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Biomedical subjects

J Guardia

Publications and source records attributed to J Guardia.

At least 73 records · Page 4Linked to original sources

Spectrum of alcohol-induced myocardial damage detected by indium-111-labeled monoclonal antimyosin antibodies.

OBJECTIVES: We sought to determine the prevalence, intensity and evolving changes of myocardial damage detected by myocardial uptake of antimyosin antibodies in patients with alcohol-induced dilated cardiomyopathy, alcohol addicts attending a detoxification unit and healthy subjects with short-term alcohol consumption. BACKGROUND: Evidence of alcohol-induced myocardial damage may be provided by myocardial uptake of indium-111-labeled monoclonal antimyosin antibodies. The spectrum of such damage in patients who are heavy drinkers (> 100 g for > 10 years), with or without cardiomyopathy, and the impact of short-term alcohol ingestion on antimyosin antibody uptake have not been adequately explored. METHODS: One hundred twenty antimyosin studies were performed in 56 patients with dilated cardiomyopathy (group I), 15 alcohol addicts attending a detoxification unit (group II) and 6 volunteers for short-term alcohol ingestion (group III). Estimation of antibody uptake was calculated through a heart/lung ratio (HLR) (normal < 1.55). RESULTS: The 56 patients in group I (54 men, 2 women; mean [+/-SD] age 46 +/- 11 years) had consumed 123 +/- 60 g/day of alcohol for 21 +/- 9 years, for a cumulative intake of 914 +/- 478 kg. Mean duration of symptoms was 46 +/- 49 months. Mean left ventricular end-diastolic diameter was 71 +/- 10 mm, and mean ejection fraction was 28 +/- 12%. No differences in New York Heart Association functional class, ventricular size or ejection fraction were noted between 28 active and 28 past consumers, except for the prevalence and intensity of antibody uptake (75% vs. 32%, p < 0.001) and HLR (1.75 +/- 0.26 vs. 1.49 +/- 0.17, p = 0.0001). In 19 patients in the active group restudied after alcohol withdrawal, antibody uptake decreased (from 1.76 +/- 0.17 to 1.55 +/- 0.19, p < 0.001), and ejection fraction improved (from 30 +/- 12% to 43 +/- 16%, (p < 0.001). No changes occurred in the 15 past consumers restudied. The 15 male patients in group II (mean age 36 +/- 4 years) had consumed 156 +/- 59 g/day for 17 +/- 5 years, for a cumulative alcohol intake of 978 +/- 537 kg, an amount similar to that in patients in group I, but antimyosin antibody uptake was detected in only 3 (20%) of 15 patients. None of six group III subjects developed antibody uptake after short-term ethanol ingestion. Despite the small sample size, the power to detect clinically relevant differences in most variables that did not reach statistical significance was amply sufficient. CONCLUSIONS: In alcohol-induced dilated cardiomyopathy, alcohol withdrawal is associated with the reduction or disappearance of myocardial damage and improvement of function. The difference in prevalence of antimyosin antibody uptake in patients with and without cardiac disease who consume similar amounts of alcohol suggests the presence of those with different myocardial susceptibilities to alcohol. Short-term ethanol ingestion in healthy subjects does not induce detectable uptake of antimyosin antibodies.

Adult↗

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↗

Immunohistochemistry of minor salivary gland biopsy specimens from patients with Sjögren's syndrome with and without hepatitis C virus infection.

OBJECTIVES: To characterise phenotypically the minor salivary glands of patients with clinical and histological features of Sjögren's syndrome (SS) infected with hepatitis C virus (HCV). PATIENTS AND METHODS: 75 consecutive patients with SS (31 primary SS, 44 secondary SS) diagnosed by preliminary European classification criteria. The presence of anti-HCV antibodies was detected by commercial third generation ELISA and by a second generation immunoblot assay. Presence of HCV genome in serum was determined by polymerase chain reaction analysis. Expression of CD3, CD4, CD8, CD20, HLA-DR, and CD25 molecules in lymphocytic and epithelial cells on minor salivary glands was detected by immunohistochemical assays. Expression of interferon gamma and interleukin 4 cytokines was determined by in situ hybridisation. RESULTS: Six of 31 primary SS (19%) and one of 44 secondary SS (2%) serum samples were positive for anti-HCV by ELISA. Three samples were positive, three indeterminate, and one sample corresponding to a secondary SS patient was negative by immunoblot. The three immunoblot positive serum samples were also HCV-RNA positive by PCR assay. The study of lymphocytic cells in the diffuse infiltrate of minor salivary glands showed a predominance of the CD3 lymphocytic population. A predominance of CD4 over CD8 T cells (ratio 2:1) was observed in HCV and non-HCV infected patients. The analysis of the lymphocytic focus showed that the HCV infected patients had a predominance of CD20 positive cells. Activation molecules (CD-25 and HLA-DR) were expressed in HCV and non-HCV infected patients in lymphocytic and epithelial cells, however epithelial cell expression of CD25 was low in HCV infected patients. As expected, a pronounced Th1 response was observed in the lymphocytic foci of HCV patients. CONCLUSIONS: HCV infected patients may develop an autoimmune sialadenitis, similar to that described in primary SS.

Adult↗

[Study of HLA-II antigens in chronic hepatitis C and B and in acute hepatitis B].

The aim of this study was to analyze the variability of the HLA-II system in a series of patients with chronic hepatitis B, chronic hepatitis C and acute hepatitis B to know whether there is any relationship between the polymorphism of the HLA system, the different types of hepatitis and the evolution of the infection. HLA-II antigens were determined by a PCR technique in serum samples of 24 controls, 22 cases of chronic hepatitis C, 38 cases of chronic hepatitis B and 11 with acute hepatitis B. The prevalence of the HLA-DR4 antigen was lower in the cases of chronic hepatitis B (10.5%) and C (13.6%) than in the controls (33.3%), particularly the DRB1*0401 allele (p = NS). The prevalence of HLA-DR6 was similar in chronic hepatitis B (42.1%) and acute hepatitis B (45.5%). Predominance of the DRB1*1301 and DRB1*1302 alleles were, however, observed in acute hepatitis B (36.4%) versus chronic hepatitis B (13%). These data suggest that immunologic factors such as HLA antigens may influence in the susceptibility to infection by HBV and HCV. The use of PCR techniques which discriminate between the different alleles of the HLA antigens may provide better knowledge of the immune response.

Acute Disease↗

[Shortened version of the Barcelona test (II): global standard score].

The aim of this study was to determine a global scoring method for a shortened and version of the Barcelona Neuropsychological test (TB) of 55 items. 341 healthy volunteers, 178 male (52.19%), and 163 female (47.1%) were studied. Age mean: 54.80, SD = 17.44. Subjects were stratified in five groups considering age and education. A scale of cut-off points was selected in order to divide the scores of each subtest into three bands (categories): 0 (lowest), 1 (intermediate), 2 (highest). Raw scores (possible range 0-110) were obtained and then were converted to a mean of 100 and SD of 15 each normative group. Tables of normative data were obtained for each group. This study shows the cognitive profiles of the TB and a global standard score related to them. This global score will provide new possibilities in the neuropsychological assessment of neurological patients.

Aged↗

[Shortened version of the Barcelona test (III): criterion validity with the ADAS-Cog].

The aim of this study was to assess the criterion validity of a global score of an abbreviated version of the Barcelona Test (BTA), normalized for age and education, as a clinical neuropsychometric test for the assessment of cognitive impairment. This study made a correlational analysis between test scores of the BTA and scores of the cognitive part of the Alzheimer's Disease Assessment Scale (ADAS-Cog) adjusted for age and education. It was made in a University Hospital (Dementia Unit). A group of 172 subjects (74 male, 98 female) was distributed according the Global Deterioration Stages (GDS) from 1 to 6. GDS-1 (normal controls), n = 60; GDS-2 (subjective complaints), n = 27; GDS-3, n = 21, GDS-4, n = 22; GDS-5, n = 16; GDS 6, n = 26. All dementia patients fulfilled the NINCDS/ADRDA criteria. BTA global scores correlated significantly with adjusted scores on the ADAS-Cog (r = 0.872, r2 = 0.761), p < 0.0001. The BTA has a criterion validity as a clinical neuropsychometric test for the study of cognitive impairment.

Adult↗

[Shortened version of the Barcelona test (I): subtests and normal profiles].

The aim of this study was to define a shortened form of the Barcelona neuropsychological test to be used in clinical neurology. There was a selection of subtests from the original test and descriptive statistics of an enlarged number of normal volunteers. 341 normal subjects were studied, 178 male (52.19%) and 163 female (47.1%). Age mean: 54.80, SD = 17.44. Education: mean 9.0 years, SD: 5.4. Subjects were stratified in five groups considering age and education. Subtest were choose according clinical criteria and considering data from a previous study. Five different age and education scoring profiles were defined. This reduced version of the Barcelona test includes the main neuropsychological areas and it takes only 30-45 minutes administration. The Barcelona test meets practical standards in neuropsychology.

Adult↗

Chronic delta hepatitis: is the prognosis worse when associated with hepatitis C virus and human immunodeficiency virus infections?

Eighty-six patients were followed for 6.5 years to study the epidemiological, virological, and histological course of chronic delta hepatitis and the relationship of this disease with HIV and HCV infection. Patients were classified into four groups according to simultaneous HCV and/or HIV infection: group 1, HDV infection (20 cases); group 2, HDV and HCV infection (11 cases); group 3, HDV and HIV infection (12 cases), and group 4, HDV, HCV, and HIV infection (43 cases). All but 14 patients were asymptomatic at presentation. Liver histology showed chronic active hepatitis in 53 cases and cirrhosis in 19 cases. During followup, 52 patients remained asymptomatic, 34 developed hepatic dysfunction, 28 died, and 1 received a liver transplant. Among the 28 patients who died, 4 had HDV infection; 3 HDV and HCV infection; 3 HDV and HIV infection; and 18 HDV, HCV, and HIV infection. Death was due to liver failure in 16 (57%), AIDS in 10 (36%), and was unrelated to liver disease in 2 (8%) cases. There results demonstrate that chronic delta hepatitis is a severe disease, especially among drug users with HIV and HCV infection. The high morbidity and mortality of chronic delta hepatitis justifies the use of antiviral therapy to modify the natural course of the disease.

Adolescent↗

Interferon vs. adenine arabinoside 5'-monophosphate in patients with anti-HBe-positive chronic hepatitis.

Anti-HBe-positive patients with precore mutants may have severe, progressive liver disease. Therapy with interferon has been effective, but relapses are frequent. To evaluate and compare two antiviral treatments, lymphoblastoid interferon (ly-IFN) and adenine arabinoside 5'-monophosphate (ARA-AMP), 20 patients with anti-HBe-positive chronic hepatitis (5 cirrhosis and 15 CAH) and viral replication (HBcAg in the liver and HBV DNA in serum) were treated. Patients were randomized into two groups: 11 patients received ARA-AMP, 5 mg/kg/day during 7 weeks, and 9 received human ly-IFN, 5,000,000 units, three times per week, during 4 months. Baseline clinical, biochemical and histological features were not significantly different between the two groups. At the end of therapy, 8 (89%) patients in the interferon group and 5 (45%) in the ARA-AMP group showed normal ALT levels and no HBV DNA in serum by a liquid hybridization assay (P < 0.05). At 1 year of follow-up, a persistent response was observed in 33% of ly-IFN patients and in 27% of ARA-AMP patients, a transient response in 56% and 18%, and nonresponse in 11% and 55%, respectively. HBV DNA remained detectable by polymerase chain reaction (PCR) in 19 of the 20 patients. Among the responders, an improvement in histological lesion and the disappearance of intrahepatic HBcAg were observed; in the nonresponders, histological lesion remained stable or worsened. In conclusion, the efficacy of interferon and ARA-AMP was similar in treating anti-HBe-positive chronic hepatitis. Although interferon treatment led to initial improvement in a larger number of patients, there was a much higher rate of relapses with this drug.

Adult↗

The value of quantitative detection of HBV-DNA amplified by PCR in the study of hepatitis B infection.

BACKGROUND/AIMS: This study aimed to evaluate the usefulness of quantifying HBV-DNA amplified by polymerase chain reaction in chronic hepatitis B infection. METHODS: Serum samples were obtained from 32 asymptomatic HBV carriers and 99 chronic hepatitis B patients (62 positive for anti-HBe and 37 positive for HBeAg). In addition, serial serum samples were analyzed from 15 HBeAg positive patients undergoing antiviral therapy and 17 anti-HBe positive patients with precore mutation. HBV-DNA quantification was carried out using an enzyme immunoassay with an HBV-DNA plasma standard. RESULTS: The digoxigenin-incorporated polymerase chain reaction method detected HBV-DNA in 34.3% of the asymptomatic HBV carriers with a median HBV-DNA concentration of about 0.18 x 10(5) mol/ml (range 0.08-0.4), in 87% of the anti-HBe positive chronic hepatitis cases with a range of 0.2 to > 2 x 10(5) mol/ml and in 100% of the HBeAg positive patients, with a value in all cases over 2 x 10(5) mol/ml. We observed that after treatment, HBV-DNA tested negative in only two of the eight HBeAg positive chronic hepatitis patients who seroconverted to anti-HBe, and was positive in the seven remaining, with a median HBV-DNA value of about 0.2 x 10(5) mol/ml (0.09-0.4). In the precore mutants HBV-DNA values ranged from 0.2 to > 2 x 10(5) mol/ml. CONCLUSIONS: Polymerase chain reaction HBV-DNA quantification is a sensitive method for managing chronic hepatitis B patients, especially those with low viremia, and may be a valuable tool for evaluating the efficacy of antiviral therapy.

Adult↗

[Hepatocarcinoma and killer cell activity].

BACKGROUND: Alterations in natural killer (NK) cell activity have been described in patients with different neoplasms including hepatocellular carcinoma (HCC). Nonetheless, the relationship between this activity and the clinical situation of the patients with HCC is not well established. METHODS: A group of 33 patients with hepatic cirrhosis and non treated HCC, a group of 22 patients with only hepatic cirrhosis, and a control group of 31 healthy blood donors were studied. In all the subjects the NK cell activity was determined against the K562 cell line marked with 51Cr by the short duration cytotoxicity test, and the number of NK cells/microliters in peripheral blood was determined by flow cytometry (FACScan) using the anti-CD3, CD16 and CD56 monoclonal antibodies. RESULTS: No statistically significant differences were observed in the NK cell activity or in the number of NK cells/microliters among the three groups studied. In the patients with HCC the NK cell activity was not related to the degree of hepatic function, however the patients with tumors greater than 5 cm in diameter or multinodular tumors showed a significant decrease in NK cell activity without a decrease in the number of NK cells/microliters. CONCLUSIONS: The natural killer cell activity in patients with hepatocellular cancer is not related to subjacent hepatic cirrhosis but is related to tumor size.

Aged↗

Hepatitis B virus infection: precore mutants and its relation to viral genotypes and core mutations.

The precore-core gene of hepatitis B virus (HBV) was directly sequenced from serum samples of 42 patients with chronic B hepatitis (19 hepatitis B e antigen [HBeAg]+ and 23 anti-HBE+). Viral genotypes were determined by comparison with 11 reference sequences and by restriction analysis. Genotype A was identified in 16 cases, genotype D in 24 cases, and other genotypes in 2 cases. Precore mutations, mainly M1 (stop at codon 28), were differently distributed among the viral genotypes: 3 cases (18.8%) with genotype A and 18 cases (75%) with genotype D. In sequences with precore mutants, the encapsidation signal was more stable (negative stabilization energy) than in sequences without precore mutants. In genotype A, the M1 mutation coexisted with a second mutation (C-->T at position 1858 in codon 15), and both mutations were paired in the secondary structure of the RNA encapsidation signal, which justified the rare presence of precore mutants in this genotype. The analysis showed different distribution of mutations depending on the viral genotype; patients with genotype D were more likely to have persistent HBV infection by selection of precore mutants. Multiple amino acid substitutions were detected in the core region, mainly in two subsequences that have been previously described as epitopes (flanked by codons 11 to 27 and 74 to 83); the presence of these mutations was significantly related to the presence of precore variants which abolished the expression of HBeAg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hepatitis E virus infection in acute hepatitis in Spain.

In order to study the prevalence of hepatitis E virus (HEV) infection in developed countries, IgG and IgM anti-HEV were determined in serum samples from 382 patients with acute viral hepatitis (244 hepatitis A, 48 hepatitis B and/or D, and 90 non-A, non-B, non-C hepatitis), 76 healthy subjects, 55 hemophiliacs and 50 patients on hemodialysis. IgG anti-HEV antibodies were detected and confirmed by a synthetic peptide-based EIA in 5 (5.6%) non-A, non-B, non-C acute hepatitis, in 3 (6.5%) B and D acute hepatitis, in 10 (4%) acute A hepatitis, in 3 (5.5%) of 54 healthy adults in none of the hemophiliacs and in 3 (6%) patients on hemodialysis. IgM anti-HEV antibodies were only detected in two cases of acute hepatitis B and/or D. Analysis of serial serum samples demonstrated IgG anti-HEV seroconversion in 3 of the 18 confirmed cases; one of them was also positive for IgM anti-HEV. All 3 acute anti-HEV-positive hepatitis cases occurred in adults, were community-acquired (two of them were intravenous drug addicts) and had a self-limited course. These results demonstrate that HEV is a minor cause of acute hepatitis in Spain. A similar low rate of IgG anti-HEV antibodies was detected in patients with different diseases, suggesting that HEV has a very low epidemiological impact. An apparent association of HEV infection with hepatitis B and D suggests a possible parenteral transmission of a mainly enteral pathogen.

Acute Disease↗

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↗

The apomorphine test in heroin addicts.

Chronic administration of opiates to laboratory animals induces supersensitivity of the dopamine receptors in the cerebral areas innervated by the mesotelencephalic dopamine pathways. In humans, the in vivo study of the sensitivity of the dopamine neurotransmitter system in Parkinson's patients can be done by means of the apomorphine test, which consists of measuring the number of yawns induced by the subcutaneous administration of low doses of apomorphine (0.005 mg/kg). If chronic opiate use in humans, as in experimental animals, results in supersensitivity of the dopamine systems, the apomorphine test could differentiate between heroin addicts and healthy volunteers, with the former showing greater number of yawns. In order to test this hypothesis we carried out the apomorphine test in two groups of subjects: a group of male heroin addicts attending our Addiction Treatment Centre for detoxification and the other group consisting of healthy volunteer male university students. Results showed that subcutaneous apomorphine administration induced a greater number of yawns (p < 0.05) in the group of heroin addicts as compared with the group of healthy volunteers, suggesting that heroin addicts present an enhanced sensitivity of the dopamine nuerotransmitter system.

Adolescent↗