Douglas L. Brand

Chronic Intestinal Pseudo-obstruction: A Report Of 27 Cases And Review Of The Literature

Twenty-seven cases of chronic intestinal pseudo-obstruction are reported. The causes of pseudo-obstruction were progressive systemic sclerosis in 14, hollow visceral myopathy in 4, visceral neuropathy in 2, sclerosing mesenteritis in 1, and jejunal diverticulosis in 1. No identifiable cause was found in five. Chronic pseudo-obstruction is a long-term illness characterized by vomiting, abdominal distention, abdominal pain and weight loss. Involvement is often present throughout the intestine so that patients may present with a variety of symptoms deriving from the esophagus, stomach, small intestine, and colon. Hollow visceral myopathy and visceral neuropathy are usually familial and urologic involvement is sometimes present in the former. Abnormalities of smooth muscle function can be discerned by radiography and esophageal manometry. The pattern and distribution of the abnormalities are helpful in differentiating pseudo-obstruction from true mechanical obstruction. They may also be helpful in differentiating one form of pseudo-obstruction from another. The majority of cases have identifiable pathology within either the smooth muscle or myenteric plexus of the bowel wall. The natural history of pseudo-obstruction is variable. Remissions and exacerbations occur and may be unrelated to anything that is done therapeutically. The illness is unresponsive to any drug known to have an effect on intestinal motility. Antibiotic treatment of small intestinal bacterial overgrowth and selected surgical procedures may occasionally be palliative. Many patients develop malnutrition and require home parenteral nutrition in order to survive.

Cimetidine in the treatment of symptomatic gastroesophageal reflux: a double blind controlled trial.

The effectiveness of cimetidine for symptomatic relief in patients with chronic gastroesophageal reflux was studied in a multicenter, double blind clinical trial. Patients were entered into the study for a total of 8 weeks, receiving either cimetidine, 300 mg four times daily, or identical placebo tablets. Throughout the trial, frequent assessments were made of symptom severity and frequency, combined with careful measurement of antacid use. Esophagoscopy, esophageal acid sensitivity, and lower esophageal pressures were performed before and at the completion of the treatment period. Significant (P less than 0.05) decreases in symptom frequency and severity were noted throughout the study in the cimetidine-treated patients, as compared with the placebo group. This subjective improvement was corroborated by a concomitant decrease in antacid use, which was significantly (P less than 0.05) reduced in the cimetidine-treated group. In addition, significant improvement in esophageal acid sensitivity resulted from cimetidine therapy. No objective improvement in esophageal endoscopic appearance or sphincter pressures was noted. The results of this double blind trial indicate that cimetidine is more effective than the placebo for the relief of symptoms of gastroesophageal reflux.

Prevalence of Colorectal Neoplasia in Smokers

OBJECTIVES:Smoking has been linked with colorectal neoplasia. Previous colonoscopy screening studies have omitted smoking and have examined only gender, age, and family history. Our aim was to use a screening population to measure the prevalence of neoplasia in smokers, the anatomic location of these lesions, and the strength of this association relative to other risk factors.METHODS:Data collected from the charts of 1988 screening colonoscopy patients included colonic findings, histology, risk factors for colorectal neoplasia, and smoking pattern. Current smokers were defined as those who had smoked more than 10 pack-years and were currently smoking or who had quit within the past 10 yr. Our outcomes were any adenomatous lesion and significant colonic neoplasia, which included adenocarcinoma, high grade dysplasia, villous tissue, large (>1 cm) adenomas, and multiple (more than two) adenomas.RESULTS:Multivariate analysis revealed that current smokers were more likely to have any adenomatous lesion (odds ratio [OR] = 1.89; 95% CI = 1.42–2.51; p < 0.001) as well as significant neoplasia (OR = 2.26; 95% CI = 1.56–3.27; p < 0.001) than those who had never smoked. The increased risk for smokers was predominantly for left-sided neoplasia. The risk for significant neoplasia was greater for smokers than for patients with a family history of colorectal cancer (OR = 1.20; 95% CI = 0.75–1.92; p > 0.05).CONCLUSIONS:Smoking is a significant risk factor for colorectal neoplasia in a screening population, especially for significant left-sided lesions. In our sample population, smoking posed a greater risk than family history of colorectal cancer.

Gallbladder dyskinesia in chronic acalculous cholecystitis

To test the hypothesis that there is an early stage of cholesterol gallstone formation in man characterized by symptoms of chronic cholecystitis, poor gallbladder emptying, and biliary cholesterol crystals, we studied cholecystokinin-stimulated gallbladder emptying by DISIDA scintigraphy and examined bile for cholesterol crystals in symptomatic patients with normal oral cholecystography and gallbladder sonography. Of 36 patients studied, 16 had biliary cholesterol crystals; their mean 30-min gallbladder ejection fraction was 25.9±14.8%. Among the 20 patients without crystals, the mean ejection fraction was 60.3±23.3%. Fifteen patients, 11 with crystals and four without, had cholecystectomy because of persistent symptoms. All with crystals preoperatively and three without had chronic cholecystitis histologically. One patient without crystals had normal histology. We conclude that poor gallbladder contractility, well-established as an etiologic factor in animal models of cholesterol cholelithiasis, is now linked to acalculous cholecystitis, an early stage of human cholesterol cholelithiasis.

Multiple Adenomatous Neoplasms Arising in Columnarlined (Barrett's) Esophagus

Multiple polypoid masses were found in the esophagus of a 62-year-old man. He underwent esophageal resection because exfoliative and brush cytological studies were positive for adenocarcinoma. The surgical specimen showed that the esophagus was lined by columnar epithelial cells which were focally hyperplastic, forming polypoid masses. In both the masses and the mucosa between them, there were atypical epithelial cell changes, ranging from dysplasia to focal carcinoma. These findings reinforce the concept that the Barretts (columnar) epithelium is a premalignant lesion deserving periodical screening.

Predictors of proximal neoplasia in patients without distal adenomatous pathology

BACKGROUND:Previous colorectal cancer screening studies have observed that some patients may have advanced proximal neoplasia without distal findings. Since these studies have included only gender, age, and family history as risk factors, they are limited in their ability to identify predictors of isolated proximal neoplasia.METHODS:Data were collected from the charts of 1,988 patients who presented for colonoscopy. Information gathered included endoscopic findings, histology, known risk factors for colorectal neoplasia, and smoking pattern. Our main outcome was the presence of proximal adenomatous neoplasia in patients who had no distal adenomas. We defined significant neoplasia as adenocarcinoma, high-grade dysplasia, villous polyps, adenomas 1 cm or greater or more than two adenomas of any size.RESULTS:Fifty-five patients had isolated significant proximal neoplasia that would have been missed on a flexible sigmoidoscopy. While patients older than 60 yr had a greater risk for this neoplasia (odds ratio = 3.01: 95% CI = 1.66–4.23; p < 0.001), those who took a daily aspirin had a reduced risk (OR = 0.60; 95% CI = 0.30–0.88; p < 0.05). A family history of colorectal cancer increased the patients risk of having any adenomas (OR = 2.01; 95% CI = 1.33–3.40; p < 0.01) or villous tissue (OR = 2.03; 95% CI = 1.27–3.51; p < 0.05) in the proximal colon without distal findings. Smoking was associated with an increased risk of large (> 1 cm) isolated proximal tubular polyps (OR = 2.71; 95% CI = 1.64–4.46; p < 0.01) as well as isolated significant proximal neoplasia (OR = 2.30; 95% CI = 1.59–3.31; p < 0.01).CONCLUSIONS:Age greater than 60 yr, a history of at least 10 pack-years of smoking, and a family history of colorectal cancer increased the risk of finding significant proximal polyps in patients without distal pathology.

Efficacy of misoprostol (twice daily dosage) in acute healing of duodenal ulcer. A multicenter double-blind controlled trial.

This study was undertaken to evaluate the efficacy of misoprostol taken twice daily for the healing of duodenal ulcer. Three hundred thirty patients with endoscopically proven duodenal ulcer participated in a multicenter, double-blind, controlled trial comparing placebo with misoprostol 200 μg and 400 μg twice daily for up to four weeks. Patient characteristics were similar in all three treatment groups. Ulcers were between 0.3 cm and 2.0 cm in length. Healing was determined by endoscopy at two weeks; if ulcers were not healed, endoscopy was repeated at four weeks. All patients were given Al(OH)3 antacid (up to 54 meq a day) to be used as needed for pain. Healing rates at four weeks for a total of 280 evaluable patients in the three treatment groups were as follows: misoprostol 400 μg bid, 65.4%; misoprostol 200 μg bid, 52.9%; and placebo, 42.2%. Misoprostol 400 μg bid was superior to placebo (P=0.002) in healing ulcers. However, the healing rate for misoprostol 200 μg bid did not differ significantly from placebo. The percentage of nonsmokers who healed at four weeks was higher than that of smokers in both misoprostoltreatment groups, although the difference was not analyzed for statistical significance. There were no differences in antacid consumption or pain relief among the three experimental groups during the study. Diarrhea was the most common side effect but was mild and self-limiting, occurring in 8.9%, 5.9%, and 1.8% of the misoprostol 400 μg, 200 μg, and placebo groups, respectively. These results indicate that misoprostol 400 μg, 200 μg, and for four weeks is effective and safe for the treatment of duodenal ulcers.

Increased interdigestive pancreatic trypsin secretion in alcoholic pancreatic disease.

Previous studies have suggested that chronic alcohol consumption in man is associated with an increased secretion of pancreatic enzymes. Precise quantitation of the output of protein and trypsin in the interdigestive state has not been possible because of large variations and small volume of pancreatic juice. We utilized a multilumen, markerperfused duodenal catheter to simultaneously monitor intraluminal pressures and collect mixed duodenal juice at the ligament of Treitz in five groups of patients: normal volunteers (group I), alcoholics without pancreatitis (group II), alcoholics who had recovered from acute pancreatitis (group III), alcoholics with chronic pancreatitis (group IV), and nonalcoholics who had recovered from acute pancreatitis secondary to biliary tract disease (group V). The output of trypsin and protein during 30 min of phase II and 60 min of CCK-OP 40 ng/kg/hr was determined in each group. The output of trypsin during phase II was 1.3±1.2 and 3.0±2.5 mg/kg/hr in groups II and III, respectively, compared to 0±0.1 in group IV (normal=0.6±0.5). The outputs in group V were similar to normals. The output of protein during the interdigestive state was 15.7±13.7 mg/min in group III, compared to 4.5±3.6 in normals (group I). The duodenal contraction rate was 4.6±3.0 and 3.3±2.7 contractions/min in groups III and II, respectively (significantly greater than the normal rate of 2.2±1.5). The pancreatic response to CCK-OP 40 ng/kg/hr was similar in all groups except group IV which had a decreased output of trypsin and protein (0.1±0.2 mg/kg/hr and 2.2±0.9 mg/min compared to group I: 3.4 mg/kg/hr and 7.7±1.9 mg/min). In summary, alcoholics and alcoholics who had recovered from acute pancreatitis were found to have a greater output of trypsin and a greater phase II duodenal contraction rate in the interdigestive state.

Amyloidosis mimics achalasia's effect on lower esophageal sphincter.

Esophageal involvement in systemic amyloidosis is common. Manometric studies have been few in number and have revealed a variety of findings compatible with deposition of amyloid in myopathic as well as neuropathic patterns. This report describes a patient with primary amyloid whose esophageal dysfunction was limited to the lower esophageal sphincter, with both a hypertensive sphincter and impaired relaxation after swallows. Pharmacologic testing confirmed a mild abnormality of the inhibitory pathway to the LES with an intact excitatory pathway and sphincter muscle. This case suggests that amyloidosis, like idiopathic achalasia and carcinoma of the lower esophagus, can produce dysphagia by selective impairment of the inhibitory neural pathway to the lower esophageal sphincter.

Autoradiographic identification of a gastrin receptor on the human parietal cell

Gastrin plays an important role in regulating gastric acid secretion and gastrointestinal mucosal growth but its cellular sites of action in man have not been determined. Using cryostat sections of gastric mucosal tissue we have identified (125I-gastrin binding followed by fixation-wet emulsion autoradiography) and characterized (125I-gastrin binding followed by counting) a gastrin receptor binding site in the human stomach. This site displayed binding characteristics similar to those observed in isolated cell systems: specifically, 125I-gastrin binding was rapid (t1/2 approximately 10 min at 37 degrees C), temperature-dependent (3.5 fold more radioligand bound at 22 degrees C than at 4 degrees C) and saturable. The binding of the radioligand was also tissue specific and was five-fold greater in the gastric body than in the gastric antrum and duodenum. In the autoradiographs, silver grains were localized only to parietal cells and not to other epithelial cell types. In the presence of 40 nM gastrin grains were no longer present over parietal cells demonstrating that these sites were both saturable and of high affinity. These data provide the first demonstration of gastrin binding sites (putative receptors) on parietal cells in the human stomach and suggest that gastrin acts directly on these cells to help regulate gastric acid secretion and/or mucosal growth.