Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammation of the lower airways is a defining characteristic of asthma. Microaspiration of refluxate may initiate an inflammatory response in the airways of patients with gastroesophageal reflux disease (GERD), thereby precipitating asthma. Airway nerves are likely to play a role in the pathogenesis of asthma and could potentially mediate airway inflammation initiated by GERD through axonal reflexes. Alternatively, refluxate may initiate airway reflexes from the esophagus that are markedly exaggerated by inflammation-induced enhancement of airway neuronal excitability. The characteristic features of inflammation in asthma are defined, and the potential role of nerves in inflammation is discussed. Mechanisms by which GERD may initiate airway inflammation or act synergistically with airway inflammation to produce asthma also are discussed.
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PMID:Role of nerves in asthmatic inflammation and potential influence of gastroesophageal reflux disease. 1174 18

Gastroesophageal reflux (GER) is a potential trigger of asthma. Approximately 77% of asthmatics report heartburn. GER is a risk factor for asthma-related hospitalization and oral steroid burst use. Asthmatics may be predisposed to GER development because of a high prevalence of hiatal hernia and autonomic dysregulation and an increased pressure gradient between the abdominal cavity and the thorax, over-riding the lower esophageal sphincter pressure barrier. Asthma medications may potentiate GER. Potential mechanisms of esophageal acid-induced bronchoconstriction include a vagally mediated reflex, local axonal reflexes, heightened bronchial reactivity, and microaspiration, all resulting in neurogenic inflammation. Anti-reflux therapy improves asthma symptoms in approximately 70% of asthmatics with GER. A 3-month empiric trial of twice-daily proton pump inhibitor given 30 to 60 minutes before breakfast and dinner can identify asthmatics who have GER as a trigger of their asthma.
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PMID:Gastroesophageal reflux: a potential asthma trigger. 1557 68

Autosomal dominant hereditary sensory neuropathy (HSN I) is a clinically and genetically heterogeneous group of disorders, and in some families it is due to mutations in the serine palmitoyltransferase (SPTLC1) gene. We have characterized two families with HSN I associated with cough and gastro-oesophageal reflux (GOR). From a large Australian family, 27 individuals and from a smaller family, 11 individuals provided clinical information and blood for genetic analysis. Affected individuals had an adult onset of paroxysmal cough, GOR and distal sensory loss. Cough could be triggered by noxious odours or by pressure in the external auditory canal (Arnold's ear-cough reflex). Other features included throat clearing, hoarse voice, cough syncope and sensorineural hearing loss. Neurophysiological and pathological studies demonstrated a sensory axonal neuropathy. Gastric emptying studies were normal, and autonomic function and sweat tests were either normal or showed distal hypohidrosis. Cough was likely to be due to a combination of denervation hypersensitivity of the upper airways and oesophagus, and prominent GOR. Most affected individuals were shown on 24 h ambulatory oesophageal pH monitoring to have multiple episodes of GOR, closely temporally associated with coughing. Hoarse voice was probably attributable to acid-induced laryngeal damage, and there was no evidence of vocal cord palsy. No other cause for cough was found on most respiratory or otorhinological studies. Linkage to chromosome 3p22-p24 has been found in both families, with no evidence of linkage to loci for known HSN I, autosomal dominant hereditary motor and sensory neuropathy, hereditary GOR or triple A syndrome. These families represent a genetically novel variant of HSN I, with a distinctive cough owing to involvement of the upper aerodigestive tract.
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PMID:Autosomal dominant hereditary sensory neuropathy with chronic cough and gastro-oesophageal reflux: clinical features in two families linked to chromosome 3p22-p24. 1631 Dec 70

Dejerine-Sottas disease (DSD) is a particular phenotype of the Charcot-Marie-Tooth (CMT) disease spectrum that is genetically heterogeneous. It represents a severe form of hypertrophic axonal and demyelinating neuropathy. Although it is predominantly inherited as an autosomal recessive condition, autosomal dominant inheritance has also been described. To date, the autosomal recessive forms of DSD are classified into several CMT type 4 (CMT4) subclasses based on allelic heterogeneity. We present a 7-year-old boy with a severe form of CMT disease consistent with the autosomal recessive phenotype of DSD. He was found to be a compound heterozygote for mutations in the PMP22 gene resulting in homozygous deletion of exons 2 and 3. The maternally inherited allele was the typical 1.5 Mb deletion involving PMP22 seen with hereditary neuropathy with liability to pressure palsy (HNPP). The paternally inherited allele was a deletion of exons 2 and 3. Both parents presented with a typical clinical picture of HNPP. To our knowledge, this is the first patient reported with large deletions involving both PMP22 alleles. Our patient has also developed severe gastroesophageal reflux disease (GERD), a clinical feature not previously reported with CMT or DSD. The correlation of the phenotype and the molecular defects observed in this patient may set a new subcategory in the classification of DSD.
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PMID:Compound heterozygous deletions of PMP22 causing severe Charcot-Marie-Tooth disease of the Dejerine-Sottas disease phenotype. 1869 10

A wide range of clinical consequences may be associated with obstructive sleep apnea (OSA) including systemic hypertension, cardiovascular disease, pulmonary hypertension, congestive heart failure, cerebrovascular disease, glucose intolerance, impotence, gastroesophageal reflux, and obesity, to name a few. Despite this, 82 % of men and 93 % of women with OSA remain undiagnosed. OSA affects many body systems, and induces major alterations in metabolic, autonomic, and cerebral functions. Typically, OSA is characterized by recurrent chronic intermittent hypoxia (CIH), hypercapnia, hypoventilation, sleep fragmentation, peripheral and central inflammation, cerebral hypoperfusion, and cerebral glucose hypometabolism. Upregulation of oxidative stress in OSA plays an important pathogenic role in the milieu of hypoxia-induced cerebral and cardiovascular dysfunctions. Strong evidence underscores that cerebral amyloidogenesis and tau phosphorylation--two cardinal features of Alzheimer's disease (AD), are triggered by hypoxia. Mice subjected to hypoxic conditions unambiguously demonstrated upregulation in cerebral amyloid plaque formation and tau phosphorylation, as well as memory deficit. Hypoxia triggers neuronal degeneration and axonal dysfunction in both cortex and brainstem. Consequently, neurocognitive impairment in apneic/hypoxic patients is attributable to a complex interplay between CIH and stimulation of several pathological trajectories. The framework presented here helps delineate the emergence and progression of cognitive decline, and may yield insight into AD neuropathogenesis. The global impact of CIH should provide a strong rationale for treating OSA and snoring clinically, in order to ameliorate neurocognitive impairment in aged/AD patients.
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PMID:Death by a thousand cuts in Alzheimer's disease: hypoxia--the prodrome. 2340 Jun 34