Protection against aspirin-induced gastric lesions by lansoprazole: simultaneous evaluation of functional and morphologic responses.

The protective effect of lansoprazole, a new proton pump inhibitor, against aspirin-induced gastric lesions was studied in a double-blind crossover trial with a simultaneous measure of the functional capacities of the mucosal barrier (by a recording of the gastric potential difference) and of the morphologic changes in the mucosa (by gastric endoscopy). After 1 week of treatment with lansoprazole (30 mg per day) or placebo, each healthy volunteer received 1 gm aspirin by mouth. Recording of the gastric potential difference lasted for 3 hours and was followed by gastric endoscopy. Morphologic lesions induced by aspirin were effectively prevented by lansoprazole: Lanza score was 0.67 +/- 0.98 (mean +/- SD) versus 2.25 +/- 1.1 with placebo (p < 0.005, ANOVA). Conversely, the decrease in the gastric potential difference was similar. The inhibition of acid secretion induced by lansoprazole was therefore sufficient to prevent aspirin-induced mucosal lesions without reinforcing the defense capacities of the mucosa. This simple pharmacologic model makes it possible to simultaneously evaluate the functional and morphologic effects of aspirin intake on the gastric mucosa.

Persistent gastric-protective effect of antacid evaluated by measurement of transmucosal gastric potential difference.

The aim of this study was to determine the effect of 1 week of antacid dosing on the aspirin-induced potential differences (PDs) across the gastric mucosa. The study design was double blind and randomized with crossover. Ten healthy subjects received aluminum hydroxide gel, 8 gm t.i.d., or placebo for 1 week. They then received 1 gm aspirin after an overnight fast and the PD across the mucosa was measured. Baseline potentials were the same before both treatment periods. Antacids reduced the aspirin-induced PDs. The mean (+/- SD) maximal PD was 27.4 +/- 1.7 mV with placebo vs. 10.7 +/- 2.2 mV with antacids (p less than 0.001). Recovery time was 65.5 +/- 5.2 minutes with placebo vs. 29.0 +/- 6.7 minutes with antacids (p less than 0.001). These results suggest the effect is due to a longer-term cytoprotective property of antacids rather than to acid-neutralizing activity.

Investigation of drug interactions with pinaverium bromide.

A series of studies was carried out at 6 centres to investigate possible drug interaction between the spasmolytic, pinaverium bromide, and cardiac glycosides, anticoagulants and hypoglycaemic agents given to patients as part of the long-term treatment of their condition. The results of clinical and laboratory investigations did not show any evidence of pinaverium bromide interfering with the action or activity of any of the drugs studied.

What is the better formulation of microencapsulated potassium chloride?

A single blind cross-over study was performed comparing a new microencapsulated potassium chloride tablet (MET) with two reference formulations of oral potassium, namely potassium chloride solution (PS), and microencapsulated potassium chloride capsules (MEC), in 18 normal healthy volunteers. The potassium chloride induced change in gastric potential difference (PD) of the mucosa was the main criterion of comparison and was assessed by the area above curve (AAC), the total duration of the effect (TDE), the maximal variation of PD (delta MAX), and the aggression index (AI). The results showed that all three formulations induced a fall in PD; the delta MAX and AAC were significantly greater for PS indicating a higher aggressive effect of the solution; MET had significantly less aggressive effect than MEC when assessed by all parameters.

Pharmacokinetics of reboxetine in healthy, elderly volunteers.

The pharmacokinetic characteristics of reboxetine, a unique selective noradrenaline reuptake inhibitor (selective NRI) for the treatment of depression, were studied in 12 healthy, elderly volunteers (mean age 81 years +/- 9 years). All subjects received a single 4-mg dose of reboxetine, and plasma reboxetine concentrations were measured by HPLC. Reboxetine was well tolerated by all subjects. Exposure to reboxetine was higher in this group of very elderly subjects, compared with data obtained in a similar study of young, healthy volunteers. Cmax in the elderly was 271 +/- 86 ng/ml, compared with 111 +/- 28 ng/ml in the young subjects after a single 4-mg dose, although in both groups Cmax was observed after 2 h. The AUC infinity was nearly four times that in the younger subjects (8345 +/- 3107 ng.h/ml vs. 2106 +/- 881 ng.h/ml) and the t1/2 was twice as long (24 +/- 6 h vs. 12 +/- 3 h). Renal clearance was also reduced. Reboxetine 8-10 mg/day has been effective and well tolerated in clinical trials in non-elderly depressed patients. The increased exposure to reboxetine observed in our very elderly subjects supports a reduction of the starting dose to 4 mg/day (in two divided doses) in the elderly.

[Critical examination of scoring systems in therapeutic trials]. / Examen critique des grilles de lecture des essais thérapeutiques.

Scoring systems give a check-list and methodological informations which have to be found in controlled therapeutic trials reports and papers. These systems try to quantify each item to give a global score. The Chalmer's list is the most wellknown. It allows a balance in scoring taking in account the quality of the endpoints. Other lists are more simple. Many check-lists allow the scoring of the methodological design or the statistical analysis. In all systems the major methodological points are: the randomization, the description of the population, the double blind, the estimation of the sample size, the handling of withdrawal and drop out, the major endpoint, the patients follow-up, the statistical analysis and the data presentation. All these scoring systems have several limits: the quantitative evaluation of each item is subjective and the point scoring has never been validated, some scoring systems are old and don't integrate new methodological methods, the scores never included the clinical interest of the trial, some items are questionable, others are forgotten (intention to treat analysis, steering comity...). Scoring systems allow a control of the methodological quality of clinical trials but don't include the clinical or scientific interest of the study. These systems are a useful methodological tool for publication process in medical journals and for new drugs authorization. The evaluation by authors themselves of the quality of their papers using a standardized scoring system could clarify the reviewers decisions.

[Methods for studying the hepatic metabolism of drugs in man]. / Méthodes d'exploration du métabolisme hépatique des médicaments chez l'homme.

Various methods can be used to investigate human hepatic drug metabolism in vivo. a) Indirect methods based on the assessment of atoxic substances metabolism in order to investigate: --hepatic oxidative activity by antipyrine or caffeine clearance and aminopyrine breath test determination. Such an activity can be modified by drug-induced enzyme induction or inhibition and in case of hepatic disease; --genetic polymorphism of hepatic drug metabolism assessed by the determination of debrisoquine or dextrometorphane metabolic ratio and of N-acetylation phénotype. Unusual therapeutic or adverse effects could be explained by such a polymorphism; --hepatic blood flow, which variations could modify hepatic clearance of drugs with a high hepatic extraction ratio, by the assessment of indocyanine green clearance. b) Direct methods based on pharmacokinetics data and their alterations under various circumstances: simultaneous administration of other drugs, liver disease.

[Prolonged effect of an antacid treatment on changes in gastric potential difference induced by aspirin in man]. / Effect prolongé d'un traitement anti-acide sur les modifications de la différence de potential gastrique induites par l'asprine chez l'homme.

In ten healthy volunteers, we evaluated the effects of a 6 days antacid treatment (Rocgel) on the aspirin induced changes in gastric potential difference (PD). In this placebo controlled cross-over study, PD was measured twelve hours after the last take of the antacid. Aspirin induced drop of PD was less pronounced after antacid compared to placebo; maximal fall of PD and area upper the curve decreased (p less than 0.001). This effect was observed twelve hours after the last take of the antacid. It may suggested a long-term protective effect on the gastric mucosa.

[Determination of erythrocyte sorbitol]. / Détermination du sorbitol érythrocytaire.

An increase in the intra-cellular concentrations of sorbitol can be responsible, at least in part, for certain long term complications of diabetes. Since the erythrocyte concentration of this polyol is a good indicator of that of other cells, we propose a simple, rapid enzymatic assay technique for red blood cells. The results already obtained reveal a significant difference between the erythrocyte sorbitol concentration in non-diabetic subjects and that in diabetic patients.

[Therapeutic principles in gastroesophageal reflux]. / Principes thérapeutiques du reflux gastroesophagien.

Gastroesophageal reflux is a common disease. Its chronic course, even if mild, is sometimes complicated by erosive oesophagitis. Drug therapy acts against gastric acidity and motility disorders. Treatment of gastroesophageal reflux disease has three aims: improvement of symptoms and quality of life, healing erosive lesions and prevention of symptomatic and endoscopic relapses. Non-drug measures are always useful, even if their efficacy is not well established. Initial therapy of a symptomatic reflux or mild oesophagitis is most of the time effective (antacids, prokinetics, H2 receptor antagonists). Proton-pump inhibitors are also effective in healing and preventing severe oesophagitis. Questions about long-term treatment adverse events with powerful acid inhibitors, such as hypergastrinemia and the risk of gastric carcinoid tumours seem to be resolved. Studies are requested to define the optimal long-term maintenance treatment with cisapride, H2 receptor antagonists or proton-pump inhibitors at low doses in prevention of symptomatic and mild oesophagitis relapses.

[Gas gangrene disclosing colonic cancer. Role of synergistic gangrene]. / Gangrène gazeuse révélant un cancer colique. Place de la gangrène synergistique.

After reporting a case of synergistic gas gangrene of the retroperitoneum spreading to the thigh, revealing a carcinoma of the descending colon, the authors review the symptomatology and management of synergistic gas gangrene defined as a gas gangrene due to anaerobic non clostridial bacilli, and aerobic flora and emphasize the exceptional nature of its association with a carcinoma of the colon.

[Can respiratory tolerance to beta-blockers be predicted?]. / Peut-on prévoir la tolérance respiratoire d'un bêta-bloqueur?

Adverse effects on respiratory function is one of the main problems associated with the use of beta-adrenoceptor antagonists. Studies on this subject in healthy volunteers or patients with obstructive airway disease have been performed by measuring air flow at rest and after exercise, but no attention has been paid to the repercussions on pulmonary circulation. The lack of standardized protocol, the inhomogeneity of groups and the absence of long-term studies preclude objective comparisons between the different beta-adrenoceptor antagonists. On the whole, cardioselective beta-blockers are better tolerated than the others, but any classification based on the respiratory effects to cardiovascular effectiveness ratio is, for the moment, impossible to establish.

[Acute suppurative myositis. 4 cases]. / Myosites aiguës suppurées. Quatre cas.

Four cases of acute pyomyositis are reported. They were diagnosed at an advanced stage, and the different complementary examinations were of uneven value. The responsible pathogen was Staphylococcus aureus in 3 cases and a strain of Streptococcus in 2 cases (one patient had both germs). Cure was obtained in 3 patients, including one who required amputation; the 4th patient died. In this disease only the finding of purulent fluid at surgery or by needle aspiration has a diagnostic value. Management consists of antibiotic therapy associated with surgical drainage.

[Prevention of gastroduodenal lesions induced by non-steroidal anti-inflammatory agents. Economic analysis from a survey of 356 physicians]. / Prévention des lésions gastro-duodénales induites par les anti-inflammatoires non stéroïdiens. Analyse économique à partir d'un sondage réalisé chez 356 médecins.

In order to obtain information on prescribing habits concerning the prevention of gastroduodenal lesions induced by non-steroidal anti-inflammatory agents (NSAI), 356 physicians practicing in 2 French departments were asked to fill a posted questionnaire. Fifty-one percent of these doctors gave an assessable answer. Among these, 84 percent occasionally prescribe "gastric protectors" associated with NSAI's in 32 percent of the prescriptions. They use antacids (48 percent), anti-H2 products (27 percent), sucralfate (11 percent) or prostaglandins (13 percent). This represents a daily cost of additional treatment ranging from 0.87 to 2.49 francs. If fibroscopies and further consultations necessitated by the prescription of NSAI's are taken into account, then 86 to 140 percent must be added to the cost of NSAI's. The profitability of these preventive measures in terms of public health will be really estimated only when the number of severe gastroduodenal lesions effectively prevented by taking topical gastric protectors or anti-secretory agents will be known.

[Surgical treatment of Basedow's disease. I--Traditions and new methods in preparation for thyroidectomy: use of dexamethasone]. / Traitement chirurgical de la maladie de Basedow. I--Traditions et nouveautés dans la préparation à la thyroïdectomie: utilisation de la dexaméthasone.

The combination of dexamethasone (2 mg every 6 hours) carbimazole (15 mg every 8 hours) and potassium iodide (XV drops every 8 hours) has been proposed in the preparation of 21 patients with hyperthyroid Graves' disease for surgery. The combination was administered for 6 days and the subtotal thyroidectomy was performed on day 7. All patients had normal serum Triiodothyronine levels after 4 days of such treatment. This combined drug therapy appears to be a rapid, sage and effective preparation for thyroid surgery in patients with Graves' disease and should replace conventional preparation with carbimazole and potassium iodide and beta-blocker preparation in all cases where there are no contra-indications to the use of corticosteroids.

[Surgical treatment of Basedow's disease. II--Evaluation of 36 subtotal thyroidectomies]. / Traitement chirurgical de la maladie de Basedow. II--Bilan de 36 thyroïdectomies sub-totales.

Results of subtotal thyroidectomy in 36 patients with Graves' disease emphasize the need for strict medical preparation, with the administration of corticoids more particularly, and the technical imperatives required during operation. Analysis of endocrine factors showed that euthyroidism was obtained in 76% of cases with a fairly stable state after 6 months. Hyperthyroidism was rare and developed before the end of the first year. Hypothyroidism, mainly biologic, was frequent during the immediate postoperative period but compensatory hypertrophy of remaining tissue was the usual outcome. It was persistent in 14% of cases, however, but easily compensated by substitutive therapy and a less severe complication than prolonged hyperthyroidism. Biologic hypocalcemia was also frequent but normal levels were reinstituted rapidly. Surgical treatment of Graves' disease is usually effective and rapidly performed, and is particularly indicated when socio-ethnic conditions make medical treatment difficult or impossible.