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Biomedical subjects

W D Johnson

Publications and source records attributed to W D Johnson.

At least 55 records · Page 3Linked to original sources

A community support group for HIV-seropositive drug users: is attendance associated with reductions in risk behaviour?

Although support groups for HIV-seropositive persons are a potential source of emotional support and information, there has been little assessment of such groups as to their role in changing risk behaviour for transmission. The present study combines observations from over 52 group sessions with baseline and follow-up interview data to assess changes in sex and drug behaviour among seropositive drug users participating in an ongoing group for African Americans. The sample of 100 adults was recruited from drug treatment centres and from the community in Atlanta, Georgia. At the 6-month interview, frequency of group attendance was associated mainly with healthier drug behaviour, the topic most frequently discussed by members. Findings suggest that training for support group facilitators needs to target two areas for technology transfer: successful strategies for reducing both high-risk sex and drug behaviour and methods for introducing these behavioural change tools into a setting designed for socio-emotional support. We conclude that community support groups are an untapped opportunity for low-cost prevention services.

Adult↗

Sources of HIV information among injecting drug users: association with gender, ethnicity, and risk behaviour. AIDS Community Demonstration Projects.

Sources of HIV information were examined for 774 male and female injecting drug users (IDUs). The majority (80.7%) had received HIV information from one or more sources in the prior 3 months. The most frequently mentioned sources were television (39.9%) and friends or family (22.2%). There were few differences in source of HIV information with regard to gender, ethnicity, or age. Differences were more frequently observed between cities. The relationship of information source and subject characteristics with HIV knowledge, perceived risk, drug-related and sexual practices was examined using logistic regression. For men, exposure to mass media sources (OR = 1.48) and small media materials (OR = 2.03) were related to HIV knowledge. Small media and interpersonal information were related to HIV testing for men (OR = 1.95 and 1.85, respectively) and women (OR = 2.25 and 2.54). Interpersonal sources of information were also associated with increased sharing of injection equipment (OR = 2.04) and bleach use (OR = 2.23) among female IDUs. Significant differences in HIV knowledge and risk-related practices were also observed for ethnicity, city, men who have sex with men, and women who had traded sex for money or drugs. Implications for targeting HIV prevention efforts for IDUs are discussed.

Adolescent↗

Generalized estimating equations for multivariate response with the variates having different distributions.

This paper addresses the problem of analyzing multivariate response with the variates having different distributions. We use the generalized estimating equations proposed by Prentice and Zhao (1) to estimate mean and covariance parameters. Wald statistics are used to test hypotheses about the parameters. Data from a two-group study of competing programs to increase memory recall in geriatric patients are analyzed. We are interested in determining whether there is a simultaneous increase in test scores with one variate being continuous and another being dichotomous. In a second example, comparisons of before-and-after treatment serum cholesterol levels and number of snacks eaten per day are made in an experiment to determine efficacy of a program aimed at simultaneously reducing both measurements.

Cholesterol↗

Sample sizes for experiments with multivariate repeated measures.

Procedures for determining sample size in multivariate repeated measures experiments are discussed. The focus is on designs with either one group or two independent groups of subjects, the point of departure being multivariate repeated measures. Determination of the minimum sample size required is based on power considerations associated with Hotelling's T2 and the F-test. We first consider procedures for determining sample size assuming an arbitrary covariance matrix. The special case where we assume that the transformed data have a multivariate spherical covariance matrix is also considered. Tables of the minimum sample sizes required for several hypotheses from multivariate analysis are presented.

Mathematical Computing↗

Analyzing multivariate data in crossover designs using permutation tests.

Studies using crossover designs typically involve observations on a large number of response variables made on each of a relatively small number of subjects. Moreover, investigators often observe the responses longitudinally over time. As the number of variates approaches the number of subjects traditional multivariate statistics based on the concept of statistical distance often are not very powerful, and when that number exceeds the total number of subjects in the study, these tests are not defined. In these situations, statisticians frequently analyze each variate separately and adjust for the multiple testing using a technique suitable for correlated data. In the case of a single variate measured repeatedly, we often make the assumption of a patterned covariance matrix and then conduct a univariate mixed-model analysis. We discuss an alternative approach using a variety of data structures in 2 x 2 crossover designs with (1) univariate response in each treatment period, (2) multivariate response in each treatment period, and (3) longitudinal repeated measures on a single variate in each treatment period.

Cross-Over Studies↗

Comparative activity of N-(4-hydroxyphenyl)-all-trans-retinamide and alpha-difluoromethylornithine as inhibitors of lymphoma induction in PIM transgenic mice.

The activities of the retinoid, N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR) and the polyamine synthesis inhibitor, alpha-difluoromethylornithine (DFMO), as inhibitors of lymphoma induction in PIM transgenic mice were evaluated. Lymphoma was induced in male PIM mice by a single intraperitoneal injection of 50 mg N-ethyl-N-nitrosourea (ENU) per kg body weight. Continuous dietary administration of 4-HPR (391, 196 or 98 mg/kg diet) or DFMO (1000, 500 or 250 mg/kg diet) was initiated immediately after ENU administration, and was continued until the end of the study at 35 weeks. At 20 weeks post-ENU, the high dose of 4-HPR reduced both lymphoma incidence and associated mortality. However, the protection conferred by 4-HPR represented a delay rather than an inhibition of neoplastic development, since both lymphoma incidence and mortality at study termination were similar in dietary controls and all groups treated with 4-HPR. DFMO had no effect on lymphoma incidence, latency or mortality at any point in the study. These results suggest that 4-HPR or other retinoids may be effective in the prevention of lymphoma induction, whereas inhibition of polyamine biosynthesis does not appear to present a useful mechanistic target for the chemoprevention of lymphoid neoplasia. The PIM transgenic mouse provides a useful in vivo model for the rapid evaluation of chemopreventive agents.

Animals↗

Interleukin-12 restores interferon-gamma production and cytotoxic responses in visceral leishmaniasis.

American visceral leishmaniasis (AVL) is associated with the absence of lymphocyte proliferative responses and interleukin (IL)-2 and interferon-gamma (IFN-gamma) production upon stimulation with Leishmania antigen. In contrast, cure of AVL is associated with restoration of these T cell functions. In the present study, the ability of IL-12, a cytokine that acts on NK and T cells to restore cellular immune responses in AVL, was evaluated. Participants of the study included 12 patients with AVL and 7 subjects cured of AVL. The [3H]thymidine uptake and IFN-gamma production in cultures of peripheral blood mononuclear cells (from AVL patients) stimulated with Leishmania chagasi antigen were 882 +/- 1393 cpm and zero, respectively. Addition of IL-12 enhanced the proliferative response to 5097 +/- 6429 cpm (P < .001) and IFN-gamma production to 305 +/- 325 pg/mL (P < .01). IL-12 also restored cytotoxic activity against the K562 cell line. These results indicate that IL-12 has an important role in the regulation of the cellular immune response in human leishmaniasis.

Animals↗

Continuous postoperative lCBF monitoring in aneurysmal SAH patients using a combined ICP-laser Doppler fiberoptic probe.

Cerebral vasospasm remains the principal cause of morbidity and mortality following successful clipping of intracranial aneurysms. Current management often requires subjective judgments concerning presumed abnormalities of cerebral blood flow. In this study, a combined intracranial pressure (ICP)-laser Doppler flowmetry (LDF) fiberoptic probe that permits continuous monitoring of local cerebral blood flow (lCBF) was used in the postoperative management of 20 aneurysm patients. Using this probe, lCBF was simultaneously recorded and integrated on a real time basis with other physiological parameters, including ICP, systemic arterial pressure, pulmonary arterial pressure, central venous pressure, and pulse oximetry. The combined probe also provided the ability to obtain precise and detailed information concerning the presence or absence of cerebral autoregulation and CO2 vascular reactivity, and allowed calculation of the cerebral vascular resistance. Continuous monitoring of lCBF in this manner complemented by transcranial Doppler and angiographic data permitted early detection of cerebral ischemia, helped to differentiate cerebral ischemia from edema and hyperemia, was useful in titrating blood pressure and fluid management, provided direct feedback about the effectiveness of instituted therapies, and determined early on when medical management was of no avail and that interventional neuroradiology was indicated. Evidence is presented that the presence of angiographic vasospasm and increased velocities on TCD do not always correlate with ischemia in the microcirculation and that direct measurements of lCBF are often at variance with calculations of cerebral perfusion pressure (CPP).

Adult↗

Differential effects of interleukin-12, interleukin-15, and interleukin-2 on human immunodeficiency virus type 1 replication in vitro.

Cytokines may have clinical utility as therapeutic agents for human immunodeficiency virus type 1 (HIV-1) infection and as an adjuvant for vaccines. The effect of interleukin-12 (IL-12) and IL-15 on in vitro HIV-1 replication was investigated. IL-12 and IL-15 at doses up to 10 ng/ml had little effect on basal HIV-1 p24 antigen production by chronically HIV-infected T (ACH-2) and monocytic (U1) cell lines. For ACH-2 cells stimulated with phorbol 12-myristate 13-acetate (PMA; 50 ng/ml), IL-12 and IL-15 significantly increased p24 antigen production by 20 and 30%, respectively (n = 6). In contrast, IL-12 and IL-15 (10 ng/ml) treatment of PMA-stimulated U1 cells decreased p24 antigen production by 16 and 15%, respectively (n = 6). We next studied the effect of IL-12 and IL-15 on HIV-infected peripheral blood mononuclear cells (PBMCs). In 10 HIV-seropositive patients' PBMCs cocultured with mitogen-activated HIV-seronegative donor cells, two patterns of p24 antigen production were observed in response to IL-2: low (p24 antigen production < 10(3) pg/ml; n = 8) and high (p24 antigen production > 10(3) pg/ml; n = 2) response. For the low-response pattern, IL-12 and IL-15 increased viral replication by 97-fold and 100-fold, respectively (P = 0.05 and 0.004, respectively). For the high-response pattern, both IL-12 and IL-15 suppressed HIV replication. The effect of IL-2, IL-12, and IL-15 on acute in vitro infection by HIV-1JRCSF was also examined. IL-12 did not increase p24 antigen production above basal levels while IL-2 and IL-15 significantly enhanced p24 antigen production (by approximately 2-fold). In conclusion, IL-12 and IL-15 may have differential effects on latent and acute HIV infection, and their ability to enhance HIV production may depend on cell activation. Thus, the use of these cytokines may be dictated by the clinical state of the patient.

Cells, Cultured↗

Combining 2 x 2 tables that contain structural zeros.

When one cell or more of a contingency table is necessarily zero, the table is said to contain structural zeros. These structural voids may be inherent to the problem at hand, or, in some applications, they may be introduced intentionally through the experimental design. With data classified by a third stratification variable, one needs a method for analysing a set of independent 2 x 2 tables. We propose Cochran-Mantel-Haenszel type analyses that combine observations across strata. We also propose tests of hypotheses pertaining to the marginal and conditional probabilities.

Data Interpretation, Statistical↗

Neutrophils from human immunodeficiency virus (HIV)-seronegative donors induce HIV replication from HIV-infected patients' mononuclear cells and cell lines: an in vitro model of HIV transmission facilitated by Chlamydia trachomatis.

Infection with a sexually transmitted disease (STD) increases the risk for human immunodeficiency virus (HIV) infection. Polymorphonuclear leukocytes (PMNs) are recruited into the genital tract by STD pathogens, such as Chlamydia trachomatis. Semen of HIV-infected men contains HIV associated with mononuclear cells. This study investigated the interaction among PMNs from HIV-uninfected persons, C. trachomatis, and HIV-infected cells and examined the mechanisms for enhanced HIV replication. We demonstrated that PMNs from HIV-seronegative donors induced HIV replication in mononuclear cells from 17 HIV-infected patients in medium without exogenous IL-2. HIV in the cell-free supernatants from cocultures of PMNs and patients' peripheral blood mononuclear cells (PBMCs) was replication competent, as indicated by their capacity to propagate HIV in a second round of culture using PBMCs from HIV-seronegative individuals and by the fact that proviral DNA was found in these cells. PMNs from HIV-seronegative donors increased HIV replication over 100-fold in chronically HIV-infected cell lines of the monocytic, T, and B cell lineages. Moreover, PMNs increased U1 cells' production of p24 antigen by as much as ninefold when compared with U1 cells cocultured with PBMCs. The addition of C. trachomatis to PMN and U1 coculture increased HIV replication by an additional ninefold at 24 h, whereas C. trachomatis alone had no effect on p24 antigen production by U1 cells. Thus, C. trachomatis serves not only to recruit PMNs, but also to interact with PMNs to increase HIV replication. HIV replication is triggered by contact of HIV-infected cells with PMNs, by the generation of reactive oxygen intermediates (ROIs), and by soluble factors such as TNF-alpha and IL-6. This is based on the findings that production of p24 antigen, IL-6, and TNF-alpha induced by PMNs is abrogated by disrupting or partitioning PMNs from HIV-infected cells; is inhibited by superoxide dismutase and catalase, enzymes that destroy ROIs; is enhanced by differentiated HL60 cells capable of producing ROIs; and is induced by PMNs tested negative for CMV. Furthermore, the production of ROIs is independent of HIV infection of mononuclear cells, since PMNs cocultured with HIV-uninfected parental monocytic and T cell lines generated ROIs. Therefore, the increased risk for acquiring HIV infection associated with chlamydia cervicitis may be related to the local recruitment of PMNs by C. trachomatis and the induction of infectious virus from mononuclear cells present in semen. These observations provide a rationale for strategies to reduce HIV transmission by control of STD.

B-Lymphocytes↗

BUN as a risk factor for mortality after coronary artery bypass grafting.

BACKGROUND: Although information on blood urea nitrogen (BUN) is universally available for patients who undergo coronary artery bypass grafting, BUN has not often been considered as a risk factor for mortality. This study assessed BUN as a risk factor for CABG patients. METHODS: Four data sets were evaluated that differed with respect to the types of patients and available patient information. In each of these data sets logistic regression analysis was used to examine the relationship between BUN and mortality after adjusting for other risk factors. RESULTS: Blood urea nitrogen level was strongly associated with mortality in each of the data sets. After adjustment for the available risk factors other than creatinine level, patients with BUN levels greater than 30 mg/dL had a relative odds of mortality ranging between 1.86 and 2.49 (p < 0.0001 in three of the data sets). Even after adjustment for creatinine level as well as the other variables, BUN was statistically significant at the p less than 0.01 level for three of the data sets. CONCLUSIONS: The results suggest that BUN provides additional information on cardiac function that supplements the information provided by other risk factors.

Aged↗

Computerized tomography (CT) localized stereotactic craniotomy for excision of a bacterial intracranial aneurysm.

BACKGROUND: The treatment of bacterial intracranial aneurysms include long-term antibiotic therapy and surgical clipping or resection. Direct surgical approaches to these aneurysms are often complicated by their peripheral location. METHODS: We report the use of a computerized tomography (CT) localized stereotactic craniotomy for the excision of a ruptured peripheral bacterial intracranial aneurysm. RESULTS: The Leksell Steiner-Lindquist microsurgical guide, with its fiberoptic helium-neon laser, allowed for rapid isolation of the distal aneurysm with minimal cerebral dissection. Since the inflammatory lesion was well demonstrated on postcontrast CT scan, this modality, rather than angiography, was used for localization. CONCLUSIONS: In the future, stereotactic craniotomy may facilitate aggressive surgical therapy for infectious aneurysms previously thought not suitable for direct operative approach.

Adult↗