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Biomedical subjects

G Vantrappen

Publications and source records attributed to G Vantrappen.

At least 19 recordsLinked to original sources

Irritable esophagus.

An esophageal origin of noncardiac chest pain is generally accepted if prolonged pH and pressure recordings show that the pain episodes correlate in time with acid reflux, esophageal motor abnormalities, or a combination of both, or if provocative testing (acid perfusion, edrophonium, balloon distention) is positive. Many patients with noncardiac chest pain of esophageal origin are said to have an irritable esophagus. Irritable esophagus has been defined in two ways. Some researchers suggest it is actually a lowered esophageal pain threshold, based on the finding that such patients feel chest pain at lower balloon volumes than controls during intraesophageal balloon distention; they are said to be hypersensitive to balloon distention. Hypersensitivity to an esophageal stimulus is generally found in patients with noncardiac chest pain of esophageal origin, and hypersensitivity to a single stimulus is one criterion for a diagnosis. Our group defines irritable esophagus as a condition in which several different stimuli result in the same type of chest pain. Accordingly, we have grouped patients with esophageal chest pain into three categories: (a) patients with an acid-sensitive esophagus, in whom spontaneous pain episodes can be related to acid reflux (with or without accompanying motor disorders), and/or the acid perfusion test is positive; (b) patients with a mechano-sensitive esophagus, in whom the spontaneous pain episodes can be related to motility disturbances (without reflux), and/or the edrophonium test or balloon distention test is positive; (c) patients with an irritable esophagus, in whom some spontaneous pain episodes are related to reflux, while others are related to abnormal motility (without reflux). The last group includes patients whose spontaneous chest pain is related to reflux, with a positive motility tests; whose pain is related to abnormal motility, with a positive reflux test; and patients with positive tests for both reflux and abnormal motility. Seven studies examined a total of 281 noncardiac chest pain patients using prolonged pH and pressure recordings and provocative tests. An acid-sensitive, a mechano-sensitive, or an irritable esophagus was found in 20%, 14%, and 24% of patients, respectively.

Chest Pain

Critique of the session on diagnostic testing.

During the session on diagnostic testing, various diagnostic tests used to identify the cause of chest pain were discussed. This critique of diagnostic assessments of the complex etiology of chest pain is presented as a contribution toward further investigation and clarification of this difficult clinical syndrome. The first step in the evaluation process is to exclude coronary artery disease. Patients with angina and normal coronary artery flow may have atypical disease, such as microvascular angina or syndrome X. The precise relationship between these disorders and esophageal disease or gastroesophageal reflux, as well as their possible involvement in chest pain of undetermined origin, requires further definition. A limitation of esophageal provocation tests is that they may identify the esophagus as the source of pain without determining the specific esophageal disorder that causes the pain. Problems associated with 24-hour pH and pressure monitoring include (a) poor correlation between reflux episodes and heartburn symptoms, (b) the lack of a good functioning swallowing signal, and (c) the huge amount of data that must be analyzed, along with shortcomings in computer-aided analysis. Nevertheless, the various available diagnostic tests can provide important information to the clinician.

Angina Pectoris

High-frequency diaphragmatic flutter: symptoms and treatment by carbamazepine.

Classic diaphragmatic flutter, a rare disorder associated with dyspnoea, thoracic or abdominal wall pain, and epigastric pulsations, is caused by involuntary contractions of the diaphragm with a frequency of 0.5-8.0 Hz. We have seen three patients with diaphragmatic flutter of higher frequency not associated with respiratory disease. The patients presented with longstanding oesophageal belching, hiccups, and retching, respectively. The diagnosis was established by the presence on electromyography of the diaphragm and scalene and parasternal intercostal muscles of repetitive discharges of 9-15 Hz. Spirographic tracings, especially those of volume or flow vs time, showed similar high-frequency oscillations superimposed on tidal respiratory movements. Treatment with carbamazepine 200-400 mg three times daily led to disappearance or great improvement of flutter and clinical symptoms in all three patients. The phenomenon was not seen in other patients with chronic hiccups or oesophageal belching or in patients without these symptoms who had undergone electromyography or spirography for other reasons. Thus, high-frequency diaphragmatic flutter seems to be a new disease entity. The response to carbamazepine, which suggests that the flutter causes the symptoms, requires further study.

Adult

Relation between slow-wave frequency and spiking activity during the migrating myoelectric complex in dogs.

The quantitative relation between slow-wave periods and spiking activity was evaluated in vivo in canine small intestine during the fasted state. Experiments were performed in three conscious dogs with three bipolar electrodes, implanted respectively 10, 25 and 40 cm beyond the ligament of Treitz. Digitized electrical recordings were automatically processed for the individual slow-wave periods and spike-burst intensities using a set of computer programs developed in our laboratory. A linear correlation existed between the degree of spiking activity and the average length of the preceding slow-wave period. The slopes of the regression lines were less steep for more distal electrodes. A second series of experiments showed that an increase in the slow-wave period precedes the onset of phase 3 of the migrating myoelectric complex and that a fall in slow-wave period precedes the end of phase 3. These data show that a low slow-wave frequency is accompanied by a facilitation of spiking activity, whereas shortening of the slow-wave period is accompanied by a decrease in spike burst intensity. This relation between slow-wave period and spiking activity shows an aboral trend that may be related to intrinsic slow-wave frequency.

Animals

Effects of acarbose on starch hydrolysis. Study in healthy subjects, ileostomy patients, and in vitro.

The effect of acarbose on hydrolysis of a pure starch meal was investigated in normal subjects and ileostomy patients by means of 13CO2 breath tests and blood glucose levels as parameters of absorption, and of H2 breath tests, serum acetate levels, and ileal loss of carbohydrate as parameters of malabsorption. Additional information on the effect of acarbose on alpha-amylase activity was obtained by in vitro experiments. Acarbose (200 and 400 mg) significantly delayed starch absorption. Serum acetate was found to be a less sensitive marker of malabsorption than breath H2 excretion. After intake of 50 g starch plus 400 mg acarbose, 23-71% of the starch load was lost in the ileostomy effluent, for a large part as starch. This suggests that acarbose considerably inhibits alpha-amylase, and not only brush-border enzymes. In vitro experiments confirm that an inhibition of two thirds of alpha-amylase activity can be expected from pharmacologically used doses of acarbose.

Acarbose

A wave of inhibition precedes primary peristaltic contractions in the human esophagus.

Animal studies have shown that primary esophageal peristalsis is preceded by a wave of inhibition spreading rapidly down the esophagus and lasting longer in more distal segments. In humans, its presence in the esophageal body cannot be demonstrated manometrically because of the absence of tone. To study deglutitive inhibition in humans, an artificial high-pressure zone was created by inflating an intraesophageal balloon to a critical level. The pressure changes at the interface between the balloon and the esophageal wall at various levels along the esophagus were measured. In this artificial high-pressure zone, deglutition induced a relaxation beginning simultaneously at various levels of the esophagus but lasting progressively longer in progressively more distal segments. Latency from onset of deglutition to onset of relaxation at 13 cm and 8 cm above the lower esophageal sphincter and at the lower esophageal sphincter was 0.06 +/- 0.19 seconds, 0.10 +/- 0.31 seconds, and 0.89 +/- 0.53 seconds, respectively; latency to contraction was 4.45 +/- 0.54 seconds, 6.04 +/- 0.79 seconds, and 9.14 +/- 1.04 seconds, respectively. This is the first direct evidence that deglutition produces in the human esophagus a wave of inhibition that precedes the primary peristaltic contraction.

Adult

Erythromycin accelerates gastric emptying by inducing antral contractions and improved gastroduodenal coordination.

Erythromycin has been shown to act as a motilin agonist by binding to motilin receptors on gastrointestinal smooth muscle and to improve the severely impaired gastric emptying in patients with diabetic gastroparesis. To elucidate the motor pattern that accounts for this accelerated emptying, the effect of 200 mg erythromycin vs. placebo on postprandial motility of the stomach and the upper small intestine was examined in 13 normal subjects. Erythromycin significantly increased the amplitude of the antral contractions during the 2-hour postprandial study period (maximal difference in mean amplitude of distal antral contractions between erythromycin and placebo recorded from 80 to 90 minutes after meal: 123 +/- 17 vs. 44 +/- 12 mm Hg; P less than 0.005). The total number of antral contractions was not affected, but the contractions could be recorded manometrically higher up in the stomach after erythromycin than after placebo (9-12 vs. 3-6 cm above the pylorus). Antroduodenal coordination was significantly improved during the first postprandial hour, and the first normal phase 3 of the migrating motor complex, indicating the reappearance of fasting motility, occurred earlier after erythromycin than after placebo (128.3 +/- 14.3 vs. 173.4 +/- 16.1 minutes; P less than 0.05). These changes in postprandial motility induced by erythromycin may well account for its accelerating effect on gastric emptying.

Adult

Major histocompatibility class II expression on the small intestinal nervous system in Crohn's disease.

Widespread alterations of the gut autonomic nervous system have been described in Crohn's disease. Immunohistochemistry shows that these alterations are associated with the expression of major histocompatibility (MHC) class II antigens (HLA-DR) on enteroglial cells in the ganglia of the submucous and myenteric plexuses and on the enteroglial sheaths of the nerve extensions. Neuronal cell bodies and extensions do not express MHC class II antigens. The class II expression is associated with the presence of UCHL1-positive T lymphocytes. MHC class II expression can also be found on endothelial cells and vascular smooth muscle cells but not on smooth muscle cells of the muscularis mucosae or propria. The intensity of MHC class II expression on the glial cells of the enteric nervous plexus and on endothelial cells correlates well with the intensity of class II expression on epithelial cells.

Adolescent

Effect of erythromycin on gastric motility in controls and in diabetic gastroparesis.

The effect of three doses of erythromycin on interdigestive gastrointestinal motility and on plasma motilin levels was studied in healthy volunteers and patients with diabetic gastroparesis. Abnormalities of interdigestive motility were observed in 40% of the patients. In healthy volunteers, 40 mg erythromycin elicited a premature phase 3 that started in the stomach. In contrast to the spontaneous gastric phase 3, this erythromycin-induced phase 3 was not accompanied by a motilin peak. In patients with diabetic gastroparesis, 40 mg erythromycin induced a premature phase 3 in three patients, no response in one patient, and a burst of antral contractions in another patient. Doses of 200 and 350 mg erythromycin elicited a burst of antral phase-3-like contractions in both volunteers and patients, which was not accompanied by a motilin peak. This phase-3-like activity did not migrate to the small intestine and was not followed by a phase 1, but by a prolonged period of antral contractile activity. The number and amplitude of antral contractions after 200 or 350 mg erythromycin were significantly higher than after 40 mg. The motor patterns induced by different doses of erythromycin offer potential therapeutic applications.

Adult

Effect of motilin on gastric emptying in patients with diabetic gastroparesis.

Erythromycin markedly accelerates gastric emptying, possibly because it acts as a motilin agonist. In the present study, the effect of an equipotent dose of motilin was tested. In six patients with severe diabetic gastroparesis, gastric emptying of liquids and solids was examined scintigraphically after motilin or placebo in a double-blind crossover study. Motilin (10 pmol.kg-1.min-1) or saline was infused over a 90-minute period starting 5 minutes before breakfast. Motilin markedly accelerated emptying. For liquids, the half-emptying time was reduced from 51 +/- 6 to 22 +/- 11 minutes (P less than 0.01) and for solids from 111 +/- 4 to 51 +/- 12 minutes (P less than 0.01). The mean increase in plasma motilin levels was 1315 +/- 342 pg/mL, corresponding to an effective infusion rate of about 4 pmol.kg-1.min-1. In the control experiments, basal motilin levels (173 +/- 17 pg/mL) were within the normal range but increased steadily postprandially, reaching 321 +/- 25 pg/mL at the end of the study period, probably reflecting gastric distension. The postprandial increase in pancreatic polypeptide level was blunted compared with accepted normal values but was more pronounced during motilin infusion, i.e., 650 +/- 217 vs. 279 +/- 66 pg/mL (P less than 0.01), probably because of the improved emptying. Our data show that motilin accelerates gastric emptying in diabetic gastroparesis and support the hypothesis that erythromycin's effect is mediated through motilin receptors.

Diabetic Neuropathies

Rifabutin and ethambutol do not help recurrent Crohn's disease in the neoterminal ileum.

We tested the efficacy of rifabutin and ethambutol in combination in healing severe recurrent Crohn's disease in the neoterminal ileum. Sixteen patients who had undergone an ileal resection with partial colectomy and ileocolonic anastomosis and who had severe recurrent lesions in the neoterminal ileum at baseline ileocolonoscopy were included in the study. The patients received rifabutin in a dose of 5 mg/kg together with ethambutol, 20 mg/kg. Ten patients were treated for 6 months; six patients dropped out because of adverse events. As no effect was observed after 6 months, five patients completed a 12-month therapy course. Follow-up ileocolonoscopy was performed at 3, 6, and 12 months. In none of the 10 patients who completed the 6-month trial and in none of the five patients who completed 12 months of therapy was endoscopic improvement of the lesions observed. In four patients the disease was clinically progressive, and two patients underwent a reresection after 6 and 8 months, respectively. This study shows that long-term therapy with rifabutin and ethambutol does not heal Crohn's disease in the neoterminal ileum and does not prevent recurrence of symptoms and complications.

Adult

Whipple's disease: a histological, immunocytochemical and electronmicroscopic study of the immune response in the small intestinal mucosa.

Whipple's disease is a multisystem disorder with protean manifestations and with poorly understood aetiopathogenesis. It is unclear how the immune system reacts, whether it functions normally or not, whether it protects the organism or is defeated in one way or another by the 'Whipple bacillus'. The purpose of our study was to assess humoral and cellular immunity at the level of the intestinal mucosa. This histochemical, immunocytochemical and electronmicroscopic study, based on 16 cases, has shown that the changes in components of the mucosal immune system in Whipple's disease are quite different from normal. The phagocytic capacity of the macrophages, assessed microscopically, is abnormal, the number of intra-epithelial lymphocytes is increased, the CD 4/CD 8 cell ratio is decreased and the IgM positive cells in the lamina propria outnumber the IgA positive cells. These changes may be inter-dependent.

Adult

Actions of 5-hydroxytryptamine on myenteric neurons in guinea pig gastric antrum.

Intracellular recording methods were used to study the actions of 5-hydroxytryptamine (5-HT) on 257 myenteric neurons in the guinea pig gastric antrum. Application of 5-HT caused three types of postsynaptic responses. A fast-activating depolarizing response was accompanied by a decreased input resistance and desensitized quickly to repeated applications. It was mediated by a 5-HT3 receptor. A slowly activating depolarization, accompanied by an increase in the input resistance and enhancement of the excitability, was mainly observed in after hyperpolarizing/type 2 neurons. It was suppressed by the prokinetic benzamide compound renzapride, while classical 5-HT1-4 receptor antagonists had no effect, suggesting the involvement of a 5-HT1p receptor as described in small intestinal neurons. A long-lasting hyperpolarizing response, accompanied by a decreased input resistance, was observed in a small subset of neurons. This response seemed to be mediated by a 5-HT1a receptor. Superfusion of 5-HT caused a dose-dependent inhibition of the stimulus-evoked nicotinic cholinergic fast excitatory postsynaptic potential (EPSP), which was mediated by a presynaptic 5-HT1a receptor. 5-HT also presynaptically inhibited the slow EPSP.

Animals

Comparison of the effects of midecamycin acetate and clarithromycin on gastrointestinal motility in man.

The gastrointestinal motor effects of the macrolide antibiotic, clarithromycin, were compared with those of midecamycin acetate. The method of investigation consisted of intraluminal pressure measurements in the gastric antrum and upper small intestine by means of a low compliance perfused catheter system. Six healthy volunteers participated in the single-blind, placebo-controlled study of both interdigestive and postprandial gastrointestinal motility. Clarithromycin was administered by mouth in a dose of 250 mg b.i.d.; midecamycin acetate was given in a dose of 600 mg b.i.d. The effect of midecamycin acetate on gastric antral and jejunal motility was not significantly different from that of placebo. This was true for both the interdigestive and the postprandial phases of gastrointestinal motility. Oral treatment with clarithromycin (250 mg, b.i.d.) resulted in a statistically significant increase in the postprandial number of antral contractions per hour as well as in the postprandial antral motility index, as compared to placebo.

Adult

Effect of midecamycin acetate on gastrointestinal motility in humans.

The effect was studied on gastrointestinal motor activity of three different macrolides (erythromycin, roxithromycin and midecamycin acetate), administered by mouth in therapeutic doses. This placebo-controlled study was performed in 12 normal human subjects by means of intraluminal pressure measurements in the gastric antrum, duodenum and upper jejunum. In each subject, three manometries were done for 5 h in the interdigestive period and for 3 h postprandially. In the interdigestive period, midecamycin acetate did not affect the characteristics of the gastric migrating motor complex (MMC) and did not increase the number of antral contractions or the gastric motility index as compared to the placebo. Erythromycin and roxithromycin increased the number of antral contractions (24.5 +/- 11 versus 15.2 +/- 7 and 28.4 +/- 12 versus 14.9 +/- 5.9 respectively) and the motility index (4.05 +/- 0.5 versus 3.17 +/- 0.6 and 4.38 +/- 0.2. versus 3.64 +/- 0.7 respectively) as compared to the placebo. In the postprandial period, the number of antral contractions was not significantly increased by any of the three antibiotics. The postprandial antral motility index was not significantly increased by midecamycin acetate. In contrast, the postprandial antral motility indexes after erythromycin (4.4 +/- 0.5) and after roxithromycin (4.3 +/- 0.2) were significantly greater than after the placebo. In the upper small intestine, erythromycin elicited an increased number of phase-III-like activity events and roxithromycin shortened the MMC cycle length. Midecamycin acetate had no effect on interdigestive upper jejunal motility. The postprandial jejunal motor activity was not altered by any of the three antibiotics neither during the interdigestive nor the postprandial periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult