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Biomedical subjects

H Moldofsky

Publications and source records attributed to H Moldofsky.

At least 19 recordsLinked to original sources

The Drosophila per gene homologs are expressed in mammalian suprachiasmatic nucleus and heart as well as in molluscan eyes.

This study presents evidence for the conservation of Drosophila per gene homologs in mammalian DNA and for their expression in a number of tissues which are involved in various aspects of circadian timekeeping. Distinct 5 kb sequences, which hybridized to a non repetitive fragment of the Drosophila per gene under stringent conditions, were detected by Southern blotting. Sequences homologous to per gene of Drosophila were also amplified from rat and mouse brain cDNA libraries and from a mouse anterior hypothalamus and human hypothalamus libraries. Degenerate PCR primer design was based on conserved segments of the per protein. The per homologs were shown directly (by RT-PCR) to be expressed in hamster and mouse SCN, in hamster heart and in Aplysia and Bulla eyes.

Animals

Sleep, Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome.

Sleep physiology, viral serology and symptoms of 14 patients with chronic fatigue syndrome (CFS) were compared with 12 healthy controls. All patients described unrefreshing sleep and showed a prominent alpha electroencephalographic nonrapid eye movement (7.5-11.0 Hz) sleep anomaly (p less than or equal to 0.001), but had no physiologic daytime sleepiness. There were no group differences in Epstein-Barr virus (EBV) antibody titers. The patient group had more fibrositis tender points (p less than 0.0001), described more somatic complaints (p less than 0.0001), and more depressive symptoms (p less than 0.0001). Patients with CFS do not show evidence for a specific chronic EBV infection, but show altered sleep physiology, numerous tender points, diffuse pain, and depressive symptoms. These features are similar to those found in fibromyalgia syndrome.

Adult

Evaluation of daytime sleepiness.

In summary, the evaluation of the tired patient requires an awareness of the various meanings of tiredness. Furthermore, it is important to differentiate normal sleepiness that is a product of circadian rhythm variation in vigilance from pathologic sleepiness. Sleepiness that results from faulty habits, e.g., altered sleep scheduling, drugs, or sleep restriction, can be readily discerned with the aid of a sleep-wake diary. Because subjective sleepiness is often unappreciated, especially in patients with sleep apnea, methods that rely on self-ratings of the severity of sleepiness, e.g., visual analogue scale, 10-cm line, or SSS may not coincide with performance tasks, observer assessments, or such physiologic methods as the MSLT. Less commonly employed neurophysiologic methods include pupillometry and averaged evoked potentials. On the other hand, the MSLT is commonly used for the detection of physiologic sleepiness. Moreover, it is helpful in evaluating response to treatment. A variation of the MSLT, the MWT, which instructs the individual to remain awake, does not discriminate between sleep onset times for wakefulness and the MSLT for sleepiness in normal subjects. The MWT may be useful for the assessment of treatment responses for excessive daytime sleepiness, e.g., narcolepsy, and for determining the frequency of daytime sleep episodes. The differences that have been observed between behavioral measures and physiologic measures of sleepiness suggest that these techniques assess different aspects of sleepiness. HLA typing (DR2, DQw1) has been shown to be a useful method for corroborating narcolepsy-cataplexy, but the antigens are neither specific for the disorder nor for sleepiness alone.

Diagnosis, Differential

Sleep physiology and psychological aspects of the fibrositis (fibromyalgia) syndrome.

Fibrositis (fibromyalgia) patients were compared with normal controls in terms of electrophysiology (EEG), self-report indicants of awakening, quality of sleep, behaviourally signalled awakenings, and Symptom Check List 90R (SCL-90R) scores. The results differentiated fibrositis patients from normal controls in terms of SCL-90R scores, with fibrositis patients showing significantly more psychopathology. Fibrositis patients had more alpha EEG sleep and less REM and Stage 1 sleep. They were better able to recall their behaviourally signalled awakenings the following morning and reported qualitatively less satisfying sleep than the normal controls. The alpha EEG sleep anomaly may reflect a vigilant arousal state during nocturnal sleep and result in the daytime experience of unrefreshing sleep, psychologic distress, that re-enforces the perpetuation of the sleep-related symptoms.

Adult

The effects of cyclobenzaprine on sleep physiology and symptoms in patients with fibromyalgia.

A double blind, placebo controlled, crossover design study examined overnight sleep physiology, pain, fatigue, and mood symptoms in 12 patients with fibromyalgia treated with cyclobenzaprine. Nine patients completed the study. Patients receiving cyclobenzaprine showed a decrease in evening fatigue (F = 4.7, p less than 0.05) and an increase in total sleep time (F = 4.4, p less than 0.05). Pain, including tender point count and dolorimetry, mood ratings, and alpha non-REM EEG sleep anomaly were unchanged by cyclobenzaprine.

Adult

Growth hormone and cortisol secretion in relation to sleep and wakefulness.

The study investigated secretory patterns of growth hormone (GH) and cortisol in relation to sleep and wakefulness. Plasma hormone levels were monitored in 10 young men during baseline waking and sleeping, during 40 hours of wakefulness, and during sleep following deprivation. The normal nocturnal GH surge disappeared with sleep deprivation, and was intensified following sleep deprivation. Mean GH levels were higher during slow wave sleep (SWS) compared with other sleep stages. During sleep after deprivation, GH secretion was prolonged, and second GH peaks occurred in three subjects which were not associated with SWS. Average 24-hour cortisol levels were not altered by sleep deprivation or sleep following deprivation, but the nocturnal cortisol rise occurred approximately one hour earlier with sleep deprivation and one hour later with resumed sleep, compared to baseline. This effect on the timing of the rise is consistent with an initial inhibitory influence of sleep on cortisol secretion. The results demonstrate that: the nocturnal growth hormone surge is largely sleep-dependent; temporal associations between GH and SWS are not reliable after sleep deprivation; although the cortisol rhythm is not sleep-dependent, the timing of the cortisol rise may be influenced by sudden changes in the sleep-wake schedule.

Adult

Tourette syndrome: a follow-up study.

We describe a long-term follow-up study (1-15 years) of 33 patients with Tourette syndrome who were treated with pimozide (2-18 mg), haloperidol (2-15 mg), or no drugs. Both drugs produced comparable relief of symptoms at follow up; however, significantly more patients on haloperidol (eight of 17), compared with those on pimozide (one of 13), discontinued treatment (p less than or equal to 0.05). Haloperidol produced significantly more acute dyskinesias/dystonias than pimozide (p less than or equal to 0.03); otherwise, the adverse effect profile was similar for the two drugs. In particular, we found no increased incidence of ECG abnormalities in patients treated with pimozide. A prospective, randomized, double-blind crossover trial is required to determine whether there are significant differences in efficacy between pimozide and haloperidol in treatment of Tourette's disorder.

Adolescent

Effects of sleep deprivation on human immune functions.

The effect of 40 h of wakefulness on a variety of immunological parameters in the peripheral blood from 10 normal male subjects was studied. Sleep deprivation led to enhanced nocturnal plasma interleukin 1-like and interleukin 2-like activities. The rise in nocturnal response of lymphocytes to pokeweed mitogen stimulation during a normal 24 h sleep-wake cycle was delayed by sleep deprivation, but the response to the phytohemagglutinin mitogen was unaffected. With resumed nocturnal sleep, there was a prolonged decline in natural killer cell activity (measured as spontaneous cytolytic activity for human tumor cells) and return of an increased response to pokeweed mitogen. The altered patterns in immune functions occurred independently of the cortisol circadian rhythm, which remained unchanged.

Adult

Sleep and fibrositis syndrome.

Chronic diffuse myalgia, localized areas of tenderness, fatigue, and unrefreshing sleep are related to a physiologic arousal disorder within sleep, that is, the alpha EEG NREM sleep anomaly. This sleep physiologic disorder, nonrestorative sleep, and symptoms of fibrositis syndrome are shown to occur with psychologic, environmental, and physiologic distress conditions. Pathogenic mechanisms that link nonrestorative sleep physiology to pain and fatigue may involve metabolic dysfunction of the brain with sleep-related alteration in immunologic and neurotransmitter functions (serotonin, substance P, endorphins). These sleep-related mechanisms have important implications for the understanding and treatment of fibrositis/fibromyalgia syndrome.

Alpha Rhythm

Sleep-wake mechanisms in fibrositis.

Patients with fibrositis experience chronophysiologic changes during sleep and when they are awake. A wide variety of factors contribute to this phenomenon. Chronobiologic research in the area of sleep-wake mechanisms need to be undertaken.

Biomechanical Phenomena

Fiscal and service analyses in general hospital psychiatry.

Fiscal matters were analyzed in four specialized programmes of the Department of Psychiatry at the Toronto Western Hospital in order to plan for service and academic activities. The resultant analysis allowed for the establishment of criteria for growth and the evaluation of clinical service performance and goals.

Cost-Benefit Analysis

Neurosarcoidosis associated with hypersomnolence treated with corticosteroids and brain irradiation.

Narcoleptic features developed in a young man with CNS sarcoidosis. This was associated with a structural lesion in the hypothalamus as demonstrated on CT scans of the head. The diagnosis of narcolepsy was established by compatible clinical history and the Multiple Sleep Latency Test. Treatment with high-dose corticosteroids was ineffective, but when the low-dose, whole-brain irradiation was added, complete resolution of the narcoleptic features ensued.

Adult

Sleep and symptoms in fibrositis syndrome after a febrile illness.

Sleep physiology and symptoms of 9 patients with fibrositis syndrome secondary to a febrile illness were compared to 9 patients with fibrositis syndrome who did not attribute their symptoms to a febrile illness and to 10 healthy controls. Both patient groups showed an alpha EEG (7.5 to 11 Hz) nonrapid eye movement sleep anomaly, had similar observed tender points, and self-ratings of musculoskeletal pain. These findings suggest that patients with postfebrile fibrositis have a nonrestorative sleep disorder characteristic of patients with fibrositis syndrome and share similar symptoms with patients who have a "chronic fatigue syndrome."

Adult