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)

Esophageal achalasia (EA) is a rare disease in man and animals and there are many discussions on its higher risk of esophageal cancer. N-Amyl-N-methylnitrosamine (AMN) which specifically induces esophageal tumors in mice and rats was given to three mutant mouse strains, i.e. 101/N, STX/Le and BXH-8, which develop a high incidence of EA. The incidence of EA in 101/N, STX/Le, BXH-8 and normal C57BL/6J mice was 38.5% (110/286), 30.1% (43/143), 91.8% (190/207) and 0% (0/167), respectively. The average numbers of AMN-induced esophageal tumors in EA(+) were significantly higher than those of EA(-) in all of the 101/N, STX/Le and BXH-8 mice. Furthermore, significantly larger size tumors and invasive squamous cell carcinomas were found in EA(+) mice than in EA(-) mice. These results indicate the higher sensitivity of EA for both tumor induction and promotion, possibly due to the longer retention of AMN. In fact, relaxation of the lower esophagus by a smooth muscle relaxing calcium-channel blocker, nicardipine hydrochloride, significantly prevented the induction of esophageal tumors.
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PMID:High incidence of esophageal cancer in esophageal achalasia by the oral administration of N-amyl-N-methylnitrosamine and its prevention by nicardipine hydrochloride in mice. 961 58

Achalasia is a primary esophageal motor disorder of unknown etiology producing complaints of dysphagia, regurgitation, and chest pain. The current treatments for achalasia involve the reduction of lower esophageal sphincter (LES) pressure resulting in improved esophageal emptying. Calcium channel blockers and nitrates, once used as initial treatment strategy for early achalasia, are now only used in patients who are not candidates for pneumatic dilation or surgery and those not responding to botulinum toxin injections. By virtue of the more rigid balloons, the current pneumatic dilators are more effective and have better efficacy than the older more compliant balloons. The graded approach to pneumatic dilation using the Rigiflex balloons (3.0, 3.5, and 4.0 cm) are now the most commonly used nonsurgical means of treating patients with achalasia, resulting in symptom improvement in up to 90% of patients. Surgical myotomy, once with high morbidity and long hospital stay, can now be performed laparoscopically with similar efficacy to the open surgical approach (94% vs. 84%, respectively), reduced morbidity, and hospitalization time. Given the advances in both balloon dilation and laparoscopic myotomy, most patients with achalasia can now choose between these two equally efficacious treatment options. Botulinum toxin injection of the LES should be reserved for patients who cannot undergo balloon dilation and are not surgical candidates.
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PMID:Current therapies for achalasia: comparison and efficacy. 1047 92

Achalasia is a primary esophageal motor disorder of unknown cause that produces complaints of dysphagia, regurgitation, and chest pain. The current treatments for achalasia involve the reduction of lower esophageal sphincter (LES) pressure, resulting in improved esophageal emptying. Calcium channel blockers and nitrates, once used as an initial treatment strategy for early achalasia, are now used only in patients who are not candidates for pneumatic dilation or surgery, and in patients who do not respond to botulinum toxin injections. Because of the more rigid balloons, the current pneumatic dilators are more effective than the older, more compliant balloons. The graded approach to pneumatic dilation, using the Rigiflex (Boston Scientific Corp, Boston, MA) balloons (3.0, 3.5, and 4.0 cm) is now the most commonly used nonsurgical means of treating patients with achalasia, resulting in symptom improvement in up to 90% of patients. Surgical myotomy, once plagued by high morbidity and long hospital stay, can now be performed laparoscopically, with similar efficacy to the open surgical approach (94% versus 84%, respectively), reduced morbidity, and reduced hospitalization time. Because of the advances in both balloon dilation and laparoscopic myotomy, most patients with achalasia can now choose between these two equally efficacious treatment options. Botulinum toxin injection of the LES should be reserved for patients who can not undergo balloon dilation and are not surgical candidates.
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PMID:Achalasia: diagnosis and management. 1043 97

Swallowing is a complex mechanism based on the coordinated collaboration of tongue, pharynx and esophagus. Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, non-cardiac chest pain or regurgitation. The major primary esophageal motility disorders--achalasia, diffuse esophageal spasm, hypercontractile esophagus ('nutcracker esophagus') and non-specific motility disorder--are of unknown etiology. Other esophageal diseases, such as cervical diverticula or gastroesophageal reflux disease, might also be caused by a primary esophageal motility disorder. Medical treatment of esophageal disorders with esophageal hyper- or dysmotility requires agents that reduce esophageal contractile force (anticholinergic agents, nitrates, calcium antagonists). Despite the beneficial effect of the various drugs on esophageal motility parameters, the clinical benefit of medical treatment of esophageal motility disorders is rather disappointing. Calcium channel antagonist, alone or in combination with anticholinergics or nitrates, can be used as a medical trial, especially in mild achalasia. However, medical therapy is clearly inferior to pneumatic balloon dilation therapy. Recently, botulinum toxin injection was suggested as a therapeutic option in achalasia patients with good results on lower esophageal sphincter pressure (LESP) and symptom scores that were similar to the results achieved by pneumatic balloon dilation. Hypercontractile esophagus shows a good manometric response to calcium channel antagonists, but only little clinical effect in terms of improvement of symptoms. Diffuse esophageal spasm is a relatively rare disease and few clinical studies are available. The use of calcium channel antagonists can be beneficial, at least in some patients with diffuse esophageal spasm. From clinical and epidemiological studies, there is some evidence of a 'psychological' component in the pathogenesis or perception of esophageal symptoms. There is some clinical benefit from centrally acting drugs such as benzodiazepines or antidepressants. With the exception of botulinum toxin for achalasia, medical therapy of primary esophageal motility disorders is rather limited and the clinical results are poor. Further understanding of esophageal pathophysiology as well as development of new receptor-selective drugs might increase our chances of a successful treatment of primary esophageal motility disorders.
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PMID:Esophageal pharmacology and treatment of primary motility disorders. 1077 Mar 58

Laparoscopic surgery for esophageal achalasia was first reported by Shimi et al. in 1991. Subsequently the procedure has been performed all over the world and laparoscopic Heller myotomy and Dor fundoplication (Heller and Dor operation) is now thought to be the operation of first choice. It is indicated for patients who are resistant to medical therapy (calcium blocker etc.) or have pneumatic dilatation and those with frequent aspiration at night. As Csendes et al. reported that surgical treatment was better than pneumatic dilatation and as laparoscopic surgery is less invasive, the indications for the laparoscopic Heller and Dor operation can include all achalasia patients except those who respond to medical therapy, do not accept surgery, or cannot tolerate surgery. We successfully performed the laparoscopic Heller and Dor operation on 22 patients, all of whom had an uneventful postoperative course. Manometric evaluation, endoscopic examination, and 24-hour pH monitoring showed good results. There are six important technical points: 1) flexible laparoscopy; 2) pneumoperitoneum; 3) gauze in the abdominal cavity to absorb blood; 4) laparosonic coagulating shears; 5) extracorporeal knot-tying technique; and 6) intracorporeal knot-tying technique. If an experienced surgeon is in charge, the laparoscopic Heller and Dor operation is an ideal, minimally invasive treatment for esophageal achalasia.
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PMID:[Laparoscopic surgery for esophageal achalasia]. 1084 98

Calcium concentration in gastric juice is lower then other electrolytes. The mechanism of its transport remained unknown. The aim of the study was to evaluate influence of pentagastrin on calcium concentration in gastric juice in humans. Ten patients were examined (4 females and 6 males, mean age 46.8 range 33-67), four with duodenal ulcer, three with achalasia cardiae and three with Addison-Biermer anemia. Pentagastrin--PG (Cambridge Laboratories, Newcastle, United Kingdom) was injected subcutaneously after overnight fast in dose of 6 micrograms/kg of body weight. Nosogastric tube was located in body of the stomach near large curvature and connected to suction of--40 mmHg pressure. Gastric juice was collected during subsequent five 15 minutes periods (first fasted and four periods after stimulation with PG). Calcium concentration was measured in each sample by fluorescentic titration method with EGTA. Statistic analysis was performed with student "t" test. Mean fasted and stimulated calcium concentrations were 0.83; 0.44; 0.54; 0.37 and 0.95 mmol/l respectively. Ca2+ concentration range in fasted state from 0.21 to 1.75 mmol/l and from 0.07 to 0.27 mmol/l by maximal stimulation. Calcium concentration decreased immediately after stimulation (significance p = 0.0025). This strong effect persisted throughout the period of stimulation. Calcium output was 0.064; 0.029; 0.032; 0.018 and 0.17 mmol/15 min respectively. Two phases of decrease of the calcium output were observed: first, fast decrease immediately after pentagastrin injection and second, slower, between 30 and 45 minute after stimulation (p < 0.01 and 0.02 respectively). Calcium concentration in gastric juice decreases after stimulation with pentagastin (p = 0.0025). Calcium concentration was lower in Addison-Biermer anemia and higher in duodenal ulcer patients then in healthy control. We conclude that calcium ions are not actively secreted by gastric mucosa. Their presence in gastric juice is a result of leak from mucosal cells and remains opposite to their metabolic activity.
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PMID:[The effect of pentagastrin on calcium ion concentration in gastric juice]. 1090 77

This article focuses on the different pharmacologic treatments for achalasia. Most smooth muscle relaxants such as nitrates and calcium antagonists are temporizing at best. Botulinum toxin, acting at the neuronal level, is effective in two thirds of the patients and has a duration of action of several months. It may be particularly suitable for the elderly or high-risk patient. The mechanism of action and efficacy of the different drugs are discussed in detail.
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PMID:Pharmacologic therapy in treating achalasia. 1131 64

Diffuse oesophageal spasm is a functional oesophageal motility disorder of unknown aetiology, which appears to be due to a disturbance of the normal pharmacological timing of propulsive contraction occurring in the oesophageal body after swallowing. The lack of pathophysiological understanding may be due to the fact that there is more than one pathophysiological pathway causing symptoms of diffuse oesophageal spasm. Barium studies, oesophageal scintigraphy and fiberoptic examination can be helpful in finding the correct diagnosis, but manometry is still the gold standard of diagnostic procedures. Similar to other spastic oesophageal motility disorders, pharmacological treatment of diffuse oesophageal spasm includes nitrates, calcium antagonists, anticholinergics and antidepressants with varying beneficial effects. Botulinum toxin, which provides sufficient treatment as measured by symptom score and manometric patterns in patients with achalasia, was recently evaluated for the treatment of diffuse oesophageal spasm in small patient selections with promising results.
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PMID:Current concepts on pathophysiology, diagnosis and treatment of diffuse oesophageal spasm. 1136 84

Achalasia is a condition of unknown etiology. It represents a motor disorder of the esophagus characterized by absent or incomplete relaxation of the lower esophageal sphincter upon swallowing and by non-propulsive swallow-induced contraction waves or amotility of the esophageal body. Dysphagia and regurgitation of ingesta are the most frequent symptoms. Medical treatment, i.e. by calcium-channel blockers and nitric oxide donors, may be tried in patients with mild dysphagia or in elderly patients but rarely yields adequate symptom relief. Mechanical dilatation of the achalasic sphincter may be performed as an initial treatment option. Intrasphincteric injections of botulinum toxin seemed to be a promising alternative, but it has become obvious that, in most cases, repeated applications of the toxin are required to maintain patients symptom-free. Myotomy of the achalasic sphincter with or without fundoplication to prevent gastroesophageal reflux, is employed mainly in patients in whom dilatations have failed, but since the introduction of minimally invasive surgery, myotomy has become the primary treatment at many centers. This article aims to provide an overview of the development of the conservative and surgical treatment of achalasia.
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PMID:[Treatment of achalasia]. 1523 54

With age, a person has "accumulation" of diseases. In patients of older age groups occurs simultaneously for at least 3-4 diseases. Assigning patients with ischemic heart disease (IHD), the physician takes into account the presence of concomitant diseases, especially diseases of the gastrointestinal tract, since the defeat of the stomach, liver, intestine may influence not only on the clinical course of heart disease, but also to change the pharmacokinetics of cardiac drugs. All groups of drugs used in treating coronary artery disease, have different effects on the digestive organs. This can be a positive influence. For example, the use of beta-blockers and nitrates for prevention of bleeding from esophageal varices at cirrhosis of the liver, calcium antagonists in achalasia cardia. It is well known, and the negative effect of cardiac drugs: erosive and ulcerative lesions of the stomach with aspirin use, increasing manifestations of GERD in patients receiving calcium antagonists (dihydropyridines group). In this regard, we need for rational pharmacotherapy.
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PMID:[Cardiovascular pathology associated with digestive system diseases]. 2191 42


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