Gastric emptying in hyperemesis gravidarum and non-dyspeptic pregnancy.

BACKGROUND: Emesis and hyperemesis are significant problems associated with early pregnancy. However, gastric emptying of solids has never been studied during early pregnancy in humans. AIM: To investigate gastric emptying of solids in patients recovering from hyperemesis gravidarum and in non-dyspeptic pregnant women and to compare these results with a group of healthy non-pregnant women. METHODS: Fourteen patients with hyperemesis gravidarum, 10 non-dyspeptic pregnant women and 36 non-pregnant women in the first half of the menstrual cycle underwent a gastric emptying study. Seven non-pregnant women repeated the test in the post-ovulatory period. RESULTS: Gastric emptying of solids was not significantly delayed in non-dyspeptic pregnant women compared with non-pregnant women. The emptying rate tended to be impaired in the post-ovulatory period of the menstrual cycle. Solid emptying was significantly accelerated in patients recovering from hyperemesis gravidarum, correlating well with thyroid function in the latter group. CONCLUSION: Pregnancy in humans is not associated with decreased solid gastric emptying. In subjects recovering from hyperemesis gravidarum, solid emptying is increased, correlating well with thyroid function abnormalities. Nausea and vomiting in hyperemesis are therefore probably not due to upper gastrointestinal disorders.

Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis.

BACKGROUND & AIMS: Anti-tumor necrosis factor alpha monoclonal antibody treatment (infliximab) reduces clinical signs and symptoms in patients with Crohn's disease. The effects of infliximab on mucosal histopathologic abnormalities in Crohn's ileocolitis were studied. METHODS: Thirteen patients with steroid-refractory Crohn's disease were treated with a single infusion of infliximab (5-20 mg/kg), and 5 were treated with placebo. Ileal and colonic biopsy specimens of all patients were collected before and 4 weeks after therapy. Severity of inflammation was assessed by a histological score. Immunohistochemical stainings with antibodies against HLA-DR, CD68, tumor necrosis factor alpha, intercellular adhesion molecule 1, lymphocyte function-associated antigen, CD4, CD8, and interleukin 4 were performed. RESULTS: Total histological activity score was reduced significantly in both ileitis and colitis after infliximab. This is caused by a virtual disappearance of the neutrophils and a reduction of mononuclear cells. Mucosal architecture returned to normal in 4 patients at 4 weeks. The number of lamina propria mononuclear cells decreased because of a global reduction of CD4(+) and CD8(+) T lymphocytes and CD68(+) monocytes. Aberrant colonic epithelial HLA-DR expression completely disappeared. The percentage of intercellular adhesion molecule 1 and lymphocyte function-associated antigen 1-expressing and interleukin 4- and tumor necrosis factor-positive lamina propria mononuclear cells sharply decreased. CONCLUSIONS: Infliximab dramatically decreases histological disease activity in Crohn's ileocolitis. Signs of active inflammation nearly disappear accompanied by a profound down-regulation of mucosal inflammatory mediators.

Gastric emptying of the liquid, solid and oil phase of a meal in normal volunteers and patients with Billroth II gastrojejunostomy.

BACKGROUND: The relationship between gastric emptying of different phases of a meal in humans has only been partly studied in normal subjects and in patients with previous gastric surgery. METHODS: In the present study, gastric emptying of the liquid, solid and oil phase and the relationship between the phases was evaluated in 10 normal control subjects and in seven patients with Billroth II gastrojejunostomy using breath test technology. RESULTS: Gastric emptying in normal subjects showed a clear separation between the emptying of the liquid, solid and oil phase. In healthy volunteers, the liquid phase emptied in the same manner in the presence of a solid phase as in the presence of an oil phase. In contrast, the oil phase emptied more slowly with liquids than with solids. The emptying rate of the oil phase was not only inversely related to the amount administered but was also dependent on its chemical composition. Gastric emptying in patients with Billroth II gastroenterostomy was characterized by a complete loss of discrimination between the different phases of the meal, with an extremely fast emptying of the oil phase compared with normal control subjects. CONCLUSION: In normal subjects, the liquid, solid and oil phase of a meal are emptied differently. In patients with Billroth II gastrojejunostomy, dumping of the oil phase is the most pronounced difference from the normal physiology of gastric emptying. This could be one of the reasons why Billroth II gastrectomy may be associated with fat malabsorption.

Gastric emptying rate of solids in patients with nonulcer dyspepsia.

The underlying role of motility disorders and delayed gastric emptying in nonulcer dyspepsia is still questioned. This study aimed to determine the role of the gastric emptying rate of solids in patients with nonulcer dyspepsia. By means of breath test technology, gastric emptying results of 344 consecutive patients with nonulcer dyspepsia were compared with those of 70 normal healthy volunteers. Although gastric emptying was significantly delayed in patients with nonulcer dyspepsia compared with normal volunteers, there was a great overlap between the two groups. Using 5-95% confidence intervals of the control group in about 30% of the patients with nonulcer dyspepsia gastric emptying was delayed. No correlation was found between gastric emptying rate and age, weight, height, or sex of the subjects in both groups. These findings suggest that, apart from gastric emptying, other mechanisms are very important in the etiology of nonulcer dyspepsia.

Gastric emptying and Helicobacter pylori infection in duodenal ulcer disease.

The pathogenetic link between Helicobacter pylori gastritis and duodenal ulcer is still unknown. Fast gastric emptying of liquids might be important in the pathogenesis of gastric metaplasia of the duodenum and duodenal ulcer through an increased exposure of the duodenum to gastric acid. In H. pylori-infected subjects, an abnormal gastric emptying could affect urea breath test results and correlate with histological gastritis. This study was performed to evaluate the gastric emptying of liquids in duodenal ulcer patients with H. pylori infection and the possible relation between the bacterial load, gastric emptying, and urea breath test results. Seventeen duodenal ulcer patients with H. pylori gastritis and 15 healthy volunteers were studied by a [14C]octanoic acid and [13C]urea breath test to evaluate gastric emptying rate and H. pylori status simultaneously. Endoscopy with antral biopsies were performed in all duodenal ulcer patients. Duodenal ulcer patients with H. pylori infection have a normal liquid gastric emptying that is unrelated with histological severity of gastritis. The urea breath test results and the gastric emptying parameters do not correlate with histology. A significant correlation between the gastric emptying and the urea hydrolysis rate is found. It is concluded that H. pylori infection and duodenal ulcer disease is not associated with abnormally fast liquid gastric emptying, and this finding should be taken into account when a casual link between H. pylori infection and duodenal ulcer disease is searched for. The correlation between gastric emptying and urea hydrolysis rate explains why no conclusions on intragastric bacterial load can be drawn from the urea breath test results.

Relation between gastric emptying rate and rate of intraluminal lipolysis.

The variable gastric emptying rate of a test meal is one of the major problems in evaluating accurately gastrointestinal physiological functions beyond the stomach. The aim of this study was to evaluate the effect of the gastric emptying rate on the rate of intraluminal lipolysis. Thirty four subjects without pancreatic disease (21 with a normal gastric emptying and 13 with a known slow gastric emptying) and 14 subjects with pancreatic disease (four without and 10 with pancreatic insufficiency) were studied using a dual labelled breath test. The test meal consisted of one egg, 60 grams of white bread, 10 grams of margarine, and 150 ml of water (350 kcal). The egg yolk was labelled with 91 mg of 13C-octanoic acid, the margarine was labelled with 296 kBq of distearyl-2-14C-octanoyl-glycerol. Breath samples were taken every 15 minutes during six hours and analysed for 13CO2 and 14CO2 content. The gastric emptying rate of the meal was evaluated by the gastric emptying coefficient, the half emptying time, and the lag phase; the rate of intraluminal lipolysis was evaluated by the six hours cumulative 14CO2 excretion. Despite a clear distinction in the rate of intraluminal lipolysis, no difference could be detected in gastric emptying rate of the test meal between subjects without and with pancreatic disease. In subjects with pancreatic insufficiency, intraluminal hydrolysis was the rate limiting process in fat assimilation; in patients without pancreatic insufficiency, however, gastric emptying could be rate limiting. Therefore, patients with known slow gastric emptying, displayed a significantly decreased rate of intraluminal lipolysis compared with normal controls. This decrease could be corrected for accurately using a correction factor based on the gastric emptying coefficient. In conclusion, the combined 13C-octanoic acid and 14C-mixed triglyceride breath test permits the measurement of gastric emptying rate and intraluminal lipolysis simultaneously in a minimally invasive way. Correction of intraluminal lipolysis rate for gastric emptying rate of the given test meal permits evaluation of fat assimilation rates in a physiological way regardless of gastric emptying disorders.

Relation between gastric emptying rate and energy intake in children compared with adults.

Measurement of gastric emptying rate of solids in children is difficult because the available methods are either invasive or induce a substantial radiation burden. In this study the newly developed 13C octanoic acid breath test was used to examine the gastric emptying rate of solids and milk in healthy children and to compare gastric emptying in children and adults. Fifteen healthy children and three groups of nine healthy adults were studied, using three different test meals labelled with 50 mg of 13C octanoic acid: a low caloric pancake (150 kcal), a high caloric pancake (250 kcal), and 210 ml of milk (134 kcal). Breath samples were taken before and at regular intervals after ingestion of the test meal, and analysed by isotope ratio mass spectrometry. The gastric emptying parameters were derived from the 13CO2 excretion curves by non-linear regression analysis. No significant difference was found between children and adults in the emptying rate of the low caloric solid test meal. In children as well as in adults, increasing the energy content of the solid meal resulted in a significantly slower emptying rate. The milk test meal, however, was emptied at a faster rate in adults and at slower rate in children compared with the low caloric solid test meal. Moreover, the emptying rate of milk in children was significantly slower than in adults. In conclusion, a similar gastric emptying rate of solids but a slower emptying of full cream milk was shown in children of school age compared with adults, using the non-radioactive 13C octanoic acid breath test.

Influence of octreotide on the gastric emptying of solids and liquids in normal healthy subjects.

BACKGROUND: The effects of octreotide on small intestinal and gall-bladder motility are well established. However, the influence of octreotide on the gastric emptying rate of both solids and liquids in normal healthy volunteers has never been studied. METHODS: In nine healthy subjects, the gastric emptying rate of liquids and solids was studied in basal condition and 30 min after subcutaneous administration of 50 micrograms of octreotide, using the combined 14C-octanoic acid/13C-glycine breath test. To determine if the results were entirely due to alterations in gastric emptying, 14/13CO2 excretion rates of intraduodenally administered 14C-octanoic acid and 13C-glycine were measured in basal condition and after subcutaneous injection of octreotide. RESULTS: After subcutaneous injection of octreotide, the gastric emptying rate of solids was decreased in all but one subject, while the gastric emptying rate of fluids was decreased in all subjects. Nevertheless, 14/13CO2 excretion rates in the breath after intraduodenally administered 14C-octanoic acid and 13C-glycine, were similar in basal condition and after subcutaneous injection of octreotide. CONCLUSIONS: Subcutaneous injection of a single physiological dose of octreotide induces a marked delay in the gastric emptying of solids and liquids in young healthy volunteers. The combined 14C-octanoic acid/13C-glycine breath test is very well suited to demonstrate this effect, since the absorption and metabolism of octanoic acid and glycine remains unaltered after administration of octreotide.

[*C]octanoic acid breath test to measure gastric emptying rate of solids.

We have developed a breath test to measure solid gastric emptying using a standardized scrambled egg test meal (250 kcal) labeled with [14C]octanoic acid or [13C]octanoic acid. In vitro incubation studies showed that octanoic acid is a reliable marker of the solid phase. The breath test was validated in 36 subjects by simultaneous radioscintigraphic and breath test measurements. Nine healthy volunteers were studied after intravenous administration of 200 mg erythromycin and peroral administration of 30 mg propantheline, respectively. Erythromycin significantly enhanced gastric emptying, while propantheline significantly reduced gastric emptying rates. We conclude that the [*C]octanoic breath test is a promising and reliable test for measuring the gastric emptying rate of solids.

Combined carbon-13-glycine/carbon-14-octanoic acid breath test to monitor gastric emptying rates of liquids and solids.

UNLABELLED: The aim of the present study was to develop a dual-carbon-labeled breath test for simultaneously measuring gastric emptying rates of liquids and solids with significantly less radiation burden to the patient than the radioscintigraphic technique. METHODS: A test meal was used in which the liquid phase was labeled with two markers, i.e., 3.7 MBq of 111In-DTPA and 100 mg of 13C-glycine; the solid phase also was dually labeled with 110 MBq of 99mTc-albumin colloid and 74 kBq of 14C-octanoic acid. Simultaneous radioscintigraphic and breath-test measurements were performed in 27 subjects, 10 normal controls and 17 patients with dyspeptic symptoms. Mathematic analysis of the excretion rate of labeled CO2 allowed the definition of four parameters, i.e., the gastric emptying coefficient, the gastric half-emptying time, the peak excretion time and the lag phase. RESULTS: There was a good to excellent correlation between the gastric emptying coefficient and the scintigraphic half-emptying time (r = 0.74 for liquids and r = 0.88 for solids), between the half-emptying time determined by breath test and the scintigraphic half-emptying time (r = 0.91 for liquids and r = 0.92 for solids), between the peak excretion time and the scintigraphic half-emptying time (r = 0.91 for liquids and r = 0.96 for solids) and between the lag phase of solid emptying determined by both techniques (r = 0.89). CONCLUSION: The dual carbon-labeled breath test is a valid, minimally invasive technique to measure the gastric emptying rate of both liquids and solids.

Pharmacological modulation of gastric emptying rate of solids as measured by the carbon labelled octanoic acid breath test: influence of erythromycin and propantheline.

The *C (13C or 14C) labelled octanoic acid breath test was recently developed to measure the gastric emptying rate of solids. This study aimed to investigate whether it is sensitive enough to detect pharmacologically induced changes in the gastric emptying rate. Nine healthy volunteers were studied in basal condition, after intravenous administration of 200 mg erythromycin, and after peroral administration of 30 mg propantheline. Erythromycin significantly enhanced gastric emptying in all subjects, with an increase of the gastric emptying coefficient (p = 0.0043) in eight of nine and a fall in both the gastric half emptying time (p = 0.0020) and the lag phase (p = 0.0044) in all nine. Propantheline significantly reduced the gastric emptying rate, with a decreased gastric emptying coefficient (p = 0.0007) and an increased gastric half emptying time (p = 0.0168) in all subjects, but no change in the lag phase (p = 0.1214). Further mathematical analysis showed that breath sampling at 15 minutes intervals over a four hour period is recommended to guarantee accuracy and the discriminative value of the breath test in various gastric emptying patterns. In conclusion the *C labelled octanoic acid breath test is sufficiently sensitive to show pharmacologically induced changes of gastric emptying rates of solids.

Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test.

BACKGROUND: The aim of the present study was to develop a breath test for measuring gastric emptying rate of solids that would induce less radiation exposure than radioscintigraphy and would be applicable to field testing. METHODS: A test meal was used in which [14C]-octanoic acid was mixed with egg yolk and prepared as a scrambled egg. The test meal was labeled with a second marker, 99mTc-albumin colloid, and simultaneous radioscintigraphic and breath test measurements were performed in 36 subjects, 16 normal controls, and 20 patients with dyspeptic symptoms. Mathematical analysis of the excretion rate of labeled CO2 resulted in the definition of three parameters, i.e., gastric emptying coefficient, gastric half-emptying time, and lag phase. RESULTS: There was an excellent correlation between the gastric emptying coefficient and the scintigraphic half-emptying time (r = -0.88); between the half-emptying time determined by the breath test and the scintigraphic half-emptying time (r = 0.89); and between the lag phases determined by scintigraphy and those determined by breath test (r = 0.92). 14C can be replaced by 13C for labeling the octanoic acid used in the breath test. CONCLUSIONS: It is concluded that the octanoic acid breath test is a reliable noninvasive test to measure gastric emptying rate of solids.

Mixed triglyceride breath test: a noninvasive test of pancreatic lipase activity in the duodenum.

A synthetic "mixed" triglyceride (1,3-distearoyl,2[13C]octanoyl glycerol), having a medium-chain fatty acid in the 2 position, was evaluated as a substrate for an exocrine pancreatic function test by comparing the 13CO2 breath excretion with the lipase output in the duodenum in 25 normal subjects, 29 patients with pancreatic disease, and 22 patients with steatorrhea of nonpancreatic origin. Excellent correlation was found in normal subjects and patients with pancreatic disease (r = 0.89) between lipase output in the duodenum and the 6-h cumulative 13CO2 excretion in breath, indicating that the mixed triglyceride breath test is an excellent noninvasive test of pancreatic lipase activity in the duodenum. As a test of exocrine pancreatic insufficiency, it has a sensitivity of 0.89 and a specificity of 0.81.