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Biomedical subjects

E Vittinghoff

Publications and source records attributed to E Vittinghoff.

At least 55 records · Page 3Linked to original sources

Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC)

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.

Acquired Immunodeficiency Syndrome↗

Diminished spontaneous apoptosis in lymphocytes from human immunodeficiency virus-infected long-term nonprogressors.

The relationship between peripheral lymphocyte apoptosis and human immunodeficiency virus disease progression was studied in infected subgroups with distinct profiles of progression. Long-term nonprogressors (LTNP) and seronegative controls had levels of spontaneous apoptosis significantly lower than those for recent seroconverters who had CD4 cell counts similar to those of nonprogressors but with a high likelihood of disease progression. Lymphocytes from nonprogressors and seronegative controls also showed negligible spontaneous caspase-3 activity, a biochemical indicator for apoptosis, whereas early progressors exhibited substantial activity. In contrast, when activated with mitogens, the lymphocytes from both LTNP and progressors displayed indistinguishable levels of heightened apoptosis. Spontaneous apoptosis and plasma viremia levels correlated positively in progressors, but not in LTNP. These findings demonstrate that increased lymphocyte apoptosis is evident prior to CD4 T cell decline and that LTNP are relatively resistant to the factors that induce accentuated levels of spontaneous but not mitogen-induced cell death.

Apoptosis↗

Reducing pregnancy and induced abortion rates in China: family planning with husband participation.

OBJECTIVES: This study assessed the effectiveness of a family planning intervention with and without husband's participation in reducing pregnancy and abortion rates in Shanghai, China. METHODS: In this 3-arm randomized trial among 1800 nonsterilized married women, educational interventions targeting both spouses and targeting the wife only were compared with usual family planning care. RESULTS: Among women not using intrauterine devices (IUDs), the intervention with husband's participation had an effect in reducing pregnancy rates (adjusted odds ratio [OR] = 0.36, 95% confidence interval [CI] = 0.12, 1.1) and abortion rates (adjusted OR = 0.29, CI = 0.09, 0.94) compared with control subjects, and a significant effect in reducing pregnancy rates (adjusted OR = 0.29, CI = 0.10, 0.85) and abortion rates (adjusted OR = 0.24, CI = 0.07, 0.77) compared with wife-only subjects. CONCLUSIONS: Family planning interventions involving husbands may reduce pregnancy and abortion rates among non-IUD users.

Abortion, Induced↗

Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study.

To examine rates of and risk factors for heterosexual transmission of human immunodeficiency virus (HIV), the authors conducted a prospective study of infected individuals and their heterosexual partners who have been recruited since 1985. Participants were recruited from health care providers, research studies, and health departments throughout Northern California, and they were interviewed and examined at various study clinic sites. A total of 82 infected women and their male partners and 360 infected men and their female partners were enrolled. Over 90% of the couples were monogamous for the year prior to entry into the study; < 3% had a current sexually transmitted disease (STD). The median age of participants was 34 years, and the majority were white. Over 3,000 couple-months of data were available for the follow-up study. Overall, 68 (19%) of the 360 female partners of HIV-infected men (95% confidence interval (CI) 15.0-23.3%) and two (2.4%) of the 82 male partners of HIV-infected women (95% CI 0.3-8.5%) were infected. History of sexually transmitted diseases was most strongly associated with transmission. Male-to-female transmission was approximately eight-times more efficient than female-to-male transmission and male-to-female per contact infectivity was estimated to be 0.0009 (95% CI 0.0005-0.001). Over time, the authors observed increased condom use (p < 0.001) and no new infections. Infectivity for HIV through heterosexual transmission is low, and STDs may be the most important cofactor for transmission. Significant behavior change over time in serodiscordant couples was observed.

Adolescent↗

Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.

The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression. A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5.

Acquired Immunodeficiency Syndrome↗

Medical abortion with oral methotrexate and vaginal misoprostol.

OBJECTIVE: To evaluate the safety and efficacy of oral methotrexate and vaginal misoprostol for medical abortion. METHODS: A prospective multicenter trial involved 300 women up to 49 days' gestation seeking elective abortion. Subjects received methotrexate 50 mg orally followed 5-6 days later by misoprostol 800 micrograms vaginally. The misoprostol dose was repeated if abortion did not occur. RESULTS: Complete abortion occurred in 273 of 299 women (91.3%; 95% confidence interval [CI] 87.5, 94.2%); one woman was lost to follow-up. Abortion occurred within 8 days of the methotrexate in 233 women (77.9%; 95% CI 72.8, 82.5%); the remaining 13.4% of women who aborted did so after a delay of 23.5 +/- 9.8 days (median 23 days, range 10-45). Vaginal bleeding lasted an average of 15 and 11 days in immediate and delayed-success abortions, respectively. Complete abortion rates decreased linearly with increasing body surface area. After methotrexate and misoprostol administration, nausea was reported in 37% and 33%, vomiting in 11% and 18%, diarrhea in 12% and 18%, and subjective fever or chills in 15% and 31% of subjects, respectively. CONCLUSION: Oral methotrexate followed by vaginal misoprostol is effective for abortion and represents an acceptable alternative to intramuscular methotrexate in regimens for medical abortion.

Abortifacient Agents, Nonsteroidal↗

Depressive affect and survival among gay and bisexual men infected with HIV.

BACKGROUND: Although depression has been related to chronic disease processes and outcomes, studies examining the relationship between depression and disease progression in persons with human immunodeficiency virus (HIV) infection have produced inconsistent results. OBJECTIVE: To investigate whether depressive affect is associated with HIV mortality. METHODS: This was a prospective cohort study (San Francisco Men's Health Study) using a population based probability sample of single men living in areas of San Francisco, Calif, with high case rates of acquired immunodeficiency syndrome. Data collection was at 6-month intervals with up to 15 waves of follow-up. Subjects included all 402 homosexual or bisexual men who in July 1984 had serologic evidence of HIV infection and who survived a minimum of 1 wave after baseline. Depressive affect was measured at each wave with the affective subscale of the Center for Epidemiologic Studies-Depression Scale. Laboratory markers, World Health Organization staging, antiretroviral use, and hospitalizations were also used as predictor variables. The primary outcome measure was survival. RESULTS: In a Cox proportional hazards model, a time-dependent measure of depressive affect was associated with greater mortality (adjusted risk ratio, 1.67; 95% confidence interval, 1.01-2.78). CONCLUSIONS: Depressive affect was associated with mortality risk, highlighting the importance of diagnosis and treatment of depression among HIV-infected gay and bisexual men. Replication of this effect in incident cohorts with well-characterized dates of HIV infection is needed and, if replicated, an exploration of mediating pathways suggested.

Adult↗

Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study.

The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4(+) T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele (CKR5Delta32) was identified that is present at a frequency of approximately0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Delta32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.

Acquired Immunodeficiency Syndrome↗

Methotrexate and misoprostol for early abortion: a multicenter trial. I. Safety and efficacy.

A prospective trial was conducted including 300 pregnant women seeking elective abortion to evaluate the safety and efficacy of methotrexate and misoprostol for abortion at < or = 56 days gestation. Subjects received methotrexate 50 mg/ m2 intramuscularly followed 7 days later by misoprostol 800 micrograms vaginally. The misoprostol dose was repeated the next day if the abortion did not occur. Outcome measures included successful abortion (complete abortion without requiring a surgical procedure), duration of vaginal bleeding, and side effects. Complete abortion occurred in 263/ 300 (87.7%, 95% CI 83.4, 91.2%) patients. The complete abortion rate was higher for early gestations: 183/202 (90.6%, 95% CI 85.7, 94.2%) at < or = 49 days gestation, and 80/98 (81.6%, 95% CI 72.5, 88.7%) from 50-56 days gestation (p = 0.038). Abortion occurred in the 24 hours following the initial or repeat misoprostol dose (immediate success) in 65.0%; the remaining 22.7% of women who aborted did so after a delay of 23.6 +/- 9.1 (mean +/- standard deviation) days. Vaginal bleeding lasted 14 +/- 7 days and 11 +/- 9 days in immediate success and delayed success patients, respectively. Overall, 69.7%, 87.7%, and 91.7% of patients had passed the pregnancy by 14, 28, and 35 days, respectively, after receiving methotrexate. Methotrexate and misoprostol side effects were minimal. This treatment regimen offers an alternative to surgical abortion or the use of antiprogestins and prostaglandin for medical abortion.

Abortifacient Agents, Nonsteroidal↗

Human immunodeficiency virus testing for patient-based and population-based diagnosis.

Laboratory testing for human immunodeficiency virus (HIV) has been introduced for individual patient-based diagnosis as well as high-risk and low-risk population-based screening. The choice of test, confirmatory algorithm, and interpretative criteria used depend on the clinical setting. In the context of general population-based testing, factors affecting test performance will have to be considered carefully in the development of testing policy.

Algorithms↗

Attributable risk of exposures associated with sexually transmitted disease.

Attributable risk combines information on the prevalence of an exposure with a measure of the associated increment in risk, providing an estimate of the proportion of incident or prevalent disease that might be avoided by eliminating the exposure. Thus, attributable risk identifies exposures most productively targeted by public health interventions. Attributable risk can be defined as the ratio of average excess risk to average risk. As with other measures of association between exposure and disease computed from observational data, adjustment must be made for confounding factors. Estimates of attributable risk are highly variable. Nonetheless, attributable risk retains its usefulness as an approximate measure of the public health significance of exposures associated with acquisition of sexually transmitted disease, provided it is estimated and interpreted cautiously.

Female↗

The efficacy of brief group counseling in HIV risk reduction among homosexual Asian and Pacific Islander men.

OBJECTIVES: The incidence of AIDS is increasing at a higher rate among homosexual Asian and Pacific Islanders (API) than white homosexual men in the United States. The number of homosexual API men engaging in unsafe sex is increasing at an alarming rate. HIV risk reduction is urgently needed in this population. SUBJECTS AND METHODS: We developed and evaluated culturally appropriate brief group counseling with 329 self-identified homosexual API recruited in San Francisco between 1992 and 1994. Participants were randomized into a single, 3-h skills training group or a wait-list control group. The intervention consisted of four components: (1) development of positive self-identity and social support, (2) safer sex education, (3) eroticizing safer sex, and (4) negotiating safer sex. Data were collected at baseline and 3 months after the intervention. RESULTS: Significant reductions in number of sexual partners were observed among all treatment subjects, regardless of ethnicity (P = 0.003). Treatment decreased the number of partners reported at 3-month follow-up by 46% [95% confidence interval (CI), 28-77]. Chinese and Filipino men further benefited from the intervention: treatment subjects from these two ethnic groups reduced unprotected anal intercourse at follow-up by more than half when compared to their counterparts (odds ratio = 0.41; 95% CI, 0.19-0.89; P = 0.024). CONCLUSIONS: We demonstrated the efficacy of brief group counseling in reducing HIV risk among homosexual API. Cities with significant API populations should adopt culturally tailored skills training as part of HIV prevention strategies for this group of homosexual men.

Adult↗

Incidence proportion of and risk factors for AIDS patients diagnosed with HIV dementia, central nervous system toxoplasmosis, and cryptococcal meningitis.

We undertook this study to determine the incidence proportion of and risk factors for AIDS patients diagnosed with human immunodeficiency virus (HIV) dementia, central nervous system (CNS) toxoplasmosis, and cryptococcal meningitis. A historical cohort of 487 consecutive inpatients with AIDS treated by San Francisco General Hospital inpatient and outpatient services entered the study. We abstracted all available records for demographic information, diagnoses, and dates of death and estimated the incidence proportion of AIDS patients diagnosed with major CNS complications using the Kaplan-Meier method. We used the Cox proportional hazards model to analyze the effect of demographic factors on the hazard (risk per unit time) of diagnosis with these CNS conditions. The estimated incidence proportion of patients diagnosed with HIV dementia within 1 and 2 years of AIDS diagnosis increased from 0.10 to 0.18. Corresponding proportions were 0.10 and 0.19 for CNS toxoplasmosis and 0.10 and 0.14 for cryptococcal meningitis. Only HIV dementia was independently associated with increasing age at AIDS diagnosis (relative hazard [RH] of 2.75 for ages 41-50 [95% confidence interval, 1.08-6.98]; RH of 4.73 for ages > 50 [95% confidence interval, 1.41-15.87]) and with injection drug use (RH of 2.03; 95% confidence interval, 1.19-3.47). HIV dementia, CNS toxoplasmosis, and cryptococcal meningitis are about equally common complications in patients with AIDS, but only HIV dementia is associated with increasing age at AIDS diagnosis and injection drug use.

AIDS Dementia Complex↗

A randomized trial comparing misoprostol three and seven days after methotrexate for early abortion.

OBJECTIVE: Our purpose was to determine whether vaginal misoprostol 7 days rather than 3 days after methotrexate injection increases the percent of successful abortions on the day of misoprostol administration. STUDY DESIGN: A randomized controlled trial was performed in women requesting an abortion at < or = 56 days' gestation. Eighty-six women were treated with methotrexate 50 mg/m2 intramuscularly followed 3 days (group 1) or 7 days (group 2) later by vaginal misoprostol 800 micrograms. The misoprostol dose was repeated if the abortion did not occur. RESULTS: Complete abortion occurred in 38 of 46 (83%) patients in group 1 and 39 of 40 (98%) in group 2 (p = 0.033). Of the women with complete abortions, 30 of 46 (65%) in group 1 and 27 of 40 (68%) in group 2 aborted the same day as the first or second dose of misoprostol (p = 0.823). Vaginal bleeding lasted 14 +/- 5 (mean +/- SD) days in group 1 and 17 +/- 9 days in group 2. The remaining women aborted after a delay of 24 +/- 6 days in group 1 and 28 +/- 13 days in group 2. For these women vaginal bleeding lasted 18 +/- 17 and 14 +/- 7 days, respectively, and the human chorionic gonadotropin-beta level was < or = 25 IU/L by 22 +/- 7 days after the abortion in group 1 and 19 +/- 9 days in group 2. Treatment failures in group 1 were four continuing pregnancies (9%), two incomplete abortions (4%), and two women who requested surgical termination after receiving both medications (4%). The treatment failure in group 2 was an incomplete abortion. Methotrexate and misoprostol side effects were infrequent. CONCLUSIONS: Methotrexate and vaginal misoprostol are more effective abortifacients when the misoprostol is given 7 days rather than 3 days after methotrexate. This treatment regimen may offer an alternative to surgical abortion or the use of antiprogestins and prostaglandin for medical abortion.

Abortifacient Agents, Nonsteroidal↗

Trauma centers in a managed care environment.

Health care reform will affect the relationship of trauma centers to health maintenance organizations and other managed care plans. We studied Kaiser Permanente Medical Center (Kaiser) members admitted to the Trauma Center at San Francisco General Hospital (SFGH) to determine: (1) variables predicting transfer from SFGH to a Kaiser Hospital (repatriation), (2) the length of hospital stay (LOS), and (3) the cost of their care. The SFGH trauma registry provided data on 7,794 patients admitted before 1994. To investigate LOS, 89 Kaiser patients over 1 year were matched with non-Kaiser patients on age, maximum Abbreviated Injury Scale score (MAIS) by body region, Injury Severity Score (ISS), head injury severity, and blunt or penetrating injury and disposition. Kaiser patients were significantly younger, more likely to have blunt injury, and had a lower death rate. Significant predictors of repatriation were an MAIS score > or = 3, abdominal or extremity injury, and an ISS score of 26 to 40. The mean LOS for all Kaiser patients was 7.6 days, compared with 4.8 for controls (p = 0.20). However, mean LOS was significantly longer in repatriated Kaiser patients compared with controls (16 vs. 7.8 days, p < 0.0005). Kaiser reimbursement rates were comparable with commercial payors, but higher than others. A relatively small number of severely injured patients account for a large percentage of costly trauma care. Analyses of patient subsets are necessary for trauma centers to negotiate suitable relationships with managed care plans. A prospective study is needed to examine the cost efficiency of early transfer of managed care patients.

Adult↗

Methotrexate and misoprostol vs misoprostol alone for early abortion. A randomized controlled trial.

OBJECTIVE: To compare the safety and efficacy of early abortion by administration of methotrexate and misoprostol vs administration of misoprostol alone. DESIGN: Randomized controlled trial. SETTING: San Francisco (Calif) General Hospital. PATIENTS: Pregnant women at 56 days' gestation or less seeking elective abortion. Sixty-three women volunteered for the trial; 61 completed the study and are included in the analysis. INTERVENTION: Intramuscular administration of 50 mg of methotrexate per square meter of body surface area followed 3 days later by vaginal administration of 800 micrograms of misoprostol (group 1) or the same dose of misoprostol given alone (group 2). The misoprostol dose was repeated 24 hours later if abortion had not occurred. MAIN OUTCOME MEASURES: Successful abortion, duration of vaginal bleeding, side effects, and change in beta-human chorionic gonadotropin (beta-hCG) level. An abortion was considered successful if the pregnancy ended without requiring a surgical procedure. RESULTS: Complete abortion occurred in 28 (90%) of 31 patients in group 1 and 14 (47%) of 30 patients in group 2 (P < .001). Seventeen (61%) of the 28 women in group 1 who aborted did so the same day as misoprostol administration; vaginal bleeding lasted a mean (+/- SD) of 10 (+/- 4) days, and beta-hCG level was less than or equal to 10 IU/L by a mean of 31 (+/- 6) days after methotrexate administration. The 11 other women in group 1 who aborted did so after a mean delay of 29 (+/- 11) days; vaginal bleeding lasted 7 (+/- 4) days, and beta-hCG level was less than or equal to 10 IU/L by a mean of 24 (+/- 11) days after the abortion. There were three treatment failures in group 1: two ongoing pregnancies (6%) and one incomplete abortion (3%). For the 14 women with successful abortions in group 2, vaginal bleeding lasted a mean of 10 (+/- 6) days and beta-hCG level was less than or equal to 10 IU/L by mean of 39 (+/- 18) days after the misoprostol. There were 16 treatment failures in group 2: eight ongoing pregnancies (27%), and eight incomplete abortions (27%). Methotrexate side effects were minimal. Misoprostol side effects were diarrhea in 18% and nausea and vomiting in 5%. CONCLUSIONS: Methotrexate and vaginal misoprostol are more effective than misoprostol alone. Both drugs are available throughout the United States, and both drugs are inexpensive. This combination may offer an alternative to the use of antiprogestin and prostaglandin for medical abortion.

Abortion, Induced↗

Estimating patterns of CD4 lymphocyte decline using data from a prevalent cohort of HIV infected individuals.

In natural history studies of chronic disease, it is of interest to understand the evolution of key variables that measure aspects of disease progression. This is particularly true for immunological variables among persons infected with the human immunodeficiency virus (HIV). The natural time scale for such studies is time since infection. Most data available for analysis, however, arise from prevalent cohorts, where the date of infection is unknown for most or all individuals. As a result, standard curve fitting algorithms are not immediately applicable. Here we propose two methods to circumvent this difficulty. The first uses repeated measurement data to provide information not only on the level of the variable of interest, but also on its rate of change, and is based on the principal curves algorithm of Hastie and Stuetzle. The second uses an external estimate of the expected time since infection. Both methods use locally-weighted linear smoothers, and are applied to data from a prevalent cohort of HIV-infected homosexual men, giving estimates of the average pattern of CD4 lymphocyte decline. These methods apply to natural history studies that use data from prevalent cohorts where the time of disease origin is uncertain, provided availability of certain information from external sources.

Algorithms↗