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Biomedical subjects

A Muñoz

Publications and source records attributed to A Muñoz.

At least 271 records · Page 15Linked to original sources
PubMed1996

Bayesian imputation of predictive values when covariate information is available and gold standard diagnosis is unavailable.

We suggest a conceptually simple Bayesian approach to inferences about the conditional probability of a specimen being infection-free given the outcome of a diagnostic test and covariate information. The approach assumes that the infection state of a specimen is not observable but uses the outcomes of a second test in conjunction with those of the first, that is, dual testing data. Dual testing procedures are often employed in clinical laboratories to assure that samples are not contaminated or to increase the likelihood of correct diagnoses. Using the CD4 count and a proxy for risk behavior as covariates, we apply the method to obtain inferences about the conditional probability of an individual being HIV-1 infection-free given the individual's covariates and a negative outcome with the standard enzyme-linked immunoad-sorbent assay/Western blotting test for HIV-1 detection. Inferences combine data from two studies where specimens were tested with the standard and with the more sensitive polymerase chain reaction test.

Algorithms↗
PubMed1996

[Immunologic reconstitution of peripheral blood lymphocytes in patients treated by bone marrow transplantation].

BACKGROUND: Lymphocyte subset reconstitution was studied in 65 patients undergoing allogeneic and autologus bone marrow transplantation (BMT). PATIENTS AND METHODS: The expression of molecules on the membrane of lymphocyte subsets was assessed by two-colour flow cytometry and a direct immunofluorescence assay. The functional capacity of the patient's T lymphocytes following transplantation was identified by stimulation whit peripheral blood lymphocytes; B cells from BMT recipients were tested for their ability to respond, in vitro, to pokeweed (PWD) mitogen. RESULTS: 1) The proportion of CD8+ T lymphocytes was higher than the CD4+ T lymphocytes until 1 1/2 year after-BMT, with high percentage of immature T cells (CD3+, CD8+, HLA-DR+, CD25-) in the first nine months post-transplant. Moreover, a large proportion of T lymphocytes lacked CD5 expression in the first year following BMT. 2) T-cell proliferative response to PHA was low with subsequent recovery until normality. 3) Low numbers of B cells in the first two months with a significant increase since then until 1 1/2 year after-BMT; the phenotype of these B cells was mainly CD19+, CD5+. 4) High in vitro spontaneous immunoglobulin production by peripheral blood B lymphocytes and an impaired response to PWM was observed. 5) Increased percentage of cells with natural killer (CD56) cell phenotype was seen during the 2nd and 3rd months after the graft infusion. After 1 1/2 year postgrafting, this percentage returned to normal level. CONCLUSIONS: Taken together, these data indicate the existence of numerous abnormalities in several subsets of peripheral blood lymphocytes after BMT and suggest a slow kinetics of immune recovery after human marrow transplantation being complete between 18 and 24 months following BMT.

Adolescent↗
PubMed1996

Models for residual time to AIDS.

The distributions of the time from Human Immunodeficiency Virus (HIV) infection to the onset of Acquired Immune Deficiency Syndrome (AIDS) and of the residual time to AIDS diagnosis are important for modeling the growth of the AIDS epidemic and for predicting onset of the disease in an individual. Markers such as CD4 counts carry valuable information about disease progression and therefore about the two survival distributions. Building on the framework set out by Jewell and Kalbfleisch (1992), we study these two survival distributions based on stochastic models for the marker process (X(t)) and a marker-dependent hazard (h(.)). We examine various plausible CD4 marker processes and marker-dependent hazard functions for AIDS proposed in recent literature. For a random effects plus Brownian motion marker process X(t) = (a + bt + BM(t))4, where a has a normal distribution, b < 0 is an unknown parameter and BM(t) is Brownian motion, and marker-dependent hazard h(X(t)), we prove that, given CD4 cell count X(t), the residual time to AIDS distribution does not depend on the time since infection t. Using simulation and numerical integration, we find the marginal incubation period distribution, the marginal hazard and the residual time distribution for several combinations of marker processes and marker-dependent hazards. An example using data from the Multicenter AIDS Cohort Study is given. A simple regression model relating the cube root of residual time to AIDS to CD4 count is suggested.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Is the addition of ECG gating to technetium-99m sestamibi SPET of value in the assessment of myocardial viability? An evaluation based on two-dimensional echocardiography following revascularization.

The main goal of this study was to evaluate whether the addition of ECG gating to technetium-99m sestamibi single-photon emission tomographic (SPET) perfusion imaging assists the prediction of recovery of regional wall motion abnormalities after revascularization. Thirty-six patients with coronary artery disease were included in the study. All had wall motion abnormalities, and 31 (86%) had a clinical history of myocardial infarction. Coronary artery bypass surgery was performed in 18 patients and angioplasty in the remainder. All underwent ECG-gated and non-gated SPET at rest and after intravenous dipyridamole. Two-dimensional echocardiography was performed at a mean of 27 days before revascularization and at a mean of 69 days following revascularization to assess segmental wall motion changes. Perfusion prior to revascularization was analysed qualitatively and quantitatively on gated and non-gated SPET, and the results compared with those of echocardiography. Bullseye parameters were obtained from a normal database, generated from data in 40 normal volunteers, using dipyridamole ECG-gated and non-gated sestamibi SPET. There was good concordance between gated and non-gated qualitative analysis (79% with kappa=0.65) for normal, viable or necrotic segments. Gated SPET predicted functional recovery in 27 of 35 (77%) segments showing echocardiographic improvement while non-gated SPET did so in 30 of 39 (77%) such segments. Gated SPET predicted no functional recovery in 20 of 45 (44%) segments that did not show improved wall motion after revascularization, while with non-gated SPET the figure was 18 of 51 (35%). The positive predictive values of gated and non-gated SPET with regard to the recovery of wall motion following revascularization were 52% and 48%, while the negative predictive values were 71% and 67%, respectively. 99mTc-sestamibi had a low predictive value for recovery of function if visual assessment was used in the analysis of SPET data. Quantitative bullseye sestamibi parameters (defect extension and severity, reversibility and percentage change in extension), from gated or non-gated studies, appear best to distinguish which segments will display improved motility on the echocardiogram after revascularization. The addition of ECG gating does not significantly increase the predictive value of SPET imaging with regard to recovery of function.

Angioplasty, Balloon, Coronary↗
PubMed1996

Bone marrow transplantation in chronic granulomatous disease.

UNLABELLED: We present a 5-year-old boy with a severe form of X-linked chronic granulomatous disease and hypersensitivity to sulphamides preventing prophylaxis with trimethoprim-sulphomethoxazole. Bone marrow transplantation was performed after preconditioning with busulphan and cyclophosphamide. The immediate post-transplant period was without complications. Complete chimerism was demonstrated and post-transplant oxidative metabolism was normal. The patient is asymptomatic 30 months after the graft. CONCLUSION: Bone marrow transplantation in cases of chronic granulomatous disease is controversial, although it could be useful in selected very severe cases in which prophylactic therapy is problematic.

Bone Marrow Transplantation↗
PubMed1996

The use of in vitro preparations of the isolated amphibian central nervous system in neuroanatomy and electrophysiology.

In the present study an isolated preparation of the complete anuran central nervous system (CNS) is described which can be kept alive for several days and allows tracing, immunohistochemical and electrophysiological studies. A simple perfusion chamber is being used in which the isolated CNS preparation is superfused with oxygenated Ringer. The use of an isolated CNS has many advantages including: (1) virtually all areas are easily accessible at the same time without having the problem of blood vessels that hinder access; (2) large lesions and massive tracer applications are possible without survival problems of the animal, and tracers will not be translocated by blood circulation; (3) since pulsations caused by the pressure changes of blood circulation do not occur, intracellular recordings are comparatively easy and stable; and (4) this approach offers the possibility of working on the same brain for several days by storing the preparation in a refrigerator overnight at low temperatures, thus allowing extensive utilization of a single preparation and reduction in the number of experimental animals required. Some applications to the anuran auditory system illustrate that the isolated anuran CNS is well-suited for a variety of neuroanatomical and physiological techniques.

Animals↗
PubMed1996

Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection.

Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human immunodeficiency virus type 1 (HIV-1). Comprehensive statistical analysis produced an HLA profile that predicted time from HIV-1 infection to the onset of AIDS. The profile was developed in a cohort of 139 men and evaluated in a second unrelated cohort of 102 men. In the evaluation cohort, the profile discriminated a sixfold difference between groups with the shortest and longest times to AIDS (P = 0.001). These findings support current theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV-1 and other infections.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Mortality trends in a cohort of opiate addicts, Catalonia, Spain.

BACKGROUND: Opiate addiction affects young adults whose life expectancy is reduced as a consequence of their habit. In the midst of the AIDS epidemic, the present study objective was to analyse recent overall and cause-specific mortality trends among opiate addicts in Catalonia (Spain). METHODS: Mortality was assessed retrospectively in an opiate addict cohort assembled from admissions to hospital emergency wards and drug treatment centres during the period 1985-1991. The cohort included 12 711 opiate addicts (12 045 men and 3666 women) aged 15-44 years. Overall and cause-specific mortality trends were analysed using age as the time scale and Cox regression with staggered entry determined by the age at entry in the study. Annual trends were adjusted by sex and source of entry, and were stratified by length of opiate use. RESULTS: Mortality rates increased throughout the entire period from 13.8 to 34.8 deaths per 1000 person-years, with a statistically significant increase in 1987-1988 and 1988-1989. In a model including age, gender, source of entry and length of drug use, risk increased significantly in men and for longer length of use, but not with age and for source of entry into the study cohort. The causes of death associated with high mortality rates were AIDS and the causes directly related to addiction. CONCLUSIONS: A threefold increase in mortality rates was observed during the period, mainly accounted for by AIDS and direct addiction-related causes. Length of opiate use was an important determinant of mortality.

Adolescent↗
PubMed1996

The effect of latent Mycobacterium tuberculosis infection on human immunodeficiency virus (HIV) disease progression and HIV RNA load among injecting drug users.

To examine the relationship between latent Mycobacterium tuberculosis infection and human immunodeficiency virus (HIV) disease progression, two studies were done among a cohort of HIV-infected injecting drug users. First, the decline in CD4 cell count after baseline tuberculin skin testing was prospectively compared for 37 tuberculin-positive (induration > or = 5 mm) and 284 tuberculin-negative (induration < or = 2 mm) persons. After adjustment for baseline immune function, the mean 6-month CD4 cell decline was not significantly different (34.5 vs. 45.6 cells, respectively, P = .14). Second, the plasma HIV burden at baseline skin testing was compared for 33 tuberculin-positive cases and 33 matched tuberculin-negative controls. HIV RNA was detected in 8 cases and 10 controls (odds ratio = 0.67, 95% confidence interval = 0.19-2.36). Among the 14 pairs with HIV detected in > or = 1 member, the HIV concentration was higher for the case in 4 and for the control in 10 (P = .18). These findings suggest that unlike active tuberculosis, latent M. tuberculosis infection does not hasten HIV progression.

Adult↗
PubMed1996

Human immunodeficiency virus infection and infective endocarditis among injecting drug users.

Human immunodeficiency virus (HIV) infection and infective endocarditis are serious complications of injection drug use. To determine whether HIV infection may increase the risk of endocarditis beyond that associated with drug injection, we performed a nested case-control study among injecting drug users taking part in an ongoing cohort. We identified 26 participants with infective endocarditis between cohort enrollment (in 1988-1989) and June 1992, through reviews of medical records and death certificates. We matched each endocarditis case with up to five controls (N = 120) on enrollment date, race/ethnicity, and follow-up time. Data were taken from baseline and from the one follow-up visit: the last visit before the endocarditis occurred for cases and the closest visit (+/- 3 months) for controls. We used conditional logistic regression to quantify the association between HIV serostatus at follow-up and subsequent endocarditis, after adjusting for a history of endocarditis or sepsis before enrollment, injection duration, current injection frequency, and a recent history of abscess at injection sites. Among current injectors at follow-up, the adjusted odds ratio (OR) of developing endocarditis for HIV-seropositive subjects with > or = 350 CD4 cells per microliter, compared with HIV-seronegative subjects, was 2.31 [95% confidence interval (CI) = 0.61-8.78]; the corresponding OR for HIV-seropositive subjects with < 350 CD4 cells per microliter was 8.31 (95% CI = 1.23-56.37). These data indicate that HIV-related immunodeficiency may independently increase the risk of infective endocarditis among injecting drug users.

Adult↗
PubMed1996

Evidence for an anuran homologue of the mammalian spinocervicothalamic system: an in vitro tract-tracing study in Xenopus laevis.

Evidence is presented for an anuran homologue of the mammalian spinocervicothalamic system. In vitro tract-tracing experiments with biotinylated dextran amine Xenopus laevis show that ascending spinal fibres from all levels of the spinal cord, passing via the dorsolateral funiculus, terminate in a cell area ventrolateral to the dorsal column nucleus. This cell area can be considered a possible homologue of the mammalian lateral cervical nucleus. After tracer applications to the ventral thalamus or to the torus semicircularis (both targets for somatosensory projections), the anuran lateral cervical nucleus was retrogradely labelled contralateral to the application sites. Tracer applications to the dorsolateral funiculus at the obex level and rostral spinal cord resulted in labelling of the cells of origin of the spinocervical tract. These were found, mainly ipsilaterally, in the ventral part of the dorsal horn, and were rather evenly distributed throughout the spinal cord. These data suggest the presence of an anuran homologue of the mammalian spinocervicothalamic system. A brief survey of the literature shows that such a system is much more common in vertebrates than previously thought.

Afferent Pathways↗
PubMed1996

Using length of stay and inactive days in the hospital to assess appropriateness of utilisation in Barcelona, Spain.

STUDY OBJECTIVE: To compare the level of inappropriate utilisation of a teaching hospital in two different calendar years and to analyse the relationship between changes in appropriateness of utilisation and changes in average length of stay. DESIGN: Retrospective evaluation of the medical records of patients admitted to a hospital in two periods: 1988 and 1990. SETTING: Hospital Universitari del Mar, a teaching hospital with 440 beds located in Barcelona, Catalònia, Spain. PARTICIPANTS: Medical records were randomly selected from records of adults discharged from hospital with a principal diagnosis other than normal delivery or any psychiatric condition. Altogether 750 records with complete data were reviewed for 1988 and 633 for 1990. MEASUREMENTS AND MAIN RESULTS: The appropriateness evaluation protocol (AEP) was used to assess whether or not the admission and each day of the hospital stay were appropriate. For data analysis we used the extension of logistic regression that allows quantification of within-patient clustering of inactive days. The average length of stay (LOS) was 11.7 days in 1988 and 9.5 in 1990 (p < 0.001). In contrast, the proportion of inappropriate admissions was 12% in 1988 and 19% in 1990 (p < 0.001). Among those patients who were appropriately admitted, the average odds of a given day being inactive in 1990 was no lower (OR = 1.09) than the odds in 1988, but the clustering of inactive days was significantly (p < 0.001) lower in 1990. CONCLUSIONS: In the hospital studied, a lower average length of stay was not associated with an improved level of appropriate utilisation. Policies exclusively focused on lowering LOS may not directly lead to a reduction in inappropriate hospital utilisation.

Adolescent↗
PubMed1996

Concentrations of methacholine for bronchial responsiveness according to symptoms, smoking and immunoglobulin E in a population-based study in Spain. Spanish Group of the European Asthma Study.

To assess the simultaneous effects of symptoms related to asthma, smoking, and Immunoglobulin E (IgE) on the concentrations of methacholine at which different individuals fall below 80% the FEV1 values obtained with saline, we used parametric survival methods that fit the dose-response nature of bronchial responsiveness (BR). A general population-based sample of 1,615 adults (aged 20 to 44 yr) from five cities in Spain participating in the European Community Respiratory Health Survey was studied. The total number of subjects whose FEV1 values dropped below 80% was 237 (14.7%). We found that individuals with symptoms related to asthma, whether they were smokers or nonsmokers, responded at lower concentrations of methacholine than individuals without symptoms. The greatest decrease in the concentrations of methacholine at which different percentages of individuals responded was due to symptoms among the nonsmokers (relative percentiles ranging from 0.53 to 0.76, and a 90% confidence band not containing a value one). Among individuals without symptoms, smokers responded at moderately but significantly lower concentrations than nonsmokers, whereas an apparent protective effect of smoking was seen in symptomatic individuals, owing in part to a self-selection bias. The higher the concentration of IgE, the lower were the concentrations of methacholine needed to obtain a given level of BR. Moreover, the magnitude of the decrease in methacholine concentrations leading to a response was constant over all percentages of individuals responding. The analytical methods used in the study permit the incorporation of complexities in the relationships between BR and symptoms, smoking, and IgE, and are generally applicable to situations in which a dose-response relationship occurs.

Adult↗
PubMed1996

Post-transcriptional induction of beta 1-adrenergic receptor by retinoic acid, but not triiodothyronine, in C6 glioma cells expressing thyroid hormone receptors.

Thyroid hormone (triiodothyronine; T3) has been shown to control the expression of beta 1-adrenergic receptors (beta 1-AR) in cardiac myocytes, but not in C6 glioma cells. This cell specificity has been attributed to low expression of T3 receptors and high expression of the c-erbA alpha 2 splice variant that interferes with the action of T3. To check this hypothesis we have expressed the c-erbA/thyroid hormone receptor (TR) alpha 1 gene in C6 glioma cells and investigated their response to thyroid hormone. Cells expressing TR alpha 1, but not wild-type cells, were responsive to T3 as shown by increased expression of mitochrondrial hydroxymethylglutaryl CoA synthase after T3 exposure. However, T3 had no effect on beta 1-AR gene expression in either set of cells. The beta 1-AR mRNA concentrations were, however, altered by retinoic acid (RA) treatment. Retinoic acid caused a rapid up-regulation of beta 1-AR mRNA levels that was blocked by cycloheximide. Retinoic acid did not increase the beta 1-AR gene transcription rate in run-on experiments. These results indicate an indirect post-transcriptional effect of RA. Control of beta 1-AR expression in C6 cells is also exerted at the translational level, because there was no correlation between mRNA and protein induction, as determined by radioligand binding studies. We conclude that lack of responsiveness of the beta 1-AR gene in C6 cells to T3 is not due to high expression of c-erbA alpha 2 but to undefined cell-specific factors.

Animals↗
PubMed1996

Temporal patterns of aflatoxin-albumin adducts in hepatitis B surface antigen-positive and antigen-negative residents of Daxin, Qidong County, People's Republic of China.

Molecular epidemiological studies of populations at high risk for liver cancer have shown that hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure are two major risk factors for this disease. These etiological agents, combined with nutritional deficiencies, are important for the initiation and promotion of liver cancer in various parts of the world. In Qidong, People's Republic of China, liver cancer accounts for 10% of all adult deaths, and both HBV and AFB1 exposures are common. To study temporal and possible chemical-viral interactions in people, serum samples were collected during a longitudinal study designed to measure aflatoxin molecular biomarkers in residents of Daxin Township, Qidong City, People's Republic of China. In this study, the temporal modulation of aflatoxin adduct formation with albumin over multiple lifetimes of serum albumin was examined in both HBV-positive and HBV-negative people in two periods: September-December 1993 (wave 1) and June-September 1994 (wave 2). During the 12-week monitoring period of wave 1, 120 individuals (balanced by gender and HBV status) provided a total of 792 blood samples. AFB1-albumin adducts were detected in all but one of the serum samples. The range of binding detected by RIA in the Daxin population was 0.17-4.39 pmol AFB11/mg albumin with an overall mean +/- SD of 1.51 +/- 0.21 pmol AFB11/mg albumin. The mean +/- SD for weeks 0, 2, 4, 6, 8, 10 and 12 of wave 1 were 1.21 +/- 0.41, 1.58 +/- 0.70, 1.36 +/- 0.52, 1.71 +/- 0.44, 1.18 +/- 0.60, 2.00 +/- 0.59, and 1.68 +/- 0.34 pmol AFB1/mg albumin, respectively. During wave 2, 103 individuals from wave 1 provided a total of 396 blood samples collected monthly over wave 2, with mean +/- SD aflatoxin-albumin adduct levels of 1.19 +/- 0.37, 0.85 +/- 0.45, 0.89 +/- 0.28, and 0.61 +/- 0.15 pmol AFB1/mg albumin. Using linear regression models, the mean aflatoxin-albumin adduct levels increased (P < 0.05) during the 12 weeks of wave 1 and decreased (P < 0.05) over the 4 months of wave 2. Neither HBV surface antigen status nor gender modified either the baseline mean or the temporal trend. High-performance liquid chromatography confirmation was done on a subset of serum samples, and the results show an excellent association between the immunoassay data and high-performance liquid chromatography. Taken together, these data demonstrate that AFB1-albumin is a sensitive and specific biomarker for assessing exposure to this carcinogen in the population in Qidong.

Adult↗