Reproducibility of 24-h heart rate variability measures in preterm infants born at 28-32 weeks of gestation.

AIMS: To determine the reproducibility and minimum detectable change (MDC) of heart rate variability (HRV) measures during two sequential 24-h periods, at week 32 of gestation, in preterm infants born between 28 and 32 weeks, hospitalized in the neonatal intensive care unit (NICU). The second aim is to assess postnatal changes in HRV measures between 32 and 35 weeks. STUDY DESIGN: 32 preterm infants born between 28 and 32 weeks of gestation were recruited. For each infant 48 h of recordings of RR interval were performed at week 32 and week 35. HRV parameters included time and frequency parameters. RESULTS: At week 32, the intra-class correlation coefficient (ICC) of all HRV values was statistically significant with high correlation coefficients (ICC = 0.83-0.97). At week 35, a significant increase was noted in the HRV parameters, characterize mainly the sympathetic tone, with over half the infants showing an increase greater than the MDC for these parameters. CONCLUSIONS: Using 24-h recording at week 32 of gestation during NICU routine is reliable, feasible, not costly and may have important implications for an early identification of premature in a state of stress such as sepsis, or as a follow-up measure.

Inhibitory potency of twice-a-day omeprazole on gastric acidity is enhanced by eradication of H. pylori in duodenal ulcer patients.

The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to be greater in the presence than in the absence of an H. pylori infection. It is unknown if this effect persists when a higher dose of omeprazole is taken. We undertook both 24-hr pH-metry and 24-hr aspiration studies in 12 H. pylori-positive patients with a history of duodenal ulcer (DU); (1) when not on omeprazole; (2) when on omeprazole 20 mg twice a day for 8 days; (3) two months after eradication of H. pylori and when not on omeprazole; and (4) after eradication of H. pylori and when on omeprazole twice a day. Eradication of H. pylori in DU results in lower mean and median pH; decreased percent pH > or = 3/ > or = 4, and greater median H+ after breakfast, after lunch, and overnight; and omeprazole appears to have less of a pH-elevating effect in the absence than in the presence of an H. pylori infection. The fall in gastric juice NH3 concentration as a result of eradicating H. pylori partially explained the lower pH-elevating effect of omeprazole. The variation in acid inhibitory effect of omeprazole after as compared with before eradication of H. pylori could not be explained by differences; (1) in gastric juice concentrations of IL-1alpha, IL-8, IL-13, or epidermal growth factor; (2) in the fasting or fed total concentration of gastric juice bile acids; (3) in the fasting concentrations or area under-the-curve (AUC) of the gastric H+ concentrations in response to food; or (4) in the pharmacokinetics of omeprazole. The difference in H+ AUC without omeprazole minus with omeprazole was actually greater when compared after versus before eradication of H. pylori. Thus, in DU the pH-elevating potency of omeprazole taken twice a day is greater in the presence than in the absence of an H. pylori infection.

Comparison of 200 mg cimetidine with multiple doses of antacid on extent and duration of rise in gastric pH in volunteers.

The effects on gastric pH of a single administration of 200 mg cimetidine (Tagamet HB) were compared to multiple doses of a liquid antacid (Mylanta) using a pH microelectrode. Gastric pH was monitored for 8 hr in 20 normal fasting volunteers in a crossover design to compare Tagamet HB (two 100-mg tablets administered as a single dose) with Mylanta Suspension, an initial 17.5-ml dose of antacid with additional doses given when gastric pH fell below 3.5. Both treatments increased the pH above 3.5 during the first hour following treatment, with Mylanta being more effective than Tagamet HB. Interestingly, to sustain the reduction in acidity during this 1-hr interval, a mean of 2.45 doses of antacid were administered. Although multiple doses of Mylanta kept the pH above 3.5 (for at least 25% of the time) for the first 4 hr, the single administration of 200 mg of Tagamet HB maintained gastric pH above 3.5 (greater than 25% of time) for the full 8 hr of the study. Compared to Mylanta, the percent of time gastric pH was >3.5 was significantly higher with Tagamet HB during the 3rd to 8th hour after dosing. This study demonstrates that 200 mg of cimetidine administered as Tagamet HB is significantly more effective and has a much longer duration of action in raising gastric pH >3.5 than six doses of Mylanta.

Food but not a chemically defined diet interferes with maintenance of intragastric pH at a predefined level using continuous pH-stat-adjusted intravenous infusion of ranitidine in healthy volunteers.

Eight healthy volunteers were used to determine the influence of a normal diet (food) versus an isocaloric chemically defined diet (CDD) on the dose of ranitidine infused continuously over 12 hr, required to maintain the intragastric pH > or = 5 or above. The dose of ranitidine used was adjusted by the pH-stat instrument, Gastrojet, and a target pH of 5.0 was selected. The average ranitidine dose was 43.5 mg for food, 28.3 mg for CDD, and 25.7 mg for fasting. Despite the higher dose of ranitidine used with food, the control of pH was lower than the desired and preset value of pH > or = 5: the average mean pH was 3.99 for food, 5.11 for CDD, and 5.75 for fasting. The percentage of time of pH > or = 5 was 32.0% for food, 73.7% for CDD, and 80.1% for fasting. Thus, when persons are fed a normal diet there is a need for higher doses of ranitidine to maintain the gastric pH > or = 5.0. Even with frequent monitoring of intragastric pH with the Gastrojet, there is much greater variability in pH control with food than with CDD or fasting, and the preset and desired pH level was not achieved. This difficulty in achieving desired end points of pH control when switching from a fasting to a fed state needs to be considered when intravenous ranitidine is used to obtain strict control of intragastric pH.

Twice daily nizatidine or ranitidine is superior to once daily dosing in elevating 24 h intragastric pH in patients with duodenal ulcer disease.

The present study was performed in six asymptomatic patients with a history of resistant duodenal ulcers in whom 24 h intragastric pH, gastric juice pepsin and PGE2 concentrations, as well as serum gastrin concentrations, were measured. We wanted to compare the effects on these parameters of a single night time (q.h.s.) dose of nizatidine 300 mg (N1), nizatidine 300 mg b.i.d. (N2), ranitidine 300 mg q.h.s. (R1) or ranitidine 300 mg b.i.d. (R2) compared with placebo (P). During the night (22.00-08.00 h), all treatments gave a higher mean pH than P, but during the day (08.00-22.00 h) the mean pH was higher than P only for patients administered R2 and N2. Doubling the dose of nizatidine (N2 vs N1) or ranitidine (R2 vs R1) increased the mean daytime pH, but had no effect on night time pH. The daytime pepsin concentration was unaffected by H2-receptor antagonists, while night time pepsin was lower with R1 and R2, but not with N1 or N2. The night time gastrin concentration was unaffected by H2-receptor antagonists; doubling the dose of the H2-receptor antagonist (R2 vs R1 and N2 vs N1) increased daytime gastrin concentration. During the night, each treatment increased PGE2 concentration by at least six-fold compared with P. Thus, where it is therapeutically indicated to achieve greater suppression of acid secretion, doubling the total daily dose by dosing with twice daily versus once daily night time nizatidine or ranitidine is efficacious.

Diurnal variation in the pharmacokinetics of nizatidine in healthy volunteers and in patients with peptic ulcer disease.

Six healthy volunteers and six patients with asymptomatic duodenal ulcer disease received placebo or 300 mg nizatidine once at night or twice daily (morning and evening) for a week in a random, cross-over fashion. Steady-state serum nizatidine concentrations and gastric pH were measured over a 24-hour period. No significant differences in the pharmacokinetic indices were observed between the healthy volunteers and patients with duodenal ulcer disease. In patients with duodenal ulcers, significantly lower peak serum concentrations, longer half-life (t1/2) and larger volume of distribution (Vd) were observed after the night doses compared with the daytime doses. The diurnal variation in drug kinetics between the nighttime and daytime doses in the twice daily regimen may be caused by a slower absorption rate, paralleled with a higher extent of distribution. Despite lower serum nizatidine concentrations, gastric pH was higher in the evening than in the daytime; it is speculated that this was due to a time-dependent enhanced distribution of the H2-receptor blocker into the site of action.

Effect of nizatidine and ranitidine on 24 hour intragastric pH, pepsin, prostaglandin E2 and serum gastrin concentrations in healthy volunteers.

In order to achieve possible greater therapeutic efficacy, ranitidine 300 mg bid (R2) may be given rather than 300 mg qhs (R1), or nizatidine 300 mg bid (N2) may be given rather than 300 mg qhs (N1). A randomized placebo-controlled crossover study was performed in six healthy volunteers (four males, two females) who ranged in age from 23 to 43 years, comparing R1, R2, N1 and N2 versus placebo (P), measuring 24 h intragastric pH by the aspiration technique, gastric juice pepsin and prostaglandin E2 (PGE2) concentrations, as well as serum gastrin concentrations. In all treatment groups, 24-h intragastric pH was higher than with P; the 24 h and daytime (0800-2200 h) pH was higher with N2 than with N1, but not with R2 versus R1. The percentage pH > or = 3 was greater with N2 than with N1 during the daytime. Night-time (2200-0800 h) and 24 h pepsin concentrations were higher in R2 than in R1, were similar in N1 and N2, and were lower in these treatment groups than in P. The gastric juice PGE2 concentration at night-time, but not at daytime, was increased in the four treatment groups compared with P. Despite the higher pH values at night-time in the treatment groups, the night-time concentrations of serum gastrin were unchanged, and yet during the daytime the higher values of pH were associated with increased gastrin concentrations when R2 or N2 were given, but not with R1 and N1. There was a negative correlation between intragastric juice pH and pepsin concentration during the daytime, and a positive correlation between pH and PGE2 concentration during the night-time. The slopes and y-axis intercepts between pH and pepsin or PGE2 concentrations differed between the placebo and the treatment groups, suggesting that these H2-receptor antagonists may have an effect on lowering pepsin and raising PGE2 concentrations in addition to their effects on pH. As the percentage of time over the 24 h period and night-time periods when the pH was greater than 3 was not different between ranitidine and nizatidine, the two regimens will likely have similar clinical efficacy.

A dose-ranging study of ranitidine and its effect on intragastric and intra-oesophageal acidity in subjects with gastro-oesophageal reflux disease.

METHODS: This randomized, double-blind, single-centre, crossover study was designed to assess the effects of three regimens of ranitidine (150 mg b.d., 300 mg b.d. and 300 mg q.d.s.) and placebo on intra-oesophageal and intragastric pH in subjects with gastro-oesophageal reflux disease (GERD). Twenty-six subjects were screened, and 9 were evaluable by the admission criteria. These 9 subjects received each of the regimens for 72 h, and a wash-out period of at least 48 h followed each dosing period. Standard meals and beverages were provided. RESULTS: With increasing doses of ranitidine, 24-h intragastric mean H+ and integrated H+ fell, and the percentage of the time the pH was equal to or greater than 4 (% time pH > or = 4) rose: the minimum effective dose for these effects was ranitidine 300 mg daily. With increasing doses of ranitidine there was also a progressive decline in mean 24-h intra-oesophageal H+ and integrated H+, and increasing % time pH > or = 4. The minimal effective dose was 300 mg daily for intra-oesophageal mean H+ and integrated H+, and 600 mg for % time pH > or = 4. The minimal effective dose to decrease the number of reflex episodes was 1200 mg ranitidine. For the daytime upright position, a dose effect of increasing ranitidine was also seen, with minimal effective ranitidine doses of 300 mg for a decrease in mean H+, and 1200 mg for % time pH > or = 4. CONCLUSION: If these higher doses of ranitidine are confirmed to be more effective than the standard 150 mg b.d. regimen for the treatment of patients with gastro-oesophageal reflux disease, then the mechanism of this action probably relates to the lower exposure of the oesophageal mucosa to acid.

Effect of intravenous infusion of ranitidine on intragastric acidity in fasting subjects: comparison with bolus or Gastrojet (pH-stat-adjusted) infusion.

This study was undertaken in nine fasting healthy volunteers to compare the effect of intravenous continuous infusion versus bolus injection of ranitidine on 12-h intragastric pH, and to compare the efficacy of these two modes of administration of pH-stat-adjusted infusion of ranitidine using the Gastrojet. Each volunteer had three study sessions with 12-h pH measurements. In the ranitidine infusion treatment arm (RAN-INF), ranitidine was continually infused intravenously using an IVAC-pump at a dose of 0.125 mg mg.kg over a 12-h period. In the ranitidine bolus treatment arm (RAN-BOL), ranitidine bolus 50 mg was given over 10 min, every 6 h. When ranitidine infusion was given by the pH stat method using the Gastrojet (RAN-JET), sufficient ranitidine was given to maintain a present value of pH > or = 5. The study was analysed with a 3 x 3 Latin square cross-over design with multiple measurements of each phase of the cross-over. No difference was found between RAN-INF and RAN-BOL in 12-h or in daytime (10.00-18.00 h) mean pH, median pH, or percentage of pH > or = 5. Using RAN-JET, 89.5% of the pH values were > or = 5., compared with 39.7% and 40.0% with RAN-INF or RAN-BOL. RAN-JET also gave higher (P < 0.05) mean and median 12-h or daytime pH values, as compared with RAN-INF or RAN-BOL. The mean doses of ranitidine given in the 12-h infusion periods were 100 mg, 109 mg and 112 mg (RAN-BOL, RAN-INF and RAN-JET, respectively). Thus, this superior inhibition of acid inhibition achieved with Gastrojet does not require higher mean doses of ranitidine. These findings cannot necessarily be applied to persons with duodenal ulcer disease or to patients in an intensive-care unit setting. However, the data do raise the possibility that much greater inhibition of acid inhibition can be achieved by individualizing the dose of ranitidine using the Gastrojet.

Effect of intravenous and oral omeprazole on 24-hour intragastric acidity in duodenal ulcer patients.

Nine patients with duodenal ulcer were on separate occasions given omeprazole, 20 mg orally, 10 mg intravenously (IV), and 40 mg IV once daily for 5 days. On day 1, the median reduction of 24-hour intragastric acidity was 42.2% for the 20-mg oral dose and 54.8% and 88.4% for the two IV doses, respectively, but the between-patient variability was considerable for all three doses. On day 5, the degree of reduction had increased for all three doses to a median value of 99.9% for the 20-mg oral dose and 95.7% and 99.9% for the two IV doses, respectively. Plasma omeprazole concentrations increased significantly from day 1 to day 5 only for the 20-mg oral and 40-mg IV doses. Thus, the increased pharmacological effect of omeprazole during repeated once daily administration can only partly be explained by increased plasma concentrations, suggesting that some additional factor(s) must influence the degree of reduction of 24-hour intragastric acidity. Thus, when determining the optimal dose of omeprazole for acid inhibition, the route and duration of administration must be taken into consideration; after 5 days of once-daily administration of doses as low as 10 mg IV and 20 mg orally are effective and dependable in reducing 24-hour intragastric acidity in patients with duodenal ulcer. However, a daily dose of 40 mg IV omeprazole is not sufficient to keep intragastric pH above 4 in all patients during the first day of treatment.

Long-term evaluation of cardiac function in obese patients treated with a very-low-calorie diet: a controlled clinical study of patients without underlying cardiac disease.

Twenty obese women were randomly assigned to consume (for 16 wk) either a 420-kcal/d liquid diet (n = 12) or a 1200-kcal/d balanced diet (n = 8). Thereafter, patients in both conditions were prescribed a 1200-kcal/d diet for the remainder of treatment (week 45). Six obese nondieters served as control subjects. Ambulatory electrocardiographic (Holter) monitor readings were obtained on all patients at baseline and weeks 3, 9, 13, 17, 19, and 45 of the study and were analyzed for ventricular premature depolarizations (VPDs) per hour, paired forms, and runs of ventricular tachycardia. There were no statistically significant changes in VPDs in any condition during treatment. Similarly, there were no significant changes in the PR, QRS, and corrected QT intervals. The results indicate that under appropriate medical supervision, very-low-calorie diets can be used safely for up to 16 wk by significantly obese patients free of pre-existing cardiac disease.

A single night-time dose of famotidine is equivalent to ranitidine in decreasing 24-hour gastric acidity in asymptomatic duodenal ulcer subjects.

Six asymptomatic, non-smoking men with endoscopically proven duodenal ulcer disease received single nocturnal doses of placebo, 40 mg famotidine and 300 mg ranitidine each for 1 week prior to serial measurement of pH, peptic activity and serum gastrin concentrations over 24 h and of acid output. The intragastric pH fluctuated between 1.53 and 5.07 when subjects were given placebo but within 2 h of taking famotidine or ranitidine it rose to 5.57 or higher; the effect lasted for 12 h from midnight. Peptic activity fell during famotidine and ranitidine treatment and the decline was somewhat greater 8-15 h after using famotidine. Serum gastrin levels did not change materially with any treatment. The study shows the equivalent effect of standard bed-time doses of famotidine and ranitidine on intragastric pH, acid output and serum gastrin concentrations in asymptomatic men with duodenal ulcer disease.

Twenty-four-hour intragastric measurements in twenty healthy subjects: effect of enisoprost, a novel and potent antisecretory and antipeptic synthetic E1 prostaglandin.

Gastric aspiration was performed continuously overnight and at hourly intervals during the daytime in 20 healthy male volunteers. Medications used included enisoprost 100, 200 or 400 micrograms, misoprostol 200 micrograms and placebo, given at bedtime. Each dose of enisoprost markedly inhibited nocturnal mean acid output, hydrogen ion activity, pH and peptic activity. The duration of these effects was up to 10 h. Misoprostol, given at bedtime, also decreased acid secretion, but the effect was significantly less than that observed with any of the doses of enisoprost. A dose-response effect for enisoprost was found for the mean nocturnal hydrogen ion activity and pH, as well as for maximum pH attained. Although enisoprost, given at bedtime, had a marked inhibitory effect on acid and pepsin secretion for the overnight interval, this did not result in rebound hyperacidity or a rise in serum total gastrin concentration. The results of this study suggest that enisoprost should be tested by clinical trial for the treatment of peptic ulcer disease.

Evaluation of antacid tablets and liquid in fasting and fed men and women.

In view of in vitro tests suggesting good performance of an experimental tablet formulation of an aluminum hydroxide-magnesium hydroxide antacid, a study was conducted to evaluate the efficacy in vivo. Twenty-three healthy men and women were enrolled in the study, which was carried out in two parts: fasting and postprandial. Eight of the volunteers failed to qualify because of repeated baseline pH greater than 2.5. In the 15 participants who qualified, the intragastric pH was monitored for up to 240 minutes after the administration of one or two experimental tablets, 5 or 10 ml of a commercially available liquid antacid, or placebo. In the fasting subjects (n = 10), the antacids rapidly increased the mean pH. One antacid tablet and 5 ml of liquid antacid yielded similar results, with mean peak pH values of 5.2 and 4.8 and durations above pH 3.5 of 25 and 40 minutes, respectively. When the doses were doubled, 10 ml of liquid produced a peak pH of 6.7 and maintained the pH above 3.5 for 40 minutes, whereas two tablets produced a peak pH of 4.8 and maintained pH above 3.5 for 15 minutes. In the fed subjects (n = 10), neither antacid formulation at either dose significantly raised intragastric pH. Further studies are needed to establish the optimal time for postprandial administration of antacids.

Effects of E2 levuglandins on the contractile activity of the rat uterus.

The effects of E2 levuglandins on the contractile activity of rat uterine horns were studied. LGE2, AnLGE2, delta 9-LGE2 and the synthetic epimer, 8-epi-delta 9-LGE2 all induced contractions in a dose-response fashion. AnLGE2 gave decreased responses with increased bath concentrations. Paired comparisons showed potent and selective inhibitory effects of AnLGE2 on the uterotonic activity of prostaglandins. AnLGE2 inhibited the uterotonic activity of PGE2 at a 0.1:1 ratio, of PGD2 at a 1:1 ratio, but did not inhibit the activity of PGF2 alpha. Exposure of spontaneously contracting uteri to high concentrations of AnLGE2, or prolonged exposure to lower concentrations, suppressed contractions.

Enprostil reduces G-cell hyperplasia and hypergastrinemia in duodenal ulcer.

A 42-year-old man with a 26-year history of duodenal ulcer volunteered for a 24-hour intragastric pH monitoring study, at which time his fasting gastrin concentration was found to be elevated. Secretin injection decreased the serum gastrin concentration. When not on treatment his total gastrin, gastrin-17 (G-17), and gastrin-34 (G-34) response to a protein-containing breakfast was marked. Immunocytochemical staining of antral biopsies showed hyperplasia of gastrin-containing cells, more pronounced for G-17 than for G-34. Cimetidine or cimetidine plus pirenzepine increased 24-hour intragastric pH, whereas pirenzepine alone rendered the gastric contents more acidic, particularly overnight. The total serum gastrin concentrations increased after meals and were unaffected by cimetidine or pirenzepine; enprostil, however, reduced the postprandial increase in total gastrin, G-34, and G-17. After six weeks of treatment with enprostil, the number of cells containing G-17 and G-34 was reduced. The findings show that G-cell hyperplasia may occur in the presence of a normal fasting serum gastrin concentration; fasting serum gastrin concentrations may fluctuate widely over time; the food-stimulated increase in G-17 was greater than that for G-34, and is associated with more pronounced antral hyperplasia for G-17 and G-34; and enprostil blunts the postprandial increase in G-17, G-34, and total gastrin. These observations suggest that enprostil may reduce G-cell hyperplasia and hypergastrinemia.

Synergistic interaction between an H2-receptor antagonist and enprostil on 24-hour intragastric pH, serum gastrin concentration, and tissue immunoperoxidase staining for gastrin, somatostatin, and serotonin in a patient with metastatic gastrinoma.

A 56-year-old woman newly diagnosed as having Zollinger-Ellison syndrome due to a metastatic gastrinoma underwent 24-hour intragastric pH monitoring, serum gastrin (total, G-17 and G-34) measurements, and immunoperoxidase staining of duodenal, antral, and gastric body biopsies for gastrin, somatostatin, and serotonin. Determinations were made while the patient was given different doses of ranitidine, enprostil (a synthetic orally administered prostaglandin E2), or ranitidine plus enprostil. Following are the findings from this single-patient study: Intragastric pH was persistently low but varied in response to food when the patient was given ranitidine. Immunocytochemical staining of antral biopsies obtained before the patient was treated revealed a reduced number of cells containing G-17 and G-34 but an increase in the antral somatostatin-containing D-cells. Treatment with 35 micrograms of enprostil BID plus 300 mg of ranitidine BID for two and 11 weeks was associated with an increased number of duodenal G-cells, a decrease in antral D-cells, and a decrease in the number of antral serotonin-containing cells. Enprostil in a dosage of 35 or 70 micrograms BID had no effect on intragastric pH, but when enprostil was given in combination with ranitidine, postprandial and nocturnal intragastric alkalinity was accentuated along with a return of duodenal and antral G-cells and a loss of the antral D-cell hyperplasia. Optimal pH control was achieved with 300 mg of ranitidine BID; more frequent dosing with ranitidine did not further increase intragastric pH. Both the total serum gastrin concentration and G-17 levels fluctuated in response to meals. The serum concentrations of total gastrin, G-17, and G-34 were reduced with enprostil and with ranitidine.

Comparison of cimetidine and ranitidine on 24-hour intragastric acidity and serum gastrin profile in patients with esophagitis.

Twenty-four-hour intragastric pH and serum gastrin profiles were monitored in six male asymptomatic patients who previously were found to have esophagitis on endoscopy and biopsy. They received cimetidine 300 mg qid (C), ranitidine 150 mg bid (R), or placebo (P) for one week each, utilizing the Latin-square design. The mean BAO was 0.4 +/- 0.2 mmol/hr, and the pentagastrin-stimulated MAO was 21.2 +/- 3.2 mmol/hr. In the P-treated patients, the pH fluctuated between 1.8 and 3.5 and over 90% of the readings were less than pH 4. As compared to P, both C and R significantly suppressed H+ after breakfast, overnight, and over the 24-hr period. The mean pH after lunch was significantly higher in R than in P, but not in C. Over the 24-hr period, a higher percentage of the readings were above pH 4.0 in R as compared to C. During the night, 50% of the pH readings were above pH 4.0 in C and R, whereas in P 50% of the pH readings were less than pH 2.0. The integrated gastrin responses after each meal were similar in C and R and were greater than in P. The biphasic response of the ratio of H+ and gastrin (H+/G) following each meal was suppressed by both H2-receptor antagonists, with numerically lower values obtained in R than in C. This study suggests that ranitidine 150 mg bid is superior to cimetidine 300 mg qid in suppressing the 24-hr intragastric acidity.

Postprandial changes in serum concentrations of gastrin-17, gastrin-34, and total gastrin in patients with duodenal or gastric ulcers and in normal subjects.

The fasting concentrations of total gastrin and gastrin-17 (G-17) were similar in healthy volunteers and in asymptomatic patients with gastric ulcers or duodenal ulcers. However, the fasting serum concentration of gastrin-34 (G-34) was higher in patients with gastric ulcers than in normal subjects, in whom it was higher than in patients with duodenal ulcers. In response to food, the increases in G-17, G-34, and total gastrin were greater in ulcer patients than in healthy subjects. Cimetidine administration was associated with further increases in G-17, G-34, and total gastrin in normal subjects and gastric ulcer patients after meals. The ratio G-17/G-34 was similar in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers. Cimetidine produced an increase in G-17/G-34 in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers, but the ratio G-17/G-34 was greater in patients with gastric ulcers than in normal subjects. These results indicate that: differences in serum gastrin concentrations between patient groups, treatment regimens, and time of day are better detected by measuring G-17 and G-34 rather than total gastrin; there are differences in fasting and food-stimulated gastrin concentrations between normal subjects and patients with gastric or duodenal ulcers; the fasting concentration of G-34 is higher than G-17 in normal subjects and patients with gastric ulcers but not in patients with duodenal ulcers; food increases G-17 in all subjects but G-34 only in subjects with gastric ulcers; cimetidine increases the fasting concentration of total gastrin in normal subjects and patients with gastric ulcers and increases G-17 and G-34 in normal subjects; cimetidine increases the ratio G-17/G-34 in normal subjects and patients with gastric ulcers, but decreases G-17/G-34 in patients with duodenal ulcers. It is proposed: that measurements of total gastrin concentration should be replaced by measurements of G-17 and G-34 and that such measurements of G-17 and G-34 indicate differences in serum gastrin concentrations between normal subjects and those with peptic ulcers and between those with gastric versus duodenal ulcers. The role of altered gastrin metabolism in the pathogenesis of ulcers needs to be established.