Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study is to see if by conducting research on sudden infant death syndrome (SIDS), one of major contributing factors to infant mortality in Japan, infant mortality can be reduced. Concrete approaches taken in this study took four different directions: elucidation of SIDS etiology, prevention, elucidation of its social aspects (education) and the investigation of administrative aspects. At the same time, an attempt was made to get better grasp on the epidemiological trends in infant mortality, including that of SIDS. The idea behind this etiological approach was to unify hitherto separate approaches taken by those in epidemiological, physiological and pathological fields. A molecular-biological approach was also added. Physiologically hypothesized causes of SIDS--apnea and arousal disorder--together with the epidemiologically presumed risk factor of sleeping position, were examined jointly from a pathological viewpoint. Research in the first 2 years of the grant found that hypoxia reflected by gliosis in the brain stem arousal pathway was related to the duration of sleep apnea. Research in the final year of the grant found the possibility of organic fragility in the brain stem arousal pathway, particularly in periaqueducal gray matter and pedunculopontine nucleus reflected by apoptosis and neuronal plasticity. These findings gave support to the arousal disorder hypothesis in SIDS. Application of the restriction landmark genomic scanning (RLGS) method supported the possibility of locating a site for a SIDS-specific gene. The US collaborative home infant monitoring evaluation (CHIME) currently in use was evaluated. In addition, three new monitoring methods were developed: a non-invasive multi-channel pressure-sensing bed, microwave radar, and a pacifier that functions as a suckometer which can be used to evaluate a neonate's autonomic nervous functions. Social (educational) activities included: surveys of the current state of educational campaigns on SIDS in other countries, epidemiological evaluation of campaigns run by the Japan SIDS families' Association to evaluate the effectiveness of the SIDS campaign, and creation of a home page, mostly to inform the public about the output from this research group. "Guidelines for Death Scene Investigation of Sudden, Unexplained Infant Deaths: Recommendations of Interagency Panel on Sudden Infant Death Syndrome" was translated into japanese. Activities that concerned administrative measures included clarification of the unique nature of SIDS-related trials in Japan when compared to those in the United States. Other concrete administrative proposals were: a pressing need to increase the rate of SIDS-related autopsies to facilitate a better etiological understanding and, for this purpose, establishing regulations in local jurisdictions and amending Article 8 of the Postmortem Examination and Corpse Preservation Act, keeping in perspective the medico-economic evaluation of the japanese medical examiner system. For these proposals to be realized, establishment of a new office in charge of administrative and approved autopsies at the national level of government is desirable. Also pointed out were the different opinions held among specialists concerning the diagnosis of SIDS and their need to hold multiple conferences to unify their views. Basic data for these conferences were provided from epidemiological examinations of infant mortality.
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PMID:Japanese national SIDS project: 1998-2000 research for the improvement of infant mortality. 1235 Feb 95

Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age; 27 infants died from sudden infant death syndrome (SIDS), 5 from congenital cardiac abnormalities, 2 from infected pulmonary dysplasia, 2 from septic shock with multi-organ failure, 1 with a prolonged seizure, and another with prolonged neonatal hypoxemia. The frequency and duration of sleep apneas recorded some 3-12 weeks prior to the infants' death were analyzed. Brainstem material was retrospectively collected from these 33 infants and studied in an attempt to elucidate the relationship between sleep apnea and hypoxic gliosis. The findings were compared between the SIDS victims and the control infants. Brainstem materials were immunohistochemically studied for quantitization of reactive astrocytes using an anti-glial fibrillary acidic protein (GFAP) antibody. The pathological materials were collected within 24h of death. This study focuses on the association between respiratory characteristics and pathology. Physiological and pathological data in the arousal pathway of the brainstem were linked for each infant and variant-covariant analyses were carried out using physiological data as dependent variables and pathological data and categorical data to evaluate the association with SIDS or non-SIDS as independent variables. The study failed to statistically support an association between hypoxic loads, reflected by the GFAP-positive reactive astrocytes in brainstems, the classification of being SIDS or non-SIDS infants, and the characteristics of sleep apnea.
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PMID:Association between sleep apnea and reactive astrocytes in brainstems of victims of SIDS and in control infants. 1235 Feb 98

Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age (including 26 infant victims of sudden infant death syndrome (SIDS), 5 with congenital cardiac abnormalities, 2 from infected pulmonary dysplasia, 2 from septic shock with multi-organ failure, 1 with a prolonged seizure, 1 from prolonged neonatal hypoxemia, 1 from meningitis and brain infarction). The frequency and duration of sleep apneas recorded some 3-12 weeks before the infants' death were analyzed. Brainstem material from these 38 infants was studied in an attempt to elucidate the relationship between sleep apnea and neuronal pathological changes in the arousal pathway. Immunohistochemical analyses included the evaluation of growth-associated phosphoprotein 43 (GAP43) as a marker for synaptic plasticity. The terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used to identify apoptosis. The positive pathological reactions were quantitatively analyzed. The pathological and physiological data were linked for each infant. Akaike Information Criterion (AIC) statistics was calculated to elucidate the relationship between the physiological and the pathological data in the SIDS victims. The findings illustrated the possibility of an organic fragility within the arousal pathway, particularly in the midbrain periaqueductal gray matter, which is associated with the "visceral alerting response". This autonomic response occurs within an acetylcholine afferent system and pedunculopontine tegmental nucleus (PPTN). The finding is, in future SIDS infants, associated with repetitive sleep apnea.
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PMID:From physiology to pathology: arousal deficiency theory in sudden infant death syndrome (SIDS)--with reference to apoptosis and neuronal plasticity. 1235 Feb 99

Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died suddenly and unexpectedly under 6 months of age. Of these, 26 died from sudden infant death syndrome (SIDS), 5 from congenital cardiac abnormalities, 2 from infected pulmonary dysplasia, 2 from septic shock with multi-organ failure, 1 from a prolonged seizure, 1 from prolonged neonatal hypoxemia, and 1 from meningitis and brain infarction. The frequency and duration of apneas recorded some 3-12 weeks prior to the infants' death were analyzed. The brainstem materials were collected and studied in an attempt to elucidate the relationship between sleep apnea, and prone sleep position and gliosis in some nuclei associated with cardiorespiratory characteristics, such as nucleus ambiguus in the medulla oblongata and the solitary nucleus, as well as structures associated with arousal phenomenon, such as the reticular formation, the superior central nucleus and the nucleus raphe magnus in the pons, the dorsal raphe nuclei in the midbrain and medulla oblongata, periaqueductal gray matter in midbrain, and locus ceruleus. Gliosis was estimated as the density of glial fibrillary acidic protein (GFAP)-positive reactive astrocytes. Variant-covariant analyses were carried out using the characteristics of apnea as an independent variable and sleep position and gliosis as dependent variables. A significant association was found only in the frequency of obstructive apnea and prone position (P<0.001) and gliosis in the raphe nuclei in the midbrain (P<0.001). Although prone position is a well-known risk factor for SIDS, the frequency of obstructive apnea has not been associated with the prone sleep position. The observed relation between prone sleep and the density of gliosis does not relate to epidemiological findings. Further studies are needed to investigate the unexpected statistical association.
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PMID:Interaction between apnea, prone sleep position and gliosis in the brainstems of victims of SIDS. 1235 Mar

Respiratory network plasticity is a modification in respiratory control that persists longer than the stimuli that evoke it or that changes the behavior produced by the network. Different durations and patterns of hypoxia can induce different types of respiratory memories. Lateral pontine neurons are required for decreases in respiratory frequency that follow brief hypoxia. Changes in synchrony and firing rates of ventrolateral and midline medullary neurons may contribute to the long-term facilitation of breathing after brief intermittent hypoxia. Long-term changes in central respiratory motor control may occur after spinal cord injury, and the brain stem network implicated in the production of the respiratory rhythm could be reconfigured to produce the cough motor pattern. Preliminary analysis suggests that elements of brain stem respiratory neural networks respond differently to hypoxia and hypercapnia and interact with areas involved in cardiovascular control. Plasticity or alterations in these networks may contribute to the chronic upregulation of sympathetic nerve activity and hypertension in sleep apnea syndrome and may also be involved in sudden infant death syndrome.
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PMID:Invited review: Neural network plasticity in respiratory control. 1257 Nov 45

Although the incidence of sudden infant death syndrome (SIDS) has been decreased by education programs to avoid sleeping in prone position, the pathological mechanisms of SIDS have not fully been understood. Basic research on sleep apnea using experimental animals may help further understanding and prevention of SIDS because the syndrome is thought as inability to wake up from respiratory arrest (apnea) during sleep. Although several animal models of sleep apnea have been described previously, mice would be useful experimental animals in that these animals are frequently used in genetic engineering. Those considerations prompted us to establish a method for measuring ventilation of mice concomitantly with electroencephalography and electromyography for assessing sleep-wake states. Normal wild-type mice developed two types of central sleep apneas (CSA), that is, post-sigh and spontaneous apneas, as normal humans do. Moreover, post-sigh apneas in mice were observed exclusively during slow-wave sleep (SWS) while spontaneous apneas were seen in both SWS and rapid eye movement (REM) sleep. These characteristics are very similar to those of sleep apneas in healthy human infants and children. Therefore, mice seem to be a promising experimental animal model for studying the genetic and molecular basis of respiratory regulation and dysregulation during sleep in humans, especially infants and children. However, we should keep in mind limitations in studying mice as an animal model of SIDS, since they are nocturnal rodents and they sleep in the prone position.
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PMID:Sleep apnea in mice: a useful animal model for study of SIDS? 1469 2

Sudden infant death syndrome is the leading cause of death in infancy, but its pathophysiological mechanism has been elusive. Sudden death in adults is a common phenomenon, but the etiology in many cases remains unknown at autopsy. We hypothesize that maladaptive sympathetic bias is the explanatory mechanism that links many cases of sudden demise among adults and infants as companion syndromes. Normally, sympathetic response occurs as an adaptation to physiologic demands of the body through various autonomic reflex arcs such as chemoreceptors. Sympathetic response can become chronic and maladaptive when the normal sympathetic response fails to correct the precipitating physiologic trigger, leading to chronic activation of autonomic reflex arcs. In conditions such as infant sleep apnea or adult heart failure, a pernicious cycle of sympathetic bias may result. Chronic sympathetic bias increases susceptibility to sudden fatal arrhythmias, QT-related and otherwise, in the setting of an exaggerated adrenergic challenge. Examples of such adrenergic stressors include trauma, hypoxia, hypercapnia, acidosis, sleep arousal, illness, medical procedures, and physical activity, all of which have associations with sudden death. Our hypothesis may not only help explain the survival benefits of drugs such as beta-blockers and devices such as synchronization therapy, but also portend new application of similar therapies for many conditions of sympathetic bias.
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PMID:Sudden death among infants and adults: companion disorders of maladaptive sympathetic bias. 1514 36

Postural medicine studies the effects of gravity on human body functions and the ability to influence various diseases by changing the body's position. Orthostasis requires numerous cardiovascular and neurohumoral adaptations to prevent hypotension and a resulting decrease in cerebral perfusion. Sitting upright or in a semi-sitting position reduces venous return in patients with heart failure, intracranial pressure in patients with intracranial hypertension, intraocular pressure in glaucoma patients and may decrease gastro-oesophageal reflux. A left recumbent posture also decreases reflux. A right lateral position results in a lower sympathetic tone than lying on the left side and is beneficial in patients with heart failure or after an infarction without bradycardia. A 40 to 70% decreased prevalence of the sudden infant death syndrome has been observed since the recommendation to avoid laying infants to sleep in a prone position. Sleeping in a supine posture increases the severity of sleep apnoea compared to a lateral position. In patients with acute respiratory distress syndrome, a prone position can rapidly improve blood oxygenation. Idiopathic oedema, orthostatic proteinuria, intradiscal pressure and venous circulation in legs are improved in the decubitus position, whereas arterial flow is reduced. Health risks due to microgravity and prolonged bed rest, such as osteoporosis, venous thrombosis or pressure sores, are discussed.
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PMID:The role of body position and gravity in the symptoms and treatment of various medical diseases. 1555 Nov 57

Several pathologies, such as central hypoventilation syndrome, central sleep apnea and cases of sudden infant death syndrome, involve defects in central breathing control. On a cellular and molecular level these disorders remain poorly defined and mechanistically not understood. A complex network of distinct brainstem neurons coordinates respiratory rhythm generation and modulation, which traditionally has been mapped by anatomical, physiological and pharmacological techniques. Recently, targeted gene inactivation of several transcription factors in mice was found to affect the development of specific groups of brainstem neurons and result in distinct respiratory phenotypes. These mutants promise a higher precision in the analysis of central breathing control and new diagnostic perspectives for respiratory syndromes, as indicated by the recent discovery of corresponding mutations in humans.
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PMID:Mutations of brainstem transcription factors and central respiratory disorders. 1564 19

Of 27,000 infants whose sleep-wake characteristics were studied under the age of 6 months, 38 died unexpectedly 2-12 weeks after the sleep recording in a pediatric sleep laboratory. Of these infants, 26 died of sudden infant death syndrome (SIDS), and 12 of definitely identified causes. The frequency and duration of sleep apneas were analysed. Sleep recordings and brainstem histopathology were studied to elucidate the possible relationship between sleep apnea and neuropathological changes within the arousal system. Immunohistochemical analyses were conducted using tryptophan hydroxylase (TrypH), a serotonin synthesizing enzyme, and growth-associated phosphoprotein 43 (GAP43), a marker of synaptic plasticity. The terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used for apoptosis. The pathological and physiological data were correlated for each infant. In the SIDS victims, statistically significant positive correlations were seen between the number of TrypH-positive neurons in the dorsal raphe nucleus of the midbrain and the duration of central apneas (p = 0.03), between the number of TUNEL-positive glial cells in the pedunculopontine tegmental nucleus (PPTN) and the average number of spines in GAP43-positive neurons in the PPTN (p = 0.04). These findings in the dorsal raphe nucleus of the midbrain and PPTN, that play important roles in the arousal pathway suggest a possible link between changes in arousal and SIDS.
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PMID:Apnea, glial apoptosis and neuronal plasticity in the arousal pathway of victims of SIDS. 1574 63


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