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Biomedical subjects

A Muñoz

Publications and source records attributed to A Muñoz.

At least 379 records · Page 21Linked to original sources
PubMed1993

Neonatal hypothyroidism affects the timely expression of myelin-associated glycoprotein in the rat brain.

Congenital hypothyroidism strongly affects myelination. To assess the role of thyroid hormone on myelin gene expression, we have studied the effect of hypothyroidism on the steady state levels of myelin-associated glycoprotein (MAG) and its mRNA in rat brain during the first postnatal month. As studied by immunoblot analysis of several brain regions, MAG increased from days 10-15 onwards, reaching constant levels by days 20-25. Hypothyroid samples showed a delay in the accumulation of MAG that was more severe in rostral regions, such as cortex and hippocampus. The effect of hypothyroidism on the accumulation of the protein correlated with mRNA levels. MAG mRNA started to accumulate in the cerebrum of normal animals by postnatal day 7, reaching maximal levels by day 20. Hypothyroid rats showed a delay of several days in the onset of mRNA expression, increasing thereafter at the same rate as in normal animals, and eventually reaching similar values. When individual brain regions were analyzed, we found strong regional differences in the effect of hypothyroidism. The cerebral cortex was most affected, with messenger levels lower than in normal animals at all ages. In more caudal regions differences between control and hypothyroid rats were evident only at the earlier stages of myelination, with spontaneous recovery at later ages. By run on analysis, we found no differences in transcriptional activities of the MAG gene in normal, hypothyroid, or T4-treated rats. Therefore, the effects of hypothyroidism on MAG mRNA and protein levels were most likely caused by decreased mRNA stability. We propose that thyroid hormone contributes to enhanced myelin gene expression by affecting the stability of newly transcribed mRNA in the early phases of myelination.

Aging↗
PubMed1993

Thyroid hormone regulation of RC3, a brain-specific gene encoding a protein kinase-C substrate.

RC3 is a brain-specific mRNA expressed in discrete neuronal groups of the forebrain that encodes a 78-amino acid protein, also called neurogranin, a calmodulin-binding, protein kinase-C substrate. Expression of RC3 mRNA was studied in normal and hypothyroid animals during the first month of life. Hypothyroid rats were produced by administration of methyl-mercapto-imidazol to the pregnant dams and subsequent surgical thyroidectomy on postnatal day 5 of the neonates. As studied by slot-blotting of total cerebrum poly(A)+ RNA, RC3 mRNA accumulates in normal brain from the fifth to seventh postnatal day, reaching maximal levels around days 10-12. RC3 mRNA accumulation in hypothyroid animals was blunted, and the maximal levels attained were about 30-50% of normal values. The effect of hypothyroidism on steady state mRNA levels was also observed by Northern blotting of RNA from cerebral cortex and striatum. As studied by immunoblotting using a polyclonal antibody, hypothyroidism also led to clear decreases in the amount of the RC3 protein in extracts from cerebral cortex, striatum, and hippocampus. A single administration of 10 micrograms T4 to hypothyroid rats on postnatal day 12 led to a steady increase in striatal RC3 mRNA from levels that were about 40% of normal to about 70% of normal at 16 h and 115% of normal at 48 h. In contrast to the effect on RC3, hypothyroidism did not affect developmental expression of the mRNA encoding GAP-43, another brain protein kinase-C substrate of axonal localization. RC3 is, thus, one of the few known neuronal genes whose expression is influenced by thyroid hormone in the brain. Thyroid hormone is required for an appropriate level of expression, not for the developmentally programmed timing of expression of the RC3 gene.

Animals↗
PubMed1993

Design and analysis of studies of the health effects of ozone.

The design and analysis of studies that investigate the effect of exposure to ozone on health outcomes need to define carefully the methods for the assessment of the exposure and to determine precisely which is the outcome of biological relevance. The estimation of sample size for longitudinal studies requires the expected rates of change among the exposed and unexposed, the variance of the outcome, and the correlation of measurements taken within an individual. Methods of analysis whose primary interest is in the combination of cross-sectional studies for the determination of the marginal distribution of the outcome are particularly appropriate for biological processes where the effect of exposure is acute. Conditional models are particularly useful for investigating the effect of changes in exposure on changes in outcome at the individual level. In addition, conditional models incorporate a dampening effect of exposure that may provide a reasonable agreement with several biological mechanisms. The identification of susceptible individuals and the description of the behavior of their outcomes over time may be better accomplished by using the within-individual variance as the outcome of interest. Discrepancies of the within- and between-individual regressions may be suggestive of chronic effects, and methodological research in this area is needed. Studies of the health effects of ozone exposure need to address the incorporation of missing data, measurement error, and the combination of complementary studies.

Acute Disease↗
PubMed1993

Changes in T and non-T lymphocyte subsets following seroconversion to HIV-1: stable CD3+ and declining CD3- populations suggest regulatory responses linked to loss of CD4 lymphocytes. The Multicenter AIDS Cohort Study.

We investigated changes in lymphocyte subsets (total, CD4+ and CD8+ T cells, as well as non-T cells) associated with human immunodeficiency virus type I (HIV-1) seroconversion in 321 homosexual or bisexual men in the Multicenter AIDS Cohort Study (MACS). These subjects had serial lymphocyte characterizations for up to 4 years before and 5 years after seroconversion. CD4+ lymphocyte levels declined rapidly in the first 18 months following seroconversion and less rapidly thereafter, while CD8 lymphocytes increased with similar kinetics. In contrast, total T (CD3+) lymphocytes declined only slightly in the first 18 months following seroconversion, and then remained stable. These results support the hypothesis of physiologic regulation of the total number of circulating T cells, such that lost CD4+ lymphocytes are replaced by newly generated CD4+ and CD8+ lymphocytes; over time, continued loss of CD4+ lymphocytes due to HIV-1 infection would result in net replacement of lost CD4+ lymphocytes with CD8+ lymphocytes. Non-T (CD3-) lymphocytes also declined after seroconversion, and this decline paralleled that of CD4+ lymphocytes. Thus, changes in both T and non-T lymphocytes after HIV-1 seroconversion may reflect the operation of homeostatic or regulatory mechanisms. Whether these mechanisms contribute to the development of immune deficiency requires further study.

CD3 Complex↗
PubMed1993

An ODA-based coder/decoder for multimedia medical documents.

This paper describes the prototype of a coder/decoder based on the Open Document Architecture (ODA) standard for management of medical documents, as well as the working environment in which it has been developed. The prototype has been assessed in an X-Windows-equipped workstation with a relational database containing patient folders (text and still images) from the departmental information system of the liver transplantation unit.

Humans↗
PubMed1993

[Platelet function after allogeneic bone marrow transplantation in Wiskott-Aldrich syndrome].

PURPOSE: To assess the platelet characteristics and functionalism in the Wiskott-Aldrich syndrome (WAS) after allogeneic BMT using cyclophosphamide and busulphan for conditioning. MATERIAL AND METHODS: Two WAS patients underwent allogeneic BMT. Platelet aggregation was studied prior to and after BMT, along with the intraplatelet amount of ADP and ATP. RESULTS: Platelet count, size and aggregation wholly recovered after BMT. The post-transplant content of platelet nucleotides was normal. CONCLUSIONS: Platelet function can be totally restored with cyclophosphamide/busulphan conditioned BMT in WAS. Platelet defects in this disease are due to defective thrombopoiesis.

Blood Platelets↗
PubMed1993

[Deafness in patients with osteogenesis imperfecta].

This study deals with 8 cases of progressive deafness in patients with abnormalities in growth and skeletal disease, suffering from Osteogenesis imperfecta (5 of them are a familial case). The work is both and audiological and radiological research of the temporal bone, done in order to uncover the reasons of the patient's deafness. This curses just like otosclerosis with a conductive component (fixation of the stapes) and a sensitive one (cochlear demineralization), starting up in adolescence as bilateral and symmetric process. Because of its progressive nature the AA, recommend as treatment the ear prostheses and refuse the surgery of the stapes.

Adolescent↗
PubMed1993

[Cerebellar medulloblastoma in childhood: supratentorial metastasis].

Reports on supratentorial metastases of medulloblastoma are infrequent. Computed tomography has increased the possibilities of detecting then in a silent clinical phase. Five children with supratentorial metastasis of medulloblastoma were retrospectively reviewed. Diagnosis was established by cranial CT between three and sixty months following treatment of the tumor. Dissemination through the ventricular system was found in all the cases. Other lesions were found in the transition zone between the white and grey matter (2/5) and the left frontal lobe (1/5). The routes of dissemination are discussed. Early diagnosis of supratentorial metastasis of medulloblastoma require periodic cranial CT or magnetic resonance imaging (MRI), at least during the first years after diagnosis and treatment of the primary tumor.

Cerebral Ventricles↗
PubMed1992

Effect of chronic substance abuse on the neuropsychological performance of intravenous drug users with a high prevalence of HIV-1 seropositivity.

Limited data are available on cognitive performance in populations of intravenous drug users during the early, asymptomatic stages of human immunodeficiency virus type 1 (HIV-1) infection. Between 1988 and 1990, 151 participants from the AIDS Link to Intravenous Experience (ALIVE) Study in Baltimore, Maryland, were evaluated neuropsychologically on a semiannual basis. This analysis focused on whether history of substance abuse influenced neuropsychological test performance. At baseline, 102 participants were HIV-1-seropositives who were free of acquired immunodeficiency syndrome and 49 participants were seronegative. Multivariate analyses, adjusting for correlation of repeated outcome measures, were conducted to determine predictors of neuropsychological functioning. Effects of the frequency of reported past use of marijuana, heroin, cocaine, barbiturates, and alcohol were not statistically associated with performance on the tests. Age and education were the most important predictors of test performance, and a significant practice effect was observed for most measures. After adjustment for age, education, the practice effect, and frequency of drug use, neuropsychological performance over time did not vary by HIV-1 serostatus. Overall, after acutely intoxicated individuals were excluded, neither frequency of drug and alcohol use nor HIV-1 seropositivity significantly influenced neuropsychological test performance over a 1-year period.

Adult↗
PubMed1992

Transmission of retroviruses from seronegative donors by transfusion during cardiac surgery. A multicenter study of HIV-1 and HTLV-I/II infections.

OBJECTIVE: To evaluate the effectiveness of serologic testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types I and II (HTLV-I/II) infections and to estimate the risk for transmission of HIV-1 and HTLV-I/II by transfusion of seronegative blood from screened donors. DESIGN: A prospective multicenter cohort study of cardiac surgery patients who received multiple transfusions between 1985 and 1991. SETTING: Cardiac surgery services of three large tertiary care hospitals. PATIENTS: The study included 11,532 patients in three hospitals who had cardiovascular surgery. MEASUREMENTS: Incident HIV-1 and HTLV-I or HTLV-II infection. RESULTS: We detected two new HIV-1 infections among patients transfused with 120,312 units of blood components from seronegative donors. In each case a donor was detected on follow-up who had seroconverted since the donation. The HIV-1 infection rate was 0.0017% with an upper limit of the 95% CI of 0.0053%. Before donor screening for HTLV-I, transfusion of 51,026 units resulted in two HTLV-I infections (0.0039%) and four HTLV-II infections (0.0078%). After HTLV-I screening was instituted, one recipient was infected with HTLV-II among participants exposed to 69,272 units, a rate of 0.0014%. A corresponding HTLV-I/II-infected donor was found for this patient. CONCLUSION: Serologic screening of donors for antibodies to HIV-1 and HTLV-I coupled with exclusion of donors from groups having a relatively high risk for infection has led to a low incidence of transfusion-transmitted HIV-1 and HTLV-I/II infection in the United States. A small risk remains, however, despite these measures. We estimate the residual risk for HIV-1 and HTLV-II infection from transfusion of screened blood during the time of this study to be about 1 in 60,000 units.

Aged↗
PubMed1992

The declining risk of post-transfusion hepatitis C virus infection.

BACKGROUND: The most common serious complication of blood transfusion is post-transfusion hepatitis from the hepatitis C virus (HCV). Blood banks now screen blood donors for surrogate markers of non-A, non-B hepatitis and antibodies to HCV, but the current risk of post-transfusion hepatitis C is unknown. METHODS: From 1985 through 1991, blood samples and medical information were obtained prospectively from patients before and at least six months after cardiac surgery. The stored serum samples were tested for antibodies to HCV by enzyme immunoassay, and by recombinant immunoblotting if positive. RESULTS: Of the 912 patients who received transfusions before donors were screened for surrogate markers, 35 seroconverted to HCV, for a risk of 3.84 percent per patient (0.45 percent per unit transfused). For the 976 patients who received transfusions after October 1986 with blood screened for surrogate markers, the risk of seroconversion was 1.54 percent per patient (0.19 percent per unit). For the 522 patients receiving transfusions since the addition in May 1990 of screening for antibodies to HCV, the risk was 0.57 percent per patient (0.03 percent per unit). The trend toward decreasing risk with increasingly stringent screening of donors was statistically significant (P less than 0.001). After we controlled for the method of donor screening, the risk of seroconversion was strongly associated (P less than 0.001) with the volume of blood transfused, but not with the use of particular blood components. CONCLUSIONS: The incidence of post-transfusion hepatitis C has decreased markedly since the implementation of donor screening for surrogate markers and antibodies to HCV. The current risk of post-transfusion hepatitis is about 3 per 10,000 units transfused.

Alanine Transaminase↗
PubMed1992

Predictors of the risk of development of acquired immunodeficiency syndrome within 24 months among gay men seropositive for human immunodeficiency virus type 1: a report from the Multicenter AIDS Cohort Study.

The natural history of infection with human immunodeficiency virus type 1 (HIV-1) is characterized by a relentless decline in CD4-positive lymphocytes and the ultimate development of acquired immunodeficiency syndrome (AIDS). However, variables other than the CD4-positive lymphocyte level contribute to the measurement of risk for AIDS and can be used as predictors of AIDS onset. This study was undertaken to identify factors that, independently of the CD4-positive lymphocyte level, would predict the risk of AIDS over 24 months in a cohort of HIV-1 seropositive homosexual men receiving no antiretroviral therapy. Demographic, clinical, and laboratory data from 1,325 white, HIV-1 seropositive participants in the Multicenter AIDS Cohort Study who have been studied for 4 years were analyzed with univariate and multivariate methods. To control for stage of infection, the baseline percentage of CD4-positive lymphocytes (a known marker of disease progression), and the decline of CD4-positive cells during the first 6 months of observation were used as continuous variables. The variables that were independently associated with an increased risk of developing AIDS were: low baseline CD4 percentage, decline in the CD4 percentage during the first 6 months of follow-up, the presence of serum immunoglobulin A at baseline, decrease in hemoglobin during the first 6 months of follow-up, incident fatigue, and the interaction of decline in the CD4 percentage and incident thrush. While low CD4 percentage and other variables have been previously described as prognostic markers, decline in the CD4 percentage and the interaction of that decline and incident thrush have not previously been described as being of prognostic importance. These variables and the analytic method for estimating prognosis may prove useful for selecting and evaluating antiretroviral therapy, instituting prophylactic measures against certain opportunistic infections, and recruitment into clinical trials. Because study participants received no antiretroviral prophylaxis during the period under analysis, the method could be used to estimate the prognosis for those receiving investigational treatment were they to remain untreated, effectively making any participant in a clinical trial his own untreated control.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Changes in T-lymphocyte subsets in intravenous drug users with HIV-1 infection.

OBJECTIVE: To evaluate changes in T-cell subsets in prevalent human immunodeficiency virus type 1 (HIV-1) seronegative and seropositive intravenous drug users (IVDUs) and in HIV-1 seropositive IVDUs with known time of seroconversion. DESIGN: Cohort study with a median 18-month follow-up. SETTING: Community-based clinic established to study the natural history of HIV infection in IVDUs. SUBJECTS: Eight hundred fifty-nine self-referred IVDUs aged 18 through 49 years who injected drugs within the last 10 years and who did not have an AIDS (acquired immunodeficiency syndrome)--defining illness; 152 were seronegative for HIV-1, 621 were seropositive, and 86 seroconverted during the study. OUTCOME MEASURES: Proportions and absolute numbers of lymphocytes and CD3, CD4, and CD8 T cells as determined at 6-month intervals by flow cytometry and complete blood cell counts with automated differential. RESULTS: Median numbers of CD4 lymphocytes at enrollment were 1061/microL (1.06 x 10(9)/L) for seronegative IVDUs, 508/microL for seropositive IVDUs, and 733/microL for those who seroconverted (enrolled a median of 4.5 months after seroconversion); the corresponding figures for CD8 lymphocytes were 628, 894, and 889/microL, respectively. Median rates of decline in absolute numbers and percentages of CD4 lymphocytes per 6 months were 7.6/microL (0.0%) for seropositive IVDUs and 55.1/microL (1.9%) for IVDUs who seroconverted (median follow-up after seroconversion was 12 months). Multivariate regression analysis that incorporated the within-individual correlation of the CD4 lymphocyte counts showed no significant change in these cells over time and no change due to use of drugs. CONCLUSION: Our data suggest that progression of HIV-1 infection in IVDUs, as reflected in decline of CD4 cell counts, is no more rapid than that reported for other risk groups.

Adult↗
PubMed1992

Estimation of time since exposure for a prevalent cohort.

In natural history studies of human immunodeficiency virus type 1 (HIV-1) infection a substantial proportion of participants are seropositive at time of enrollment in the study. These participants form a prevalent subcohort. Estimation of the unknown times since exposure to HIV-1 in the prevalent subcohort is of primary importance for estimation of the incubation time of AIDS. The subset of the cohort that tested negative for antibody to HIV-1 at study entry and was observed to seroconvert forms the incident subcohort that provides longitudinal data on markers of maturity (that is, duration) of infection. We use parametric life table regression models incorporating truncation to describe the conditional distribution (imputing model) of the times since seroconversion given a vector of the markers of maturity. Using the fitted model and the values of the markers of maturity of infection provided by the seroprevalent subcohort at entry into the study, we can impute the unknown times since seroconversion for the prevalent subcohort. We implement multiple imputation based on a model-robust estimate of the covariance matrix of parameters of the imputing model to provide confidence intervals for the geometric mean of the time since seroconversion in the prevalent subcohort, and to compare maturity of infection of cohorts recruited in different cities. The accuracy of imputation is further validated by comparisons of imputation-based estimates of AIDS incubation distribution in the seroprevalent subcohort with more direct estimates obtained from the seroincident subcohort.

Acquired Immunodeficiency Syndrome↗