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Biomedical subjects

G Vantrappen

Publications and source records attributed to G Vantrappen.

At least 145 records · Page 8Linked to original sources

Effect of rioprostil, 600 micrograms, on the interdigestive myoelectrical activity of the humans small intestine.

The effect of rioprostil, a PGE1 analogue, on the interdigestive motility of the upper human small intestine was investigated in 8 normal volunteers in a double-blind, placebo-controlled study. Rioprostil was administered intraduodenally in a dose of 600 micrograms. The myoelectrical activity was recorded simultaneously at 8 different levels of the jejunum, at 10 cm intervals. Rioprostil, 600 micrograms, does not disrupt the migrating motor complex (MMC) and does not change the characteristics of phase 3 of the MMC, except for an increased propagation velocity. The main effect of rioprostil, 600 micrograms, is a marked inhibition of phase 2 contractions without induction of propulsive motility patterns during phase 2. This may explain why rioprostil in a dose of 600 micrograms is not markedly diarrheogenic in man.

Adult↗

Gastro-oesophageal reflux disease, an important cause of angina-like chest pain.

Angina-like chest pain in patients with coronary arteriography raises difficult diagnostic problems. The pain may be due to microvascular angina (or syndrome X). It is postulated that during the typical angina of these patients, the ST segment shifts on exercise electrocardiogram and the abnormal electrophysiologic tests on cardiac catheterisation are due to a decreased coronary flow reserve related to microvascular abnormalities. Angina-like chest pain may also be of oesophageal origin. Gastro-oesophageal reflux and oesophageal motility disorders are the two commonest oesophageal abnormalities held responsible for the pain. Recent observations suggest that sensitivity of the oesophagus to several stimuli may be another important cause of chest pain of oesophageal origin. This condition is called irritable oesophagus. Twenty-four hour pH- and pressure-recording is at present the best way to reach a specific diagnosis about the nature of the oesophageal abnormality.

Angina Pectoris↗

Measurement of 13C-glucose oxidation rate using mass spectrometric determination of the CO2: Ar ratio and spirometry.

A new method was developed and validated for measuring the CO2 concentration in the breath by mass spectrometric analysis. Argon, an inert gas that is present in air in a constant concentration of 0.923%, was used as an internal standard. By determining the ratio of CO2 (mass 44) to Ar (mass 40) in a breath sample, it was possible to read the CO2 concentration from a standard curve, relating CO2 concentration to CO2: Ar ratio. By combining mass spectrometric determination of CO2 concentration in breath with spirometric measurement of expired volumes, the CO2 production was determined in 67 subjects at rest. The mean value was 8.86 mmol kg-1 h-1, but there was considerable interindividual variation. This new method was applied to glucose oxidation studies in 10 normal subjects, 10 post-gastrectomy patients and 7 obese type II diabetic subjects. Measurement of the 13CO2 exhalation with quantitative determination of CO2 production allowed more accurate determination of the CO2 excretion rate in relation to blood levels of glucose, insulin and free fatty acids than assuming the constant CO2 production of 300 mmol unit body surface -1 h-1 or 9 mmol kg-1 h-1. It also resulted in a better discrimination between normal subjects and diabetics.

Adult↗

Measurement of the rate of assimilation of oligo- and polysaccharides by 13CO2 breath tests and isotope ratio mass spectrometry.

13CO2 breath tests were developed to study the digestion and absorption of (13C)lactose, (13C)sucrose, (13C)starch and (13C)glucose using naturally enriched substrates. Measurements of 13CO2 breath excretion were done in steady state conditions in order to study the assimilation rate of these carbohydrates as reflected by their oxidation rate. The reproducibility of the tests in the same individual was excellent. The excretion rate of 13CO2 after administration of (13C)glucose and (13C)sucrose was identical, while the excretion rate of 13CO2 after lactose was somewhat slower, although not significantly. In contrast, the excretion of 13CO2 after 50 g (13C)starch was significantly slower than the 13CO2 excretion after 50 g (13C)glucose or 50 g (13C)disaccharides. As the monosaccharide constituents used in this study have comparable absorption rates, the delayed excretion of 13CO2 after a (13C)starch load must be due to a slower digestion. It is concluded that (i) digestion and not monosaccharide transport is the rate-limiting step in the assimilation of polysaccharides and (ii) that the present breath tests are suitable to study the digestibility of naturally labelled carbohydrates.

Adult↗

Intestinal nodular lymphoid hyperplasia in patients with common variable immunodeficiency: local accumulation of B and CD8(+) lymphocytes.

Common variable immunodeficiency (CVI) with hypogammaglobulinemia is often complicated by nodular lymphoid hyperplasia of the intestine. In this study the lymphoid constituents of intestinal nodular hyperplasia of five CVI patients were characterized with monoclonal antibodies. Few CD4(+) but abundant CD8(+) T lymphocytes were found around the follicles. The follicles were populated mainly by B cells expressing surface IgM. A few cells in the lamina propria expressed Leu7. No intracytoplasmic immunoglobulin-containing plasma cells were seen. Peyer's patches in gut biopsies from controls were also composed of follicles with B lymphocytes. A ring of T lymphocytes surrounded the follicles. CD4(+) helper cells largely outnumbered CD8(+) cells in this ring. Moreover, plasma cells were present in the lamina propria and the mixed cell zone covering the follicles. In peripheral blood of the patients, B cells were present in normal proportions but they could not be induced to produce IgG in vitro by T cell-dependent (pokeweed mitogen) or T cell-independent (Staphylococcus aureus Cowan I) mitogens. In two of the patients, IgM production could be induced in vitro. Peripheral blood T cells were predominantly CD8(+) in three of the five patients, and in these same patients an increase in suppressor-cell activity of peripheral blood T cells on immunoglobulin production was observed. The data demonstrate a block in B-cell differentiation in the gut and in peripheral blood. Whether the local increase in CD8(+) cells in the nodular lymphoid hyperplasia is a primary event or is secondary to chronic immune stimulation and whether it contributes to local inhibition of B-cell differentiation remain to be investigated.

Adult↗

Cisapride stimulates propulsive motility patterns in human jejunum.

The effects of cisapride on upper gut motility were studied in seven healthy volunteers by means of a novel intraluminal electromyographic technique in a placebo-controlled study. In the interdigestive state, cisapride (10 mg intravenous bolus injection) markedly increased the number of spike bursts. The most obvious effect was observed during the first 5-min period when a nonmigrating phase-3-like activity (stationary phase 3) occurred, which lasted for 2.6 +/- 0.4 min. This initial pattern was followed by an intense phase 2 activity, characterized by a 10-fold increase in the number of groups of repetitive spike bursts and a sixfold increase in the number of ultrarapid single propagated spike bursts (ultrarapid peristaltic rushes). Cisapride induces in the human upper gut a remarkable pattern of aborally propagated (peristaltic) contractions, which are very likely responsible for the active propulsion of intestinal contents in the interdigestive state.

Adult↗

Changes in small intestinal epithelial expression of MHC class II antigen after terminal ileal resection for Crohn's disease.

Aphthous lesions in the neoterminal ileum from patients operated for Crohn's disease are an early sign of recurrence that can be identified during ileocolonoscopy. The origin of these lesions was studied in nine patients treated by terminal ileal resection and right hemicolectomy for complicated Crohn's disease. During surgery the neoterminal ileum was turned inside out, the mucosa was carefully inspected and two large mucosal biopsies were obtained. The same procedure was carried out in seven patients operated for other diseases. Four to six months after surgery endoscopy of the neoterminal ileum was carried out and multiple biopsies were obtained from the neoterminal ileum. Another follow-up colonoscopy with biopsies was carried out one year after the operation. The operative specimens and the per- and postoperative biopsies were submitted to routine microscopy and immuno- and enzyme-histochemistry. None of the Crohn's patients had macroscopic lesions in the neoterminal ileum at operation and only one had microscopic signs of inflammation and a positive section margin. Four-six months after operation all Crohn's patients had active aphthous lesions in a 5-20 cm segment of the neoterminal ileum at endoscopy. Biopsies taken at this time showed microscopic features which were not observed in biopsies from control subjects: an increase of HLA-DR+, ATPase+ dendritic cells in the ileal mucosa and a defective expression of MHC class II antigens by the small intestinal epithelial cells. MHC class II expression by the small intestinal epithelial cells returned towards normal after one year.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

Omeprazole (40 mg) is superior to ranitidine in short-term treatment of ulcerative reflux esophagitis.

The efficacy and safety of omeprazole, 40 mg once daily for four to eight weeks of treatment, were studied in 61 patients with ulcerative reflux esophagitis. A double-blind controlled study design was used, and the patients were randomly allocated to treatment with either omeprazole 40 mg once daily or ranitidine 150 mg twice daily. Endoscopy was performed prior to inclusion into the study, after four weeks and, if unhealed, again after eight weeks. Healing of esophagitis was defined as complete disappearance of all esophageal ulcerations. Symptoms were recorded before entry, after four weeks, and again after eight weeks in unhealed patients. Fifty-one patients were included in the per-protocol analysis at day 29, and 50 patients at day 57. The healing rate after four weeks of treatment was 22 of 26 patients (85%) treated with omeprazole and 10 of 25 patients (40%) treated with ranitidine (P less than 0.001). The corresponding figures after eight weeks were 24 of 25 (96%), and 13 of 25 (52%) (P less than 0.001). These results were confirmed in the intent-to-treat analysis. Patients treated with omeprazole showed a significantly faster and more profound relief in heartburn than patients treated with ranitidine: 85% had no heartburn after four weeks of treatment with omeprazole compared to 24% in patients treated with ranitidine (P = 0.00007). The percentage of patients who were free of all reflux symptoms was significantly greater in the omeprazole-treated group as compared to the ranitidine-treated group (62% and 12% respectively; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of different calcium modulators on motilin-induced contractions of the rabbit duodenum. Comparison with acetylcholine.

Motilin and acetylcholine (ACh) have a direct contractile effect on rabbit small intestinal smooth muscle. To explore the role of calcium influx in these contractions, we studied the effect of extracellular calcium concentration and of calcium antagonists on the response of longitudinal muscle preparations from rabbit duodenum. Motilin- (10(-7) M) and ACh- (10(-4) M)-induced contractions were abolished in Ca2+-depleted medium. ACh (10(-4) M) or motilin (10(-8) and 10(-7) M) increased the contractile response to added Ca2+ to 130 +/- 6%, 129 +/- 10% and 145 +/- 5% of the maximal response to Ca2+ added alone (10 mM in a cumulative concentration response curve). The sensitivity to Ca2+ was greater in the presence of ACh and motilin (EC50 = 1.0 and 1.1 mM Ca2+) than in the absence of any agonist (1.7 mM). In cumulative concentration response (CCR) curves for motilin and ACh, pD2'-values were 7.0 and 6.6 for diltiazem, 8.4 and 7.8 for verapamil (two calcium entry blockers), 5.6 and 5.2 for TMB-8 (an inhibitor of intracellular calcium), 5.3 and 5.2 for TFP (a calmodulin-antagonist). All CCR-curves showed metactoid-like action of the antagonistic drugs. We conclude that ACh and motilin cause calcium to enter the smooth muscle cell. They are probably operating via separate channels, and use a mechanism which differs from K+-induced influx. Intracellular calcium stores appear to play a minor role in these contractions.

Acetylcholine↗

Comparison of motilin binding to crude homogenates of human and canine gastrointestinal smooth muscle tissue.

Pharmacological studies indicate that in man and in rabbit, but not in dog, motilin has a direct influence upon gastrointestinal smooth muscle. In accordance with this hypothesis we have presented direct biochemical evidence for the presence of motilin receptors on rabbit smooth muscle tissue. We have now extended our studies to human and canine tissue. Tissue homogenates were studied in binding experiments with iodinated porcine [Leu13]motilin and iodinated canine motilin. It was ascertained that the iodination procedure had little effect on the biological activity of the porcine analogue. In the human antrum specific binding of the iodinated porcine analogue was only found in the smooth muscle layer. It was absent in mucosal or serosal preparations. At 30 degrees C and pH 8.0, binding was maximal after 60 min of incubation, and was reversed by the addition of unlabeled porcine motilin. Binding was enhanced in the presence of calcium and magnesium ions. At a concentration of 10 mM MgCl2, binding was 220% of the binding observed in its absence. Displacement studies with synthetic porcine [Leu13]motilin or synthetic natural porcine motilin indicated a dissociation constant (Kd) of 3.6 +/- 1.6 nM and a maximal binding capacity (Bmax) of 77 +/- 9 fmol per mg protein. Canine motilin displaced iodinated porcine motilin with an apparent Kd of 2.2 +/- 0.9 nM. Compared to antral binding, receptor density decreased aborally and orally, and was absent in jejunum and ileum. In dog specific binding could not be demonstrated in antral and duodenal tissue, neither with labeled porcine nor with labeled canine motilin. However, labeled canine motilin was equipotent to labeled porcine motilin in binding studies with human tissue: the dissociation constant was 0.9 +/- 0.6 nM. The present studies therefore demonstrate the existence of a specific motilin receptor in the antroduodenal region of the human gut. Apparently, such receptors are not present in the canine gut. Our data support the hypothesis that in the human gastrointestinal tract, the gastroduodenal area is motilin's target region.

Animals↗

Transendoscopic Doppler ultrasound: usefulness for diagnosis and treatment of vascular malformations.

Vascular malformations of the GI tract can be treated by thermal methods, including the YAG laser. The diagnosis of these lesions is not always easy, and it is difficult to evaluate the completeness of therapy of these lesions. We investigated the value of Doppler ultrasound in this respect. The TVD-1 (Key Med) transendoscopic vascular detector using the 2.5 mm diameter probe emitting at 7 MHz, was used through standard endoscopes. Outputs were monitored through a loudspeaker, and imaged on an oscilloscope, or recorded on a mingograph. Diagnostic usefulness was studied in 64 vascular lesions, 36 in the colon and 28 in the upper GI tract in ten patients. A Doppler signal was detected in 75% of the lesions, including all lesions larger than 5 mm in diameter. Forty-five lesions in 13 patients were studied before and immediately after laser therapy. Three out of five patients in whom Doppler-positive lesions persisted after laser treatment rebled, as compared with 2 out of 8 patients with Doppler-negativity. Disappearance of the signal, however, may be transient, and is probably due to laser-induced edema. These results suggest that endoscopic Doppler ultrasound may have a role in the diagnosis and treatment of vascular anomalies of the GI tract, and should stimulate further research.

Adult↗

Symptomatic gastrointestinal metastases from malignant melanoma. A clinical study.

Gastrointestinal metastases from malignant melanomas are not uncommon but rarely cause symptoms. We report six patients hospitalized because of gastrointestinal (GI) symptoms due to metastases from a primary extraintestinal melanoma. The clinical symptoms are nonspecific and include abdominal pain, weight loss, and occasionally GI bleeding. The diagnosis may, therefore, be unduly delayed, even though the prognosis of GI metastases from malignant melanomas is poor and the results of adjuvant chemotherapy, as well as of surgery, are not encouraging. Screening of patients with malignant melanoma for GI metastases is not yet routinely indicated, but should be considered in prospective studies evaluating adjuvant therapy.

Aged↗

Estrogen-progesterone treatment of Osler-Weber-Rendu disease.

A 56-year-old woman with Osler-Weber-Rendu disease had longstanding iron deficiency anemia from recurrent melena. Since neither laser photocoagulation nor surgery were successful in stopping the increasing transfusion need, combined estrogen-progesterone therapy was started. Except for slight bleeding from a temporary ileostomy, the bleeding and need for transfusion terminated promptly. This experience confirms that estrogen-progesterone therapy may promote cessation of bleeding gastrointestinal telangiectasias and indicates the need for controlled investigations.

Estradiol Congeners↗

The effect of long-term fibre and starch intake by man on faecal bile acid excretion.

Parameters of bile acid metabolism were studied in two populations with different dietary fibre and starch intake over a period of at least 5 years. Subjects with a high fibre and starch intake have significant increases in faecal wet weight (288.5 g day-1 vs. 136.1), faecal dry weight (39.3 g day-1 vs. 20.2), faecal bile acid excretion (393.0 mg day-1 vs. 115.4) and faecal bile acid:faecal dry weight ratio (13.6 vs. 5.8). There was no difference in bowel transit time measured with 3H-PEG 4000 as marker of the liquid phase. The cumulative 14CO2 excretion during the bile acid breath test was higher in the high-fibre group, compared with the low-fibre group (4.6% dose cumulative at 8 h vs. 2.5%). Serum triglyceride and cholesterol levels were comparable in both groups. It is suggested that increased faecal weight and bile acid secretion is due to the synergic effect of high fibre and starch intake upon colonic bacterial proliferation.

Adult↗

Cisapride restores the decreased lower oesophageal sphincter pressure in reflux patients.

The effect of the new prokinetic drug cisapride on the resting lower oesophageal sphincter pressure and on the strength of peristaltic contractions was studied in 10 healthy controls and in 10 reflux patients with abnormally low (less than 10 mm Hg) basal lower oesophageal sphincter pressure. A slow intravenous injection of cisapride 10 mg significantly increased the sphincter pressure in the controls but even more in the patients in whom it almost doubled the resting lower oesophageal sphincter pressure of 8.7 (0.5) mm Hg to between 15 and 20 mm Hg for at least 90 min. Results are expressed as mean (SE). Cisapride also significantly increased the amplitude of peristaltic contractions in controls and reflux patients. Therefore, cisapride might be useful in the treatment of reflux.

Adult↗

Effect of the long-acting somatostatin analogue SMS 201-995 on small-intestinal interdigestive motility in the dog.

The long-acting somatostatin analogue SMS 201-995, also called Sandostatin, is used in the treatment of acromegaly and peptide-secreting tumors. Little is known about its effect on gut motility, although such an effect might be expected considering the spectrum of activities of its parent molecule, somatostatin. We have studied the effect on the interdigestive motility of intravenous boluses of 0, 0.1, 0.5, 1.5, and 5.0 micrograms/kg of this analogue in 10 dogs with bipolar electrodes implanted along the entire small bowel. All doses induced, within 5 min of administration, premature phase-3 activity that was isolated to one segment, normally progressive, or simultaneous (stationary) in all channels. Only low doses induced isolated phase 3, whereas the frequency of the induction of stationary phase 3 increased with higher doses. In the next cycle of the migrating motor complex the duration of phase 1 was increased, although the duration of the whole cycle was not changed. This cycle ended with mostly ectopic phase-3 activity. During phase 2 of the following cycle ultra-rapid rushes of spiking activity progressing at a speed of 25 +/- 3 cm/sec in the upper jejunum were regularly observed. Although this pattern occurs very rarely under control conditions, it was present in 20%, 80%, and 100% of the experiments after doses of 0.5, 1.5, and 5.0 micrograms/kg, respectively. We conclude that gastrointestinal side effects observed during administration of SMS 201-995 might be related to these motility effects, which warrant further investigation. SMS 201-995 may be a tool to study the mechanism of the induction of ultra-rapid rushes and of stationary phase 3.

Animals↗