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Biomedical subjects

J C Chaput

Publications and source records attributed to J C Chaput.

At least 19 recordsLinked to original sources
PubMed1998

In vitro inhibition of human colonic motility with SR 59119A and SR 59104A: evidence of a beta3-adrenoceptor-mediated effect.

The new beta3-adrenoceptor is present in the gastrointestinal tract of various species. This study aimed to show that this receptor modulates human colonic motility in vitro. We used circular muscle strips from the human colon suspended in single organ baths containing Krebs solution and subjected to an initial 1.5-2 g tension. We measured the effects of different beta3-adrenoceptor agonists, including SR 59104A (N-[(6-hydroxy-1,2,3,4-tetrahydronaphthalen-(2R)-2-yl)methyl]-(2 R)-2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride), SR 59119A (N-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-(2R)-2-yl)methyl]-(2R) -2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride), BRL 37344 (R,R + S,S) [4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino] propyl] phenoxy] acetic acid), and of isoprenaline and salbutamol in the absence or in the presence of propranolol alone or in combination with the beta3-adrenoceptor antagonist SR 59230A (3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydro-naphthalen-1- ylamino]-(2S)-2-propanol oxalate) on amplitude of spontaneous contractions. To evaluate a possible beta2-adrenoceptor-mediated effect, we studied the action of these compounds on human isolated bronchi. On the human isolated colon, SR 59119A, SR 59104A and isoprenaline reduced the initial amplitude of spontaneous contractions by 60%. The curves obtained in the presence of antagonists suggested an action mediated by beta3-adrenoceptor stimulation, since propranolol did not antagonize the action of SR 59119A and SR 59104A, whereas the combination of propranolol and SR 59230A significantly displaced the concentration-response curve of these agonists to the right. This study provides pharmacological evidence of modulation of human colonic motility, and especially of the amplitude of spontaneous contractions, by the atypical beta-adrenoceptor, the beta3-adrenoceptor.

Adrenergic beta-Agonists↗
PubMed1998

Plasma levels of soluble tumor necrosis factor receptors p55 and p75 in patients with alcoholic liver disease of increasing severity.

BACKGROUND/AIMS: Correlations between serum levels of soluble tumor necrosis factor receptors p55 (TNFsRp55) and Child Pugh index have previously been reported in alcoholic patients with cirrhosis. We have undertaken this study to improve understanding of the role of tumor necrosis factor soluble receptors (TNFsRs) in alcoholic liver disease. METHODS: One hundred and two patients with alcoholic liver disease of various severity (23 pure steatosis, 22 fibrosis, seven acute alcoholic hepatitis without cirrhosis, 12 cirrhosis without acute alcoholic hepatitis, 14 cirrhosis with mild acute alcoholic hepatitis and 24 cirrhosis with severe acute alcoholic hepatitis) were studied. Blood was collected on EDTA and plasma was tested for TNFsR concentrations using ELISA assays. RESULTS: Plasma levels of TNFsRp55 and p75 increased progressively with the severity of liver disease, reaching a maximum in cirrhotic patients with severe acute alcoholic hepatitis. Plasma levels of TNFsRp55 in patients with fibrosis and of TNFsRp75 in patients with acute alcoholic hepatitis without cirrhosis were already higher than in healthy controls. In cirrhotic patients with or without acute alcoholic hepatitis TNFsRp55 and p75 were significantly increased compared with controls. In cirrhotic patients, plasma levels of TNFsRp55 correlated positively with all parameters of liver injury, whereas the TNFsRp75/ TNFsRp55 ratio correlated negatively. In cirrhotic patients with severe acute alcoholic hepatitis, the TNFsRp75/TNFsRp55 ratio was significantly lower than in all other groups. In cirrhotic patients with severe acute alcoholic hepatitis treated by prednisolone, the decrease in TNFsRp55 plasma levels between day 1 and day 15 was significantly more important in patients still alive at 2 months than in patients who died within 2 months. CONCLUSIONS: These results show that the expression of TNF-soluble receptors (TNFsRs) participates in the early phases of the alcoholic liver disease and that the TNFsRp75/TNFsRp55 ratio and plasma levels of TNFsRp55 may help to determine the diagnosis and the prognosis of severe acute alcoholic hepatitis in cirrhotics.

Adult↗
PubMed1998

Post-traumatic membranous obstruction of the inferior vena cava associated with a hypercoagulable state.

It has been hypothesized that abdominal trauma may be one of the factors involved in membranous obstruction of the inferior vena cava. We present two cases of membranous obstruction of the inferior vena cava associated with trauma. One asymptomatic case, associated with an occult myeloproliferative disorder, developed within 3 years of a violent abdominal trauma. The other case, associated with familial plasminogen deficiency, was discovered at surgery 3 days after a road accident with obvious abdominal trauma, since superimposed extensive thrombosis of the inferior vena cava caused acute Budd-Chiari syndrome. We conclude that underlying prothrombotic conditions are probably necessary for the development of membranous obstruction of the inferior vena cava and that minor trauma may contribute to the development of thrombosis through indirect mechanisms.

Adolescent↗
PubMed1998

[Predictive risk factors for progression to cirrhosis in early stage alcoholic liver disease].

OBJECTIVE: To assess the risk factors of cirrhosis in early stage alcoholic liver disease. PATIENTS: We investigated 83 heavy drinkers (60 males and 23 females) in whom the first of two liver biopsies showed normal or pure alcoholic fatty liver. RESULTS: When the six following variables: sex, age, delay between the first and last biopsy, total duration of alcohol consumption before the first biopsy, daily alcohol consumption for the last 5 years before the first biopsy and the extent of fatty liver in the first biopsy, were considered together in stepwise regression analysis, the delay between the first and last biopsy (p < 0.0001), sex (P < 0.004) and the extent of fatty liver in the first biopsy (P < 0.06) significantly improved the prediction of cirrhosis. The odds ratio of cirrhosis for a women was 19.1 (confidence interval 95% [1.85-197]). The odds ratio for cirrhosis for a percentage of fatty liver > or = 5/10 was 7.4 (confidence interval 95% [1-92]). CONCLUSION: With the same delay between two liver biopsies, the female sex and the extent of fatty liver are two independent risk factors for the development of cirrhosis in heavy drinkers.

Adult↗
PubMed1997

Excess weight risk factor for alcoholic liver disease.

Though the hepatotoxicity of ethanol has been established, only 8% to 20% of chronic alcoholics develop cirrhosis. The aim of this study was to assess whether being overweight is a risk factor for alcoholic liver disease. One thousand six hundred four alcoholic patients were studied. According to the liver biopsies, 194 patients had a normal liver; 402 had steatosis without fibrosis; 281 presented with fibrosis, with or without steatosis; 119 presented with acute alcoholic hepatitis (AAH) without cirrhosis; 232 indicated cirrhosis without AAH; and 179 presented with cirrhosis with AAH. One hundred ninety-seven patients had clinically obvious cirrhosis. In the study, five variables were studied as risk factors: age, sex, daily consumption of alcohol during the previous 5 years, the total duration of alcohol abuse, and tendency to be overweight (body mass index [BMI] > or = 25 in women and > or = 27 in men). The BMI was calculated according to the minimum weight over the 10 previous years. In the first stepwise logistic regression analysis, age, being overweight for at least 10 years, being of the female sex, and the total duration of alcohol abuse were independently correlated with the presence of cirrhosis. In the second analysis, female sex being overweight were the two independent risk factors of AAH. In the third analysis, being overweight for at least 10 years was the only independent risk factor of steatosis. These results show that the presence of excess weight for at least 10 years is a risk factor for cirrhosis, AAH, and steatosis. Our results suggest that there is a possible potential for the metabolic effects of ethanol ingestion caused by excess weight in patients with alcoholic liver disease.

Adult↗
PubMed1997

Interleukin-1 receptor antagonist plasma concentration is specifically increased by alpha-2A-interferon treatment.

BACKGROUND/AIMS: The mechanism of action of recombinant interferon-alpha (rIFN alpha) treatment in chronic hepatitis C is not fully understood, and may include modulation of the immune system as well as a direct antiviral effect. We have therefore evaluated the plasma concentrations of pro- and anti-inflammatory cytokines in patients with chronic hepatitis C before and during treatment with rIFN alpha. METHODS: Twenty-three patients were studied. Plasma concentrations of IL-1 beta, IL-6, TNF, IL-1 receptor antagonist (IL-1RA) and soluble TNF receptors (sTNFRs) type I and type II were determined twice before rIFN alpha treatment (on day -11 and day 1), and on days 11, 32 and 120 of treatment. RESULTS: IL-1 beta, IL-6 and TNF plasma concentrations were rarely increased before treatment (in one, six and seven patients, respectively), and usually declined during treatment. sTNFRs I and II plasma concentrations were not increased either before or during treatment. This was not the case for IL-1RA. In untreated patients, the plasma concentration of IL-1RA was higher than normal in 16 out of 23 patients. When rIFN alpha treatment was initiated, there was a constant and dramatic increase in IL-1RA levels, which reached 8 times the upper limit of the normal range (p < 0.001 as compared to pretreatment values). This increase was sustained up to day 120. CONCLUSIONS: These results indicate that induction of an anti-inflammatory status through modulation of the IL-1/IL-1RA balance may be a key mechanism of action of rIFN alpha treatment in chronic hepatitis C.

Adult↗
PubMed1997

Beyond guanine quartets: cation-induced formation of homogenous and chimeric DNA tetraplexes incorporating iso-guanine and guanine.

BACKGROUND: iso-Guanine (iso-G) is the purine component of an isomeric Watson-Crick base pair that may have existed prebiotically. By comparing the abiotic molecular recognition properties of iso-G and its complement, iso-cytosine (iso-C), with those of genomic nucleotide bases, it may be possible to explain the exclusion of the iso-G-iso-C base pair from modern genomes. Whether a nucleobase forms quartets may have a key role in determining its functionality. Biotically, nucleic acid tetraplexes have been implicated in cellular functions; prebiotically, tetraplexes would probably interfere with replication. Recently, in vitro selection has yielded receptors and catalysts that incorporate G quartets. The versatility of these structures could be enhanced by expanding the range of bases that can form the quartet motif. RESULTS: Native polyacrylamide gel electrophoresis of oligonucleotides bearing runs of iso-G provides strong support for tetraplex formation via cation-promoted DNA strand association. In particular, when strands of different lengths bearing the same iso-G tetrad recognition element were combined, five bands were observed after electrophoresis, corresponding to all possible heterotetraplexes with parallel strand alignment. An analogous experiment with a mixture of strands bearing iso-G or G tetrad recognition domains supports the existence of mixed iso-G/G tetraplexes with antiparallel strand alignment at chimeric junctions. iso-G tetraplex and quartet structure has also been probed by a photo-crosslinking experiment, ultra-violet spectroscopy and theoretical calculations. CONCLUSIONS: As iso-G and G both have a marked tendency to form tetraplexes, their tandem inclusion in genetic material may be problematic, leading to double-stranded DNA half composed of bases that have a tendency to auto-associate. The resulting density of 'selfish' bases could undermine Watson-Crick pair formation, especially in a prebiotic context devoid of enzymes. Nevertheless, the ability of iso-G to form mixed quartets with G may provide a basis for altering the properties of tetraplexes in the domain of artificial receptors or catalysts from in vitro selections.

Cations↗
PubMed1996

Quantification of apolipoprotein A-I and B messenger RNA in heavy drinkers according to liver disease.

It has previously been shown that, in heavy drinkers, serum apolipoprotein A-I (ApoA-I) levels are closely related to the degree of liver injury: they are at a maximum in patients with steatosis, begin to decrease in patients with fibrosis, and reach a minimum in patients with severe cirrhosis. In contrast with serum ApoA-I variations, serum apolipoprotein B (ApoB) levels are stable. The assessment of messenger RNA (mRNA) levels of ApoA-I and ApoB using a quantitative competitive polymerase chain reaction (PCR) method was performed in 18 alcoholic patients: 8 with normal livers or steatosis (group I), 6 with fibrosis or nonsevere cirrhosis (group II), and 4 with severe cirrhosis (group III). For ApoA-I, group I had higher serum levels (208.4 +/- 37.6 mg/dL mean +/- SE) and mRNA levels (0.51 +/- 0.12) than group II (serum 116 +/- 19 mg/dL, P < .01, mRNA 0.40 +/- 0.11, P < .09) or group III (serum 56.5 +/- 28.6 mg/dL, P < .01, mRNA 0.27 +/- .02, P = .008). For ApoB, the three groups had similar serum ApoB levels: 129.9 +/- 37.7, 121 +/- 51, 120.7 +/- 57.4 mg/dL. Group I presented higher levels of ApoB mRNA than those of group III (0.68 +/- 0.21 vs. 0.41 +/- 0.18, P < .06). There was a significant correlation between serum and mRNA levels of ApoA-I (r = .65, P = .003) but no correlation between serum and mRNA levels of ApoB (r = .19, NS). We suggest that (1) steatosis is associated with increased ApoA-I mRNA; (2) fibrosis is associated with decreased serum ApoA-I, probably caused by a posttranscriptional mechanism; (3) severe alcohol-induced cirrhosis is associated with a nonspecific decrease in ApoA-I and ApoB mRNA; and (4) in contrast to ApoA-I mRNA, the ApoB mRNA level makes a slight contribution to the ApoB serum concentration.

Adult↗
PubMed1996

Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone.

BACKGROUND & AIMS: Corticosteroids have been shown to significantly decrease short-term mortality in patients with severe alcoholic hepatitis. However, independent factors associated with a favorable outcome and long-term survival are unknown. The aim of this study was to examine prognostic factors and long-term survival in patients with biopsy-proven severe alcoholic hepatitis. METHODS: Of 183 patients studied, 61 had been randomized in a previous trial; 32 of them were treated with prednisolone (group I) and 29 were not treated (group II); 61 were treated from the end of this randomized trial (group III); and 61 were simulated (group IV). RESULTS: At 1 year, survival in group I (69%; confidence interval [CI], 57%-81%) and group III (71%; CI, 55%-87%) was better than in the nontreated groups (group II, 41%; CI, 23%-59%; P = 0.01) (group IV, 50%; CI, 37%-63%; P = 0.05). At 2 years, survival was not significantly different. Treated patients with marked liver polymorphonuclear infiltrate had better 1-year survival (76%; CI, 64%-88%) than the others (53%; CI, 35%-71%; P = 0.05). Treated patients with polymorphonuclear counts of > 5500/mm3 had better 1-year survival (77%; CI, 65%-89%) than the others (40%; CI, 14%-66%; P = 0.003). In the 93 treated patients, liver polymorphonuclear infiltrate (P < 0.03) and polymorphonuclear count (P < 0.001) were independently correlated with 1-year survival. CONCLUSIONS: Prednisolone reduced mortality by at least 1 year. Liver polymorphonuclear infiltrate and polymorphonuclear count were independent prognostic factors.

Female↗
PubMed1996

[Prevalence of serum anti-hepatitis C virus antibodies and risk factors of contamination in the personnel of a hospital in the Paris region. A prospective survey].

OBJECTIVES: The aim of this prospective study was to estimate the prevalence of subjects with serum anti-HCV antibodies in a University Hospital in the Paris area, and to identify the risk factors associated with contamination. METHODS: Over an 18 month period, each person working in the hospital was systematically requested to fill out an anonymous questionnaire including 23 questions and to undergo a blood test for an anti-HCV assay during their annual medical visit. RESULTS: 557 (33%) of 1693 employees accepted to fill out the questionnaire and the anti-HCV assay. Serum anti-HCV antibodies were present in 9 subjects, which represents a prevalence of 1.6%, and serum RNA was positive by PCR, m 7. The prevalence was significantly higher in subjects working in clinical units (3.0%) compared to subjects working in non-clinical units (0.7%: P = 0.04) and in subjects with a history of acute hepatitis (5.5% vs 0.9%; P = 0.002%) Anti-HCV-positive subjects had more history of manipulating blood products than HCV-negative subjects (17.0 vs 8.8 years of exposure; P = 0.01), other human samples (17.0 vs 7.6 years; P = 0.01), and of having at risk contacts (16.7 vs 6.2 years; P = 0.0004). CONCLUSION: These results suggest the importance of systematic anti-HCV screening among health care workers particularly those in contact with patients.

Adult↗
PubMed1995

Nonhereditary colonic angiodysplasias: histomorphometric approach to their pathogenesis.

The pathogenesis of colonic angiodysplasias, more accurately termed vascular ectasias (VE) has not been definitely established. The aim of this study was to assess that the VE of noncirrhotic patients are not associated with diffuse abnormalities of the colonic mucosal microvasculature unlike the VE of cirrhotic patients. Three groups of nine consecutive patients were studied: group I, control patients with an irritable bowel syndrome; group II, noncirrhotic patients with VE; and group III, alcoholic cirrhotics with VE. A histomorphometric analysis of normal-appearing colonic mucosa was achieved from biopsies taken at six predetermined sites. Noncirrhotics with VE had a significantly lower mean number of mucosal capillaries and a significantly lower mean cross-sectional area of mucosal capillaries than alcoholic cirrhotics with VE. Alcoholic cirrhotics with VE had a significant increase of all the vascular parameters compared to the control group. There was no difference between the control patients and the noncirrhotic patients with VE. These results suggest that the VE of noncirrhotic and cirrhotic patients are entities of distinct pathogenesis.

Angiodysplasia↗
PubMed1995

Weak immunogenicity of the preS2 sequence and lack of circumventing effect on the unresponsiveness to the hepatitis B virus vaccine.

The preS2 sequence is known to circumvent immunological unresponsiveness to the S protein and to induce a 'carrier' effect on the anti-S antibody production, in mice. In humans, an anti-S response was found in 100% and 97% of healthy subjects vaccinated with the S and S + preS2 preparations, respectively, whereas less than 50% of drinkers responded whatever the vaccine used. Anti-preS2 were found in 44% of healthy recipients of the S + preS2 vaccine, whereas there were no anti-preS2 responders in drinkers. Anti-preS2 remained undetectable in 32% of the blood donors hyperimmunized with the S + preS2 vaccine, whereas anti-S antibody boosted in all cases. In humans, in contrast to mice, immunogenicity of the preS2 sequence appears weak and the preS sequence does not circumvent the anti-S unresponsiveness.

Adult↗
PubMed1995

Prevalence of cholelithiasis according to alcoholic liver disease: a possible role of apolipoproteins AI and AII.

Moderate alcohol intakes decreases the risk of gallstones; in contrast, the prevalence of gallstones is increased in patients with alcoholic cirrhosis. The aims of this prospective study were to assess the prevalence of cholelithiasis among drinkers according to the histological severity of liver disease, and to estimate the importance of serum apolipoproteins AI and apolipoprotein AII as risk factors for gallstones. Among the 320 drinkers included, 53 patients had cholelithiasis. The prevalence increased (p < 0.0001) from 5% in patients with normal liver (1 of 22) and 6% in patients with steatosis only (3 of 47) to 13% in patients with fibrosis (7 of 54), reaching 27% among patients with biopsy-proven cirrhosis (28 of 103). Among patients with clinically obvious cirrhosis on whom biopsy was not performed mainly because of the severity of liver disease, the prevalence of cholelithiasis reached a maximum of 46% (6 of 13). Among drinkers with nonsevere liver disease, patients with cholelithiasis were older (59 +/- 9 years, mean +/- SD vs. 45 +/- 11, p = 0.003) with lower apolipoprotein AI (118 +/- 37 vs. 163 +/- 45 mg/dl; p = 0.002) and apolipoprotein AII (30 +/- 12 vs. 53 +/- 20 mg/dl; p = 0.0002) in comparison with patients without cholelithiasis. These differences persisted after considering by multiple logistic regression analysis, sex, and ideal body weight. Alcohol consumption during the last 5 years was lower in patients with cholelithiasis (83 g/day) in comparison with patients without cholelithiasis (142 g/day; p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Alpha-2-macroglobulin and hepatic fibrosis. Diagnostic interest.

Alpha-2-macroglobulin (A2M) is a proteinase inhibitor. Cells synthesizing A2M are in first-order hepatocytes and in second-order activated Ito cells (in culture starting at day 4-5 after seeding). This study was undertaken in 525 alcoholic patients with different histological stages of alcoholic liver disease to assess if the A2M could improve the diagnostic value of PGA index for detection of cirrhosis or fibrosis among drinkers, particularly in patients without clinical symptoms of liver failure and portal hypertension, and to assess the specific correlation of serum A2M with the score of liver fibrosis adjusted for steatosis and alcoholic hepatitis and thereafter adjusted for GGT, PT, and ApoA1, the three components of the PGA index. In 525 alcoholic patients, we have demonstrated the independent diagnostic value of A2M. The predictive values of the weighted score, using linear discriminant function combining PT, GGT, ApoA1 and A2M of the PGAA score and of the PGA score were assessed in a training step and validated in a second step. Then, 316 alcoholic clinically asymptomatic patients were studied. In these patients, the discriminant function permitted correct classification of 72% of patients. The PGAA index had comparable diagnostic value with 70% of patients correctly classified. On the other hand, the PGA index including only PT, GGT, and ApoA1 had classified correctly less patients (65%) than the discriminant function and the PGAA index (P < 0.01). For a value of 7, PGAA had 79% specificity and 89% sensitivity for the diagnosis of cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗
PubMed1994

Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome.

AIM: To assess the efficacy of smooth muscle relaxants in the treatment of patients with irritable bowel syndrome, a meta-analysis of 26 selected double-blind randomized trials vs. placebo was performed. METHODS: Five end-points were assessed: global assessment, abdominal pain, constipation, abdominal distension and the absence of adverse reactions. Analyses were performed according to the intention-to-treat method. For each end-point, the drug efficacy was assessed by the Der Simonian and Peto methods. When a significant difference was observed, sensitivity analyses were performed by successive stratifications according to the type of drug, the treatment duration, the prevalence of constipated patients, the trial design and the methodological quality. RESULTS: All myorelaxants analysed were significantly better than placebo for the improvement of global assessment (62% improvement rate vs. 35% on placebo, that is 27% improvement rate, P < 0.01) and for pain improvement (64% improvement rate vs. 45% on placebo, that is 19% improvement rate, P < 0.01). No significant differences were observed for constipation and abdominal distension. The percentage of patients with adverse reactions was significantly higher in patients receiving myorelaxants than placebo (6% mean difference, P < 0.01). CONCLUSION: According to this overview five drugs have proved their clinical efficacy in patients with irritable bowel syndrome, without significant adverse reactions: cimetropium bromide, pinaverium bromide, trimebutine, octilium bromide and mebeverine.

Colonic Diseases, Functional↗