The Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination and Infection on Neutralizing Antibodies: A Nation-wide Cross-sectional Analysis.

BACKGROUND: Neutralising antibodies (nAbs) play a critical role in the protection against severe COVID-19. In the era of vaccine boosters and repeated SARS-CoV-2 outbreaks, identifying individuals at risk represents a public health priority. METHODS: Relying on the Monaco COVID Public Health Programme, we evaluated nAbs from July 2021-June 2022 in 8,080 SARS-CoV-2 vaccinated and/or infected children and adults, at their inclusion visit. We stratified by infection status and investigated variables associated with nAbs using a generalised additive model. RESULTS: Infected and vaccinated participants had high and consistent nAbs (>800 IU/mL), which remained stable over time since injection, regardless of the number of vaccine doses, body mass index, sex, or age. By contrast, uninfected participants showed larger variability (two doses [V2] median 157.6; interquartile range [IQR] 43.3-439.1 IU/mL) versus three doses [V3] median 882.5; [829.5-914.8] IU/mL). NAbs decreased by 20% per month after V2 (adjusted ratio 0.80; 95%CI [0.79-0.82]), but remained stable after V3 (adjusted ratio 0.98; 95%CI [0.92-1.05]). CONCLUSIONS: Hybrid immunity provided stable, high and consistent nAbs over time. The benefit of boosters was marked to restore decaying nAbs in uninfected participants. NAbs could identify individuals at risk of severe COVID-19 and provide more targeted vaccine boosters' campaigns.

Saccharomyces boulardii does not prevent relapse of Crohn's disease.

BACKGROUND & AIMS: Saccharomyces boulardii is a probiotic yeast that has been shown to have beneficial effects on the intestinal epithelial barrier and digestive immune system. There is preliminary evidence that S boulardii could be used to treat patients with Crohn's disease (CD). We performed a randomized, placebo-controlled trial to evaluate the effects of S boulardii in patients with CD who underwent remission during therapy with steroids or aminosalicylates. METHODS: We performed a prospective study of 165 patients who achieved remission after treatment with steroids or salicylates; they were randomly assigned to groups given S boulardii (1 g/day) or placebo for 52 weeks. The primary end point was the percentage of patients in remission at week 52. Time to relapse, Crohn's disease activity index scores, and changes in parameters of inflammation were secondary end points. RESULTS: CD relapsed in 80 patients, 38 in the S boulardii group (47.5%) and 42 in the placebo group (53.2%, a nonsignificant difference). The median time to relapse did not differ significantly between patients given S boulardii (40.7 weeks) vs placebo (39.0 weeks). There were no significant differences between groups in mean Crohn's disease activity index scores or erythrocyte sedimentation rates or in median levels of C-reactive protein. In a post hoc analysis, nonsmokers given S boulardii were less likely to experience a relapse of CD than nonsmokers given placebo, but this finding requires confirmation. CONCLUSIONS: Although the probiotic yeast S boulardii is safe and well tolerated, it does not appear to have any beneficial effects for patients with CD in remission after steroid or salicylate therapies.

Correction: Interaction of Saccharomyces boulardii with Salmonella enterica Serovar Typhimurium Protects Mice and Modifies T84 Cell Response to the Infection.

[This corrects the article DOI: 10.1371/journal.pone.0008925.].

Human Health and Ocean Pollution.

Background: Pollution - unwanted waste released to air, water, and land by human activity - is the largest environmental cause of disease in the world today. It is responsible for an estimated nine million premature deaths per year, enormous economic losses, erosion of human capital, and degradation of ecosystems. Ocean pollution is an important, but insufficiently recognized and inadequately controlled component of global pollution. It poses serious threats to human health and well-being. The nature and magnitude of these impacts are only beginning to be understood. Goals: (1) Broadly examine the known and potential impacts of ocean pollution on human health. (2) Inform policy makers, government leaders, international organizations, civil society, and the global public of these threats. (3) Propose priorities for interventions to control and prevent pollution of the seas and safeguard human health. Methods: Topic-focused reviews that examine the effects of ocean pollution on human health, identify gaps in knowledge, project future trends, and offer evidence-based guidance for effective intervention. Environmental Findings: Pollution of the oceans is widespread, worsening, and in most countries poorly controlled. It is a complex mixture of toxic metals, plastics, manufactured chemicals, petroleum, urban and industrial wastes, pesticides, fertilizers, pharmaceutical chemicals, agricultural runoff, and sewage. More than 80% arises from land-based sources. It reaches the oceans through rivers, runoff, atmospheric deposition and direct discharges. It is often heaviest near the coasts and most highly concentrated along the coasts of low- and middle-income countries. Plastic is a rapidly increasing and highly visible component of ocean pollution, and an estimated 10 million metric tons of plastic waste enter the seas each year. Mercury is the metal pollutant of greatest concern in the oceans; it is released from two main sources - coal combustion and small-scale gold mining. Global spread of industrialized agriculture with increasing use of chemical fertilizer leads to extension of Harmful Algal Blooms (HABs) to previously unaffected regions. Chemical pollutants are ubiquitous and contaminate seas and marine organisms from the high Arctic to the abyssal depths. Ecosystem Findings: Ocean pollution has multiple negative impacts on marine ecosystems, and these impacts are exacerbated by global climate change. Petroleum-based pollutants reduce photosynthesis in marine microorganisms that generate oxygen. Increasing absorption of carbon dioxide into the seas causes ocean acidification, which destroys coral reefs, impairs shellfish development, dissolves calcium-containing microorganisms at the base of the marine food web, and increases the toxicity of some pollutants. Plastic pollution threatens marine mammals, fish, and seabirds and accumulates in large mid-ocean gyres. It breaks down into microplastic and nanoplastic particles containing multiple manufactured chemicals that can enter the tissues of marine organisms, including species consumed by humans. Industrial releases, runoff, and sewage increase frequency and severity of HABs, bacterial pollution, and anti-microbial resistance. Pollution and sea surface warming are triggering poleward migration of dangerous pathogens such as the Vibrio species. Industrial discharges, pharmaceutical wastes, pesticides, and sewage contribute to global declines in fish stocks. Human Health Findings: Methylmercury and PCBs are the ocean pollutants whose human health effects are best understood. Exposures of infants in utero to these pollutants through maternal consumption of contaminated seafood can damage developing brains, reduce IQ and increase children's risks for autism, ADHD and learning disorders. Adult exposures to methylmercury increase risks for cardiovascular disease and dementia. Manufactured chemicals - phthalates, bisphenol A, flame retardants, and perfluorinated chemicals, many of them released into the seas from plastic waste - can disrupt endocrine signaling, reduce male fertility, damage the nervous system, and increase risk of cancer. HABs produce potent toxins that accumulate in fish and shellfish. When ingested, these toxins can cause severe neurological impairment and rapid death. HAB toxins can also become airborne and cause respiratory disease. Pathogenic marine bacteria cause gastrointestinal diseases and deep wound infections. With climate change and increasing pollution, risk is high that Vibrio infections, including cholera, will increase in frequency and extend to new areas. All of the health impacts of ocean pollution fall disproportionately on vulnerable populations in the Global South - environmental injustice on a planetary scale. Conclusions: Ocean pollution is a global problem. It arises from multiple sources and crosses national boundaries. It is the consequence of reckless, shortsighted, and unsustainable exploitation of the earth's resources. It endangers marine ecosystems. It impedes the production of atmospheric oxygen. Its threats to human health are great and growing, but still incompletely understood. Its economic costs are only beginning to be counted.Ocean pollution can be prevented. Like all forms of pollution, ocean pollution can be controlled by deploying data-driven strategies based on law, policy, technology, and enforcement that target priority pollution sources. Many countries have used these tools to control air and water pollution and are now applying them to ocean pollution. Successes achieved to date demonstrate that broader control is feasible. Heavily polluted harbors have been cleaned, estuaries rejuvenated, and coral reefs restored.Prevention of ocean pollution creates many benefits. It boosts economies, increases tourism, helps restore fisheries, and improves human health and well-being. It advances the Sustainable Development Goals (SDG). These benefits will last for centuries. Recommendations: World leaders who recognize the gravity of ocean pollution, acknowledge its growing dangers, engage civil society and the global public, and take bold, evidence-based action to stop pollution at source will be critical to preventing ocean pollution and safeguarding human health.Prevention of pollution from land-based sources is key. Eliminating coal combustion and banning all uses of mercury will reduce mercury pollution. Bans on single-use plastic and better management of plastic waste reduce plastic pollution. Bans on persistent organic pollutants (POPs) have reduced pollution by PCBs and DDT. Control of industrial discharges, treatment of sewage, and reduced applications of fertilizers have mitigated coastal pollution and are reducing frequency of HABs. National, regional and international marine pollution control programs that are adequately funded and backed by strong enforcement have been shown to be effective. Robust monitoring is essential to track progress.Further interventions that hold great promise include wide-scale transition to renewable fuels; transition to a circular economy that creates little waste and focuses on equity rather than on endless growth; embracing the principles of green chemistry; and building scientific capacity in all countries.Designation of Marine Protected Areas (MPAs) will safeguard critical ecosystems, protect vulnerable fish stocks, and enhance human health and well-being. Creation of MPAs is an important manifestation of national and international commitment to protecting the health of the seas.

Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections.

The yeast Saccharomyces boulardii CNCM I-745 is one of the probiotics recommended for the prevention of antibiotic-associated diarrhea. Studies conducted in vivo and in vitro demonstrated that in the case of infectious diseases there are two potential sites of action of Saccharomyces boulardii CNCM I-745: (1) An action on enteropathogenic microorganisms (adhesion of bacteria and their elimination or an effect on their virulence factors: Toxins, lipopolysaccharide, etc.); and (2) a direct action on the intestinal mucosa (trophic effects, effects on epithelial reconstitution, anti-secretory effects, anti-inflammatory, immunomodulators). Oral administration of Saccharomyces boulardii CNCM I-745 to healthy subjects does not alter their microbiota. However, in the case of diseases associated with the use of antibiotics or chronic diarrhea, Saccharomyces boulardii CNCM I-745 can restore the intestinal microbiota faster. The interaction of Saccharomyces boulardii CNCM I-745 with the innate immune system have been recently demonstrated thus opening up a new therapeutic potential of this yeast in the case of diseases associated with intestinal infections but also other pathologies associated with dysbiosis such as inflammatory diseases.

Saccharomyces boulardii prevents TNF-alpha-induced apoptosis in EHEC-infected T84 cells.

Induction of apoptosis and necrosis by enterohemorrhagic Escherichia coli (EHEC) has been reported in vivo and in vitro, but features of cell death were not noted in those reports. Since tumor necrosis factor-alpha (TNF-alpha) has been implicated in the apoptosis of invasive bacteria, we investigated the role of this cytokine in EHEC-induced apoptosis. We hypothesize that the probiotic yeast strain Saccharomyces boulardii that interferes with EHEC-induced pro-inflammatory pathways delays EHEC-induced apoptosis. By 6 h of infection, flow cytometry analysis of T84 cells demonstrated that 40% of cells were FITC-annexin-V-positive and 40% of cells incorporated both annexin and propidium iodide (PI). Simultaneously, western blot analysis demonstrated that procaspases-8 and -3 were cleaved. Fragmentation of internucleosomal DNA revealed evidence of apoptotic leader formation after 8 and 9 h of infection. Procaspase-9 activation and 3',3-dihexyloxacarbocyanine iodide (DiOC(6)) incorporation were observed at 3 h of infection. In cells preincubated with S. boulardii and infected with EHEC in the presence of yeast, the quantities of procaspases-8, -9 and -3 did not vary, and no DNA fragmentation was observed. The TNF-alpha transcript level and the level of secreted TNF-alpha increased considerably (P<0.001vs control cells) at 6 h of infection in EHEC-alone-infected cells, but were significantly reduced in cells infected in the presence of S. boulardii (P<0.001vs EHEC-alone-infected cells). The presence of anti-TNF-alpha antibody during infection reduced by 30% the level of FITC-annexin V-positive cells. Altogether, these findings demonstrated that: (i) EHEC infection stimulated TNF-alpha synthesis that is implicated in apoptosis of T84 cells; and (ii) S. boulardii induced a decrease in TNF-alpha and related apoptosis in EHEC-infected T84 cells.

Lactobacillus casei DN-114 001 inhibits the increase in paracellular permeability of enteropathogenic Escherichia coli-infected T84 cells.

Probiotics are living microorganisms which, when ingested in adequate amounts, exert health benefits toward the host. For instance, probiotics might act through reinforcement of the intestinal epithelial barrier function. The goal of the present study was to determine whether Lactobacillus casei DN-114 001 could abrogate the increase in paracellular permeability induced by enteropathogenic Escherichia coli. We used the human colon T84 cell line infected with a wild-type enteropathogenic E. coli (strain E2348/69). Paracellular permeability was followed by monitoring transepithelial electrical resistance variations and by observing zonula occludens-1 distribution. Two infection procedures were used: co-incubation (the pathogenic and probiotic strains were simultaneously incubated with T84 cells) and post-infection (the probiotic was added in the presence of pathogenic bacteria 3 h after the beginning of the infection). We also investigated the effect of L. casei on enteropathogenic E. coli adhesion. L. casei DN-114 001 inhibited, in a dose-dependent-manner, the decrease in enteropathogenic E. coli-induced transepithelial electrical resistance and zonula occludens-1 redistribution using two different infection procedures. However, L. casei did not inhibit pathogenic strain adhesion. L. casei DN-114 001 inhibited the increase in EPEC-induced paracellular permeability. This property could partially explain the previously observed health benefits of this probiotic for human natural defenses, such as those associated with prevention of diarrhea.

Serum fibrosis markers can detect large oesophageal varices with a high accuracy.

OBJECTIVES: The aim of this study was to determine the value of serum fibrosis markers for the diagnosis of oesophageal varices in alcoholic patients. METHODS: Fifty-four sets of clinical and biochemical data, including serum markers of fibrosis, obtained from 146 heavy alcohol drinkers (106 men, 40 women; mean age 49.2+/-9.0 years) without any history of variceal bleeding were analysed. Gastroscopy and liver biopsy were performed in all patients. Multivariate analysis was performed to identify the markers best correlated with oesophageal varices. RESULTS: Fifty-nine patients (40.4%) had severe fibrosis (3+) and 48 (32.9%) had oesophageal varices (all grades considered together). In multivariate analysis, a prothrombin index below 60%, alkaline phosphatase activity over 110 IU/l, and hyaluronate over 100 g/l were the best markers for the prediction of oesophageal varices. The diagnostic accuracy for medium to large oesophageal varices using these three factors was 86%. Eight patients (16.7%) with oesophageal varices presented no or moderate fibrosis (F<3): one patient (12.5%) had an alkaline phosphatase level >110 IU/l. However, all eight of these patients had small oesophageal varices. CONCLUSIONS: These three non-invasive markers correctly predict the presence or absence of medium to large oesophageal varices in 86% of alcoholic patients.

Effects of Saccharomyces boulardii on fecal short-chain fatty acids and microflora in patients on long-term total enteral nutrition.

AIM: Diarrhea is a significant problem in patients on total enteral nutrition (TEN) and may involve changes in intestinal short chain fatty acids or microflora. Recent studies suggest that the probiotic yeast Saccharomyces boulardii (Sb) may decrease its incidence. The aim of this study was to assess the effects of Sb on fecal flora and short-chain fatty acids (SCFA) in patients on long-term TEN. METHODS: Ten patients (3 females, 7 males, 59+/-5.5 years), on TEN for a median of 13 mo (1-125), and 15 healthy volunteers (4 females, 11 males, 32+/-2.0 years) received Sb (0.5 g bid PO) for 6 d. Two stool samples were taken before, on the last 2 d and 9-10 d after treatment, for SCFA measurement and for culture and bacterial identification. Values (mean+/-SE) were compared using sign tests and ANOVA. RESULTS: Fecal butyrate levels were lower in patients (10.1+/-2.9 mmol/kg) than in controls (19.2+/-3.9, P = 0.02). Treatment with Sb increased total fecal SCFA levels in patients (150.2+/-27.2 vs 107.5+/-18.2 mmol/kg, P = 0.02) but not in controls (129.0+/-28.6 vs 113.0+/-15.2 mmol/kg, NS). At the end of treatment with Sb, patients had higher fecal butyrate (16.0+/-4.4 vs 10.1 [2.9] mmol/kg, P = 0.004). Total SCFAs remained high 9 d after treatment was discontinued. Before the treatment, the anaerobe to aerobe ratio was lower in patients compared to controls (2.4+/-2.3 vs 69.8+/-1.8, P = 0.003). There were no significant changes in the fecal flora of TEN patients. CONCLUSION: Sb-induced increase of fecal SCFA concentrations (especially butyrate) may explain the preventive effects of this yeast on TEN-induced diarrhea.

Nitric oxide-releasing non steroidal anti-inflammatory drugs: a new generation of anti-tumoral molecules.

Colorectal cancer is the second most common cause of cancer-related mortality in the west. The high incidence and mortality make effective prevention an important public-health and economic issue. The regular intake of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with decreased incidence of certain types of cancer particularly those with an inflammatory component, and then are among the few agents known to be chemopreventive. Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are new chemical entities obtained by adding a nitric oxide-releasing moiety to classical molecules. This new class of molecules has been demonstrated to be much more safe than NSAIDs due to their ability to reduce gastric toxicity. They could therefore represent an alternative to classical NSAIDs treatment. In this review, we sumarise the recent findings in the mechanisms and pathways involved in the antitumoral effects of both NSAIDs and NO-NSAIDs as well as the clinical trials performed with these compounds.

Gallbladder motility and gut hormone plasma levels in subjects with and without gallstones.

Hormonal control of gallbladder motility is still unclear in patients with cholelithiasis. In a case-control study, we determined the characteristics of gallbladder emptying evaluated sonographically and the hormone levels of somatostatin, gastrin, and pancreatic polypeptide, before and after a fatty meal in 10 gallstone patients compared with 20 healthy subjects. Patients with lithiasis had a larger residual volume (median 12,0 ml vs 6,5 ml; P = 0.01) and a lower gallbladder ejection fraction (43% vs 70%, P = 0.02) than healthy subjects. During fasting, plasma pancreatic polypeptide concentrations were significantly higher in lithiasis patients (P < 0.03). In contrast, no differences between the two groups of patients were observed during the post prandial period. Somatostatin and gastrin plasma levels were similar in the two groups. Lastly, the serum bile salt levels were in the normal range and were not different between groups both during fasting and postprandial states. We conclude that large basal plasma concentrations of pancreatic polypeptide, a gut peptide inducing gallbladder relaxation, may constitute a factor facilitating lithogenesis.

The Saccharomyces boulardii CNCM I-745 strain shows protective effects against the B. anthracis LT toxin.

The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT) of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax.

Experimental effects of Saccharomyces boulardii on diarrheal pathogens.

Saccharomyces boulardii is a selected strain of yeast that may have applications in the prevention and treatment of intestinal infections. The animal models and in vitro studies developed to elucidate the mechanisms of this protection are reviewed and discussed.

Effects of fatty acids on the growth of Caco-2 cells.

Epidemiological studies suggest that polyunsaturated fatty acids may protect against colorectal neoplasia. In order to explore this observation, cell proliferation and viability, lipid composition, membrane fluidity, and lipid peroxidation were measured in Caco-2 cells after 48h incubation with various fatty acids. Saturated and monounsaturated fatty acids incorporated less well in the membranes than polyunsaturated fatty acids (PUFAs). All of the PUFAs tested had an inhibitory effect on cell proliferation/viability whereas the saturated and monounsaturated fatty acids did not. Addition of palmitic acid had no significant effect on membrane fluidity whereas unsaturated fatty acids increased membrane fluidity in a dose-dependent manner. PUFAs strongly increased tumor cell lipid peroxidation in a dose-dependent manner. Saturated and monounsaturated fatty acids increased lipid peroxidation in this cell line only at high concentration. Preincubation of Caco-2 cells with vitamin E prevented the inhibition of proliferation/viability, the elevation of the MDA concentration and the increased membrane fluidity induced by PUFAs. Our data indicate that PUFAs are potent inhibitors of the growth of colon cancer cells in vitro.

Assessing medical students' clinical sciences knowledge in France: a collaboration between the NBME and a consortium of French medical schools.

PURPOSE: The French government, as part of medical education reforms, has affirmed that an examination program for national residency selection will be implemented by 2004. The purpose of this study was to develop a French multiple-choice (MC) examination using the National Board of Medical Examiners' (NBME) expertise and materials. METHOD: The Evaluation Standardisée du Second Cycle (ESSC), a four-hour clinical sciences examination, was administered in January 2002 to 285 medical students at four university test sites in France. The ESSC had 200 translated and adapted MC items selected from the Comprehensive Clinical Sciences Examination (CCSE), an NBME subject test. RESULTS: Less than 10% of the ESSC items were rejected as inappropriate to French practice. Also, the distributions of ESSC item characteristics were similar to those reported with the CCSE. The ESSC also appeared to be very well targeted to examinees' proficiencies and yielded a reliability coefficient of.91. However, because of a higher word count, the ESSC did show evidence of speededness. Regarding overall performance, the mean proficiency estimate for French examinees was about 0.4 SD below that of a CCSE population. CONCLUSIONS: This study provides strong evidence for the usefulness of the model adopted in this first collaborative effort between the NBME and a consortium of French medical schools. Overall, the performance of French students was comparable to that of CCSE students, which was encouraging given the differences in motivation and the speeded nature of the French test. A second phase with the participation of larger numbers of French medical schools and students is being planned.

Lack of adaptation to severe malnutrition in elderly patients.

BACKGROUND & AIMS: Sarcopenia is a common feature in the healthy elderly. However, little is known on age-related modifications of body composition in malnourished patients. The aims of this cross-sectional study were to evaluate the effects of aging per se on body composition and resting energy expenditure (REE) in malnourished patients. METHODS: Ninety-seven non-stressed patients referred for chronic malnutrition (C-reactive protein <5 mg/l) were separated into two groups: middle-aged (26 female, 19 male, 48+/-15 yr), and elderly (26 female, 26 male, 79+/-6 yr). Body composition was assessed by bioelectrical impedance analysis and REE by indirect calorimetry. RESULTS: In middle-aged patients, body composition remained stable between moderate (body-mass index [BMI; in kg/m(2)] 16-18.5) and severe (BMI < 16) malnutrition, with similar values of fat-free mass (FFM), body cell mass (BCM) and fat mass (FM) as percentages of body weight, whereas in elderly patients malnutrition occurred at the expense of FFM and BCM, with unchanged FM absolute values. REE/FFM values remained stable in middle-aged patients at every stage of malnutrition, whereas they increased in elderly patients along with their degree of malnutrition. In multivariate analysis, both body composition and REE/FFM were influenced by sex, age, BMI and mid-arm circumference. CONCLUSION: Compared to younger patients, weight loss in the elderly leads to cachexia, with a preferential loss of FFM and BCM that may participate in the more severe outcomes observed in these patients. They also show elevated REE/FFM values that induce higher energy needs.

Diagnostic accuracy of a rapid urine-screening test (Multistix8SG) in cirrhotic patients with spontaneous bacterial peritonitis.

OBJECTIVE: To assess the diagnostic accuracy of a rapid urine-screening test (Multistix8SG) for spontaneous bacterial peritonitis (SBP) in cirrhotic patients. METHODS: Seventy-two consecutive patients (44 males, 28 females; mean age 61.6 years) with cirrhosis and ascites were included in the study. A diagnostic paracentesis was performed on hospital admission in all patients and 2 days after antibiotic treatment in the case of SBP (polymorphonuclear [PMN] count over 250/mm in ascitic fluid). Each fresh sample of ascitic fluid was also tested using the Multistix8SG urine test, and the results were scored as negative, trace or positive. RESULTS: Nine of the 72 patients had SBP and the Multistix8SG urine test was positive. After 48 h of antibiotic therapy, the PMN count of three of these nine patients was still above 250/mm and the Multistix8SG test remained positive. In three other patients with SBP, the PMN count dropped below 250/mm and the Multistix8SG test result had become negative. Two of the nine SBP patients died before 48 h, and paracentesis was not performed in the ninth case. In the other 63 patients, the PMN count in ascitic fluid was below 250/mm; the Multistix8SG test revealed 17 trace results and 46 negative results. At the threshold of 250 PMN/mm in ascitic fluid, this test had a sensitivity and a specificity of 100%. CONCLUSION: A positive Multistix8SG urine test result in ascitic fluid appears to be an indication for antibiotic treatment.

Effect of age on substrate oxidation during total parenteral nutrition.

OBJECTIVE: Parenteral nutrition is increasingly used in the elderly. Aging is accompanied by metabolic changes that can modify substrate use. We compared substrate oxidation during cyclic total parenteral nutrition (TPN) in elderly and middle-aged patients. METHODS: Twelve elderly patients (eight women, four men; 72 +/- 5 y) and 12 middle-aged patients (nine women, three men; 39 +/- 13 y) who were on cyclic TPN for intestinal failure were investigated while in stable condition after at least 15 d of TPN. No patient was diabetic. Indirect calorimetry was performed during fasting and every 30 min during the 3 h of TPN infusion and 3 h after infusion, allowing the measurement of nutrient oxidation. Blood samples were obtained every hour for the measurement of glucose, insulin, triacylglycerols, and free fatty acids. RESULTS: In the fasting state, resting energy expenditure was significantly higher in the elderly patients than in the middle-aged patients (39.3 +/- 8.1 versus 31.9 +/- 4.3 kcal/kg of fat-free mass per day, P = 0.008). During TPN, lipid oxidation was significantly higher in the elderly patients than in the middle-aged patients (1.09 +/- 0.17 versus 0.84 +/- 0.27 mg x kg(-1) x min(-1), P = 0.011); glucose oxidation was significantly lower in the elderly patients than in the middle-aged patients (2.19 +/- 0.93 versus 3.22 +/- 1.54 mg x kg(-1) x min(-1), P = 0.038). Areas under the curves of glycemia and free fatty acids were significantly higher in the elderly patients. CONCLUSION: In the elderly, TPN was associated with significantly higher lipid oxidation and lower glucose oxidation than in younger patients. TPN formulas and flow rates should therefore be adapted in the elderly.

[Is combined treatment with interferon alpha and ribavirin for 3 months enough in selected patients with a genotype 2 or 3 hepatitis C virus?]. / Un traitement combiné par interféron-alpha et ribavirine pendant 3 mois pourrait-il suffire chez des malades sélectionnés infectés par un virus de l'hépatite C de génotype 2 ou 3?

Peginterferon plus ribavirin for 24 weeks is the recommended treatment, for previously untreated patients infected by genotype 2 or 3 hepatitis C virus. We report 2 patients with genotype 3 and 2a, with a sustained virological response, after bitherapy with interferon plus ribavirin with 16 and 14 weeks respectively. Thus in selected patients having genotype 2 or 3, and other predictive factors of a sustained virological response, shorter bitherapy could be enough and improve the effectiveness/tolerance ratio.

[Registry of liver biopsies from hepatitis C infected patients in the Alpes-Maritimes (France). Results from the first 2 years]. / Registre des ponctions-biopsies hépatiques réalisées chez les malades atteints d'hépatite chronique C dans le département des Alpes-Maritimes.

OBJECTIVE: To perform a descriptive analysis of patients with chronic hepatitis C based on a local registry of liver biopsies. PATIENTS AND METHOD: Collection of clinical, biological and histological data from all HCV-infected patients who underwent liver biopsy between January 1997 and December 1998 in the Alpes-Maritimes (France). RESULTS: One thousand and fifty six patients including 924 who lived in the Alpes-Maritimes (515 male, 409 female, mean age: 44.9 years old) were included. Intravenous drug use (30.1%) was the major suspected source of infection before blood transfusion (28.2%). Among intravenous drug users, 38% of patients were infected with genotype 1a and 37.4% with genotype 3. The METAVIR fibrosis severity score was distributed as follows: F0: 10.8%, F1: 53.7%, F2: 15.9%, F3: 14.7%, and F4: 4.9%. In a multivariate analysis adjusted for the duration of infection, independent risk factors associated with the severity of fibrosis were age at contamination >=30 years, genotype other than 1a and alcohol intake >=50 g/day. Determination of HCV antibody and liver biopsy were performed an average of 12.5 and 14 years after presumed date of contamination, respectively. CONCLUSIONS: These data provide a clearer view of the impact of this condition in this area and could help to define a comprehensive policy for patient management.