Biomedical subjects

D Hom

Publications and source records attributed to D Hom.

34 records · Page 2Linked to original sources

PubMed1996

Maternal HIV-1 RNA serum levels at delivery and vertical transmission in Uganda.

OBJECTIVE: To evaluate the clinical utility of maternal HIV-1 RNA serum levels at delivery in predicting the rate of HIV-1 vertical transmission. DESIGN AND METHODS: HIV-1 RNA levels were determined by the Roche Amplicor Monitor assay in serum specimens collected at the time of delivery from 94 transmitting and 107 nontransmitting infected mothers and 12 seronegative mothers in Uganda. Nonparametric Wilcoxon-Rank sum tests were used to identify significant differences in medians and RNA level distributions by transmission status. RESULTS: Mean HIV-1 RNA copies/mL for transmitters was 3419 +/- 7489 copies/mL versus 2483 +/- 8954 copies/mL for nontransmitters. There was a significant difference in medians and HIV-1 RNA serum level distributions between transmitting and nontransmitting mothers (p = 0.0039). However, the predictive value for any given HIV-1 RNA level for HIV-1 vertical transmission was poor. CONCLUSION: Maternal HIV-1 RNA serum levels at delivery are significantly higher in transmitting mothers versus nontransmitting mothers, but appear to be of limited value in predicting HIV-1 vertical transmission using the Roche Amplicor Monitor assay in Uganda.

Case-Control Studies↗

PubMed1995

Accelerated course of human immunodeficiency virus infection after tuberculosis.

To determine the effect of active tuberculosis on survival and the incidence of opportunistic infections in HIV-infected patients, we performed a retrospective cohort study at four U.S. medical centers to compare the survival and incidence rate of opportunistic infections in 106 HIV-infected patients with active tuberculosis (cases) with that of 106 HIV-infected patients without tuberculosis (control subjects) but with a similar level of immunosuppression (measured by the absolute CD4+ lymphocyte count) as the cases. Cases and control subjects were similar with regard to age, sex, race, previous opportunistic infection, and use of antiretroviral therapy, but they were more likely than control subjects to have a history of intravenous drug use (49 versus 19%). The mean CD4+ counts were similar for cases and control subjects (154 versus 153 cells/microliters, respectively). The incidence rate of new AIDS-defining opportunistic infections in cases was 4.0 infections per 100 person-months compared with 2.8 infections per 100 person-months in control subjects for an incidence rate ratio (RR) of 1.42 (95% confidence interval: 0.94-2.11). Cases also had a shorter overall survival than did controls subjects (p = 0.001). Active tuberculosis was associated with an increased risk for death (odds ratio = 2.17), even when controlling for age, intravenous drug use, previous opportunistic infection, baseline CD4+ count, and antiretroviral therapy. Although active tuberculosis may be an independent marker of advanced immunosuppression in HIV-infected patients, it may also act as a cofactor to accelerate the clinical course of HIV infection.

AIDS-Related Opportunistic Infections↗

PubMed1995

Pitney Bowes: using comprehensive cost information to build provider networks.

Wishing to develop a work partnership with a managed care organization, Pitney Bowes decided to select its own network providers. The company reached out to the medical community for input and participation in crafting both a clinical and a business partnership that would set new standards for health care delivery in the country. A methodology--described here--was developed for comparing medical plans and selecting providers.

Cluster Analysis↗

PubMed1994

Effect of specimen storage on absolute CD4 counts.

We have evaluated the effect of specimen storage on absolute CD4 counts by a commercially available manual assay. This assay utilizes latex particles coated with CD4 monoclonal antibodies that are mixed with lymphocytes in whole blood. Thirty blood samples were analyzed on days 1, 2, 4, and 7 postcollection. Linear regression analysis and Pearson correlation coefficients were used to determine the relationship between the absolute CD4 count and the storage time after sample collection. There was a significant decrease in absolute CD4 counts from baseline over time, dropping 3.6% at day 2, 10.1% at day 4, and 18.8% at day 7. However, the standard error of the B coefficient was constant [SE (B) = 0.031] up to day 4, indicating that reliable estimates of the baseline CD4 counts could be made from the CD4 counts determined up to day 4 from the time of sample collection. In addition to being sample, rapid, and inexpensive, the manual assay is capable of giving a reliable absolute CD4 count after specimen storage of up to 4 days. The application of this assay in the limited facilities of developing countries' laboratories is attractive.

Blood Specimen Collection↗

PubMed1994

Lack of association between anti-V3 loop antibodies and perinatal transmission of HIV-1 in Kampala, Uganda.

This study evaluated the association between reactivity of maternal antibody to human immunodeficiency virus type 1 (HIV-1) V3 loop peptides and perinatal transmission in Uganda. Plasma from 40 HIV-1-infected mothers (20 transmitting and 20 nontransmitting mothers) and 31 uninfected mothers in Uganda were tested for reactivity and antibody titer to synthetic peptides representing V3 loop sequences from HIV-1 strains MN, SF2, LAI, ZR6, and CM235 and consensus peptides CA, CB, and CD. No significant differences were found between 20 transmitting mothers and 20 nontransmitting mothers in terms of percent reactivity or titer of antibody to any of the V3 loop peptides tested. Use of a multivariable logistic model to adjust for beta-2 microglobulin level as a confounding variable of stage of infection did not help demonstrate an association except possibly for the ZR6 peptide. These data suggest that neither reactivity nor maternal antibody titer to V3 loop peptides are protective against perinatal transmission of HIV-1 in Uganda.

Acquired Immunodeficiency Syndrome↗

PubMed1993

A rapid manual method for CD4+ T-cell quantitation for use in developing countries.

OBJECTIVE: To evaluate a manual method (Cytosphere) for quantifying CD4+ T-cell numbers. DESIGN: Cross-sectional study of HIV-1-seronegative and HIV-1-seropositive individuals evaluated for absolute CD4 counts by both standardized flow cytometric measurements and manual Cytosphere technology using a hemacytometer. SETTING: University research hospitals in both the United States and Africa. PATIENTS, PARTICIPANTS: Blood specimens from 382 patients were evaluated. These were broken down into 294 samples obtained from HIV-1-seropositive patients and 88 samples obtained from HIV-1-seronegative patients. INTERVENTIONS: None. OUTCOME MEASURED: Absolute CD4 cell number. RESULTS: Evaluation of samples obtained from HIV-1 patients in both the United States and Africa demonstrated an overall correlation of the Cytosphere assay with flow cytometry of 0.912 (95% confidence interval, 0.895-0.928; P < 0.001). When samples were stratified based on CD4+ T-cell counts determined by flow cytometry, the Cytosphere assay had a 96% predictive value for correctly identifying individuals with CD4 T-cell counts > 200 x 10(6)/l and a 92% predictive value for correctly identifying individuals with CD4 T-cell counts < 200 x 10(6)/l. CONCLUSIONS: This assay appears to have the potential for the quantitation of CD4 cells in the limited laboratory facilities in developing countries and to have a strong correlation with standard flow cytometric technology.

Adult↗

PubMed1991

Nasal tip projection. Quantitative changes following rhinoplasty.

Fifty-one patients were enrolled in a study and underwent primary rhinoplasty. Serial nasal tip projection measurements were made preoperatively, intraoperatively, and 6 months postoperatively. Actual changes in measured nasal tip projection were evaluated with respect to preoperative goals and specific procedures used to accomplish these goals in the nasal tip. Several useful observations are made from these data: (1) The most important components of nasal tip projection in the postsurgical nasal tip are the medial crura, their attachment to the caudal septum, and the presence of additional cartilaginous grafts placed between the medial crura or beneath the crural feet. (2) Actual nasal tip projection will decrease postoperatively, unless measures to increase the length and strength of the medial crural segment are taken (ie, McCollough-modified Goldman tip procedure, cartilage struts, plumping grafts, etc), regardless of the preoperative goal. (3) The double-dome unit procedure is effective in narrowing the wide or bulbous lobule but alone does not permanently increase nasal tip projection. (4) Conservative tip procedures, such as a complete strip, result in decreased nasal tip projection and should therefore be used in patients in whom retrodisplacement of the nasal tip is the intended result.

Adult↗

PubMed1991

A 19-year follow-up of tuberculin reactors. Assessment of skin test reactivity and in vitro lymphocyte responses.

Tuberculin skin test reactivity decreases with time such that repeat PPD skin testing may result in reactions of less than 10 mm. This reactivity may be boosted in some individuals with a second tuberculin skin test. The immunologic basis of these observations remains unclear. We studied the relationship between skin-test reactivity and in vitro blastogenic response to PPD in a cohort of 22 individuals (aged 28 to 81 years) known to be tuberculin reactors (induration greater than or equal to 10 mm) in 1970. In 1989, 18 subjects remained reactive to PPD on the first skin test and responded to PPD in vitro (mean incorporation of 3H-thymidine by peripheral blood mononuclear cells, 22,650 cpm). Three subjects reverted (induration in response to PPD less than 10 mm) and lost in vitro reactivity to PPD (mean incorporation of 3H-thymidine, 2,205 cpm). One subject boosted (increase of induration of at least 6 mm to greater than or equal to 15 mm) on the second skin test and showed a concomitant in vitro boost in the blastogenic response to PPD (from 1,008 cpm to 47,837 cpm). In this cohort, interpretation of the two-step tuberculin skin test correlated closely with in vitro proliferative responses. Over a 19-year period, the majority of individuals maintained skin test reactivity and strong in vitro responses to PPD despite a lack of ongoing exogenous exposure to Mycobacterium tuberculosis. The immunologic basis for reversion appears to depend in part on a loss of lymphocyte blastogenic capacity. In the one individual who exhibited the booster phenomenon, repeat antigen stimulation resulted in a dramatic increase in the in vitro blastogenic responses.

Adult↗

PubMed1989

Comparison of the synergistic potentiation of etoposide, doxorubicin, and vinblastine cytotoxicity by dipyridamole.

Dipyridamole (DPM) enhanced sensitivity to etoposide (VP-16), doxorubicin (DOX), and vinblastine (VBL) in a human ovarian carcinoma cell line that was already relatively sensitive to all three agents. This interaction was shown to be truly synergistic by median effect analysis over a 2 log cell kill. The combination index at 50% cell kill (CI50) was used to quantitate the extent of synergy. The CI50s were 0.42, 0.66, and 0.30 for VP-16, DOX, and VBL, respectively. We compared the effect of DPM on the cellular pharmacology of each chemotherapeutic drug. DPM increased the steady state cellular content of VP-16 by a maximum of 3.2-fold, and that of DOX and VBL by 1.7- and 3.7-fold, respectively. There was a good correlation between the CI50 and the DPM-induced increase in cellular drug content (r = 0.94). DPM had no effect on the initial influx VP-16 or DOX but did increase the initial influx of VBL by 3.5-fold. DPM inhibited the initial efflux of all three compounds. However, there was no relation between the extent of efflux inhibition and the magnitude of the DPM-induced increase in cellular drug content, indicating that DPM must have other effects as well. DPM has chemical characteristics similar to other known modulators of VP-16, DOX, and VBL sensitivity. When compared to verapamil, DPM was as efficacious but twice as potent in its synergistic enhancement of VP-16 sensitivity. These results demonstrate that DPM can markedly increase the cytotoxicity of VP-16, DOX, and VBL and suggest possible clinical applications.

Animals↗

PubMed1988

An efficient selection producing structural gene mutants of yeast alcohol dehydrogenase resistant to pyrazole.

Selection for resistance to allyl alcohol in respiration-incompetent Saccharomyces cerevisiae produces a high proportion of mutants that can be localized within the ADH2 structural gene and that still, because of the type of selection employed, retain enzyme activity. We show here that a similar type of selection produces a similarly high proportion of mutants resistant to the competitive inhibitor pyrazole. The first four mutants examined, picked at random from a collection of spontaneous pyrazole-resistant mutants, show altered--usually increased--KM values for ethanol and NAD+, and markedly increased K1 values for pyrazole, compared with the wild type. When these kinetic measures and their electrophoretic mobilities were compared, all the mutants could be clearly distinguished from each other as well as from wild type. Genetic analysis shows these mutants to be close to and probably resident in the structural gene. For a variety of reasons, these mutants are even more favorable subjects for population genetic analysis and the dissection of molecular microevolution than are allyl alcohol-resistant mutants.

Alcohol Dehydrogenase↗

PubMed1986

Anti-SS-A antibodies and fetal outcome in maternal systemic lupus erythematosus.

In 155 women with systemic lupus erythematosus, there were no significant differences in the rates of fertility or adverse fetal outcome between the 47 (30%) with serum anti-SS-A antibody and the 108 without anti-SS-A, except in the frequency of congenital heart block. This complication occurred in 6 of 96 pregnancies in women with anti-SS-A and was associated with high-titer maternal antibody. The overall risk of a woman with lupus having an infant with congenital heart block was estimated to be 1:60, but the risk was considerably higher (1:20) if anti-SS-A antibody was present.

Abortion, Spontaneous↗

PubMed1985

Calcitonin as a tumor marker for nonthyroid neoplasia.

Plasma levels of calcitonin have been utilized as a tumor marker for medullary carcinoma of the thyroid. Elevated calcitonin levels have been noted with other tumors as well. The present case documents a marked decrease in calcitonin levels following therapy for breast carcinoma, supporting further evaluation of calcitonin as a clinically useful tumor marker for nonthyroid neoplasm.

Breast Neoplasms↗

PubMed1982

Effects of naloxone on d-amphetamine- and apomorphine-induced behavior.

The effects of acute naloxone administration on d-amphetamine- and apomorphine-induced behavior were studied. Naloxone, in doses of 0.3-10 mg/kg (s.c.), antagonized the increase in ambulation and rearing induced by 1 mg/kg of d-amphetamine. When the dose of d-amphetamine was increased to 3 mg/kg, naloxone (3 mg/kg) antagonized only the increase in rearing activity. No dose (0.3-10 mg/kg, s.c.) of naloxone significantly affected d-amphetamine- or apomorphine-induced stereotyped activity. Naloxone (3 mg/kg) significantly augmented the apomorphine (1 mg/kg, s.c.)-induced increase in ambulation but attenuated the apomorphine (0.3 mg/kg)-induced increase in rearing activity. Naloxone (3 mg/kg) or apomorphine (0.03 mg/kg) significantly decreased the ambulation and rearing induced by a novel environment. In combination and in these doses, naloxone and apomorphine produced an additive effect on these behaviors. The neurochemical mechanisms by which naloxone affects d-amphetamine- and apomorphine-induced behavior were investigated. Naloxone (10(-6) M) had no significant effect on [3H]spiroperidol binding in either the caudate nucleus or nucleus accumbens except for a modest inhibition (24%) of both the Km and Bmax in the accumbens microsomal fraction. Similarly, naloxone (10(-6) M) had no significant effect on [3H]dopamine(DA) uptake into either brain region nor did naloxone alter the d-amphetamine-inhibition of uptake. Using perfused tissue slices, naloxone (10(-6)-10(-5) M) significantly attenuated the increase in [3H]DA release induced by d-amphetamine (10(-5) M) in both brain regions. Naloxone (1 mg/kg) had no significant effect on DA or dihydroxyphenyl-acetic acid (DOPAC) levels or on the DA/DOPAC ratio in the caudate nucleus or nucleus accumbens. However, naloxone did reverse the marked increases in the DA-DOPAC ratio induced by d-amphetamine (1 mg/kg) in both brain regions.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1980

Brain locations controlling the behavioral effects of chronic amphetamine intoxication.

Rats were administered D-amphetamine repeatedly for 4 days. After day 1 of treatment, the amphetamine-induced increases in ambulation, rearing, and stereotyped activity were augmented. However, after 4 days treatment, the rearing and ambulatory responses became attenuated while the stereotyped activities remained augmented. Micro-injection studies revealed that both the augmentation and attenuation of nonstereotyped ambulation were generated from the nucleus accumbens. The augmentation of stereotyped behaviors was generated from the caudate nucleus. Chronically treated animals who were administered 0.7 but not 1.0 mg/kg apomorphine showed augmented behavioral response. Chronic amphetamine treatment significantly decreased (3H) spiroperidol binding in both the nucleus accumbens and caudate nucleus. However, no effect on the DA-stimulated adenyl cyclase activity was observed in either brain region. It is concluded that repeated D-amphetamine administration selectively augments and attenuates D-amphetamine-induced behaviors and that these selective effects are mediated by different dopamine systems.

Adenylyl Cyclases↗

PubMed1977

An electron microscopic cytochemical study on concanavalin A binding sites and their mobility in normal and cystic fibrosis fibroblasts in vitro.

Concanavalin A (Con A) binding sites were visualized ultrastructurally in the cultured fibroblasts from cystic fibrosis patients, obligatory heterozygotes, and normal individuals by peroxidase labeling technique. Con A binding sites were localized as a continuous layer on the external side of the plasma membrane in fixed fibroblasts of the three genotypes. In living cells, Con A induces both lateral and vertical movements of binding sites as expressed by cap formation and internalization of the plasma membrane. Fibroblasts of the three genotypes responded similarly to Con A treatment and failed to show significant detectable differences.

Binding Sites↗

PubMedDate not supplied

Risk factors for HIV infection in homosexual men: the Cleveland men's study of risks in a low-prevalence area.

Detailed questionnaires concerning alcohol and drug use, sexual practices, and medical history were completed by 301 homosexual men living in the Cleveland metropolitan area. Their sera were subsequently tested for antibodies to the human immunodeficiency virus. Fifty-six (18.6%) were seropositive. In a univariate analysis, age, drug use, and four specific sexual practices were associated with seropositivity. In a multiple logistic regression analysis, intravenous drug use and receptive anal-genital sex remained independent predictors of seropositivity.

Adolescent↗