Should we eradicate Helicobacter pylori before prescribing an NSAID? Result of a placebo-controlled study.

OBJECTIVE: (1) To determine the prevalence of gastrointestinal (GI) symptoms in patients with and without Helicobacter pylori infection and treated with non-steroidal anti-inflammatory drugs (NSAIDs) and (2) to estimate the impact of H. pylori eradication on these symptoms. METHODS: This was a multicentric, community-based, randomized, case-control study. Patients presenting with a rheumatic disorder motivating the prescription of an NSAID for at least 2 wks were stratified in two groups (H. pylori-positive and H. pylori-negative) by a serological doctor test and H. pylori-positive patients divided further into two subgroups, receiving either an eradication treatment (group 1) or a placebo (group 2). The main outcome measure was the prevalence of GI symptoms estimated in groups 1 and 2 and in noninfected patients (group 3) at weeks 2, 6, and 12. RESULTS: Among H. pylori-negative patients (n=145), GI symptoms were present in 42.6%, 21.4%, and 10.0% at weeks 2, 6, and 12, respectively. In groups 1 and 2, GI symptoms were present in 57.7% and 40.7%, respectively, at week 2 (p= 0.03); 24.7% and 23% at week 6 (p= 0.85); and 9.4% and 17.3% at week 12 (p= 0.13). The prevalence of GI symptoms at week 2 was similar in group 2 and in the H. pylori-negative group (p= 0.77). The highest prevalence of symptoms at week 2 in group 1 was essentially due to diarrhea. The prevalence of GI symptoms was the same for groups 1 and 3 at week 12, and higher in group 2, but the difference did not reach statistical significance. CONCLUSIONS: The short-term (6 wks) GI tolerance of conventional NSAIDs does not differ whether or not the patients are infected by H. pylori. The tendency observed for the medium term (12 wks) deserves to be confirmed.

Effects of lansoprazole on human gastric lipase secretion and intragastric lipolysis in healthy human volunteers.

BACKGROUND: Lansoprazole is a potent proton-pump inhibitor (PPI) of parietal cells, which reduces the secretion of gastric acid. Although human gastric lipase (HGL) is produced only by the chief cells of the stomach, the possibility that interactions may occur between lansoprazole and HGL has never been addressed so far in humans. The aim of this study was therefore to quantify the effects of lansoprazole on HGL secretion and intragastric lipolysis during the ingestion of test meals by healthy human volunteers. METHODS: Six healthy volunteers were intubated twice with a gastric and a duodenal tube, before ingesting a standard liquid test meal alone (-PPI experiments) and after 7 days of lansoprazole treatment (+PPI experiments). The HGL concentration was assessed in gastric and duodenal samples by measuring the lipase activity using a pH-stat, and the lipolysis products were quantified by performing thin layer chromatography. The level of intragastric lipolysis was defined as the percentage acyl chains released from the meal triglycerides. The pyloric outputs of HGL and lipolysis products were calculated, based on the use of a non-absorbable marker added to the meal. RESULTS: The pH of the gastric contents was significantly higher in the +PPI experiments than in the -PPI experiments (p < 0.05), since mean values of 4.3 +/- 2.5 and 2.2 +/- 1.6, respectively, were recorded at the end of the gastric emptying of the meal. The HGL concentrations recorded during the meal were found to be higher in the experiments with lansoprazole (p < 0.05) than in those without lansopra- zole, but the HGL secretion levels (-PPI: 15.4 +/- 8.0 mg; +PPI: 19.0 +/- 7.4 mg) and the intragastric lipolysis (-PPI: 24.0 +/- 8.0%; +PPI: 23.6 +/- 6.8%) were not significantly affected by lansoprazole (p > 0.05 in both cases). CONCLUSION: Lansoprazole affected neither the HGL secretion nor the intragastric lipolysis levels, although an increase was observed in the intragastric pH at the end of the gastric emptying of the meal. The HGL concentration increased, however, due to the decrease in the acid secretion process, resulting in less diluted gastric contents.

[Treatment of Helicobacter pylori infection with lansoprazole 30 mg or 60 mg combined with two antibiotics for duodenal ulcers]. / Traitement de l'infection par Helicobacter pylori par lansoprazole 30 mg ou 60 mg associé à deux antibiotiques chez les ulcéreux duodénaux.

OBJECTIVE: The primary objective of the present study was to evaluate the efficacy of 30 and 60 mg of lansoprazole administered in combination with two antibiotics for 7 or 10 days in eradicating Helicobacter pylori in duodenal ulcer patients. METHODS: This multicenter double-blind study randomized for the lansoprazole dose was carried out by 325 gastroenterologists. The H. pylori-positive diagnosis was based on three antral biopsies (one for a rapid urease test and two for histological examination). Eradication was checked by a (13) C-urea breath test. Patients were given 30 or 60 mg of lansoprazole with 2 g of amoxicillin and 1 g of clarithromycin for 10 days or 7 days, followed by 30 mg of lansoprazole daily for 18 or 21 days, i.e. the total duration of antisecretory therapy was 28 days. RESULTS: Out of the 665 patients included, 620 were analyzed on the intent-to-treat basis and 567 on the per protocol basis. The eradication rates were significantly higher in the group receiving 60 mg of lansoprazole than in the 30 mg group in both the intent-to-treat analysis (P=0.003) and the per protocol analysis (P=0.006). In the intent-to-treat analysis 60 mg group, the rates (95% confidence intervals) in the 7-day and 10-day sub-groups were 82.5 (CI: 75.2 - 89.8) and 86.8% (CI: 82.2 - 91.4), respectively, and in the per protocol analysis 84.2 (CI: 76.9 - 91.5) and 91.5% (CI: 87.6 - 95.4), respectively. With either lansoprazole dose, the eradication rates seemed higher when therapy was administered for 10 days. CONCLUSION: The double dose of lansoprazole optimizes H. pylori eradication rates. The highest eradication rates were obtained after 10 days of therapy. Additional studies should be carried out to determine the optimal duration of triple therapy for eradicating H. pylori.

Dual therapy using a double dose of lansoprazole with amoxicillin versus triple therapy using a double dose of lansoprazole, amoxicillin, and clarithromycin to eradicate Helicobacter pylori infection: results of a prospective randomized open study.

OBJECTIVES: The eradication of Helicobacter pylori is recommended in duodenal ulcer disease. The aim of this randomized open trial was to evaluate and compare H. pylori eradication and safety after a dual therapy consisting of lansoprazole (30 mg b.i.d.) and amoxicillin (1 g b.i.d.) versus a triple therapy consisting of lansoprazole (30 mg b.i.d.), amoxicillin (1 g b.i.d.), and clarithromycin (500 mg b.i.d.) administered from day 1 to day 14. METHODS: All patients with an ulcer received lansoprazole (30 mg) from day 15 to day 28. H. pylori status was determined from antral biopsies using histology, culture, and polymerase chain reaction (PCR) upon inclusion and 1-3 months after the end of the treatment. RESULTS: Of the 50 patients included in the study, five did not adhere to the protocol. H. pylori eradication was obtained in 37.5% of the patients receiving lansoprazole-amoxicillin (n = 9/24) and in 95.2% of the patients receiving lansoprazole-amoxicillin-clarithromycin (n = 20/21, p < 0.0002). Minor side effects appeared in 8.3% of the cases during dual therapy (n = 2/24) and in 52% during triple therapy (n = 13/22, p < 0.001). These side effects consisted mainly of diarrhea and a metallic taste. CONCLUSION: Concomitant administration of double doses of lansoprazole with amoxicillin and clarithromycin is very efficacious against H. pylori infection compared with dual therapy.

Treatment of central precocious puberty with depot leuprorelin. French Leuprorelin Trial Group.

We evaluated the pituitary and gonadal suppression in 40 girls and nine boys treated with depot leuprorelin (3.75 mg sc if body weight > or = 20 kg, 1.87 mg if body weight < 20 kg) every 28 days for central precocious puberty. Gonadal suppression was obtained in most of the children with this dose: 3 months after initiation of the treatment, 85% of children had a peak plasma luteinizing hormone response to gonadotropin-releasing hormone < 3 IU/l and the gonadal axis remained suppressed throughout the duration of the study (up to 24 months). Four patients required higher doses of leuprorelin to achieve suppression. In two girls, a cutaneous reaction to the drug was associated with incomplete suppression and the treatment had to be interrupted. Plasma leuprorelin levels tended to increase from day 3 to day 28 after injection. Residual leuprorelin levels measured 28 days after injection were stable during the first year of the study. We conclude that an initial dose of depot leuprorelin of 3.75 mg sc every 28 days is efficient in most children with central precocious puberty.

[Efficacy and tolerance of cefotiam hexetil in the super-infected chronic sinusitis. A randomized, double-blind study in comparison with cefixime]. / Efficacité et tolérance du céfotiam hexétil dans le traitement de surinfection de la sinusite chronique. Etude randomisée, en double aveugle, comparison au céfixime.

Efficacy and safety of a new oral third generation Cephalosporin, Cefotiam Hexetil (CTM) 200 mg bid were compared with those of Cefixime (CX) 200 mg bid over 10 day duration of treatment. One hundred and twenty two ambulatory adults suffering from chronic sinusitis were randomized by ENT specialists in this multicentre prospective double blind, doubled dummy study. Sinusitis diagnosis evocated in front of fascial pain, purulent nasal discharge and/or obstruction was confirmed with sinus X-ray. Use of antibiotics or corticosteroids concomitantly or 15 days prior inclusion represented one of the major exclusion criterion. One hundred and seventy one patients were evaluated for efficacy analysis (62 and 59 respectively in CTM and CX groups). Regarding demographic data, clinical and radiological signs, the two populations were comparable at inclusion excepted for sex and weight (female: 73% in CTM group versus 47% in CX group). The overall clinical success rate at the end of treatment (cure+improvement) was not significantly different between the two groups (CTM: 82% versus CX: 80%). The incidence of adverse events was less frequent in the CTM group (14.5% versus 19%). In conclusion, CTM 200 mg bid is as efficacious and as well tolerated as CX 200 mg bid in the treatment of chronic sinusitis in adults.

[Dose-response effect of lansoprazole in patients with Zollinger-Ellison syndrome]. / Effet dose-réponse du lansoprazole chez des malades atteints d'un syndrome de Zollinger-Ellison.

Lansoprazole, a new substituted benzimidazole, is an effective acid proton pump inhibitor acting by inhibiting selectively H+/K+ ATPase of the gastric parietal cell. This study was performed to assess the effect of successive 30, 60, 90 and 120 mg dosages of lansoprazole in 4 patients suffering from Zollinger-Ellison syndrome. The basal gastric acid output was markedly inhibited in comparison with baseline values (mean maximal reduction: 87%; extremes: 75-99%) and was dose-related. Lansoprazole inhibited pepsin output globally with a dose range effect between 30 and 90 mg/day. The treatment induced a rapid relief of clinical symptoms. No biological abnormality was noted. These data proved that lansoprazole is efficient for treating gastric acid hypersecretion in patients suffering from ZES.

[Comparative efficacy of lansoprazole and omeprazole on the intragastric pH measured over a period of 24 hours and on the basal]. / Efficacité comparée du lansoprazole et de l'oméprazole sur le pH intragastrique mesuré sur 24 heures et sur le débit acide basal chez 9 malades atteints de syndrome de Zollinger-Ellison.

OBJECTIVES: This paper aimed at evaluating the comparative efficacy of lansoprazole and omeprazole in reducing gastric acid secretion in patients suffering from Zollinger-Ellison syndrome. METHODS: Nine patients with non-resected gastrinoma(s) an previously well controlled by omeprazole (mean dosage 75 +/- 12.4 (SEM) mg/day; extremes: 20-160 mg/day) underwent 24-hour intragastric pH-metry, baseline acid output before next dosing and serum gastrin dosages, receiving their usual therapy and thereafter lansoprazole at a weight equivalent posology (mean dosage 81.6 +/- 12.5 (SEM) mg/day; extremes: 30-165 mg/day). RESULTS: Lansoprazole maintained intragastric pH and basal acid output at therapeutic levels, but a discrete reacidification, that deserves confirmation on a larger group of patients, was observed between the meals. CONCLUSIONS: The possible long-term benefit of this phenomenon, especially on gastrinemia and the fundic ECL-cells density and gastric bacterial content, remains to be evaluated.

[Prevention of postoperative infections with cefotiam (Pansporine) in orthopedic surgery]. / Prophylaxie par le céfotiam (Pansporine) des complications infectieuses post-opératoires en chirurgie orthopédique.

This prospective, randomized study was carried out in the Orthopaedic Traumatology service, Hôpital Bichat, from March 1987 to June 1989 in order to compare the efficacy of an antibiotic prophylaxis either with cefotiam in "flash" administration or with cefazolin in continued administration (48 hours). This study included 207 patients undergoing a total hip or knee-joint replacement. The both groups (89 patients with cefotiam, 118 patients with cefazolin) were comparable with regard to all criteria. The general and local evolution did not show statistical significant difference in the occurrence of complications in the both groups. No infectious complication occurred after the operation for the two groups. Then, cefotiam, in "flash" administration (2 g with the anesthetic induction) proves to be as effective as a conventional antibiotic prophylaxis with cefazolin in the prevention of infectious complications in orthopaedic surgery.