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Biomedical subjects

J Guardia

Publications and source records attributed to J Guardia.

At least 37 records · Page 2Linked to original sources
PubMed2001

Morphologic capillary changes and manifestations of connective tissue diseases in patients with primary biliary cirrhosis.

The objective of this study was to investigate the presence of nailfold capillary abnormalities and extrahepatic signs of connective tissue disease in patients with primary biliary cirrhosis (PBC), as compared to patients with other chronic liver diseases. We evaluated 22 patients with PBC and 15 patients with other chronic liver diseases as a control group. Nailfold capillaroscopy was performed by two observers blinded to clinical findings using a Wild M3 stereomicroscope with an Intralux 5000 Volpi cold light lamp. We detected nailfold capillary abnormalities in 20 out of 22 (91%) PBC patients. Twelve of these 20 patients (54%) showed capillary alterations characteristic of systemic sclerosis. In the control group only two out of 15 patients (13%) presented alterations and in both cases they were a non-specific type. The presence of nailfold capillary abnormalities was significantly greater in PBC patients than in the control group (P < 0.001). Eleven out of the 22 PBC patients (50%) had extrahepatic signs of connective tissue disease and most of them were related to systemic sclerosis; patients with other chronic liver diseases did not present rheumatic manifestations (P < 0.001). In PBC patients there was a significant association between systemic sclerosis capillary pattern and rheumatic manifestations (P < 0.03). The high prevalence of nailfold capillary abnormalities characteristic of systemic sclerosis in patients with PBC and the correlation with sclerodermal manifestations suggests that this capillaroscopic finding could be a useful indicator to investigate rheumatic manifestations in these patients.

Adult↗
PubMed2000

Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding.

UNLABELLED: BACKGROUND The relation between medications that release nitric oxide, such as nitroglycerin and other nitrovasodilators, and upper gastrointestinal bleeding is uncertain. In animals, these medications reduce the gastric damage induced by nonsteroidal antiinflammatory drugs. Nitric oxide, however, inhibits platelet aggregation and may contribute to bleeding from an ulcer. METHODS: We performed a case-control study to determine the risk of bleeding in patients taking nitrovasodilators, low-dose aspirin, or other nonsteroidal antiinflammatory drugs. The case group was made up of 1122 consecutive patients admitted to one of four hospitals with bleeding from a peptic lesion. The 2231 control subjects were 1109 patients hospitalized for other reasons and 1122 outpatients from the same geographic area. RESULTS: In the week before admission, 520 (46.3 percent) of the patients with bleeding had taken a nonsteroidal antiinflammatory drug other than low-dose aspirin, 120 (10.7 percent) had taken low-dose aspirin (< or = 300 mg per day), 60 (5.3 percent) a nitrovasodilator, and 135 (12.0 percent) an antisecretory agent such as a histamine H2-receptor antagonist or a proton-pump inhibitor. In multivariate models that adjusted for age, sex, and clinical risk factors, the use of a nonsteroidal antiinflammatory drug other than low-dose aspirin was independently associated with an increased risk of bleeding from a peptic ulcer (odds ratio, 7.4; 95 percent confidence interval, 4.5 to 12.0), as was the use of low-dose aspirin alone (odds ratio, 2.4; 95 percent confidence interval, 1.8 to 3.3). The use of a nitrovasodilator was associated with a decreased risk of bleeding (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 0.9), as was antisecretory therapy (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 0.8). In patients taking any type of nonsteroidai antiinflammatory drug, the use of a nitrovasodilator or antisecretory therapy was independently associated with a decreased risk of bleeding. CONCLUSIONS: The use of nitrovasodilator drugs is independently associated with a decreased risk of upper gastrointestinal bleeding.

Aged↗
PubMed2000

[Prevalence and incidence of hepatitis A in patients with hepatitis B and C].

BACKGROUND: Patients with chronic hepatitis are in risk to acquire a fulminant hepatitis associated with hepatitis A virus superinfection. PATIENTS AND METHODS: Antibodies against hepatitis A were study in serum from 353 patients with chronic hepatitis B or C. RESULTS: The prevalence of IgG-HAV antibodies was 81% in chronic hepatitis C patients, and 77% in chronic hepatitis B patients. The presence of anti-HAV antibodies was related to the patients' age. None case of acute hepatitis A in chronic hepatitis patients was detected. CONCLUSIONS: The prevalence of anti-HAV antibodies is high in patients with chronic viral hepatitis but the incidence of the disease is low. Hepatitis A vaccination should do with previously screening.

Adolescent↗
PubMed2000

Utility of early testing for HCV viremia as predictive factor of sustained response during interferon or interferon plus ribavirin treatment.

BACKGROUND/AIM: To evaluate the utility of early testing for hepatitis C viremia as a predictor of treatment outcome during interferon or combination therapy. METHODS: We studied 184 patients with chronic hepatitis C who received interferon and were monitored for HCV RNA. Sixty-two patients received interferon alone for 12 months and 122 patients, who were still HCV RNA positive at 2 months, received an additional 12-month course of interferon and ribavirin combination therapy. RESULTS: Using this strategy, sustained response occurred in a total of 34 patients (18.5%). Independent variables associated with sustained response were HCV genotype (p=0.06), viral load < or = 5.1 logs/ml (p= 0.005) and negative HCV RNA at 1 month (p<0.0001) in the interferon group, and female sex (p=0.04), genotype (p=0.03), viral load < or = 5.5 logs/ml (p=0.01), normal ALT (p=0.001) and decline in viral load > or = 1.2 logs/ml after 2 months of interferon monotherapy (p<0.001) and negative viremia at 5 months of ribavirin onset (p<0.0001) in the combination therapy group. Persistence of viremia at 1 month of interferon monotherapy and at 5 months of combination therapy were the strongest predictors of non-response (negative predictive value of 100% and 99%, respectively). CONCLUSIONS: Qualitative assessment of HCV RNA during treatment is the strongest predictor of sustained response during interferon or combination therapy for chronic hepatitis C.

Adult↗
PubMed2000

Nitric oxide may contribute to nocturnal hemodynamic changes in cirrhotic patients.

OBJECTIVE: Patients with liver cirrhosis have a nocturnal worsening of hemodynamic parameters that has been associated with an increased risk of variceal bleeding at nighttime. The aim of this study was to investigate whether nitric oxide and cytokines are implicated in these hemodynamic changes. METHODS: Ten cirrhotic patients and eight controls were studied. Mean blood pressure, heart rate, plasma norepinephrine, tumor necrosis factor alpha and interleukin-6 levels, and serum nitrite + nitrate levels were determined at 0800, 1600, and 2400 h. All determinations were performed in supine rest and at least 4 h after meals. In a second study, nitrite + nitrate levels were assessed in 10 cirrhotic patients before and after eating a standard meal. RESULTS: Mean arterial pressure levels that were always lower in the patient group showed a nocturnal decrease in both groups of subjects. Heart rate values that were always higher in cirrhotic patients showed a nocturnal fall in controls, whereas cirrhotics maintained elevated values at nighttime. Norepinephrine levels were higher in cirrhotics and maintained similar values during the study, whereas controls had a significant nocturnal decrease. Nitrite + nitrate levels that were higher in cirrhotic patients showed a significant mean increase of 40% from morning (0800 h) to night (2400 h) in the patient group, whereas in controls no change was observed (p < 0.05). Tumor necrosis factor alpha and interleukin-6 levels did not change either in patients or controls during the entire period. Cirrhotic patients with or without ascites maintained a pattern of hemodynamic and biochemical changes similar to the pattern observed in the entire group of patients. Finally, no changes in serum nitrite + nitrate levels were observed in patients before and after eating the standard meal. CONCLUSION: An increased nocturnal nitric oxide production might contribute to the hemodynamic changes observed in cirrhotic patients during nighttime.

Aged↗
PubMed2000

Striatal dopaminergic D(2) receptor density measured by [(123)I]iodobenzamide SPECT in the prediction of treatment outcome of alcohol-dependent patients.

OBJECTIVE: The authors' goal was to study striatal dopaminergic dopamine 2 (D(2)) receptors as a biological marker of early relapse in detoxified alcoholic patients by using [(123)I]iodobenzamide ([123I]IBZM) single photon emission computed tomography (SPECT). METHOD: The authors performed [(123)I]IBZM SPECT on 21 alcohol-dependent inpatients during detoxification and on nine healthy volunteers, using the ratios of basal ganglia to occipital lobes for SPECT quantification. Depending on treatment outcome 3 months after hospital discharge, patients were determined to be relapsers or nonrelapsers. RESULTS: Alcohol-dependent subjects with early relapse (within 3 months after hospital discharge) showed a higher uptake of [(123)I]IBZM in the basal ganglia during detoxification (mean ratio=1.83, SD=0.9) than patients who did not have early relapse (mean ratio=1.69, SD=0.11). CONCLUSIONS: These results suggest that low levels of dopamine, or an increased density of free striatal dopaminergic D(2) receptors, could be related to early relapse in alcohol-dependent patients. Therefore, [(123)I]IBZM SPECT could become a biological marker of vulnerability to relapse for alcoholic patients in recovery.

Adult↗
PubMed2000

Treatment with interferon plus ribavirin in anti-HIV negative patients with congenital coagulation disorders and chronic hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) infected hemophiliacs respond at low rate to interferon (IFN) monotherapy. AIMS: To assess efficacy of IFN and RBV in HIV negative hemophiliacs with chronic hepatitis C and identify early predictive factors of response. METHODS: Twenty naive patients were treated with interferon and RBV for twelve months. Response was assessed by both serial ALT and HCV RNA levels. RESULTS: Normalization of ALT with clearance of HCV RNA occurred in seven (35%) patients. Age and age at infection were the only features associated with a higher likelihood of response. In all responders the viral load had decreased by at least one log within two months of starting treatment. CONCLUSIONS: Combination of interferon and ribavirin is well tolerated by hemophiliacs who achieve similar sustained response rates to non-hemophiliacs. Quantitative assessment of viral load at two months of treatment is a useful method to identify non-responders at an early stage.

Adolescent↗
PubMed1999

Rapid detection of lamivudine-resistant hepatitis B virus polymerase gene variants.

The amino acid substitution from methionine to valine or isoleucine at the YMDD (tyrosine, methionine, aspartate, aspartate) motif of the HBV polymerase gene is the main mutation responsible for resistance to lamivudine treatment. Detection of emerging HBV variants by direct sequencing of the HBV genome is excessively time-consuming for studying large numbers of clinical samples. The aim of the study was to analyse the emergence of lamivudine-resistant HBV genotypes by means of restriction fragment length polymorphism (RFLP) of the PCR product generated from a fragment of domain C of the polymerase gene, in clinical samples from patients receiving treatment. The results with this method were compared with those obtained with a direct sequencing technique. In total, 139 serum samples were studied from 37 patients with chronic hepatitis B, obtained at pre-treatment and at 9, 12, 18 and 24 months of treatment. Variants were detected by cleavage of the products of the three PCRs with the following enzymes: FokI (identifies the normal variant, YMDD, and the mutant variant YVDD), SspI (identifies the mutant variant, YIDD) and Alw44I (identifies the variant, YVDD). The digested fragments were separated by electrophoresis in 3% agarose gel. Of the 139 serum samples analysed, the wild-type YMDD sequence was detected in 106 (76%), the YVDD variant in 20 (15%) and the YIDD variant in 13 (9%) cases. The non-mutated variant, YMDD, was detected in all the pre-treatment samples. After 9 months of treatment the mutant variant was detected in four of 37 serum samples analysed (11%) (two YVDD and two YIDD). At 12 months, 12 of the 37 serum samples (32%) showed mutations in the YMDD sequence (seven YVDD and five YIDD). Among the 16 serum samples obtained at 18 months, nine had the YMDD variant (56%) (seven YVDD and two YIDD). At 24 months, variants in the YMDD sequence were detected in eight of the 12 patients treated (66%) (four YVDD and four YIDD). HBV genotypes were confirmed by direct sequencing, with consistent results. In 45% of cases, the emergence of HBV variants was not associated with ALT breakthrough. The PCR-RFLP assay used in this study, in perfect concordance with direct sequencing, is an accurate method for genotyping lamivudine-resistant HBV variants. Since it is a rapid low-cost technique, PCR- RFLP is suitable for large-scale screening of these polymorphisms in clinical samples.

Antiviral Agents↗
PubMed1999

Adrenomedullin, a vasodilator peptide implicated in hemodynamic alterations of liver cirrhosis: relationship to nitric oxide.

This prospective cohort study was aimed at investigating the role of adrenomedullin, a potent vasodilator peptide, in liver cirrhosis and its relationship with nitric oxide and cytokines. Overall, 66 consecutive patients with liver cirrhosis and 15 controls matched for age and sex distribution were included. Adrenomedullin levels in patients with cirrhosis were higher than in controls [28.1 (23.5-34.8) vs 21.9 (21.1-26.4) pmol/liter, P = 0.002]. Child class A patients had adrenomedullin levels similar to those of controls, but lower than patients in class B and C, respectively (P = 0.01). Patients with ascites showed more elevated adrenomedullin levels than patients without (P = 0.001). Adrenomedullin levels had significant correlations with aldosterone (r = 0.55; P < 0.001), plasma renin activity (r = 0.49; P < 0.001) and nitrates-nitrites levels (r = 0.52; P < 0.001). Weak correlations were found with tumor necrosis factor-alpha and interleukin-6. This study shows that high levels of adrenomedullin in liver cirrhosis correlate with features associated with plasma volume expansion, and suggests that, in late stages of cirrhosis, adrenomedullin might contribute to vasodilatation by increasing the generation of nitric oxide.

Adrenomedullin↗
PubMed1999

Evaluation of RNA and E2 antibodies in prospectively followed recipients of hepatitis G virus-infected blood.

BACKGROUND: Hepatitis G virus (HGV) has recently been cloned and tests for HGV RNA and envelope antibodies (anti-E2) have been developed. HGV infection is widespread among blood donors worldwide, but the clinical and serologic outcome of transfusion-associated HGV infection has not been fully characterized. STUDY DESIGN AND METHODS: Consecutive blood donors (n = 2210) were investigated for HGV markers (RNA and anti-E2). The recipients of HGV RNA-positive blood were followed for 1 year after transfusion. RESULTS: Forty-two blood donors (1.9%) were positive for HGV RNA. Eight recipients of HGV RNA-positive blood were retrospectively identified within 2 weeks of transfusion and prospectively followed. In four patients, the presence of anti-E2 before transfusion or an early antibody response protected them from reinfection or prevented HGV persistence, while, in the remaining four patients, transient or persistent viremia was detected shortly after exposure. None of the infected recipients had any evidence of liver disease. CONCLUSION: These results do not support the screening of donors to prevent transfusion-associated HGV infection.

Blood Donors↗
PubMed1999

Genetic alterations in the S gene of hepatitis B virus in patients with acute hepatitis B, chronic hepatitis B and hepatitis B liver cirrhosis before and after liver transplantation.

BACKGROUND: Several studies have shown that hepatitis B immunoglobulin (HBIG) imposes a selection pressure on the hepatitis B virus (HBV) S gene, and that the emergence of mutations in this region would make reinfection after orthotopic liver transplantation (OLT) possible. AIMS: This study was undertaken to analyze the presence of HBV S-gene mutations in the different stages of HBV infection and the relationship between HBIG therapy and the emergence of mutations in liver transplant recipients. METHODS: The frequency and location of mutations in the coding region of the HBV S gene were studied by PCR and direct sequencing in 30 patients (7 with acute self-limited hepatitis B, 16 with chronic hepatitis B and 7 recipients of (OLT) for HBV-related end stage liver disease who became reinfected). RESULTS: The average number of amino acid changes was higher in patients with a more advanced stage of disease, 0.57 mutations/100 positions in acute hepatitis B and 1.57 in chronic hepatitis B (1.28 in HBeAg-positive and 1.8 in anti-HBe-positive patients). The average number of substitutions in the transplanted patients was 2.7 before OLT and 3 after OLT. No amino acid substitutions were detected in the "a" determinant of HBsAg in acute hepatitis B, however, 8 substitutions were observed in 6 chronic patients. In 3 OLT patients, 4 substitutions were observed in samples before and after OLT. One of these patients, who had protective levels of anti-HBs, showed 3 additional new amino acid substitutions after OLT, suggesting escape mutant selection by the effect of HBIG therapy. No changes were observed between the consensus sequences obtained several years before and after transplantation, indicating consensus sequence stability. CONCLUSION: These results show that there is an accumulation of HBV S-gene mutations in HBV-related end-stage liver disease. Prophylaxis with HBIG mainly obtained from acute self-limited hepatitis patients who have a highly homogeneous viral population, may be one factor underlying the reinfection after liver transplantation.

Acute Disease↗
PubMed1999

Interleukin-6, nitric oxide, and the clinical and hemodynamic alterations of patients with liver cirrhosis.

OBJECTIVE: Nitric oxide has been proposed as a mediator of hyperdynamic circulation in cirrhosis. Endotoxin and cytokines induce the synthesis of nitric oxide. The aim of this study was to investigate the relationship between endotoxemia, cytokines, and nitric oxide in patients with cirrhosis, and to correlate these findings with clinical, biochemical, and hemodynamic parameters. METHODS: Clinical, biochemical, and hemodynamic parameters were assessed in 66 patients with cirrhosis and 15 controls. Levels of antidiuretic hormone, plasma renin activity, aldosterone, interferon gamma, interleukin-1, interleukin-6, tumor necrosis factor alpha, endotoxin, and nitrates-nitrites were determined. RESULTS: Mean arterial pressure was lower and interleukin-6, tumor necrosis factor alpha, nitrites-nitrates levels, and endotoxin positivity rates were higher in cirrhotics than in controls (p < 0.005). Mean arterial pressure decreased and interleukin-6 levels increased with worsening of Child score (p < 0.005). Patients with ascites had higher levels of interleukin-6, tumor necrosis factor alpha, and nitrates-nitrites than patients without ascites (p < 0.01). Elevated levels of interleukin-6 were found in patients with encephalopathy grade I, compared with patients without (p < 0.001); this association was independent of the severity of liver disease. In patients with low mean arterial pressure, interleukin-6 levels were higher than in patients with high mean arterial pressure (p = 0.001), whereas tumor necrosis factor alpha and nitrates-nitrites levels were not different. By multivariate analysis, high interleukin-6 levels showed independent associations with the presence of ascites, encephalopathy, and low mean arterial pressure. Only interleukin-6 levels had significant correlations with Child score, plasma renin activity, serum and urinary sodium, and mean arterial pressure (r > or = 0.4, p < 0.005). CONCLUSIONS: Although the activity of the nitric oxide pathway is increased in patients with cirrhosis and might contribute to the hemodynamic alteration, other factors are involved. Interleukin-6, possibly through nitric oxide-independent mechanisms, also might play a role in the vasodilatation of cirrhosis and the pathogenesis of hepatic encephalopathy.

Aged↗
PubMed1999

High-throughput real-time reverse transcription-PCR quantitation of hepatitis C virus RNA.

We describe a rapid and reproducible method for assessment of the hepatitis C virus (HCV) load in serum samples. The method combines Taqman technology (Roche) and the ABI Prism 7700 (Perkin Elmer) real-time sequence detection system. We have optimized a single-tube reverse transcription-PCR (RT-PCR) that contains a dual-labeled fluorogenic probe to quantify the 5' noncoding region (5' NCR) of HCV. The probe contains a fluorescent reporter at the 5' end and a fluorescent quencher at the 3' end. The use of such a probe combined with the 5'-3' nuclease activity of Taq polymerase allows direct quantitation of the PCR product by the detection of a fluorescent reporter released in the course of the exponential phase of the PCR. For accurate quantitation of the number of copies of HCV in samples containing unknown quantities, we have used serial dilutions of a synthetic 5' NCR RNA standard of HCV that was previously quantified with an isotopic tracer. The method has a 5-log dynamic range (10(3) to 10(7)). The coefficient of regression of the standard curve was, on average, 0.98. The intra-assay and the interassay coefficients of variation of the threshold cycle were 1% and 6.2%, respectively. Seventy-nine RNA samples from the sera of infected patients were quantified by this method. Comparison of the results with those obtained by other quantitation methods (the Quantiplex 2.0 branched-DNA assay and the Superquant assay from the National Genetics Institute) revealed a significant correlation with all of the results. The mean values were also statistically comparable. In conclusion, the high sensitivity, simplicity, and reproducibility of the real-time HCV RNA quantitation which allows the screening of large numbers of samples, combined with its wide dynamic range, make this method especially suitable for monitoring of the viral load during therapy and tailoring of treatment schedules.

Adult↗