness (EDS). Three of the four patients with SOREM displayed a paternally derived deletion of chromosome 15q11-q13, whereas the fourth exhibited maternal uniparental heterodisomy in this chromosomal region (UPD). Two of the four patients that did not display SOREM carried paternally derived deletions; the remaining two demonstrated UPD. Four of the five patients with EDS displayed paternal deletions, and the fifth exhibited UPD. One of three patients without evidence of EDS demonstrated paternal deletion; the remaining two showed UPD. Although neither EDS nor SOREM was not consistently associated with a specific genetic abnormality, these phenotypes may be more common in patients with paternal deletions than in those UPD. Sleep abnormalities in PWS cannot be explained by a single genetic model.

Adolescent↗

PubMed1996

Narcolepsy-cataplexy and loss of sphincter control.

We describe the case of a 34-year-old man who presented intermittent faecal incontinence as a manifestation of cataplexy. The patient's sleep history was positive for the full narcoleptic tetrad (sleep attacks, cataplexy, sleep paralysis and hypnagogic hallucinations) while extensive neuropsychiatric work up was negative for any neurologic or psychiatric illness. Repeat polysomnograms (including a polysomnogram with a full seizure montage) were positive for pathologic sleepiness, but there was no evidence of a seizure disorder. The course of the patient's symptomatology and the favourable response of his symptoms to stimulants and imipramine support the theory that his intermittent loss of sphincter control is part of his narcolepsy-cataplexy.

Adult↗

PubMed1996

Daytime sleepiness and REM abnormalities in Prader-Willi syndrome: evidence of generalized hypoarousal.

The aim of this study was to clarify the nature of the sleep abnormalities (excessive daytime sleepiness [EDS] and rapid eye movement [REM] sleep alterations) in Prader-Willi; Syndrome (PWS). Eight PWS patients, 15 normal, 16 narcoleptic, and 16 obese subjects were recorded in the sleep laboratory, both during daytime and nighttime. A principal-finding was that EDS in PWS was associated with an increased amount and depth of sleep. In PWS patients with EDS, compared to those PWS patients without EDS or the narcoleptic, obese, and normal groups, there were significant decreases in wakefulness and increases in percentage of sleep time (ST) and slow-wave sleep (SWS) both during daytime and nighttime testing. Also, in the adult PWS subjects (n = 6), in contrast to normal narcoleptic subjects, intensity of EDS was correlated with increased nocturnal percentage of ST and SWS and % SWS was positively correlated with % ST (both during daytime and nighttime testing). Another principal finding was that in PWS there is a unique alteration of the distribution of REM sleep in relation to controls. PWS patients with EDS or shortened nocturnal REM latencies showed a significantly increased number of REM periods, and a decreased average REM interval between REM periods compared to PWS patients with nonshortened nocturnal REM latencies or to the three control groups. Our data suggest that EDS and REM abnormalities in PWS are not manifestations of a narcoleptic-type syndrome or consequences of obesity. We propose that generalized 24-hour hypoarousal is the primary mechanism underlying the sleep abnormalities in PWS patients.

Adolescent↗

PubMed1995

Delta sleep-inducing peptide in normal humans and in patients with sleep apnea and narcolepsy.

We measured morning plasma concentrations of delta sleep-inducing-peptide-like-immunoreactivity (DSIP-LI) in 9 sleep apnea patients, 10 narcolepsy patients, and 11 normal controls. Comparisons between the three groups showed no significant differences, although there was a trend toward association with low levels of DSIP-LI in the narcoleptic group, particularly in patients not using medications. No differences were found in the morning or evening plasma DSIP-LI levels in a second group of 11 normal controls and 8 sleep apneics. Our findings do not appear to support a biological marker role of disease activity for single measures of plasma DSIP in sleep apnea.

Adult↗

PubMed1995

Prader-Willi syndrome: effects of weight loss on sleep-disordered breathing, daytime sleepiness and REM sleep disturbance.

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Adult↗

PubMed1995

Benzodiazepine side effects: role of pharmacokinetics and pharmacodynamics.

Benzodiazepines have a wide variety of indications. However, CNS and psychiatric adverse reactions, tolerance, and withdrawal effects of benzodiazepines are becoming increasingly recognized and must be better understood for proper drug use. Certain benzodiazepines are associated with memory impairment and other cognitive defects and hyperexcitability phenomena during treatment (early-morning insomnia, daytime anxiety) and following withdrawal (rebound insomnia and anxiety, seizures). Elimination half-life, receptor-binding affinity, effects on the locus coeruleus-norepinephrine (LC-NE) and hypothalamic-pituitary-adrenal (HPA) axes, and the interaction of these factors appear to be major determinants of frequency and severity of these untoward effects. Rapid drug elimination and high receptor-binding affinity were initially suggested as primary underlying factors which determine frequency, severity, and type of the side effects of benzodiazepines during administration and withdrawal. Newer data and information on triazolobenzodiazepines indicate that these psychiatric adverse reactions also relate to whether the benzodiazepine has strong direct effects on the LC-NE and HPA systems. Initial suppression of the LC-NE and HPA systems is followed, on an interdose basis, by a significant rebound and activation. This repetitive pattern of suppression followed by rebound results in a neurophysiologic and behavioral sensitization (kindling) of the limbic system and consequently contributes to central nervous system and psychiatric adverse reactions. The tendency of certain of these side effects to worsen over time supports empirically this neurophysiologic and biochemical model.

Amnesia↗

PubMed1995

Usefulness of polysomnographic studies in the differential diagnosis of insomnia.

The prevalence of sleep apnea, sleep apneic activity, nocturnal myoclonus, and nocturnal myoclonic activity was assessed in 375 outpatient insomniacs and 150 normal controls. Only a small percentage of insomniacs (n = 8, 2.3%) and normal controls (n = 2, 1.3%) presented > or = 30 apneic events per night. Only one of these subjects, an insomniac, met the laboratory and clinical criteria of sleep apnea sufficient to recommend treatment. A limited amount of sleep apneic activity per subject (only 3-29 apneic events per night) was evenly distributed between insomniacs (n = 52, 13.9%) and normal controls (n = 22, 14.7%). Also, small percentages of insomniacs (n = 43, 11.5%) and normal controls (n = 11, 8.5%) displayed nocturnal myoclonus (five or more leg movements per hour) or nocturnal myoclonic activity (less than five movements per hour). Thus, these results do not support the claim that sleep apnea or nocturnal myoclonus are common causes of insomnia. In addition, different cutoff points of REM latency (based on first-night recordings) were associated with very low sensitivity and moderately high specificity resulting in inadequate levels of diagnostic accuracy in differentiating depressed insomniacs from non-depressed insomniacs. Finally, empirically optimized values for REM variables were less successful than similarly optimized MMPI values in differentiating depressed insomniacs from nondepressed ones. In conclusion, with our current level of knowledge, polysomnography has limited clinical usefulness in the differential diagnosis of insomnia.

Adolescent↗

PubMed1994

Sleep apnea and sleep disruption in obese patients.

OBJECTIVES: To describe the frequency and severity of sleep apnea in obese patients without a primary sleep complaint and to assess the sleep patterns of obese patients without apnea and compare them with the sleep patterns of nonobese controls. DESIGN AND SETTING: Prospective case series with historical controls in an obesity and sleep disorders clinic. SUBJECTS: Two hundred obese women and 50 obese men (mean body mass index, 45.3) consecutively referred for treatment of their obesity and 128 controls matched for age and sex. MAIN OUTCOME MEASURES: Eight-hour sleep laboratory recording, including electroencephalogram, electro-oculogram, electromyogram, and respirations. Subjectively reported sleep-related symptoms and signs were also recorded. RESULTS: Twenty men (40%) and six women (3%) demonstrated sleep apnea warranting therapeutic intervention. Another four men (8%) and 11 women (5.5%) showed sleep apneic activity that warranted recommendation for evaluation in the sleep laboratory. In contrast, none of the 128 controls demonstrated sleep apneic activity severe enough for therapeutic intervention. The best clinical predictors of sleep apnea in the obese population were severity of snoring, subjectively reported nocturnal breath cessation, and sleep attacks. Obese patients, both men and women, without any sleep-disordered breathing demonstrated a significant degree of sleep disturbance compared with nonobese controls. Wake time after sleep onset, number of awakenings, and percentage of stage 1 sleep were significantly higher in obese patients than in controls, while rapid eye movement sleep was significantly lower. CONCLUSION: Severely or morbidly obese men are at extremely high risk for sleep apnea and should be routinely evaluated in the sleep laboratory for this condition, while for severely or morbidly obese women the physician should include a thorough sleep history in the clinical assessment.

Adolescent↗

PubMed1994

Temazepam 7.5 mg: effects on sleep in elderly insomniacs.

Temazepam, 7.5 mg was evaluated in the sleep laboratory in 8 elderly insomniacs, using a 14-night protocol (4 placebo-baseline nights, 7 drug nights, and 3 placebo-withdrawal nights). With short-term use temazepam was found to be effective, producing a significant improvement in total wake time from baseline (100 vs. 145 min). With continued drug administration, total wake time remained below baseline but not significantly so (125 vs. 145 min). During drug administration, there were no major CNS and behavioral adverse effects reported such as daytime sedation, memory impairment or hyperexcitability (daytime anxiety). Following drug withdrawal, there was no significant increase in wakefulness, i.e., no rebound insomnia (150 vs. 145 min). In summary, temazepam, 7.5 mg is effective in elderly subjects with short-term use and has a minimum of adverse effects. Use of hypnotic drugs is an adjunctive therapy which should be for a short-term period with subsequent short-term intermittent use as needed. Because of its low propensity for producing rebound insomnia, temazepam can be effectively used in this manner.

Aged↗

PubMed1994

Clinical diagnoses in 216 insomnia patients using the International Classification of Sleep Disorders (ICSD), DSM-IV and ICD-10 categories: a report from the APA/NIMH DSM-IV Field Trial.

Three diagnostic classifications for sleep disorders have been developed recently: the International Classification of Sleep Disorders (ICSD), the Diagnostic and Statistical Manual, 4th edition (DSM-IV), and the International Classification of Diseases, 10th edition (ICD-10). No data have yet been published regarding the frequency of specific diagnoses within these systems or how the diagnostic systems relate to each other. To address these issues, we examined clinical sleep disorder diagnoses (without polysomnography) in 257 patients (216 insomnia patients and 41 medical/psychiatric patients) evaluated at five sleep centers. A sleep specialist interviewed each patient and assigned clinical diagnoses using ICSD, DSM-IV and ICD-10 classifications. "Sleep disorder associated with mood disorder" was the most frequent ICSD primary diagnosis (32.3% of cases), followed by "Psychophysiological insomnia" (12.5% of cases). The most frequent DSM-IV primary diagnoses were "Insomnia related to another mental disorder" (44% of cases) and "Primary insomnia" (20.2% of cases), and the most frequent ICD-10 diagnoses were "Insomnia due to emotional causes" (61.9% of cases) and "Insomnia of organic origin" (8.9% of cases). When primary and secondary diagnoses were considered, insomnia related to psychiatric disorders was diagnosed in over 75% of patients. The more narrowly defined ICSD diagnoses nested logically within the broader DSM-IV and ICD-10 categories. We found substantial site-related differences in diagnostic patterns. These results confirm the importance of psychiatric and behavioral factors in clinicians' assessments of insomnia patients across all three diagnostic systems. ICSD and DSM-IV sleep disorder diagnoses have similar patterns of use by experienced clinicians.

Adolescent↗

PubMed1994

Diagnostic concordance for DSM-IV sleep disorders: a report from the APA/NIMH DSM-IV field trial.

OBJECTIVE: The frequency and ranking of DSM-IV sleep disorder diagnoses of clinical patients with complaints of insomnia, as well as rates of diagnostic agreement and disagreement between two types of interviewers, were investigated. METHOD: Interviewers at five clinical sites assessed 216 patients referred for insomnia complaints. One sleep specialist and one general clinician interviewed each patient in an unstructured clinical interview, assigned DSM-IV diagnoses, and indicated their reactions to the diagnostic system. RESULTS: Insomnia due to another mental disorder was the most frequent DSM-IV diagnosis across sites, followed by primary insomnia. Interviewers at the five sites differed significantly in the rankings they assigned to different diagnoses. In addition, sleep specialists at most sites diagnosed psychiatric forms of insomnia more frequently than nonspecialists. Kappa values for agreement between the two types of clinicians on multiple DSM-IV sleep diagnoses ranged from 0.26 to 0.80 across sites, indicating moderate agreement overall. Kappa values for individual diagnoses varied across sites and specific diagnoses and ranged from poor to excellent. Interviewers' ratings of their confidence in diagnoses and the fit and ease of use of the DSM-IV categories also showed significant variability related to site and type of interviewer. CONCLUSIONS: The distribution of diagnoses highlights the importance of psychiatric and behavioral factors in the assessment of insomnia. Site-related variability indicates a need for greater standardization in the application of sleep disorder diagnostic criteria. Diagnostic concordance for these diagnoses, while only moderately good, likely reflects actual clinical practice and would be improved through the use of standardized (or structured) interviews and increased training.

Adult↗

PubMed1994

Validity and clinical utility of sleep laboratory criteria for insomnia.

The sensitivity, specificity, and positive predictive value of two proposed sleep laboratory criteria for the diagnosis of insomnia were evaluated in 375 adults with a primary complaint of insomnia and 150 noninsomniac controls. The two criteria used results in either low sensitivity and moderately strong specificity or high sensitivity and low specificity and, accordingly, in both cases weak positive predictive values (diagnostic accuracy), both for one night and multiple nights of recordings. Further, an empirically optimized criterion also resulted in an unsatisfactory diagnostic accuracy. Finally, the optimized MMPI criteria were superior to optimized sleep criteria in differentiating insomniacs from controls. In conclusion, sleep laboratory recordings provide little relevant information for confirming or excluding the presence of insomnia.

Adolescent↗

PubMed1993