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Biomedical subjects

C G Bremner

Publications and source records attributed to C G Bremner.

At least 127 records · Page 7Linked to original sources
PubMed1970

Barrett's esophagus: congenital or acquired? An experimental study of esophageal mucosal regeneration in the dog.

The mucosa was removed from the distal esophagus in 35 dogs divided into three groups according to the presence or absence of gastroesophageal reflux and gastric hypersecretion. Partial or complete re-epithelization of the denuded segment by columnar mucus-secreting cells took place. Re-epithelization by squamous epithelium predominated in preparations with a competent inferior esophageal sphincter, while total or nearly total replacement by columnar cells characterized those preparations with gastroesophageal reflux and gastric hypersecretion. Peristalsis persisted in the operated portion of the esophagus as disclosed by esophageal manometry, although contractions were sometimes repetitive and prolonged. Measurement of potential difference was useful in monitoring the re-epithelization process. These experiments support the concept that the columnar-lined distal esophagus ("Barrett's esophagus") may be an acquired condition in which squamous epithelium destroyed by gastroesophageal reflux is replaced, through creeping substitution, by columnar cells of gastric or junctional origin.

Action Potentials↗
PubMedDate not supplied

Gastritis in Barrett's esophagus.

Duodenogastric reflux has been implicated in the pathogenesis of complicated Barrett's esophagus and gastric ulceration. A group of 123 Barrett's patients were followed for a mean of 41 months; 9 (7%) developed gastric ulceration (GU). Of the Barrett's patients treated by antireflux surgery, 14% developed GU. We reviewed the gastric histology on 54 Barrett's patients (34 men, 20 women; average age 64 years) at presentation and classified the gastritis according to the Sydney system. A normal histologic pattern was present in seven patients; 15 patients had chronic pangastritis, 9 chronic antral gastritis, and 18 chronic gastritis of the corpus. Five patients had acute gastritis only, and in 74% there was reactive chronic gastritis. Of the patients with chronic gastritis, 45% (19 of 42) had histologic evidence of duodenogastric reflux, established by the bile reflux index. The presence of reactive chronic gastritis in Barrett's patients may have important pathophysiologic and therapeutic implications.

Aged↗
PubMedDate not supplied

Duodenogastric reflux potentiates the injurious effects of gastroesophageal reflux.

Experimental studies have shown that the severity of esophageal mucosal injury in gastroesophageal reflux disease is related to the reflux of both gastric and duodenal juice. The purpose of this study was to determine whether duodenal juice potentiates esophageal injury in patients with reflux disease or, in fact, causes no harm allowing acid and pepsin to do the damage. A total of 148 consecutive patients who had no previous gastric or esophageal surgery underwent endoscopy and biopsy, manometry, and 24-hour esophageal pH and bilirubin monitoring. Esophageal injury was defined by the presence of erosive esophagitis, stricture, or biopsy-proved Barrett's esophagus. Exposure to duodenal juice, identified by the absorbance of bilirubin, was defined as an exposure time exceeding the ninety-fifth percentile measured in 35 volunteers. To separate the effects of gastric and duodenal juice, patients were stratified according to their acid exposure time. One hundred patients had documented acid reflux on pH monitoring, and in 63 of them it was combined with reflux of duodenal juice. Patients with combined reflux (50 of 63) were more likely to have injury than patients without combined reflux (22 of 37; P < 0.05). When the acid exposure time was greater than 10%, patients with injury (n = 40) had a greater exposure to duodenal juice (median exposure time 17.2% vs. 1.1%, P = 0.006) than patients without injury (n = 5), but there was no difference in their acid exposure (16.9% vs. 13.4%). Patients with dysplasia of Barrett's epithelium (n = 9) had a greater exposure to duodenal juice (median exposure time 30.2% vs. 7.2%, P = 0.04) compared to patients without complications (n = 25), whereas acid exposure was the same (16.4% vs. 15%). Duodenal juice adds a noxious component to the refluxed gastric juice and potentiates the injurious effects of gastric juice on the esophageal mucosa.

Adult↗
PubMedDate not supplied

Suppression of gastric acid secretion in patients with gastroesophageal reflux disease results in gastric bacterial overgrowth and deconjugation of bile acids.

The aim of this study was to test the hypothesis that gastric bacterial overgrowth is a side effect of acid suppression therapy in patients with gastroesophageal reflux disease (GERD) and that the bacteria-contaminated gastric milieu is responsible for an increased amount of deconjugated bile acids. Thirty patients with GERD who were treated with 40 mg of omeprazole for at least 3 months and 10 patients with GERD who were off medication for at least 2 weeks were studied. At the time of upper endoscopy, 10 ml of gastric fluid was aspirated and analyzed for bacterial growth and bile acids. Bacterial overgrowth was defined by the presence of more than 1000 bacteria/ml. Bile acids were quantified via high-performance liquid chromatography. Eleven of the 30 patients taking omeprazole had bacterial overgrowth compared to one of the 10 control patients. The median pH in the bacteria-positive patients was 5.3 compared to 2.6 in those who were free of bacteria and 3.5 in the control patients who were off medication. Bacterial overgrowth only occurred when the pH was >3.8. The ratio of conjugated to unconjugated bile acids changed from 4:1 in the patients without bacterial overgrowth to 1:3 in those with bacterial growth greater than 1000/ml. Proton pump inhibitor therapy in patients with GERD results in a high prevalence of gastric bacterial overgrowth. The presence of bacterial overgrowth markedly increases the concentration of unconjugated bile acids. These findings may have implications in the pathophysiology of gastroesophageal mucosal injury.

Anti-Ulcer Agents↗
PubMedDate not supplied

Telomerase reverse transcriptase expression is increased early in the Barrett's metaplasia, dysplasia, adenocarcinoma sequence.

Barrett's esophagus is a multistage polyclonal disease that is associated with the development of adenocarcinoma of the esophagus and esophagogastric junction. Telomerase activation is associated with cellular immortality and carcinogenesis, and increased expression of the telomerase reverse transcriptase catalytic subunit (hTERT) has been used for the early detection of malignant diseases. To identify biomarkers associated with each stage of the Barrett's process, relative mRNA expression levels of hTERT were measured using a quantitative reverse transcription-polymerase chain reaction method (ABI 7700 Sequence Detector (TaqMan system) in Barrett's intestinal metaplasia (n = 14), Barrett's dysplasia (n = 10), Barrett's adenocarcinoma (n = 14), and matching normal squamous esophagus tissues (n = 32). hTERT expression was significantly increased at all stages of Barrett's esophagus, including the intestinal metaplasia stage, compared to normal tissues from patients without cancer (intestinal metaplasia vs. normal esophagus, P <0.0001; dysplasia, P = 0.001; adenocarcinoma, P = 0.007; all Mann-Whitney U test ). hTERT expression levels were significantly higher in adenocarcinoma tissues than in intestinal metaplasia tissues (P = 0.003), and were higher in dysplasia compared with intestinal metaplasia tissues (P = 0.056). hTERT levels were also significantly higher in histologically normal squamous esophagus tissues from cancer patients than in normal esophagus tissues from patients with no cancer (P = 0.013). Very high expression levels ([hTERT x 100: beta-actin] >20) were found only in patients with cancer. These findings suggest that telomerase activation is an important early event in the development of Barrett's esophagus and esophageal adenocarcinoma, that very high telomerase levels may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer "field" effect is present in the esophagus of patients with Barrett's cancer.

Adenocarcinoma↗
PubMedDate not supplied

Static and dynamic function of the lower esophageal sphincter before and after laparoscopic Nissen fundoplication.

The means by which fundoplication protects against reflux is disputed. We studied the resting and dynamic features of the lower esophageal sphincter (LES) and 24-hour pH monitoring in 26 patients before and after laparoscopic Nissen fundoplication. Resting features were LES pressure, abdominal length, and total length. Dynamic function was assessed by the residual pressure in the LES during a swallow measured as the bolus flowed though the LES. All patients experienced near-total relief of heartburn and all but one had normal postoperative acid scores. Resting LES characteristics were restored to normal. Mean residual pressure on swallowing was 7.1+/-3.2 mm Hg in the patients postoperatively compared with 1.2+/-1 mm Hg preoperatively and 4.0+/-2.4 mm Hg in normal subjects. Eighteen of 26 patients had residual LES pressure within the normal range (<8.2 mm Hg). There was a tendency for residual pressures to be lower as experience with the procedure was gained. Incomplete LES relaxation is not necessary for effective functioning of a Nissen fundoplication. In construction of a Nissen fundoplication, creating a large retroesophageal window and deliberate dissection of the back of the posterior fundus from the left crus allows the creation of an effective antireflux procedure with restoration of static LES parameters to normal and minimal limitation of LES relaxation.

Adult↗
PubMedDate not supplied

Short-segment Barrett's esophagus: A prevalent complication of gastroesophageal reflux disease with malignant potential.

The significance of finding specialized intestinal epithelium localized to the region of the gastroesophageal junction is unclear. We tested the hypothesis that short segments of specialized intestinal epithelium are a consequence of gastroesophageal reflux disease and are premalignant. Two hundred forty-one patients with reflux symptoms underwent gastroscopy with rigorous biopsy. Barrett's esophagus was diagnosed when specialized intestinal epithelium was present on biopsy. Patients with Barrett's esophagus were subdivided according to the length of Barrett's mucosa: short-segment Barrett's (<3 cm) and extended Barrett's (> or =3 cm). Esophageal function was evaluated by manometry and 24-hour pH monitoring. In another 16 patients with small noncircumferential adenocarcinomas, the endoscopic length of Barrett's mucosa was recorded. Thirty-three patients (14%) had short-segment Barrett's and 37 (15%) had extended Barrett's esophagus. Patients with short-segment Barrett's esophagus had significantly more acid exposure than patients without specialized intestinal epithelium. Eighty-one percent of patients with short-segment Barrett's esophagus had increased esophageal acid exposure as did 100% of those with extended Barrett's esophagus. All lengths of Barrett's mucosa were associated with poor esophageal sphincter function and reduced contraction amplitudes in the distal esophagus. Twelve percent of patients with short-segment Barrett's esophagus had dysplasia. The length of Barrett's mucosa was > or =3 cm in 25% (4 of 16) of patients with early Barrett's adenocarcinoma. Short-segment Barrett's esophagus is commonly associated with gastroesophageal reflux disease. Further, short segments of specialized intestinal epithelium are premalignant in nature.

Adenocarcinoma↗
PubMedDate not supplied

Duodenoesophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen.

In the rat model, esophageal adenocarcinoma reproducibly develops following surgically induced duodenal reflux into the esophagus and administration of nitrosamine. In addition, decreasing gastric acid via partial or total gastrectomy increases the prevalence of adenocarcinoma in this model. We questioned whether carcinogen was necessary for cancer development in the gastrectomized model and whether esophageal acidification could reverse the effect of gastrectomy. Three groups of 26 rats each were randomized to a surgical procedure to produce one of the following reflux models: gastroduodenal reflux by esophagojejunostomy, duodenal reflux by total gastrectomy and esophagojejunostomy, or no reflux by Roux-en-Y reconstruction. In a second experiment, 42 rats were operated on to induce duodenal reflux. One week following surgery, they were randomized to receive acidified water (pH 1.8) or tap water. The animals were killed at 24 weeks of age, and the esophagus was evaluated histologically. All animals with reflux had severe esophagitis and 87% developed columnar lining of the distal esophagus. Nearly half (48%) developed adenocarcinoma at the anastomotic site 16 weeks postoperatively and without carcinogen administration. Cancer prevalence did not differ between animals with gastroduodenal or duodenal reflux but tended to be lower in animals receiving acidified water. Duodenoesophageal reflux is carcinogenic in the rat model. Exogenous carcinogen is not necessary for cancer development in gastrectomized rats.

Adenocarcinoma↗
PubMedDate not supplied

Outcome after laparoscopic fundoplication is not dependent on a structurally defective lower esophageal sphincter.

With the advent of laparoscopic surgery and the recognition that gastroesophageal reflux disease often requires lifelong medication, patients with normal resting sphincter characteristics are now being considered for surgery. The outcome of these patients after fundoplication is unknown and formed the basis of this study. The study population consisted of 123 patients undergoing laparoscopic Nissen fundoplication between 1992 and 1996. All patients had increased esophageal acid exposure on 24-hour esophageal pH monitoring. Patients were divided into those with a normal (n = 36) and those with a structurally defective (n = 87) lower esophageal sphincter (LES), based on LES resting pressure (normal >6 mm Hg), overall length (normal >2 cm), and abdominal length (normal >1 cm), and their outcomes were assessed. Each group was subsequently divided into patients presenting with a primary symptom that was "typical" (heartburn, regurgitation, or dysphagia) or "atypical" (gastric, respiratory, or chest pain) of gastro-esophageal reflux, and outcome was assessed. Median duration of follow-up was 18 months after surgery. Overall, laparoscopic fundoplication was successful in relieving symptoms of gastroesophageal reflux in 90% of patients. Patients with a typical primary symptom had an excellent outcome irrespective of the resting status of the LES (95% and 97%, respectively). Atypical primary symptoms were significantly more common in patients with a normal LES (29%) than in those with a structurally defective LES (10%; P <0.05), and these symptoms were less likely (50%) to be relieved by antireflux surgery. Laparoscopic antireflux surgery is highly successful and not dependent on the status of the resting LES in patients with increased esophageal acid exposure and primary symptoms "typical" of gastroesophageal reflux. Antireflux surgery should be applied cautiously in patients with atypical primary symptoms.

Adult↗
PubMedDate not supplied

Postprandial gastroesophageal reflux in normal volunteers and symptomatic patients.

A structurally intact and competent lower esophageal sphincter in the experimental model shortens and becomes incompetent during gastric distention. The aim of this study was to evaluate postprandial reflux as an indirect measure of this volume-induced sphincter shortening and incompetency. Reflux (pH <4) in the 2-hour period following a meal was retrospectively analyzed from the 24-hour esophageal pH recordings of 94 healthy volunteers and 609 symptomatic patients. Forty-six percent of patients had pathologic postprandial reflux (>95th percentile of normal). The prevalence was lower in patients with a structurally intact compared to a defective lower esophageal sphincter (32% vs. 58%; P <0.001). Pathologic postprandial reflux was greater in patients with abnormal compared to normal findings on 24-hour pH study (76% vs. 21%; P <0.001). Patients with a normal 24-hour pH study and postprandial reflux had shorter sphincter lengths (2.33 vs. 2.82 cm; P <0.001) and lower pressures (10.78 vs. 14.24 mm Hg; P <0.005). A hiatal hernia increased the prevalence of postprandial reflux (P <0.001) in all patients (67% vs. 38%) and in the subgroup with a structurally intact sphincter (75% vs. 27%, P <0.001). Postprandial reflux is a dynamic indicator of sphincter competency, and increases as the structural sphincter characteristics deteriorate and is augmented by a hiatal hernia.

Adolescent↗