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Biomedical subjects

W G Paterson

Publications and source records attributed to W G Paterson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Role of mast cell-derived mediators in acid-induced shortening of the esophagus.

It has recently been demonstrated that acid-induced esophageal mucosal injury leads to esophageal shortening, raising the possibility that reflux esophagitis per se may contribute to the development of hiatal hernia. The aim of the present study was to determine whether mast cell-derived mediators are involved in this acid-induced esophageal shortening. Changes in esophageal length were continuously monitored in anesthetized opossums while the esophageal lumen was perfused with 100 mmol/l HCl or normal saline. Changes in esophageal length were compared between animals perfused with acid, with or without pretreatment with the mast cell stabilizers doxantrazole or disodium cromoglycate (DSCG), and animals perfused with normal saline, with or without pretreatment with DSCG. In separate in vitro studies the effect of the mast cell stabilizers on electrical field stimulation-induced esophageal longitudinal muscle contraction was determined. Gradual esophageal lengthening occurred during saline perfusion, irrespective of whether animals were pretreated with DSCG. In contrast, acid perfusion induced esophageal shortening, which was abolished by pretreatment with either doxantrazole or DSCG in doses sufficient to attenuate the acid-induced mucosal histamine release. In vitro, the mast cell stabilizers had no effect on electrical field stimulation-induced esophageal shortening. This study suggests that esophageal shortening associated with acute acid-induced esophageal mucosal injury in the opossum is dependent on mast cell-derived mediators.

Animals↗
PubMed1997

Esophageal and lower esophageal sphincter response to balloon distention in patients with achalasia.

Achalasia is characterized by absent or incomplete lower esophageal sphincter (LES) relaxation and aperistalsis in the smooth muscle esophageal body in response to swallowing. The esophageal and LES response to distention has not previously been studied. I aimed to characterize the responses to esophageal balloon distention in achalasia patients in comparison to controls. Sixteen consecutive achalasia patients and 11 healthy volunteers underwent standard esophageal manometry followed by graded midesophageal balloon distention during which LES (as measured by the Dent sleeve) and esophageal body pressures were monitored. Subject perception of distention was also recorded using a standardized scoring system. The LES relaxation response to esophageal balloon distention was markedly impaired in achalasia patients, irrespective of whether the patient had radiological evidence of a dilated or nondilated esophagus. However, phasic contractions proximal to the distending balloon were preserved. The esophageal body responses below the balloon were inconsistent in both groups, and not significantly different from one another. Pain-sensation scores were significantly lower in achalasia patients at the highest distending volumes, but this difference was attributable to the subgroup of patients with a dilated esophagus. Distention-induced LES relaxation is markedly impaired in achalasia patients in keeping with loss of intrinsic inhibitory innervation. Preservation of the proximal excitation suggests that extrinsic vagal reflexes are intact.

Catheterization↗
PubMed1997

The effect of cisapride in patients with reflux esophagitis: an ambulatory esophageal manometry/pH-metry study.

OBJECTIVES: The mechanisms responsible for the efficacy of cisapride in gastroesophageal reflux disease remain unclear. The current study was designed to test the hypothesis that cisapride decreases esophageal acid exposure by augmenting esophageal motility and improving acid clearance. METHODS: Eighteen patients with reflux esophagitis underwent combined 24-h ambulatory esophageal manometry/pH-metry at baseline and then again after 2 wk of cisapride therapy (10 mg q.i.d.). RESULTS: Esophageal acid exposure was significantly decreased during cisapride therapy (total percentage of time pH was < 4: 8.3 +/- 2.0% at baseline vs 3.8 +/- 0.6% on cisapride). This was not associated with significant changes in contraction amplitude or duration, peristaltic velocity, or the proportion of peristaltic contractions. The number of reflux episodes per hour was unchanged by cisapride therapy; however, cisapride significantly decreased the number of prolonged duration reflux episodes as well as the duration of the longest reflux episode. Although the relative proportion of peristaltic versus nonperistaltic contractions occurring during reflux episodes was unchanged by cisapride therapy, there was a significant increase in the mean number of contractions per minute (both peristaltic and nonperistaltic combined) occurring during reflux episodes. CONCLUSIONS: These data suggest that cisapride decreases esophageal acid exposure by improving esophageal clearance and that this occurs because of an increase in the number of esophageal contractions rather than by augmenting contraction amplitude or duration or the proportion of peristaltic sequences.

Adult↗
PubMed1997

Studies on opossum esophageal longitudinal muscle function.

To characterize the neuromuscular mechanisms responsible for control of esophageal longitudinal muscle function, in vivo and in vitro preparations of the intact opossum esophagus were studied using both miniature strain gauge transducers and a specially designed transducer that measured longitudinal axis movement of the entire esophagus. Esophageal shortening in response to swallowing was abolished by atropine in virtually all animals, whereas in 4 of 11 animals there was a significant noncholinergic component to shortening evoked by vagal efferent nerve stimulation. Balloon distention evoked atropine-sensitive esophageal shortening due to contractions occurring at and below the site of distention, which was then followed, upon balloon deflation, by noncholinergic longitudinal muscle contractions aboral to the balloon. A similar two-component response was recorded in response to electrical stimulation or balloon distention in vitro. Although the shortening occurring during stimulation was atropine sensitive, both components could be activated in the presence of tetrodotoxin. These studies indicate that the primary functional innervation to the opossum longitudinal muscle esophagus is cholinergic; noncholinergic and myogenic mechanisms are also demonstrable, but it is unclear whether they have a significant functional role.

Animals↗
PubMed1997

Esophagitis as the outcome of progressive failures of the defensive repertoire.

Pre-epithelial defences include the coordinated actions of the lower esophageal sphincter and the esophageal muscles, which minimize reflux of gastric contents and promote clearance of refluxed material. The esophageal epithelium also possesses innate resistance to luminal damaging agents and may be protected luminally by a mucus or 'mucus bicarbonate' barrier and possibly a layer of hydrophobic surfactants. These components are derived from submucosal glands located in the submucosal connective tissue and from salivary secretions that may bind to the esophageal surface. Epithelial defences include the glycocalyx, permeability properties of the epithelial cell plasma membrane, junctional barriers to proton permeation through the paracellular pathway and ion transport processes for regulation of intracellular pH. Subepithelial defences involve mainly regulation of blood supply via responses of nerves, mast cells and blood vessels to influxing protons. Although the epithelium can withstand prolonged exposure to physiologically relevant concentrations of acid, the presence of pepsin or bile salts may overcome the permeability barrier, which probably resides in the superficial layers of epithelial cells. Focal destruction of these cells allows access of luminal acid and other aggressive agents to the vulnerable basolateral cell membranes and to the submucosa. The result is lesion production, although an efflux of alkaline plasma may protect the underlying submucosa and allow healing. Salivary-derived epidermal growth factor (EGF) is present in the luminal fluid, and lesion development may also provide access of EGF to receptors within the epithelium and in the underlying vasculature. Accelerated cell proliferation would then contribute to healing. Inflammation and healing should also be viewed as defensive responses, as can the development of Barrett's esophagus, in which the stratified squamous epithelium is replaced by a potentially acid-resistant columnar epithelium. Chronic inflammation and esophagitis only result when this multilayered set of defences is overcome. The challenge for research is to identify those components of the defensive repertoire that are defective in individuals who suffer from chronic esophagitis.

Animals↗
PubMed1997

Extraesophageal complications of gastroesophageal reflux disease.

With the widespread availability of ambulatory esophageal pH monitoring, there has been recently renewed interest in the so-called 'extraesophageal' complications of gastroesophageal reflux disease (GERD). There are two proposed mechanisms by which reflux can cause extraesophageal symptoms or disease: refluxed acid may reach the oropharynx and/or respiratory tract and cause direct irritation; or acid contact with the esophageal mucosa may trigger neural reflexes, which, in turn, produce symptoms. Evidence is most compelling for an association between GERD and unexplained dental erosions, posterior laryngitis, chronic unexplained cough and intrinsic asthma. The clinician should be aware of these associations, and patients with these conditions should be questioned carefully about associated GERD symptoms. When GERD and any of these conditions coexist, intensive medical antireflux therapy is indicated. Twenty-four hour pH monitoring may be required in selected patients to document the relationship between reflux and the extraesophageal complication or to ensure that the medical therapy provided has eliminated acid reflux.

Asthma↗
PubMed1997

Management of complicated gastroesophageal reflux disease: atypical chest pain.

Although most patients with gastroesophageal reflux disease (GERD) present with the classic symptoms of heartburn and acid regurgitation, many complain of atypical chest pain suggestive of cardiac disease. Once cardiac ischemia has been excluded, it is important to consider GERD because this may be established as the cause of pain in 10% to 50% of such patients. If GERD is suspected or documented, vigorous antireflux treatment, preferably with proton pump inhibitory therapy, is indicated.

Chest Pain↗
PubMed1996

Ambulatory esophageal manometry/pH-metry discriminates between patients with different esophageal symptoms.

Ambulatory esophageal manometry/pH-metry has been used primarily in patients with chest pain of presumed esophageal origin, and it is unclear whether the discriminating power of this test applies to other esophageal symptoms. In the present study, prolonged ambulatory manometry/pH recordings were compared in 17 healthy controls, 12 patients with atypical chest pain, and 11 patients with chest pain and nonstructural dysphagia using the Synectics microdigitrapper system. Chest pain patients tended to have higher values for all the pH variables, but their esophageal motility parameters were no different than controls. On the other hand, the chest pain plus dysphagia group was characterized by a significantly lower proportion of propagated contractions between 10 and 5 cm above the lower esophageal sphincter. This group also tended to have a higher frequency of high-amplitude or prolonged-duration contractions. In comparison to the results of standard stationary esophageal manometry, the prolonged ambulatory recordings were more sensitive in detecting esophageal motor dysfunction in the two patient groups. This study suggests that quantitative analysis of ambulatory pH/motility recordings is a sensitive method of evaluating patients with suspected esophageal dysfunction.

Adult↗
PubMed1996

Mast cells mediate acid-induced augmentation of opossum esophageal blood flow via histamine and nitric oxide.

BACKGROUND & AIMS: Increased esophageal blood flow during reflux episodes may play an important role in mucosal resistance to injury, although the mechanism remains unclear. Decreased stainable mast cells and increased luminal histamine release during acid exposure has been previously documented. Therefore, the role of mast cells, nerves, histamine, and nitric oxide in mediating increased blood flow during acid challenge of the distal esophagus was investigated. METHODS: The effects of the mast cell stabilizers disodium cromoglycate and doxantrazole, the neurotoxin tetrodotoxin, the histamine H1 receptor antagonist promethazine, and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester were examined by monitoring opossum esophageal histamine release and blood flow during perfusion with 100 mmol/L HCl. RESULTS: Luminal acid challenge significantly increased both histamine release and blood flow (P < 0.05). Disodium cromoglycate, promethazine, and N omega-nitro-L-arginine methyl ester attenuated the increase in blood flow to basal (saline-perfused) levels. Tetrodotoxin did not prevent an acute increase in blood flow that rapidly returned to baseline, likely from the ensuing hypotension. CONCLUSIONS: These findings provide evidence that mast cell-derived histamine, acting through an NO-dependent mechanism, plays a central role in the response of the esophageal microcirculation to luminal acid.

Animals↗
PubMed1996

Reproducibility and physiological characteristics of 24-hour ambulatory esophangeal manometry/pH-metry.

OBJECTIVES: To assess the reproducibility and physiological characteristics of ambulatory esophageal manometry/pH-metry. METHODS: Ten healthy volunteers were studied on two separate occasions (2 wk apart) using the Synectics Microdigitrapper System. The pH recording failed in one subject; thus, pH data were analyzed in nine, and motility measurements in all 10 subjects. RESULTS: A high degree of reproducibility was established for the five pH and seven manometry variables assessed. Using the paired t test and Wilcoxon signed rank test to compare the two sets of data, all p values were >0.05. Narrow 95% confidence intervals containing the zero measures were also obtained on the differences of the data from both sessions for all variables. Better correlation coefficients were obtained for the motility parameters than for the pH parameters. As would be expected, reflux occurred more often in the upright than in the supine position. Furthermore, esophageal contractions were of higher amplitude and longer duration in the distal esophagus, and the frequency of propulsive contractions sequences was higher during meals and in the upright position than in the supine position. CONCLUSIONS: This study demonstrates the reproducibility of ambulatory esophageal manometry/pH-metry, suggesting that this technology may be useful in assessing the effect of pharmacological intervention on esophageal motor function.

Adult↗
PubMed1996

Dysphagia in the elderly.

OBJECTIVE: To review the problem of dysphagia in the elderly so that primary care physicians are better able to recognize and manage it. QUALITY OF EVIDENCE: Dysphagia, a prevalent problem in the elderly, causes significant morbidity and even mortality. Age-related deterioration of the oropharyngeal phase of swallowing is well documented. Diagnosis and treatment of dysphagia in the elderly is based mainly on clinical experience with large groups of patients. Few controlled clinical trials have been conducted. MAIN FINDINGS: Oropharyngeal dysphagia in the elderly is often due to irreversible neuromuscular disease. These patients benefit from swallowing therapy performed by speech pathologists. Esophageal causes of dysphagia are similar in the elderly and young patients, and the approach to treatment is also similar, although noninvasive forms of therapy play a larger role for elderly patients. CONCLUSIONS: Dysphagia is a common problem that lowers quality of life for the elderly. Primary care physicians must be aware of causes of dysphagia for which specific treatments are available, as well as of the role of nonspecific treatments offered by ancillary health professionals.

Age Factors↗
PubMed1995

Increasing pain sensation to repeated esophageal balloon distension in patients with chest pain of undetermined etiology.

Previous studies have demonstrated lowered sensory thresholds to esophageal balloon distension in patients with chest pain of undetermined etiology. Whether this finding is specific to patients with chest pain or is simply related to an underlying esophageal motility disorder is unclear. In the present study, distension-induced pain-sensation scores and the effect of repeated balloon distension were compared in patients with chest pain, dysphagia secondary to esophageal dysmotility, and healthy controls. All subjects underwent standard esophageal manometry followed by mid-esophageal balloon distension. Volumes 2.5, 5, 7.5, and 10 ml (each volume repeated three times) were applied in random order in a single-blind fashion, and the pain-sensation score was recorded after each distension. Pain-sensation scores varied directly with balloon volume. Mean pain scores were significantly higher (P < 0.001) in the chest pain group than in either the controls or dysphagia group. There was no significant difference between controls and the dysphagia group, and the motor response to distension was no different between groups. In the controls and dysphagia groups, pain-sensation score was not significantly different between the first, second, or third distension at a given volume. However, in the chest pain group, pain-sensation scores increased significantly with the second (P = 0.004) or third (P = 0.002) distension using the same balloon volume. These studies suggest that abnormal esophageal nociception in patients with chest pain of undetermined etiology is not simply related to underlying esophageal motor dysfunction. In addition, chest pain patients display a conditioning phenomenon, further supporting the presence of a visceral sensory abnormality.

Adult↗
PubMed1995

Morphological evidence of mast cell degranulation in an animal model of acid-induced esophageal mucosal injury.

In previous studies we have demonstrated that microvascular permeability increases early in the course of experimental acid-induced esophageal mucosal injury. This is associated with an increase in the intraluminal appearance of histamine, suggesting a possible role for mast cells in this form of injury. In the present study, quantitative analysis of esophageal mast cells was undertaken using both light and electron microscopy in opossums undergoing intraluminal esophageal acid perfusion or normal saline control perfusion. Light microscopy showed that animals perfused with either 50 or 100 mM hydrochloric acid had an approximate 50% decrease in the number of stainable esophageal mast cells. Stereologic analysis of electron micrographs revealed that within the mucosa, the mean area of the mast cells as well as nuclear area and area of intact granules were also significantly reduced in acid perfused animals. Taken together these quantitative morphological analyses suggest that intraluminal acid exposure is associated with degranulation and/or lysis of esophageal mast cells and that released mediators from esophageal mast cells may play a role in the pathophysiology of reflux esophagitis.

Animals↗
PubMed1995

Descending peristaltic reflex in the opossum esophagus.

To test the hypothesis that the distension-induced esophageal peristaltic reflex involves a polysynaptic pathway, a triple-chamber organ bath was used to chemically isolate different regions of the opossum smooth muscle esophagus while leaving in continuity the intramural neuromuscular apparatus. Balloon distension in the oral chamber evoked membrane hyperpolarization in the aboral chamber, which was followed, on balloon deflation, by depolarization, spike burst, and circular smooth muscle contraction. This reflex was abolished by adding tetrodotoxin to any of the chambers. Addition of Ca(2+)-free 20 mM Mg2+ Krebs solution (to block synaptic transmission) to the intermediate chamber did not affect the descending peristaltic reflex. However, Ca(2+)-free 20 mM Mg2+ Krebs solution markedly attenuated the reflex when placed in either the oral or the aboral chamber. Furthermore, the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester, when placed in the aboral chamber, abolished the reflex. Other putative neurotransmitter antagonists were without effect when placed in any chamber. These studies suggest that the intramural neural pathway that mediates the descending peristaltic reflex in the opossum esophagus is not polysynaptic, but rather involves long descending neurons that depend on nitric oxide as a final mediator.

Animals↗
PubMed1995

Determination of the test performance of less costly methods of Helicobacter pylori detection.

Since Helicobacter pylori (Hp) has become so important in the management of peptic ulcers, it is imperative that noninvasive and inexpensive methods of diagnosis be available. The objective of this prospective, double-blind study was to determine the performance of the noninvasive 14C-urea breath test and the less expensive hematoxylin-phloxin-saffron (HPS) and Giemsa stains in the detection of this infection. As well, we set out to determine the minimal number of biopsies required to make an accurate diagnosis. Fifty consenting adults referred for gastroscopy underwent antral biopsies for HPS, Giemsa and Steiner silver staining and a 14C-urea breath test. The ability of HPS, Giemsa, and the breath test to differentiate between the presence or absence of Hp infection as defined by the silver stain was assessed using contingency table analysis. Hp was detected in 24 patients with the silver stain. Half of these patients had evidence of ulcer disease, compared to 3 of 26 patients who were negative for Hp on silver stain (p < 0.01). The Hp positive group were more frequently male (62% vs. 31%, p < 0.05) and more often had chronic active gastritis (96% vs. 7.7%, p < 0.001). The sensitivity of the breath test, HPS, and Giemsa stains were 95.8% (95% confidence interval: 79-100%), 75% (53-90%), and 95.8% (79-100%), respectively. Specificity was 100% (87-100%) for all 3 methods of detection. The breath test was also able to discriminate between heavily infected and moderately infected patients as defined by silver stain (p < 0.05), and could be shortened from 30 to 15 min without any loss of accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Evaluation of red blood cell transfusion practices with the use of preset criteria.

OBJECTIVE: To assess current red blood cell (RBC) transfusion practices and to determine the potential impact of implementing recently published guidelines on RBC transfusion from the American College of Physicians (ACP). DESIGN: Medical chart review. SETTING: A 219-bed teaching hospital in Kingston, Ont. PARTICIPANTS: All patients over 12 years of age who received RBC transfusions in March 1992. MAIN OUTCOME MEASURES: Need for transfusion according to the ACP guidelines and the number of blood units ordered for each transfusion. RESULTS: A total of 55 patients received 170 RBC units. According to the ACP guidelines 94 (55.3%) of the units were judged unnecessary. The departments of Surgery and Internal Medicine did not differ significantly in the number of unnecessary units (56.4% v. 52.8%). Among the surgical subspecialties, unnecessary transfusion was most common in the orthopedics service (73.5%, p < 0.05). Blood was most frequently ordered 2 units at a time (51.8% of units). Transfusion in normovolemic, hemodynamically stable patients with anemia and unnecessary multiple-unit transfusions were the most common violations of the ACP guidelines. CONCLUSIONS: According to the ACP guidelines, there was significant unnecessary blood use in the hospital surveyed. The guidelines provide a useful framework for assessing transfusion practices but may require further refinement to apply to a broader spectrum of clinical settings.

Adolescent↗
PubMed1994

Combined ambulatory esophageal manometry and dual-probe pH-metry in evaluation of patients with chronic unexplained cough.

Fifteen consecutive patients referred because of suspicion that gastroesophageal reflux was the cause of their chronic, unexplained cough underwent combined ambulatory esophageal manometry and pH-metry in order to correlate cough episodes with gastroesophageal and gastrohypopharyngeal acid reflux. Cough episodes, which were recognized manometrically as phasic bursts of brief simultaneous elevations in all intraesophageal pressure leads, were markedly underreported by patients. If all cough events were considered, that is, single coughs plus "bursts" of coughing, patients reported on average 10% of the total manometrically recorded coughs, whereas if only cough bursts were considered, patients reported an average of 23%. Gastrohypopharyngeal acid reflux preceded 1% and 1.8%, whereas gastroesophageal reflux preceded 9% and 13%, of the total coughs and cough bursts, respectively. One percent and 1.6% of total coughs and cough bursts, respectively, appeared to precipitate reflux. Gastrohypopharyngeal reflux events were rare, with only 15 episodes recorded in nine of the 15 patients. In 13 asymptomatic volunteers, no episodes of gastrohypopharyngeal acid reflux were recorded. This study suggests that ambulatory esophageal manometry/pH-metry provides an objective measure of temporal relationships between cough episodes and acid reflux events that is superior to relying on the patients' reporting of cough episodes. In this study population, the incidence of a direct temporal correlation between reflux and cough episodes was relatively low. However, a high proportion of patients had gastrohypopharyngeal reflux, suggesting that acid reflux to the laryngeal inlet may indirectly play a role in chronic unexplained cough.

Adult↗