PubMed Health⌕ Search

Biomedical subjects

Harvey Moldofsky

Publications and source records attributed to Harvey Moldofsky.

10 recordsLinked to original sources
PubMed2006

Fatigue in systemic lupus erythematosus: contributions of disordered sleep, sleepiness, and depression.

OBJECTIVE: To clarify the role of sleep disorders, sleepiness, and depression in patients with systemic lupus erythematosus (SLE) who complain of disabling tiredness. METHODS: Patients with SLE (31 women, 4 men) with disabling tiredness were evaluated with the Epworth Sleepiness Scale (ESS) and overnight polysomnography, followed by daytime multiple sleep latency tests (MSLT) and the Beck Depression Inventory (BDI). Their polysomnography was compared with 17 healthy, asymptomatic controls. RESULTS: Polysomnography of the patients in comparison with healthy controls showed impaired sleep efficiency (p < 0.02), high arousal frequencies (p < 0.01), increased stage 1 sleep (p < 0.02), decreased stage 3/4 slow-wave sleep (p < 0.02), and a high percentage (77% of patients) with increased alpha-EEG non-REM sleep. In 23% of patients periodic limb movement (PLM) disorder was observed (mean PLM index 31.1 +/- 15); 26% of patients had obstructive sleep apnea (mean apnea/hypopnea index 19.3 +/- 10), and one patient had narcolepsy-cataplexy. Remarkably, 51% of patients were excessively sleepy on both the ESS and MSLT (mean sleep latency < 10 min). This excessive daytime sleepiness was not related to sleep restriction. There was no association between sleepiness and SLE disease features such as neuropsychiatric SLE, medications, fibromyalgia, or disease activity. As a whole, the study group reported mild to moderate depression (mean BDI = 15.8 +/- 9.9). Within the group, the sleepy patients had lower BDI scores than the non-sleepy patients (p < 0.02), and fewer of the sleepy patients were depressed (p < 0.04). CONCLUSION: Primary sleep disorders, sleepiness, and depression are common in tired SLE patients. Tiredness in SLE that is the result of excessive daytime sleepiness can be distinguished from tiredness of depression. Such distinctions will help identify appropriate treatment for tired patients with SLE.

Adult↗
PubMed2005

Sleep disturbance induced by substance P in mice.

UNLABELLED: Substance P (SP) and neurokinins have been implicated in modulating pain and mood but little is known about their effect on sleep-wake behavior. The purpose of the present study was to examine the possible involvement of SP in sleep-wake mechanisms without activation of painful responses. Electrophysiological recordings of the sleep-wake cycle were conducted in C57BL/6J male mice that had intracerebral ventricular cannula inserted for drug administration. Initially, in order to determine the highest dose of SP that would not induce nociceptive response, 10 animals per group received administration of either SP doses or artificial cerebrospinal fluid (CSF-sham group) through the cannula and were assessed by the hot plate test. The sleep-wake cycle of two other groups of mice was recorded for 24 h before (baseline) and after receiving CSF (n=10) or SP-1 mM (n=11), dose that had been determined in the previous hot plate test. SP interfered with sleep, when compared to baseline and to sham group, by reducing sleep efficiency, increasing latency of sleep and the number of awakening bouts. To examine the reversal of SP effects, eight mice were administered with an NK1 receptor antagonist before SP administration. Prior administration of the NK1 antagonist prevented the disturbances in sleep. CONCLUSIONS: The results suggest that SP produces disturbances in sleep, likely mediated by the NK1 receptor.

Analysis of Variance↗
PubMed2004

Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity.

The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro-orexin/hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS.

Amino Acid Sequence↗
PubMed2004

Sleep assessment in a population-based study of chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling condition that affects approximately 800,000 adult Americans. The pathophysiology remains unknown and there are no diagnostic markers or characteristic physical signs or laboratory abnormalities. Most CFS patients complain of unrefreshing sleep and many of the postulated etiologies of CFS affect sleep. Conversely, many sleep disorders present similarly to CFS. Few studies characterizing sleep in unselected CFS subjects have been published and none have been performed in cases identified from population-based studies. METHODS: The study included 339 subjects (mean age 45.8 years, 77% female, 94.1% white) identified through telephone screen in a previously described population-based study of CFS in Wichita, Kansas. They completed questionnaires to assess fatigue and wellness and 2 self-administered sleep questionnaires. Scores for five of the six sleep factors (insomnia/hypersomnia, non-restorative sleep, excessive daytime somnolence, sleep apnea, and restlessness) in the Centre for Sleep and Chronobiology's Sleep Assessment Questionnaire (SAQ) were dichotomized based on threshold. The Epworth Sleepiness Scale score was used as a continuous variable. RESULTS: 81.4% of subjects had an abnormality in at least one SAQ sleep factor. Subjects with sleep factor abnormalities had significantly lower wellness scores but statistically unchanged fatigue severity scores compared to those without SAQ abnormality. CFS subjects had significantly increased risk of abnormal scores in the non-restorative (adjusted odds ratio [OR] = 28.1; 95% confidence interval [CI]= 7.4-107.0) and restlessness (OR = 16.0; 95% CI = 4.2-61.6) SAQ factors compared to non-fatigued, but not for factors of sleep apnea or excessive daytime somnolence. This is consistent with studies finding that, while fatigued, CFS subjects are not sleepy. A strong correlation (0.78) of Epworth score was found only for the excessive daytime somnolence factor. CONCLUSIONS: SAQ factors describe sleep abnormalities associated with CFS and provide more information than the Epworth score. Validation of these promising results will require formal polysomnographic sleep studies.

Adult↗
PubMed2004

Special considerations in insomnia diagnosis and management: depressed, elderly, and chronic pain populations.

Patients with insomnia who also have chronic pain or depression or who are elderly represent segments of the population that are particularly difficult to treat. These populations tend to be at higher risk for experiencing difficulty sleeping and are more likely to experience chronic insomnia, sleep maintenance problems, and/or nonrestorative sleep. Worsening insomnia may exacerbate other somatic and psychological symptoms and vice versa. Conversely, there is evidence that appropriate recognition and management of the sleep complaint may alleviate other symptoms related to the associated condition and help interrupt this vicious cycle.

Adult↗
PubMed2002

Management of sleep disorders in fibromyalgia.

In summary, the treatment of patients with FM requires a proper assessment of the reason for the unrefreshing sleep, which is an important component of the FM syndrome. Sleep laboratory investigations provides a suitable rationale for management where a specific primary sleep disorder is determined. Nonspecific treatments include various behavioral approaches to improve sleep hygiene, fitness, and regular proper nutrition that serve to regularize disturbances in circadian sleep-wake rhythms. As yet, no medication is known to improve the EEG sleep arousal disorders that include phasic (alpha-delta), tonic alpha non-REM sleep disorders, or the periodic K alpha cycling alternating pattern disorder. Traditional hypnotic agents, while helpful in initiating and maintaining sleep and reducing daytime tiredness, do not provide restorative sleep or reduce pain. Tricyclic drugs, such as amitriptyline and cyclobenzaprine, may provide long term benefit for improving sleep but may not have a continuing benefit beyond one month for reducing pain. The use of a biologic agent that facilitates sleep-related neuroendocrine functions, for example growth hormone, is reported to improve symptoms but the need for injection and high cost restrict its use. No systematic studies have been reported on the use of remedial measures for the management of PLMS/restless legs syndrome and sleep apnea that occur in some patients with FM.

Fibromyalgia↗
PubMed2001

Sleep and pain.

Noxious stimuli and painful disorders interfere with sleep, but disturbances in sleep also contribute to the experience of pain.Chronic paroxysmal hemicrania and possibly cluster headaches are related to REM sleep. Whereas headache is associated with snoring and sleep apnea, morning headaches are not specific for any primary sleep disorder. Nevertheless, the management of the sleep disorder ameliorates both morning headache and migraine.Noxious stimuli administered into muscles during slow-wave sleep (SWS) result in decreases in delta and sigma but an increase in alpha and beta EEG frequencies during sleep. Noise stimuli that disrupt SWS result in unrefreshing sleep, diffuse musculoskeletal pain, tenderness, and fatigue in normal healthy subjects. Such symptoms accompany alpha EEG sleep patterns that often occur in patients with fibromyalgia. The alpha EEG patterns include phasic and tonic alpha EEG sleep as well as periodic K alpha EEG sleep or frequent periodic cyclical alternating pattern. Moreover, alpha EEG sleep, as well as sleep-related breathing disorder and periodic limb movement disorder, occur in some patients with fibromyalgia, rheumatoid arthritis and osteoarthritis. Depression and not alpha EEG sleep are features of somatoform pain disorder. Disturbances in sleep, pain behaviour and psychological distress influence return to work in workers who have suffered a soft tissue injury, e.g. low back pain. Patients with irritable bowel disorder have disturbed sleep and have increased REM sleep. In conclusion, there is a reciprocal relationship between sleep quality and pain. The recognition of disturbed or unrefreshing sleep influences the management of painful medical disorders.

Journal Article↗