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Biomedical subjects

F Fontaine

Publications and source records attributed to F Fontaine.

At least 19 recordsLinked to original sources

[Reactivation of ocular toxoplasmosis after laser in situ keratomileusis].

Laser in situ keratomileusis (LASIK) is a safe and efficient refractive surgical procedure that provides excellent results in most cases. Several complications have been reported, most of them related to the posterior segment of the eye. Although they are quite rare, a growing number of vitreoretinal pathologic conditions after LASIK have been reported. To date no article has reported an inflammatory or infectious disease of the posterior segment after a LASIK procedure. We report a case of reactivation of toxoplasmic chorioretinitis that occurred 5 days after a LASIK procedure. Clinical outcome was spontaneously favorable after 1 month, with no loss of vision. Although a causal effect between LASIK and toxoplasmic chorioretinitis reactivation cannot be proven with a single case report, we stress the importance of dilated fundus examination in LASIK preoperative assessment: our case suggests that in the presence of preoperative toxoplasmic chorioretinitis scars, increased retinal monitoring is required.

Adult↗

Early development of stricturing or penetrating pattern in Crohn's disease is influenced by disease location, number of flares, and smoking but not by NOD2/CARD15 genotype.

BACKGROUND: Crohn's disease is a heterogeneous entity. Disease behaviour, characterised as stricturing, penetrating, or non-stricturing non-penetrating, is a clinically important phenotype as it is associated with complications and need for surgery. It has recently been showed that the behaviour of Crohn's disease changes over the course of the disease. AIM: To assess the association between rapid development of a penetrating or stricturing pattern of Crohn's disease and demographic and clinical characteristics as well as NOD2/CARD15 genotype. PATIENTS AND METHODS: A total of 163 patients with a firm diagnosis of Crohn's disease and who had non-penetrating non-stricturing disease at diagnosis were studied. Various demographic and clinical characteristics as well as antisaccharomyces cerevisiae antibody status and NOD2/CARD15 genotype were documented in these patients. These characteristics were compared in subgroups of patients according to evolution of disease behaviour five years after diagnosis. RESULTS: Five years after diagnosis there were 110 (67.5%) patients with non- structuring non-penetrating disease, 18 (11%) with stricturing disease, and 35 (21.5%) with penetrating disease. In multivariate analysis, only disease location and number of flares per year were significantly discriminant between the three subgroups (p=0.0009 and 0.0001, respectively). Ileal location of the disease was associated with a stricturing pattern while a high number of flares was associated with a penetrating pattern. Active smoking was also associated with a penetrating pattern compared with a non-stricturing non-penetrating pattern only. CONCLUSIONS: Early development of stricturing or penetrating behaviour in Crohn's disease is influenced by disease location, clinical activity of the disease, and smoking habit, but not by NOD2/CARD15 genotype.

Adult↗

Adhesion of Escherichia coli, Citrobacter freundii and Klebsiella pneumoniae isolated from milk: consequence on the efficiency of sanitation procedures.

The effects of adhesion and of biofilm development on the efficiency of cleaning and disinfection procedures were investigated on three strains belonging to the E. coli, C. freundii and K. pneumoniae species, which were able to raise more or less complex biofilms. Resistance to a rinsing procedure was strain dependent but not related to the biofilm structure: E. coli was poorly adherent although embedded in an organic matrix. Conversely, a similar increase in the heat- and disinfectant-resistance was observed, regardless of the complexity of the biofilm (more or less significant organic matrix). These result suggested the essential role of the bacterial physiological state in resistance to sanitation procedures.

Animals↗

[Barrett's esophagus: overview].

Barrett's oesophagus (BE) is a segment of columnar lined epithelium in the distal oesophagus, above the gastrooesophageal junction. So it is important to localize this junction endoscopically; the proximal margin of the gastric folds is the anatomic landmark. Another important feature of BE is the specialized intestinal metaplasia. In the aetiology of this condition, acid reflux is a primary event but there is evidence that other factors are causal. As BE is a well known premalignant condition, detection of dysplastic epithelium and its severity is the crucial element. Practical guidelines are presented for endoscopic surveillance program. The purpose is the early detection of high grade dysplasia and carcinoma to advise oesophagectomy or endoscopic ablation therapy for patients unfit to undergo surgery.

Algorithms↗

Extensive protein carbonylation precedes acrolein-mediated cell death in mouse hepatocytes.

Allyl alcohol hepatotoxicity is mediated by an alcohol dehydrogenase-derived biotranformation product, acrolein. This highly reactive alpha,beta-unsaturated aldehyde readily alkylates model proteins in vitro, forming, among other products, Michael addition adducts that possess a free carbonyl group. Whether such damage accompanies acrolein-mediated toxicity in cells is unknown. In this work we established that allyl alcohol toxicity in mouse hepatocytes involves extensive carbonylation of a wide range of proteins, and that the severity of such damage to a subset of 18-50 kDa proteins closely correlated with the degree of cell death. In addition to abolishing cytotoxicity and glutathione depletion, the alcohol dehydrogenase inhibitor 4-methyl pyrazole strongly attenuated protein carbonylation. Conversely, cyanamide, an aldehyde dehydrogenase inhibitor, enhanced cytotoxicity and protein carbonylation. Since protein carbonylation clearly preceded the loss of membrane integrity, it may be associated with the toxic process leading to cell death.

Acrolein↗

Potential occurrence of adhering living Bacillus spores in milk product processing lines.

AIMS: The hygienic risk associated with microbial soil on surfaces of milk processing lines was evaluated, based on experimental results. METHODS AND RESULTS: From a panel of Bacillus spores isolated from milk products, B. cereus CUETM 98/4, was found to be highly resistant to heat (D100=3.32 min in whole milk) and oxidant disinfectant (70% lethality of adherent spores with Ikalin 2%). From adhesion trials, up to 1.1 x 10(7) spores cm(-2) were found to be adherent to solid surfaces when suspended in saline or in custard (10(5) and 10(7) cfu ml(-1)), and over 10% of these adherent spores would resist the cleaning procedure. CONCLUSION: A highly contaminated milk (10(5) cfu ml(-1)) subjected to a current sterilization process (8 log reduction) led to a residual contamination of less than 1 cfu in the representative processing line after a complete production run. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlighted the fact that under appropriate processing conditions (efficient sterilization and cleaning procedures), even disinfection would be sufficient to eliminate any contamination risk. Conversely, the disinfection procedure becomes an essential step under inappropriate processing conditions.

Bacillus↗

Binding interactions between barley thaumatin-like proteins and (1,3)-beta-D-glucans. Kinetics, specificity, structural analysis and biological implications.

The specificity and kinetics of the interaction between the pathogenesis-related group of thaumatin-like proteins (PR5) in higher plants and (1,3)-beta-D-glucans have been investigated. Two thaumatin-like proteins with 60% amino-acid sequence identity were purified from extracts of germinated barley grain, and were designated HvPR5b and HvPR5c. Purified HvPR5c interacted with insoluble (1,3)-beta-D-glucans, but not with cellulose, pustulan, xylan, chitin or a yeast mannoprotein. Tight binding was observed with unbranched and unsubstituted (1,3)-beta-D-glucans, and weaker binding was seen if (1,6)-beta-linked branch points or beta-glucosyl substituents were present in the substrate. The HvPR5b protein interacted weakly with insoluble (1,3)-beta-D-glucans and did not bind to any of the other polysaccharides tested. This indicated that only specific barley PR5 isoforms interact tightly with (1,3)-beta-D-glucans. The complete primary structures of HvPR5b and HvPR5c were determined and used to construct molecular models of HvPR5b and HvPR5c, based on known three-dimensional structures of related thaumatin-like proteins. The models were examined for features that may be associated with (1,3)-beta-D-glucan binding, and a potential (1,3)-beta-D-glucan-binding region was located on the surface of HvPR5c. No obvious structural features that would prevent binding of (1,3)-beta-D-glucan to HvPR5b were identified, but several of the amino acids in HvPR5c that are likely to interact with (1,3)-beta-D-glucans are not present in HvPR5b.

Adsorption↗

Isolation of a member of ets gene family in the polychaete annelid Perinereis cultrifera.

Numerous genes belonging to the ets gene family have been described for a few years. The founder of this family is the v-ets proto-oncogene, which is the viral counterpart of the chicken c-ets-1 proto-oncogene. Main research was carried out both on Vertebrates, Drosophila and the nematod Caenorhabditis elegans. Previously, two genes of this family named Nd ets and Nd erg, were isolated in the polychaete annelid Hediste (Nereis) diversicolor. Here we have described the isolation of one gene from the ets family in another polychaete annelid named Perinereis cultrifera. By polymerase chain reaction using degenerated primers, we have amplified an approximatively 515 pb genomic region encoding the ETS domain and another domain designed as "R" domain by Qi et al. (1992) and which can mediate transactivation. By using this method for isolating members of the ets gene family, we are going to realize a phylogenetic study of the phylum of polychaete annelids.

Amino Acid Sequence↗

[Prevalence and treatment of Helicobacter pylori in gastro-duodenal ulcers. An experience in Liege].

Between April 1998 and July 1999, we prospectively investigated 152 patients with gastric or duodenal ulcer and we observed concomitant H. pylori infection in 72.8% and 78.5% respectively. We proposed to the GPs of these patients the recommended triple therapy (omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg (OAC) twice daily for 7 or 10 days). H. pylori eradication was tested using the C13-urea breath test. Our results showed a modest overall eradication rate of about 70%. We have to persuade the patients and the GPs of the benefit of antibiotics and of the importance of the correct dosages. We have to continue to follow the resistance against antibiotics.

Adult↗

Role of cytochrome P450 3A in the metabolism of mefloquine in human and animal hepatocytes.

We studied mefloquine metabolism in cells and microsomes isolated from human and animal (monkey, dog, rat) livers. In both hepatocytes and microsomes, mefloquine underwent conversion to two major metabolites, carboxymefloquine and hydroxymefloquine. In human cells and microsomes these metabolites only were formed, as already demonstrated in vivo, while in other species several unidentified metabolites were also detected. After a 48 hr incubation with human and rat hepatocytes, metabolites accounted for 55-65% of the initial drug concentration, whereas in monkey and dog hepatocytes, mefloquine was entirely metabolized after 15 and 39 hrs, respectively. The consumption of mefloquine was less extensive in microsomes, and unchanged drug represented 60% (monkey) to 85-100% (human, dog, rat) of the total radioactivity after 5 hr incubations. The involvement of the cytochrome P450 3A subfamily in mefloquine biotransformation was suggested by several lines of evidence. Firstly, mefloquine metabolism was strongly increased in hepatic microsomes from dexamethasone-pretreated rats, and also in human and rat hepatocytes after prior treatment with a cytochrome P450 3A inducer. Secondly, mefloquine biotransformation in rifampycin-induced human hepatocytes was inhibited in a concentration-dependent manner by the cytochrome P450 3A inhibitor ketoconazole and thirdly, a strong correlation was found between erythromycin-N-demethylase activity (mediated by cytochrome P450 3A) and mefloquine metabolism in human microsomes (r=0.81, P < 0.05, N=13). Collectively, these findings concerning the role of cytochrome P450 3A in mefloquine metabolism may have important in vivo consequences especially with regard to the choice of agents used in multidrug antimalarial regimens.

Animals↗

Tumour necrosis factor (TNF) gene polymorphism in Crohn's disease (CD): influence on disease behaviour?

Crohn's disease (CD) is a multifactorial disease with genetic heterogeneity. TNF-alpha plays a key role in the development of the mucosal lesions. The aim of our work was to study a single base pair polymorphism located in the promoter region of TNF gene, in a large population of CD patients with well defined phenotypes. One hundred and ninety-three patients with CD and 98 ethnically matched controls were studied. The -308 single base pair polymorphism of TNF gene was studied using an allele-specific polymerase chain reaction. Genotype and allelic frequencies were compared between patients and controls and between subgroups of patients defined by sex, age at diagnosis, familial history, location of disease, type of disease, extra-intestinal manifestations, and response to steroid treatment. In 29 patients a measure of TNF-alpha production by colonic biopsies was performed. The frequency of the allele TNF2 as well as the proportion of carriers of the allele TNF2 were slightly but not significantly lower in CD than in controls (11.9% versus 14.8% and 21.5% versus 27.6%, respectively). A more prominent difference in frequencies of allele TNF2 and in proportions of TNF2 carriers was found when comparing subgroups of patients. The frequency of allele TNF2 was significantly higher in steroid-dependent than in non-steroid-dependent disease (28.1% versus 10.3%; Delta = 17.8%, 95% confidence interval (CI) = 6.3-29.5%, P = 0.0027) and tended to be higher in colonic than in small bowel disease and in fistulizing than in stricturing disease. Furthermore, TNF2 carriers tended to be more frequent in patients with steroid-dependent than non-steroid-dependent disease (43.8% versus 19.3%; Delta = 24.5%, 95% CI = 3.6-45.4%, P = 0.022), in patients with fistulizing than stricturing disease (26.5% versus 9.6%; Delta = 16.9%, 95% CI = 1. 1-32.6%, P = 0.036), and in patients with colonic than small bowel disease (26.5% versus 11.1%; Delta = 15.4%, 95% CI = -0.8-31.6%, P = 0.063). Finally, patients carrying at least one copy of allele 2 were found to produce slightly more TNF-alpha at the colonic level. The -308 TNF gene polymorphism may have a slight influence on the behaviour of CD. The carriage of allele 2 may favour steroid-dependent disease and to a lesser extent fistulizing and colonic disease, possibly secondary to a more intense TNF-alpha-driven inflammatory reaction at the mucosal level.

Adult↗

The antihypertensive hydralazine is an efficient scavenger of acrolein.

Recent work indicates the highly toxic alpha,beta-unsaturated aldehyde acrolein is formed during the peroxidation of polyunsaturated lipids, raising the possibility that it functions as a 'toxicological second messenger' during oxidative cell injury. Acrolein reacts rapidly with proteins, forming adducts that retain carbonyl groups. Damage by this route may thus contribute to the burden of carbonylated proteins in tissues. This work evaluated several amine compounds with known aldehyde-scavenging properties for their ability to attenuate protein carbonylation by acrolein. The compounds tested were: (i) the glycoxidation inhibitors, aminoguanidine and carnosine; (ii) the antihypertensive, hydralazine; and (iii) the classic carbonyl reagent, methoxyamine. Each compound attenuated carbonylation of a model protein, bovine serum albumin, during reactions with acrolein at neutral pH and 37 degrees C. However, the most efficient agent was hydralazine, which strongly suppressed carbonylation under these conditions. Study of the rate of reaction between acrolein and the various amines in a protein-free buffered system buttressed these findings, since hydralazine reacted with acrolein at rates 2-3 times faster than its reaction with the other scavengers. Hydralazine also protected isolated mouse hepatocytes against cell killing by allyl alcohol, which undergoes in situ alcohol dehydrogenase-catalysed conversion to acrolein.

Acrolein↗

[Epidemiological aspects, risk factors, and detection of pancreatic cancer].

The incidence of pancreatic cancer (PC) is increasing in developing countries. Smoking, reduced consumption of fruits and vegetables, chronic pancreatitis appear to be the best established risk factors. PC is often diagnosed at a late stage. We have to look for it when dyspepsia with weight loss, pancreatic pain or impaired glucose tolerance occurs. Tumor markers are briefly exposed and we discuss the place of endoscopic retrograde cholangiopancreatography (ERCP) after non invasive imaging techniques.

Biomarkers, Tumor↗

[Endoscopic ultrasonography in the diagnosis and staging of pancreatic and ampullary cancer: influence on patient management].

Accurate preoperative staging is now more prerequisite in the management of cancer of the pancreas and ampulla in order to orientate the patient toward the best selected treatment: either a curative or a palliative surgery associated or not with a pre- or postoperative multimodal therapy, or an endoscopic palliative technique which does not require surgery. Endoscopic ultrasonography (EUS) appears to be a highly accurate diagnostic procedure in the assessment of local resectability because it enables detailed visualization of the pancreatic gland, the depth of infiltration into the surrounding tissue and organs and visualisation of regional lymph nodes involvement. EUS-guided fine needle aspiration for cytology will provide a tissue diagnosis. The likelihood of successful resection for palliative or cure can be predicted before surgery. The following overview will point out the clinical impact of EUS on diagnosis, staging and management of these tumors.

Ampulla of Vater↗

Effects of macrolide antibiotics on CYP3A expression in human and rat hepatocytes: interspecies differences in response to troleandomycin.

The effects of various macrolide antibiotics [triacetyloleandomycin (TAO), clarithromycin, azithromycin, roxithromycin, erythromycin base] and the new ketolide HMR3004 on CYP3A expression were evaluated in human and rat hepatocytes. Cells were treated for 3 days with nontoxic concentrations of the drugs, and CYP3A induction was assessed through midazolam hydroxylase activity and Western and Northern blot analyses. In rat hepatocytes, no induction of CYP3A1 expression was observed following exposure to macrolides, even to erythromycin base and TAO (well known in vivo CYP3A1 inducers), whereas dexamethasone and phenobarbital were confirmed to induce this enzyme. In contrast, treatment of fresh and thawed human hepatocytes with TAO, produced an increase of midazolam hydroxylation (4-fold over control). This result was in agreement with the high amount of CYP3A4 protein and mRNA revealed by Western and Northern blot analyses. Other tested macrolides had no induction effect on CYP3A expression. These results confirmed the interspecies variability of CYP3A regulation in hepatocytes and raised the question of its mechanism of induction by macrolides in human liver.

Animals↗

Postoperative radiotherapy in the management of adult soft tissue sarcoma of the extremities: results with two different total dose, fractionation, and overall treatment time schedules.

PURPOSE: This retrospective study was performed to evaluate two postoperative radiotherapy schedules in terms of dose, fractionation, and overall treatment time in soft tissue sarcoma (STS) of the extremities. METHODS AND MATERIALS: Between January 1984 and December 1993, 62 patients with newly diagnosed localized STS of the extremities were treated with maximal conservative surgery and postoperative radiotherapy (RT). Forty-five patients received 50 Gy with conventional fractionation plus a boost dose (5 to 20 Gy). Seventeen patients had hyperfractionated accelerated radiotherapy (HFART) up to a dose of 45 Gy in 3 weeks. RESULTS: With a median follow-up of 72 months, the 5-year local failure rate was 25%, the 5-year disease-free and overall survival rates were respectively 42% and 62%. The 3-year local relapse, disease-free, and overall survival rates were respectively 16%, 44%, and 70% in the conventional radiotherapy group, and 36%, 47%, and 82% in the HFART group (NS). No factor significantly influenced local control with a trend, however, in favor of conventional RT (p = 0.10). CONCLUSION: HFART at the dose of 45 Gy does not seem to be superior to the standard RT schedule, neither in terms of local control, survival, nor in terms of long-term side effects. However this dose could be considered too low as well as the power of comparison between the two groups to draw definitive conclusions.

Adolescent↗

Cytochrome 1A1 induction by primaquine in human hepatocytes and HepG2 cells: absence of binding to the aryl hydrocarbon receptor.

Malaria remains the most prevalent infectious disease of tropical and subtropical areas of the world. It represents a crucial problem in public health care, affecting 750 million people annually, of whom at least two million die. Various antimalarials currently used were studied for their capability to induce expression of the cytochrome P450 1A1 (CYP1A1) gene, an enzyme that plays an important role in the activation of xenobiotics to genotoxic derivatives. Studies on human hepatocytes and HepG2 cell lines showed that primaquine was capable of dose dependently increasing both the ethoxyresorufin-O-deethylase activity and CYP1A1 mRNAs, suggesting a transcriptional activation of this gene. Moreover, alpha-naphthoflavone, a partial aryl hydrocarbon receptor (AhR) antagonist, and 8-methoxypsoralen, which interferes with the binding of activated AhR to the xenobiotic responsive element, were shown to suppress CYP1A1 induction when added to the cultures. However, neither primaquine nor its metabolites were able to displace [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin from AhR in competitive binding studies using 9S-enriched fractions of human cytosol. These data, together with the induction of CYP1A1 promoter-directed chloramphenicol acetyl transferase gene expression, suggest that CYP1A1 induction involves the participation of the AhR but not a direct primaquine-receptor interaction. This supports the notion that an alternative ligand-independent mechanism has to be considered. Given the pharmaco-toxicological significance of CYP1A1 induction, these findings may have important implications in the treatment of malaria with primaquine and new analogs.

Benzoflavones↗

Acute lower gastrointestinal bleeding in Crohn's disease: characteristics of a unique series of 34 patients. Belgian IBD Research Group.

OBJECTIVE: Acute lower gastrointestinal bleeding is a rare complication of Crohn's disease, which represents a diagnostic and therapeutic challenge. The aim of this study was to define epidemiological characteristics and therapeutic options of hemorrhagic forms of Crohn's disease. METHODS: Thirty-four cases of hemorrhagic forms of Crohn's disease were studied retrospectively. Acute lower gastrointestinal hemorrhage was defined as acute rectal bleeding originating in diseased bowel and requiring a transfusion of at least 2 units of red blood cells within 24 h. Upper gastrointestinal tract hemorrhage or anal lesions and postoperative bleeding were excluded. RESULTS: Mean age at time of hemorrhage was 34.2 +/- 14 yr. Mean duration of disease before the hemorrhage was 5.6 +/- 6 yr. The hemorrhage occurred during a flare up of the disease in 35% of cases. The hemorrhage revealed Crohn's disease in 23.5% of cases. The hemorrhage was more frequent in colonic disease (85%) than in isolated small bowel disease (15%) (p < 0.0001). The origin of bleeding was identified in 65% of cases, by colonoscopy (60%), by angiography (3 patients), or at surgery (1 patient). The bleeding lesion was an ulcer in 95% of cases, most often in the left colon. The treatment was surgical in 20.5% (colectomy in 36%), endoscopical (7 patients, including 5 successes), or medical. Hemorrhage recurred in 12 patients (35%) within a mean time of 3 yr (4 days-8 yr), requiring surgery in 3 cases. No death was observed. CONCLUSIONS: This study performed in a series characterized by a nonsurgical recruitment, the largest to date, shows that hemorrhagic forms of Crohn's disease may reveal disease in 23.5%, occurs in quiescent Crohn's disease in two-thirds of cases. Given the potential efficacy of endoscopical or medical treatment, as well as the absence of mortality, a conservative approach may be suggested as first-line therapy in the majority of patients.

Acute Disease↗