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M Delvaux

Publications and source records attributed to M Delvaux.

At least 37 records · Page 2Linked to original sources
PubMed2003

Clinical trial guidelines for pharmacological treatment of irritable bowel syndrome.

Appropriate guidelines for clinical trials in irritable bowel syndrome are needed because of the inadequacy of previously performed trials, the use of new and more adequate patient definition, new emerging pathophysiological models and the unique requirements related to the assessment of treatment outcome that, in the absence of a biological marker, can rely only on the evaluation of clinical manifestations. This consensus report highlights the following points. (a) A 4-week period is considered to be adequate to assess drug efficacy for the control of symptoms. (b) For the cyclic and non-life-threatening nature of the disease, a long-term study of 4-6 months or more of active treatment to establish efficacy is considered to be inappropriate in the large majority of patients. (c) In the initial assessment phase of drug efficacy, the withdrawal effect of treatment can be ascertained during a follow-up period prolonged for a sufficient time (4-8 weeks) after stopping treatment. Subsequent trials with proper withdrawal phase design and duration can then ascertain the drug post-treatment benefit. (d) Considering the intermittent clinical manifestations of irritable bowel syndrome, designing trials with on-demand or repeated cycles of treatment could be envisaged. However, the lack of a definition of what constitutes an exacerbation is a major obstacle to the design of such trials. In the absence of an established gold standard, appropriately justified novel trial designs are welcome. (e) Patients eligible for inclusion should comply with the Rome II diagnostic criteria for irritable bowel syndrome. (f) The main efficacy outcome of the treatment should be based on one primary end-point. (g) The primary efficacy end-point could combine, in a global assessment, the key symptoms (abdominal pain, abdominal discomfort, bowel alterations) of irritable bowel syndrome or rate any single symptom for drugs considered to target specific symptoms. (h) A 50% improvement in the primary efficacy end-point seems to be a reasonable definition of a responder.

Clinical Trials as Topic↗
PubMed2003

Diagnostic value of endoscopic capsule in patients with obscure digestive bleeding: blinded comparison with video push-enteroscopy.

BACKGROUND AND STUDY AIMS: This study was designed to prospectively compare the diagnostic yield of the M2A endoscopic capsule with that of video push-enteroscopy in exploring the small intestine in patients with obscure digestive bleeding. PATIENTS AND METHODS: Patients with either occult or overt obscure digestive bleeding and a negative endoscopic work-up underwent a double intestinal investigation, with video push-enteroscopy and a wireless capsule, performed blindly by separate examiners. The diagnostic yield for each technique was defined as the frequency of detection of clinically relevant intestinal lesions, i. e. those having the potential for bleeding. RESULTS: 60 patients (27 men, 33 women; age 58 +/- 18 years; hemoglobin 9.4 +/- 2.5 g/dl) were included, 32 with occult and 28 with overt bleeding. Results were analyzed for 58 patients, who completed both examinations. Lesions were detected in 43 patients: with both techniques in 19, only by capsule in 21, and, conversely, only by push-enteroscopy in 3 ( P = 0.04). Final diagnoses were as follows: a P2 lesion with high bleeding potential in 28 patients (19 angiomata, 6 ulcerations, 2 tumors, 1 case of intestinal varices); a P1 lesion with intermediate bleeding potential in 15 patients (2 patients with mucosal erosions, 13 patients with mucosal red spots); and there were normal findings from 15 procedures. No procedure induced any complication. CONCLUSION: The use of the wireless endoscopy capsule detects significantly more clinically relevant intestinal lesions than video push-enteroscopy in patients with obscure digestive bleeding, raising the diagnostic yield to 67.2 %. Its influence on the clinical outcome for patients needs further investigation.

Adult↗
PubMed2002

Role of visceral sensitivity in the pathophysiology of irritable bowel syndrome.

Visceral hypersensitivity has been recognised as a characteristic of patients with irritable bowel syndrome (IBS). It may be involved in the pathogenesis of abdominal pain/discomfort, and seems to result from the sensitisation of nerve afferent pathways originating from the gastrointestinal tract. From a clinical point of view, hypersensitivity, although frequent, is not a constant finding among patients with IBS and cannot therefore be considered as a diagnostic marker of the condition. The advances made in understanding visceral hypersensitivity in patients with IBS are reviewed: the factors that influence abdominal distension are defined and different therapeutic perspectives are examined.

Colonic Diseases, Functional↗
PubMed2001

An evaluation of selenium concentrations in water, sediment, invertebrates, and fish from the Republican River Basin: 1997-1999.

The Republican River Basin of Colorado, Nebraska, and Kansas lies in a valley which contains Pierre Shale as part of its geological substrata. Selenium is an indigenous constituent in the shale and is readily leached into surrounding groundwater. The Basin is heavily irrigated through the pumping of groundwater, some of which is selenium-contaminated, onto fields in agricultural production. Water, sediment, benthic invertebrates, and/or fish were collected from 46 sites in the Basin and were analyzed for selenium to determine the potential for food-chain bioaccumulation, dietary toxicity, and reproductive effects of selenium in biota. Resulting selenium concentrations were compared to published guidelines or biological effects thresholds. Water from 38% of the sites (n = 18) contained selenium concentrations exceeding 5 microg L(-1), which is reported to be a high hazard for selenium accumulation into the planktonic food chain. An additional 12 sites (26% of the sites) contained selenium in water between 3-5 microg L(-1), constituting a moderate hazard. Selenium concentrations in sediment indicated little to no hazard for selenium accumulation from sediments into the benthic food chain. Ninety-five percent of benthic invertebrates collected exhibited selenium concentrations exceeding 3 microg g(-1), a level reported as potentially lethal to fish and birds that consume them. Seventy-five percent of fish collected in 1997, 90% in 1998, and 64% in 1999 exceeded 4 microg g(-1) selenium, indicating a high potential for toxicity and reproductive effects. However, examination of weight profiles of various species of collected individual fish suggested successful recruitment in spite of selenium concentrations that exceeded published biological effects thresholds for health and reproductive success. This finding suggested that universal application of published guidelines for selenium may be inappropriate or at least may need refinement for systems similar to the Republican River Basin. Additional research is needed to determine the true impact of selenium on fish and wildlife resources in the Basin.

Animals↗
PubMed2001

Intrarectal injection of glycerol induces hypersensitivity to rectal distension in healthy subjects without modifying rectal compliance.

BACKGROUND: Rectal sensory thresholds are lowered in patients with irritable bowel syndrome (IBS), reflecting visceral hyperlagesia, which might be related to subclinical inflammation. AIM: To evaluate the effects of an intraluminal injection of glycerol, a mucosal irritant, on rectal tone and perception of distension in 12 healthy subjects. METHODS: Rectal tone was evaluated with a barostat. First sensation, need to defecate and pain thresholds were evaluated during isobaric phasic distensions, before and 20 and 120 min after injection of 10 ml glycerol in the rectum. RESULTS: Baseline bag volume (97.9 +/- 56.2 ml) significantly decreased 20 min (49.7 +/- 42.2 ml; P= 0.026) and 120 min (66.5 +/- 38.3 ml; P= 0.050) after injection of glycerol, indicating its hypertonic effect. The pressure defining sensory thresholds was decreased significantly 20 min after glycerol injection: first sensation, 14.6 +/- 2.9 versus 18.3 +/- 7.2 mm Hg (P = 0.01); need to defecate, 19.6 +/- 3.7 versus 26.0 +/- 6.9 mm Hg; pain, 23.8 +/- 4.5 versus 35.6 +/- 9.5 mm Hg (P = 0.001). This effect was maintained for 120 min after injection of glycerol. Slopes of the compliance curves did not differ before and after injection of glycerol. CONCLUSIONS: Intraluminal injection of glycerol significantly increases rectal tone and sensitizes healthy volunteers to rectal distension, since they show significantly lower thresholds after glycerol. This could constitute a model of visceral hypersensitivity in healthy volunteers.

Administration, Rectal↗
PubMed2001

The management of irritable bowel syndrome: a European, primary and secondary care collaboration.

OBJECTIVE: To develop recommendations for the diagnosis and management of irritable bowel syndrome for European doctors delivering primary care. These recommendations can be adapted by local medical groups according to their language, custom and health-care systems. METHODS: Twenty-one general practitioners and gastroenterologists from Europe attended a workshop planned by a steering committee. After a state-of-the-art symposium, four working groups considered the following aspects of irritable bowel syndrome management: what to tell the patient, diagnosis, non-medical treatment and psychosocial management. Current and future drug management was reviewed by the steering committee. The resulting recommendations were considered at two plenary sessions during the meeting, and by circulation of the material during development of the manuscript. RESULTS: The process permitted a unique dialogue between general practitioners and gastroenterologists, in which it was necessary to reconcile the specialists' emphasis on thoroughness with the practical, epidemiological and economic realities of primary care. Despite this dichotomy, consensus was achieved. CONCLUSIONS: European general practitioners and gastroenterologists have produced recommendations that emphasize education of the patient, a positive symptom-based diagnosis, diet and lifestyle advice, psychological support and a critical analysis of current specific psychological and pharmacological treatments.

Colonic Diseases, Functional↗
PubMed2001

Pharmacology and clinical experience with fedotozine.

Fedotozine [(1R)-1-phenyl-1-[(3,4,5-trimethoxy)benzyloxymethyl]-N,N- dimethyl-n-propylamine, (2S,3S-tartrate] is derived from the arylacetamide series. As with other compounds of this series, fedotozine is more or less selective of kappa(1)-opioid receptors and particularly for the kappa(1a)-receptor subtype, where it acts as an agonist. Pharmacological studies have shown that fedotozine exerts a peripheral antinociceptive action, comparable with that of other kappa-agonists. Its main effects have been demonstrated at the level of the afferent nerve pathways originating from the gut. Fedotozine alters the processing of visceral sensations along these pathways and hence, the perception of gut stimuli at the brain level. It modifies reflexes induced in various pathological conditions, like experimental inflammation of the gut, chemically-induced peritonitis or post-operative ileus. Fedotozine also decreases the nociceptive reflexes triggered by noxious gut distension in animals. In humans, fedotozine decreases the perception of gut distension, both in physiological and pathological conditions. Clinical trials undertaken in patients with functional digestive disorders, non-ulcer dyspepsia and irritable bowel syndrome, have shown that fedotozine relieves abdominal pain in these patients in 6-week treatments. kappa-Opioid receptors remain an interesting area for future development of new treatments for abdominal pain in patients with functional digestive disorders.

Animals↗
PubMed2000

Minimal standard terminology for digestive endoscopy: results of prospective testing and validation in the GASTER project.

BACKGROUND AND STUDY AIMS: Standardization of the endoscopic report is a key issue for future research in the field of digestive endoscopy. The Minimal Standard Terminology (MST) has been proposed by the European Society for Gastrointestinal Endoscopy (ESGE) as a structured language for production of computerized endoscopic reports. The aim of this study was to validate version 1.0 of this terminology prospectively, by collecting cases in a multicenter, multilingual trial. METHODS: Endoscopic cases (esophagogastroduodenoscopy [EGD], colonoscopy, endoscopic retrograde cholangiopancreatography [ERCP]) were prospectively collected in nine university hospitals in Europe, using the same software. Reports were produced in the local language, but the software allowed comparison of reports between languages, and global analysis of the database. Outcome measures were the adequacy of terms proposed in the MST to describe "reasons for performing an endoscopy", "findings", and "endoscopic diagnoses", frequency of use and content of free-text fields, and types of lesions described. RESULTS: A total of 6,232 reports were analyzed, including 3,447 gastroscopies, 1,743 colonoscopies, and 1,042 ERCPs. Overall, terms originally contained in the MST were adequate to describe fully 91.0% of all examinations where "reasons for endoscopy" were described, 99.5 % of examinations where "findings" were described, 95.8% of all examinations containing descriptions of "endoscopic diagnosis", 98.9% of examinations containing descriptions of "additional diagnostic procedures", and 94.8 % of examinations containing descriptions of "additional therapeutic procedures". Free-text fields were only used in the other cases (less than 5% of cases in average). CONCLUSIONS: The MST appeared adequate to cover a large part of routine endoscopy reports, and could thus be used as a tool for standardization of endoscopic reports in clinical practice. The latter could be significantly improved by the use of a structured and standardized terminology for the production of endoscopic reports.

Clinical Trials as Topic↗
PubMed2000

Single-dose pharmacokinetics of amprenavir, a human immunodeficiency virus type 1 protease inhibitor, in subjects with normal or impaired hepatic function.

Amprenavir (141W94) is extensively metabolized by P450 cytochromes, specifically, CYP3A4. Because hepatic insufficiency reduces P450-mediated metabolism, the concentrations in plasma of drugs metabolized through this pathway are often increased in subjects with liver disease. Following administration of a single, oral dose of 600 mg of amprenavir, pharmacokinetic parameters were determined for 10 subjects with severe cirrhosis, 10 subjects with moderate cirrhosis, and 10 healthy volunteers. Model-independent methods for determining the area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC(0-infinity)) showed an increase in amprenavir AUC(0-infinity) of 2.5-fold in the group with moderate cirrhosis and 4.5-fold in the group with severe cirrhosis compared with that in the control group of healthy volunteers (P < 0.05). AUC(0-infinity) was linearly related to the severity of liver disease, as assessed by the Child-Pugh score. Of the laboratory data used to calculate the Child-Pugh score, only the mean total bilirubin concentration showed a significant relationship with AUC(0-infinity). The relationship between the total bilirubin concentration and the AUC(0-infinity) of amprenavir was well characterized by a simple E(max) model, suggesting that the total bilirubin concentration may be a useful parameter for predicting the amprenavir AUC in subjects with hepatic insufficiency. Finally, the sera of cirrhotic subjects showed significant decreases in the levels of alpha(1)-acid glycoprotein, the primary plasma binding protein for amprenavir. On the basis of the results of this study, for an exposure equivalent to a clinical dose of 1,200 mg twice daily in subjects without cirrhosis, subjects with Child-Pugh scores of 5 to 8 should receive a twice-daily 450-mg dose of amprenavir, and subjects with Child-Pugh scores of 9 to 15 should receive a twice-daily 300-mg dose of amprenavir.

Adult↗
PubMed1999

The kappa agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome.

BACKGROUND & AIMS: Visceral hypersensitivity plays a major role in the pathophysiology of inflammatory bowel syndrome (IBS). Opioid kappa receptors on afferent nerves may modulate it and may be the target of new IBS treatments. The aim of this study was to evaluate the effects of fedotozine, a potent and selective kappa agonist, on responses to colonic distention and colonic compliance in patients with IBS. METHODS: Fourteen patients with IBS (Rome criteria; 50 +/- 12 years; 6 men and 8 women) were included in a randomized double-blind, crossover trial comparing the effect of an intravenous infusion of 100 mg fedotozine or saline on sensory thresholds elicited by left colon phasic distention (4-mm Hg steps for 5 minutes) up to a sensation of abdominal pain. Colonic compliance was compared by the slope of the pressure-volume curves built on placebo and on fedotozine. RESULTS: In the fedotozine group, thresholds of first perception (28.7 +/- 5.9 mm Hg) and pain (34.7 +/- 5.5 mm Hg) were significantly greater than with placebo (23.3 +/- 4.5 and 29.0 +/- 3.5 mm Hg, respectively; P = 0.0078). Colonic compliance was 9. 20 +/- 3.87 mL. mm Hg-1 with placebo and 8.73 +/- 3.18 mL. mm Hg-1 with fedotozine (not significant). CONCLUSIONS: Fedotozine increases thresholds of perception of colonic distention in patients with IBS without modifying colonic compliance. Fedotozine seems capable of reversing visceral hypersensitivity observed in these patients and could have some beneficial action on their symptoms.

Adult↗
PubMed1999

Influence of age on rectal tone and sensitivity to distension in healthy subjects.

Hypersensitivity to rectal distension is frequently observed in patients with irritable bowel syndrome (IBS). However, few data are available about the influence of age on rectal sensory thresholds and tone. The aim of this study was to measure rectal sensory thresholds and tone with a barostat in 12 healthy subjects (aged 86 +/- 4 years, eight females, four males) as compared with 12 young healthy male controls (26 +/- 1 years). Isobaric phasic distensions were performed in the fasted state (increment of 4 mmHg, steps of 5 min, interval of 5 min). Rectal tone changes were then measured as changes in volume of the barostat bag, the pressure being kept constant. After a baseline recording of 1 h, a 1000-kcal meal was served and the tone recorded until return to baseline. Rectal sensory thresholds were significantly higher in aged subjects. First sensation, sensation of urge to defaecate and sensation of pain were triggered at 21.1 +/- 3.2 mmHg, 30.4 +/- 5.4 mmHg and 40.5 +/- 5.0 mmHg, respectively, in aged subjects, vs 13.3 +/- 4.6 mmHg (P < 0.05), 20.7 +/- 1.0 mmHg (P < 0.001) 31.3 +/- 1.7 mmHg (P < 0.001) in controls. Rectal compliance was not significantly different between the two groups. Mean barostat bag volume was 104 +/- 13 mL in fasting aged subjects and 125 +/- 23 mL in controls (NS). After the meal, the barostat bag volume decreased by 69 +/- 11% during 85 +/- 17 min in aged subjects and 75 +/- 14% during 89 +/- 15 min in young controls (NS). Rectal sensory thresholds triggered by distension are increased in aged healthy subjects while compliance and tone are not different. Age should be considered as a confounding factor when studying rectal sensitivity and further studies in aged patients with IBS should include a group of control subjects within the same range of age as studied patients.

Adult↗