This study was conducted to determine the effectiveness of transcranial electrotherapy (TCE) in reducing gastric secretion in man. TCE has been proposed as a therapeutic modality which induces a relaxed psychological state by the application of low intensity diffuse electrical current and has been purported by Soviet investigators to be beneficial in the treatment of peptic ulcers. Secretion rates were monitored in adult male volunteers by a method of intragastric titration utilizing a pH-sensitive telemetry capsule. In one study 5 subjects had their basal secretion rates monitored before, during, and after the application of TCE at graduated current intensities. A threshold of inhibition was observed for currents of 0.9 ma and greater. In a second study, 12 subjects had histamine-stimulated maximum acid output determined for control and during TCE application. Gastric acid secretion was reduced by an average of 30% when 1-ma TCE was applied, with individual reductions ranging from 5.7% to 53.2%. Since the application of relatively high TCE currents may produce discomfort in some subjects, a third study was conducted to determine whether the inhibition might not merely be the result of nonspecific noxious stimuli. For this study the electrical connections to the TCE electrodes were altered so that the same uncomfortable sensation was produced on the forehead, but no current was actually applied transcranially. This "placebo" TCE produced no reduction in the maximal acid output of 6 volunteers, but when the currents were applied transcranially, the gastric acid secretion was reduced by an average of 27% below control values.

The cause of pseudomembraneous colitis is not known but has been attributed to an alteration in the microbial flora of the colon. To test this hypothesis, a blind, prospective study was undertaken in which fecal samples were cultured quantitatively for aerobic and anaerobic organisms. The patients from which these samples were taken were all receiving clindamycin and had diarrhea secondary to the use of the drug. We were able to show definite differences in the colonic microflora which correlated with the presence of pseudomembranes on biopsy. Those patients who had diarrhea and pseudomembranous colitis showed a striking decrease, both quantitatively and qualitatively, in the number of anaerobes present. Those patients who had diarrhea but no pseudomembranes had large numbers of anaerobes which qualitatively approximated normal fecal cultures but quantitatively were fewer in number. A third group of patients, which had resolving pseudomembranous colitis, and were no longer symptomatic, had large numbers of anaerobic organisms which approximated those found in normal fecal cultures. There were no differences among the three groups with regard to facultative anaerobic microflora. Thus, the presence of pseudomembranous colitis correlated directly with a striking quantitative and qualitative decrease in the anaerobic microflora of the colon. The symptom of diarrhea alone appeared to have no meaning with regard to changes in the bacterial flora. Resolution of pseudomembranous colitis was associated with a return of the anaerobic microflora.

To determine the efficacy of azathioprine in the treatment of ulcerative colitis, a 6-month double blind trial was carried out. Thirty patients with chronic ulcerative colitis who required the equivalent of at least 10 mg of prednisone per day over the 3 months prior to entering the study were randomized into placebo and azathioprine (1.5 mg per kg) treatment groups. Reduction of steriods was a major objective of the trial. Age and sex distribution, number of bowel movements, sense of well being, steroid dosage, and findings on proctoscopy, rectal biopsy, and colon X-ray initially were similar in the two groups. No side effects were associated with azathioprine. Although steroid dose was lower (p less than 0.05) in the azathioprine group at the termination of the study, no difference between the two groups could be detected in the number of bowel movements, sense of well being, and findings on proctoscopy during the first 3 weeks compared with the last 3 and during the first 3 months compared with the last 3. Although azathioprine does not confer dramatic benefit upon patients with chronic ulcerative colitis who require steroids, it does permit reduction of steroid dosage without apparent worsening of the disease. Its major value in ulcerative colitis may be in facilitating significant decreases or complete discontinuance of steroids.

This study compares the efficacy of intravenous adrenocorticotropic hormone (ACTH) with intravenous hydrocortisone in the treatment of patients with symptomatic inflammatory bowel disease. Drug doses were pharmacologically equivalent on the basis of achieved plasma cortisol levels and continuously monitored urinary corticoid excretion rates. Drug selection and patient evaluation were accomplished with a random double blind technique. Evaluation of 22 consecutive hospital patients indicates that ACTH and hydrocortisone, when administered intravenously in pharmacologically equivalent dosage, are therapeutically equivalent, that response to ACTH is rapid, with no therapeutic lag, and that differences in therapeutic responses cannont be corrrelated with differences in systemic steroid levels.

Chloroquine and metronidazole were compared in a randomized trial for the treatment of amoebic liver abscess in 36 patients. An additional 30 patients were treated without randomization. Chloroquine was given according to the standard protocol at Los tangeles County-University of Southern California Medical Center, which is 500 mg daily for 10 weeks, whereas metronidazole was given in a dose of 750 mg three times daily for 10 days. Criteria for the diagnosis of amoebic abscess included (a) a suitable clinical picture, (b) filling defect on hepatic scan, (c) high titer of antibody to Entamoeba histolytica by indirect hemagglutination, and (d) eventual complete recovery with treatment or appropriate findings on autopsy examination. Treatment failure, defined as illness that persisted beyond 10 days or recurred after that time, occurred in 1 of 28 patients treated with chloroquine and in 2 of 36 treated with metronidazole. In 2 patients who died it was difficult to assess the result of drug therapy. We conclude that both drugs are highly effective. Metronidazole has the advantage of effectiveness against intestinal amoebiasis and the probability of cure with a shorter course of treatment. Speed of response was slightly greater with metronidazole and was somewhat related to abscess size.

The colonic concentrations of the combustible gases, H2 and CH4, were well below hazardous levels in 60 consecutive patients at the time of colonoscopy. Independent analysis of the effect of a low residue liquid diet, a 12-hr fast, and bowel cleansing on the pulmonary excretion of these gases suggest that the low colonic concentrations encountered were largely the result of our patient preparation procedure. Both ingestion of the liquid diet and fasting decreased the pulmonary excretion of H2 markedly but caused only a slight fall in CH4 excretion. Thus H2, but not CH4, production appears to depend on the delivery to the colonic bacteria of exogenous fermentable substrate. Bulk removal of bacteria from the colon resulted in about a 10-fold reduction in the excretion of both gases. The results of these studies do not support the need for routine CO2 insufflation prior to colonoscopic electrosurgical polypectomy.

A major criterion for the selection of patients with gallstones for treatment with chenodeoxycholic acid is the radiographic demonstration of lucent gallstones. In this study, we sought to evaluate the degree of selectivity of that criterion for distinguishing patients with cholesterol stones from those with pigment stones and to define the determinants of stone lucency or opaqueness. Of 92 lucent stones, 14% were pigment stones; and of 18 of opaque stones, 33% were cholesterol. Thus, the criterion of stone lucency allows inclusion of a significant number of subjects (14%) with lucent pigment stones, which may account for about one-half of the reported 33% incidence of treatment failures with chenodeoxycholic acid. Conversely, of patients with opaque stones, the one-third with cholesterol stones would be excluded from chenodeoxycholic acid treatment. Calcium is the major metal of both types of stones. However, opaque stones contain 6 times more calcium than lucent stones, which accounts for the difference in radiographic appearance.

The serum alkaline phosphatase was fractionated by polyacrylamide gel electrophoresis in 317 patients with elevated serum alkaline phosphatase activity. In 253 patients the source of the elevation was the isoenzyme of presumed liver origin, band L. In 87 of these patients, there was either no obvious liver disease or the alkaline phosphatase elevation was inappropriately high. In 19 of the 87, liver disease was further excluded by liver biopsy or by laparotomy. Because of this, biochemical studies were done to verify the hepatic origin of band L. Band L and alkaline phosphatase extracted from human liver migrated together on polyacrylamide gel electrophoresis before and after digestion with Vibrio cholerae neuraminidase. They had identical pH optima, sedimentation coefficients, Michaelis constants, and rates of inactivation at 55.5 degrees C. They had different rates of inactivation in 3 M urea. Over-all, the data indicate that band L is of liver origin, and that elevation of the hepatic alkaline phosphatase isoenzyme may be a nonspecific finding in certain patients.

The effects of oral metoclopramide, 10 and 20 mg, bethanechol, 25 mg, and placebo on lower esophageal sphincter pressure (LESP) were studied in 15 men with symptoms of gastroesophageal reflux and basal LESP less than 11 mm Hg. Each drug produced a significant increase in LESP when compared to placebo. Metoclopramide, 20 mg, produced a greater increase than either metoclopramide, 10 mg, or bethanechol, 25 mg. Serum gastrin concentrations were not altered by any of the drugs. Side effects were unremarkable. The LESP increasing effect of metoclopramide might be useful in treatment of gastro-esophageal reflux.

The purpose of this study was to measure the effect of alkaline intragastric pH on lower esophageal sphincter pressure (LESP) and on serum gastrin concentration in man. One hundred ten milliliters each of 0.1 N NaHCO3 and control solution were instilled into the stomach for 30 min in random order. Neither LESP nor serum gastrin were higher during the alkali instillation than during the control instillation. Individual subject's peak gastrin and peak LESP during the alkali period were not significantly higher than the corresponding basal values. We conclude that intragastric alkalinization did not increase total radioimmunoassayable serum gastrin concentration or LESP.

Because disadvantages are inherent in the conventional station pull-through technique (SPT) currently used for recording lower esophageal sphincter pressure (LESP), a more suitable recording method is needed. In study, we evaluated a rapid pull-through technique (RPT) for recording LESP and compared the results with those obtained by SPT. The RPT features rapid withdrawal of recording sensors across the LES during a 10- to 20-sec interval of suspended respiration. This method avoids recording "artifact" caused by respiratory LES motion and provides precise end points for scoring and measurement. In 12 normal subjects, LESP measured by RPT (24.3 plus or minus 0.5 mm Hg) was comparable, but significantly greater, than LESP measured by SPT (21.1 plus or minus 9.1 mm Hg). Analysis of LESP scores for the two recording methods revealed that both intraobserver and interobserver error were substantially less for RPT than SPT (P less than or equal to 0.01). Further correlation of LESP between studies was greater for the RPT than the SPT recording method. We conclude that RPT represents a convenient method for recording LESP which is easier to perform and yields more reproducible values than LESP recording by SPT.

It is now well documented that a characteristic mucosal lesion of the proximal small intestine is present in acute nonbacterial gastroenteritis. To determine whether a gastric mucosal lesion also accompanies this illness, stool filtrate containing Norwalk agent was given orally to 15 volunteers after base line biopsies of gastric fundal and/or antral mucosa had been obtained. Gastric fundal and/or antral biopsies were then obtained serially between 24 and 168 hr after administration of the inoculum. Nine volunteers developed symptoms of gastroenteritis. gastric biopsies from those with normal base line fundal and/or antral biopsies remained normal during and after clinical illness. Those volunteers who had mild to moderate gastritis in their base line biopsies showed persistence but no progression of the lesion during illness. In 4 of the volunteers who became ill, intestinal biopsies were available and showed the typical gastroenteritis lesion. These results indicate that acute infectious nonbacterial gastroenteritis induced by Norwalk agent is not associated with histologically detectable gastric mucosal lesion.

Intraarterial vasopressin has been reported to be effective in the treatment of massive upper gastrointestinal hemorrhage. A prospective, controlled clinical trial comparing conventional treatment with conventional therapy plus intraarterial vasopressin was undertaken. Sixty episodes of upper gastrointestinal hemorrhage were evaluated during a 40-month period; 32 received conventional and 28 conventional plus vasopressin therapy. The two groups of patients were similar in type and severity of their bleeding lesions and in their underlying diseases. Vasopressin was more effective in controlling hemorrhage from nonvariceal lesions (P less than 0.05) and from varices (P less than 0.01) than conventional therapy. Transfusion requirements were significantly reduced in those patients who received vasopressin. Paradoxically, survival was not affected by vasopressin administration. The failure of cessation of hemorrhage to improve survival is thought to be due to the degree of advancement of the underlying disease, to the torrential nature of the hemorrhage, to the frequency of recurrent hemorrhage, and to the use of intraarterial vasopressin in some patients in the conventional treatment group in whom conventional therapy had failed.

The incidence of peptic ulcer is increased in cirrhosis and is widely believed to be even greater in cirrhotic patients with portacaval anastomosis (PCA). Two prospective, controlled investigations of prophylactic PCA were evaluated to compare the frequency of peptic ulcer in two groups of cirrhotic patients with similar clinical and laboratory manifestations of cirrhosis randomly selected to be an unoperated Control Group (60 patients) or to have PCA (Shunt Group, 48 patients). In addition, nonrandomized groups of cirrhotic patients, 77 of whom were excluded from the randomized study and 44 of whom had therapeutic PCA, were studied. A diagnosis of chronic peptic ulcer was based on the demonstration of an ulcer crater by X-ray, endoscopy, surgery, or autopsy. Prior to inclusion in these studies, approximately 10% of patients had had peptic ulcer. After inclusion, during a mean follow-up period of 45 months, 12% of both the Control and Shunt Groups developed peptic ulcers. The frequency of complications of peptic ulcer, of recurrence of peptic ulcer, or of acute or symptomatic (unproved) ulcer were similar in both groups. Ulcers tended to develop later in shunted than in unshunted patients. Similar data were obtained from three of four other controlled investigations of PCA. This investigation does not find an increased occurrence of peptic ulcer after PCA. The frequency of ulcer in cirrhosis appears to increase with the duration of the disease independent of the presence or absence of PCA.