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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.

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.

To determine whether informed consent in a therapeutic trial modifies the analgesic effect of naproxen and placebo, we conducted a prospective, randomised, single dose, placebo-controlled trial. Patients were randomly selected to receive or not information concerning the study. All patients included were then given a single dose of naproxen and placebo according to a crossover, double-blind design. Forty-nine patients with mild or moderate cancer pain which did not need narcotic analgesics entered the study. Twenty-five received both treatments without any information and constituted the uninformed group. Twenty-four had a complete information about the trial; six refused to participate. The 18 others constituted the informed-consent group. Visual analogue scales of pain before and 30, 60, 120 and 180 min after the intake of naproxen and placebo were recorded. As an analgesic, naproxen was more effective than placebo in both groups of patients (p = 0.001). For naproxen as well as for placebo, the analgesic effect was better in the informed-consent group compared to the uninformed group (p = 0.012). The difference in therapeutic activity between naproxen and placebo was moderately higher in the uninformed patients (p = 0.08). We concluded that, in contrast with parallel studies, giving information in a crossover, placebo-controlled trial may increase the apparent efficacy of both the tested agent and the placebo, and decrease the perceived difference the two.

Ethanol undergoes gastric first pass metabolism by alcohol dehydrogenase (ADH). We have shown that cimetidine and famotidine both cause competitive inhibition of human gastric ADH in vitro. However, in a randomized 4-way cross-over study in 12 healthy subjects a 7-day course of treatment with cimetidine (800 mg day-1), ranitidine (300 mg day-1) or famotidine (40 mg day-1), did not modify the pharmacokinetics of ethanol given as a post-prandial 0.3 g kg-1 dose. We conclude that gastric mucosal concentrations of histamine H2-receptor blockers achieved after oral dosing are probably too low to cause significant inhibition of gastric ADH in vivo.

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.

Tuberculosis choroidal granulomas ("tubercules de Bouchut") are rare, even in patients with AIDS and active tuberculosis. The authors report the clinical and angiographical findings of three cases. Choroidal involvement was bilateral, with multiple lesions, mostly located at the posterior pole. The size of the granuloma ranged from 1/8 to 1/2 of a disc diameter. Fluorescein angiography showed early prolonged hypofluorescence and late moderate hyperfluorescence. The lesions remained stable for months despite treatment of tuberculosis, and then gradually subsided. In two cases, the choroidal granulomas were discovered before the diagnosis of disseminated tuberculosis and guided the investigations, which allowed the identification of Mycobacterium Tuberculosis bacillus in the body. In the third case, pulmonary tuberculosis had already been diagnosed. The number of tuberculosis cases is increasing together with the number of AIDS cases. This should make the observation of tuberculosis choroidal granulomas more frequent. The discovery of the typical aspects of granulomas described above during fundus examination of AIDS patients can help in diagnosing tuberculosis.

Four hundred and thirty patients with grade 2 or 3 esophagitis were treated after 2/1 randomization for 8 weeks with omeprazole 20 mg (n = 294) or ranitidine 150 mg bid (n = 136). Apart from treatment, 8 epidemiological factors (gender, age, occupation, obesity, smoking, alcohol, NSAID, and coffee or tea consumption), 5 clinical factors (day/night pain distribution, burning score, severity of regurgitation and of dysphagia, number of painful episodes requiring prescription of an antisecretory agent during the previous year, and onset of symptoms before age 30) and 3 endoscopic factors (grade and upward extension of esophagitis, and existence of hiatal hernia > or = 5 cm) were analysed. The influence of these factors on healing at 8 weeks and on changes in symptoms was evaluated by multivariate analysis. 92.1% of patients enrolled were analyzed. In comparison with ranitidine, omeprazole increased the percentage of healed patients (93% v. 67.5%, p < 0.001) and the rapidity of disappearance of symptoms (5 days v. 7 days, p < 0.001). Independent good prognostic factors associated with healing rate were treatment with omeprazole (p < 0.001) and grade 2 esophagitis (p < 0.001) while those associated with the disappearance of symptoms were a low burning score (p = 0.001), advanced age (p = 0.004), treatment with omeprazole (p = 0.005), the absence of any occupation (p = 0.01) and male gender (p = 0.017). The results of this study show that, apart from treatment, endoscopic factors are predictive of the healing of reflux esophagitis treated by antisecretory agents while clinical factors are more important with regard to the disappearance of symptoms.

Gaucher's disease is characterized by accumulation of glucocerebroside (caused by an autosomally inherited deficiency of glucocerebrosidase) in the cells of the reticuloendothelial system. We report the clinical, laboratory, radiologic features of 17 patients with type 1 Gaucher's disease.

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.

The correlation between ultrasonographic gastric emptying and appetite was studied. Echographic evaluation of gastric emptying by measurement of the antral vertical diameter and assessment of sensations of hunger and satiety using analogue visual scales were performed simultaneously in 12 healthy volunteers. Measurements were carried out after the intake of 10.8 g psyllium or placebo in a randomised, crossover, double blind trial. The correlation between echographic gastric emptying and sensations of hunger and satiety was excellent (p < 0.001) after the intake of either psyllium or placebo. Psyllium significantly delayed gastric emptying from the third hour after a meal. It increased the sensation of satiety and decreased hunger at the sixth hour after the meal. The association between echographic measurement and visual scales is a simple method of evaluating the relationship between the stomach and appetite. The pharmacodynamic effect of psyllium should be confirmed by longterm therapeutic trials.

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.

Acetorphan is a potent enkephalinase inhibitor displaying antidiarrhoeal activity attributable to its intestinal antisecretory action mediated by endogenous enkephalins. The effect of acetorphan on digestive motility was studied in 12 healthy volunteers. Oro-caecal transit time was evaluated using the sulphasalazine/sulphapyridine method and colonic transit times using radiopaque markers. These measurements were successively performed after one week treatment with an antidiarrhoeal dose of acetorphan (100 mg t.d.s.) or placebo. There was no significant modification in transit time linked to acetorphan treatment: total oro-caecal times were 303 +/- 32 min vs. 287 +/- 27 min and colonic transit times 25.8 +/- 5.8 h vs. 31.3 +/- 5.5 h after acetorphan and placebo, respectively (means +/- S.E.M.). There was no significant modification either in right colonic, left colonic or rectosigmoid segmental transit times, or in the mean number of stools. These results, consistent with those from animal studies, confirm that, unlike classical antidiarrhoeal mu opiate receptor agonists, which act by delaying intestinal transit, acetorphan does not affect the transit. Antidiarrhoeal activity not accompanied by a delayed intestinal transit could have beneficial therapeutic consequences in the management of infectious diarrhoea. In addition, we show that the sulphasalazine and radiopaque markers methods can be simultaneously applied in the same study.

The aim of the study was to use a novel combination of two methods for the simultaneous evaluation of two effects of oral cisapride in 10 diabetic patients with autonomic neuropathy; gastric empyting time was measured by following radio-opaque markers and orocaecal transit time by the sulphasalazine-sulphapridine method. The study was of double-blind, randomized, placebo-controlled, cross-over design. It was possible to evaluate the effect of a prokinetic drug on gastric emptying and orocaecal transit times using these two noninvasive techniques at the same time. Cisapride significantly reduced both the gastric empyting (1.2 h versus 2.1 h) and orocaecal tansit (5.9 h versus 7.7 h) times.

Endoscopic lesions of the gastric mucosa were evaluated in 12 healthy volunteers after administration of single doses of ketoprofen (25 mg), ibuprofen (200 mg) and aspirin (500 mg) in a randomized, double-blind, cross-over study. The grades of the lesions (according to Lanza's scale) were lower after the administration of ketoprofen than aspirin and were comparable to ibuprofen. An endoscopic score greater than 1 was observed in 3 cases after ibuprofen or ketoprofen, and in 8 cases after aspirin. At a time when low, single doses of NSAIDs are widely used as analgesics, gastroscopy makes it possible directly to assess the local aggressivity of these molecules. In this way it was possible to demonstrate that the local toxicity of NSAIDs was lower than that of aspirin.

The measurement of transgastric electric potential difference (DDP) is an easy and reproducible method for evaluation of the gastrotoxicity of aspirin. This randomised crossover placebo-controlled trial in 12 healthy volunteers involved study of the protective effect of misoprostol (Cytotec) against the fall in DDP induced by a gram of aspirin. One day of treatment with misoprostol 200 micrograms morning and evening led to a statistically lower fall in DDP than with the placebo: area under the curve 130 +/- 315 mV.min cf. 589 +/- 465 mV.min (p = 0.012), maximum variation 11.4 +/- 11.3 mV cf. 24.9 +/- 13.2 mV (p = 0.04). This result independent of the antisecretory action of the compound, confirms the protective effect of this prostaglandin analogue against the gastric damage caused by aspirin.

This study investigated the effect of three different mental stress tests on gastric transmucosal electric potential difference (GPD). GPD measurement was carried out in six healthy volunteers using the agar-KCl bridges method during dichotomous listening, the ringing of a telephone and 90 dB noise. Cardiac, pulmonary and psychological responses to stress were evaluated at the same time. During the stress period, two of the subjects had no change in GPD as well as no extragastric modification due to the stressor. The four other volunteers had a significant stress-induced fall in GPD (12.5 + 5.6 mV) with a simultaneous acceleration of heart and respiration rates and an increase in systolic blood pressure and anxiety feelings which were evaluated on a visual scale. Such mental stress, possibly mediated by autonomous nervous system, may cause some gastric mucosa changes inducing the retrodiffusion of H+ ions and a fall in GPD. This model could be useful in therapeutic research into the prevention and treatment of stress-induced gastric lesions.

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.

The presence of antibodies to Ebola virus among 1,517 apparently healthy persons in five regions of the Cameroons was tested using indirect immunofluorescence. A positive rate of 9.7% was found, confirming that the virus circulates in the absence of clinical cases. Highest rates were found among Pygmies, young adults, and rain forest farmers.

The presence of CA 125, an ovarian cancer-associated antigen, was assessed in serum and ascites from patients with ovarian cancer (n = 47), hepatocellular carcinoma (n = 21), and liver cirrhosis (n = 40). Abnormal levels of serum CA 125 were observed in 49% of ovarian cancer patients, and in 89% of these same patients with ascites. In all cases of cirrhosis or hepatocellular carcinoma with ascites, CA 125 levels were above 35 U/ml. The specificity and sensitivity of CA 125 measurement for detecting ascites in chronic liver diseases were 73% and 100%, respectively. Furthermore, the CA 125 level was always higher in ascites than in serum. The authors conclude that CA 125 is a nonspecific marker of ascites. This result must be considered in the interpretation of CA 125 elevation in patients with ovarian cancer. Moreover, CA 125 may be of value in the diagnosis and monitoring of peritoneal diseases.

The gastric potential difference (PD) was measured in ten healthy volunteers after sodium taurocholate intake. This bile salt was given after treatment with dimethicone or placebo in a cross-over design study. With dimethicone the fall in PD was lower (16.1 vs. 24.8 mV,) and shorter (32.5 vs. 51.0 min) than with the placebo. Our result suggests that the silicone can prevent the formation of the gastric lesions induced by bile salts.

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.

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.

We describe immunoscintigraphy using a radiolabelled anti-tumor monoclonal antibody 181-23 in 6 patients with squamous lung cancer. Double-label method using simultaneous injections of 131I MAB and 125I control immunoglobulin was performed to evaluate the specificity of MAB localization in the tumor. Immunohistological localization of MAB in resected specimen was obtained by immunoperoxidase technique. All our data are negative but correlated.

The ingestion of radio-opaque granules during a meal enables the radiological study of gastric emptying under physiological conditions. The evacuation of the granules is well correlated with that of solids. After the development of a pharmaco-clinical model of hyposthenic dyspepsia, this technique was used by the authors to evaluate the influence of Primperan on gastric emptying after a dyspeptogenic meal in 12 volunteers. Following the randomised intravenous injection of either 20 mg of Primperan or a placebo, 5 to 7 minutes before the dyspeptogenic meal, the number of granules remaining in the stomach over time was used to measure the rate of gastric emptying. Primperan significantly accelerated the gastric emptying of the dyspeptogenic meal in comparison with the placebo (p less than 0.01).

A series of 121 consecutive patients with abdominal (96 cases) and retroperitoneal (25 cases) masses was studied in order to evaluate the contribution of cytology in establishing a definite diagnosis of the tumors. The cytologic results on aspirates were obtained with 22 or 23 gauge Chiba needles. At the same time, percutaneous fine needle aspiration biopsy was performed with 19 or 21 gauge fine needles having circumferentially bevelled tips that produced tiny tissue cores suitable for histologic study in 88 cases. These diagnoses were controlled with larger pathological specimens in 78 cases and appeared to be consistent with the clinical and biological course in 43 cases. The sensitivity of the cytologic diagnosis was 83 per cent, and its overall accuracy 87.6 per cent. There were no false-positive results. Furthermore, the method proved to be safe and well-tolerated, with low morbidity (0.8 per cent) and no mortality.

Two high affinity monoclonal antibodies, designated AF01 and AF04, directed against distinct epitopes of human alpha-fetoprotein (AFP) and the Fab fragments of one of them, were labelled with 131I and injected into 18 patients with AFP producing hepatocellular carcinoma (HCC) in order to carry out imaging studies by tomoscintigraphy. Twelve patients were injected with whole antibody, only three of seven patients injected with AF01 and two of five patients injected with AF04 had a positive scan. In contrast, five out of six patients injected with labelled Fab fragments of AF04 had positive imaging. These results confirm that tumour imaging of HCC using 131I labelled monoclonal antibody against AFP is feasible. Moreover, utilization of tomoscintigraphy in place of linear scintigraphy and Fab fragments instead of whole immunoglobulin may improve the sensitivity of radioimmunolocalization. This technique provides useful information on the in vivo distribution of monoclonal antibodies directed against AFP and on the practicability of the eventual therapeutic use of anti-AFP antibodies in HCC.

The presence of Ca 125, an ovarian cancer-associated antigen, was assessed in serum from patients with liver diseases with (n = 26) and without (n = 26) ascites. Abnormal levels of serum CA 125 were observed in all patients with ascites and in 4 patients without ascites (15%). We conclude that CA 125 is a non-specific marker of ascites whatever the origin: ovarian carcinoma, cirrhosis or peritoneal inflammatory process.

A case of sclerosing cholangitis after a two-month treatment by hepatic artery infusion of FUDR is reported. The patient presented with jaundice and a marked increase in serum alkaline phosphatase activity which persisted after withdrawal of FUDR infusion. Endoscopic retrograde cholangiogram revealed a stricture of the middle part of the common bile duct, which was treated by endoprosthesis insertion. From this report, as well as those previously published, it is concluded that sclerosing cholangitis may complicate continuous hepatic artery infusion with FUDR. This lesion could be secondary to an FUDR-induced arteritis in the branches of hepatic artery which supply bile ducts.

A 53-year-old man with hepatitis concurrent with cirrhosis was simultaneously positive for hepatitis B surface antigen and heterotypic anti HBs antibody. This could be explained by a state of tolerance, with chronic carrying of B virus (subtype a y w3), but would not preclude B virus (subtype d) reinfection, inducing the synthesis of specific anti-d antibodies. In the same patient, the very high level of 3460 ng/ml was reached for alpha-fetoprotein; this was transitory and returned to normal within 8 months; it was probably due to the acute hepatitis. Thus it appears that, even in cases of cirrhosis, a major rise in this marker does not absolutely imply the presence of hepatocellular carcinoma.