Preclinical discovery and initial clinical data of WVT078, a BCMA × CD3 bispecific antibody.

B-cell maturation antigen (BCMA) is an ideal target in multiple myeloma (MM) due to highly specific expression in malignant plasma cells. BCMA-directed therapies including antibody drug conjugates, chimeric antigen receptor-T cells and bispecific antibodies (BsAbs) have shown high response rates in MM. WVT078 is an anti-BCMA× anti-CD3 BsAb that binds to BCMA with subnanomolar-affinity. It was selected based on potent T cell activation and anti-MM activity in preclinical models with favorable tolerability in cynomolgus monkey. In the ongoing first-in-human phase I dose-escalation study (NCT04123418), 33 patients received intravenous WVT078 once weekly at escalated dosing. At the active doses of 48-250 µg/kg tested to date (n = 26), the overall response rate (ORR) was 38.5% (90% CI: 22.6-56.4%) and the complete response rate (CRR, stringent complete response + complete response) was 11.5%, (90% CI: 3.2-27.2%). At the highest dose level tested, the ORR was 75% (3 of 4 patients). 26 (78.8%) patients reported at least one Grade ≥3 AE and 16 of these AEs were suspected to be drug related. 20 patients (60.6%) experienced cytokine release syndrome. WVT078 has an acceptable safety profile and shows preliminary evidence of clinical activity at doses tested to date.

[Prognostic factors of neurofibromatosis type 1-associated optic pathway gliomas in children]. / Facteurs pronostiques des gliomes des voies optiques associés à la neurofibromatose de type 1 chez les enfants.

INTRODUCTION: Optic pathway glioma (OPG) is a classic complication of neurofibromatosis type 1 (NF1) and can impair visual function in children with this condition. The objective of this study is to describe clinical, paraclinical and prognostic characteristics of OPG associated with NF1. MATERIALS AND METHODS: In this retrospective observational study of children followed for OPG associated with NF1 in a University Hospital, we analyzed the ophthalmological examination, brain and orbital imaging, management and the presence of associated endocrinopathy. RESULTS: We examined 114 children with NF1, of which 26 (22.81%) presented with OPG. Mean ages at diagnosis of NF1 and OPG were 3.83 years and 6.23 years, respectively. Mean visual acuity was 20/24.4 for the worse eye and 20/23.1 for the better eye. The RNFL (retinal nerve fiber layer) was thinner in subjects than in age-matched controls (p <0.0001). Retrochiasmal location of the OPG (DodgeC) was associated with lower binocular visual acuity than other locations and <20/32 (p=0.028); 28.03% of OPG (5 girls and 1 boy) were treated with chemotherapy, and the others were monitored; 19.23% had an associated endocrinopathy. CONCLUSIONS: OPG complicates 22.81% of NF1 cases in our series. Our study shows that retrochiasmal location of the glioma and female sex are poor prognostic factors. It also highlights the important role of OCT, since a decrease in RNFL is statistically associated with the presence of an OPG.

Herpes simplex virus glycoprotein B associates with target membranes via its fusion loops.

Herpes simplex virus (HSV) glycoproteins gB, gD, and gH/gL are necessary and sufficient for virus entry into cells. Structural features of gB are similar to those of vesicular stomatitis virus G and baculovirus gp64, and together they define the new class III group of fusion proteins. Previously, we used mutagenesis to show that three hydrophobic residues (W174, Y179, and A261) within the putative gB fusion loops are integral to gB function. Here we expanded our analysis, using site-directed mutagenesis of each residue in both gB fusion loops. Mutation of most of the nonpolar or hydrophobic amino acids (W174, F175, G176, Y179, and A261) had severe effects on gB function in cell-cell fusion and null virus complementation assays. Of the six charged amino acids, mutation of H263 or R264 also negatively affected gB function. To further analyze the mutants, we cloned the ectodomains of the W174R, Y179S, H263A, and R264A mutants into a baculovirus expression system and compared them with the wild-type (WT) form, gB730t. As shown previously, gB730t blocks virus entry into cells, suggesting that gB730t competes with virion gB for a cell receptor. All four mutant proteins retained this function, implying that fusion loop activity is separate from gB-receptor binding. However, unlike WT gB730t, the mutant proteins displayed reduced binding to cells and were either impaired or unable to bind naked, cholesterol-enriched liposomes, suggesting that it may be gB-lipid binding that is disrupted by the mutations. Furthermore, monoclonal antibodies with epitopes proximal to the fusion loops abrogated gB-liposome binding. Taken together, our data suggest that gB associates with lipid membranes via a fusion domain of key hydrophobic and hydrophilic residues and that this domain associates with lipid membranes during fusion.

Impact of image-space resolution modeling for studies with the high-resolution research tomograph.

UNLABELLED: Brain PET in small structures is challenged by low resolution inducing bias in the activity measurements. Improved spatial resolution may be obtained by using dedicated tomographs and more comprehensive modeling of the acquisition system during reconstruction. In this study, we assess the impact of resolution modeling (RM) during reconstruction on image quality and on the estimates of biologic parameters in a clinical study performed on a high-resolution research tomograph. METHODS: An accelerated list-mode ordinary Poisson ordered-subset expectation maximization (OP-OSEM) algorithm, including sinogram-based corrections and an experimental stationary model of resolution, has been designed. Experimental phantom studies are used to assess contrast and noise characteristics of the reconstructed images. The binding potential of a selective tracer of the dopamine transporter is also assessed in anatomic volumes of interest in a 5-patient study. RESULTS: In the phantom experiment, a slower convergence and a higher contrast recovery are observed for RM-OP-OSEM than for OP-OSEM for the same level of statistical noise. RM-OP-OSEM yields contrast recovery levels that could not be reached without RM as well as better visual recovery of the smallest spheres and better delineation of the structures in the reconstructed images. Statistical noise has lower variance at the voxel level with RM than without at matched resolution. In a uniform activity region, RM induces higher positive and lower negative correlations with neighboring voxels, leading to lower spatial variance. Clinical images reconstructed with RM demonstrate better delineation of cortical and subcortical structures in both time-averaged and parametric images. The binding potential in the striatum is also increased, a result similar to the one observed in the phantom study. CONCLUSION: In high-resolution PET, RM during reconstruction improves quantitative accuracy by reducing the partial-volume effects.

Influence of chronic lactulose ingestion on the colonic metabolism of lactulose in man (an in vivo study).

The effects of a chronic load of nonabsorbable sugars on intracolonic bacterial metabolism of carbohydrates and on H2 breath excretion are disputed. However, most of the discussion relies on indirect evidence or on results of in vitro studies. Thus, we attempted to assess directly and in vivo the effects on intracolonic metabolism of lactulose of a chronic oral load of this nonabsorbable disaccharide. 20 g of lactulose was given orally twice daily during 8 d to eight normal volunteers. In all, breath H2 concentration was measured on days 1 and 8 after ingestion of the morning lactulose dose. In four subjects, stools were collected during 2 d at the beginning and at the end of the lactulose maintenance period to measure fecal pH and daily outputs of carbohydrates and beta-galactosidase. The four other subjects were intubated on days 1 and 8 to measure the pH and the concentrations of carbohydrates, lactic acid, and volatile fatty acids (VFA) in the distal ileum and cecal contents. Moreover, 14C-lactulose was added to cold lactulose and 14CO2 breath outputs determined. Pulmonary H2 excretion fell from day 1 to day 8 (P less than 0.05), whereas 14CO2 excretion increased (P less than 0.01). Fecal water pH, lactic acid, and VFA concentrations did not vary between the two stool collection periods. 24-h fecal weight, fecal water, and carbohydrate outputs showed a trend to decrease between days 1 and 2 and days 7-8, whereas beta-galactosidase activity rose markedly (P less than 0.01). No significant variations were observed for all parameters measured in ileal fluid. In the cecum, areas under the concentration curves decreased from day 1 to day 8 for lactulose, galactose, and fructose (P less than 0.01), while an increase was found for lactic acid (P less than 0.001), acetic acid (P less than 0.0001), and total VFA (P less than 0.001). Cecal fluid pH dropped faster (P less than 0.05) and to a lower level (P less than 0.05) on day 8 than on day 1. These data clearly show that a chronic load of a nonabsorbable sugar induces changes in colonic bacterial metabolic pathways resulting in a better efficiency of the flora to digest the carbohydrate.

Differential insertion of GPI-anchored GFPs into lipid rafts of live cells.

Partitioning of proteins in cholesterol and sphingolipid enriched plasma membrane microdomains, called lipid rafts, is critical for many signal transduction and protein sorting events. Although raft partitioning of many signaling molecules remains to be determined, glycosylphosphatidyl-inositol (GPI)-anchored proteins possess high affinity for lipid rafts and are currently exploited as markers to investigate fundamental mechanisms in protein sorting and signal transduction events. In this study, we demonstrate that two recombinant GPI-anchored green fluorescent proteins (GFP-GPIs) that differ in their GPI signal sequence confer distinct localization in plasma membrane microdomains. GFP fused to the GPI signal of the decay accelerating factor GFP-GPI(DAF) partitioned exclusively in lipid rafts, whereas GFP fused to the GPI signal of TRAIL-R3, GFP-GPI(TRAIL-R3), associated only minimally with microdomains. In addition, we investigated the unique ability of purified GFP-GPIs to insert into membrane microdomains of primary lymphocytes. This cell surface painting allows rapid, stable, and functional association of the GPI-anchored proteins with the target cell plasma membrane. The distinct membrane localization of the two GFP-GPIs was observed irrespective of whether the GPI-anchored molecules were painted or transfected. Furthermore, we show that painted GFP-GPI(DAF) was totally dependent on the GPI anchor and that the membrane insertion was increased by the addition of raft-associated lipids such as cholesterol, sphingomyelin, and dipalmitoyl-phosphatidylethanolamine. Thus, this study provides evidence that different GPI signal sequences lead to distinct membrane microdomain localization and that painted GFP-GPI(DAF) serves as an excellent fluorescent marker for lipid rafts in live cells.

Joint estimation of dynamic PET images and temporal basis functions using fully 4D ML-EM.

A fully 4D joint-estimation approach to reconstruction of temporal sequences of 3D positron emission tomography (PET) images is proposed. The method estimates both a set of temporal basis functions and the corresponding coefficient for each basis function at each spatial location within the image. The joint estimation is performed through a fully 4D version of the maximum likelihood expectation maximization (ML-EM) algorithm in conjunction with two different models of the mean of the Poisson measured data. The first model regards the coefficients of the temporal basis functions as the unknown parameters to be estimated and the second model regards the temporal basis functions themselves as the unknown parameters. The fully 4D methodology is compared to the conventional frame-by-frame independent reconstruction approach (3D ML-EM) for varying levels of both spatial and temporal post-reconstruction smoothing. It is found that using a set of temporally extensive basis functions (estimated from the data by 4D ML-EM) significantly reduces the spatial noise when compared to the independent method for a given level of image resolution. In addition to spatial image quality advantages, for smaller regions of interest (where statistical quality is often limited) the reconstructed time-activity curves show a lower level of bias and a lower level of noise compared to the independent reconstruction approach. Finally, the method is demonstrated on clinical 4D PET data.

Can diarrhea induced by lactulose be reduced by prolonged ingestion of lactulose?

Twelve healthy volunteers were studied for two test periods, at the beginning of which they ingested a diarrheogenic load (60 g) of lactulose in 350 mL water with 10 g polyethylene glycol 4000 (PEG); the two periods were separated by a lactulose feeding period of 8 d, during which a nondiarrheogenic load (20 g) of lactulose was taken twice daily. The transit time and flow rates of water and lactulose in the distal ileum of four subjects were not different before and after the lactulose feeding period. In the other eight subjects, stool weight and frequency, fecal pH, and fecal outputs of carbohydrates and osmotic moieties after the ingestion of 60 g lactulose dropped significantly (P < 0.05) after the lactulose feeding period, whereas the orofecal transit time and fecal concentrations of beta-galactosidase and lactic acid increased (P < 0.05). We conclude that changes in colonic function induced by prolonged exposure to a nondiarrheogenic amount of lactulose mitigate the severity of the diarrhea because of the larger dose of lactulose.

Starch absorption by healthy man evaluated by lactulose hydrogen breath test.

The amounts of hydrogen produced from starch and lactulose were compared to assess the accuracy of the hydrogen breath test with lactulose as standard to quantify starch malabsorption. The mean amounts of hydrogen produced from starch and lactulose were not different in fecal homogenates and in breath excretion after carbohydrate infusions into the cecum. Known amounts of starch infused into the cecum of 18 subjects were compared with amounts calculated from the total excess excretion of hydrogen in breath computed in relation to hydrogen production after the ingestion of 10 g lactulose; calculated amounts were 3.6 +/- 1.0, 9.9 +/- 1.3, and 22.0 +/- 3.4 g for the infusion of 5, 10, and 25 g of starch, respectively. The lactulose hydrogen breath test based on total excess hydrogen volume provides a valid measurement of the mean amount of starch metabolized in the colon in a group of subjects. However, large individual variations preclude its use in a given subject.

Progress with proton pump inhibitors in acid peptic disease: treatment of duodenal and gastric ulcer.

To date, the primary therapeutic approach to peptic ulcer disease, either gastric or duodenal ulcer, remains the inhibition of gastric acid secretion. The major therapeutic goals in peptic ulcer disease are symptom relief, acceleration of crater healing, and the prevention of relapse or recurrence. Since the introduction of H2-receptor antagonists and proton pump inhibitors, the full control of acid secretion can be achieved. In the treatment of gastric ulcer, analysis of all studies that have compared lansoprazole, a newly developed proton pump inhibitor, and H2-receptor antagonists has shown a statistically significant difference for a higher healing rate with lansoprazole. In most of the comparative studies, the time to epigastric pain relief was shorter after receiving lansoprazole than after H2-receptor antagonists. In a single study comparing lansoprazole with omeprazole in 126 gastric ulcer patients, the healing rate at 8 weeks was significantly higher (P = 0.04) for lansoprazole than for omeprazole (93% vs 82%). In most studies comparing lansoprazole to H2-receptor antagonists in the treatment of duodenal ulcer, the healing rates at 4 weeks were significantly higher in the lansoprazole group. The time to achieve epigastric pain relief was significantly shorter with lansoprazole. In a single study comparing lansoprazole with omeprazole, ulcer healing rates at 2 weeks were significantly higher for lansoprazole (74% vs 58%) but not at 4 weeks (94% vs 94%). In conclusion, lansoprazole is more effective than H2-receptor antagonists in relieving ulcer pain and has a similar safety profile in the healing of gastric and duodenal ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-four-hour monitoring of intragastric acidity: comparison between lansoprazole 30mg and pantoprazole 40mg.

OBJECTIVE: To date, there is no published study, comparing the effects of lansoprazole and pantoprazole on gastric acid secretion inhibition. The aim of this study, was to compare the effects of these two drugs on 24-h intragastric pH-metry. DESIGN: Twelve healthy volunteers were included in an open, randomized, crossover study. Each subject received lansoprazole 30mg during 7 days followed, after a 14-day wash-out period, by pantoprazole 40 mg for 7 days or vice versa. Intragastric 24-h pH monitoring was performed before the treatment, and then after the first and seventh intake in each treatment period. RESULTS: The decrease in gastric acidity on daytime, night-time and total 24-h periods during both treatments was significantly different from the base value. Significant differences in acid inhibition were found between lansoprazole 30mg and pantoprazole 40 mg during daytime and 24 h after the first intake. After repeated dose regimens, a significant difference was detected between treatment periods but only for pH above 4. After the first dose, the median pH value with lansoprazole was also significantly greater than for pantoprazole. Pantoprazole activity increased significantly from first to seventh intake, in contrast to lansoprazole. CONCLUSION: Lansoprazole 30 mg was significantly more potent than pantoprazole 40 mg on 24-h pH profiles on the first and seventh days. The antisecretory effect of lansoprazole was maximum after the first intake whereas pantoprazole activity increased significantly between the first and last intake.

Placebo-controlled clinical trial of mesalazine in the prevention of early endoscopic recurrences after resection for Crohn's disease. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID).

OBJECTIVE: Endoscopic postoperative recurrences occur early after 'curative' surgery for Crohn's disease. Pentasa has been shown to be effective in the maintenance treatment of quiescent Crohn's disease. The aim of this study was to test the efficacy of a 12-week oral intake of Claversal in the prevention of endoscopic recurrences after 'curative' resection for ileal, colonic or ileocolonic Crohn's disease. We conducted a multicentre double-blind controlled trial comparing Claversal (1g tid) with placebo, starting within 15 days after surgery. The macroscopic normality of the two anastomotic segments was assessed at surgery. Patients were clinically and biologically evaluated twice (6-week interval), and colonoscopy was performed at 12 weeks. Endoscopic relapse was defined by any anastomotic ulcerations or stenosis and staged according to a four-grade score. RESULTS: Between May 1989 and May 1991 12 centres included 126 patients, 70 women and 56 men, aged 33 +/- 12 years (range 16-70) in the study. Disease locations were ileal, colonic and ileocolonic in 45, 6 and 49%, respectively. Claversal and placebo groups were similar at inclusion, except for ESR (37 +/- 26 vs. 27 +/- 23 mm/h in the Claversal and placebo groups, respectively; P < 0.05). Nine patients were withdrawn from the study. Adverse reactions occurred only in six patients. Five patients were excluded for protocol violation. Finally, 106 patients could be evaluated at 12 weeks (55 Claversal and 51 placebo). An endoscopic relapse was observed in 50% and 63% of the Claversal and placebo groups, respectively (P = 0.16), with a similar grade distribution. Claversal was well tolerated. CONCLUSIONS: Our study confirms that a large proportion of endoscopic recurrences occur within 3 months of resection in Crohn's disease. There was a slight trend towards greater efficacy of Claversal; it could be worthwhile trying higher dosages and/or 5-ASA compounds with different intestinal release profiles.

[Effects of a shielding antacid on changes in the gastric potential difference induced by aspirin in man]. / Effets d'un pansement anti-acide sur les modifications de la différence de potentiel gastrique induites par l'aspirine chez l'homme.

Acetyl salicylic acid (AAS) disrupts the gastric mucosal barrier, causing a drop in the transmural potential difference (PD) and mucosal injuries. The decrease of PD correlates with endoscopic assessment and mucosal damage. The gastric PD may be used as a sensitive model for the assessement of drug-induced damage to the gastric mucosa. We have studied the effects of a shielding antacid ( Gelox ) on PD modifications induced by 500 mg of AAS in 12 healthy volunteers. Measures were performed after administration of one unit of Gelox and after a 3 day treatment period (1 unit, three times daily). Gelox induced a significant decrease of maximal PD drop (10.7 +/- 3.1 mV and 7.5 +/- 2.8 mV respectively; p less than 0.001) and of PD recovery time (p less than 0.05). After the 3 day treatment period and 14 h after the last intake, there was an increase of basal PD values and a very significant decrease (p less than 0.001) of maximal PD drop induced by AAS alone and AAS + Gelox (5.33 +/- 2.42 mV and 3.66 +/- 2.18 mV, respectively). Since the antacid effect had disappeared 14 h after the last intake of Gelox ; these results suggest an increase of the gastric mucosal barrier and a real "shielding effect".

[Cerebrovascular accidents after endoscopic obturation of esophageal varices with isobutyl-2-cyanoacrylate in 2 patients]. / Accidents vasculaires cérébraux après obturation endoscopique des varices oesophagiennes par l'isobutyl-2-cyanoacrylate chez deux malades.

We report 2 cases of cerebral stroke in cirrhotic patients following endoscopic obturation of esophageal varices with Isobutyl-2-Cyanoacrylate. In both cases, hemiplegia appeared several hours after the procedure. A brain CT scan showed radiodense material in the cerebral arteries due to dissemination of Isobutyl-2-Cyanoacrylate. One patient died, the other improved slowly. Different hypotheses may be raised: defectuous injection into the arterial circulation, systemic emboli via portopulmonary venous shunts, delayed polymerization of Isobutyl-2-Cyanoacrylate. Systemic emboli have been reported previously following percutaneous transhepatic obliteration of esophageal varices, suggesting portopulmonary venous shunts. In spite of these 2 complications, this procedure remains useful in stopping acute variceal bleeding and in preventing recurrent bleeding.

Use of scanning electron microscopy to investigate dental calculus in dogs.

The formation of dental calculus in dogs is a major problem. Scanning electron microscopy of tartar specimens from dogs revealed on the outer surface of the plaque polymorphic configurations, more or less arranged as free filaments, corn-cobs or swab-like structures. Uninhabited bacterial recesses were found on the inner surface of the calculus. Calcification may occur between or within the bacteria. Elucidating the mechanisms of calculus formation should help in the development of prophylactic measures.

[Effects of enprostil on changes in the gastric transepithelial potential differential induced by aspirin]. / Effets de l'enprostil sur les modifications de la différence de potentiel transépithéliale gastrique induites par l'aspirine.

Enprostil (E), is a semisynthetic E2 prostaglandin with wide-range antisecretory properties. Administered orally E reduced mucosal injury in rats exposed to NSAID and gastric acid. The aim of the present study was to analyze the cytoprotective effect of 7 micrograms of E on the aspirin-induced (500 mg) decrease in gastric transepithelial difference of potential (DP) in a) five healthy volunteers and b) five patients with epigastric heartburn, normal endoscopy and a low gastric DP (mucosal barrier weakness). Aspirin-induced decrease of gastric DP was measured during two four hour periods separated by an interval of two days: a) during a one hour basal period and after three hours after 7 micrograms of E, and b) during a second basal period and one hour after aspirin, E, and then aspirin again. The following parameters were analyzed: maximal drop of DP DP Max (mV), area under the curve of DP drop, AUC (mV.min), and time to return to basal values, TRB (min). In the control group, when E was administered after aspirin, the decrease in DP Max (11.4 +/- 2.3 vs 6.6 +/- 2.1) and in AUC (68 +/- 22 vs 35 +/- 11) was significant (p less than 0.05) as compared with values obtained after aspirin alone. In the patient group, E produced a significant decrease in aspirin-induced DP Max (11.8 +/- 1.9 vs 6.8 +/- 2.4) (p less than 0.003) and in AUC (117 +/- vs 48 less than 22) (p less than 0.006) as well as in TRB (52 +/- 2 vs 37 +/- 10) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of pentagastrin and cimetidine on gastric protein loss in exudative gastropathies]. / Effet de la pentagastrine et de la cimétidine sur les pertes protéiques gastriques au cours des gastropathies exsudatives.

The effectiveness of cimetidine in decreasing protein loss in protein-losing gastropathies has recently been questioned. The present investigation was designed to test the effects of pentagastrin and cimetidine on gastric protein loss in 6 patients with this type gastropathy: 4 with Ménétrier's disease and 2 with Stempien's disease. Fecal and gastric loss of 51Cr-labelled proteins were measured and expressed as ml of plasma per unit of time +/- SEM. Gastric protein loss was measured during intravenous infusion of normal saline, pentagastrin alone (6 microgram/kg/h), combined pentagastrin and cimetidine (1.5 mg/kg/h), and cimetidine alone. Each solution was perfused during 105 min to obtain a steady state effect upon gastric protein loss during one hour. Fecal clearance was increased in all patients: 193 +/- 16 ml/day (N less than 40 ml/day). Gastric 51Cr albumin loss was increased by pentagastrin stimulation (15.9 +/- 1.2 ml/h); cimetidine resulted in a reduction of the pentagastrin induced loss (7.0 +/- 3.8 ml/h) while cimetidine alone had no effect (3.8 +/- 0.6 ml/h) on basal loss. Our results suggest that cimetidine therapy may be of benefit in decreasing protein loss in patients with this type of gastropathy.

Chronic gastritis: prevalence in the French population. CIRIG.

Chronic gastritis (CG) which can be associated with severe complications, is a frequent phenomenon in gastroenterological practice. No data concerning the prevalence of GC are available in France. The aim of this study was to evaluate the prevalence of CG on biopsy specimens in the French population. All outpatients coming from different towns of seven French areas and undergoing an upper endoscopy on one or two randomly selected consecutive days were included in the study. A case report form was filled out and 5 biopsy specimens were taken from the fundus and antrum. Pathologists graded the specimens on the basis of Whitehead's classification. Seven hundred and forty-two patients were enrolled by 102 private gastroenterologists. Mean age was 53 years; 52% were males. Endoscopically, the gastric mucosa was abnormal in 53%. Superficial and atrophic CG was diagnosed in 53% of cases. Superficial gastritis was observed in 101 patients (14%), antral chronic atrophic gastritis (CAG) in 189 (26%) and fundic CAG in 17 (2%). Patients with CAG were significantly older than the other patients. There were more smokers and heavy alcohol drinkers in the group of CAG patients. Endoscopy and histology were in accordance in only 55.2% of the patients: most cases of CAG were not detected by endoscopy. These results are similar to other studies in European populations. The principal pattern among the various types of gastritis was CAG. The other forms were rare. Autoimmune gastritis was uncommon in this French population (4% of the CAG patients).

[Gastric protein loss and alcoholic cirrhosis. Study by measurement of gastric clearance of alpha 1-antitrypsin]. / Pertes protéiques gastriques et cirrhose alcoolique. Etude par la mesure de la clairance gastrique de l' alpha 1-antitrypsine.

OBJECTIVE: The aim of the study was to assess gastric protein loss in alcoholic cirrhotic patients, and to determine its role in the low serum albumin levels frequently observed in these patients. METHODS: Twenty-six alcoholic cirrhotic patients with ascites and serum albumin levels < 30 g/L were studied and compared to 6 healthy volunteers. Gastric protein loss was determined by measuring gastric clearance of alpha 1-antitrypsin. RESULTS: Gastric clearance of alpha 1-antitrypsin was 0.96 +/- 1.42 mL/h (median : 0.52; range: 0.11-6.54) in cirrhotic patients and 0.48 +/- 0.20 mL/h (median: 0.51) in healthy volunteers. Values in cirrhotic patients were not significantly different from healthy volunteers. However, 3 cirrhotic patients had high values of gastric clearance of alpha 1-antitrypsin (2.84, 3.99 and 6.54 mL/h). Their serum albumin and protein levels were significantly lower than those in the 23 other patients (P < 0.05 and < 0.03, respectively). Severe portal hypertensive gastropathy was present in two out of these 3 patients and in two out of the 23 other patients. CONCLUSION: Gastric protein loss is not significantly increased in liver cirrhosis. However, in a few patients, this loss is high and may play a role in low serum albumin levels.