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Biomedical subjects

A Muñoz

Publications and source records attributed to A Muñoz.

At least 415 records · Page 23Linked to original sources

The unseen sample in cohort studies: estimation of its size and effect. Multicenter AIDS Cohort Study.

Recruitment of disease-free subjects into cohort studies and measurement of their time from exposure/infection to disease selectively excludes individuals (the unseen sample) who had earlier exposure and who have shorter times to disease. The unseen and observed samples may differ in other characteristics in addition to incubation period and exposure/infection time. For data with known truncation times, we develop non-parametric maximum likelihood estimates of the size, exposure/infection dates and distribution of incubation time in the unseen sample. We provide procedures to estimate and compensate for the biasing effects due to exclusion of the unseen sample in descriptive and survival analysis. We give consistency properties of these estimates and assess variability using bootstrap methods. One can use imputation to derive the above estimates from data with unknown truncation times that have been estimated parametrically. Application is made to an AIDS cohort study of over 5000 homosexual men. Important estimates obtained from this application are the annual seroconversion rates from 1978 to 1983, not otherwise obtainable in this study population.

Acquired Immunodeficiency Syndrome↗

HIV seroconversion and disinfection of injection equipment among intravenous drug users, Baltimore, Maryland.

To examine the putative protective effect of disinfectant use on HIV seroconversion among intravenous drug users, we conducted a nested case-control study comparing 22 black heterosexual HIV seroconverters with 95 persistent seronegatives matched on gender, use of cocaine, date of study entry, and duration of follow-up. For intravenous drug users who reported using disinfectant all the time, the odds of seroconversion was 0.77 (95% CI: 0.25-2.38) compared with those who reported no use of disinfectants; for those who used disinfectants some of the time, the corresponding odds ratio was 0.91 (95% CI: 0.26-3.31). The odds ratio for use of disinfectant all the time was 0.63 (95% CI: 0.10-3.91) for those injecting at galleries and 1.08 (95% CI: 0.35-3.11) for those not injecting at galleries. These data suggest a limited protective effect of disinfectant use in the field which may be more beneficial to those injecting in shooting galleries.

Adult↗

Increased CD5-positive B lymphocytes in type I diabetes.

CD5+ B lymphocytes have been implicated in the production of polyspecific and monospecific antibodies that bind self-antigens, and increased proportions of this B cell subset occur in patients with some autoimmune diseases. We investigated the proportion of peripheral blood CD5+ B lymphocytes in type I diabetic patients. Compared with 18 age-matched healthy subjects, 11 out of 28 (39.2%) type I diabetic patients had increased proportions of circulating CD5. B lymphocytes with no alterations in the numbers of circulating B and T lymphocytes. Although all patients with increased CD5 B lymphocytes also had serum islet cell antibodies and/or insulin autoantibodies, the occurrence of increased proportions of CD5+ B lymphocytes and serum autoantibodies was not significantly correlated. Increased proportions of CD5+ B lymphocytes was not related to the time elapsed since the clinical onset of diabetes. In addition, regardless of being increased or normal, the proportion of CD5+ B lymphocytes appeared as a relatively constant phenotype after 1 year of follow-up studies at 3-month intervals in eight patients. Although the significance of these findings remains to be established, the possibility exists that CD5+ cells play a role in the pathogenesis of type I diabetes.

Adolescent↗

Acute renal failure in visceral leishmaniasis.

We describe the case of a 33-year-old male patient with an acute visceral leishmaniasis (Leishmania donovani) associated with an acute renal failure. The clinical manifestations were dominated by fever, oliguric renal failure and hepatic alterations. Serum C3 and C4 fractions of complement were decreased, and a renal biopsy demonstrated an interstitial nephritis with no glomerular involvement. The clinical course was favorable with recuperation of renal function without sequels.

Acute Kidney Injury↗

Effects of neonatal hypothyroidism on rat brain gene expression.

To define at the molecular biological level the effects of thyroid hormone on brain development we have examined cDNA clones of brain mRNAs and identified several whose expression is altered in hypothyroid animals during the neonatal period. Clones were identified with probes prepared by subtractive or differential hybridization, and those corresponding to mRNAs altered in hypothyroidism were further studied by Northern blot analysis. Using RNA prepared from whole brains, no effect of hypothyroidism was found on the expression of the astroglial gene coding for glial fibrillary acidic protein. Among genes of neuronal expression, no significant alterations were found in the steady state levels of mRNAs coding for neuron-specific enolase, microtubule-associated protein-2, Tau, or nerve growth factor. N-CAM mRNA increased slightly in hypothyroid brains. In contrast a 2- to 3-fold decrease was found in the mRNA coding for a novel neuronal gene, RC3. This is the first neuronal gene known to be significantly altered at the mRNA level by thyroid hormone deprivation. The abundance of the mRNAs for the major myelin proteins proteolipid protein, myelin basic protein, and myelin-associated glycoprotein, expressed by oligodendrocytes, were also decreased in hypothyroid brains. Developmental studies on RC3 and myelin-associated glycoprotein expression indicated that the corresponding mRNAs accumulate in the brain of normal rats during the first 15-20 days of neonatal life. A similar accumulation occurred in hypothyroid brains, but at much reduced levels. The results demonstrate that thyroid hormone controls the steady state levels of particular mRNAs during brain development.

Animals↗

Serum TATI levels and clinical correlation in tumors of the head and neck.

By radioimmunoassay (RIA) we studied tumor-associated trypsin inhibitor (TATI) in 152 serum samples, divided into three groups: 35 healthy subjects, used as controls; 25 individuals with benign pathology of the ear, nose and throat (ENT) region; 92 serial samples obtained from 69 patients with malignant disease of the head and neck. The malignant ENT group were classified in four stages according to the degree of tumor activity. The TATI concentrations (mean +/- SD) were as follows: control group, 16.0 +/- 3.4; benign group, 17.1 +/- 6.7; A0, 14.8 +/- 11.5; A1, 12.1 +/- 3.5; A2, 17.01 +/- 1.4; A3, 43.0 +/- 54.9.

Biomarkers, Tumor↗

[Ewing's sarcoma in childhood: the therapeutic results].

We evaluated 27 patients with localized Ewing's sarcoma diagnosed in our hospital. In 9 cases the lesion was centroaxial and in 18 it was located in the limbs. The treatment consisted of: 1) chemotherapy with 6 drugs (vincristine, cyclophosphamide, methotrexate, bleomycin, actinomycin D and adriamycin) during one year in all patients, and 2) radiotherapy in 24 patients with a dose of 30-40 Gy in the involved bone with a 10-15 Gy superimpression on the tumor area. In 7 patients nonradical surgery followed by radiotherapy was carried out. In 2 cases with rib localization and in 1 with tibial localization and large bone destruction radical surgery was undertaken. One patient had a local relapse (femur) and six had distant metastases. The remaining 20 patients (74%) are alive and without evidence of disease, with follow-up periods ranging from 17 to 80 months (median 38 months). The estimated actuarial free from disease survival was 64% after 58 months. Sequelae of therapy were evaluated in the 12 survivors with primary localization in the limbs. In 7 cases (58%) there were minimal sequelae, in two moderate and in three there was a severe limitation, but amputation was not required in any patient. The results of our study show that the local control of the disease can be achieved in most cases without radical surgery and with an acceptable limb function.

Adolescent↗

v-erbA oncogene activation entails the loss of hormone-dependent regulator activity of c-erbA.

The v-erbA oncogene, one of the two oncogenes of the avian erythroblastosis virus, efficiently blocks erythroid differentiation and suppresses erythrocyte-specific gene transcription. Here we show that the overexpressed thyroid hormone receptor c-erbA effectively modulates erythroid differentiation and erythrocyte-specific gene expression in a T3-dependent fashion, when introduced into erythroid cells via a retrovirus. In contrast, the endogenous thyroid hormone receptor does not detectably affect erythroid differentiation. The analysis of a series of chimeric v-/c-erbA proteins suggests that the v-erbA oncoprotein has lost one type of thyroid hormone receptor function (regulating erythrocyte gene transcription in response to T3), but constitutively displays another function: it represses transcription in the absence of T3. The region responsible for the loss of hormone-dependent regulator activity of v-erbA has been mapped to the very C-terminus of c-erbA, encompassing a cluster of highly conserved amino acid residues with the potential to form an amphipathic alpha-helix.

Alpharetrovirus↗

The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter AIDS Cohort Study Group.

We assessed the risk of pneumonia due to Pneumocystis carinii in 1665 participants in the Multicenter AIDS Cohort Study who were seropositive for human immunodeficiency virus type 1 (HIV-1) but did not have the acquired immunodeficiency syndrome (AIDS) and were not receiving prophylaxis against P. carinii. During 48 months of follow-up, 168 participants (10.1 percent) had a first episode of P. carinii pneumonia. The risk was greatly increased in participants with CD4+ cell counts at base line of 200 per cubic millimeter or less (relative risk, 4.9; 95 percent confidence interval, 3.1 to 8.0). Although most participants (60.7 percent) described no HIV-1-related symptoms at the clinic visit at which a CD4+ cell count of 200 per cubic millimeter or less was first noted, this finding during follow-up was also associated with an increased risk of P. carinii pneumonia. The development of thrush or fever significantly and independently increased the risk of P. carinii pneumonia in these patients (adjusted relative risks, 1.86 and 2.15 for thrush and fever, respectively). Most participants with CD4+ cell counts above 200 per cubic millimeter who had P. carinii pneumonia within six months were symptomatic. We conclude that P. carinii pneumonia is unlikely to develop in HIV-1-infected patients unless their CD4+ cells are depleted to 200 per cubic millimeter or below or the patients are symptomatic, and therefore that prophylaxis should be reserved for such patients.

Adolescent↗

Estimating the distribution of times from HIV seroconversion to AIDS using multiple imputation. Multicentre AIDS Cohort Study.

Multiple imputation is a model based technique for handling missing data problems. In this application we use the technique to estimate the distribution of times from HIV seroconversion to AIDS diagnosis with data from a cohort study of 4954 homosexual men with 4 years of follow-up. In this example the missing data are the dates of diagnosis with AIDS. The imputation procedure is performed in two stages. In the first stage, we estimate the residual AIDS-free time distribution as a function of covariates measured on the study participants with data provided by the participants who were seropositive at study entry. Specifically, we assume the residual AIDS-free times follow a log-normal regression model that depends on the covariates measured at enrolment on the seropositive participants. In the second stage we impute the date of AIDS diagnosis for the participants who seroconverted during the course of the study and are AIDS-free with use of the log-normal distribution estimated in the first stage and the covariates from each seroconverter's latest visit. The estimated proportions developing AIDS within 4 and within 7 years of seroconversion are 15 and 36 per cent respectively, with associated 95 per cent confidence intervals of (10, 21) and (26, 47) per cent. We discuss the Bayesian foundations of the multiple imputation technique and the statistical and scientific assumptions.

AIDS Serodiagnosis↗

Factors associated with AIDS and AIDS-like syndrome among homosexual and bisexual men in Minas Gerais, Brazil.

A case-control study to determine factors associated with AIDS and AIDS-like syndrome among homosexual/bisexual men was conducted in the State of Minas Gerais (Brazil). Eighty-three per cent (45 patients) of all AIDS/AIDS-like syndrome cases in homosexual/bisexual men reported in Minas Gerais between February, 1986 and June, 1987 were compared to 133 seronegative controls seen at the same clinic. Blood samples were tested by ELISA and confirmed by Western blot. Sex with men from the USA, sex with someone who developed AIDS, number of male partners (greater than or equal to 100 lifetime), age (greater than or equal to 30 years old) and ethnicity (white) were independently associated with AIDS/AIDS-like syndrome (Odds Ratios = 5.5, 4.3, 3.9, 3.5 and 2.7, respectively). Thirty-nine per cent of cases and 44% of controls reported bisexual activity during the previous two years. From these, a high proportion reported anal intercourse with women in the same period (53% of bisexual cases and 33% of bisexual controls). Bisexual men had more male partners than female partners in the previous two years (median male partners = 20 for cases and five for controls; median female partners = three for both cases and controls). This explains in part why the epidemic has increased more rapidly among men then among women in Minas Gerais, despite the large proportion of bisexuals with the disease.

AIDS-Related Complex↗

Association of drug injection patterns with antibody to human immunodeficiency virus type 1 among intravenous drug users in Baltimore, Maryland.

During 1988 and 1989, intravenous drug users recruited through extensive community outreach efforts in Baltimore, Maryland, were interviewed about drug injection and sex practices in the prior 11 years, with screening for antibody to human immunodeficiency virus type 1 (HIV-1). Neither interviewers nor subjects were aware of HIV-1 serostatus until 2 weeks after the interview. Among 2,616 intravenous drug users who last injected drug within the same calendar year as screening, HIV-1 seroprevalence was 30.1% for those with any use of shooting galleries, 23.3% for those who shared needles but did not use shooting galleries, and 16.3% for drug users who denied both needle-sharing and gallery use between 1977 and 1987. Among 608 drug users who reported persistent use of shooting galleries since 1977 or subsequent initiation into drug use, there was a tendency for HIV-1 seroprevalence to increase with more recent onset of an injection career. Combined with a milder but similar tendency among 739 drug users who reported persistent sharing of needles, and a seroprevalence of 15.1% among participants who had just started injecting drugs in the 18 months prior to baseline, these data provide indirect evidence that a high risk for HIV-1 infection might occur early during a drug injection career.

Acquired Immunodeficiency Syndrome↗