Lower esophageal sphincter as a barrier to gastroesophageal reflux before and after antireflux surgery.
Explore the source record for details and available documents.
SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Medical management of reflux esophagitis includes physical manipulations, antacids, and antireflux medications (bethanechol and alginic acid). Their combined usage in the continuous dyspeptic and the problem case help "break the cycle," providing relief for long periods of time. Identification of possible inciting factors in cases of recurrence should be pointed out to the patient so that he will develop an instinctive antireflux behavior. The effect of this combined therapy on the pathophysiology and natural history of the disease remains to be determined.
Esophageal motor disorders may be clearly primary, as in achalasia or diffuse esophageal spasm (DES), or clearly secondary, as in scleroderma or intrathoracic malignancy. In patients with gastroesophageal reflux, abnormal motility of the esophageal body and stomach, and lower esophageal spasm (LES) appear to predispose patients to reflux. It is possible that esophagitis caused by refluxed gastric material then further impairs motility, propagating the injury. Therapeutically, appropriate use of recently available medications, such as calcium channel blockers and metoclopramide, and new applications of previously available agents, such as hydralazine and bethanechol, have improved our ability to relieve symptoms and at times restore more normal motility.
In recent years, much has been learned about the pathogenesis, diagnosis, and treatment of gastroesophageal (GE) reflux disease. Mucosal resistance, gastric contents, esophageal acid clearance, gastric emptying, and incompetency of the lower esophageal sphincter are contributing factors to GE reflux. Use of the various diagnostic tests and an overview of current therapy are summarized.
According to established diagnostic and therapeutic guidelines for chronic pulmonary aspiration, clinical suspicion is raised by coughing and choking with feeding, coughing during sleep, recurrent pneumonia, failure to thrive, and radiologic signs of chronic lung injury. The upper gastrointestinal series accurately defines anatomy and function, can differentiate between direct and reflux aspiration, and identifies conditions that predispose to aspiration. Gastroesophageal scintigraphy lacks anatomic detail but increases observation time, may differentiate between direct and reflux aspiration, and identifies delayed gastric emptying and gastroesophageal reflux. The lipid-laden macrophage index improves identification of aspiration, but cannot differentiate between direct and reflux aspiration. The esophageal pH probe identifies gastroesophageal reflux. Treatment options include medical therapy (thickened feedings, prone positioning, and metoclopramide) and surgical intervention (gastrostomy, fundoplication, and definitive correction of predisposing conditions). Therapy is determined by severity of illness and results of diagnostic evaluation.
We have studied the effect of cyclosporine on the exocrine pancreas of rats submitted to treatment with different parenteral doses (15, 30, 50 mg/kg/day) for different time periods (7 and 30 days). Serum amylase levels, pancreas weight, and total pancreatic amylase and protein content showed a dose-dependent decrease. Basal amylase secretion from isolated lobules remained unchanged. Furthermore, the pancreatic lobules from animals under cyclosporine treatment exhibited a decreased response to bethanechol stimulation. Our data suggest that cyclosporine produces a toxic effect on exocrine pancreatic function.
Recently, investigation into an experimental treatment for patients with Alzheimer's disease has begun utilizing surgical implantation of a continuous infusion device to deliver a muscarinic agonist, bethanechol chloride, directly into the cerebrospinal fluid (CSF). The nurse research assistant has been very active in this study being involved in patient evaluation, preoperative and postoperative patient education, collection of data, and refill of the infusion device. The neurosurgical nurse also plays an active role in patient education, immediate preoperative and postoperative care, and careful observation and recording of patient behavior and general well-being. Success of continued research based on this protocol will be enhanced by the contributions of the nurse research assistant and neurosurgical nurse familiar with the study and with her/his anticipated role.
Intracellular potassium ion activities (aiK+) and membrane potentials were measured with double-barrelled, potassium-specific microelectrodes in superfused mouse pancreas and submandibular gland. Stimulation with the cholinergic agonist bethanechol caused a marked decrease in aiK+ in the submandibular gland, whereas no change in aiK+ could be detected in the pancreas. This indicates that bethanechol increases the permeability of the cell membranes to potassium ions in the submandibular gland but not in the pancreas. Pancreatic acinar cells hyperpolarized promptly when the extracellular potassium ion activity was restored after a prolonged period of potassium deprivation. In comparison, the recovery of aiK+ was a slow process. This finding gives support to the view that the hyperpolarization is due to electrogenic sodium pumping.
BMY-25368, 1-amino-2-[3-(3-piperidinomethylphenoxy) propylamino]-1-cyclobutene-3,4-dione, a new histamine H2-receptor antagonist, has been compared to ranitidine as an inhibitor of gastric acid secretion in the Heidenhain pouch dog. Intravenous infusion of BMY-25368 antagonized histamine-stimulated gastric secretion in a competitive manner. BMY-25368 also antagonized gastric secretion stimulated by pentagastrin, bethanechol and food. When compared to ranitidine in histamine-stimulated dogs, BMY-25368 was nine times more potent after bolus intravenous administration. Oral potency relative to ranitidine and ranged from 2.8 to 4.4, depending on the secretagogue used. BMY-25368 also exhibited a significantly longer duration of action than ranitidine. Thus, its potency relative to ranitidine after oral administration, in histamine-stimulated dogs, increased from 3.2 to 28 when determined 1-3 and 10-12 h post dose, respectively. BMY-25368 administered orally also antagonized aspirin-induced gastric lesions in the dog and was nine times more potent than ranitidine in this respect.
Prokinetic agents are drugs that increase contractile force and accelerate intraluminal transit. They are often used in treating disorders of gastrointestinal motility including gastro-oesophageal reflux disease (GERD). The most widely studied agents include bethanechol, metoclopramide, domperidone and cisapride. These drugs act either by enhancing the effect of acetylcholine or by blocking the effect of an inhibitory neurotransmitter such as dopamine. With the exception of cisapride, the clinical efficacy of the various prokinetic agents in treating GERD has not been confirmed consistently. These agents have variable effects on oesophageal and gastric motor function and are fraught with side-effects. They are effective in relieving mild reflux symptoms but do not predictably heal oesophagitis. On the other hand, cisapride is thus far the most effective prokinetic agent studied for the treatment of GERD. It relieves reflux symptoms and promotes healing of grade I-II oesophagitis, with few side-effects or tachyphylaxis. Its most important role may be in the maintenance treatment of GERD either as a single agent or in combination therapy with an H2-antagonist after oesophagitis healing.
Explore the source record for details and available documents.
The contractile activity of the equine large intestine exhibited a biphasic response to feeding: enhancement of migrating complexes passing along the colon and an increase of 50% in cyclic variations in smooth muscle at intervals of 20 min on the left ventral colon for a period of 5 to 7 h postfeeding. The cholinergic agonist, bethanechol (50 micrograms/kg subcutaneously), induced both the migrating complexes and the cyclic variations at intervals of 10-15 min. In contrast, the intra-arterial infusion of PGF2 alpha (3 micrograms/kg/min) increased the contractile activity during infusion, but without inducing distinct patterns of activity. Atropine but not indomethacin or flunixin pre-treatment prevented the effects of postprandial, cholinergic and PGF2 alpha stimulation of colonic motility, suggesting that the gastrocolonic reflex involved mainly cholinergic stimulation of the caecum and replicated colon, including the prostaglandin F2 alpha excitatory effects.
The effects of metoclopramide on pancreatic exocrine secretion were investigated in the pentobarbitone-anaesthetized dog. All drugs were injected into the femoral vein. Metoclopramide (10-1000 micrograms/kg) did not change the resting rate of pancreatic secretion. Pancreatic secretion, induced by bethanechol (3 micrograms/kg), was dose-dependently enhanced by simultaneous injections of metoclopramide (10 and 30 micrograms/kg), but the protein and bicarbonate concentrations of the pancreatic juice were not affected. Secretions induced by secretin (0.1 units/kg) and dopamine (3 micrograms/kg) were not modified by metoclopramide at up to 30 micrograms/kg. A larger dose of metoclopramide (1000 micrograms/kg) suppressed dopamine-induced secretion to a lesser extent than the same dose of sulpiride. From these results, it is concluded that metoclopramide enhances secretory responses to cholinergic stimulations by peripherally sensitizing the muscarinic receptor-mediated exocrine process and this drug is a weaker antagonist of the dopamine D2 receptors than sulpiride.
1. The proposition that stimulation of the secretomotor nerve to the ovine parotid gland might involve co-release of vasoactive intestinal peptide (VIP) was tested by studying responses to infusion of VIP directly into the gland's arterial blood supply and by assay of VIP in parotid venous blood. 2. In unstimulated glands, an arterial blood concentration of 1.5 - 2.5 X 10(-9) mol/L VIP did not evoke fluid secretion but it increased K+ and phosphate secretion and glandular blood flow. The same blood concentration of VIP potentiated the stimulation of salivary flow rate caused by intraarterial infusion of bethanechol but nerve stimulation was not potentiated. VIP increased glandular blood flow in both conditions of stimulation. 3. Atropine blocked neurally stimulated salivary secretion but an increase in glandular blood flow was still detectable. There was therefore no evidence for a non-cholinergic neural mechanism for salivary secretion. 4. Furthermore, VIP concentrations in glandular venous blood were not increased by nerve stimulation. 5. The results indicate that exogenous VIP can affect the flow and composition of ovine parotid secretion but was not involved in the response to secretomotor nerve stimulation.
Explore the source record for details and available documents.
A system for objective assessment of drug activity on voiding parameters is presented. Two groups of spinal cord injured patients with reflex micturition were given bethanecol chloride 50 mg or carbachol 4 mg orally. Carbachol produced a much greater change in recorded voiding parameters.