Search

Senior Loken Syndrome (SLS) is a rare genetic disorder having juvenile nephronophthisis and retinal degeneration progressing to blindness and end stage renal disease. The present case report is about two sisters who presented with decreased visual acuity and end stage renal disease. Both had decreased vision, pallor, deranged renal function test and chronic malnutrition. Investigations revealed anaemia, uraemia, raised creatinine, low Glomerular Filteration Rate (GFR). Ophthalmology examination revealed nystagmus, retinal examination depicted pale optic disc and pigmentary changes in the retina. Renal ultrasound showed grade III renal parenchymal changes and bilateral cortico-medullary cysts. These cases are presented to highlight the importance of timely recognition of renal derangement in patients with retinal disease to delay end stage renal disease.

A number of new classes of antihypertensive drugs have become available in the recent years which appear to hold therapeutic potential for better management of hypertension. Losartan, an angiotensin II receptor antagonist, does not produce cough which is classically seen with ACE inhibitors. Fenoldopam, a dopamine D1-receptor agonist, has a rapid and short duration of action and is ideally suited by intravenous infusion for quick control of BP in hypertensive emergencies. Kentaserin, a serotonin (5-HT2A) receptor antagonist, has a long duration of action and can be given once daily. It has the added benefit of having antiplatelet effect. Monatepil, a dual alpha-receptor and calcium channel blocker, has potent antihypertensive effect, lowers serum cholesterol and also has antiatherosclerotic effect. Dual ACE and endopeptidase inhibitor, such as alatriopril, has a "broad spectrum" antihypertensive effect and may be effective in majority of hypertensive patients. Many other classes of antihypertensive drugs are still in the investigative stage, and their therapeutic potentials and safety need to be ascertained in long-term controlled clinical trials.

We have studied the effect spironolactone (20 mg/kg/day) on cardiovascular complications in neonatal model of diabetes in rats, induced by administering 90 mg/kg streptozotocin (STZ), i.p. in 2 day old rats. Diabetes was checked after 12 weeks. At the end of 8 weeks of treatment, various biochemical and cardiac parameters were measured. STZ produced hyperglycemia, hyperinsulinemia, dyslipidemia, increased creatinine, cardiac enzyme and C-reactive protein (CRP) levels, worsened hemodynamic parameters, cardiac hypertrophy and oxidative stress. Chronic treatment with spironolactone significantly reduced serum glucose levels but did not alter insulin levels. It also significantly prevented the dyslipidemia and reduced elevated Lactate de-hydrogenase, creatinine kinase, CRP and creatinine levels. Chronic treatment with spironolactone prevented STZ-induced hypertension, tachycardia and elevated rate of pressure development and decay. Spironolactone also produced beneficial effect by preventing cardiac hypertrophy as evident from left ventricular collagen levels, cardiac and left ventricular hypertrophic indices and prevented oxidative stress. In conclusion, our data suggests that spironolactone prevents STZ induced metabolic abnormalities and cardiovascular complications in animal model of type 2 diabetes.

The care of the critically-ill patient in the acute setting, an ‘everyday’ occurrence in most urban emergency departments, often proceeds through the dictates of Parsonian paternalism: the Physician knows best. But through a discussion of three such ‘everyday’ encounters, we hope to complicate this notion and find a place for healthcare users in the decision making process while developing a language and analytic basis for thinking seriously about the clinical dyad and the construction of knowledge in relationship economies. Finally, we discuss the escalation and de-escalation (terms derived from the military industrial complex) of care as it relates to medical futility.

Studies revealed that Stevia has been used throughout the world since ancient times for various purposes; for example, as a sweetener and a medicine. We conducted a systematic literature review to summarize and quantify the past and current evidence for Stevia. We searched relevant papers up to 2007 in various databases. As we know that the leaves of Stevia plants have functional and sensory properties superior to those of many other high-potency sweeteners, Stevia is likely to become a major source of high-potency sweetener for the growing natural food market in the future. Although Stevia can be helpful to anyone, there are certain groups who are more likely to benefit from its remarkable sweetening potential. These include diabetic patients, those interested in decreasing caloric intake, and children. Stevia is a small perennial shrub that has been used for centuries as a bio-sweetener and for other medicinal uses such as to lower blood sugar. Its white crystalline compound (stevioside) is the natural herbal sweetener with no calories and is over 100-300 times sweeter than table sugar.

Aim: To evaluate the combined phacoemulsification with acrylic intraocular lens implantation and trabeculectomy with releasable sutures, without the use of antimetabolites, performed by one surgeon. Methods: A retrospective analysis was performed on 251 eyes of 198 patients after a combined phaco/trabeculectomy procedure, followed up for an average of 16 months for vision, intraocular pressure (IOP), and number of glaucoma medications. Cox proportional hazard regression analysis provided measures of relative risk (RR) or hazards ratios and 95% confidence intervals (CIs) associated with the occurrence of several conditions or complications of surgery. Results: Mean preoperative variables were best corrected vision, 0.6 (SD 0.4) logMAR (20/80 Snellen); IOP, 18.7 (4.9) mm Hg; and number of glaucoma medications, 1.7 (0.8). Mean postoperative results were best corrected vision, 0.2 (0.4) logMAR (20/32 Snellen); IOP, 15.1 (3.2) mm Hg; and number of glaucoma medications, 0.3 (0.6). Postoperatively, the mean decreases from baseline were 19.2% for IOP and 84.1% for number of glaucoma medications; 85% of eyes required fewer glaucoma medications and 78% of eyes were medication free, with IOP control. There were no significant operative or postoperative complications. Conclusion: Combined phacoemulsification and trabeculectomy with releasable sutures, in the absence of antimetabolites, is a safe, effective, and stable alternative for patients with cataracts and glaucoma.

Angiotensin converting enzyme (ACE) inhibitors produce a number of beneficial effects in a condition where diabetes - mellitus and hypertension co-exist. The present investigation was undertaken to study the effect of chronic treatment with losartan (2mg/kg, p.o.) on streptozotocin (STZ)-induced (45mg/kg, single dose, tail vein) diabetic nephropathy in rats. Treatment of rats with STZ produced a significant loss of body weight, polyuria. polydipsia, hypoinsulinemia, hyperglycemia and increase in blood pressure. There was a significant increase in blood glucose levels in STZ-diabetic rats. Serum cholesterol, creatinine, urea and blood urea nitrogen (BUN) levels were found to be increased significantly in the STZ group diabetic rats. Treatment with losartan significantly prevented the raise in cholesterol, creatinine, urea and blood urea nitrogen levels. Creatinine clearance was significantly less in STZ-diabetic rats as compared to control animals and treatment with losartan significantly increased creatinine clearence. Our data suggest a beneficial effect of losartan in STZ-induced nephropathy in rats.

Background Myocardial bridging (MB) is an intramyocardial coronary artery segment commonly found in the left anterior descending coronary artery (LAD). Correlation of symptoms with the presence of the MB is controversial. Methods 108 patients with MB detected by 64-slice multidetector computed tomographic angiography (MDCTA) were followed prospectively for the evaluation of cardiac symptoms. Patients were contacted by telephone at 6 months and 1 year, and a standardized questionnaire was completed. Patients were divided into two groups: group 1, patients with MB; group 2, age- and gender-matched controls without MB. Results There was no significant difference between the presenting cardiac symptoms (chest pain, shortness of breath, or palpitations) between the two groups (34 vs 39% p value = NS). During the 6- and 12-month follow-ups, there was a significant and equal decrease in the symptoms in both groups (Table). Conclusions In an age- and gender-matched population, the presence of MB detected by MDCTA was not associated with an increase in cardiac symptoms, either at presentation or during a 12-month follow-up period. MDCT provides a unique opportunity to accurately and noninvasively diagnose MB; the clinical relevance requires further evaluation.

Studies were performed in anesthetized opossums to investigate the electrical activity that may characterize the lower esophageal sphincter. The stomach and lower end of the esophagus were immobilized on a specially prepared stage to eliminate movement artifacts. Extracellular electrical activity was recorded with bipolar needle electrodes. The sphincter pressure was measured with a continuously perfused catheter system. The lower esophageal sphincter showed continuous spike activity with or without phasic variations in their occurrence. The usual frequency of the spikes was 20 to 50 per min, and their duration was 81.2 ± 8.9 msec (mean ± se). The spike potentials ceased with esophageal distention, which also caused a fall in the sphincter pressure. The spikes were abolished by isoproterenol and they increased with bethanechol. Correlation of the spike activity with the pressure revealed that the sphincter pressure was higher when the spike potentials were present, but a major part of the pressure existed in the absence of any spike activity. These studies show that: (1) the opossum lower esophageal sphincter is characterized by continuous spike potentials, and (2) the major fraction of the basal pressure is, however, independent of the spike potentials.

The purpose of the present investigation was to identify and compare cholinergic intramural neurons in the lower esophageal sphincter and esophageal body by histochemical staining for acetylcholinesterase and the enzyme that synthesizes acetylcholine, choline acetyltransferase. Opossums were anesthetized and their abdominal cavity was opened by a midline incision to expose the esophagogastric junction. The lower esophageal sphincter was identified manometerically and localized in situ with markers. Tissues were removed, rapidly frozen in freon cooled with liquid nitrogen and serial cryostat sections were obtained from the lower esophageal sphincter and esophageal body. Sections were stained with one of the above histochemical procedures and adjacent sections were stained with Solachrome cyanin , which differentially stains nerve elements from muscle fibers. The muscle of the lower esophageal sphincter and esophageal body was stained with nonspecific cholinesterase with some selectivity of intensity of reaction in the various smooth muscle layers. All identifiable plexus neurons in the esophagus stained for nonspecific cholinesterase and acetylcholinesterase. Nerve fiber tracts were also stained for acetylcholinesterase within the longitudinal and circular layers of the tunica muscularis. Reaction for choline acetyltransferase showed no staining in the muscle layers or nerve fiber tracts of either part of the esophagus studied; however, selected neurons within the myenteric plexus of both regions (approximately 38%) were reactive. There was no significant difference in the number of positive choline acetyltransferase neurons in the lower esophageal sphincter or esophageal body.

Studies were performed in anesthetized and awake opossums to define the genesis of resting pressure and opening of the upper esophageal sphincter. Intraluminal pressures were measured with low compliance, perfused catheters. Electromyograms were recorded using miniature concentric bipolar electrodes from the cricopharyngeus, inferior pharyngeal constrictor, middle pharyngeal constrictor, proximal end of the esophagus, and geniohyoid muscles. Upper esophageal sphincter pressure showed radial as well as axial asymmetry; the pressures were higher in awake than in anesthetized animals. Electromyographically, only the cricopharyngeus and inferior pharyngeal constrictor fired continuously at rest and ceased to fire during swallowing. d -Tubocurarine or section of the motor nerve abolished electrical activity in the cricopharyngeus and inferior pharyngeal constrictor and caused marked reduction but not obliteration of upper esophageal sphincter pressure. Contraction of the geniohyoid muscle abolished the remaining pressure in the upper esophageal sphincter. Moreover, contraction of the geniohyoid muscle caused a fall in upper esophageal sphincter pressure, even when the cricopharyngeus and inferior pharyngeal constrictor were kept contracted. These studies indicate: (1) upper esophageal sphincter corresponds mainly to the cricopharyngeus and inferior pharyngeal constrictor; (2) the resting upper esophageal sphincter pressure is attributable to continuous active muscle contraction as well as the elasticity of the surrounding structures; and (3) the opening of the upper esophageal sphincter is attributable to inhibition of the contraction of the cricopharyngeus and inferior pharyngeal constrictor and the forward displacement of the larynx by the geniohyoid muscle.

Gastrin I or pentagastrin caused contraction of the lower esophageal sphincter in anesthetized opossums. The contraction was not modified, either qualitatively or quantitatively, by 30 or 1000 μg per kg atropine pretreatment. Moreover, neural block with tetrodotoxin did not influence the effect of gastrin on the sphincter pressure. H 2 receptor antagonist, metiamide, did not modify the magnitude of the contractile response of the lower esophageal sphincter to gastrin I. These studies show: a) gastrin does not cause sphincter contraction by stimulating cholinergic neurons; and b) gastrin does not exert an inhibitory effect on the sphincter pressure by stimulating H 2 receptors. We suggest that gastrin may contract the lower esophageal sphincter by a direct action on the sphincter muscle.

Transhepatic cholangiography is indicated in diagnosing the cause of jaundice when routine radiographic methods of visualizing the biliary tract cannot be undertaken or when they do not show the etiology of biliary obstruction. Transhepatic cholangiography can help to distinguish intrahepatic from extrahepatic obstruction and can show whether common duct stones, stricture or neoplasm is the cause of obstruction. Complications from this procedure are usually avoided when surgery follows immediately.

Studies were performed to investigate the effect of prostaglandin E2 on esophageal motility in 12 healthy volunteers. PGE2 infusion caused a dose-dependent reduction in the lower esophageal sphincter pressure. The threshold dose was less than 0.05 mug-kg-1-min-1 and maximal reduction of pressure (60%) occurred with a dose of 0.4 mug-kg-1-min-1. In contrast to its effect on the lower esophageal sphincter, PGE2 did not alter the pressure in the upper esophageal sphincter. PGE2 did not influence resting esophageal pressures; the amplitude of peristaltic contractions was reduced in the lower but not in the upper part of the body of the esophagus. These studies show that in man PGE2 exerts selective inhibitory influence on the activity of the lower part of the esophagus and lower esophageal sphincter which are composed of smooth muscle fibers.

Clinical study of an insulin-like compound obtained from vegetable source (vegetable insulin) was carried out on nine patients with diabetes mellitus. The active hypoglycaemic principle, purified protein extract, was obtained from fruits as well as from tissue cultures of the plant Momordica charantia L. This extract was homologous to insulin obtained from animal pancreas. It showed a consistent hypoglycaemic effect in patients with diabetes mellitus. The average fall in blood sugar level at the peak effect of vegetable insulin was found to be statistically significant. The onset of action was within 30-60 min with the peak effect six hours after the administration of the dose of plant insulin. No hypersensitivity reaction to this extract was observed in the group of patients studied.

A case of seleroma involving only the oesophagus is described, this is the first case of involvement of oesophagus by scleroma recorded in the literature.

Studies were performed in anesthetized opossums to determine the influence of binding of circulating gastrin with a high titer gastrin antiserum on lower esophageal sphincter pressure. Gastrin antiserum or control antiserum was administered intravenously in successive doses of 0.02, 0.1, and 0.5 ml/kg on separate days. The lower esophageal sphincter pressures were measured for 1 h before and for 1 h after antiserum administration. The control serum caused no binding of opossum circulating gastrin, nor did it modify lower esophageal sphincter pressure. On the other hand, the administration of gastrin antiserum resulted in the binding of 85-90% of circulating gastrin, but it did not reduce sphincter pressure. A continuous infusion of 0.25 mug-kg-1-h-1 of synthetic human gastrin I caused a significant (P less than 0.05) increase in the sphincter pressure, a 30-fold increase in gastric acid output, and a fourfold increase in immunoreactive gastrin in the opossum blood. Prior treatment with 0.1 ml/kg of gastrin antiserum antagonized and 0.2 ml/kg of the antiserum abolished the gastrin-stimulated gastric acid secretion and the stimulating effect of gastrin on lower esophageal sphincter pressure. However, neither dose of antiserum modified basal lower esophageal sphincter pressure. It is concluded that circulating gastrin may be an important determinant of basal sphincter pressure.

Intravenous administration of 5-hydroxytryptamine (5-HT) caused a dose-dependent contraction in the lower esophageal sphincter in the opossum. The smallest dose of 5-HT which caused a detectable contraction of the sphincter was 0.5 mug/kg, and a maximal sphincter contraction was produced by a dose of 40 mug/kg. Methysergide converted the contractile effect of 5-HT to a dose-dependent fall in the sphincter pressure; maximal inhibition of 77.2 +/- 7.2% of the resting pressure occurred with a dose of 40 mug/kg. The inhibitory effect of 5-HT was antagonized by tetrodotoxin, 5 MeO-DMT, and 5-HT tachyphylaxis. 5 MeO-DMT enhanced 5-HT-induced contraction of the sphincter. In the presence of 5 MeO-DMT and methysergide, 5-HT still caused a brief contraction of the sphincter; this contraction appeared to be due to stimulation of postganglionic cholinergic neurons as it was antagonized by tetrodotoxin or atropine. Reserpinization caused enhancement of the sphincter contraction by 5-HT. In the reserpinized animals in the presence of methysergide, 5-HT caused a small initial contraction followed by prolonged inhibition; atropine antagonized the initial contraction, while inhibition was antagonized by 5 MeO-DMT. These studies are consistent with the view that 5-HT exerts several different effects on the sphincter. 5-HT causes contraction of the sphincter by its direct action on the muscle and also by stimulation of cholinergic excitatory neurons. In addition, 5-HT inhibits the sphincter by stimulation of nonadrenergic inhibitory neurons.

Experiments were performed in anesthetized opossums to study the nature of vagal control on the small bowel. Electrical activity was recorded in the duodenum, jejunum, and ileum with silver chloride electrodes. Slow waves and spike potentials were observed at all three sites. There was a decreasing frequency gradient of slow waves and the incidence of slow waves with spikes in the aboral direction. Vagotomy had no effect on the electrical activity. Vagal stimulation at threshold stimuli inhibited spike potentials in all three segments of small intestine, but slow waves were not affected. Vagal stimulation after sectioning of the gut proximal to the electrodes converted the response from inhibition to excitation. These studies suggest that a) vagus carries both excitatory and inhibitory influences to the small bowel; b) inhibitory influences are dominant in the intact opossum small intestine; and c) the nature of the response obtained with vagal stimulation may be explained on the basis of the paths taken by inhibitory and excitatory fibers.

The investigation was undertaken to study the mechanism of the inhibitory effects of clonidine on the oestrogen-primed rat isolated uterus. Clonidine produced dose-dependent relaxations of the rat isolated uterus which were competitively blocked by yohimbine but not by prazosin. Metiamide, a specific H2-histamine receptor antagonist, inhibited clonidine-induced responses only at a high concentration (1.0 X 10(-6)M). Propranolol, a beta-adrenoreceptor antagonist produced competitive antagonism of the clonidine responses. Like clonidine, noradrenaline also produced dose dependent relaxations of the rat isolated uterus. The responses to noradrenaline were not antagonized by either prazosin or yohimbine but were competitively antagonized by propranolol. The responses to clonidine were significantly inhibited by reserpine pretreatment (5 mg/kg; i.p., 24 h before) whilst responses to noradrenaline were significantly increased by this treatment. It is concluded that clonidine inhibits the uterus via an action on alpha 2-adrenoreceptors and possibly also to a lesser extent on H2-histamine receptors, leading ultimately to release of noradrenaline from endogenous stores which causes relaxation by acting on beta-adrenoreceptors.

Experiments were performed in anesthetized opossums. Electrical and mechanical activity was recorded simultaneously from the esophageal body at 5, 3, and 1 cm above the lower esophageal sphincter (LES). Esophageal responses were evoked by electrical stimulation of vagal efferents or by induced swallowing. Electrical and mechanical activity was associated in 86% and dissociated in 14% of the 1,200 responses examined. The frequency of dissociation was dependent on the site in the esophagus and the frequency of vagal efferent stimulation (P less than 0.05). The interval between the onset of electrical and mechanical events, called electromechanical delay, had a regional gradient: 5 cm above LES greater than 3 cm greater than 1 cm (P less than 0.01). This delay was also dependent on the frequency of stimulation. The amplitude of spike burst and the number of spikes in a burst closely correlated with the amplitude of contraction. These studies show that electromechanical responses and dissociations are dependent on the regional level in the esophagus and the frequency of vagal stimulation.

Isolated lower esophageal sphincter (LES) relaxation, defined as a transient sphincteric relaxation unaccompanied by esophageal peristalsis, has been shown to precede most episodes of gastroesophageal reflux in humans. We studied the genesis of isolated LES relaxation in anesthetized opossums by observing the response of four components of the deglutition reflex (mylohyoid electrical activity, pharyngeal contraction, esophageal peristalsis, and LES relaxation) to pharyngeal tactile stimulation, electrical stimulation of superior laryngeal nerve (SLN) afferents or cervical vagal efferents, and to balloon distention of the esophageal body. A single pharyngeal stroking evoked isolated LES relaxation in 56% of 160 instances. The proportion of isolated relaxations in response to SLN electrical stimulation varied inversely with the stimulus frequency, occurring in 64% of the responses at 5 Hz and 4% of the responses at 30 Hz. A full four-component deglutition sequence was most likely to occur at the higher frequencies of SLN electrical stimulation. Esophageal balloon distention elicited isolated LES relaxations or no response at low distending volumes, whereas at higher volumes LES relaxation and esophageal contraction predominated. Isolated LES relaxation had significantly less magnitude than relaxations accompanied by esophageal contractions. Bilateral cervical vagotomy abolished all LES and esophageal body responses induced by pharyngeal stroking and SLN stimulation, and rendered the esophageal body and LES less responsive to small volumes of distention. Vagal efferent stimulation produced isolated LES relaxation at lower frequency stimulation and LES relaxation with esophageal contractions at higher frequency stimulation. These studies show that isolated LES relaxation represents incomplete expression of either the deglutitive reflex or the peripheral reflex mediating secondary peristalsis.

Ranitidine in lower doses, (100 ng and 1 microgram) accelerated the rate of reaction of the enzyme acetylcholinesterase with the substrate acetylthiocholine. However, in higher doses (10 micrograms and 100 micrograms) it inhibited the enzyme activity. In rat anococcygeus muscle preparation, the responses to acetylcholine were significantly inhibited in lower doses whereas in higher doses there was a dose-dependent potentiation of the responses to acetylcholine by ranitidine. The responses to carbachol were however, not affected by ranitidine in the same preparation. Our data suggest cholinomimetic as well as cholinolytic activity of ranitidine.

Anticholinergic drugs in a patient with Z-E syndrome were only temporarily successful in suppressing gastric hypersecretion and producing symptomatic relief. After escape from control with propantheline bromide, glycopyrrolate was only partially successful in suppressing basal acid secretion. Eventually, complete escape from anticholinergic control occurred with a recurrence of significant gastric hypersecretion and the development of severe peptic esophagitis, necessitating total gastrectomy.

Mechanical events and membrane potential changes in response to evoked swallows and cervical vagal stimulation (10 and 40 Hz) were recorded in anesthetized opossums. Miniature strain-gauge transducers monitored the mechanical activity of the two layers. A suction electrode recorded from the intact esophagus, from a proximally based pedicle flap of longitudinal muscle (LM), and from circular muscle (CM). The onset of swallowing was marked by the onset of mylohyoid activity. During swallows LM contraction preceded CM contraction and was of longer duration. The latencies of LM and CM contraction were 1,980 +/- 38 and 2,250 +/- 101 ms, respectively. The durations of contraction of LM and CM were 5,590 +/- 260 and 3,330 +/- 67 ms, respectively. LM showed no hyperpolarization but showed depolarization and spike burst. The CM showed prompt hyperpolarization followed by depolarization and spike burst. Responses to vagal stimulation were qualitatively similar to swallows. The different components of the responses were quantitatively modified by changes in stimulus frequency. These studies show that, during peristalsis in response to swallows and vagal stimulation, 1) LM contraction occurs before CM and is of longer duration, and 2) unlike CM, LM does not hyperpolarize prior to depolarization.

Infusions of verapamil (V) and sodium nitroprusside (NP) caused dose-dependent reductions in the lower esophageal sphincter pressure (LESP) in anesthetized opossums. Verapamil caused a gradual fall during the infusion and a gradual recovery upon cessation of the infusion. On the other hand, NP caused a prompt reduction and a prompt recovery. Both the agents also caused a fall in arterial blood pressure, but the fall in LESP was not related to the fall in the blood pressure. Both the agents antagonized the tonic and the phasic components of the LESP and, in large doses, both drugs almost abolished the LESP. Esophageal contractions were also antagonized by both agents, although verapamil was more effective than nitroprusside in this regard. These studies show that phasic and tonic components of LESP are not related to distinctive verapamil and nitroprusside sensitive calcium activation systems. Moreover, the V- and NP-sensitive calcium activation systems may lie in series rather than parallel.

We examined the mechanical activity of the longitudinal and circular muscles of the esophagus at three different levels (9, 5, and 1 cm above the lower esophageal sphincter) during peristalsis induced by swallows or vagal stimulation in anesthetized opossums with miniature strain gauges applied in the axis of muscle fibers. The onset of longitudinal muscle contraction occurred in an aboral sequence with swallows but simultaneously with vagal stimulation. The speed of longitudinal muscle activation with swallows was 7.6 +/- 1.7 cm/s. Circular muscle contraction occurred in an aboral sequence with vagal stimulation and swallowing with speeds of 4.1 +/- 0.8 and 2.3 +/- 0.1 cm/s, respectively. Longitudinal muscle contracted before the circular muscle at all sites. The duration of longitudinal muscle contraction increased aborally (P less than 0.05) with swallowing or vagal stimulation. These studies show that 1) during swallowing, esophageal longitudinal and circular smooth muscle contract in a sequential fashion, 2) the longitudinal muscle sequential contraction is due to central mechanisms, whereas circular muscle sequential contraction may be due to both central and peripheral mechanisms, and 3) peripheral neuromuscular mechanisms produce regional differences in the duration of longitudinal muscle contraction.

Studies were performed in anesthetized opossums to investigate the nature of vagal-stimulated sphincter relaxation, which is resistant to antagonism by a combination of hexamethonium and atropine. The sphincter pressures were measured with water-filled and continuously perfused catheters anchored in the lower esophageal sphincter. Neither increase in the doses of hexamethonium and atropine nor addition of diphenhydramine further modified the vagal response. However, administration of 5-methoxydimethyltryptamine in the presence of hexamethonium and atropine abolished vagally stimulated sphincter relaxation. In animals pretreated with parachlorophenylalanine, addition of atropine and hexamethonium also abolished vagally stimulated sphincter relaxation. In the experiments in which lower esophageal sphincter relaxation on vagal stimulation was abolished, the local stimulation of intramural neurons still produced normal lower esophageal sphincter relaxation. These studies suggest that 5-hydroxytryptamine may participate in the vagal inhibitory pathway to the lower esophageal sphincter.