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)

Achalasia of the esophagus may be associated with abnormalities of the myenteric plexus (hypo- and anganglionosis). This report evaluates this relationship by studying the effect of benzalkonium chloride (BK, a topical neurotoxin) on the lower esophagus. Following midline laparotomy, topical BK (0.5%) was applied to the muscularis of the lower 1.0 cm of the esophagus for 30 min in 38 Sprague-Dawley rats (200 g). Thirty-eight additional rats acted as controls (unoperated, n = 19; sham laparotomy, n = 19). At 1 and 3 months animals were evaluated for weight gain, daily food intake (g/100 gm body wt), lower esophageal sphincter (LES) manometry, and contrast esophagram. At 3 months, the esophagus was evaluated for histologic study and acetylcholinesterase staining. Esophagram showed distal narrowing with proximal dilatation in BK rats (inner diameter 4.71 +/- 0.61 vs 6.17 +/- 0.58 in controls, P less than 0.001). Daily food intake was significantly less in BK rats (5.57 +/- 0.41 g vs controls 7.69 +/- 0.33 g P less than 0.001). Daily weight gain was also less in BK rats (1.13 +/- 0.34 vs controls 1.83 +/- 0.25, P less than 0.001). An increased LES pressure was noted in BK rats (5.45 +/- 0.89 mmHg vs controls 4.04 +/- 1.04 mmHg; P less than 0.1). A histologic study showed aganglionosis in BK rats with positive cholinesterase staining fibers compared to controls. Topical BK results in distal esophageal aganglionosis characterized by distal narrowing, proximal dilatation, decreased food intake, and limited weight gain when compared to controls. These findings are similar to those observed in achalasia and support a primary neurogenic cause for its etiology.
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PMID:The effect of a neurotoxin (benzalkonium chloride) on the lower esophagus. 275 16

We studied the internal anal sphincter (IAS) muscle from 10 patients with achalasia and five normal controls using histochemical staining for NADPH-diaphorase and acetylcholinesterase (AChE). Normal control IAS muscle contained occasional AChE-positive nerve fibers, whereas IAS achalasia specimens demonstrated prominent AChE-positive nerve fibers in muscle layers. NADPH-diaphorase activity was strongly expressed in nerves in the normal IAS muscle but was absent or scanty in the muscle of patients with IAS achalasia. Our findings of increased AChE-positive nerves and the absence of NADPH-diaphorase activity taken in conjunction with reports of abnormal peptidergic innervation indicate that complex neural abnormalities occur in IAS achalasia. The primary event remains obscure, but it is possible that a single defect, such as nitrergic nerve depletion, may lead to compensatory changes in the other nerve fibers.
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PMID:Absence of NADPH-diaphorase activity in internal anal sphincter (IAS) achalasia. 885 94

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

Intestinal Dysganglionoses (IDs) represent a heterogeneous group of Enteric Nervous System anomalies including Hirschsprung's disease (HD), Intestinal Neuronal Dysplasia (IND), Internal Anal Sphincter Neurogenic Achalasia (IASNA) and Hypoganglionosis. At present HD is the only recognised clinico-pathological entity, whereas the others are not yet worldwide accepted and diagnosed. This report describes the areas of agreement and disagreement regarding definition, diagnosis, and management of IDs as discussed at the workshop of the fourth International Meeting on "Hirschsprung's disease and related neurochristopathies." The gold standards in the preoperative diagnosis of IDs are described, enlighting the importance of rectal suction biopsy in the diagnostic workup. The most important diagnostic features of HD are the combination of hypertrophic nerve trunks and aganglionosis in adequate specimens. Acetylcholinesterase staining is the best diagnostic technique to demonstrate hypertrophic nerve trunks in lamina propia mucosae, but many pathologist from different centers still use H&E staining effectively. Moreover, the importance of an adequate intraoperative pathological evaluation of the extent of IDs to avoid postoperative complications is stressed. Although it is not clear whether IND is a separate entity or some sort of secondary acquired condition, it is concluded that both IND and IASNA do exist. Other interesting conclusions are provided as well as detailed results of the discussion. Further investigation is needed to resolve the many controversies concerning IDs. The fourth International Conference in Sestri Levante stimulated discussion regarding these entities and led to the International guidelines to serve the best interest of our patients.
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PMID:Controversies concerning diagnostic guidelines for anomalies of the enteric nervous system: a report from the fourth International Symposium on Hirschsprung's disease and related neurocristopathies. 1622 77

Variants of Hirschsprung disease are conditions that clinically resemble Hirschsprung disease, despite the presence of ganglion cells in rectal suction biopsies. The characterization and differentiation of various entities are mainly based on histologic, immunohistochemical, and electron microscopy findings of biopsies from patients with functional intestinal obstruction. Intestinal neuronal dysplasia is histologically characterized by hyperganglionosis, giant ganglia, and ectopic ganglion cells. In most intestinal neuronal dysplasia cases, conservative treatments such as laxatives and enema are sufficient. Some patients may require internal sphincter myectomy. Patients with the diagnosis of isolated hypoganglionosis show decreased numbers of nerve cells, decreased plexus area, as well as increased distance between ganglia in rectal biopsies, and resection of the affected segment has been the treatment of choice. The diagnosis of internal anal sphincter achalasia is based on abnormal rectal manometry findings, whereas rectal suction biopsies display presence of ganglion cells as well as normal acetylcholinesterase activity. Internal anal sphincter achalasia is either treated by internal sphincter myectomy or botulinum toxin injection. Megacystis microcolon intestinal hypoperistalsis is a rare condition, and the most severe form of functional intestinal obstruction in the newborn. Megacystis microcolon intestinal hypoperistalsis is characterized by massive abdominal distension caused by a largely dilated nonobstructed bladder, microcolon, and decreased or absent intestinal peristalsis. Although the outcome has improved in recent years, survivors have to be either maintained by total parenteral nutrition or have undergone multivisceral transplant. This review article summarizes the current knowledge of the aforementioned entities of variant HD.
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PMID:Variants of Hirschsprung disease. 2298 36