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Biomedical subjects

W G Paterson

Publications and source records attributed to W G Paterson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Esophageal shortening induced by short-term intraluminal acid perfusion in opossum: a cause for hiatus hernia?

BACKGROUND/AIMS: Reflux esophagitis and hiatal hernia commonly coexist, yet a cause and effect relationship remains unclear. This study examined whether acute acid-induced esophageal injury induces longitudinal esophageal shortening in the opossum model. METHODS: Esophageal length was measured continuously using a specially designed strain gauge transducer in anesthetized opossums while the midesophagus was perfused intraluminally with either normal saline or 100 mmol/L HCl. After a stabilization period, the test solution was perfused for 150 minutes. The effect of bilateral cervical vagotomy and atropine (60 microns/kg intravenously) were determined in separate groups. Parallel studies in which resting lower esophageal sphincter pressure was measured before and after prolonged intraesophageal acid perfusion were performed. RESULTS: Esophageal acid perfusion induced acute epithelial injury as determined histologically. This was associated with significant esophageal shortening compared with saline-perfused controls and was not affected by vagotomy or atropine. In contrast, acid perfusion invariably induced a decrease in resting lower esophageal sphincter pressure. CONCLUSIONS: Acute acid-induced esophageal mucosal injury induces longitudinal esophageal shortening that does not involve vagal pathways or cholinergic neurons. This raises the possibility that esophagitis could contribute to the development of hiatal hernia by inducing esophageal long axis shortening.

Animals↗
PubMed1994

Role of nitric oxide in esophageal peristalsis.

In vitro studies have suggested that NO may be a nonadrenergic, noncholinergic inhibitory mediator in the esophageal body. We examined the role of NO in physiological peristalsis in anesthetized opossums by assessing the effect of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on esophageal contractions induced by swallows, prolonged vagal efferent nerve stimulation, and midesophageal balloon distension. A perfused manometry system measured intraluminal pressures 1 and 5 cm orad to the lower esophagus, and suction electrodes monitored membrane potential changes at the same locations. NO synthase inhibition 1) decreased swallow-induced contraction amplitude in the distal esophagus and, when combined with atropine, abolished these contractions; 2) diminished swallow-induced contraction latencies, predominantly in the distal esophagus, thereby decreasing the latency gradient and increasing the peristaltic velocity; 3) abolished vagal-stimulation-induced, end-of-stimulus "B" contractions and either unmasked or increased the amplitude of intrastimulus "A" contractions; 4) abolished the contractions occurring at the end of balloon distension; and 5) inhibited the membrane hyperpolarization and the subsequent nonadrenergic, noncholinergic depolarization induced by all three stimuli. These data support the hypothesis that NO is a mediator of nonadrenergic, noncholinergic neurotransmission in the opossum esophagus. Furthermore, the data suggest that esophageal peristalsis is mediated by a "blended" activation of cholinergic and nonadrenergic, noncholinergic (via NO) neurons.

Animals↗
PubMed1993

Ambulatory esophageal manometry, pH-metry, and Holter ECG monitoring in patients with atypical chest pain.

Standard Holter electrocardiographic (ECG) monitoring was combined with ambulatory esophageal manometry and pH-metry in 25 patients with atypical chest pain in order to determine whether an association could be found between spontaneous pain episodes and ischemic ECG changes or esophageal dysfunction. Results of ambulatory testing were compared to those obtained with standard esophageal manometry and provocative testing. Twenty-two of the 25 patients experienced a total of 88 pain episodes during ambulatory testing. Although 15 of the 22 patients (68%) experiencing pain during testing had at least one pain episode that correlated temporally with gastroesophageal reflux, esophageal dysmotility or ischemic ECG changes, 65% of all pain episodes were unrelated to abnormal esophageal events or ECG changes. Seventeen percent of pain episodes were associated with gastroesophageal reflux, 15% with esophageal dysmotility, and 2% with a combined acid reflux and esophageal dysmotility event. Only one pain episode was associated with ischemic ECG changes. Twelve of the 15 patients with chest pain episodes associated with reflux or esophageal dysmotility had other identical pain episodes in which there was no correlation. Reproduction of a patient's pain during standard manometry with provocative testing did not predict a strong correlation between the patient's spontaneous pain episodes and esophageal dysfunction during ambulatory recordings. In summary, patients with atypical chest pain have relatively few spontaneous pain episodes that correlate with gastroesophageal reflux, esophageal dysmotility, or ischemic ECG changes. It appears that different stimuli can trigger identical episodes of chest pain, which suggests that many of these patients may have dysfunction of their visceral pain sensory mechanisms.

Adult↗
PubMed1992

Pharmacological characterization of lower esophageal sphincter relaxation induced by swallowing, vagal efferent nerve stimulation, and esophageal distention.

To characterize the neural pathways involved in lower esophageal sphincter relaxation, intraluminal pressures from the lower esophageal sphincter of the opossum were monitored during swallowing, vagal efferent nerve stimulation, and intraluminal balloon distention in the presence and absence of pharmacologic antagonism of putative neurotransmitters. The combination of atropine, hexamethonium, and 5-methoxydimethyltryptamine, which is known to block ganglionic transmission in the vagal inhibitory pathway to the lower esophageal sphincter, significantly antagonized LES relaxation induced by both swallowing and vagal stimulation, but did not affect the LES relaxation induced by balloon distention. Administration of the nitric oxide synthase inhibitor N omega nitro-L-arginine methyl ester, on the other hand, markedly inhibited LES relaxation induced by vagal stimulation, swallowing, and balloon distention, and this effect was reversed by administration of the nitric oxide synthase substrate L-arginine. These studies indicate that the distension-induced intramural pathway mediating LES relaxation does not involve ganglionic transmission similar to that of the vagal inhibitory pathway to the LES. However, the LES relaxation induced by all forms of stimuli appears to depend on nitric oxide as a final mediator.

Animals↗
PubMed1991

Effect of intraesophageal location and muscarinic blockade on balloon distension-induced chest pain.

Intraesophageal balloon distension has been introduced recently as a provocative test in the assessment of patients with noncardiac chest pain. In order to examine the effect of balloon location and muscarinic blockade on distension-induced pain, 10 asymptomatic male volunteers were studied on two separate days using a low-compliance perfused manometry system that incorporated a silicone rubber balloon. Five-second-duration balloon distensions using balloon volumes of 2.5, 5, 7.5, and 10 ml of air were performed with the balloon located both 16 cm (proximal site) and 6 cm (distal site) above the lower esophageal sphincter (LES) before and after administration of atropine (10 micrograms/kg intravenously) or placebo in a randomized double-blind fashion. A standardized scoring system was used to assess the balloon distension-induced pain. Pain scores varied directly with balloon volume but were consistently higher with the balloon located at the proximal site versus the distal site. This was not associated with any differences in intraballoon pressures between the two sites; however, contraction amplitude orad to the balloon was greater with balloon distension at the proximal site. Atropine significantly decreased pain sensation scores with the balloon located distally but not proximally. This attenuation was not associated with significant changes in intraballoon pressures; however, contractions orad to the balloon were markedly inhibited by atropine with distal but not with proximal distension. These studies indicate that balloon distension-induced pain varies depending on the location of distension. This difference is not explained by differences in esophageal wall tension at the site of distension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Microvascular permeability increases early in the course of acid-induced esophageal injury.

To test the hypothesis that microvascular injury is involved in the pathophysiology of acid-induced esophagitis, the effect of acid perfusion on intraluminal plasma protein loss was studied in relation to histological changes. Four groups of opossums (n = 6 in each) were perfused with either normal saline control) or 10, 20, or 100 mmol/L isoosmolar hydrochloric acid at 2 mL/min for 90 minutes using a midesophageal catheter. The distal esophagus was cannulated via a gastrostomy, and the effluent was collected and measured for intraluminal loss of IV injected 125I-bovine serum albumin. Plasma protein loss in the control group was constant with a total loss of 3.40 +/- 0.69 mg/g dry wt. Perfusion of 10, 20, and 100 mmol/L hydrochloric acid increased total protein loss to 8.06 +/- 2.62, 13.94 +/- 2.72, and 27.34 +/- 4.34 mg/g dry wt, respectively. The protein loss was not associated with intraluminal blood loss, as measured by previously injected 51Cr-labeled autologous red blood cells. Histological changes, scored by a blinded observer, were significant only between control animals and those perfused with 100 mmol/L hydrochloric acid. Separate studies using the vascular tracer monastral blue B demonstrated an increase in labeling of lamina propria blood vessels that varied directly with the concentration of acid perfusate, thereby providing direct morphological evidence of microvascular injury. These studies suggest that increased microvascular permeability occurs early in the course of acid-induced esophageal injury.

Animals↗
PubMed1991

Transition from nutcracker esophagus to achalasia. A case report.

We report a middle-aged woman with nutcracker esophagus who progressed to classic achalasia in two years. Several previous reports have documented progression of nutcracker esophagus to diffuse esophageal spasm and diffuse esophageal spasm to achalasia, but the only previous report of nutcracker esophagus progressing to achalasia was in a child. Our case suggests that, in some instances, nutcracker esophagus and achalasia may share the same pathogenesis.

Esophageal Achalasia↗
PubMed1991

Neuromuscular mechanisms of esophageal responses at and proximal to a distending balloon.

To determine the neuromuscular mechanisms involved in esophageal responses at and proximal to a distending stimulus, a manometric catheter incorporating a latex balloon at its distal end was positioned in the smooth muscle esophagus of alpha-chloralose-anesthetized opossums and used to record intraluminal pressures over the balloon and at several sites proximal to the balloon. Air inflation of the balloon evoked simultaneous phasic contractions at several sites proximal to the balloon that were abolished by bilateral cervical vagotomy. With the balloon located in the midesophagus, these proximal contractions were also abolished by atropine, and simultaneous suction electrode recordings indicated that they were associated with smooth muscle membrane depolarization and spike burst without preceding hyperpolarization. With the balloon located in the distal esophagus, the evoked proximal contractions were less atropine sensitive. Phasic pressure fluctuations recorded by the balloon itself were not affected by atropine or bilateral cervical vagotomy but were increased in amplitude by tetrodotoxin. These opossum studies suggest that unlike responses below a distending balloon, which have been shown to be noncholinergic and mediated by intramural neuromuscular mechanisms, proximal contractions depend on vagal pathways and, depending on esophageal location, muscarinic-cholinergic transmission. Contractions at the level of the distending balloon appear to be myogenic in origin.

Analysis of Variance↗
PubMed1991

Comparison of primary and secondary esophageal peristalsis in humans: effect of atropine.

To determine whether physiological differences exist between primary (swallow-induced) and secondary (distension-induced) peristalsis in humans, 10 healthy male volunteers underwent esophageal manometry on 2 consecutive days using a perfused intraluminal catheter system that incorporated a latex balloon. Initially the catheter was positioned so that the balloon was centered 16 cm above the lower esophageal sphincter (LES), and intraluminal pressures were recorded 21, 11, 6, and 1 cm above the LES. After a series of wet swallows, dry swallows, and balloon distensions, the catheter was repositioned so that the balloon was 6 cm above the LES and pressures were recorded 1 and 11 cm above the LES. A series of balloon distensions were repeated in this position, and the subject was then given either atropine (10 micrograms/kg iv) or placebo in a double-blind randomized fashion (on consecutive days). The protocol was then repeated in reverse order. Distension-induced responses aboral to the balloon with the balloon located 16 cm above the LES were 1) of lower amplitude, 2) more often nonperistaltic, and 3) less atropine sensitive than swallow-induced contractions at comparable sites. With the balloon located distally (6 cm above LES) contractions induced at the 11-cm site (i.e., orad to the balloon) were much more atropine sensitive than contractions induced at the same site when the balloon was located proximally (i.e., 16 cm above LES). These data suggest that, contrary to previous reports, secondary peristalsis differs significantly from primary peristalsis. Furthermore, atropine differentially effects these two types of peristalsis, suggesting that the neural pathways involved are dissimilar.

Adult↗
PubMed1990

Omeprazole in H2 receptor antagonist-resistant reflux esophagitis.

We conducted a retrospective review of 25 patients with severe reflux esophagitis treated with omeprazole because of failure of H2 receptor antagonists to heal their esophagitis. Prior to beginning omeprazole (40 mg/day), all patients were on H2 antagonists for at least 9 months and still had endoscopic evidence of longitudinal (grade II) or circumferential (grade III) distal esophageal ulceration. Omeprazole therapy brought about complete endoscopic healing in 24 of 25 patients (96%). Twenty-three of 24 healed patients were then restarted on H2 antagonists as maintenance therapy. Repeat endoscopy was performed if symptoms recurred. Fourteen of 24 patients (58%) had recurrence of endoscopic esophagitis documented between 26 and 300 days from the time of starting maintenance therapy. Two of these 14 patients opted for antireflux surgery, whereas the remaining 12 were once again given omeprazole, which again resulted in symptom resolution in all patients. These data suggest that most patients with H2 receptor antagonist-resistant ulcerative esophagitis cannot be successfully maintained on H2 antagonists even after the ulcers have been healed with omeprazole. Further studies are required to determine the role of omeprazole compared to other treatments in the long-term maintenance therapy of these patients.

Adolescent↗
PubMed1990

Gastrointestinal blood flow in the opossum with special reference to the esophagus.

The opossum esophagus, like that of the human, is composed of striated muscle fibres proximally and smooth muscle fibres distally. Because of this similarity the opossum has been used extensively as an animal model for esophageal studies, but to date no data on esophageal blood flow have been reported in this species. The purpose of this study was to establish the basal blood flow characteristics of different regions of the opossum gastrointestinal tract with particular reference to the esophagus. Intracardiac injection of 15-microns microspheres was used to provide an estimate of blood flow (mL.min-1.g-1 dry tissue) to the whole wall, the combined layer of mucosa plus submucosa, and the muscularis propria. Basal blood flow in the whole tissue and mucosa-submucosa was significantly higher in the lower esophageal sphincter than in the proximal or distal esophagus. The muscularis propria blood flow displayed an aborally increasing gradient with flow to proximal esophagus (striated muscle) less than distal esophagus (smooth muscle) less than lower esophageal sphincter. Regional differences in blood flow to other regions of the gastrointestinal tract were similar to that described in other species. In addition, no changes in basal blood flow occurred despite repeated microsphere injections, suggesting that this species provides a good animal model for the study of gastrointestinal blood flow.

Animals↗
PubMed1990

A randomized prospective trial comparing oral sodium phosphate with standard polyethylene glycol-based lavage solution (Golytely) in the preparation of patients for colonoscopy.

One hundred and two patients were randomized to receive either oral sodium phosphate or standard polyethylene glycol-based lavage solution (Golytely) prior to colonoscopy in order to establish whether the much smaller volume of the former agent enhanced patient tolerance while maintaining or improving effectiveness and safety. Overall, patients found sodium phosphate preparation much easier to complete. In 37 patients who had had a previous colonoscopy prepared with Golytely, 100% of those now receiving sodium phosphate found it easier to complete and over 90% felt it caused less discomfort, compared with their previous experience with Golytely. Colonoscopists, unaware of the type of lavage solution used, scored the degree of colonic cleansing significantly higher for sodium phosphate-prepared colons compared with colons prepared with Golytely. Serial measurements of blood tests and postural pulse and blood pressure changes did not reveal any clinically significant changes in intravascular volume. Hyperphosphatemia was noted with sodium phosphate, but was transient, and no concomitant decrease in calcium was seen. Histological assessment for possible preparation-induced changes revealed no difference between the two agents. Sodium phosphate is significantly less expensive than Golytely. We conclude that, in the group of patients studied, sodium phosphate is a safe colonic cleansing agent that is better tolerated and more effective than Golytely.

Colonoscopy↗
PubMed1989

Electrical correlates of peristaltic and nonperistaltic contractions in the opossum smooth muscle esophagus.

The electrical correlates of peristaltic and nonperistaltic esophageal contractions were characterized in anesthetized opossums using simultaneous suction electrode and intraluminal pressure recordings from sites 1 and 5 cm above the lower esophageal sphincter. Transient midesophageal balloon distention produced peristaltic contractions with faster propagation velocity than swallow-induced peristalsis. This was associated with prompt circular smooth muscle hyperpolarization at both sites, then depolarization, spike burst, and esophageal contraction. At the 5-cm site hyperpolarization was followed by rapid depolarization, whereas at the 1-cm site there was a much slower rate of depolarization after the initial hyperpolarization. Thus the longer latency to contraction at the 1-cm site correlated with the timing of the depolarization phase and not with the duration of the initial hyperpolarization. With prolonged balloon distention the inflation-related membrane hyperpolarization was followed by either partial or complete repolarization during sustained distention. Upon balloon deflation there was rapid membrane depolarization and spike burst at both sites such that the resultant contractions were usually nonperistaltic. In some instances balloon distention evoked contractions of slow peristaltic velocity. These correlated with membrane potential oscillations at the 1-cm site, with threshold depolarization being reached at the second depolarization in the hyperpolarization-depolarization sequences that followed balloon deflation. A similar pattern was seen with swallow-induced peristalsis. These studies demonstrate that differences in timing of the depolarization that follows initial hyperpolarization, and not differences in the duration of the initial hyperpolarization, are important in the genesis of peristaltic esophageal contractions.

Animals↗
PubMed1988

Esophageal responses to transient and sustained esophageal distension.

With the use of intraluminal manometry in alpha-chloralose-anesthetized opossums, distal esophageal and lower esophageal sphincter responses to prolonged midesophageal balloon distension were compared with those evoked by single transient distensions, vagal efferent stimulation, and swallowing. Balloon inflation caused sphincteric relaxation that recovered during small volume but persisted during large volume-prolonged distension. The esophageal body was either quiescent or exhibited nonperistaltic contractions during prolonged distension. Balloon deflation induced non-peristaltic esophageal and sphincteric contractions as well as further sphincter relaxation. Responses to prolonged large and small volume balloon distension resembled those evoked by high- and low-frequency vagal efferent stimulation, respectively. However, vagal-stimulated "on" contractions were not seen with balloon distension, and atropine did not modify excitatory responses occurring during or after prolonged distension. Although transient distension induced peristaltic esophageal contractions, the peristaltic velocity was faster than swallow-induced peristalsis. With transient distension, atropine prolonged the latency to contraction in the mid but not the distal smooth muscle segment and thus increased peristaltic velocity. These studies demonstrate that 1) esophageal distension evokes a wide spectrum of lower esophageal sphincter and esophageal body response, and 2) cholinergic neurons play a minimal role in distension-induced responses of the distal esophageal circular muscle below the distending balloon.

Animals↗
PubMed1987

Atypical localization of myenteric neurons in the opossum lower esophageal sphincter.

This study investigated sphincter-body differences in neuronal density and morphometry between the esophageal sphincter and body with a view to determining whether previously reported differences are authentic. The anatomical limits of the opossum lower esophageal sphincter were correlated with its physiological behavior by manometric demarcation. Following this, peeled whole mounts and paraffin and cryosections were used to study the morphology and morphometry of the esophageal myenteric plexus. Thirty animals were used and seven quantitated. The plexus of the esophageal body was located as usual in a plane between the longitudinal and circular muscle, which coincided with the plane of cleavage when these muscle layers were peeled apart for studying the plexus in whole mounts. In contrast, the plexus was located in several planes in the lower esophageal sphincter, which had no cleavage plane. Therefore, peeling the sphincter removes neurons and yields falsely low counts, making peel preparations of this region unsuitable for neuronal quantitation. In paraffin sections, the neuron density in the esophageal body 7 cm above the sphincter was 6,353 +/- 850/cm2, but decreased significantly to 2,254 +/- 353/cm2 at the 1-cm segment. In the lower esophageal sphincter, the neuronal count increased again to 8,530 +/- 1,606/cm2. Flash-frozen cryosections, which produced neuronal morphology similar to the in vivo condition, showed that there was no difference in neuronal size between esophageal body and sphincter. These studies show that atypical myenteric plexus localization causes spuriously low neuronal counts reported in the lower esophageal sphincter and that reported neuronal size differences are technique-dependent.

Animals↗
PubMed1987

Indium-111-labeled autologous leukocyte imaging and fecal excretion. Comparison with conventional methods of assessment of inflammatory bowel disease.

This study was designed to evaluate the role of 111In-labeled leukocyte imaging and fecal excretion in the assessment of inflammatory bowel disease. We compared these tests to various indices of disease activity in Crohn's disease, to Truelove's grading in ulcerative colitis, and to endoscopy, x-ray, and pathology in both diseases. Eleven controls, 16 patients with Crohn's disease, 13 with ulcerative colitis, and 3 with other types of acute bowel inflammation were studied (positive controls). Indium scanning was performed at 1, 4, and 24 hr. Fourteen of 16 patients with active Crohn's disease had positive scans but in only five was localization accurate. One patient had inactive ulcerative colitis, and the scan was negative. Of 12 patients with active ulcerative colitis, 10 had positive scans but disease localization was accurate in only four. Disease extent was correctly defined in 1 of the 3 Positive Controls. There was no significant difference in the accuracy of scanning at 1, 4, or 24 hr. 111In fecal excretion was significantly higher in patients with inflammatory bowel disease than in controls, and there was correlation between 111In fecal excretion and most of the indices of disease activity in Crohn's disease. In ulcerative colitis, 111In fecal excretion did not correlate with Truelove's grading but reflected colonoscopic assessment of severity. In conclusion, 111In-labeled leukocyte scanning lacks sensitivity with respect to disease extent, but fecal excretion of 111In correlates well with disease severity as determined by other methods.

Colectomy↗
PubMed1986

The effect of acid and bethanechol stimulation in patients with symptomatic hypertensive peristaltic (nutcracker) esophagus. Evidence that this disorder may be a precursor of diffuse esophageal spasm.

The hypertensive peristaltic (nutcracker) esophagus represents a motility disorder characterized clinically by squeezing retrosternal chest pain and manometrically by high amplitude esophageal peristaltic contractions. This study was designed to examine whether the nutcracker esophagus is: (a) a distinct entity, (b) a member of the spectrum of primary esophageal dysmotilities (e.g., diffuse esophageal spasm and achalasia), or (c) is secondary to reflux-induced acid sensitivity. Thirteen patients with a nutcracker esophagus by baseline manometry were subsequently studied after acid perfusion and bethanechol stimulation (0.08 mg/kg). Records were analyzed for symptomatic response and motility changes. Eight of 13 (62%) experienced chest pain during acid perfusion, but none had significant motility changes documented during this period. After bethanechol injection, chest pain occurred in six of 12 (50%) patients; two had burning pain and in the other four (33%) their squeezing chest pain was reproduced. Changes in the motility tracing with evidence of disordered motility suggestive of diffuse esophageal spasm were seen after bethanechol in seven of the 12 tracings analyzed (58%), including all six patients who developed chest pain. We conclude that patients with nutcracker esophagus on baseline manometry may develop motility patterns consistent with diffuse esophageal spasm after provocation with bethanechol. We take this to suggest that the nutcracker esophagus is part of the continuum of primary motility disorders and may actually be a precursor of diffuse esophageal spasm.

Adult↗