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Biomedical subjects

Rafael Esteban

Publications and source records attributed to Rafael Esteban.

34 records · Page 2Linked to original sources
PubMed2004

Oral glutamine challenge and magnetic resonance spectroscopy in three patients with congenital portosystemic shunts.

BACKGROUND/AIMS: Congenital portosystemic shunts are rare abnormalities of liver vasculature that can cause neurological symptoms, probably secondarily to the effects of the metabolism of ammonia in the brain. Our aim was to investigate the relationship between capillary blood ammonia after oral glutamine challenge and magnetic resonance spectroscopy in three patients with congenital portosystemic shunts. METHODS: Neuropsychological tests, oral glutamine challenge and magnetic resonance spectroscopy were performed at baseline and after 6 months of follow-up in three patients with congenital portosystemic shunts. The results were compared to those obtained in a group of six cirrhotic patients with prior episodes of hepatic encephalopathy and healthy controls. RESULTS: Patients with congenital portosystemic shunts exhibited abnormalities of neuropsychological tests, magnetic resonance spectroscopy and a response to the oral glutamine challenge similar to those observed in patients with cirrhosis. The intensity of the rise of brain glutamine was correlated to the area under the curve of ammonia after the oral glutamine challenge (R=0.72). CONCLUSIONS: Neurological manifestations of patients with congenital portosystemic shunts are mediated through similar mechanisms that are involved in the pathogenesis of hepatic encephalopathy. The area under the curve appears to be the better parameter that defines the response to the oral glutamine challenge.

Administration, Oral↗
PubMed2004

Sporadic cases of acute autochthonous hepatitis E in Spain.

BACKGROUND/AIMS: In industrialized countries hepatitis E virus (HEV) infection is rare and its diagnosis is difficult because the utility of available tests is not well established. METHODS: We studied the presence of acute HEV infection markers in a cluster of 11 cases of acute hepatitis with IgG anti-HEV antibodies. RESULTS: Three cases were confirmed as acute hepatitis E and 8 as presumptive hepatitis E, two as a past HEV infection and one could not be determined. Three different HEV strains were identified in serum from 3 patients. Two strains belonged to genotype 3, the predominant genotype found in local urban sewage and the other strain belonged to genotype 1 and was considered an imported strain. CONCLUSIONS: Our findings demonstrate the presence of some autochthonous, sporadic acute hepatitis E cases as well as an imported case in our area and the transitory nature of virological and serological markers for HEV.

Acute Disease↗
PubMed2004

Normal protein diet for episodic hepatic encephalopathy: results of a randomized study.

BACKGROUND/AIMS: Protein-restricted diets are usually prescribed for cirrhotic patients with hepatic encephalopathy. However, protein restriction may worsen the nutritional status without resulting in an improvement of hepatic encephalopathy. We designed a study to assess the effects of the amount of protein in the diet on the evolution of episodic hepatic encephalopathy. METHODS: Cirrhotics admitted to the hospital because of an episode of encephalopathy (n=30) were randomized to receive a low-protein diet with progressive increments or a normal protein diet for 14 days, in addition to standard measures to treat hepatic encephalopathy. Protein synthesis and breakdown were studied at day 2 and day 14 with the glycine-N(15) infusion method. RESULTS: The outcome of hepatic encephalopathy was not significantly different between both groups of treatment. Protein synthesis was similar for low and normal protein diet, but those of the low-protein diet group showed higher protein breakdown. CONCLUSIONS: Diets with a normal content of protein, which are metabolically more adequate, can be administered safely to cirrhotic patients with episodic hepatic encephalopathy. Restriction of the content of protein of the diet does not appear to have any beneficial effect for cirrhotic patients during an episode of encephalopathy.

Aged↗
PubMed2003

Quality of life and cognitive function in hepatitis C at different stages of liver disease.

BACKGROUND/AIMS: Hepatitis C has been associated with a decrease in quality of life and with neurological abnormalities. The aim of our study was to investigate the relationship between quality of life and cognitive function. METHODS: Quality of life, clinical variables and neuropsychological function were evaluated in 120 patients with hepatitis C (mild chronic hepatitis, compensated cirrhosis and decompensated cirrhosis) and in healthy controls (n=40, in each group). RESULTS: Patients with chronic hepatitis or compensated cirrhosis showed a decrease in quality of life, in spite of unimpaired neuropsychological tests. Patients with decompensated cirrhosis exhibited a further decrease in quality of life and neuropsychological abnormalities. The decrease in quality of life was associated with the severity of liver failure, neuropsychological abnormalities and treatment with beta-blockers or diuretics. However, in the multivariable analysis, only treatment with beta-blockers or diuretics (which was limited to decompensated cirrhosis) was independently associated with quality of life. CONCLUSIONS: Hepatitis C causes a decrease in quality of life even in the absence of major cognitive impairment. The mechanisms that worsen quality of life are unknown. However, in cirrhotic outpatients with prior decompensations, treatment with beta-blockers or diuretics appears to have an important effect on quality of life.

Cognition↗
PubMed2003

Entecavir, FTC, L-FMAU, LdT and others.

To summarize, the future of chronic hepatitis B therapy seems to be the combination of different drugs. Ideally, the optimal drugs to combine would meet the following criteria: they should be orally applicable, they should have an excellent safety profile and the duration of therapy should limited. Currently, the drugs most likely to fulfill these criteria are the nucleoside analogs.

Antiviral Agents↗
PubMed2003

Sexual transmission of hepatitis C virus from a patient with chronic disease to his sex partner after removal of an intrauterine device.

BACKGROUND: Approximately 40% of patients infected with hepatitis C virus (HCV) have no history of blood transfusion or other high-risk practice. Other causes should be considered. GOAL: The goal was to describe sexual transmission of HCV from a chronic carrier to his female partner during unprotected vaginal intercourse after removal of an intrauterine device. STUDY DESIGN: A heterosexual woman who was a regular blood donor acquired acute HCV infection from her sex partner, who was chronically infected. The study included an interview and phylogenetic analysis of sequences of virus obtained from the couple. RESULTS: Risk factors other than vaginal sexual relations with her partner were ruled out. Phylogenetic analysis showed that sequences from the couple clustered together in all trees generated, in comparison with local and GenBank controls. CONCLUSION: The temporal relationship between removal of the intrauterine device and the acute hepatitis suggests that vaginal mucosal damage might have favored transmission of HCV. Barrier precautions should be suggested whenever damage of the vaginal tract has occurred.

Adult↗
PubMed2003

Adefovir dipivoxil.

In chronic hepatitis B therapy there are new and exciting developments in antivirals such as nucleotide analogues. Adefovir is the latest drug approved for therapy of chronic hepatitis B. This agent has a potent in vitro and in vivo effect against herpes virus, retroviruses and hepadnaviruses. In the hepatitis B virus setting, adefovir dipivoxil inhibits both the wild type and HBV lamivudine-resistant strains. Adefovir is an oral drug and the recommended dose for chronic hepatitis B is 10 mg daily. The safety profile of this dose is excellent but higher doses can produce renal tubular damage, particularly when the drug is used for prolonged therapy. Up to now, no evidence of HBV resistance to adefovir dipivoxil has been detected, and this constitutes one of its main advantages as it permits longer duration of therapy. Adefovir is an important new addition to current first-line treatments for HBeAg and anti-HBe-positive chronic hepatitis B, as well as being rescue therapy for lamivudine-resistant HBV strains.

Adenine↗
PubMed2002

Specific cleavage of hepatitis C virus RNA genome by human RNase P.

We have found that RNase P from HeLa cells specifically and efficiently cleaves hepatitis C virus (HCV) transcripts in vitro. The evidence includes identification of the 5'-phosphate polarity of the newly generated termini at position A(2860) as well as immunological and biochemical assays. Active cleavage has been shown in five dominant sequences of HCV "quasispecies" differing at or near the position of cleavage, demonstrating that this is a general property of HCV RNA. During the analysis, a second cleavage event was found in the 3' domain of the internal ribosome entry site. We have found that HCV RNA competitively inhibits pre-tRNA cleavage by RNase P, suggesting that HCV RNA has structural similarities to tRNA. This finding sets HCV apart from other pathogens causing serious human diseases and represents the first description of human RNase P-viral RNA cleavage. Here we discuss the possible meaning of these RNase P-accessible structures built into the viral genome and their possible role in vivo. Moreover, such structures within the viral genome might be vulnerable to attack by therapeutic strategies.

Base Sequence↗
PubMed2002

Viral kinetics in genotype 1 chronic hepatitis C patients during therapy with 2 different doses of peginterferon alfa-2b plus ribavirin.

Pegylated interferon (peginterferon) alfa-2b plus ribavirin achieves a higher sustained response rate in patients with genotype 1 chronic hepatitis C virus (HCV) than standard combination therapy. This study evaluated HCV kinetics throughout therapy with 2 doses of peginterferon alfa-2b and ribavirin in 55 patients. Twenty-eight patients were randomized to receive a high once-weekly dose of peginterferon alfa-2b (3 microg/kg for 1 week, 1.5 microg/kg for 3 weeks, and 1.0 microg/kg for 44 weeks), and 27 patients were randomized to receive a low dose (0.5 microg/kg) for 48 weeks. Both groups also received 800 mg ribavirin daily. Mean baseline HCV RNA load, measured by reverse-transcription polymerase chain reaction, was similar in both groups (5.32 +/- 0.86 log vs. 5.15 +/- 1.04 log). The 3-microg/kg dose of peginterferon alfa-2b inhibited HCV RNA more significantly than the 0.5-microg/kg dose during the first 48 hours (2.08 +/- 0.93 log vs. 1.09 +/- 0.80 log; P <.001) and both increased at 72 hours (0.54 +/- 0.73 log vs. 0.03 +/- 0.36 log; P = not significant [NS]), but the high dose showed a greater reduction at the end of the week (1.07 +/- 0.99 log vs. 0.72 +/- 0.73 log). Both doses showed a progressive, slower viral decrease throughout therapy; however, HCV RNA became undetectable faster and in more patients with the high dose (22% vs. 7% at week 4, 56% vs. 44% at week 12, 69% vs. 63% at week 24, and 71% vs. 61.5% at the end of therapy). In conclusion, peginterferon alfa-2b/ribavirin produces an initial rapid decline in HCV RNA levels, followed by a slower, progressive decrease, similar to the biphasic kinetic profile of standard combination therapy. Higher doses of peginterferon alfa-2b also accelerate viral clearance.

Adult↗
PubMed2002

Clinical impact and efficacy of lamivudine therapy in de novo hepatitis B infection after liver transplantation.

De novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) in patients negative for hepatitis B surface antigen (HBsAg) is between 1.7% and 3.5% in areas with a low prevalence of HBV infection. The importance of this problem and the efficacy of lamivudine treatment has not been defined in areas with a high prevalence of positivity to antibody to hepatitis B core antigen (Anti-HBc). To define the characteristics and the clinical impact of de novo HBV infection in OLT recipients and to evaluate the efficacy of lamivudine treatment in this context, 229 HBsAg (-) donors (145 men, 84 women) were retrospectively evaluated between June 1994 and June 2000. Forty-eight recipients were excluded for various reasons. The final study population included 181 patients that were prospectively followed up for more than 6 months after OLT. When de novo HBV infection was detected, liver allograft biopsy was performed and treatment with lamivudine was indicated if patients were HBV-DNA-positive with elevated ALT levels. Survival time was defined as the interval between diagnosis of HBV infection and death or last follow-up visit. Thirty-one of 229 liver donors (13.5%) were anti-HBc(+). After a mean follow-up of 54.4+/-30 months, 9 of the 181 recipients (5%) developed de novo HBV infection; 8 of 27 recipients (29.6%) of livers from anti-HBc(+) donors as compared with only one of 154 recipients (0.6%) of livers from anti-HBc(-) donors P < 0.005). Liver biopsies performed in 8 of 9 cases showed chronic active hepatitis in 7 patients and acute hepatitis in one patient who cleared HBV spontaneously during the first 3 months. Seven patients were treated with lamivudine for a mean period of 24.5 months; HBV-DNA became negative in 5 of 7 (71.4%), and HBeAg became undetectable in 3 of 6 patients (50%). Patient actuarial survival rates at 1, 3, and 5 years were 100%, 94.7%, and 81.2% for recipients of anti-HBc (+) livers and 95.2%, 83%, and 77.3% for recipients of anti-HBc (-) livers P = ns). In our area, the appearance of de novo HBV infection after OLT is related to grafting livers from anti-HBc (+) donors is associated with a benign outcome, with no liver failure or graft loss, and treatment with lamivudine is highly effective in the control of HBV replication.

Biopsy↗
PubMed2002

Management of chronic hepatitis B: an overview.

Approximately 400 million individuals worldwide have developed chronic hepatitis B after exposure to the hepatitis B virus (HBV). Up to 40% of these will eventually develop serious hepatic complications. Although widespread immunization, improved blood supply testing, and emphasis on safe sex have significantly decreased new HBV infections, the large reservoir of infected individuals (400 million) remains a serious health problem. At present, only two agents are available for the treatment of chronic hepatitis B: interferon alfa and lamivudine. Both are associated with important limitations of efficacy or safety, or both. These limitations and other problems associated with the evaluation of current and investigational therapies for chronic hepatitis B give rise to several key issues in management of HBV: duration of therapy, goals of therapy, need for standardization of the measurement of clinical responses, and definitions of response to therapy. The last two of these key issues are of particular concern. The lack of similarity in study designs, the use of inconsistent definitions of and criteria for therapeutic response, and the lack of uniformity in assays to detect HBV DNA titers hamper consistent evaluations of treatment. Therefore, there is a need for the scientific community to standardize the measures of performance and methods of analysis and reporting of clinical trials for current and new drugs.

Antiviral Agents↗
PubMed2002

Spontaneous bacterial peritonitis caused by quinolone-resistant Escherichia coli: could steroid therapy play a role?

Prophylaxis with norfloxacin has been shown to be effective in preventing spontaneous bacterial peritonitis (SBP) in liver cirrhosis. This therapy is associated with the appearance of quinolone-resistant Escherichia coli. However, only four cases of SBP caused by quinolone-resistant E. coli have been reported so far. We present four cases of quinolone-resistant E. coli SBP in three patients receiving oral quinolones, and who were on corticosteroid therapy to treat associated disorders.

Aged↗