Biomedical subjects
G Vantrappen
Publications and source records attributed to G Vantrappen.
Effect of erythromycin and of octreotide on motilin receptor density in the rabbit.
Recent studies have shown that erythromycin lactobionate (EMLB) acts as a motilin agonist and is able to accelerate gastric emptying in diabetic gastroparesis. Using the rabbit as a model, we have studied the changes in motilin receptor density induced by EMLB (a motilin agonist) and octreotide (a somatostatin analogue and an inhibitor of motilin secretion). Binding studies were performed with antral smooth muscle tissue homogenates using iodinated nor-leucine13-porcine-motilin, and binding parameters were obtained from computerized fits to displacement curves. The contractile capacity towards motilin (10(-7) M) and EMLB (10(-5) M) was measured isotonically on duodenal segments and the response was expressed relative to the maximum obtained with ACh (10(-4) M). The first hours after the last i.v. administrations of EMLB (50 mg/day given on 3 consecutive days), motilin binding was completely abolished to 0.02 +/- 0.006 fmol/mg protein, compared to the control group (0.64 +/- 0.12 fmol/mg protein). The effect was dose-related: total doses of 17.5 mg, 87.5 mg, 175 mg EMLB reduced motilin binding and contractility towards motilin and EMLB to respectively 95 +/- 10, 82 +/- 5%; 36 +/- 9, 38 +/- 9%; 3 +/- 1, 24 +/- 2% of the control values. The effect was also long lasting: binding was still reduced to 60% of the control value 48 h after the highest dose. In contrast, octreotide induced a marked but short lasting upregulation. After 3 daily s.c. injections of 5 micrograms, Bmax rose to 13.6 +/- 1.9 fmol/mg protein (P less than 0.05). It was already obtained 1 h after 3 x 2.5 micrograms/24 h. The changes in receptor-density were not related to changes in affinity. We conclude that motilin receptors can be regulated by EMLB and octreotide presumably because one compound mimicks hypermotilinemia, the other one induces hypomotilinemia.
Ca2+ dependence of motilide-induced contractions in rabbit duodenal muscle strips in vitro.
Recent studies suggested that certain erythromycin A (EM-A) derivatives are motilin receptor agonists. As proposed by Itoh they may be called "motilides". We have investigated the Ca2(+)-dependence of contractions induced by two potent motilides, ME-34 [de(N-methyl) 8,9-anhydroeryhtromycin A 6,9-hemiacetal] and EM-523 [de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal], in duodenal tissues and compared the results with those previously obtained with motilin. Isometric and isotonic contractile responses of isolated longitudinal muscle sheets from the rabbit duodenum were tested under normal, Ca2(+)-free and depolarizing conditions. Prior to stimulation with motilides, the maximal response to acetylcholine was recorded and all responses were always expressed as a percentage of this response. Both motilides induced contractions in normally polarized tissue, with an EC50 of 26 +/- 5 nM for ME-34 (n = 7), and 27 +/- 5 nM for EM-523 (n = 16) and maximal responses of respectively 88 +/- 4% and 80 +/- 3%. Like motilin, both compounds induced an 'extra'-contraction in depolarized tissues. The EM-523 response in 140 mM K+ under isotonic conditions was 84 +/- 3% (n = 5) at 10(-5) M, with an EC50 that was shifted to 65 +/- 18 nM. Similar figures were obtained for ME-34. When Ca2+ was added to Ca2(+)-depleted strips, half-maximal Ca2+ values (in mM) were 1.10 +/- 0.11 (n = 9) for EM-523 and 1.13 +/- 0.12 (n = 3) for ME-34, as compared with 1.12 +/- 0.13 (n = 7) for motilin and 2.8 +/- 1.1 (n = 9) for K+. Both ME-34 and EM-523 also induced a transient contraction in Ca2(+)-free solutions under isometric conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Prospective study on prevalence of esophageal chest pain in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia.
The prevalence of esophageal chest pain was studied prospectively in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. A group of 248 consecutive patients without previously documented heart disease was admitted for elective diagnostic coronary angiography. The clinical history classified 185 patients as having anginal pain and the coronary angiogram was normal in 48 of them. In 37 of these 48 patients full esophageal testing was performed including 24-hr intraesophageal pH and pressure recordings with indication of chest pain episodes as well as a number of esophageal provocation tests, ie, acid perfusion, edrophonium stimulation, balloon distension, and ergonovine stimulation, all performed under continuous esophageal manometric and electrocardiographic monitoring. In 19 of these 37 patients, the familiar chest pain could be reproduced by esophageal provocative testing without ischemic ST-T segment alterations; six of these 19 patients had also a positive 24-hr pH and pressure recording. These data strongly suggest an esophageal origin of chest pain in half the patients with typical angina and a normal coronary angiogram.
Inversion of the slow-wave frequency gradient in symptomatic patients with Roux-en-Y anastomoses.
Patients with Roux-en-Y anastomoses may have chronic symptoms of nausea, vomiting, epigastric fullness, and abdominal pain. To investigate the mechanism of these symptoms, the electrical activity of the Roux limb was studied in five symptomatic and four asymptomatic patients with Roux-en-Y anastomoses. Slow-wave and spike activity in the Roux limb were recorded using six bipolar suction electrodes positioned 10 cm apart. Ten healthy volunteers were studied as a control. In the control subjects, the mean slow-wave frequency decreased from 11.27 +/- 0.2 cycles/min at 30 cm below the ligament of Treitz to 10.96 +/- 0.2 cycles/min at 80 cm past Treitz. By contrast, in five patients the slow-wave frequency in the Roux limb increased from 11.12 +/- 0.2 cycles/min 10 cm below the gastrojejunal anastomosis to 11.42 +/- 0.4 cycles/min 50 cm more distally. Four of these five patients had severe symptoms. In the other four patients, of whom three were completely symptom-free, an aborally decreasing slow-wave frequency was observed. In both the controls and the patients with Roux-en-Y anastomoses, the direction of propagation of phase 3 spike bursts of the migrating motor complex was always aboral. During phase 2, most spike bursts were uncoordinated at adjacent recording sites. Propagated spike bursts, single or repetitive, were rare. The propagation direction of these spike bursts was always aboral in healthy controls. In symptomatic patients with inverted slow wave frequency gradients, however, the rare propagated spike bursts always propagated orally. The observed electrical abnormalities may in part be responsible for the symptoms of patients with the Roux-en-Y syndrome.
Influence of nutritional substrates on the formation of volatiles by the fecal flora.
The influence of metabolic substrates on the formation of volatile compounds by the colonic flora was measured in a fecal incubation system. The presence of carbohydrates (0, 25, and 50 mg/20 mL fecal suspension) led to a dose-related increase in the formation of alcohols and H2 and to a dose-related decrease in the formation of toxic mercaptans. This effect seemed to be independent of pH. The presence of albumin or fat (50 mg/20 mL fecal suspension) as substrates for the colonic flora gave rise to the formation of significantly higher amounts of methanethiol. Small amounts of pentane were found in the headspace after incubation with oil. These data show that the formation of volatile metabolites by the colonic flora is greatly influenced by the available substrates.
Effects on bowel motility of misoprostol administered before and after meals.
Prostaglandin analogues, used in the treatment of duodenal and benign gastric ulcer and in the prevention of gastric ulceration caused by non-steroidal anti-inflammatory drugs, are frequently associated with gastrointestinal side effects, particularly diarrhoea and abdominal cramps. We investigated the effects of misoprostol, a prostaglandin E1 derivative, on bowel motility and faecal loss of fat, water and bile acids in relation to its postprandial vs. preprandial administration. Twelve healthy subjects participated in a double-blind crossover study comparing three 5-day courses of therapy with a washout period of 1-2 weeks between courses. Following a Latin Square design, the dosing regimens were (a) 400 micrograms misoprostol b.d. after meals and placebo b.d. before meals; (b) 400 micrograms misoprostol b.d. before meals and placebo b.d. after meals; (c) placebo before and after meals. Orocaecal transit time measured by H2 breath tests following lactulose administration, was shortest during pre-prandial dosing but was also significantly decreased during post-prandial dosing. The overall treatment difference was highly significant (P less than 0.001), and the difference between each pair of treatments was also statistically significant. Whole bowel transit time studied by means of 3H-PEG 4000 determination in stools, was shorter for the two misoprostol regimens but statistical significance was borderline. The number of stools passed per day was similar in the three groups. During both misoprostol dosing periods, stools were less formed and their content of water, fat and bile acids was higher. There was also more urgency, flatulence, abdominal pain and nausea. It is concluded that the gastrointestinal side effects caused by misoprostol are mainly based on an increased orocaecal transit time. The effects are more important when the drug is administered before meals than after meals.
Variation of slow-wave frequency and locking during the migrating myoelectric complex in dogs.
Slow waves determine rhythm and polarity of spike bursts. We measured the variation of slow-wave frequency (swf) and locking (swl) in the canine jejunum during the various phases of the migrating myoelectric complex (MMC) and during induced phase III (erythromycin 125 micrograms/kg iv bolus or somatostatin 2.5 micrograms.kg-1.h-1 iv infusion), blocked phase III (atropine 20 micrograms/kg iv bolus), and so-called stationary phase III activity (cisapride 150 micrograms/kg iv bolus). The EMG of 4 dogs, implanted with 10 bipolar electrodes, was recorded on a polygraph. Our results indicate that swf and swl change during the MMC from a stepwise swf gradient with slow waves locked in plateaus during phase I to a continuous swf gradient without or with significantly reduced phase locking during phase III. The length of the first swf plateau decreases significantly from 42 +/- 12 cm post Treitz during phase I to 11 +/- 4 cm during spontaneous phase III. Atropine block of phase III activity prevents phase unlocking and development of a continuous swf gradient. Our hypothesis is that phase unlocking may be one of the induction mechanisms of spike-burst activity.
Epidemiology and clinical aspects of esophageal cancer.
A review of the literature is done about the epidemiology and aetiology of esophageal cancer. Esophageal cancer is a relatively uncommon neoplasm in Western countries with a very poor prognosis. In industrialized countries alcohol and tobacco are the major risk factors. Nutritional factors play also an important role in the aetiology of esophageal cancer, particularly a diet rich in cereal but poor in fresh fruit and vegetables, accounts for some of the geographic differences. Several predisposing disorders for esophageal cancer are known and include Barrett's esophagus, achalasia, chronic strictures due to corrosive substances, tylosis, coeliac disease, and the Plummer-Vinson syndrome. The clinical manifestations are also discussed.
The role of laser therapy in the palliative treatment of esophageal cancer.
Laser has become in the recent years an important therapeutic tool for treating esophageal cancer in a palliative setting aiming to reopen the tumor stenosis. The literature shows that the initial enthusiasm for laser, compared with other methods--especially endoprosthesis--has somewhat been tempered because the success rate in restoring a normal food intake was lower than expected (65-68%). Although the complication rate is low, repeated therapy sessions are needed to maintain the lumen open. This constitutes a major drawback in terms of patient acceptability. Variations in the therapeutical methods (contact laser, photodynamic therapy, ...) have not added up to now significant value to laser therapy. Specific indications for laser therapy versus endoprosthesis are discussed and should bring both therapeutic modalities to a more considered application.
Is the irritable bowel really irritable?
We studied 5 healthy volunteers and 9 patients with irritable bowel syndrome (IBS) during infusion of the colon with saline solution, bile acids, fatty acids and balloon distension. Our results show that the pain threshold was significantly (p less than 0.001) higher in controls than in IBS patients. Bile acids and fatty acids brought on the habitual pain in 5/7 and 7/8 patients respectively, while they did not have any effect in the control group. On the basis of our data we can conclude that the IBS patients are more sensitive to colonic distension and perfusions, thus suggesting a non-specific irritability of the colon which could be a characteristic of these patients.
[Electromyographic and manometric studies of stomach motility after vagotomy].
Vagotomy coincides not only with a reduction of the cephalic phase of secretion but also with a significant reduction of the motor activity of the stomach. Electrical and mechanical activity of the gastric wall after truncal vagotomy were verified in animal experiments (dog n = 5) by means of implanted electrodes and pressure transducers. Longlasting motility disturbances expressed as a disorganisation of the basic electrical rhythm occurred in the gastric wall. According to the pattern periods of tachygastria and tachyarrhythmia were identified. Those periods interrupted the regular fasted motility and persisted in the postprandial period. Simultaneous registration of the mechanical activity of the gastric wall during disorders of the electrical rhythm revealed a complete absence of contractility which probably is the pathophysiological correlate for the frequently described delayed gastric emptying after vagotomy.
Non-surgical treatment of achalasia.
The present-day treatment of achalasia is palliative and is aimed at reducing the lower esophageal sphincter pressure. Drug therapy with nitrates and nifedipine is beneficial for short-term relief in patients with relatively mild symptoms or as a temporary measure before a more definitive form of therapy. Balloon dilatation is the traditional non-surgical treatment of achalasia. Balloon dilatation is a safe procedure that can be used even when the esophagus is widened and tortuous, or when the patient is cachectic. The method of balloon dilatation used by the authors is described in detail. The immediate and late clinical, manometric and radiographic results of such dilatation are excellent and compare favorably with those of surgery. With balloon dilatation improvement is immediate, complications are rare and the risks are low. Morbidity and costs and the occurrence of stenosing reflux are considerably less than after surgical cardiomyotomy. Balloon dilatation is considered the treatment of choice for most patients with achalasia.
Inflammatory disorders of the esophagus.
Esophagitis is a very common disorder. The etiology cna be highly variable and is not always clear from the biopsy. The main microscopic inflammatory lesions are located in the epithelium. They consist of an increase in inflammatory cells, either polymorphs or mononuclear cells, or both. They are associated with architectural mucosal changes. It is often difficult or impossible to distinguish reflux esophagitis from drug-induced or viral esophagitis. Yet some microscopic patterns are characteristic and provide information on the etiology of the lesions.
[Gastroduodenal hemorrhage: endoscopic treatment].
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Treatment of bleeding gastrointestinal vascular malformations with oestrogen-progesterone.
10 patients with frequent and severe bleeding from gastrointestinal vascular malformations took part in a double-blind, placebo-controlled, cross-over trial of a daily dose of 0.05 mg ethinyloestradiol plus 1 mg norethisterone given by mouth. Each arm of the trial lasted 6 months. Oestrogen-progesterone significantly decreased the transfusion need from 10.9 to 1.1 units packed cells (p less than 0.003). While on oestrogen-progesterone 2 of 9 patients required transfusions (mean 1.1 units packed cells per patient over 6 months), whereas all patients had to be transfused while on placebo (mean 10.9 units per patient over 6 months; p = 0.002 for number of patients). No significant excess of side-effects was noted with the active agents. The findings indicate that oestrogen-progesterone is an effective treatment for severely bleeding gastrointestinal vascular malformations.
Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies.
Erythromycin mimics the effect of the gastrointestinal polypeptide motilin on gastrointestinal motility, probably by binding to motilin receptors and acting as a motilin agonist. Erythromycin may thus have clinical application in patients with disturbances of gastroduodenal motility, such as diabetic gastroparesis. To examine this possibility, we studied the effect of erythromycin on gastric emptying in 10 patients with insulin-dependent diabetes mellitus and gastroparesis. We studied the emptying of liquids and solids simultaneously on separate days after the intravenous administration of erythromycin (200 mg) or placebo, using a double-isotope technique and a double-blind, crossover design. Erythromycin shortened the prolonged gastric-emptying times for both liquids and solids to normal. For example, 120 minutes after the ingestion of a solid meal, mean (+/- SE) retention was 63 +/- 9 percent with placebo and 4 +/- 1 percent with erythromycin, as compared with 9 +/- 3 percent in 10 healthy subjects. The corresponding values 120 minutes after the ingestion of a liquid meal were 32 +/- 4, 9 +/- 3, and 4 +/- 1 percent, respectively. Gastric emptying also improved, but to a lesser degree, in the 10 patients after four weeks of treatment with oral erythromycin (250 mg three times a day). These preliminary results suggest that erythromycin may have therapeutic value in patients with severe diabetic gastroparesis.
Adaptive spectral analysis of cutaneous electrogastric signals using autoregressive moving average modelling.
The recording of the human gastric myoelectrical activity by means of cutaneous electrodes is called electrogastrography (EGG). It provides a noninvasive method of studying electrogastric behaviour. The normal frequency of the gastric signal is about 0.05 Hz. However, sudden changes of its frequency have been observed and are generally considered to be related to gastric motility disorders. Thus, spectral analysis, especially online spectral analysis, can serve as a valuable tool for practical purposes. The paper presents a new method of the adaptive spectral analysis of cutaneous electrogastric signals using autoregressive moving average (ARMA) modelling. It is based on an adaptive ARMA filter and provides both time and frequency information of the signal. Its performance is investigated in comparison with the conventional FFT-based periodogram method. Its properties in tracking time-varying instantaneous frequencies are shown. Its applications to the running spectral analysis of cutaneous electrogastric signals are presented. The proposed adaptive ARMA spectral analysis method is easy to implement and is efficient in computations. The results presented in the paper show that this new method provides a better performance and is very useful for the online monitoring of cutaneous electrogastric signals.