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Biomedical subjects

A Muñoz

Publications and source records attributed to A Muñoz.

At least 361 records · Page 20Linked to original sources
PubMed1993

Tracking of markers and onset of disease among HIV-1 seroconverters.

Repeated measurements on persons infected with HIV-1 indicate that infection has a dynamic impact on several markers of immune suppression and activation. The objectives of this report are: (a) to provide a statistical model for the correlation structure of serial measurements of immunological markers, and (b) to identify features of marker profiles associated with the timing of AIDS diagnoses. We analyse data obtained from 328 seroconverters participating in the Multicenter AIDS Cohort Study on whom the date of HIV-1 seroconversion is known within +/- 4.5 months. Immunological markers considered here are CD4 cell counts, serum beta 2-microglobulin and serum neopterin. The statistical model for HIV-related changes in markers consists of (1) a piecewise linear regression model for the trajectories of markers over time and (2) a two-parameter autocorrelation function that generalizes Markovian and simple random effects autocorrelation structures. Application of this model for marker measurements revealed a high degree of tracking, as the estimated autocorrelation function exhibited sub-exponential decay over time. Though current marker levels are most informative on future values, there is substantial information (memory) in previous measurements. A feature suggested by the analysis of groups formed according to the length of the AIDS-free period, is the sequential divergence of the CD4 trajectories where steeper declines occurred with a two-year lag prior to AIDS onset. For AIDS cases diagnosed 3-5 and 5-7 years after seroconversion, the rates of decline compared with those free of AIDS for at least 4 years were steeper by 95 and 46 per cent respectively at two years prior to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Brain-specific prostaglandin D2 synthetase mRNA is dependent on thyroid hormone during rat brain development.

We have previously described several cDNA clones whose expression is affected by thyroid hormone during rat brain development. We now report the identification of one of these, the E2 clone, as the brain-specific prostaglandin D2 (PGD2) synthetase gene. Sequence comparison shows a nearly complete identity between the 356 nucleotides of the E2 clone and nucleotides 403 to 759 of PGD2 synthetase cDNA. The pattern of E2 expression corresponds to that expected for brain specific PGD2 synthetase gene, i.e. the corresponding mRNA is not detected in any other tissue analyzed apart of the brain, and it was present at different levels in all brain regions. Hypothyroidism decreased E2 mRNA concentrations in cerebral cortex and cerebellum. Control of the level of expression of PGD2 synthetase gene may contribute the complex effects of thyroid hormone on brain development and function.

Animals↗
PubMed1993

[Allogenic bone marrow transplantation in Wiskott-Aldrich syndrome].

Two males of 3 and 3 1/2 years of age with the Wiskott-Aldrich syndrome who underwent bone marrow transplantation from an HLA compatible brother following conditioning treatment with busulphan and cyclophosphamide are described. In both patients the taking of the graft was proven by study of blood subgroups and correction of the immunodeficiency, normalization of platelet number and function and disappearance of cutaneous eczema were seen. At 3 and 1 year respectively of the transplantation the patients showed no evidence of graft versus host disease and no severe infections or hemorrhagic episodes have seen.

Bone Marrow Transplantation↗
PubMed1993

Transient intervention with oltipraz protects against aflatoxin-induced hepatic tumorigenesis.

Oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione] protects against aflatoxin B1-induced hepatocarcinogenesis in rats when fed before and during carcinogen exposure; however, such an exposure-chemoprotection intervention paradigm is not directly relevant to most human populations. To model and assess the possible efficacy of short term interventions targeted at individuals at risk for sustained exposure to aflatoxins, 175-g male F344 rats were treated daily with 25 micrograms of aflatoxin B1, p.o., for 28 days. One week after the start of aflatoxin B1 exposure, half of the animals were fed a diet supplemented with 0.075% oltipraz for 10 days; these rats were then restored to the unsupplemented AIN-76A diet for the remainder of the experimental period. Livers were analyzed 2 or 3 months after the last aflatoxin B1 dose for burden of glutathione S-transferase P (GST-P)-positive foci, as an index of presumptive preneoplastic tumors. The transient intervention with oltipraz reduced the volume percent of hepatic GST-P-positive foci by 54% (P = 0.047) and 72% (P = 0.004) at 2 and 3 months, respectively. A strong positive correlation was also observed between the extent of fibrosis in the livers of these animals and the hepatic burden of GST-P-positive foci, implying that cytotoxicity is associated with the tumorigenic process. This protection may reflect alterations in the metabolism and disposition of aflatoxin B1 induced by oltipraz. Glutathione S-transferase catalyze the detoxication of aflatoxin-8,9-oxide and were found to be rapidly induced in the livers of animals after the beginning of the oltipraz intervention. Glutathione S-transferase activity remained significantly (P < 0.05) higher until 9 days after the end of the oltipraz intervention. In contrast, levels of hepatic aflatoxin-DNA adducts were not significantly reduced until 4 days after the beginning of the intervention but remained significantly (P < 0.05) lower up to 11 days after the end of the intervention. The cumulative reduction in levels of hepatic aflatoxin-DNA adducts (approximately 25%) by the oltipraz intervention underestimated the reduction in the hepatic burden of GST-P-positive foci. The significant protection against presumptive preneoplastic tumors, despite the delay of intervention, suggests that oltipraz may exert substantial activity against the cytotoxic and autopromoting action of repeated exposures to aflatoxin B1 and supports the utility of intervention trials with oltipraz in individuals chronically consuming aflatoxin B1-contaminated foods, particularly in regions with high incidences of liver cancer.

Aflatoxin B1↗
PubMed1993

Who should be screened for HIV infection? A cost-effectiveness analysis.

BACKGROUND: The advent of effective prophylactic treatments for asymptomatic persons infected with human immunodeficiency virus has led to interest in widespread screening programs. However, the costs of screening programs and therapy are high, and the prevalence of infection above which screening becomes an appropriate use of scarce health care dollars remains undetermined. METHODS: To examine the cost-effectiveness of screening in populations with differing prevalences of infection, we developed a Markov model to compare costs and life expectancy for two strategies: (1) screening and prophylactic treatment for infected persons who have or who develop low CD4+ (T4) cell counts, and (2) no screening. Based on studies in the literature, we estimated the prevalence of HIV infection, the rate of T4-cell loss, the rates of developing the acquired immunodeficiency syndrome and Pneumocystis pneumonia stratified by T4 cell counts, the life expectancy with the acquired immunodeficiency syndrome, the efficacy of prophylactic therapies, and costs. RESULTS: In populations with a prevalence of infection more than 5%, which includes known risk groups, screening costs less than $11,000 per life-year gained. In populations with a prevalence as low as 0.15%, screening costs only $29,000 per life-year gained. Even when the efficacy of zidovudine is assumed to be limited to 3 years, screening still costs less than $40,000 per life-year gained in populations with a prevalence of 0.5% or greater. However, in populations with a very low prevalence of infection (two to 10/100,000), such as members of the general population without reported risk factors, screening costs rise to between $290,000 and $1,277,400 per life-year gained. CONCLUSIONS: When considering only direct medical benefits, screening for asymptomatic human immunodeficiency virus infection in the general population, without regard to reported risk factors or seroprevalence data, would be expensive. In populations with a prevalence of infection of 0.5% or greater, however, the cost-effectiveness of screening falls within the range of currently accepted medical practices. These results suggest that screening be offered routinely to all persons in defined populations, such as persons receiving care at hospitals or clinics, or residing in geographic areas, where the seroprevalence is 0.5% or more, and underscore the need to conduct seroprevalence studies to identify such populations.

AIDS Serodiagnosis↗
PubMed1993

Differences in risk factors for human immunodeficiency virus type 1 seroconversion among male and female intravenous drug users.

To examine sex-specific risk factors for human immunodeficiency virus (HIV) type 1 seroconversion among intravenous drug users, the authors conducted a nested case-control study in Baltimore, Maryland, from 1988 to 1992 comparing 146 seroconverters and 539 HIV seronegative controls. Controls were matched on sex, race, date of study entry, and duration of follow-up. Risk factor data were obtained from interviews conducted at the first seroconversion visit for the case and the closest visit for the corresponding seronegative control. Since test results were not available until several weeks after interview, both interviewers and participants were unaware of seroconversion status at the time of interview. When data were analyzed using conditional logistic regression techniques, the variables which were significantly associated with seroconversion among male intravenous drug users included age less than 35 years, a sexually transmitted disease within the past 6 months, lifetime history of syphilis, and current intravenous drug use with an abscess at the injection site. Among women, only a history of three or more sex partners was positively associated with seroconversion and having a biological child under age 18 years was inversely associated with HIV seroconversion. Although the small sample size may have limited the ability to ascertain differences in risks of seroconversion among males and females, these data suggest that sexual transmission contributes to HIV infection among intravenous drug users, especially women.

Adult↗
PubMed1993

Trends in the incidence of outcomes defining acquired immunodeficiency syndrome (AIDS) in the Multicenter AIDS Cohort Study: 1985-1991.

Incidence of clinical outcomes defining acquired immunodeficiency syndrome (AIDS) may be expected to change as a consequence of progressive immunosuppression and use of chemoprophylaxis before the onset of AIDS. Using Poisson regression methods, we examined trends in the incidence of initial and secondary AIDS-defining illnesses from 1985 to 1991 among 2,627 homosexual men participating in the Multicenter AIDS Cohort Study who were seropositive for human immunodeficiency virus type 1. The incidence of Pneumocystis carinii pneumonia rose steeply until 1987 but has declined since then (p < 0.001), while the other AIDS-defining conditions have showed significant (p < or = 0.039) upward trends. Trends for Kaposi's sarcoma, lymphoma, neurologic disease, and cytomegalovirus/herpes simplex virus infections were explained by progressive immunosuppression, but residual downward and upward trends were present for P. carinii pneumonia and other opportunistic infections (bacterial, fungal, and protozoal infections and wasting syndrome). Despite selection bias, those receiving P. carinii pneumonia chemoprophylaxis showed a significantly lower incidence of P. carinii pneumonia (relative risk = 0.32, 95% confidence interval 0.16-0.63), and the time trends of P. carinii pneumonia were explained by progressive immunosuppression and use of prophylaxis. No significant effects on all other diagnoses were seen in those selected to receive antiretroviral therapy. Secondary diagnoses showed a strongly significant (p < 0.001) increase in non-P. carinii pneumonia and non-Kaposi's sarcoma among those with initial diagnoses of Kaposi's sarcoma. Overall, the trend observed in the incidence of other opportunistic infections underscores the need for developing and testing new strategies to curtail or delay the onset of these diseases.

AIDS-Related Opportunistic Infections↗
PubMed1993

Clinical factors associated with weight loss related to infection with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study.

The relation between a number of potential risk factors and change in body mass index per semester was examined in a community-based cohort of 1,809 homosexual and bisexual men seropositive for human immunodeficiency virus type 1 (HIV-1). The men were followed semiannually for up to 6.5 years between 1984 and 1990. A total of 9,735 person-semesters of observations were available for analysis. A Markov-type autoregressive model, adjusting for previous body mass index, was used to predict the change in body mass index over each person-semester. Overall, the cohort was gaining weight. An asymptomatic participant 1.8 m in height whose CD4+ cell count was > 750/microliters gained a mean of 0.5 kg each person-semester. In bivariate autoregressive models, diarrhea, fever, oral thrush, acquired immunodeficiency syndrome (AIDS), and CD4+ lymphocyte counts of < 100 and 100-199 cells/microliters were all associated with a significant decrease in body mass index. A significant inverse association was also found between change in body mass index and lymphadenopathy and herpes zoster, but when the intercept coefficient was added, no overall decrease in body mass index was seen in these models. In a final multivariate model, diarrhea was less strongly associated with a change in body mass index (p = 0.057), although AIDS (p = 0.009), fever (p = 0.006), thrush (p = 0.002), and a CD4+ lymphocyte count of < 100 cells/microliters (p < 0.001) all remained independently associated with a decrease in body mass index. Lymphadenopathy and a CD4+ lymphocyte count of 100-199 cells/microliters were also significant covariates in the final model, but neither of the beta coefficients exceeded that of the intercept, indicating that they were not independently associated with a decrease in body mass index. These findings suggest that the importance of diarrhea as a cause of HIV-related weight loss may have been over-estimated in previous clinic-based studies. AIDS and nonspecific markers of progression (fever, thrush, and a CD4+ count of < 100 cells/microliters) were the best predictors of weight loss during a semester.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Trigeminal primary afferent projections to the spinal cord of the frog, Rana ridibunda.

The distribution in the spinal cord of the trigeminal primary projections in the frog Rana ridibunda was studied by means of the anterograde transport of horseradish peroxidase (HRP). Upon entering the medulla via the single trigeminal root, a conspicuous descending tract that reaches the cervical spinal cord segments is established. This projection arises in the ophthalmic (V1), maxillary (V2), and mandibular (V3) trigeminal nerve subdivisions. In the spinal cord, only a minor somatotopic arrangement of the trigeminal fibers was observed, with the fibers arising in V3 terminating somewhat more medially than those from V1 and V2. A dense projection to the medial aspect of the spinal cord, above the central canal, primarily involves V3. Each trigeminal branch sends projections at cervical levels to the contralateral dorsal field, and those from V2 are most abundant. Bilateral experiments with HRP application show convergence of primary trigeminal and spinal afferents within the dorsal field of the spinal cord. The pattern of arrangement of the trigeminal primary afferent fibers in the spinal cord of this frog largely resembles that of amniotes. However, the organization seems simpler and the slight somatotopic distribution of V1, V2, and V3 fibers is similar to the condition in other anamniotes.

Afferent Pathways↗
PubMed1993

A comparison of risk factors for human immunodeficiency virus and hepatitis B virus infections in homosexual men.

We analyzed cross-sectional data from 1062 homosexual men recruited in Baltimore during 1984, to directly compare risk factors for human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Using polychotomous logistic regression, risk factor odds ratios (ORs) and 95% confidence intervals were determined for men with HIV alone, men with HBV alone, and men with both HIV and HBV, compared to seronegative men, and paired comparisons among these subgroups. Factors associated with the serologic prevalence of HIV alone and HBV alone (with respective ORs) included and receptive intercourse (HIV OR = 1.23; HBV OR = 1.12), history of gonorrhea (HIV OR = 4.58; HBV OR = 2.52), and rectal douching (HIV OR = 1.41; HBV OR = 1.20). Additional factors associated with HBV alone were years of homosexual activity (OR = 1.65), sexual activity with a person who developed acquired immunodeficiency syndrome (AIDS) (OR = 1.98), and lifetime number of male sex partners (OR = 1.25). HIV and HBV coprevalence was associated with anal receptive intercourse (OR = 1.36), history of gonorrhea (OR = 2.94), rectal douching (OR = 1.45), sexual activity with a person who developed AIDS (OR = 3.87), lifetime number of male sex partners (OR = 1.21), and the lifetime sum of sexually transmitted diseases (OR = 1.47). These findings reinforce the need for following safer-sex guidelines to prevent both infections and in the case of HBV, the prevention strategies should include vaccination.

Adult↗
PubMed1993

Thyroid hormone receptor/c-erbA: control of commitment and differentiation in the neuronal/chromaffin progenitor line PC12.

The c-erbA proto-oncogenes encode nuclear receptors for thyroid hormone (T3), a hormone intimately involved in mammalian brain maturation. To study thyroid hormone receptor (TR) action on neuronal cells in vitro, we expressed the chicken c-erbA/TR alpha-1 as well as its oncogenic variant v-erbA in the adrenal medulla progenitor cell line PC12. In the absence of T3, exogenous TR alpha-1 inhibits NGF-induced neuronal differentiation and represses neuron-specific gene expression. In contrast, TR alpha-1 allows normal differentiation and neuronal gene expression to occur in the presence of T3. Finally, TR alpha-1-expressing cells become NGF-responsive for proliferation when T3 is absent, but NGF-dependent for survival in presence of T3. A similar differentiation induction by NGF plus T3 was observed in a central nervous system-derived neuronal cell line (E 18) expressing exogenous TR alpha-1. Together with the finding that TR alpha-1 constitutively blocked dexamethasone-induced differentiation of PC12 cells into the chromaffin pathway, these results suggest that TR alpha-1 plays an important role in regulating commitment and maturation of neuronal progenitors. In contrast, the v-erbA oncogene, a mutated, oncogenic version of TR alpha-1, partially but constitutively inhibited NGF-induced neuronal differentiation of PC12 cells and potentiated dexamethasone-induced chromaffin differentiation, giving rise to an aberrant "interlineage" cell phenotype.

Animals↗
PubMed1993

Interaction of lectins with Cryptosporidium parvum.

Cell surface carbohydrates from four clinical isolates of Cryptosporidium parvum were analyzed by agglutination assays using a battery of 20 highly purified lectins with affinity for receptor molecules containing N-acetyl-D-glucosamine (GlcNAc), N-acetyl-D-galactosamine, galactose, mannose, glucose, fucose, and N-acetyl-neuraminic acid. Tomentine, a lectin from the green seaweed Codium tomentosum, and UEA-II lectin, from Ulex europeus, both of them GlcNAc-specific lectins, agglutinated the oocysts. Subsequent inhibition assay confirmed the presence of this sugar on the surface of Cryptosporidium parvum oocysts. Codium fragile lectin, from another green seaweed, also exhibited agglutination activity against the oocysts. This is the first published demonstration of such an interaction between a human coccidian and lectins from seaweeds.

Animals↗
PubMed1993

Detection of human immunodeficiency virus type 1 infection by polymerase chain reaction in a cohort of seronegative intravenous drug users.

The frequency of serologically undetected human immunodeficiency virus type 1 (HIV-1) infection among a large cohort of seronegative intravenous drug users (IVDUs) was determined by polymerase chain reaction (PCR). In total, 2159 blood specimens were obtained from 945 seronegative IVDUs; of these, 182 had 1 specimen, 339 had 2, 397 had 3, and 27 had 4 semiannual specimens. No proviral DNA was detected in 2134 (98.8%) of the samples. Specimens from 7 persons (0.3%) were reactive by PCR. Within 6 months, all 5 of these 7 who returned for follow-up visits had seroconverted. Serum from 19 persons (0.9%) were equivocal by PCR analysis, that is, single primer pair amplification; 1 person seroconverted while others subsequently remained seronegative and nonreactive by PCR. The concordance between PCR and serology was 98.6%. It is concluded that immunosilent HIV-1 infection is uncommon and that serologic screening for HIV-1 antibodies is highly sensitive in this population.

Adolescent↗
PubMed1993

Elevated serum levels of neopterin but not beta 2-microglobulin in HIV-1-seronegative injecting drug users.

OBJECTIVE: To determine whether injecting drug use is associated with cellular immune activation in the absence of HIV-1 infection. DESIGN: Serum levels of neopterin and beta 2-microglobulin (beta 2M) were measured cross-sectionally in injecting drug users (IDU) enrolled in a prospective study. SUBJECTS AND METHODS: Two hundred and nineteen HIV-1-seronegative, healthy heterosexual black male IDU aged 21-49 years were selected from the Baltimore-based AIDS Linked to Intravenous Experiences (ALIVE) study. The possibility of including subjects in the process of seroconverting to HIV-1 was minimized by restricting the study to individuals who remained seronegative 6 months after the specimens used for analysis were collected. RESULTS: Mean serum beta 2M levels were not statistically different among groups of IDU whose usual pattern of injection was at least once a day for up to 3 consecutive days (daily users; n = 65), less than once per day (less-than-daily users; n = 75), or not at all for at least 2 weeks (non-recent users; n = 79). In contrast, the mean neopterin level was significantly (P = 0.039) greater in daily users (6.17 nmol/l) than in the other two groups (5.07 and 5.19 nmol/l, respectively, which were not statistically different). These results were not affected, by the frequency of using borrowed non-sterile works or by other demographic and risk factor variables. CONCLUSIONS: Frequent injecting drug use may be independently associated with a small elevation of serum neopterin levels, but not beta 2M levels. Although the occurrence of a type I error in this sample cannot be completely excluded, serum neopterin may be more sensitive than serum beta 2M in detecting activation of immunocompetent cells associated with frequent injecting drug use in this population.

Adult↗
PubMed1993

Laryngeal carcinoma: sclerotic appearance of the cricoid and arytenoid cartilage--CT-pathologic correlation.

PURPOSE: To assess the significance of sclerotic-appearing cricoid and arytenoid cartilage with computed tomography (CT) in patients with laryngeal carcinoma. MATERIALS AND METHODS: CT scans obtained in 75 patients with laryngeal carcinoma were prospectively studied; laryngeal CT studies obtained in 50 patients without laryngeal carcinoma were retrospectively reviewed. RESULTS: Twenty-four of the 75 patients (32%) with laryngeal carcinoma had sclerotic cartilage. Evaluation of pathologic specimens obtained in 12 of these 24 patients showed 11 cases of sclerotic arytenoid cartilage and two cases of sclerotic cricoid cartilage. Tumor infiltration was demonstrated in six of these cases but not in the seven others. In 11 of the 12 cases with pathologic proof, however, tumor was adjacent to the perichondrium. In the 12 cases without pathologic proof, the proportion was similar. The positive predictive value of this sign for cartilaginous invasion was 46%. CONCLUSION: Although it is not a reliable sign of cartilaginous invasion, sclerotic-appearing cricoid and arytenoid cartilage in patients with laryngeal carcinoma is predictive of the tumor to this cartilage.

Adult↗