[Prevalence and treatment of Helicobacter pylori in gastro-duodenal ulcers. An experience in Liege]. / Prévalence et traitement de l'Helicobacter pylori dans les ulcères gastro-duodénaux. Une expérience liégeoise.

Between April 1998 and July 1999, we prospectively investigated 152 patients with gastric or duodenal ulcer and we observed concomitant H. pylori infection in 72.8% and 78.5% respectively. We proposed to the GPs of these patients the recommended triple therapy (omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg (OAC) twice daily for 7 or 10 days). H. pylori eradication was tested using the C13-urea breath test. Our results showed a modest overall eradication rate of about 70%. We have to persuade the patients and the GPs of the benefit of antibiotics and of the importance of the correct dosages. We have to continue to follow the resistance against antibiotics.

[Chronopharmacologic approach to the administration of anticancer agents in pancreatic adenocarcinoma. Pilot experience]. / Approche chronopharmacologique de l'administration des agents anticancéreux dans l'adénocarcinome pancréatique. Expérience pilote.

The authors first analyzed the potential interest of the delivery of anticancer agents according to chronobiological concepts for human pancreatic cancer. They report their experience on 41 patients treated in adjuvant (12 cases) or palliative (29 cases) situations. The excellent therapeutic index observed warrants further evaluations of this concept in randomized trials.

[Epidemiological aspects, risk factors, and detection of pancreatic cancer]. / Epidémiologie, facteurs de risque et dépistage du cancer du pancréas.

The incidence of pancreatic cancer (PC) is increasing in developing countries. Smoking, reduced consumption of fruits and vegetables, chronic pancreatitis appear to be the best established risk factors. PC is often diagnosed at a late stage. We have to look for it when dyspepsia with weight loss, pancreatic pain or impaired glucose tolerance occurs. Tumor markers are briefly exposed and we discuss the place of endoscopic retrograde cholangiopancreatography (ERCP) after non invasive imaging techniques.

[Endoscopic ultrasonography in the diagnosis and staging of pancreatic and ampullary cancer: influence on patient management]. / Apport de l'échoendoscopie (EE) au diagnostic et à la stadification des cancers pancréatiques et ampullaires: influences sur la prise en charge du patient.

Accurate preoperative staging is now more prerequisite in the management of cancer of the pancreas and ampulla in order to orientate the patient toward the best selected treatment: either a curative or a palliative surgery associated or not with a pre- or postoperative multimodal therapy, or an endoscopic palliative technique which does not require surgery. Endoscopic ultrasonography (EUS) appears to be a highly accurate diagnostic procedure in the assessment of local resectability because it enables detailed visualization of the pancreatic gland, the depth of infiltration into the surrounding tissue and organs and visualisation of regional lymph nodes involvement. EUS-guided fine needle aspiration for cytology will provide a tissue diagnosis. The likelihood of successful resection for palliative or cure can be predicted before surgery. The following overview will point out the clinical impact of EUS on diagnosis, staging and management of these tumors.

Evaluation of polyps by endoscopic ultrasonography (eus): implication for endotherapy.

UNLABELLED: EUS is the single best imaging modality in precise visualization of the five layers structure of G.I. tract wall, space occupying lesion and surrounding structures. In case of "protruding lesion" into the G.I. lumen, the site of origin of the tumor can be easily determined by EUS, and then its nature can be presumed (1). However, despite of these tiny details of the G.I. wall obtained by EUS, histology is still mandatory, especially when dealing with lesion suspected of malignancy (2). In case of sessile malignant "polypoid" lesion, Endoscopic Mucosal Resection (EMR) guided by EUS, could be considered in specific cases of selected patients. Conventional EUS transducer (7.5 and 12 Mhz) employed for this purpose is not sufficient for differentiating cancers invading the muscularis mucosae from those invading the sub-mucosa. A Miniature Ultrasonic Probe (20 and 30 Mhz) which can be used through the biopsy channel of an endoscope has recently been developed and is accurate in measuring such a superficial infiltration and in assessing regional lymph nodes allowing then an exact pre-treatment staging. In patient not fitted for surgery, with a lesion less than 2 cm and involving less than half circumference of the lumen, EMR could be performed according to the parietal infiltration (T), the nodal involvement (N) and the related involved organs (Esophagus, Stomach, Colo-rectum). CONCLUSIONS: EUS may be usefull and sometimes is mandatory for assessing the G.I. tract polyps before resection.

[Multiplicity of endothelin receptors of aortic smooth muscle cells in rats]. / Multiplicité des récepteurs de l'endothéline sur les cellules musculaires lisses d'aorte de rat en culture.

Among the different endothelin (ET) isoforms, ET-3 has been reported to exhibit a less potent constrictor activity than ET-1 and ET-2. Furthermore, distinct endothelin receptor subtypes have been identified in several tissues or cell types. In this study, we investigated the binding characteristics of the three endothelin isoforms in cultured rat aortic smooth muscle cells. [125I]ET-3 exhibited an apparent affinity and a number of binding sites 10 and 6 times smaller, respectively, than [125I]ET-1 and [125I]ET-2. In contrast to ET-1 and ET-2, ET-3 appeared to elicit a reversible binding and did not modify ET-1 binding characteristics in receptor-regulation experiments. In competition experiments ET-1 and ET-2 equally inhibited the binding of the three endothelin isoforms, whereas ET-3 was less potent in competing with [125I]ET-1 and [125I]ET-2 than [125I]ET-3. These results suggest that rat aortic smooth muscle cells possess 2 subtypes of endothelin receptors (A and B) differing by their affinity for ET-3, their proportion, the reversibility of the binding and their sensitivity to down-regulation.

[Endothelin receptors and endothelin-1 immunoreactivity in the human lung]. / Récepteurs de l'endothéline et immunoréactivité de l'endothéline-1 au niveau des poumons humains.

We investigated in human lung preparations the characteristics of endothelin-1 (ET-1) binding and the amount of ET-1-like immunoreactivity. Saturation experiments revealed the presence of a large number of high affinity specific ET-1 binding sites with a dissociation constant (Kd) of 1.35 nM and a binding capacity (Bmax) of 9.74 pmol/mg of protein. The binding was time- and temperature-dependent and dissociated by only 10% by the addition of 1 microM unlabeled ET-1. In competition experiments, [125I]ET-1 binding was totally inhibited by unlabeled ET-1 and ET-2 with inhibition constant (Ki) values of 0.20 and 0.21 nM respectively, and 80% inhibited by ET-3 with Ki value of 0.50 nM. The binding was not affected by 1 microM structurally unrelated compounds. Moreover a high level of ET-1-like immunoreactivity (2.3 pg/mg wet weight) was found in human lung by using a specific radioimmunoassay of ET-1 after extraction. HPLC analysis revealed the presence of both ET-1 and Big-ET. These results suggest that the lung may be an important target organ for ET-1 action and/or metabolism in human.

Effects and specific binding sites of endothelin in human lung preparations.

Endothelin binding in human isolated lung membrane fractions revealed a single class of high affinity recognition sites with a Kd of 1.33 +/- 0.15 nM and a Bmax of 9.61 +/- 1.44 pmol/mg protein. Endothelin inhibited [125I]endothelin binding with a Ki of 1.90 +/- 0.15 nM whereas structurally unrelated compounds had no effect. Endothelin was a potent contractile agonist on human isolated pulmonary arterial (HPA) and venous (HPV) muscle preparations (pD2 values: 9.64 and 10.36, respectively). Neither indomethacin (1 microM), nicardipine (0.01, 0.10, 1.0 microM) nor diltiazem (1, 10, 100 microM) altered the sensitivity of HPA to endothelin. Human isolated bronchial muscle preparations were less sensitive to endothelin than vascular tissues. These data suggest that pulmonary veins may be a major target for this constrictory peptide in the human lung.

Binding characteristics of endothelin isoforms (ET-1, ET-2, and ET-3) in vascular smooth muscle cells.

The existence of distinct endothelin (ET) receptor subtypes has been reported in several tissues. In the present study, we investigated the binding characteristics of the three endothelin isoforms to cultured rat aortic smooth muscle cells. [125I]ET-1, [125I]ET-2, and [125I]ET-3 bound to an apparent single class of binding sites with apparent dissociation constants (Kd) of 111, 123, and 1410 pM and binding capacities (Bmax) of 54.1, 46.0, and 7.9 fmol/10(6) cells, respectively. The binding of the three radiolabeled endothelin isoforms was equally inhibited by ET-1 and ET-2. ET-3 was more effective in competing with [125I]ET-3 than with [125I]ET-1 or [125I]ET-2. In contrast to ET-1 and ET-2, the binding of ET-3 was reversible. Furthermore, 18 h of pre-exposure of the cells to 1 nM ET-1 or ET-2 decreased the ET-1 binding capacity, whereas ET-3 (10 nM) was ineffective. ET-3 binding characteristics were not affected by pretreatment of the cells with any of the endothelin isoforms. These results suggest the presence of two distinct endothelin receptor subtypes in rat aortic smooth muscle cells. The ET-1 and ET-2 preferring receptor (80-85%), sensitive to downregulation or internalization, elicits an irreversible binding. The second subtype (15-20%) binds the three endothelin isoforms with the same affinity in a reversible manner, and is insensitive to downregulation or internalization.

[Homologous and heterologous regulations of endothelin receptors on smooth muscle cells]. / Régulations homologue et hétérologue des récepteurs de l'endothéline sur cellules musculaires lisses.

In vascular smooth muscle cells, the vasoconstrictor peptide, endothelin (ET-1) possesses specific binding sites sensitive to homologous and heterologous regulation. In this study, we have compared the regulation of ET-1 receptors induced by ET-1 and by angiotensin II. After 18 hours preincubation of cultured rat aortic smooth muscle cells at 37 degrees C in presence of vasoactive substances (1 microM) such as norepinephrine, Met- and Leu-enkephalins, bradykinin, serotonin, histamine or carbachol, the binding characteristics of [125I]ET-1 were not modified. On the same conditions, Arg-vasopressin (1 microM) was able to down-regulate ET-1 receptors by less than 30 p. 100 whereas both ET-1 (1 nM) and angiotensin II (10 nM) reduced the number of ET-1 binding sites (Bmax) by more than 50 p. 100 without modification of the affinity (Kd). The time course of the effect of the two peptides showed a rapid decrease of ET-1 binding sites induced by ET-1 and a comparatively slow regulation elicited by angiotensin II. Sar1-Ile8-angiotensin II blocked the effect of angiotensin II. These results show that ET-1 and angiotensin II can regulate ET-1 receptors and suggest a possible modulation of ET-1 activity by endogenous levels of the two peptides.