Jeffrey L. Barnett

Upper Gastrointestinal (GI) pH in Young, Healthy Men and Women

The pH in the upper gastrointestinal tract of young, healthy men and women was measured in the fasting state and after administration of a standard solid and liquid meal. Calibrated Heidelberg capsules were used to record the pH continuously over the study period of approximately 6 hr. In the fasted state, the median gastric pH was 1.7 and the median duodenal pH was 6.1. When the meal was administered the gastric pH climbed briefly to a median peak value of 6.7, then declined gradually back to the fasted state value over a period of less than 2 hr. In contrast to the pH behavior in the stomach, feeding a meal caused a reduction in the median duodenal pH to 5.4. In addition, there was considerable fluctuation in the postprandial duodenal pH on an intrasubject basis. The pH in the duodenum did not return to fasted state values within the 4-hr postprandial observation period. There was no tendency for the duodenal pH to be related to the gastric pH in either the fed or fasted phases of the study. Furthermore, pH in the upper GI tract of young, healthy subjects appears to be independent of gender. The differences in upper GI pH between the fasted and the fed state are discussed in terms of dosage form performance and absorption for orally administered drugs.

Risk factors for post-ERCP pancreatitis: a prospective multicenter study.

OBJECTIVES:Pancreatitis is the most common and serious complication of diagnostic and therapeutic ERCP. The aim of this study is to examine the potential patient- and procedure-related risk factors for post-ERCP pancreatitis in a prospective multicenter study.METHODS:A 160-variable database was prospectively collected by a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group and participating in a randomized controlled study evaluating whether prophylactic corticosteroids will reduce the incidence of post-ERCP pancreatitis. Data were collected prior to the procedure, at the time of procedure, and 24–72 h after discharge. Post-ERCP pancreatitis was diagnosed and its severity graded according to consensus criteria.RESULTS:Of the 1,115 patients enrolled, diagnostic ERCP with or without sphincter of Oddi manometry (SOM) was performed in 536 (48.1%) and therapeutic ERCP in 579 (51.9%). Suspected sphincter of Oddi dysfunction (SOD) was the indication for the ERCP in 378 patients (33.9%). Pancreatitis developed in 168 patients (15.1%) and was graded mild in 112 (10%), moderate in 45 (4%), and severe in 11(1%). There was no difference in the incidence of pancreatitis or the frequency of investigated potential pancreatitis risk factors between the corticosteroid and placebo groups. By univariate analysis, the incidence of post-ERCP pancreatitis was significantly higher in 19 of 30 investigated variables. In the multivariate risk model, significant risk factors with adjusted odds ratios (OR) were: minor papilla sphincterotomy (OR: 3.8), suspected SOD (OR: 2.6), history of post-ERCP pancreatitis (OR: 2.0), age <60 yr (OR: 1.6), ≥2 contrast injections into the pancreatic duct (OR: 1.5), and trainee involvement (OR: 1.5). Female gender, history of recurrent idiopathic pancreatitis, pancreas divisum, SOM, difficult cannulation, and major papilla sphincterotomy (either biliary or pancreatic) were not multivariate risk factors for post-ERCP pancreatitis.CONCLUSION:This study emphasizes the role of patient factors (age, SOD, prior history of post-ERCP pancreatitis) and technical factors (number of PD injections, minor papilla sphincterotomy, and operator experience) as the determining high-risk predictors for post-ERCP pancreatitis.

Upper gastrointestinal pH in seventy-nine healthy, elderly, North American men and women.

Gastric and duodenal pH levels were measured in 79 healthy, elderly men and women (mean ± SD = 71 ± 5 years) under both fasted and fed conditions using the Heidelberg capsule technique. The pH was recorded for 1 hr in the fasted state, a standard liquid and solid meal of 1000 cal was given over 30 min, then the pH was measured for 4 hr postprandially. Results are given as medians and interquartile ranges: fasted gastric pH, 1.3 (1.1–1.6); gastric pH during the meal, 4.9 (3.9–5.5); fasted duodenal pH, 6.5 (6.2–6.7); and duodenal pH during the meal, 6.5 (6.4–6.7). Although fasted gastric pH, fasted duodenal pH, and duodenal pH during the meal differ statistically from those observed in young subjects, the differences are not expected to be clinically significant in terms of drug absorption for the majority of elderly subjects. Following a meal, gastric pH decreased from a peak pH of 6.2 (5.8–6.7) to pH 2.0 within 4 hr in most subjects. This rate of return was considerably slower than in young, healthy subjects. Nine subjects (11%) had a median fasted gastric pH >5.0, and in five of these subjects the median pH remained >5.0 postprandially. In this group, drugs and dosage forms which require an acidic environment for dissolution or release may be poorly assimilated.

Serum glucose concentration as a modulator of interdigestive gastric motility

The objective of this study was to examine the effect of serum glucose concentration on interdigestive gastrointestinal motility and plasma motilin levels in humans. Motility studies were performed for a 3-h baseline period and a 3-h test period during which serum glucose levels were maintained with a glucose clamp at 250, 175, 140, or 120 mg/dl. During the basal recording, three phases of the interdigestive migrating motor complex (MMC) were easily recognizable, with a mean cycle duration of 97 +/- 12 min. Plasma motilin levels fluctuated in phase with the MMC. Gastric contractions were nearly absent at a serum glucose level of 250 mg/dl and markedly reduced at 175 and 140 mg/dl. Gastric phase III activity was inhibited during these infusions. Gastric contractions and phase III activity were not affected by glucose infusion at 120 mg/dl. In contrast, the frequency of duodenal phase III activity was unchanged at all levels of glucose infusion. Mean motilin levels were significantly reduced during glucose infusion at 250 and 175 mg/dl (p less than 0.05), but not at 140 and 120 mg/dl. We conclude that hyperglycemia inhibits the occurrence of the MMC in the stomach and suppresses plasma motilin levels. The differential sensitivity of motility and motilin concentration to different degrees of hyperglycemia suggests that hyperglycemia can inhibit antral motility independent of plasma motilin. In contrast, the duodenal MMC appears to be insensitive to hyperglycemia. This suggests that the antral and duodenal MMCs are mediated by different mechanisms. Our observations indicate the importance of serum glucose in regulating gastric motility.

A double-blind multicenter comparison of domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis

Objective:A double-blind, multicenter, randomized trial was conducted to compare the side effects and efficacy of domperidone and metoclopramide in symptomatic diabetic gastroparesis.Methods:Ninety-three insulin-dependent diabetes patients with a ≥ 3-month history of gastroparesis symptoms were recruited; 48 received domperidone 2 × 10-mg tablets 4 times daily, and 45 received metoclopramide 1 × 10-mg tablet + 1 placebo tablet 4 times daily. Nausea, vomiting, bloating/distension, and early satiety were evaluated for severity after 2 and 4 wk. Adverse central nervous system (CNS) effects of somnolence, akathisia, asthenia, anxiety, depression, and reduced mental acuity were elicited and graded for severity at 2 and 4 wk.Results:Domperidone and metoclopramide were equally effective in alleviating symptoms of diabetic gastroparesis. Elicited adverse CNS effects were more severe and more common with metoclopramide. Somnolence was acknowledged by 49% of patients (mean severity score, 1.03) after 4 wk of metoclopramide compared with 29% of patients (mean severity score, 0.49) after 4 wk of domperidone (incidence, p= 0.02; severity; p= 0.03). A reduction in mental acuity was acknowledged by 33% of patients (mean severity score, 0.62) after 4 wk of metoclopramide, compared with 20% of patients (mean severity score, 0.27) after 4 wk of domperidone (incidence, p= 0.04; severity, p= 0.04). Akathisia, asthenia, anxiety, and depression were also acknowledged less often, and at a lower severity, after 4 wk of domperidone, although these differences were not statistically significant.Conclusions:Domperidone and metoclopramide effectively reduce the symptoms of diabetic gastroparesis; CNS side effects are more pronounced with metoclopramide.

Can endoscopic ultrasound or magnetic resonance cholangiopancreatography replace ERCP in patients with suspected biliary disease? A prospective trial and cost analysis.

OBJECTIVES:ERCP is the gold standard for pancreaticobiliary evaluation but is associated with complications. Less invasive diagnostic alternatives with similar capabilities may be cost-effective, particularly in situations involving low prevalence of disease. The aim of this study was to compare the performance of endoscopic ultrasound (EUS) with magnetic resonance cholangiopancreatography (MRCP) and ERCP in the same patients with suspected extrahepatic biliary disease. The economic outcomes of EUS-, MRCP-, and ERCP-based diagnostic strategies were evaluated.METHODS:Prospective cohort study of patients referred for ERCP with suspected biliary disease. MRCP and EUS were performed within 24 h before ERCP. The investigators were blinded to the results of the alternative imaging studies. A cost-utility analysis was performed for initial ERCP, MRCP, and EUS strategies for these patients.RESULTS:A total of 30 patients were studied. ERCP cholangiogram failed in one patient, and another patient did not complete MRCP because of claustrophobia. The final diagnoses (n = 28) were CBD stone (mean = 4 mm; range = 3–6 mm) in five patients; biliary stricture in three patients, and normal biliary tree in 20. Two patients had pancreatitis after therapeutic ERCP, one after precut sphincterotomy followed by a normal cholangiogram. EUS was more sensitive than MRCP in the detection of choledocolithiasis (80%vs 40%), with similar specificity. MRCP had a poor specificity and positive predictive value for the diagnosis of biliary stricture (76%/25%) compared to EUS (100%/100%), with similar sensitivity. The overall accuracy of MRCP for any abnormality was 61% (95% CI = 0.41–0.78) compared to 89% (CI = 0.72–0.98) for EUS. Among those patients with a normal biliary tree, the proportion correctly identified with each test was 95% for EUS and 65% for MRCP (p < 0.02). The cost for each strategy per patient evaluated was

The influence of the interdigestive migrating myoelectric complex on the gastric emptying of liquids

1346 for ERCP,

Endoscopic and histological patchiness in treated ulcerative colitis

1111 for EUS, and

Safety and effectiveness of temperature-controlled radio-frequency energy delivery to the anal canal (Secca® Procedure) for the treatment of fecal incontinence

1145 for MRCP.CONCLUSIONS:In this patient population with a low disease prevalence, EUS was superior to MRCP for choledocholithiasis. EUS was most useful for confirming a normal biliary tree and should be considered a low-risk alternative to ERCP. Although MRCP had the lowest procedural reimbursement, the initial EUS strategy had the greatest cost-utility by avoiding unnecessary ERCP examinations.

Single-day, divided-dose oral sodium phosphate laxative versus intestinal lavage as preparation for colonoscopy: Efficacy and patient tolerance

It is unknown how the interdigestive migrating motor complex influences the gastric emptying of liquids. Therefore, the gastric emptying rate of 50- and 200-mL volumes of phenol red solution were measured while monitoring contractile activity. Motor activity was recorded using a hydraulic manometric system and expressed as either the proximity of dosing time to time of appearance of phase III or as a motility index, defined as (contractile area)/(sampling interval time). After an initial lag period, emptying was log linear. With a 50-mL oral dose, the mean gastric emptying rate of the log-linear phase was successively faster during phase I (0.018 +/- 0.003 min-1), phase II (0.083 +/- 0.031 min-1), and late phase II/III (0.171 +/- 0.066 min-1) (P less than 0.05). Similarly, the mean lag time decreased successively with phases I, II, and late II/III (19.1 +/- 12.4, 7.6 +/- 5.6, and 3.8 +/- 2.8 minutes, respectively). At a 200-mL oral dose, there was no difference in the emptying rate between phase I and phase II (0.104 +/- 0.0014 vs. 0.110 +/- 0.041 min-1), but the emptying rate during late phase II/III was significantly greater (0.236 +/- 0.069 min-1); lag time was not dependent on phase. There was a statistical difference in the overall mean emptying rate between the 50- and 200-mL volumes. Also, during phase I, the emptying rate was faster for the 200-mL volume. This study shows a strong dependence of liquid gastric emptying rate and lag time on interdigestive antral motility, the emptying of small volumes being more dependent on motility phase than that of large volumes. Phase-related fluctuations in contractile activity can account for much of the reported variability in gastric emptying data. Furthermore, this study suggests that dose volume and interdigestive motor activity at the time of drug administration can affect absorption and onset of therapeutic response for some drugs.