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Biomedical subjects

J Genescà

Publications and source records attributed to J Genescà.

At least 19 recordsLinked to original sources
PubMed2003

Role of immunosuppression in the development of quinolone-resistant Escherichia coli spontaneous bacterial peritonitis and in the mortality of E. coli spontaneous bacterial peritonitis.

BACKGROUND: Norfloxacin decreases the incidence of spontaneous bacterial peritonitis in cirrhotics, but promotes the appearance of quinolone-resistant Escherichia coli. AIM: : To define the characteristics of quinolone-resistant E. coli spontaneous bacterial peritonitis. METHODS: E. coli-positive ascitic fluid cultures were identified during a 6-year period. Data on quinolone-sensitive and quinolone-resistant E. coli spontaneous bacterial peritonitis were compared. RESULTS: One hundred and two E. coli-positive ascitic fluid cultures were detected. Cirrhotics accounted for 67 cases. Spontaneous bacterial peritonitis was found in 47 of the 67 (70%) cases [35 (74%) caused by quinolone-sensitive and 12 (26%) caused by quinolone-resistant E. coli]. Norfloxacin prophylaxis was higher in the quinolone-resistant group (92% vs. 6%, P < 0.001). Compared with patients with quinolone-sensitive E. coli spontaneous bacterial peritonitis, those with quinolone-resistant E. coli spontaneous bacterial peritonitis showed a higher prevalence of associated immunosuppressive factors (immunosuppressive drugs, human immunodeficiency virus infection or cancer) (92% vs. 20%, P < 0.001). Steroid therapy was independently associated with quinolone-resistant E. coli spontaneous bacterial peritonitis (odds ratio, 49; 95% confidence interval, 3.4-699; P = 0.004). The Child-Pugh score (P = 0.03), immunosuppression (P = 0.02) and renal failure (P = 0.01) were independent predictors of E. coli spontaneous bacterial peritonitis-related mortality. CONCLUSIONS: Associated immunosuppression is an important co-factor for the development of quinolone-resistant E. coli spontaneous bacterial peritonitis and for E. coli spontaneous bacterial peritonitis-related mortality.

Anti-Infective Agents↗
PubMed2003

Increased tumour necrosis factor alpha production in mesenteric lymph nodes of cirrhotic patients with ascites.

BACKGROUND: Cytokines produced in mesenteric lymph nodes of cirrhotic rats with bacterial translocation may participate in circulatory alterations of cirrhosis. AIM: To investigate whether cirrhotic patients present an increased local generation of cytokines in mesenteric lymph nodes. METHODS: Mesenteric lymph nodes from 26 cirrhotic and 10 control patients were assessed for tumour necrosis factor alpha (TNF) and interleukin 6 mRNA and protein expression by competitive reverse transcription-polymerase chain reaction, and by enzyme immunoassay and immunohistochemistry, respectively. RESULTS: Interleukin 6 levels were not different between cirrhotics and controls. Protein and mRNA TNF levels in mesenteric lymph nodes from cirrhotics were higher than in controls (p<0.05). Tissue expression of TNF by immunohistochemistry was more abundant in cirrhotics. Ascitic patients showed higher TNF levels (47 (34-54) pg/mg protein) than patients without ascites (18 (17-25) pg/mg protein) (p<0.001). Elevated TNF levels (>28 pg/mg protein) in cirrhotics were associated with a higher Child-Pugh score, the antecedent of ascites, a lower prothrombin rate, and higher bilirubin and blood TNF levels. The strongest association, confirmed by multivariate analysis, was with the presence of ascites (p<0.001). Bacterial infections after transplantation, mainly by enteric bacteria, were only detected in patients with high TNF levels in mesenteric lymph nodes (33% of patients; p=0.05). CONCLUSION: Patients with advanced liver cirrhosis, and especially with ascites, have increased local production of TNF in mesenteric lymph nodes that, in common with experimental cirrhosis, may also be induced by bacterial translocation.

Ascites↗
PubMed2001

Islet cell and thyroid antibody prevalence in patients with hepatitis C virus infection: effect of treatment with interferon.

An increased prevalence of hepatitis C virus (HCV) infection in patients with diabetes and a higher prevalence of diabetes in HCV-infected patients have been reported. However, the relationship between these two conditions remains controversial. In addition, although the effect of interferon treatment on thyroid autoimmunity has been extensively reported, its influence on beta-cell autoantibodies has not been investigated. The aims of the study were (1) to evaluate whether autoimmune beta-cell damage could be involved in the development of diabetes mellitus in HCV-infected patients and (2) to determine whether interferon treatment influences the appearance of beta-cell and thyroid autoantibodies. The prevalence of islet cell autoantibodies (glutamic acid decarboxylase antibodies [GADAs], tyrosine phosphatase antibodies [IA-2s], islet cell antibodies [ICAs]) was assessed in 303 non-selected HCV-infected patients (277 non-diabetic and 26 type 2 diabetic patients) and in 273 sex- and age-matched control subjects. ICAs and thyroid autoantibodies were also determined before and 6 and 12 months after treatment with interferon for 24 weeks in a subgroup of 46 HCV-infected patients. GADAs were detected in 4 of 277 (1.4%) HCV-infected non-diabetic patients, 1 of 273 (0.3%) control subjects, and 0 of 26 (0%) HCV-infected patients with diabetes. Anti-IA2s and ICAs were negative in all subjects. Both GADAs and anti-IA2s were negative in all HCV-infected patients treated with interferon. After therapy, only thyroid antibodies became positive in 5 of 46 (10.9%) treated patients, disappearing in all but 1 of these at the 12-month follow-up. Our results suggest that beta-cell autoimmunity is not associated with HCV infection, thus making it unlikely that the increased diabetes mellitus prevalence among HCV-infected patients could be mediated by autoimmune mechanisms. In addition, interferon treatment induces a transient increase in thyroid autoantibodies but does not influence the appearance of beta-cell autoantibodies.

Adult↗
PubMed2001

Isosorbide mononitrate in the prevention of first variceal bleed in patients who cannot receive beta-blockers.

BACKGROUND & AIMS: Nonselective beta-blockers (beta-blockers) are very effective in preventing first variceal bleeding (FVB) in patients with cirrhosis. However, 15%-25% of patients have contraindications or develop severe side effects precluding its use. The present study evaluates whether isosorbide-5-mononitrate (Is-MN) effectively prevents variceal bleeding in patients with contraindications or who could not tolerate beta-blockers. METHODS: One hundred thirty-three consecutive cirrhotic patients with gastro-esophageal varices and contraindications or intolerance to beta-blockers were included in a multicenter, prospective, double-blind randomized controlled trial. Sixty-seven were randomized to receive Is-MN, and 66 to receive placebo. RESULTS: There were no significant differences in the 1- and 2-year actuarial probability of experiencing a FVB between the 2 treatment groups. Presence of variceal red signs at endoscopy was the only variable independently associated with an increased risk of variceal bleeding on follow-up (relative risk 3.4; P < 0.01). Survival and adverse events were similar in the 2 groups. There were no significant differences in the incidence of ascites or changes in renal function. CONCLUSIONS: Is-MN does not reduce the incidence of FVB in patients with cirrhosis and esophageal varices who cannot be treated with beta-blockers because contraindications or intolerance to these drugs, suggesting that Is-MN has no place in the primary prophylaxis of variceal bleeding.

Adrenergic beta-Antagonists↗
PubMed2000

[Relationship between iron stores and diabetes mellitus in patients infected by hepatitis C virus: a case-control study].

BACKGROUND: To investigate whether the high prevalence of diabetes observed in patients infected by the hepatitis C virus (HCV) is associated to iron stores. PATIENTS AND METHODS: Serum ferritin levels were determined in 123 patients infected by HCV (55 diabetic and 68 non-diabetic). RESULTS: Serum ferritin concentrations were higher in diabetic than in non-diabetic patients (205 ng/ml [14-861] vs. 58 ng/ml [15-494]; p < 0.0001). CONCLUSIONS: Serum ferritin levels are related with the presence of diabetes in patients infected by HCV.

Biopsy↗
PubMed1997

Structure of replicating hepatitis C virus (HCV) quasispecies in the liver may not be reflected by analysis of circulating HCV virions.

We have analyzed the population of hepatitis C virus (HCV) sequences in paired liver and serum samples from four patients with chronic hepatitis C. Sequences from three different biopsy specimens from a liver explant from one patient were compared with each other and with the circulating sequences. Our results demonstrate that the circulating quasispecies does not necessarily reflect the viral population replicating in the liver and that this is not due to a macroscopic anatomic compartmentalization of HCV replication. This finding has important implications for the pathogenesis and natural history of chronic HCV infection.

Chronic Disease↗
PubMed1996

High prevalence of hepatitis C virus infection in diabetic patients.

OBJECTIVE: To evaluate the prevalence of hepatitis C virus (HCV) infection in diabetic patients and to investigate the influence of several epidemiological and clinical factors on HCV infection. RESEARCH DESIGN AND METHODS: A total of 176 consecutive diabetic patients were compared with 6,172 blood donors, matched by recognized risk factors to acquire HCV infection. Serologic testing for anti-HCV was done using a second-generation commercial enzyme-linked immunosorbent assay (ELISA) and an immunoblot assay was performed in anti-HCV positive samples to confirm HCV specificity. Diabetic patients were divided in two groups according to their HCV antibody status and analyzed for the following variables: age, sex, type of diabetes, duration of disease, mode of therapy, late diabetic complications, previous blood transfusions, intravenous drug addiction, hospital admissions, major surgical procedures, and liver function tests (LFTs). RESULTS: A higher prevalence of HCV infection was observed in diabetic patients in comparison with blood donors (11.5 vs. 2.5%; P < 0.001; odds ratio 4.39; 95% Cl2.61-7.24). We did not detect any particular epidemiological factor for HCV infection in anti-HCV positive diabetic patients. In these patients, abnormal LFTs were observed in 72.3%, compared with only 24.7% of anti-HCV negative diabetic patients (P < 0.001). CONCLUSIONS: A high prevalence of HCV infection was detected in diabetic patients, and most of anti-HCV positive patients presented with abnormal LFTs. Therefore, testing for HCV infection of diabetic patients with an abnormal LFT is mandatory. The lack of any particular epidemiological factor for HCV infection in our diabetic population suggests that HCV may have a direct role in the development of diabetes.

Adult↗
PubMed1995

Hepatitis C virus infection in renal transplant recipients: epidemiology, clinical impact, serological confirmation and viral replication.

The presence and significance of hepatitis C virus infection was evaluated in 241 renal transplant recipients from our hospital. Hepatitis C virus antibodies were tested by second-generation enzyme immunoassay, followed by second- and third-generation immunoblot assays (RIBA-2 and RIBA-3); hepatitis C virus RNA was measured by nested polymerase chain reaction. Hepatitis C virus antibodies, which were detected in 46.5% of patients, were mainly present before transplantation and independently associated with the total amount of transfused blood, time in hemodialysis and duration of posttransplant follow up. Liver dysfunction (alanine aminotransferase elevation) was observed in 50% of antibody-positive recipients, and 92.5% of patients with chronic liver disease without hepatitis B infection were infected with hepatitis C virus. Most antibody-positive patients (78.4%) tested positive by RIBA-2, but 21.6% were indeterminate; RIBA-3 was positive in 90% of these indeterminates. Hepatitis C virus RNA detection was positive in 96% of antibody-positive cases tested, in 20% of patients who were already anti-HCV negative before transplantation and also demonstrated persistence of HCV infection in all cases who, being antibody positive prior to transplantation, lost these antibodies during follow up (9% of transplanted patients). In conclusion, hepatitis C virus infection is extremely prevalent in renal transplant recipients from Spain and is the main cause of chronic liver disease in these patients. Confirmation by supplemental assays of anti-HCV antibodies is not necessary, but hepatitis C virus RNA testing is indispensable to detect those cases who lose or do not develop hepatitis C virus antibodies.

Adult↗
PubMed1992

Interferon-alpha in acute posttransfusion hepatitis C: a randomized, controlled trial.

To assess the efficacy of interferon-alpha in acute hepatitis C, 28 patients with acute posttransfusion hepatitis were randomized to receive 3 million units of recombinant interferon-alpha three times weekly for 12 wk or no treatment. Biochemical, histological and serological parameters were monitored during 1 yr of follow-up. Serum ALT levels were normal at the end of therapy in 73% of treated patients and only in 38% of control patients (p = 0.06); these differences disappeared at 6 and 12 mo of follow-up. Anti-hepatitis C virus seroconversion occurred later and at a lower rate in the group of patients who received interferon-alpha. Treated patients had a trend toward less severe hepatic lesions with lower histological activity as compared with the control group, but no statistical differences were observed. No severe side effects of interferon-alpha were detected during the study. In summary, a 3-mo course of interferon-alpha in acute hepatitis C is safe and might have some effect in diminishing disease activity only during the treatment period; however, and probably because of a small sample size, no benefit of interferon-alpha in the long-term outcome of this disease was demonstrated.

Adolescent↗
PubMed1992

Evaluation of anti-HCV positive blood donors identified during routine screening.

Of 30,231 donors tested, 368 (1.2%) were anti-HCV positive. Of these, 254 have been evaluated, with the following results: only 25% have a history of parenteral risk, seroprevalence increases with age and approximately 80% of those that are anti-HCV positive in our population are probably infected with HCV. In addition, an unexpectedly large number of these persons have chronic and/or severe liver disease and will require combined diagnostic approaches for accurate evaluation.

Age Factors↗
PubMed1992

Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution.

Sequencing of multiple recombinant clones generated from polymerase chain reaction-amplified products demonstrated that the degree of heterogeneity of two well-conserved regions of the hepatitis C virus (HCV) genome within individual plasma samples from a single patient was consistent with a quasispecies structure of HCV genomic RNA. About half of circulating RNA molecules were identical, while the remaining consisted of a spectrum of mutants differing from each other in one to four nucleotides. Mutant sequence diversity ranged from silent mutations to appearance of in-frame stop codons and included both conservative and nonconservative amino acid substitutions. From the relative proportion of essentially defective sequences, we estimated that most circulating particles should contain defective genomes. These observations might have important implications in the physiopathology of HCV infection and underline the need for a population-based approach when one is analyzing HCV genomes.

Amino Acid Sequence↗
PubMed1991

High rate of infectivity and liver disease in blood donors with antibodies to hepatitis C virus.

OBJECTIVE: To determine the epidemiologic, clinical, serologic, and histologic importance of antibodies to hepatitis C virus (anti-HCV) in blood donors. DESIGN: Cross-sectional identification and prospective evaluation of seropositive donors; retrospective assessment of infectivity; and nested case-control study for risk factors. SETTING: Liver unit of a referral-based university hospital. SUBJECTS: Of 30,231 consecutive donors, 368 (1.2%) were found to be anti-HCV-reactive by enzyme-linked immunosorbent assay (ELISA). Two hundred and fifty-four of these 368 donors were evaluated for risk factors by comparison with 284 age- and sex-matched controls. Eighty-six spouses of seropositive donors were also evaluated. MEASUREMENTS AND MAIN RESULTS: Twenty-four percent of the seropositive donors had a history of percutaneous exposure to blood. This rate increased to 45% when only those donors confirmed to be anti-HCV positive by a second-generation recombinant immunoblot assay (RIBA-2) were considered. A family history of liver disease (odds ratio, 2.8; 95% Cl, 1.6 to 4.8), previous blood transfusion (odds ratio, 6.1; 95% Cl, 3 to 12.5), and a history of tattooing or intravenous drug abuse (odds ratio, 8.4; 95% Cl, 2.3 to 31) were associated with anti-HCV seropositivity. An elevated alanine aminotransferase (ALT) level was found in 58% of the seropositive donors. Of the 150 donors tested, 104 (69%; Cl, 62% to 77%) were confirmed by RIBA-2 to be anti-HCV positive. Of the 105 donors who had a biopsy, 16% had normal histologic findings, 11% had minimal changes, 21% had chronic persistent hepatitis, 45% had chronic active hepatitis, and 7% had active cirrhosis. All 77 donors with RIBA-2-confirmed seropositivity had histologic abnormalities. Of 43 donors evaluated in an infectivity study, 82% were implicated in previous HCV transmission. Only 2.3% of the spouses were anti-HCV positive. The ELISA, RIBA-2, and ALT results correlated with infectivity and abnormal histologic findings. CONCLUSIONS: In our geographic area, almost 70% of donors who are anti-HCV positive by ELISA are confirmed to be positive by RIBA-2; most of these donors appear to be chronic carriers of HCV and have substantial liver disease.

Adolescent↗
PubMed1989

Hepatitis C virus antibodies among risk groups in Spain.

The frequency of hepatitis C virus (HCV) infection in Spain was assessed by means of a recombinant-based immunoassay for serum anti-HCV antibodies. 836 serum samples were tested from 676 patients selected according to their risk of blood-borne viral infections and presence of liver disease. Among patients at high risk of infection (with or without liver disease) anti-HCV antibodies were found in 85% of prospectively followed patients with post-transfusion non-A, non-B hepatitis, 62% of patients with chronic hepatitis or cirrhosis and a history of blood transfusion, 70% of haemophiliacs receiving replacement therapy, 70% of intravenous drug abusers, and 20% of haemodialysis patients. Only 8% of homosexual men infected with human immunodeficiency virus and 6% of female contacts of drug abusers were positive. Among patients with liver disease and no history of parenteral exposure to blood, anti-HCV antibodies were detected in 38% with cryptogenic, alcoholic, or primary biliary cirrhosis and in 44% with chronic active hepatitis. Among healthy subjects without risk factors for hepatitis the overall prevalence of anti-HCV was 1.2%.

Adolescent↗