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Biomedical subjects

M E Paul

Publications and source records attributed to M E Paul.

15 recordsLinked to original sources

Identification and first report of Inonotus (Phellinus) tropicalis as an etiologic agent in a patient with chronic granulomatous disease.

Although isolates of filamentous basidiomycetes can usually be recognized in a clinical laboratory setting, identification is problematic, as they seldom exhibit diagnostic morphological features formed in nature. This paper is the first report of Inonotus (Phellinus) tropicalis inciting human disease and describes the methods used to support the identification.

Adult↗

Comparison of CD8(+) T-cell subsets in HIV-infected rapid progressor children versus non--rapid progressor children.

BACKGROUND: CD8(+) T-cell subsets have not been adequately described in HIV-infected (HIV(+)) children classified with respect to disease progression as rapid-progressors (RPs) and non-rapid progressors (non-RPs). OBJECTIVE: The purpose of this investigation was to determine the distribution of CD8(+) T-cell subsets in HIV(+) children and correlate the findings with degree of immunosuppression and HIV viral burden. METHODS: By means of 3-color flow cytometry, percentages of CD38(+)DR(+), CD28(+), and CD57(+) CD8(+) T-cell subsets were examined in RP (n = 15) and non-RP (n = 36) HIV(+) children and in HIV-exposed but uninfected (n = 11) and HIVunexposed (n = 8) children. The CD8(+) T-cell subsets were correlated with mean CD4(+) T-cell percentages and HIV RNA levels. Analysis of covariance was used for group comparisons for the control of the covariate of age. RESULTS: The HIV-exposed and HIV-unexposed controls were not different from each other in CD8(+) T-cell subset percentages, except that the DR(-)CD38(+)CD8(+) T-cell percentages were higher in the exposed controls than in the unexposed controls. RPs had a higher mean percentage of DR(+)CD38(+)CD8(+) T cells than non-RPs and both control groups, and RPs had higher viremia than non-RPs. CD38(+)CD8(+) T-cell percentages did not correlate with viral burden as it has been seen to do in HIV(+) adults. Percentages of CD28(+)CD8(+) T cells were lower in HIV-infected children than in controls. There was a positive correlation of percentage of CD28(+)CD57(-)CD8(+) T cells with CD4(+) T-cell percentages in each HIV-infected group. CONCLUSION: CD8(+) T cells become activated (dual expression of DR and CD38) and lose CD28, some acquiring CD57, in relation to rapidity of disease progression in pediatric HIV infection.

ADP-ribosyl Cyclase↗

Objective measures of allergic disease in children with human immunodeficiency virus infection.

BACKGROUND: Available information suggests that IgE levels are elevated in adults infected with human immunodeficiency virus (HIV), and that increased IgE levels correlate with allergic disease, with decreased CD4 counts, and with a poor prognosis. Data with respect to these factors in children are scant. OBJECTIVE: We investigated whether serum IgE levels are elevated in children with HIV and, if so, whether the serum IgE level correlates with the degree of immunodeficiency and/or objective indicators of allergic disease. METHODS: Serum IgE levels, CD4 counts, absolute eosinophil counts, and immediate hypersensitivity skin test (IHST) results were collected from 43 children with symptomatic HIV infection (mean age 7.2 years). Associations between serum IgE levels, CD4 counts, and eosinophil counts were investigated by multiple stepwise linear regression analysis. Data were stratified according to IHST positivity, and analysis of variance was used to compare mean values for age, CD4 counts, IgE levels, and eosinophil counts between the two groups. RESULTS: Serum IgE values were elevated more than 2 SDs above control age-matched mean values in 17 of 43 patients (40%). IHST results were positive in 12 of 43 patients (28%). CD4 counts were less than 200/mm3 in 17 of 43 patients (40%). Stepwise linear regression failed to demonstrate any correlation between serum IgE levels and either CD4 or eosinophil counts. With data divided into two groups according to IHST results (positive vs negative), analysis of variance failed to reveal significant differences between means for patient age, CD4 counts, IgE levels, or eosinophil counts. CONCLUSIONS: Our findings confirm that serum IgE levels are increased in children infected with HIV, just as in adults. However, an elevated serum IgE level did not correlate with allergic disease as measured by IHST results and eosinophil counts, nor with the degree of immune dysfunction as approximated by CD4 counts. The mechanism and significance of elevated serum IgE levels remain unclear in children with HIV, and warrant further investigation.

Acquired Immunodeficiency Syndrome↗

Characteristics of children surviving to 5 years of age or older with vertically acquired HIV infection.

The objective of this study was to examine characteristics of long-term survivors (aged 5 years or older) of vertical human immunodeficiency virus (HIV) infection. A retrospective cohort study design was employed. Forty-eight (68%) of 71 children who were born before 1990 and evaluated in our center survived to at least 5 years of age; 41 (58%) children remain alive (median age, 7.3 years). Only one (11%) of nine children with initial acquired immunodeficiency syndrome (AIDS)-defining conditions in the first year of life survived to age 5, whereas 47 (76%) of 62 children who did not have AIDS by age 1 year were alive at 5 years of age (p = .0003). Seventeen (43%) of 40 children with AIDS-defining conditions before age 5, and all 31 children without such conditions, survived to age 5 years (p = .000001). All eight children with lymphoid interstitial pneumonitis/pulmonary lymphoid hyperplasia (LIP/PLH) as their sole AIDS-defining condition survived to age 5. All 24 children who had neither an AIDS-defining condition nor severe immunosuppression by 5 years of age, and 24 (51%) of 47 children who had either or both of these findings, survived to age 5 years (p = .00008). To date, only 16 (39%) of 41 surviving children older than 5 years of age have had an AIDS-defining condition. However, true nonprogression of HIV disease (no clinical signs or symptoms; no evidence of immunosuppression) was unusual, occurring in only two (5%) of the same 41 children. In our center, most children with vertical HIV infection survive to at least 5 years of age, but the prognosis is not as good for those who experience an AIDS-defining condition or severe immunosuppression in the first 5 years of life.

Acquired Immunodeficiency Syndrome↗

Disorders of reproduction.

Human reproduction is an exceedingly complex process susceptible to insult at many stages. The targets of reproductive injury include the male and female worker as well as the conceptus. Because research into the reproductive and developmental effects of occupational exposures is relatively new, there are significant gaps in our knowledge of specific agents, their mechanisms of action, and their adverse effects. At the same time, workers increasingly are turning to their primary health care providers with concerns about potential reproductive hazards. Evaluation of patients includes identifying occupational agents with suspected reproductive or developmental effects, defining exposure parameters, and making estimates of risk based on the best available data. Management includes patient counseling and intervention to decrease hazardous exposures through workplace controls or temporary job transfers and leaves. By taking an occupational history, identifying possible work-related problems, and making appropriate referrals, primary care physicians can have an important role in the diagnosis, treatment, and prevention of adverse reproductive outcomes.

Abortion, Spontaneous↗

Evidence for tight coupling of receptor occupancy by thyrotropin-releasing hormone to phospholipase C-mediated phosphoinositide hydrolysis in rat pituitary cells: use of chlordiazepoxide as a competitive antagonist.

Chlordiazepoxide (CDE) has been shown to antagonize the effects of TRH to stimulate the hydrolysis of phosphoinositides and elevate cytoplasmic free calcium in rat pituitary tumor (GH3) cells. Herein, we show that CDE inhibits TRH stimulation of PRL secretion and that the effect of CDE to antagonize TRH action is caused by its ability to compete with TRH for binding to receptors on GH3 cells. We also use CDE to explore whether continued receptor occupancy is required for prolonged stimulation of cellular responses. CDE had no effect on basal PRL secretion, but caused a dose-dependent inhibition of TRH-induced PRL secretion. CDE decreased the affinity of TRH binding to intact GH3 cells without affecting the maximum binding capacity. As shown previously, CDE had no effect on phosphoinositide metabolism, which was monitored because it appears to be a mechanism for signal transduction by TRH, and when added simultaneously with TRH, caused a dose-dependent inhibition of TRH-induced phosphoinositide metabolism. When CDE was added to cells 2.5 or 5 min after TRH, CDE rapidly terminated the stimulation by TRH of phosphoinositide hydrolysis, shown as inhibition of the continued formation of inositol phosphates and inositol, and of the decrease in phosphoinositides. Lastly, when cells were stimulated with 50 nM TRH, then exposed to 100 microM CDE, and finally to 1000 nM TRH, inositol phosphate formation was stimulated, then inhibited, and then restimulated. These data demonstrate that CDE acts as a competitive antagonist of TRH action on GH3 cells by competing with TRH for binding to its receptor and that continued stimulation by TRH of phospholipase C-mediated hydrolysis of phosphoinositides is tightly coupled to receptor occupancy.

Animals↗

Delayed primary closure in colon operations.

Secondary closure of incisions by tape is a simple, safe procedure. In a retrospective series of 179 contaminated surgical wounds (incisions for colon operations) delayed wound closure resulted in a lower incidence of wound infection (5.8%) than did primary closure of similar wounds (11.8%). Although wounds left open do become infected, the acute swelling and systemic signs typical of an infection in a closed wound never develop. Delayed closure facilitated wound healing in hospital: only 3.8% of patients thus treated left hospital with open wounds, but 9.5% of patients whose wounds were closed primarily left hospital with wounds that were partially or completely open.

Anti-Bacterial Agents↗

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. II. Female reproductive disorders.

Members of the workgroup on female reproductive disorders discussed methods to evaluate five principal functions: menstrual dysfunction, infertility, pregnancy loss, lactation disorders, and pregnancy complications. To test each function, a nested strategy was considered, based on progressive levels of effort available to conduct field investigations. This strategy was analogous to the three-tier classification of biomarkers used by other workshops. The lowest level of effort, corresponding to Tier 1, consists only of questionnaires, diaries, and reviews of maternal and infant medical records. The medium level of effort (Tier 2) collects data from questionnaires and diaries, and some biologic specimens. Suggested laboratory analyses included measurement of progesterone in saliva and several glycoprotein hormones in urine that evaluate menstrual dysfunction, infertility, and pregnancy loss. The highest level of effort (Tier 3) involves prospective collection of diary information and simultaneous collection of biological specimens.

Abortion, Spontaneous↗

Reproductive fitness and risk.

Increased attention to issues related to reproductive fitness and risk are related to two factors: first, public and scientific concerns about the problem of human reproductive dysfunction and second, economic concerns. The author discusses reproductive fitness related to job tasks and reproductive risk, including clinical considerations, risk evaluation, and policy considerations.

Breast Feeding↗