Robert S. Fisher

Biphasic nature of gastric emptying.

The existence of a lag phase during the gastric emptying of solid foods is controversial. It has been hypothesised that among other early events, the stomach requires a period of time to process solid food to particles small enough to be handled as a liquid. At present no standardised curve fitting techniques exist for the characterisation and quantification of the lag phase or the emptying rate of solids and liquids. We have evaluated the ability of a modified power exponential function to define the emptying parameters of two different solid meals. Dual labelled meals were administered to 24 normal volunteers. The subjects received meals consisting of either Tc-99m in vivo labelled chicken liver or Tc-99m-egg, which have different densities, and In-111-DTPA in water. The emptying curves were biphasic in nature. For solids, this represented an initial delay in emptying or lag phase followed by an equilibrium emptying phase characterised by a constant rate of emptying. The curves were analysed using a modified power exponential function of the form y(t) = 1-(1-e-kt)beta, where y(t) is the fractional meal retention at time t, k is the gastric emptying rate in min-1, and beta is the extrapolated y-intercept from the terminal portion of the curve. The length of the lag phase and half-emptying time increased with solid food density (31 +/- 8 min and 77.6 +/- 11.2 min for egg and 62 +/- 16 min and 94.1 +/- 14.2 min for chicken liver, respectively). After the lag phase, both solids had similar emptying rates, and these rates were identical to those of the liquids. In vitro experiments indicated that the egg meal disintegrated much more rapidly than the chicken liver under mechanical agitation in gastric juice, lending further support to the hypothesis that the initial lag in emptying of solid food is due to the processing of food into particles small enough to pass the pylorus. We conclude that the modified power exponential model permits characterisation of the biphasic nature of gastric emptying allowing for quantification of the lag phase and the rate of emptying for both solids and liquids.

Role of opiate receptors in the regulation of colonic transit

The effects of morphine and the opiate antagonist naloxone on human colonic transit were investigated. In a crossover, double-blind fashion, two groups of 6 normal volunteers were studied using colonic transit scintigraphy during the administration of a test drug or control. The test drugs were morphine (0.1 mg/kg every 6 h s.c.) or naloxone (0.8 mg every 6 h s.c.); control was saline (1 ml every 6 h s.c.). Morphine significantly delayed transit in the cecum and ascending colon (p less than 0.05), slowed the progression of the geometric center (p less than 0.01), and decreased the number of bowel movements per 48 h (p less than 0.005). Naloxone accelerated transit in the transverse colon and rectosigmoid colon (p less than 0.05) and accelerated the progression of the geometric center (p less than 0.05), but had no effect on the number of bowel movements per 48 h (p greater than 0.05). These results suggest that narcotic analgesics may cause constipation in part by slowing colonic transit in the proximal colon and by inhibiting defecation. Acceleration of transit by naloxone suggests that endogenous opiate peptides may play an inhibitory role in the regulation of human colonic transit.

Colonic Transit Scintigraphy: A Physiologic Approach to the Quantitative Measurement of Colonic Transit in Humans

Colonic transit scintigraphy was developed to quantitatively evaluate colonic transit. Using this technique the progression of a radiolabeled marker from cecal instillation to defecation was studied in 7 normal male volunteers. An 8-ml bolus containing 50 mu Ci of indium 111-diethylene triamine pentaacetic acid was instilled into the cecum via a 2-mm tube, which was passed orally, and serial scintigrams were obtained over 48 h. By 48 h, 70.7% +/- 9.1% (mean +/- SEM) of the instilled activity had been defecated. The cecum and ascending colon emptied rapidly, with a half-emptying time of 87.6 +/- 27.0 min. Geometric center analysis showed an initial logarithmic progression of activity in the proximal colon and a linear progression distally. This study suggests that the transverse colon, not the cecum and ascending colon, may be the primary site for fecal storage. Colonic transit scintigraphy is a safe, physiologic, and quantitative method for evaluating the colonic transit of fecal material and may provide a useful tool for evaluating normal and abnormal large intestinal physiology.

Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy

Abstract  Gastric emptying of digestible solids occurs after trituration of food particles. Non‐digestible solids are thought to empty with phase III of the migrating motor complex (MMC). The aim of this study was to determine if a non‐digestible capsule given with a meal empties from the stomach with return of the fasting phase III MMC or during the fed pattern with the solid meal. Fifteen normal subjects underwent antroduodenal manometry and ingestion of a radiolabelled meal and SmartPill wireless pH and pressure capsule. In five subjects, emptying of the SmartPill was studied in the fasting period by ingesting the SmartPill with radiolabelled water. The SmartPill emptied from the stomach within 6 h in 14 of 15 subjects. SmartPill pressure recordings showed high amplitude phasic contractions prior to emptying. SmartPill gastric residence time (261 ± 22 min) correlated strongly with time to the first phase III MMC (239 ± 23 min; r = 0.813; P < 0.01) and correlated moderately with solid‐phase gastric emptying (r = 0.606 with T‐50% and r = 0.565 with T‐90%). Nine of 14 subjects emptied the capsule with a phase III MMC. In five subjects, the SmartPill emptied with isolated distal antral contractions. In five subjects ingesting only water, SmartPill gastric residence time (92 ± 44 min) correlated with the time to the first phase III MMC (87 ± 30 min; r = 0.979; P < 0.01). The non‐digestible SmartPill given with a meal primarily empties from the stomach with the return of phase III MMCs occurring after emptying the solid‐phase meal. However, in some subjects, the SmartPill emptied with isolated antral contractions, an unappreciated mechanism for emptying of a non‐digestible solid.

Gastroesophageal (GE) Scintiscanning to detect and Quantitate Ge Reflux

To evaluate the gastroesophageal (GE) scintiscan, a technique which detects and quantitates GE reflux, 30 patients with heartburn and a positive acid-reflux test and 20 normal control subjects were studied. Conventional diagnostic tests including barium esophagography, fluoroscopy, esophagogastroscopy, esophageal biopsy, acid perfusion testing, and esophageal manometry were performed on each patient with GE reflux. None of these techniques was sufficiently sensitive in detecting GE reflux. In contrast, GE reflux was visualized by scintiscanning in 27 out of 30 (90%) of patients. The GE reflux index was significantly greater in reflux patients, 11.7 +/- 1.8%, compared to controls 2.7 +/- 0.3%. These studies suggest that GE scintiscanning can detect GE reflux accurately, rapidly, noninvasively, and with greater sensitivity than other diagnostic techniques. In addition, it can be employed to quantitate GE reflux.

Effect of gastric acid suppressants on human gastric motility

Background—The effect of histamine H2receptor antagonists on gastric emptying is controversial. Aims—To determine the effects of ranitidine, famotidine, and omeprazole on gastric motility and emptying. Patients and methods—Fifteen normal subjects underwent simultaneous antroduodenal manometry, electrogastrography (EGG), and gastric emptying with dynamic antral scintigraphy (DAS). After 30 minutes of fasting manometry and EGG recording, subjects received either intravenous saline, ranitidine, or famotidine, followed by another 30 minutes recording and then three hours of postprandial recording after ingestion of a radiolabelled meal. Images were obtained every 10–15 minutes for three hours to measure gastric emptying and assess antral contractility. Similar testing was performed after omeprazole 20 mg daily for one week. Results—Fasting antral phase III migrating motor complexes (MMCs) were more common after ranitidine (9/15 subjects, 60%), famotidine (12/15, 80%), and omeprazole (8/12, 67%) compared with placebo (4/14, 29%; p<0.05). Postprandially, ranitidine, famotidine, and omeprazole slowed gastric emptying, increased the amplitude of DAS contractions, increased the EGG power, and increased the antral manometric motility index. Conclusions—Suppression of gastric acid secretion with therapeutic doses of gastric acid suppressants is associated with delayed gastric emptying but increased antral motility.

Treatment of idiopathic gastroparesis with injection of botulinum toxin into the pyloric sphincter muscle.

OBJECTIVES:We aimed to determine if botulinum toxin injection into the pyloric sphincter improves gastric emptying and reduces symptoms in patients with idiopathic gastroparesis.METHODS:Patients with idiopathic gastroparesis not responding to prokinetic therapy underwent botulinum toxin (80–100 U, 20 U/ml) injection into the pyloric sphincter. Gastric emptying scintigraphy was performed before and 4 wk after treatment. Total symptom scores were obtained from the sum of eight upper GI symptoms graded on a scale from 0 (none) to 4 (extreme).RESULTS:Ten patients were entered into the study. The mean percentage of solid gastric retention at 4 h improved from 27 ± 6% (normal < 10%) before botulinum toxin injection into the pylorus to 14 ± 4% (p = 0.038) 4 wk after treatment. The symptom score decreased from 15.3 ± 1.7 at baseline to 9.0 ± 1.9 (p = 0.006) at 4 wk, a 38 ± 9% decrease. Improvement in symptoms tended to correlate with improved gastric emptying of solids (r = 0.565, p = 0.086).CONCLUSIONS:This initial pilot study suggests that botulinum toxin injection into the pylorus in patients with idiopathic gastroparesis improves both gastric emptying and symptoms.

Scintigraphic evaluation of gastric emptying

There has been recent, renewed interest in studies of gastric emptying due in part to the introduction of new therapies for peptic ulcer diseases and attempts to better understand gastric physiology. Of the methods available for studying gastric emptying patterns, nuclear medicine techniques are optimal due to their noninvasive character, reproducibility and quantitative ability. The modulation of gastric emptying is multifactorial, and includes motor control, electrical activity, hormonal influences, and the composition of the meal itself: liquid vs solid; protein, carbohydrate and fat content; fiber or particle size; osmolality; pH; and pharmacologic agents. Because of the ease of performing gastric emptying studies using radiolabeled physiologic meals, these tests are being employed with increasing frequency in the evaluation of patients with disorders such as diabetic gastroparesis, postgastrectomy gastroparesis or dumping syndrome, and in the study of normal gastric physiology in man. Present data suggests that combined liquid-solid, dual radionuclide studies afford the greatest information regarding simultaneous gastric emptying patterns of liquid and solid components of a meal, and that single radionuclide, solid tests of gastric emptying are the more sensitive technique for determining subtle abnormalities of gastric emptying, when only a single tracer is employed.

Gastroparesis-Related Hospitalizations in the United States: Trends, Characteristics, and Outcomes, 1995–2004

OBJECTIVESGastroparesis is an increasingly recognized disorder. Its prevalence in the United States is unknown. We examined the trends, characteristics, and outcomes of gastroparesis-related hospitalizations during 1995–2004.METHODSThe publicly available Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) comprises a nationally representative sample of 5–8 million hospitalizations per year. Gastroparesis-related hospitalizations were identified using the International Classification of Diseases (ICD-9) code 536.3 and compared with other hospitalizations. Multivariate regressions were used to compare for differences in the outcomes including length of stay, total charges, and in-hospital deaths.RESULTSHospitalizations with gastroparesis as the primary diagnosis increased from 3,977 in 1995 to 10,252 in 2004 (+158%) and hospitalizations with gastroparesis as the secondary diagnosis increased from 56,726 to 134,146 (+136%). These compared to smaller changes in diabetes-related hospitalizations (+53%), all hospitalizations (+13%), and hospitalizations with gastroesophageal reflux disease (GERD), gastric ulcer, gastritis, or nonspecific nausea/vomiting as the primary diagnosis (−3% to +76%). Of the five upper gastrointestinal conditions studied as the primary diagnosis, gastroparesis had the longest length of stay (+15.4% to +66.2%, all P < 0.001) and the highest or second highest total charges (−7.2% to +60.6%, all P < 0.01) in 2004, with similar results in 1995.CONCLUSIONSThe number of gastroparesis-related hospitalizations has been increasing in the United States, suggesting an increasing prevalence of gastroparesis. The economic impact of gastroparesis-related hospitalizations is significant and increasing.

Abnormal gallbladder emptying in patients with gallstones

In this study, gallbladder and gastric emptying were compared in 15 normal subjects and 15 patients with gallstones. A noninvasive technique which uses two gamma-emitting radiopharmaceutical agents to image the gallbladder and stomach simultaneously was employed. Technetium-99m-HIDA was used as a gamma-emitting marker for the gallbladder and indium-111-DTPA was mixed with a standard liquid meal in order to stimulate gallbladder emptying and to measure gastric emptying. In patients with gallstones, gallbladder emptying was diminished significantly compared to normal subjects. In contrast, emptying of the stomach was normal. The gallbladder emptying responses to octapeptide of cholecystokinin, administered either as bolus or infusion doses, were similar in normal subjects and patients with gallstones. These studies suggest that gallbladder emptying may be abnormal in patients with gallstones. The explanation for this abnormality and its relationship to the development of gallstones has not been determined.