Biomedical subjects

J Crespo

Publications and source records attributed to J Crespo.

At least 19 recordsLinked to original sources

PubMed2002

Apoptosis mediated by the Fas system in the fulminant hepatitis by hepatitis B virus.

The pathogenesis of the fulminant hepatitis B is poorly understood and both viral factors and the hosts immune response play a role. Previous studies in liver tissues of patients with chronic hepatitis B showed overexpression of Fas antigen and this was correlated with the activity of the hepatitis. The present study was done to determine the role of Fas in fulminant hepatitis B and the virological characteristics of hepatitis B infection. We studied three patients with fulminant hepatitis B. HBV-DNA was detected by dot-blot hybridization and polymerase chain reaction. The S and C gene were sequenced. Levels of serum soluble Fas antigen were detected by enzymoimmunoassays procedure. Apoptosis was determined by the TUNEL technique. Fas antigen expression was evaluated by a immunoperoxidase method. Ten healthy subjects acted as controls. The three patients showed a high expression of Fas antigen particularly among infiltrating lymphocytes; in these areas we also found many cells with in situ DNA nick labelling signals in the nuclei of most viable hepatocytes. Serum levels of soluble Fas antigen were higher in patients with fulminant hepatitis B than in controls. No specific genome mutations of hepatitis B virus were found. These data suggest that the Fas system involved in the liver injury of patients with fulminant hepatitis B.

Adult↗

PubMed2002

Involvement of the Fas system in liver allograft rejection.

OBJECTIVE: Recent studies suggest that apoptosis is an important mechanism of cell death in the rejection of liver allografts and that this process is mediated via Fas. The aim of this study was to analyze the expression of the Fas system during the liver allograft rejection and its evolution after treatment. METHODS: We evaluated 14 patients with liver allograft rejection before and after treatment. Fas immunostaining was performed by the labeled streptavidin-biotin peroxidase method using a 200-fold dilution of a monoclonal antibody. Assessment of apoptosis was determined by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) technique on deparaffined liver samples. Serum levels of soluble Fas antigen (sFas) were detected by an enzyme immunoassay procedure. Twelve liver transplant patients without allograft rejection were analyzed as a control group. RESULTS: The number of hepatocytes expressing Fas antigen, the percentage of apoptotic hepatocytes, and the sFas levels were higher in patients with liver allograft rejection than in controls (27.9+/-23.1% vs 1.4+/-1.2%, p < 0.001; 2.2+/-0.9% vs 1.0+/-0.1%, p = 0.02; 24.2+/-39.6 vs 2.8+/-4.0 IU/ml, p = 0.03, respectively). There was a correlation between the levels of sFas, AST (r = 0.86, p < 0.001), ALT (r = 0.78, p = 0.02), and gamma-globulin levels (r = 0.86, p < 0.001). After the rejection treatment we found a significant decrease in the Fas antigen expression (18.6+/-13.3%, p < 0.05), TUNEL index (0.2+/-0.4, p < 0.05), and levels of sFas (9.9+/-30.25 IU/ml, p = 0.005). CONCLUSIONS: 1) The demonstration of hepatocytes with Fas antigen expression and the labeling of the nuclei by the TUNEL assay suggest that apoptosis mediated by the Fas system plays a role in the pathogenesis of liver allograft rejection. 2) The Fas expression and the sFas levels decreased in patients with treatment response.

Adult↗

PubMed2002

Theory, abstraction and design in medical informatics.

OBJECTIVE: To analyze the scientific and engineering components of Medical Informatics. A clear characterization of these components should be undertaken to categorize different areas of Medical Informatics and create a research agenda for the future. METHODS: We have adapted a classical ACM and IEEE report on computing to analyze Medical Informatics from three different viewpoints: Theory, Abstraction, and Design. RESULTS: We suggest that Medical Informatics can be considered from these three perspectives: (1) Theory, from which medical informaticians formally characterize the properties of the objects of study, creating new theories or using and adapting existing theories (e.g., from mathematics), (2) Abstraction, from which medical informaticians deal with all aspects of medical information and create new abstractions, methods, and technology-independent models, which can be experimentally verified, and (3) Design, from which medical informaticians develop systems or act as information brokers or advisors between medical and technology professionals, to improve the quality of computer applications in medicine. CONCLUSION: Based on this framework, we suggest that Medical Informatics has an independent scientific character, different from other applied informatics areas. Finally, we analyze these three perspectives using data mining in medicine.

Medical Informatics↗

PubMed2002

Rationale and design of TeraViC-4 study: a phase III, randomized clinical trial to evaluate the effects of treatment duration with peginterferon alfa-2a (40-kDa) and ribavirin in naïve patients with chronic hepatitis C virus infection without early virological response at week 4.

Several studies are available on the efficacy and safety of 40 kDa branched peginterferon alfa-2a (40-kDa) combined with ribavirin in the treatment of chronic hepatitis C patients. The TeraViC-4 study is a phase III, randomized, parallel group, multicenter study that includes two additional open arms. The main objective is to investigate if extended therapy over 72 weeks increases the rate of sustained virological response induced by a standard 48-week treatment period in naïve patients with chronic hepatitis C who do not show an early virological response. All patients will be treated with peginterferon alfa-2a (40-kDa), 180 micrograms subcutaneous (s.c.) once-weekly, and ribavirin, 400 mg b.i.d. Virological response will be assessed by a hepatitis C virus ribonucleic acid (HCV-RNA) qualitative polymerase chain reaction (PCR) test. Non-early responders (HCV-RNA still detectable after 4 weeks of therapy) will be randomly separated to receive combination therapy for 44 or 68 additional weeks. Early responders (undetectable HCV-RNA at week 4) will be allocated into two open arms according to HCV genotype and basal viral load, and they will be treated for 20 or 44 additional weeks. All patients will be followed for 24 weeks on no therapy. A total of 504 patients are planned to be included in the study in order to reach the required sample size in the two randomized groups. Efficacy of treatment will be assessed by determination of HCV-RNA and the primary efficacy variable is the rate of sustained virological response (after 24 weeks of treatment-free follow-up) in patients without early virological response. Secondary efficacy variables are the rate of sustained biochemical response, the rate of response in function of HCV genotype, viral load and treatment duration. Safety data will also be recorded and analyzed.

Antiviral Agents↗

PubMed2001

Medical informatics and bioinformatics: European efforts to facilitate synergy.

Over the past decade there have been several attempts to rethink the basic strategies and scope of medical informatics. Meanwhile, bioinformatics has only recently experienced a similar debate about its scientific character. Both disciplines envision the development of novel diagnostic, therapeutic, and management tools, and products for patient care. A combination of the expertise of medical informatics in developing clinical applications and the focused principles that have guided bioinformatics could create a synergy between the two areas of application. Such interaction could have a great influence on future health research and the ultimate goal, namely continuity and individualization of health care. This article summarizes current activities related to facilitating synergy between medical informatics and bioinformatics, emphasizing activities in Europe while relating them to efforts in other parts of the world. The report provides examples of the analysis that European investigators are carrying out, aiming to propose new ideas for collaborations between medical informatics and bioinformatics researchers in a variety of areas.

Computational Biology↗

PubMed2001

Asialofetuin liposome-mediated human alpha1-antitrypsin gene transfer in vivo results in stationary long-term gene expression.

The development of nonviral vectors for in vivo gene delivery to hepatocytes is an interesting topic in view of their safety and tremendous gene therapy potential. Since cationic liposomes and liposome uptake by receptor-mediated mechanisms could offer advantages in the efficacy of liposome-mediated gene transfer, we studied the effect of liposome charge (anionic vs. cationic) and the covalently coupled asialofetuin ligand on the liposome surface in mediating human alpha1-antitrypsin (hAAT) gene transfer to mice in vivo. The changes in liposome charge were made by adding the following lipids to the backbone liposomes: anionic phosphatidylserine, cationic N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethyl-ammonium methylsulfate or a lipopeptide synthesized from dipalmitoylphosphatidylethanolamine and covalently coupled to the cationic nuclear localization signal peptide. Two plasmids containing the hAAT gene were used: pTG7101, containing the complete genomic sequence of the human gene driven by the natural promoter, and p216, containing the human hAAT cDNA under the control of the CMV promoter. The results indicate that both untargeted anionic and cationic liposomes mediate plasma levels of hAAT that decline over time. However, asialofetuin liposomes increase the plasma levels of hAAT and can mediate long-term gene expression (>12 months) with stationary plasma levels of protein. Results from quantitative and qualitative reverse transcriptase polymerase chain reaction match those from protein plasma levels and confirm both the human origin of the message and the liver as source of the protein. The use of asialofetuin liposomes in hepatic gene therapy may both increase and prolong in vivo gene expression of hAAT and other clinically important genes.

Animals↗

PubMed2001

[Why are not all patients with chronic liver disease associated with hepatitis C virus treated?].

AIMS: To analyze the prevalence of patients with chronic liver disease associated with hepatitis C virus (HCV) not undergoing antiviral treatment and the reasons for which this treatment was not indicated. PATIENTS AND METHODS: 718 patients with HCV infection referred for therapeutic evaluation between January 1990 and January 1998. Demographic, clinical, biological and histological variables were prospectively analyzed. The patients were divided into two groups: treated and untreated. RESULTS: 393 patients were treated and in 325 patients antiviral treatment was not considered to be indicated. The most frequent reasons for not starting therapy were advanced age, the presence of decompensated cirrhosis and the patients' refusal to undergo antiviral treatment. CONCLUSIONS: A broad subgroup of patients with chronic liver disease associated with HCV do not receive antiviral treatment. This is related with: a) patients' advanced age at diagnosis, b) diagnosis at the advanced stages of the disease, and c) patients' refusal to undergo such treatment after being informed of its potential risks and benefits.

Adolescent↗

PubMed2001

Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients.

The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor alpha (TNF-alpha) system in the development of nonalcoholic steatohepatitis (NASH). Fifty-two obese patients were studied. We investigated: (1) the expression of mRNA of TNF-alpha and their p55 and p75-receptors by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in hepatic and adipose tissues; and (2) the relationship between TNF-alpha, p55, and p75 and the severity of NASH. Obese patients without NASH were the control group. A remarkable increase in the expression of mRNA of TNF-alpha was found in patients with NASH in hepatic tissue (0.65 +/- 0.54) and in peripheral fat (0.43 +/- 0.45); in the control samples, the mRNA expression was 0.28 +/- 0.32, P <.007, and 0.26 +/- 0.22, P <.018, respectively. Furthermore, we found a significant increase in the mRNA levels of p55 receptor (2.42 +/- 1.81 vs. 1.56 +/- 1.17; P <.05); however, the mRNA expression of the p75 receptor was similar in both patients. Those patients with NASH with significant fibrosis presented an increase in the expression of mRNA TNF-alpha in comparison with those with a slight or nonexistent fibrosis. An overexpression of TNF-alpha mRNA is found in the liver and in the adipose tissue of NASH patients. The levels of mRNA-p55 are increased in the liver tissue of NASH patients. This overexpression is more elevated in patients with more advanced NASH. These findings suggest that the TNF-alpha system may be involved in the pathogenesis of NASH.

Adipose Tissue↗

PubMed2001

Dendroaspis natriuretic peptide in hepatic cirrhosis.

OBJECTIVES: Dendroaspis natriuretic peptide (DNP) is a novel peptide that is structurally similar to atrial, brain, and C-type natriuretic peptides. Many natriuretic peptides are increased in hepatic cirrhosis, but the role of DNP in cirrhosis is unknown at present. The aim of the study was to investigate plasma levels of dendroaspis natriuretic-like immunoreactivity in cirrhosis. METHODS: We measured plasma concentrations of DNP by radioimmunoassay methods in 12 cirrhotic patients without ascites and 44 cirrhotic patients with ascites, and compared these values with 20 age-matched healthy subjects. Renal function, plasma cGMP concentration, plasma renin activity, and plasma endothelin concentration were measured in each patient. RESULTS: Patients without ascites had circulating levels of DNP similar to those of healthy subjects. By contrast, patients with ascites had increased circulating DNP levels compared to both patients without ascites and healthy subjects. In addition, circulating levels of DNP increased in relation to the severity of cirrhosis. Significant positive correlations were also found between DNP levels, endothelin concentrations, and plasma renin activity. CONCLUSIONS: The results of this study indicate that plasma DNP is increased in cirrhotic patients with ascites.

Adult↗

PubMed2001

Are there predictive factors of severe liver fibrosis in morbidly obese patients with non-alcoholic steatohepatitis?

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a clinicopathological entity characterized by the presence of steatosis and lobular and/or portal inflammation with or without fibrosis. Patients with non-alcoholic fatty liver and fibrosis on liver biopsy have increased liver-related deaths. METHODS: 181 wedge liver biopsies, taken at the time of bariatric surgery from patients with a mean body mass index (BMI) of 47, were studied. In all cases, the liver biopsy was performed without knowledge of the patient's clinical and biochemical data, which were then examined with univariate and multivariate analysis. RESULTS: Diagnosis of NASH was established in 105 patients (91%); 74 patients (70%) showed mild steatosis, 20 (19%) had moderate inflammation and fibrosis, and 11 (10%) had steatosis with severe fibrosis. None of the liver biopsies showed cirrhosis. Age was the only independent predictor of moderate and severe fibrosis (p = 0.001). CONCLUSIONS: Since only age was a predictor of moderate or severe fibrosis, and no clinical or biochemical abnormalities detected slowly progressive hepatic fibrosis, liver biopsy is the only means of detecting progression to more advanced liver disease in a NASH patient.

Adult↗

PubMed2000

Different time course of circulating adhesion molecules and hyaluran during hepatic allograft rejection.

BACKGROUND: Inducible adhesion molecules are involved in cell-mediated allograft rejection. In addition, the endothelium is the main target of this process. This study investigated, whether soluble (s) forms of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) are elevated during cellular rejection and whether hyaluran is a useful marker of endothelial function in liver transplantation. METHODS: Serum levels of sICAM-1, sVCAM-1, and hyaluran were determined in 24 controls and 27 hepatic transplant recipients. These patients were divided in two groups: group I, 14 patients without rejection; and group II, 13 patients with rejection. Samples were collected on day 1 and 7 after transplantation, on the day of liver biopsy, and after treatment of the rejection. RESULTS: We found a significant increase in sICAM-1 levels in the postoperative period in the rejection group compared with the non rejection group. It persisted significantly elevated until the diagnosis of rejection was made. In contrast, sVCAM-1 was only significantly elevated in the rejection group when diagnosis of rejection was evident. Hyaluran levels were also significantly elevated in the rejection group at diagnosis of rejection. We noticed a significant decline in sICAM-1, sVCAM-1, and hyaluran levels after successful treatment of rejection. In addition, we observed in the non-rejection group a stable lower levels of hyaluran during the entire postoperative period. CONCLUSIONS: The release of circulating adhesion molecules is a prominent feature coinciding with the first episode of hepatic rejection. Differential patterns of sICAM-1 and sVCAM-1 exist during rejection. In addition, hyaluran levels may be a sensitive marker of liver endothelial cell function in the postoperative period of liver transplantation.

Adult↗

PubMed2000

Active recombinant human tyrosine kinase c-Yes: expression in baculovirus system, purification, comparison to c-Src, and inhibition by a c-Src inhibitor.

C-Yes is a non-receptor-type tyrosine kinase of the Src family that is most closely related to c-Src. C-Yes has been implicated in development of some human cancers. Here we report on the expression, purification, and characterization of the active human recombinant c-Yes. A full-length human c-Yes clone has been generated and the protein was expressed in insect Sf9 cells. Active c-Yes was purified by liquid chromatography to yield a preparation with a high specific activity (160 nmol/min/mg using an optimal Src substrate peptide). In a comparison between human c-Yes and c-Src enzymes, relative phosphorylation efficiencies on nine protein and four peptide substrates were different. However, the recently described Src inhibitor CGP77675 inhibited human c-Yes with a potency similar to that of c-Src (IC(50) value of 6.5 nM). The purified preparation of active c-Yes provides a good basis for further enzymatic characterization and for the development of c-Yes-specific inhibitors.

Animals↗

PubMed2000

Involvement of the fas system in hepatitis C virus recurrence after liver transplantation.

To date, there have been no reports of the involvement of the Fas system in recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT). In 25 patients who underwent OLT for HCV-related liver cirrhosis, we evaluated the expression of the Fas antigen (FasAg) on hepatocytes, apoptic hepatocytes, and serum levels of soluble Fas (sFas). The level of HCV viremia and HCV genotype were determined by polymerase chain reaction. Serum sFas levels were determined by an enzyme immunoassay procedure. DNA fragmentation was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) technique on deparaffinized liver samples. FasAg expression was evaluated by an immunoperoxidase method. Sixteen patients had evidence of recurrent HCV disease. The number of hepatocytes expressing FasAg and the percentage of apoptotic hepatocytes was greater among patients who developed recurrent hepatitis than among those who did not (P <.01 and P <.0001, respectively). There was a correlation between hepatic expression of FasAg, intensity of lobular inflammation (P =.007), and TUNEL index (P <.001). The levels of sFas were greater among the patients with recurrent HCV hepatitis than those without recurrent hepatitis (P <.04). We conclude that (1) Fas expression is up-regulated in recurrent HCV after OLT and is related to the grading of liver disease; likewise, levels of sFas were greater in the patients with recurrent HCV hepatitis; and (2) the demonstration of hepatocytes with FasAg expression and the labeling of the nuclei by TUNEL assay suggest that hepatic apoptosis mediated by the Fas system may have a role in the pathogenesis of recurrent HCV hepatitis after OLT.

Adult↗

PubMed2000

[Soluble Fas in acute rejection in patients with liver transplantation. Response to treatment].

UNLABELLED: It has been suggested that in the cellular rejection of hepatic graft, the lesion provoked by cytotoxic T-lymphocytes might be mediated by the Fas antigen/Fas ligand system, producing cell death by apoptosis. AIM: To determine whether soluble Fas (sFas) is increased during treatment and to evaluate response to treatment. MATERIAL AND METHODS: Fourteen patients with orthotopic liver transplantation who presented an episode of acute cellular rejection were studied. Serum levels of sFas were detected by enzyme-immunoanalysis at diagnosis and again 5 days after treatment was completed. As control groups, sFas was analyzed in 12 patients with liver transplantation without rejection and in 10 healthy subjects. RESULTS: sFas levels were found to be significantly higher in patients with rejection than in those without rejection and in healthy subjects (24.2 +/- 39.1 vs. 2.8 +/- 4.0 vs. 0.6 +/- 1.5 UI/ml; p = 0.03). In patients with acute cellular rejection, immunosuppressive treatment significantly decreased sFas levels compared with basal values (24.2 +/- 39.1 vs. 9.9 +/- 30.2 UI/ml; p = 0.005). A clear correlation between the serum levels of sFas, glutamate oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase/glutamic-pyruvic transaminase (GPT) and gamma-glutamyl transferase (GGT). CONCLUSIONS: a) The increase of sFas during rejection and the decrease in patients with a good evolution suggests that the Fas system may play an important role in the hepatocyte lesion produced by an apoptosis mechanism in these patients. b) Monitoring sFas could be useful in diagnosing rejection and in evaluating response to treatment.

Acute Disease↗

PubMed2000

[An unusual complication of esophageal foreign body].

Esophageal foreign bodies must be carefully managed because they carry a high risk of potentially severe complications. A case of a sharp foreign body located in a previously unsymptomatic pharyngoesophageal diverticulum is described. The management protocol for esophageal foreign bodies is reviewed. Fiberesophagoscopy is the therapeutic technique of choice, but it may be dangerous if patients are not selected properly.

Aged↗

PubMed1999

Severe clinical course of de novo hepatitis B infection after liver transplantation.

The aim of this study is to determine the origin, clinical outcome, allograft histological characteristics, and virological outcome of de novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). We studied 136 hepatitis B surface antigen (HBsAg)-negative liver transplant recipients. HBV DNA was detected by dot-blot hybridization and polymerase chain reaction (PCR). The S gene was sequenced. Hepatitis C virus (HCV) RNA was assessed by PCR. The long-term clinical and histological outcome was determined. Six of 136 HBsAg-negative patients (4.4%) became HBsAg positive after transplantation. The source of HBV infection was reactivation of latent HBV infection in 2 patients and was not identified in 4 patients. Two donors had isolated core antibody. Two of these 6 patients developed acute liver failure related to hepatitis B. The 4 other patients had severe chronic hepatitis related to hepatitis B. All patients had high-level HBV replication. No significant mutations in the S gene were found. These data suggest that de novo hepatitis B infection is not a mild disease and might represent a significant cause of graft dysfunction. This is the first report of fulminant hepatitis caused by de novo hepatitis B infection after OLT.

Female↗

PubMed1999

Adrenomedullin in liver transplantation and its relationship with vascular complications.

Adrenomedullin (AM) is a potent vasodilating peptide that increases rat platelet cyclic adenosine monophosphate levels and acts on endothelial cells to stimulate nitric oxide release. Both mechanisms inhibit platelet function. Considering these effects, AM may have a role in cardiovascular regulation after orthotopic liver transplantation (OLT) and could have an antithrombotic effect. The aim of the present study is to investigate plasma AM levels in the early postoperative period after OLT and their relationship with vascular complications in OLT. We measured plasma AM levels in 35 patients with cirrhosis who underwent OLT at baseline and 1, 7, and 15 days postoperatively. We found that AM levels were significantly greater in patients with cirrhosis compared with healthy subjects. Of the 35 patients, 10 had vascular complications. In these 10 patients, AM concentrations were significantly greater than those observed in the nonthrombotic group in the early postoperative period. In addition, we also noticed in the nonthrombotic group a significant increase in AM levels from baseline to day 1, then a decrease to baseline levels in the early postoperative period. Our study shows that AM might act as a new humoral factor involved in the response to surgery in OLT and is significantly associated with vascular thrombosis in OLT.

Adrenomedullin↗

PubMed1999

Variceal ligation compared with endoscopic sclerotherapy for variceal hemorrhage: prospective randomized trial.

BACKGROUND: To evaluate the safety and efficiency of variceal ligation compared with endoscopic sclerotherapy, 88 patients with cirrhosis with recent variceal bleeding were randomized to undergo either treatment. METHODS: Sclerotherapy was performed using ethanolamine and polidocanol injection at 1, 2, and 3 weeks and every 3 weeks thereafter. The Stiegmann-Goff device was used for variceal ligation at the same intervals. RESULTS: The rate of variceal eradication was the same for both groups, but eradication was accomplished sooner in patients undergoing variceal ligation (5.3+/-1.6 vs. 6.6+/-2.4 endoscopic sessions, p < 0.05) and with fewer complications (19 vs. 6, p < 0.005). The rate of recurrent bleeding was lower in patients treated by ligation (31% vs. 50%, p < 0.05). After eradication, variceal recurrence was more frequent in patients treated by variceal ligation at 1 and 3 years (47% and 92% vs. 23% and 55%, p < 0.01). Portal hypertensive gastropathy was significantly worse in the patients who had variceal ligation (17 patients vs. 6, p < 0.01). Survival and treatment failure were similar in both groups. CONCLUSIONS: Variceal ligation was superior to sclerotherapy in terms of the rate of recurrent bleeding and the occurrence of complications but worse with respect to recurrence of varices and the evolution of portal hypertensive gastropathy. Long-term follow-up studies are required to find out whether there are deleterious effects of variceal ligation.

Esophageal and Gastric Varices↗