Comparison of maximal postprandial serum cholylglycine concentration with the retention of 75Se-homotaurocholic acid in ileal dysfunction

The retention of 75Se-homotaurocholic acid (75SeHCAT) was measured in 12 healthy controls and in 21 patients with Crohn's disease and compared with the maximum postprandial rise in the serum concentration of cholylglycine (CG) in order to detect bile acid malabsorption. The retention of 75SeHCAT was lowered in all patients with inflammation or resection of the terminal ileum over a length more than 20 cm. In 64% of these patients bile acid malabsorption could also be detected by the absence of a significant rise of the postprandial CG serum level but only if the loss of the ileal function exceeded 30 cm. Although less sensitive than the 75SeHCAT retention, the CG method is simpler to apply in terms of laboratory technology and does not involve exposure to radioactivity. The CG method appears to be of use to detect bile acid malabsorption in certain cases. In the case of negatively if still bile acid malabsorption is suspected more sensitive tests such as 75SeHCAT retention should be carried out to further evaluate bile acid malabsorption.     

Ileal dysfunction in Crohn's disease assessed by the postprandial serum bile acid response.

We assessed ileal functional integrity in 20 consecutive patients with Crohn's disease by sequential measurement of the postprandial serum bile acid concentration. In all 14 patients with active Crohn's disease involving the terminal ileum, the mean (+/- SEM) peak response in the cholylglycine (0.4 +/- 0.04 mumol/l, n = 14) as well as in the total serum bile acid concentration (2.0 +/- 0.4 mumol/l, n = 10) was similar to that seen in a group of children who had undergone ileal resection. A significantly greater increase in the cholylglycine (1.8 +/- 0.18 mumol/l, n = 16, P less than 0.01) and in the total serum bile acid concentration (9.8 +/- 2.4 mumol/l, n = 11, P less than 0.025) was noted in normal children. In five of the six remaining patients (three with Crohn's disease shown not to involve the ileum and two of three with asymptomatic, treated Crohn's ileitis) and in seven patients with ulcerative colitis, the meal stimulated responses were normal. These preliminary results suggest that measurement of the serum bile concentration after a meal stimulus may provide a valuable index of ileal inflammation in patients with Crohn's disease.     

COMPARATIVE SENSITIVITY OF SERUM CHOLYLGLYCINE CONCENTRATION AND BROMSULPHALEIN RETENTION IN PATIENTS WITH EARLY AND LATE ALCOHOLIC LIVER DISEASE

Measurement of serum bile acids has been claimed to be a sensitive and specific biochemical test of hepatic function. We have prospectively measured post-prandial serum glycocholate (cholylglycine) concentrations in 31 patients with alcoholic liver disease and compared these measurements with those of bromsulphalein (BSP) retention, prothrombin time, and serum albumin. In the patients with early (non-cirrhotic) alcoholic liver disease (N = 14) BSP retention was abnormal significantly more frequently than was serum cholylglycine concentration (100% vs 29%, p < 0.001). In contrast, amongst patients with late (cirrhotic) alcoholic liver disease, BSP retention and serum cholylglycine were abnormal with equal frequency (94%). In both groups of patients BSP retention and serum cholylglycine were abnormal significantly more often than were prothrombin time and serum albumin concentrations. We conclude that moderately severe hepatocellular dysfunction is required before serum cholylglycine can become a reliable biochemical indicator of liver disease.     

Serum bile acid concentrations during pregnancy and their relationship to obstetric cholestasis

We have prospectively studied changes in serum postprandial cholylglycine (CG) concentration during 297 pregnancies. We found an increase in CG concentration from 0.3 mumol/L at 15 weeks' pregnancy to 0.6 mumol/L at 40 weeks' pregnancy. Although this increase was statistically significant (p less than 0.005), median concentrations of CG remained well within the normal range (0-1.5 mumol/L). However, 10% of the group showed markedly elevated serum CG concentrations at 30 weeks' pregnancy, and the CG level in this group continued to rise during the third trimester. Pruritus was significantly more common in the group with elevated CG concentrations (48%) than in the group with normal CG levels (20%) (p less than 0.005). Serum CG was a much more sensitive predictor of pruritus during pregnancy than other biochemical liver tests. Elevated CG levels were found more commonly in Mediterranean and Asian patients than patients of other ethnic origins (p less than 0.025). No statistically significant associations were found between elevated CG concentrations and maternal age, number of previous pregnancies, pruritus during previous pregnancies, contraceptive-induced cholestasis, and fetal maturity. We conclude that obstetric cholestasis is probably much more common than previously suspected and that consideration should be given to the measurement of serum bile acids in all pregnant individuals with unexplained pruritus.     

Fasting and postprandial serum concentrations of glycine- and taurine-conjugated bile acids in Crohn's disease

Fasting and postprandial serum concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid were measured with a high-pressure liquid chromatographic-enzymatic assay in 17 patients with ileal Crohn's disease and in 17 controls. The postprandial concentrations of the taurine-conjugated bile acids in the patients were significantly lower than in the controls, whereas the concentrations of the glycine conjugates were not significantly different. The total glycine to taurine ratios of serum bile acids were significantly higher in the patients (means, 2.9 fasting and 4.8 postprandial) than in the controls (1.9 and 2.6). Of the patients, 65% had a postprandial total G/T ratio of serum bile acids which was above the control interval.     

Fasting and meal-stimulated plasma levels of neurotensin in obese patients after jejunoileal bypass with 3:1 or 1:3 jejunoileal ratio

The functional role of the jejunum and ileum with regard to peripheral plasma levels of intact neurotensin and NH2-terminal immunoreactivity of neurotensin was studied by using jejunoileal bypass as a model. Plasma levels were measured by radioimmunoassay before and after jejunoileal bypass randomized to different jejunoileal ratios. Seven patients were studied before bypass surgery and 28 were examined after end-to-side jejunoileal bypass with 50 cm intestine in continuity and a 3:1 or 1:3 ratio between the length of the jejunal and ileal segments. Fasting levels of intact neurotensin were unchanged by surgery, whereas levels of NH2-terminal immunoreactivity were higher in bypass patients with a long ileal segment (37.5 cm) than in unoperated patients and in those with a short ileal segment (12.5 cm). Meal-stimulated levels of intact neurotensin were higher after 1:3 than 3:1 jejunoileal bypass. The levels of NH2-terminal immunoreactivity in patients with a short ileal segment and in controls were lower than in patients with a long ileal segment. The results show that postprandial levels of both intact neurotensin and NH2-terminal immunoreactivity are related to the length of the functioning ileum and that even a difference in length of 25 cm is reflected in the circulating levels of neurotensin.     

Diagnostic value of serum primary bile acids in detecting bile acid malabsorption.

Serum cholic and chenodeoxycholic acid conjugates were measured in fasting conditions and after meals in 14 patients with bile acid malabsorption due to ileal resection. Mean serum fasting levels of both primary bile acids did not differ from the controls. After meals, serum cholic acid peaks were lower in patients with ileal resection than in control subjects (p less than 0.001), while chenodeoxycholic acid peaks were reduced in colectomised patients (p less than 0.01). In the sera from patients with ileal resection, the glycine/glycine + taurine ratio for cholic and chenodeoxycholic acid increased (p less than 0.001) from morning to evening, and glycine/glycine + taurine ratio for chenodeoxycholic acid was significantly (p less than 0.01) different from the controls in the sera collected in the evening. The results are consistent with the concept of a better intestinal conservation of chenyl, mainly of the glycine conjugated from, than of cholylconjugates, in patients with ileal resection; this is probably because of passive absorption in the intestine. The postprandial peaks of serum cholic acid conjugates may therefore be regarded as a test of ileal dysfunction, while peaks of chenodeoxycholic acid conjugates suggest colonic impairment.     

Bile salt malabsorption in pancreatic insufficiency secondary to alcoholic pancreatitis

Twenty patients with exocrine pancreatic insufficiency secondary to alcohol abuse were studied for the presence of bile salt malabsorption. Fecal bile salts and fecal fat excretion were determined in 15 patients receiving pancreatic enzyme therapy, not receiving enzyme therapy, and on a regimen of pancreatic enzymes plus cimetidine. Serum bile salt levels were measured during fasting and postprandial conditions both during enzyme therapy and after it was stopped in 8 cases. In addition, 5 patients underwent [14C]cholylglycine breath testing during and after discontinuation of enzyme therapy. The fecal bile salt excretion varied between 610 and 3460 mg/day in the untreated patients. Treatment with pancreatic enzymes was associated with significant (p less than 0.05) reduction in fecal bile salt and fecal fat excretion. Cimetidine therapy in addition to enzyme therapy further reduced steatorrhea but failed to alter bile salt excretion significantly. Serum cholylglycine level showed significant (p less than 0.05) postprandial increase in patients receiving enzyme therapy, suggesting improved bile salt absorption. These data suggest a wide range of bile salt malabsorption in alcoholic patients with pancreatic insufficiency, which improves with pancreatic enzyme therapy.     

Initiation of anastomotic recurrence of Crohn's disease after ileocolic resection. Onset proximal to the junction and preceded by increased phospholipase A2 activity.

Colono-ileoscopy was performed on 11 patients after ileocolic resection for Crohn's disease, to observe development of recurrent anastomotic inflammation and its relationship to mucosal phospholipase A2 (EC 3.1.1.4) activity. Ileal inflammation appeared soon after surgery in eight cases but in none of nine controls with noninflammatory bowel disease. The ileal inflammation was more severe 1-3 cm above than greater than 5 cm above the ileocolic junction (p less than 0.05), whereas the postanastomotic colonic mucosa remained unchanged. Ileal phospholipase A2 activity in the mucosa was equally raised at the two ileal sites (p less than 0.01 and less than 0.02), irrespective of the presence or absence of inflammation. In colonic postanastomotic mucosa the phospholipase A2 activity was the same as in the controls. Further followup showed preanastomotic ileal inflammation at both investigated levels in all patients with Crohn's disease but still with greater severity close to the mucosal junction (p less than 0.05). The study indicates that recurrent inflammation in Crohn's disease is initiated in the terminal ileum close to the ileocolic junction. Progression of severity is accompanied by greater proximal involvement. The increase in mucosal phospholipase A2 activity, which precedes endoscopically detectable inflammation, implies a role for this enzyme in Crohn's disease.     

Effect of intestinal resection on human small bowel motility.

BACKGROUND: Few data are available on adaptive changes of human small bowel motility after intestinal resection. AIM: To characterise jejunal motility after extensive and limited distal intestinal resection. METHODS: Seven patients with a short bowel syndrome after total ileal and partial jejunal resection (residual jejunal segments between 60 and 100 cm) and six patients with limited distal ileal resection (resected segment between 30 and 70 cm) underwent ambulatory 24 hour jejunal manometry 15 (6-24) months after the operation. Normal values were obtained from 50 healthy subjects. Fasting motility and the motor response to a 600 kcal solid meal were analysed visually and by a computer program. RESULTS: Limited ileal resection did not result in changed jejunal motility. After extensive distal resection, patients had a significantly shorter migrating motor complex (MMC) cycle and a significantly shorter duration of the postprandial motor response compared with controls (p < 0.005). Intestinal resection had no influence on jejunal contraction frequency and amplitude and did not lead to any abnormal motor pattern. CONCLUSION: Extensive distal resection of the small intestine produces distinct abnormalities of fasting and postprandial motility in the intestinal remnant. The shortening of digestive motility and the increased frequency of MMC cycling could contribute to malabsorption and diarrhoea in the short bowel syndrome.     

Clinical value of serum bile acid levels in chronic hepatitis

A prospective study was undertaken to determine if individual serum bile acid (SBA) levels are clinically useful in differentiating patients with asymptomatic chronic active hepatitis (CAH) from patients with chronic persistent hepatitis (CPH). Fasting and postprandial SBA levels were obtained from 16 patients with CAH, 12 with CPH, and 18 control subjects. Levels of cholylglycine (CG) and total cholic acid conjugates (CCA) were determined by radioimmunoassay. Alanine aminotransferase (ALT) levels were also obtained from each subject. There were no significant differences in the mean fasting and 3-hr postprandial CG or CCA levels between the CPH group and the control subjects. The mean fasting and 3-hr CG and CCA levels were significantly higher for the CAH group than the CPH group (P<0.05 for each comparison). A combination of the 3-hr postprandial CG and CCA levels with the ALT levels resulted in a better separation of the two groups. All patients with CAH had either a 3-hr CCA level of 200 g/dl, a 3-hr CG level of 170 g/dl, or an ALT level of 120 IU/liter. Using these values, only three patients with CPH were misclassified as having CAH, and no control subject reached any of these levels. Although the differences obtained were statistically significant, the separation based on a combination of CG, CCA, or ALT levels may have been fortuitous. Nevertheless, these data suggest that postprandial serum bile acid levels may have clinical utility in identifying patients with asymptomatic chronic hepatitis who are likely to have CAH.This study was supported in part by USPHS Grant RR865.     

Gut hormone responses after reconstructive surgery for ulcerative colitis.

After colectomy, continent ileal reservoirs are an accepted alternative to conventional ileostomy for patients with ulcerative colitis. To assess the effect of these reservoirs on digestive function, circulating and morphologic gut endocrine responses were measured in patients with a continent ileostomy or with a pelvic pouch and compared to patients with conventional ileostomy, with active ulcerative colitis and healthy controls. Eight subjects were studied in each group. Basal and postprandial plasma gastrin, enteroglucagon, neurotensin, vasoactive intestinal polypeptide, insulin, pancreatic glucagon, and pancreatic polypeptide in both groups with ileal reservoirs were equivalent to controls. Basal plasma motilin and postprandial plasma gastric inhibitory polypeptide were raised in ileal reservoir patients, but similar changes also occurred in ulcerative colitis patients and those with conventional ileostomy. In one half of patients, cell populations of enteroglucagon, peptide YY, and neurotensin were decreased in pouch mucosa that corresponded with the presence of mucosal inflammation. On the other hand, with pouch inflammation vasoactive intestinal polypeptide immunoreactive nerves were increased and a proportion of the fibres were moderately coarsened. Mucosal concentrations of vasoactive intestinal polypeptide did not, however, exceed that of controls. After an ileal reservoir sufficient reserve remains for gut hormone release into the circulation, suggesting compensation for the presence of a reservoir and the absence of a colon; circulating hormone changes do occur but are consequent upon previous ulcerative colitis. Reservoirs may show neuromorphologic alterations that appear to be related to mucosal inflammation.     

Prognostic significance of cholestatic alcoholic hepatitis

Tissue cholestasis is a histologic feature in some patients with alcoholic liver disease, but its significance is unknown. We studied prospectively the clinical, laboratory, and histologic findings of 306 chronic male alcoholics in whom liver tissue was available. Tissue cholestasis permitted identification of two groups: group I, absent or mild cholestasis (239 patients), and group II, moderate to severe cholestasis (67 patients). Statistical evaluation was performed by Student's ttest and regression analyses. In patients with tissue cholestasis, 97% had elevated serum cholylglycine levels, while only 61% had significant jaundice (serum bilirubin > 5 mg/dl). In patients without tissue cholestasis, 66% had elevated serum cholylglycine and 13.5% jaundice. Highly significant statistical correlations (P <0.0001) were found between cholestasis and malnutrition, prothrombin time, AST, alkaline phosphatase, bilirubin, Maddrey's discriminant function, serum cholylglycine level, albumin, and histologic severity score. In group I, 54% survived 60 months versus 22% in group II (P <0.0001). Highly significant statistical correlations (P <0.0001) were noted between serum cholylglycine levels and the parameters enumerated earlier, but not with survival. We conclude that tissue cholestasis is a highly significant prognostic indicator of outcome in alcoholic hepatitis and is more consistently associated with bile salt retention than jaundice.     

Serum bile acid concentration after a test meal.

Total serum bile acid concentrations were studied by an enzymatic-fluorimetric method employing a highly purified 3 alpha-hydroxysteroid dehydrogenase. In 28 control subjects mean total serum bile acid concentration was 2.5 mumoles/1 (S.D. 1.4). In 6 healthy subjects a significant postprandial increase in total serum bile acids occurred with maximal values at 90 and 120 minutes after ingestion of a liquid test meal. The maximal postprandial increase for each subject was 1.5 to 3 times the fasting value. In 7 patients with various hepatobiliary diseases the maximal postprandial elevation of serum bile acids was higher than in the normals, and the duration of serum bile acid elevation was significantly prolonged. In the patients with normal fasting concentration of bile acids the postprandial elevation was also significantly greater than in the controls. A 2-hour postprandial sample seems suitable for the study of the bile acid test meal response for clinical use.     

The effect of the site of lesion and extent of resection on duodenal bile acid concentration and vitamin B12 absorption in Crohn's disease.

Duodenal bile acid concentration following a standard meal, glycine/taurine (G/T) ratio, vitamin B12 absorption, and faecal fat were determined in 79 patients with Crohn's disease. Intestinal resection had been made in 50 patients before the study, and no evidence of recurrence was present at the time of the study. Among 46 patients subjected to ileal resection of 10-180 cm, a reduced duodenal bile acid concentration and vitamin B12 malabsorption was almost invariably present when 50 cm or more of ileum had been removed. Patients with smaller resections and unoperated patients did not show a consistent pattern. Vitamin B12 absorption and duodenal bile acids were of equal value as indicators of ileal dysfunction with the exception that, in 10 ileostomy patients, duodenal bile acids were decreased in every case, but vitamin B12 absorption only when 80 cm of ileum or more had been resected. G/T-ratio was related to the extent of ileal resection-being elevated after large resections (80 cm or more)-but not to the presence of an abnormal flora. Faecal fat was much more elevated in ileostomy patients with large ileal resection (80 cm or more) than in unoperated patients and patients without an ileostomy.     

Oral bile acids reduce bacterial overgrowth,bacterial translocation,and endotoxemia in cirrhotic rats

Experiments were performed to test whether conjugated bile acid administration would decrease bacterial overgrowth, bacterial translocation, and endotoxemia in ascitic cirrhotic rats. Cholylsarcosine, a deconjugation-dehydroxylation resistant and cholylglycine, a deconjugation-dehydroxylation susceptible bile acid were used. Rats with CCl(4)-induced cirrhosis and ascites were fed cholylsarcosine, cholylglycine (both at 70 mg/kg/d), or placebo for 2 weeks. Healthy rats, as controls, were treated similarly. In cirrhotic rats receiving placebo, bile secretion from an acute biliary fistula was lower than in healthy rats (27.2 +/- 6.5 vs. 53.0 +/- 3.1 microL/kg/min; mean +/- SE, P<.05). The administration of conjugated bile acids to cirrhotic rats normalized bile secretion (cholylsarcosine, 51.8 +/- 6.29; cholylglycine, 52.72 +/- 8.9 microL/kg/min). Total ileal bacterial content was 6-fold higher in ascitic cirrhotic rats than in healthy rats. Conjugated bile acid administration reduced bacterial content to normal levels. Bacterial translocation was less in cirrhotic animals receiving conjugated bile acids (cholylsarcosine, 33%; cholylglycine, 26%) than in animals receiving placebo (66%). Endotoxemia was decreased in cirrhotic rats by conjugated bile acid feeding (cholylsarcosine, 0.098 +/- 0.002; cholylglycine 0.101 +/- 0.007 EU/mL) compared with placebo (0.282 +/- 0.124, P <.001). Survival was greater in animals receiving conjugated bile acids (cholylsarcosine, 10/15; cholylglycine, 11/15; placebo, 5/15). In conclusion, the administration of conjugated bile acids to ascitic cirrhotic rats increased bile acid secretion, eliminated intestinal bacterial overgrowth, decreased bacterial translocation, decreased endotoxemia, and increased survival. Oral conjugated bile acids may be useful in preventing bacterial translocation, endotoxemia, and spontaneous bacterial perotonitis in cirrhotic patients.     

Serum measurements of pancreatitis associated protein in active Crohn's disease with ileal location

BACKGROUND AND AIMS: Pancreatitis-associated protein (PAP) is a pancreatic stress protein also expressed in the ileum but not in the colon. Its serum concentration is increased in patients with small bowel inflammation due to untreated celiac disease. We searched to determine whether PAP could be a serum marker for ileal location of active Crohn's disease (CD).METHODS: A multicenter prospective study was conducted, including 54 healthy controls and 124 patients with CD of whom 38 had quiescent ileal or ileocolonic disease (group A), 45 had active ileal or ileocolonic disease (group B), 18 had quiescent colon-only CD (group C), and 28 had active colonic disease (group D). Active disease was defined by a Crohn's disease activity index > 150 and serum C-reactive protein (CRP) > 10 mg/mL. Location of lesions was assessed by endoscopy. PAP was assayed in serum, the upper threshold for normal values being 50 ng/mL.RESULTS: In group B, 27 patients (60%) had elevated serum PAP, compared to one in group A (2.5%), one in group C (5.3%), three in group D (10.7%) and none in the control group (P<0.01). By contrast, serum levels of C-reactive protein did not differ between patients with active CD and either ileal location (group B) or pure colonic location (group D) (38 +/-10.5 vs 41.6 +/- 6.4 mg/mL, NS). Within group B, serum PAP concentration was correlated with none of the epidemiological, clinical or biological data available. Increased serum level of PAP diagnosed ileal location in active CD with a sensitivity of 60%, a specificity of 94%, a positive predictive value of 84% and a negative predictive value of 81%.CONCLUSION: Elevated serum PAP (> 50 ng/mL ) is significantly associated with disease activity and ileal location     

Evaluation of postprandial serum bile acid response as a test of hepatic function

Commercial assays for serum bile acids (SBA) have made this measurement practical. The purpose of this study was to examine the utility of SBA measured every 30 min after a standardized meal in controls and in patients with acute viral hepatitis, cholestasis, and anicteric cirrhosis. In five controls, repeated examination of the area under the bile acid curve (AUC) was not statistically different, whereas the fasting and 2-hr postprandial levels were significantly different. In the group of patients with anicteric cirrhosis, AUC identified disease in 18/20 using total serum bile acids (TSBAs) and in 15/20 using cholylglycine (CG). AUC can be calculated from three samples obtained at 0, 60, and 120 min without losing the sensitivity achieved with seven serial samples. SGOT, alkaline phosphatase, and serum albumin were compared for sensitivity to the total SBA response curve in 20 patients with anicteric cirrhosis. SGOT and alkaline phosphatase identified only 50% and 55% as abnormal and serum albumin was less sensitive. Using total SBA, combining the fasting level and AUC identified 100% as abnormal; using CG, 85% of these patients were detected. As a stepwise cost-effective approach, the fasting level of SBAs can identify most patients with anicteric liver disease. In cases with normal fasting levels where liver disease is suspected, the three-point AUC determination may identify additional patients.Supported in part by a grant from the Diagnostic Division, Abbott Laboratories, North Chicago, Illinois.     

Comparison of triplicated (S) and quadruplicated (W) pelvic ileal reservoirs. Studies on manovolumetry, fecal bacteriology, fecal volatile fatty acids, mucosal morphology, and functional results.

Capacity and compliance, efficiency of evacuation, fecal bacteriology, fecal volatile fatty acids, mucosal morphology, and functional outcome were studied in 20 patients with triplicated (S) and 20 patients with quadruplicated (W) reservoirs after ileal pouch-anal anastomosis. Compared with patients with S reservoirs, patients with W reservoirs were found to have greater efficiency of evacuation of radiolabeled synthetic stool [97% (91%-98%) vs. 74% (62%-89%); P less than 0.05], and their reservoirs were more capacious [350 mL (320-400 mL) vs. 228 mL (175-290 mL); P less than 0.01] and compliant [16.0 mL/cm H2O (13.8-19.0 mL/cm H2O) vs. 12.3 mL/cm H2O (7.4-14.6 mL/cm H2O); P less than 0.01]. Effluent from S reservoirs contained significantly greater numbers of bacteroides (P less than 0.05) and concentrations of acetic and propionic acids (P less than 0.05) than effluent from W reservoirs. The degree of mucosal inflammation and villous atrophy in each design of reservoir was not significantly different. The ratio of anaerobes to aerobes in pouch effluent was significantly correlated with the degree of mucosal inflammation (rs = 0.433; P = 0.035). Fecal volatile fatty acids were significantly correlated with the percentage of stool retained after defecation and degree of mucosal inflammation. The frequency of bowel action was significantly less in patients with W reservoirs than in patients with S reservoirs [3.5/day (3-4/day) vs. 6.0/day (4-7/day); P less than 0.01]. The results indicate marked differences between these two ileal reservoir designs.     

Effect of parietal cell vagotomy on acid secretory responsiveness to circulating gastrin in humans. Relationship to postprandial serum gastrin concentration

To study the relationship between gastric acid secretion and serum gastrin concentration after vagotomy, gastric acid output and serum gastrin concentration were measured simultaneously during intravenous infusion of graded doses of human gastrin heptadecapeptide (G-17) in duodenal ulcer patients with parietal cell vagotomy and in unoperated patients with duodenal ulcer disease (controls). The curve relating serum gastrin concentration to gastric acid output was shifted downward and to the right after vagotomy; the peak acid output to G-17 was reduced by 50% (p less than 0.001). The serum gastrin concentration that produced half of peak acid output (EC50%) averaged 185.5 pg/ml after vagotomy and 74.1 pg/ml in controls (p less than 0.01). Mean basal and postprandial serum gastrin concentrations were twofold to threefold higher in vagotomy patients than in controls (p less than 0.005). However, when peak postprandial serum gastrin concentrations were used to predict acid secretion from curves relating serum gastrin to acid output, predicted acid secretion was only 12.6 mmol/h in vagotomy patients compared to 24.4 mmol/h in controls. Parietal cell vagotomy decreases "functional" parietal cell mass, as reflected by a 50% decrease in peak acid output, and also reduces the responsiveness of "functional" parietal cells to gastrin to such an extent that acid secretion is reduced after vagotomy despite basal and postprandial hypergastrinemia.