Drug-induced sleep disorders]

Mismatch repair genes are involved in increasing the fidelity of replication by specific repair of DNA polymerase incorporation errors. In Escherichia coli, the best studied mismatch repair (MMR) pathway is the methyl-directed long patch repair system which is mediated by three gene products; MutS, MutL and MutH. These are conserved in higher eukaryotes. Mutations in human homologues of these proteins have been shown to be implicated in hereditary non-polyposis colorectal cancer (HNPCC). Alterations in the coding regions of MMR genes result in a mutator phenotype with marked instability of microsatellite sequences, indicative of a deficiency in DNA repair.     

Obstructive sleep apnea and related disorders

OSAS, a common cause of disrupted sleep and EDS, result from repetitive closure of the upper airway during sleep. It probably represents the most severe syndrome related to obstruction of the upper airway; less severe forms include UARS, a syndrome characterized by the need for increased effort to breath but no prominent apneas or hypopneas, and primary snoring. Initial clues to the presence of OSAS and related disorders are derived from the history and include loud snoring, EDS or insomnia, and witnessed apneas. Some patients, especially women, may complain mostly of tiredness or fatigue, and children may present with behavioral abnormalities. Obesity, a large neck circumference, and a crowded oropharynx are common on physical examination. Nonobese patients, in particular, often have retrognathia, a high-arched narrow palate, macroglossia, enlarged tonsils, temporomandibular joint abnormalities, or chronic nasal obstruction. The clinical suspicion of obstructed nocturnal breathing is confirmed by overnight polysomnography, and an MSLT may be used to assess sleepiness. Esophageal manometry during polysomnography facilitates diagnosis of UARS. Treatment most commonly consists of nasal CPAP or BPAP, although problems with compliance make surgical treatment preferable in some cases. Although UPPP eliminates sleep apnea only in a minority of patients, combining UPPP with maxillofacial procedures appears to improve outcomes. Other treatments such as the use of dental appliances or medications, weight loss, and positional therapy may be useful as adjunctive therapy for moderate to severe OSAS or as primary treatments for UARS or mild OSAS.     

The Taskforce 2000 survey on medical education in sleep and sleep disorders

A 71-year-old woman underwent radical resection in May 1994 for a mediastinal mass invading the anterior chest wall. Histopathological examination revealed adenosquamous cell carcinoma. She was treated with postoperative chemotherapy including 5-fluorouracil (5-FU) and 4'-D-tetrahydropyrayl-doxorubicin (THP), based on in vitro chemosensitivity testing (CST), by MTT assay, using a surgical specimen. In December 1994, a recurrent tumor was detected on the left anterior chest wall and the patient received two courses of 5-FU, THP and methotrexate (MTX). The size of the chest-wall tumor decreased 25%. In July 1995, the patient had involvement of the left axillary lymph node and brain metastases in addition to the mass on the chest wall. Therefore, cisplatin, 5-FU and MTX were selected as treatment agents, based on CST using a metastatic axillary lymph node. After two courses of these agents, chest computed tomography showed a 91% reduction in the size of the chest wall tumor. Radiation was administered for the brain metastasis. In March 1997, the patient died of thymic carcinoma.     

Sleepiness and sleep disorders. Causes and consequences

Sleepiness and sleep disorders are prevalent in our society. Symptoms of sleepiness and complaints referable to sleep disorders have generally--and incorrectly--been discounted as being of minor importance and are often thought to be manifestations of psychological problems or character defects. It is now apparent that the cost to the American public--both to individuals and the larger society--is substantial. Sleep medicine has become established as an independent field, and knowledge of sleep, sleepiness, and sleep disorders has grown dramatically. This knowledge, when applied to individuals, will enhance the lives of patients with sleep disorders, and when applied to society as a whole, will have important socioeconomic implications.     

Treatment of sleep disorders in children

Sleep disorders require careful evaluation, precise diagnosis and a systematic search for a cause before considering treatment. Hypnotics must never be prescribed directly and when necessary it must be used precautionally during a short period of time, as little is known on their long term effects in children. In addition some psychotropic drugs may lead to tolerance and addiction. Educational and behavioural therapy together with sleep hygiene, have proven to be efficient in most situations. Awaking stimulants are indicated in primary hypersomnia.     

Association of physical activity and human sleep disorders

BACKGROUND: It is generally believed that exercise exerts a beneficial effect on the quality of sleep. However, most studies regarding exercise and sleep have been concerned with the influence of exercise on sleep architecture and efficiency, and not on its effects in the prevention and treatment of sleep disorders. Moreover, epidemiological evidence of the benefits of exercise on sleep are limited. OBJECTIVE: To investigate the influence of moderate exercise or physical activity on self-reported sleep disorders among a randomly selected population of adults. SUBJECTS AND METHODS: Study subjects were participants in the Tucson Epidemiological Study of Obstructive Airways Disease who in the 12th survey completed health questionnaires that included several questions on physical exercise and sleep disorders. Sleep disorders were classified as disorders in maintaining sleep, excessive daily sleepiness, nightmares, and any sleep disorder. Six questions regarding exercise and physical activity were asked. Analyses were performed using multivariate logistic regression models with selected measures of sleep disorders as dependent variables and measures of exercise and physical activity as the independent or predictor variables. RESULTS: There were 319 men and 403 women included in the analyses. The results showed that more women than men reported participating in a regular exercise program and having sleep symptoms of disorders in maintaining sleep and nightmares and that more men than women did regular vigorous activity and walking at a brisk pace for more than 6 blocks per day. Both men and women had significantly reduced risk of disorders in maintaining sleep associated with regular activity at least once a week, participating regularly in an exercise program, and walking at a normal pace for more than 6 blocks per day. Reduced risk of any sleep disorder was associated with regular activity at least once a week, and for men, walking at a brisk pace for more than 6 blocks. Among women increases in age also reduced the risk of nightmares. CONCLUSIONS: These data provide additional evidence that a program of regular exercise may be a useful therapeutic modality in the treatment of patients with sleep disorders.     

Child sleep disorders: Associations with parental sleep duration and daytime sleepiness.

This study examined the associations between childhood sleep disorders and mothers' and fathers' sleep duration and daytime sleepiness. One hundred seven families of children (ages 2-12 years) presenting to a pediatric sleep disorders clinic completed questionnaires assessing the sleep symptoms of the mother, father, and child. Parents of children with more than 1 type of sleep disorder experienced more daytime sleepiness than parents of children with a single sleep disorder. The pattern of results suggested more associations between maternal and child sleep than between paternal and child sleep. Within families, mothers reported significantly more daytime sleepiness than fathers, although there were no parental differences in sleep duration. Results provide preliminary evidence for an association between child sleep problems and parental daytime sleepiness, which may, in turn, extend previous research linking young children's sleep problems and parental functioning. Implications for treatment of both children and adults with sleep problems are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic stress and posttraumatic stress disorders.

Examined the relationship between chronic stress and symptoms of posttraumatic stress (PTS) syndrome in 52 people living within 5 miles of the Three Mile Island (TMI) nuclear power station. 35 residents of a town 80 miles from TMI were used as a control population. Chronic stress levels were evaluated using self-report, behavioral, and biochemical measures. Symptoms of PTS were also measured. Measures included the SCL-90 (Revised) and the Sensation Seeking Scale. TMI-area residents experienced more symptoms of chronic stress as well as more symptoms of PTS than the control group. Residents at TMI were particularly bothered by intrusive thoughts about the damaged reactor. There was a strong relationship between self-report, behavioral, and psychological measures of chronic stress and characteristics central to PTS as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-III). Data provide evidence of substantive links between chronic stress and development of mild symptoms of PTS disorder. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Homeostatic reconditioning in stress-related disorders: A preliminary study of migraine headaches.

18 19–55 yr old migraine headache patients were assigned to a group that learned (1) to raise finger temperature, via visual biofeedback, after neutral imaginal experiences or (2) to raise finger temperature after stressful imaginal experiences. At the completion of training, Ss participated in an outcome session without feedback. Laboratory training, combined with home practice using the same respective imaginal experiences, resulted in Ss' being able, with on-task concentration, to raise finger temperature without feedback and also resulted in significant clinical reductions in headache activity. Improvement was more marked at 4-wk follow-up. Ss trained in vascular recovery after stress showed more improvement than did other Ss. Overall, the Ss who showed the most reliable vascular recovery conditioning effects were those whose migraine prodromal symptomatology was not an accurate predictor of headache or absence of headache. The significance of what is called homeostatic reconditioning, after stress, in stress-related disorders, rather than the "aspirin" approach of many biofeedback treatments, is discussed. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperprolactinemia and headaches

We investigated the frequency of headaches in women with menstrual abnormalities and hyperprolactinemia. Twenty-seven of 46 (58%) women with hyperprolactinemia indicated that headache episodes occur once or more per week; patients with sellar abnormalities (macroadenoma) or previous cranial or pituitary operation were excluded from this group of hyperprolactinemic patients. The headache episodes occurred significantly more frequently than in the control group (N = 56), where 27% indicated one or more headaches per week (p less than 0.01). In the vast majority of the women with hyperprolactinemia, headaches had preceded the finding of elevated prolactin levels for years and had not developed after the patients had become concerned about the pituitary gland. The clinical impression was that the headaches of these patients typically lack features of prodromal signs and unilaterality and resemble, in general, tension headaches; they may last for hours and often require medication. We could not demonstrate a relationship between prolactin levels and frequency or severity of these headache episodes. The etiology of these headaches is unclear. The therapeutic effect of bromocriptine deserves further investigation. In conclusion, we present data to suggest that headaches are commonly an associated finding in hyperprolactinemic women who have no evidence of significant pituitary enlargement.     

Phototherapy. An alternative for seasonal affective disorders or sleep disorders

Although clinicians have observed for centuries that som depressed patients become worse in the winter, it was first in 1984 that Norman Rosenthal and co-workers described a syndrome which they called seasonal affective disorder (SAD), characterised by winter depression, lethargy and a craving for carbohydrate. Phototherapy was proved to be an effective treatment right from the start. Recently it has been reported that not only depression, but also panic disorder and obsessive compulsive disorders may exhibit a seasonal pattern and thus benefit from phototherapy. Phototherapy may also benefit patients suffering from "sun-downing", a syndrome of confusion and agitation in the evening in persons with Alzheimer's disease. Based on the observation that bright light may both elevate brain serotonin and ameliorate sleep abnormalities, the authors report the results of phototherapy for treatment of non-seasonal depressions, either alone or in combination with antidepressants or sleep deprivation.     

Melatonin treatment for circadian rhythm sleep disorders

We administered 1-3 mg melatonin to 11 patients (eight men, three women, aged 16-46 years) with circadian rhythm sleep disorders; nine with delayed sleep phase syndrome and two with non-24-hour sleep-wake syndrome. Sleep logs were recorded throughout the study periods and actigraph and rectal temperature were monitored during treatment periods. Melatonin was administered 1-2 h before the desirable bedtime for expected phase-shifting, or 0.5-1 h before habitual bedtime for gradual advance expecting an hypnotic effect of the melatonin. Melatonin treatments were successful in 6/11 patients. Timing and dose of melatonin administration, together with its pharmacological properties for circadian rhythm sleep disorders, should be further studied.     

Diagnosis and differential diagnosis of sleep disorders in children

Sleep disorders in children are very common and their impact on emotional and cognitive functions is considerable. Clinical work necessitates an interdisciplinary access to the subject because the scope of sleep medicine is related to various medical disciplines (e.g. paediatric neurology, pulmology and child psychiatry). Although many sleep problems are seen in both children and adults diagnoses, symptoms and pathogenetic factors are quite different in the two groups. In childhood especially parent-child interactional factors and developmental aspects of the sleep architecture and the sleep-wake cycle have to be taken into account leading to different diagnostic and therapeutic approaches. In this article we focus on important developmental aspects of childrens' sleep problems. Their relationship to neurologic, paediatric and psychiatric diseases is demonstrated and finally clear indications to diagnostic procedures, especially polysomnography, are given.     

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.