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Biomedical subjects

W J Hogan

Publications and source records attributed to W J Hogan.

At least 109 records · Page 6Linked to original sources

Salivary response to esophageal acid in normal subjects and patients with reflux esophagitis.

We studied the effect of esophageal acid perfusion on salivation in patients with reflux esophagitis and in normal subjects. Serial 10-min saliva collections were obtained by expectoration during perfusion of the esophagus with water, and then 0.1 N HCl (pH 1.2) for 50 min or 0.01 N HCl (pH 2.1) for 120 min. Within 1-5 min of beginning 0.1 N HCl perfusion, all 8 patients with esophagitis developed heartburn accompanied by an increase in saliva flow. By the time the severity of heartburn required discontinuation of HCl perfusion (10-40 min), saliva flow had increased nearly fourfold. With 0.1 N HCl perfusion, 8 of 10 volunteers developed mild heartburn after 22 +/- 3 min (mean +/- SE), whereas 0.01 N HCl induced heartburn in 6 of 10 volunteers after 57 +/- 12 min of perfusion. Saliva flow increased concurrently with the onset of heartburn and doubled in those volunteers who developed heartburn. Saliva flow did not change in those volunteers who were without heartburn. We conclude that esophageal acid perfusion unaccompanied by heartburn does not affect salivation. However, saliva flow increases concurrently with the onset of heartburn, a phenomenon called "water brash" when clinically evident. The increased saliva flow that accompanies heartburn may act as an endogenous antacid that serves as a protective response to symptomatic gastroesophageal reflux.

Acids↗

Dysfunction of the belch reflex. A cause of incapacitating chest pain.

We report a 25-yr-old woman who suffered incapacitating chest pain caused by upper esophageal sphincter (UES) dysfunction. She presented with a long history of severe episodic chest pain associated with gurgling noises in her chest and was unable to belch despite feeling a need to do so during pain episodes. Fluoroscopic and manometric studies confirmed that the patient's chest pain and gurgling noise were associated with dysfunction of the belch reflex. Although reflux of gas from the stomach into the esophageal body occurred normally, the extreme esophageal distention resulting from the gas reflux failed to trigger UES relaxation. Consequently, there was no venting of gas across the UES. The gurgling noise was caused by the gastroesophageal reflux of gas and the pain was associated with profound esophageal distention. A manometric study of the UES revealed absent or incomplete UES relaxation in response to abrupt esophageal distention by gastroesophageal gas reflux, so that the nadir of UES pressure always exceeded esophageal body pressure. The distended esophagus was repeatedly cleared by secondary peristalsis. To our knowledge this is the first description of chest pain caused by dysfunction of the belch reflex. We speculate that the mechanism described in this patient may account for a subgroup of patients with "chest pain of esophageal origin."

Adult↗

Endoscopic treatment of biliary duct strictures in sclerosing cholangitis: follow-up assessment of a new therapeutic approach.

Endoscopic sphincterotomy was performed on 10 patients with sclerosing cholangitis to improve biliary tract drainage and to remove bile duct sludge and stones. In addition, Gruentzig-type balloons were placed endoscopically to dilate severe biliary duct strictures in eight of these patients, and endoprostheses were inserted to bridge high grade strictures in three patients. In order to assess the effectiveness of endoscopic treatment, we compared the number of hospitalizations for clinical episodes of cholangitis in this patient group for similar periods of time before and after therapy. Episodes of cholangitis requiring hospitalization decreased from 2.5 +/- 0.4 per patient in the 12 months prior to endoscopic therapy to 0.2 +/- 0.2 episodes per patient in the year following treatment and to 0.33 +/- 0.2 episodes per patient in the additional follow-up period during the second year. Liver function tests have improved significantly over the follow-up period of 19.1 +/- 2.6 months from the time of endoscopic treatment. The serum bilirubin decreased from 6.9 +/- 2.0 mg/dl to 2.7 +/- 1.4 mg/dl; serum alkaline phosphatase decreased from 959 +/- 214 IU to 385 +/- 89 IU; and serum transaminase decreased from 117 +/- 17 IU to 77 +/- 12 IU. Endoscopic treatment appears to be effective in patients with severe sclerosing cholangitis.

Adult↗

Endoscopic retrograde cholangiopancreatography in children.

Endoscopic retrograde cholangiopancreatography (ERCP) is a universally used diagnostic and therapeutic modality in adults with pancreaticobiliary tract disease; its use in children with similar problems has been limited. We have performed ERCP procedures in 39 children and adolescents (aged 6 months to 18 years; mean 12.5 years), using the standard adult and pediatric side-viewing endoscopes. In selected cases, ERCP manometric study of the sphincter of Oddi, endoscopic sphincterotomy, or balloon extraction of common bile duct stones was performed. Nineteen patients had significant or abnormal structural findings, including pancreas divisum (four patients); sclerosing cholangitis (three); and choledochal cyst, chronic pancreatitis, choledochocele, pancreatic pseudocyst, common bile duct stone, and sphincter of Oddi motor dysfunction (two each). In all instances in which patients required operation, ERCP examination provided specific anatomic detail that was useful for planning appropriate intervention. The only significant complication after ERCP was mild pancreatitis, which occurred in four patients and responded to supportive, short-term measures.

Adolescent↗

Upper esophageal sphincter function during belching.

We studied the mechanism of belching with specific attention to the upper esophageal sphincter (UES) in 14 normal volunteers. Belching occurred by the following sequence of events: lower esophageal sphincter relaxation; gastroesophageal gas reflux, recorded manometrically as a gastroesophageal common cavity phenomenon; UES relaxation; esophagopharyngeal gas reflux; and restoration of intraesophageal pressure to baseline by a peristaltic contraction. Upper esophageal sphincter relaxations comparable to those associated with belches were induced by abrupt esophageal distention with air boluses. In contrast, fluid boluses injected into the midesophageal body either had no effect on UES pressure or increased UES pressure. Thus, the UES responded to esophageal body distention in two distinct ways: abrupt relaxation in response to air boluses and pressure augmentation in response to fluid boluses. Mucosal anesthesia did not alter the UES response to esophageal boluses of gas or liquid thereby making it unlikely that these substances are differentiated by a mucosal receptor. Rapid distention of the proximal esophagus with a cylindrical balloon (15 cm long) elicited UES relaxation. These findings suggest that the rapidity and spatial pattern of esophageal distention, rather than discrimination of the type of material causing the distention, determines whether or not UES relaxation occurs.

Adult↗

Esophageal peristaltic dysfunction in peptic esophagitis.

Esophageal exposure to acid is a major determinant in the pathogenesis of reflux esophagitis. In this study, we analyzed the esophageal peristaltic function of 177 patients and asymptomatic volunteers for abnormalities that could lead to prolonged esophageal acid clearance. The subjects were divided into five groups: normal volunteers, patient controls, patients with noninflammatory gastroesophageal reflux disease, patients with mild esophagitis, and ones with severe esophagitis. Manometric data were analyzed for the occurrence of failed primary peristalsis, for the occurrence of feeble peristalsis in the distal esophagus, and for hypotensive lower esophageal sphincter pressure. From an analysis of the data on control patients, peristaltic dysfunction was defined as the occurrence of either failed primary peristalsis or hypotensive peristalsis in the distal esophagus for over half of the test swallows. Peristaltic dysfunction was increasingly prevalent with increasing severity of peptic esophagitis, occurring in 25% of patients with mild esophagitis and 48% of patients with severe esophagitis. A correlation did not exist between the occurrence of peristaltic dysfunction and hypotensive lower esophageal sphincter pressure (less than or equal to 10 mmHg). We conclude that peristaltic dysfunction occurs in a substantial minority of patients with peptic esophagitis and could contribute to increased esophageal exposure to refluxed acid material.

Adult↗

Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia.

The human lower esophageal sphincter (LES) is believed to be innervated by nonadrenergic, noncholinergic inhibitory nerves, and cholinergic excitatory nerves. In idiopathic achalasia, LES relaxation is abnormal because the inhibitory nerves to the sphincter are either absent or functionally impaired. The integrity of cholinergic excitatory nerves to the LES, however, has not been thoroughly evaluated. In 27 patients with untreated idiopathic achalasia, and 21 healthy volunteers, we investigated the hypothesis that postganglionic cholinergic nerves to the LES are functionally intact in achalasia. The LES responses to atropine, edrophonium, methacholine, amyl nitrite, and pentagastrin were assessed. In 2 achalasia patients, patterns of fasting motor activity in the LES were investigated during overnight manometric studies. Resting LES pressure was significantly greater in the achalasia patients, 41 +/- 4 mmHg (mean +/- SE), than in the normal subjects, 20 +/- 2 mmHg. Atropine significantly reduced LES pressure in both groups by 30%-75%. Edrophonium increased LES pressure in the achalasia patients but had negligible effect on the normal subjects. The LES in achalasia patients exhibited an increased sensitivity to both methacholine and pentagastrin compared with the normal subjects. In both patients who underwent an overnight manometric study, the LES exhibited cyclic phasic contractile activity synchronous with gastric contractions during the migrating motor complex. We conclude that the study findings support the hypothesis that postganglionic cholinergic LES innervation in achalasia patients is either normal or only minimally impaired, in contrast to the marked impairment of the inhibitory nerves governing LES relaxation.

Adult↗

Contraction pattern of opossum gallbladder during fasting and after feeding.

Our major aims in this study were to determine in unanesthetized opossums the gallbladder volume, pressure, and tone during fasting as well as after feeding, model the kinetics of changes in gallbladder volume, and correlate gallbladder contractility with concurrent spike burst activity in the upper gastrointestinal tract and sphincter of Oddi (SO). In 10 animals, we implanted electrodes on the gastric antrum, duodenum, SO, and jejunum. An indwelling catheter monitored gallbladder pressure and volume. In two animals, a force transducer sutured to the gallbladder wall monitored gallbladder tone. In each animal, fasting migrating myoelectric complexes (MMCs) were recorded in the stomach and small bowel. Cyclic changes in SO spike bursts occurred in synchrony with the MMCs. During fasting, gallbladder pressure, tone, and volume showed cyclic variations. During the second half of the duodenal MMC cycle, the gallbladder exhibited phasic as well as tonic contractions associated with net gallbladder emptying, whereas during the first half of the cycle the gallbladder relaxed and refilled. Minimal gallbladder volume during the MMC cycle averaged 4.8 +/- 0.7 (SE) ml compared with a maximal volume of 7.0 +/- 0.9 ml. Decreases in gallbladder volume occurred as an exponential function, whereas increases in gallbladder were linear. After feeding, the gallbladder underwent a sustained tonic contraction, without superimposed phasic contractions. Decreases in gallbladder volume occurred exponentially to a residual volume of 2.0 +/- 0.5 ml. Net postprandial gallbladder emptying was maximal by 40 min; then the volume remained unchanged for 2-3 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Radiologic amyl nitrite test for distinguishing pseudoachalasia from idiopathic achalasia.

In a simple radiologic test, amyl nitrite inhalation seems to distinguish patients with pseudoachalasia from those with idiopathic achalasia. In three pseudoachalasia patients with tumor infiltration of the distal esophagus, the narrow lower esophageal sphincter segment was unaffected by the smooth-muscle relaxant effect of amyl nitrite. In contrast, amyl nitrite caused a measurable increase of 2 mm or more in sphincter diameter in nine patients with idiopathic achalasia. The amyl nitrite test may be a useful method for distinguishing patients with pseudoachalasia from those with idiopathic achalasia.

Adult↗

Multipeaked esophageal peristaltic pressure waves in patients with diabetic neuropathy.

We evaluated esophageal function in 14 consecutive insulin-dependent diabetic patients who had evidence of peripheral and autonomic neuropathy, but no esophageal symptoms. One to three contraction waves immediately followed a primary peristaltic contraction wave. The majority of these multipeaked pressure complexes consisted of two peaks. Multipeaked contractions were observed with all peristaltic waves in 12 of the 14 diabetic patients and with most of the peristaltic complexes in the remaining 2 patients. Multipeaked peristaltic waves were present in 1 of 6 diabetic patients without neuropathy, in 1 of 100 consecutive nondiabetic patients referred for suspected esophageal disease, and in 1 of 10 healthy volunteers. Double-peaked peristaltic pressure complexes in the nondiabetic control subjects differed from those present in the insulin-dependent patients by their low incidence and by a tendency to be limited to the distal esophagus. Pharmacologic responses to edrophonium and atropine suggested a possible increased cholinergic tone as the basis of the multipeaked peristaltic waves in diabetics with autonomic neuropathy.

Adolescent↗

Sleeve device functions as a Starling resistor to record sphincter pressure.

In 1976 Dent (Gastroenterology 71: 263-267) introduced a sleeve-catheter device for obtaining continuous recording of lower esophageal sphincter pressure. The infused sleeve accommodates for axial sphincter movement by providing a large surface of collapsible membrane that is capable of sensing maximal sphincter pressure at any point along the sleeve. Although sleeve performance was tested previously, the precise physical principal of its function has not been delineated. This study tests the hypothesis that the sleeve device functions as a Starling resistor. The term "Starling resistor" is an eponym that designates the physics of fluid flow through collapsible tubes. When pressure at any point along an infused collapsible conduit is greater than the intraluminal pressure at the distal end of the conduit, partial collapse occurs at some axial location along the conduit where the transmural pressure equals zero. The location of zero transmural pressure is termed the "equal pressure point" (EPP). The partial collapse at the EPP causes a local change in luminal resistance that is directly related to the magnitude of the external pressure at the EPP and accompanied by a corresponding change in the pressure upstream from the EPP. A correlate to the performance of Starling resistors is that the pressure upstream to the EPP is not affected by the downstream pressure, so long as the downstream pressure is less than the external pressure. To test our hypothesis, we evaluated sleeve performance in vitro using a two-chambered model that allowed application of static or oscillatory pressures at one or two sites along the sleeve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Variability of lower esophageal sphincter pressure in the fasted unanesthetized opossum.

The opossum has served as a useful animal model for in vivo studies of lower esophageal sphincter (LES) function. Previous investigations, however, have been confined to studies on anesthetized animals. In 10 opossums we investigated LES pressure during fasting cycles of the gastrointestinal migrating myoelectric complex (MMC) and examined the influences of anesthesia and feeding on LES pressure. Intraluminal pressure from the esophageal body, LES, and gastric antrum was recorded by a manometric assembly that incorporated a sleeve device. Myoelectric activity was recorded from the gastric antrum and duodenum via implanted electrodes. MMCs were readily recorded from all animals. MMC cycle length was 86 +/- 2.9 (SE) min. The LES exhibited cyclic changes in intraluminal pressure that occurred in synchrony with the gastric MMC cycle. During phase I of the gastric MMC cycle, LES pressure was essentially stable, although intermittent spontaneous oscillations at 3-4/min were sometimes noted. Forceful phasic LES contraction started during phase II of the gastric MMC, became maximal during phase III, and disappeared during phase I. The MMC-related phasic LES contraction occurred at a maximal rate of 1.4 +/- 0.05/min with amplitudes of 60-150 mmHg and were temporally associated with spike bursts and contractions in the gastric antrum. Pentobarbital sodium-induced anesthesia abolished MMC-related phasic LES activity and caused a transient rise in basal sphincter pressure. Phasic LES activity was also inhibited by atropine and feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

Effect of esophageal emptying and saliva on clearance of acid from the esophagus.

We studied clearance of acid from the esophagus and esophageal emptying in normal subjects. A 15-ml bolus of 0.1 N hydrochloric acid (pH 1.2) radiolabeled with [99mTc]sulfur colloid was injected into the esophagus, and the subject swallowed every 30 seconds. Concurrent manometry and radionuclide imaging showed nearly complete emptying of acid from the esophagus by an immediate secondary peristaltic sequence, although esophageal pH did not rise until the first swallow 30 seconds later. Esophageal pH then returned to normal by a series of step increases, each associated with a swallow-induced peristaltic sequence. Saliva stimulation by an oral lozenge shortened the time required for acid clearance, whereas aspiration of saliva from the mouth abolished acid clearance. Saliva stimulation or aspiration did not affect the virtually complete emptying of acid volume by the initial peristaltic sequence. We conclude that esophageal acid clearance normally occurs as a two-step process: (1) Virtually all acid volume is emptied from the esophagus by one or two peristaltic sequences, leaving a minimal residual amount that sustains a low pH, and (2) residual acid is neutralized by swallowed saliva.

Acids↗

Computerized analysis of spike-burst activity of the upper gastrointestinal tract.

Although the electrical recording of spike-burst activity is a well-established technique, the visual-manual analysis of the electrical tracings is laborious and time consuming. Current automated methods for analyzing upper gastrointestinal spike-burst activity involve the use of computer systems capable of storing large quantities of data. We describe herein an automated system for counting myoelectrical spike bursts that provides online detection of spike bursts using a laboratory computer. Because only the parameters that describe each burst are stored, only a minimal amount of computer memory is required. Subsequent analysis of stored information yields tabular or graphical output of data. Results of the computer analysis are comparable with those obtained by visual-manual assessment.

Animals↗

Relationship between swallow rate and salivary flow.

Recent studies indicate that swallow-induced, primary peristalsis is a major determinant of normal esophageal acid clearance. However, factors that regulate the rate of spontaneous swallowing in normal subjects are incompletely understood. We postulated that the rate of salivary flow influences the rate of spontaneous swallows. To test this hypothesis, we did a total of 60 studies measuring salivary flow or the rate of spontaneous swallowing in 10 healthy volunteers, age 10-30 years. Saliva was collected by expectoration. Swallow rate was recorded by a small, transnasal catheter stationed in the pharynx and also, in some circumstances, by cervical electrodes. On separate sessions, we evaluated the effect of five test manipulations on salivary flow and swallowing rate, respectively. The test manipulations consisted of: (1) pharyngeal intubation, (2) sucking of a dummy lozenge, (3) sucking of a peppermint lozenge, (4) bethanechol injection (5 mg subcutaneously), and atropine administration (12 micrograms/kg intravenously). Pharyngeal intubation caused a small, but significant increase in the rate of salivation and spontaneous swallows. Sucking of a peppermint lozenge caused a sixfold increase in salivary flow while nearly doubling the swallowing rate whereas the dummy lozenge caused only a modest increase in salivary flow and swallowing. Cholinergic stimulation by bethanechol elicited a substantial increase in salivary flow and swallowing rate. In contrast, atropine caused a significant decrease in both salivary flow and swallowing. We conclude that in awake, normal subjects the rate of spontaneous swallows is influenced directly by salivary flow. Because oral lozenges substantially increase both swallowing rate and salivary flow, such agents merit investigation as a potentially useful ancillary treatment for the relief of heartburn.

Adolescent↗