Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014848 (achalasia)
 2,804 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enteric nervous system (ENS) can be thought of as the third component of the autonomic nervous system. It is a vast network of neurons widely dispersed throughout the gut. The ENS is a dominant regulator of gut function through the action of peptide and non-peptide neurotransmitters. The most intensively studied roles of the ENS have been the regulation of secretory processes, such as gastric acid secretion, and motility. It is clear, however, that the ENS plays a broader role in the regulation of other gut functions, including mucosal defense, the gut immune response, and sphincter function. Alterations in the regulation of gut function by the ENS are likely or suspected in a number of conditions, including achalasia, Hirschsprung's disease, inflammatory bowel disease, Chagas' disease, chronic intestinal pseudoobstruction, biliary dyskinesia, tachygastria, and irritable bowel syndrome. Improved knowledge of the pathophysiology of these troublesome conditions makes effective therapy more likely in the future.
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PMID:Neuroendocrine design of the gut. 167 22

Vasoactive intestinal peptide (VIP), first isolated from the gut, was originally considered a candidate gastrointestinal hormone. Since about 1975, however, it has become increasingly clear that it is primarily a neurotransmitter or neuromodulator and that it exerts its functions mainly by local release from nerve endings. VIP plays a hormonal role only when it is released in large amounts from a tumor, with a consequent overflow into the circulation and grossly elevated plasma concentrations of the peptide. Moderately increased VIP plasma and tissue concentrations that cause mainly local effects are found in intestinal ischemia. Crohn's disease and some other chronic inflammatory diseases of the bowel. VIP is also measured in increased amounts in the normal fetus and neonate, where it may play an important physiological role. Such an increase of VIP levels in the circulation could enhance perfusion and metabolic activity of tissues during their rapid-growth period. On the other hand, disorders with a disturbed VIP function such as achalasia and Hirschsprung's disease and possibly also asthma and cystic fibrosis seem to be characterized mainly by a derangement of smooth muscle activity and/or exocrine secretion. Considering this list of disorders where VIP has either a proven or suspected role, it is easy to imagine the significance of this peptide in pediatric pathophysiology.
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PMID:[Vasoactive intestinal polypeptide (VIP)--possible importance in diseases of childhood]. 299 82

Destruction of the myenteric plexus impairs ongoing peristalsis and produces dilatation of the gut lumen with thickening of the gut wall. Achalasia of the cardia, hypertrophic pyloric stenosis and non-Hirschsprung megacolon are well-known examples of damage to the bowel nerve supply. There are many causes, some of which are unknown, but the common ones can be divided into three groups. Congenital developmental failure may be total and incompatible with life, or less severe, in which case resection may be possible. Acquired inflammatory damage, other than Chagas' disease, can occur anywhere in the gut. Autonomic neuropathy may involve either the neurons or the Schwann cells. The former is often due to drugs because the autonomic ganglia are outside the blood-brain barrier. The latter is frequently associated with metabolic disease, such as diabetes mellitus.
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PMID:The neuropathology of pseudo-obstruction of the intestine. 695 Dec 64

Autonomic dysfunction leads to a variety of clinical disorders involving all parts of the gut. These neural disorders are distinct from the four other recognised categories of disorders involving myogenic function, myoelectric activity, hormonal regulation and abnormal humoral factors. Criteria for establishing that a disorder has a neurogenic aetiology vary in different diseases. Absence of a neural mediated response with intact muscle function has been the major criterion used in most studies. Neural mediated responses of peristalsis, sphincteric relaxation and intestinal contraction following distension or feeding are the major parameters of assessment. Abnormalities in neural function have been demonstrated in achalasia, symptomatic diffuse oesophageal spasm, diabetes mellitus, amyloidosis, scleroderma and chronic idiopathic intestinal pseudoobstruction. The anatomical site and type of gut neurological disorder varies in each condition. Morphological studies have been helpful in demonstrating specific intranuclear inclusion bodies in some pseudoobstruction patients, and vagal and ganglionic lesions in achalasia. Intact muscle ad myoelectric function as well as normal responsiveness to drugs acting directly upon muscle may be established by morphological study. Advancement in basic technology should provide a rewarding area for future study of the pathogenesis and treatment of the gut neurological disorders.
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PMID:Clinical aspects of autonomic nerve dysfunction of the gut. 695 Dec 65

The regulation of gastrointestinal function is known to involve elements of the enteric nervous system. Processes such as secretion, motility, blood flow, and immune function are all influenced by a complex network of neurons whose cell bodies lie in the gut. These neurons use a wide spectrum of substances as neurotransmitters, although the majority use peptides once thought to function only as gut hormones. It has been increasingly recognized that abnormalities of this neuroendocrine regulatory system underlie many gastrointestinal disorders. The most obvious are states of peptide excess found in patients with gut endocrine tumors such as carcinoid, gastrinoma, and somatostatinoma. Conversely, other disorders appear to be related to deficiency states. Examples include both achalasia and Hirschsprung's disease (congenital megacolon), where the loss of inhibitory neural action leads to abnormalities of peristalsis and sphincter function. Evidence for abnormal neuroendocrine regulation leading to disease states is increasing for many other gastrointestinal disorders.
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PMID:Neuroendocrine disorders of the gut. 853 22

From the fragmentary studies performed to date of both functional obstruction and the ontogeny of intestinal motility, several conclusions can be drawn. The development of motor activity that is primarily dependent on neuronal activity, such as sucking, swallow-induced peristalsis of the esophagus, and cyclic fasting small intestinal motor activity, occurs according to a timetable that is similar in all species studies is gestationally dependent, but its timing during gestation is species specific. Postprandial events, including gastric emptying and continuous postprandial motor activity in the small intestine, in contrast seem to be dependent on the nature of the humoral response to food, provided that the musculature of the gut and enteric nerves are able to respond to it. Although these activities are primarily determined by neuronal development, there is a limited amount of information to suggest that their appearance may be pharmacologically manipulated to advance the timing and rate of development. It is commonplace now for cortisol to be used to induce the production of surfactant in mothers of babies who are at risk of hyaline membrane disease. A limited amount of information suggests that cortisol may have similar effects in inducing duodenal motor activity, and, thus, it may be possible to advance the timing and rate of development of intestinal motility in the very preterm infant by its use. There are, however, no studies to date to prove this. It is now clear that intestinal pseudo-obstruction is a heterogeneous disorder associated with various pathologies, some of which are intrinsic to the gut, whereas others are multisystem diseases affecting the intestine. In addition, although intestinal pseudo-obstruction was originally thought to involve the small intestine, it is now realized that it may not affect only one region, as in achalasia or Hirschsprung's disease, but also it may present diffusely throughout the gut. The motility changes caused by the disease processes are nonspecific, although neuropathic and myopathic changes are distinct and due to the destruction of the particular motor control system involved. The mechanisms of the ontogenic and disease changes described in this article are, however, almost totally unexplored. The recent upsurge of interest in the area with the development of advances in cellular and molecular biology, at least the early events, is now beginning to unravel. At the present time, the stage is being set for probably the most exciting phase of understanding of the nature of the ontogeny of intestinal motor activity, which the author expects will enable us to manipulate motor activity in normal preterm infants and, it is hoped, congenital dysmotile states.
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PMID:Intestinal motility during ontogeny and intestinal pseudo-obstruction in children. 861 13

Eosinophilic gastroenteritis is an unusual disease entity characterized by eosinophilic infiltration of the gut with gastrointestinal disturbance. The disease commonly involves the stomach and small bowel. Esophageal involvement is rarely reported. We present a patient with simultaneous achalasia, pyloric stenosis, and ascites. Macroscopically, the esophagus, stomach and small intestine were involved. Microscopically, the mucosa was involved to the serosa. The patient has remained well under low dose prednisolone treatment for 7 years since his condition was diagnosed.
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PMID:Eosinophilic gastroenteritis with esophageal involvement. 868 8

The morphology of the intrinsic innervation of internal anal sphincter (IAS) in Hirschsprung's disease (HSCR) and allied disorders has not been clearly defined. At the time of IAS myectomy, specimens of the IAS were taken from four patients with HSCR, five patients with intestinal neuronal dysplasia (IND), five patients with IAS achalasia, and two patients with hypoganglionosis. Specimens also were taken from five normal controls. The specimens were examined using neural cell adhesion molecule (NCAM) immunohistochemistry, NADPH-diaphorase histochemistry, and acetylcholinesterase (AChE) histochemistry. The number of AChE-positive nerve fibers was markedly increased in the IAS of patients with HSCR, IND, and IAS achalasia compared with controls. NCAM and NADPH-diaphorase activity was absent or markedly reduced in the IAS of patients with HSCR, IND, and IAS achalasia. The IAS of patients with hypoganglionosis show markedly reduced NCAM and NADPH-diaphorase activity and occasional AChE-positive nerve fibers. These findings show that patients with HSCR, IND, hypoganglionosis, or IAS achalasia have abnormal innervation of the IAS and this may contribute to disturbances in gut motility in these conditions.
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PMID:Abnormal internal anal sphincter innervation in patients with Hirschsprung's disease and allied disorders. 878 6

Both achalasia and Hirchsprung's disease arise from defects of innervation of the oesophagus and distal large bowel respectively. Their consequences are confined to disorders of motility in the relevant part of the gastrointestinal tract. Many neurogenic and primary muscle disorders are associated with abnormalities of gut motility. Stroke, even when unilateral, is commonly associated with dysphagia. Transcranial magnetoelectric stimulation has established that the pharyngeal phase of swallowing tends to receive its innervation principally from one hemisphere. In many neurological disorders, dysphagia is only one part of the clinical picture but in some--for example, the Chiari malformation--dysphagia may be the sole or major feature. Disturbances of small and large bowel motility, when seen in neurogenic disorders, are associated with autonomic neuropathy and are particularly common in diabetes mellitus. Primary muscle disorders can lead to dysphagia (for example, with polymyositis or oculopharyngeal dystrophy) or defects of large bowel motility (for example, with Duchenne's muscular dystrophy). Primary gut disorders particularly associated with neurological disease include pernicious anaemia, nicotinamide and thiamine deficiencies, selective vitamin E deficiency, and coeliac disease. Inflammatory bowel disease is associated with thromboembolic complications which may include the CNS, inflammatory muscle disease, and abnormalities on MRI of the brain of uncertain relevance. Whipple's disease is a rare condition which sometimes is largely or entirely confined to the CNS. In such cases, a particular neurological presentation can indicate the diagnosis.
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PMID:Neurology and the gastrointestinal system. 1040 May 14

Gastric function is finely modulated by a series of neurological mechanisms, so that gastric digestion is normally not perceived. Alteration of these control mechanisms may lead to different situations, which are frequently associated with symptoms. An impaired tonic contraction of the proximal stomach, that is, an impaired gastric tone, results in gastroparesis. Patients with functional dyspepsia, and also patients with achalasia, have impaired meal accommodation of the stomach. Interestingly, patients with functional dyspepsia may also have a sensory dysfunction, and both dysfunctions could play a synergistic role. However, the sensory dysfunction in dyspepsia, particularly the types of afferent fibres affected, and the mechanisms of impaired accommodation, still remain to be characterized. Evaluation of gastric function has been approached using the barostat. However, the barostat has limitations and potential technical pitfalls that require proper attention. Meal ingestion induces a variety of reflexes and the net result is a relaxation of the stomach. However, gastric reflexes can be best evaluated with the stomach empty, when the stimuli are applied at a different site. Nevertheless, altered reflex responses may be difficult to interpret. For instance, absent or decreased relaxatory responses may equally correspond to a gastroparetic stomach without tone or to a dyspeptic stomach unable to relax. In this context, it may be important to measure basal tone. Distension of the stomach by means of the barostat has been also used to test gastric sensitivity. However, recent studies have shown that perception of gastric distension relays on stimulation of tension receptors; since wall tension depends on both pressure and volume, distension with the barostat may be difficult to standardize. Hopefully, a battery of tests may become available in the near future for a complete neuromuscular evaluation of the gut.
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PMID:Gastric neurology: evolving concepts and techniques. 983 Dec 67


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