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Biomedical subjects

W J Snape

Publications and source records attributed to W J Snape.

At least 109 records · Page 6Linked to original sources

Clinical and manometric findings in benign peptic strictures of the esophagus.

To determine the possible factors that may contribute to the development of peptic stricture of the esophagus, clinical and manometric features were compared in patients with symptomatic gastroesophageal reflux and those with peptic strictures of the esophagus. Patients with stricture were older and had a longer duration of heartburn than patients without a stricture. Most importantly, patients with stricture had a more marked decrease in lower esophageal sphincter (LES) pressure, 4.9 +/- 0.5 mm Hg, than patients without a stricture, 7.5 +/- 0.6 mm Hg, P less than 0.01. The LES pressure in all patients with stricture was below 8 mm Hg, and did not overlap with normal values. Patients with stricture had either a nonspecific motor abnormality of aperistalsis (64%), compared to patients with symptomatic reflux (32%), P less than 0.05. Thus, peptic stricture of the esophagus is commonly associated with a long duration of reflux symptoms in patients with a very low LES pressure and esophageal motor disorder.

Age Factors↗

Herpes simplex esophagitis: a cause of upper-gastrointestinal bleeding.

Two patients with hemorrhagic esophagitis secondary to esophageal invasion with herpes simplex virus, type 1, are reported. Microscopic examination of the esophageal mucosa revealed multinucleated cells and intranuclear inclusions which are typical of herpes simplex infection. Herpes virus was cultured from each patient. Thus, hemorrhagic esophagitis due to esophageal invasion by herpes simplex virus may be a more frequent cause of upper-gastrointestinal bleeding than previously recognized.

Aged↗

Effect of bethanechol, gastrin I, or cholecystokinin on myoelectrical activity.

The purpose of this study was to determine the effect of bethanechol, gastrin I, or the octapeptide of cholecystokinin (CCK-OP) on the smooth muscle of the isolated cat colon. Myoelectrical activity was recorded with monopolar glass-pore electrodes. Slow-wave frequency was 5.9 +/- 0.2 cycles/min during the basal period. Slow waves were generally coupled during the control period and the apparent propagation velocity was predominantly aborad at a velocity of 3.8 +/- 0.4 mm/s. Spike activity was superimposed on 11.9 +/- 1.5% of the slow waves during the control period. Bethanechol stimulated a dose-dependent increase in colonic spike activity, with a threshold concentration of 10(-7) M. Bethanechol did not alter the congruence of the colonic slow-wave frequency at any concentration. Gastrin I or CCK-OP increased colonic spike activity. The threshold concentrations for gastrin I and CCK-OP were 2 X 10(-11) M and 4 x 10(-11) M, respectively. Unlike bethanechol, gastrin I (2 X 10(-9) M - 2 X 10(-8) M) and CCK-OP (4 X 10(-9) - 4 X 10(-8) M) altered slow-wave frequency and decreased slow-wave congruence. These studies suggest that 1) bethanechol, gastrin I, or CCK-OP increases colonic spike activity, and 2) only gastrin I or CCK-OP alters the slow-wave frequency of colonic muscle. Thus neurohumoral substances may act independently on colonic spike activity and colonic slow-wave frequency.

Action Potentials↗

Comparison of proximal and distal colonic muscle of the rabbit.

Mechanical length-tension properties and response to neurohumoral agents were compared for proximal and distal colonic muscle. Resting tension during stretch, acetylcholine-stimulated tension, and the total tension were determined. Proximal circular muscle developed a maximum total tension of 0.96 +/- 0.18 kg/cm2 (mean +/- SE) compared to 0.86 +/- 0.06 kg/cm2 for the distal colon (P greater than 0.05). Resting tension was 0.33 +/- 0.03 kg/cm2 for the proximal colon and 0.05 +/- 0.01 kg/cm2 for the distal colon at the length of optimal acetylcholine-stimulated tension (Lo) (P less than 0.01). Longitudinal muscle showed a similar difference for the proximal and distal colon. The high resting tension in the proximal colonic muscle was reduced by nitroprusside or calcium-free Krebs with EGTA. Dose-response curves to acetylcholine, histamine, phenylephrine, and isoproterenol were similar for the muscle of either part of the colon. Gastrin or cholecystokinin had no effect on the muscle. In summary, the circular or longitudinal muscles of the proximal and distal colon have different length-tension properties but only minimal differences in response to neurohumoral agents.

Acetylcholine↗

Modulation of lower esophageal sphincter relaxation in the opossum.

The relationship of lower esophageal sphincter (LES) relaxation and sphincter pressure was studied in the basal state and after neurohumoral stimulation in the anesthetized opossum. LES relaxation was induced by electrical vagal stimulation, balloon distension, and swallowing, whereas LES pressure was increased by infusions of gastrin I, histamine, phenylephrine, or bethanechol. Each agent was selected to give an approximately twofold increase in LES pressure, at the highest dosage. The lower dosage gave a submaximal increase in LES pressure. Neither gastrin nor histamine modified sphincter relaxation as induced by vagal stimulation, esophageal distension, or swallowing. Phenylephrine or bethanechol made the LES less sensitive to vagal stimulation or esophageal distension without reducing maximal LES relaxation. Only bethanechol significantly decreased sphincter relaxation in response to swallowing (P less than 0.05). The results of this study suggest that LES relaxation is not a fixed response simply dependent on the inhibitory stimulus or the resting tonic level of LES pressure, but may be modulated by both alpha-adrenergic and cholinergic drugs.

Animals↗

Sympathetic control of lower esophageal sphincter function in the cat. Action of direct cervical and splanchnic nerve stimulation.

The purpose of this study was to determine the effect of direct stimulation of the sympathetic nerves on the lower esophageal sphincter (LES) in the anesthetized cat. Neither unilateral nor bilateral cervical sympathectomy, or splanchnicectomy significantly modified basal LES pressure in animals with intact vagi, or animals having undergone bilateral cervical vagotomy. Electrical stimulation of the cut, peripheral, cervical sympathetic trunk increased mean arterial blood pressure, but had no effect on LES pressure or LES relaxation as induced by vagal stimulation. Stimulation of the central end of the cervical sympathetic trunk had no effect on LES pressure. Stimulation of the central end of the cut splanchnic nerve produced a decrease in LES pressure with a maximal response of 69.1+/-16.0% (mean+/-SEM). This inhibitory response was not modified by either propranolol or bilateral cervical vagotomy. Stimulation of the peripheral end of the cut, greater splanchnic nerve gave an increase in LES pressure with a maximal response of 38.2+/-7.19 mm Hg. Guanethidine, in the presence or absence of the adrenal glands, significantly augmented this excitatory response. This response was also slightly increased by phentolamine alone at 10 V, 1 Hz, but was not altered by propranolol. The excitatory response was completely antagonized by atropine or by trimethaphan camsylate. Stimulation of the peripheral end of the splanchnic nerve inhibited LES relaxation as induced by vagal stimulation. The results of this study suggest that: (a) the LES in the cat is not affected by either central or peripheral stimulation of the cervical sympathetic trunk; (b) the central portion of the splanchnic nerve carries an afferent inhibitory response to the LES through yet unknown pathways; (c) the peripheral splanchnic nerve carries an atropine-sensitive excitatory response to the LES; and (d) the splanchnic nerves may modulate LES relaxation as induced by vagal stimulation.

Adrenalectomy↗

Internal fixation versus nontreatment of hip fractures in senile patients.

Institutionalized senile patients with hip fractures have a high mortality regardless of whether treatment consists of internal stabilization or is non-operative. In an effort to select the best therapeutic approach in this type of patient, 150 patients were examined in 3 comparable groups. In the first group of 50 patients treatment consisted of surgical stabilization of the fracture. In the second group of 45 patients treatment was non-operative; mortality in these 2 groups was over 50% at the end of 16 weeks. In an effort to improve this degree of risk we transferred 53 patients from the psychiatric hospital to a general hospital for prompt internal stabilization of the hip fractures. There was a striking decrease in mortality to 28% in the third group. We have concluded that under optimal conditions, prompt surgical stabilization of hip fractures in elderly senile individuals offers them the best opportunity of surviving the injury and is preferable to nontreatment.

Aged↗

The gastrocolic response: evidence for a neural mechanism.

The aim of this study is to determine the effect of anticholinergic therapy on the gastrocolonic response to a standard meal or its major constituent fat. A rapid increase in rectosigmoidal spike activity occurs after ingesting the standard meal or the fat meal (P less than 0.01). Distal colonic motility returns to fasting levels 50 min after both meals. There is no further increase in spike activity after the 1000-calorie meal, but spike activity increases again 70 min after ingesting the fat (P less than 0.02). The anticholinergic drug, clidinium bromide, inhibits the early increase in spike activity after both meals. However, the anticholinergic has no effect on the delayed peak of activity following the ingestion of fat. This study suggests that (a) the early gastrocolic response to a standard meal and a fat meal is cholinergically mediated and (b) the late increase in rectosigmoidal motility occurs only after fat ingestion and may be controlled by other neural mediators or possibly the gastrointestinal hormones.

Adult↗

Colonic myoelectrical activity in irritable-bowel syndrome. Effect of eating and anticholinergics.

To determine the effect of a standard meal on colonic myoelectrical and motor activity in the irritable-bowel syndrome and to determine the effect of a single dose of an oral anticholinergic drug (clidinium bromide) on this response, we studied 10 patients. These patients showed a prolonged increase in both colonic spike (P less than 0.05) and motor activity (P less than 0.05) after eating as compared to normal subjects. Clidinium did not affect the frequency of colonic slow waves or the basal colonic spike and motor activity. However, the anticholinergic reduced the prolonged postprandial colonic spike and motor response in the patients and also reduced the postprandial increase in colonic contractions at 3 cycles per minute (P less than 0.05). These studies indicate that patients with the irritable-bowel syndrome show an abnormally prolonged post-prandial increase in colonic spike and motor activity. An anticholinergic drug reduces the duration and the magnitude of this abnormal colonic response.

Administration, Oral↗

Effect of thoracic vagotomy and vagal stimulation on esophageal function.

The purpose of this study was to determine the effect of thoracic vagotomy and thoracic vagal stimulation upon esophageal peristalsis and lower esophageal sphincter (LES) function in the opossum. The thoracic portion of the vagus nerve was sectioned in the upper or lower thorax. Bilateral, but not unilateral, thoracic vagotomy above the level of the heart abolished peristalsis and LES relaxation in response to swallowing or cervical vagal electrical stimulation. Thoracic vagotomy at the level of the ventricle or below did not alter either peristalsis or LES relaxation during swallowing or cervical vagal stimulation. Secondary peristalsis and its associated LES relaxation was unaltered by thoracic vagotomy at any level. Electrical stimulation of the distal end of the upper thoracic vagus elicited both peristalsis and LES relaxation. Electrical stimulation of the distal end of the lower thoracic vagus elicited both peristalsis and LES relaxation. Electrical stimulation of the distal end of the lower thoracic vagus, as well as stimulation of the vagal branches to the terminal esophagus, gave only LES relaxation. These studies suggest that: a) the major extrinsic vagal innervation mediating primary peristalsis terminates in the upper portion of the esophagus, whereas the vagal innervation mediating LES relaxation responses are present throughout the length of the esophagus; and b) secondary peristalsis and its associated LES relaxation occurs independent of extrinsic vagal innervation.

Animals↗

Achalasia secondary to carcinoma: manometric and clinical features.

The clinical and diagnostic features of a secondary type of achalasia of the esophagus are described in seven patients with various types of malignancies. Patients with secondary achalasia presented with dysphagia of short duration and marked weight loss; mean age was 64 years. Esophageal manometry showed features identical to those of idiopathic primary achalasia: aperistalsis, poor lower esophageal sphincter relaxation, and elevated sphincter pressure. Endoscopy and barium swallow showed evidence of a tumor in only two cases. Various types of malignancies may produce a secondary form of achalasia that has diagnostic features identical to those of primary achalasia and is best identified by its clinical presentation.

Adult↗

Effect of histamine and histamine antagonists on human lower esophageal sphincter function.

The purpose of this study was to evaluate the effect of histamine phosphate and specific histamine antagonists on human lower esophageal sphincter (LES) pressure. Continuous intravenous infusions of histamine at doses of 2.0 to 40.0 microgram/kg-hr gave graded increases in LES pressure with a peak response of 378 +/- 4.6 mm Hg at 20.0 microgram kr-hr. The LES response was not altered by an H1-antogonist, diphenhydramine (50 mg, intravenously), but was completely blocked by infusion of the H2-antagonist, cimetidine (4.0 mg/kg-hr). Also, oral cimetidine (300 mg) antagonized any increase in LES pressure during histamine infusion at a dose shown to give the maximal LES response. Despite this effect of cimetidine in antagonizing the maximal LES response to histamine, oral cimetidine at 200, 300, and 400 mg failed to alter basal LES pressure over a 3-hr period. Cimetidine also failed to alter the LES response to intravenous pentagastrin or oral beef hydrolysate. These studies suggest that: (1) human LES pressure increases in response to intravenous histamine phosphate through its action at an H2-receptor; (2) the H1-receptor has no apparent role in the human LES response to histamine; and (3) H2-antagonism with cimetidine has no effect on the human LES basal pressure or its response to gastrin stimulation.

Cimetidine↗

The pathophysiology and treatment of gastroesophageal reflux disease: new concepts.

In summary, the recent understanding of the pathogenesis of gastroesophageal reflux disease as owing to LES incompetence has led to improvement in both the diagnosis and the treatment of this disorder. Diagnosis now dependent on demonstrating the presence of reflux, an incompetent sphincter mechanism, or some complication of reflux. Treatment is focused on reducing the endogenous factors that contribute to reflux, or actually restoring the sphincteral barrier to reflux by pharmacologic or surgical means.

Bethanechol Compounds↗

Gastrointestinal myoelectrical activity in idiopathic intestinal pseudo-obstruction.

We evaluated the myoelectrical and motor function of the esophagus, small intestine, colon and anal sphincter in four patients with chronic idiopathic intestinal pseudo-obstruction. All patients had aperistalsis of the esophagus, with incomplete relaxation of the lower esophageal sphincter after swallowing or balloon distension. Duodenal slow-wave frequency was normal at 11.4+/-0.3 (+/-S.E.M.) cycles per minute. The patients did not have a normal increase in duodenal spike or motor activity after intestinal distension, but duodenal activity increased after stimulation with intravenous secretin. Colonic slow-wave activities were present at two frequencies, 6.2+/-0.3 and 3.3+/-0.1 cycles per minute. Neostigmine administration increased both colonic spike and motor activity normally. These studies suggest that in this disorder, physiologic neural responses to swallowing or intestinal distension are impaired but the intestinal smooth-muscle slow-wave activity and the spike and motor responses to exogenous neurohormonal stimulation are intact.

Adult↗

Human colonic myoelectric activity in response to prostigmin and the gastrointestinal hormones.

Colonic myoelectric activity was determined using a mucosal clip electrode in normal human subjects, in the basal state and following the administration of prostigmin, pentagastrin, cholecystokinin, or secretin. Slow-wave activity was present 49 +/- 3.0% of the recording time and occurred at two frequencies, 6.5 +/- 0.1 cycles/min and 3.5 +/- 0.1 cycles/min, in the rectum. Spike potentials were infrequent in the basal state. Prostigmin, pentagastrin, or cholecystokinin did not affect the slow-wave activity or frequency, but these agents significantly increased the number of spike potentials (P less than 0.05). Secretin had no effect on myoelectric activity. The electrode system was tested in the cat and showed excellent correlation of the myoelectric activity between the mucosal clip electrode and a serosal electrode. These studies indicate: (1) a mucosal clip electrode provides an accurate method of recording colonic myoelectric activity when compared to a serosal electrode in the cat; (2) in man, slow-wave activity is present only intermittently and exists at two frequencies, approximately 6 cycles/min and 3 cycles/min; (3) gastrointestinal hormones and prostigmin increase spike potential discharge without altering slow-wave activity or frequency.

Adult↗