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R S Klein

Publications and source records attributed to R S Klein.

At least 37 records · Page 2Linked to original sources
PubMed2001

A multicenter study of bacterial vaginosis in women with or at risk for human immunodeficiency virus infection.

BACKGROUND: Bacterial vaginosis is a common gynecologic infection that has been associated with a variety of gynecologic and obstetric complications, including pelvic inflammatory disease, postabortal infection and premature delivery. Recent studies suggest that bacterial vaginosis may increase a woman's risk for human immunodeficiency virus (HIV). We undertook this study to assess whether the prevalence and characteristics of bacterial vaginosis differed according to HIV status in high-risk US women. METHODS: Prevalence of bacterial vaginosis was assessed by Gram's stain and clinical criteria for 854 HIV-infected and 434 HIV-uninfected women enrolled in the HIV Epidemiology Research (HER) Study. Multiple logistic regression techniques were used to determine whether HIV infection independently predicted bacterial vaginosis. RESULTS: Almost half (46%) the women had bacterial vaginosis by Gram's stain. The prevalence of bacterial vaginosis was 47% in the HIV-positive women compared with 44% in the HIV-negative women; this difference was not statistically significant (p = 0.36). After adjustment for other covariates, HIV-positive women were more likely than HIV-negative women to have bacterial vaginosis (odds ratio (OR) 1.31; 95% confidence interval (CI) 1.01-1.70) by Gram's stain but not by clinical criteria (OR 1.16; CI 0.87-1.55). Among HIV-positive women, use of antiretroviral drugs was associated with a lower prevalence of bacterial vaginosis (adjusted OR 0.54; Cl 0.38-0.77). CONCLUSIONS: In this cross-sectional analysis of high-risk US women, HIV infection was positively correlated with bacterial vaginosis diagnosed by Gram's stain.

AIDS-Related Opportunistic Infections↗
PubMed2001

SDF-1 alpha induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells.

The chemokine SDF-1 alpha (CXC12) and its receptor CXCR4 have been shown to play a role in the development of normal cerebellar cytoarchitecture. We report here that SDF-1 alpha both induces chemotactic responses in granule precursor cells and enhances granule cell proliferative responses to Sonic hedgehog. Chemotactic and proliferative responses to SDF-1 alpha are greater in granule cells obtained from cerebella of animals in the first postnatal week, coinciding with the observed in vivo peak in cerebellar CXCR4 expression. SDF-1 alpha activation of neuronal CXCR4 differs from activation of CXCR4 in leukocytes in that SDF-1 alpha-induced calcium flux is activity dependent, requiring predepolarization with KCl or pretreatment with glutamate. However, as is the case in leukocytes, neuronal responses to SDF-1 alpha are all abolished by pretreatment of granule cells with pertussis toxin, suggesting they occur through G(alpha i) activation. In conclusion, SDF-1 alpha plays a role in two important processes of granule cell maturation - proliferation and migration - assisting in the achievement of appropriate cell number and position in the cerebellar cortex.

Animals↗
PubMed2001

The incidence of tuberculosis in drug users with small tuberculin reaction sizes.

SETTING: In persons infected with the human immunodeficiency virus (HIV), a decreased tuberculin reaction cut-point of > or = 5 mm induration is recommended. OBJECTIVE: To determine tuberculosis risk in non-anergic HIV-infected persons with 5-9 mm tuberculin reactions. DESIGN: A prospective study with semi-annual tuberculin and anergy testing, HIV antibody and T cell subset assays, and active surveillance for tuberculosis. RESULTS: Participants were 572 HIV-seronegative and 241 HIV-seropositive non-anergic drug users. No tuberculosis occurred in HIV-seronegative persons. Tuberculosis incidence among HIV-seropositive drug users was 3.3, 7.7, 0, and 0.34 per 100 person-years in those with tuberculin reaction sizes of > or = 10 mm, 5-9 mm, 1-4 mm, and 0 mm, respectively, and was significantly increased in persons with 5-9 mm induration compared with those with 0-4 mm induration (rate ratio 27.7, 95%CI 2.9-268). Among persons with reaction sizes of 5-9 mm, tuberculosis occurred exclusively in those with CD4+ lymphocyte counts <500/mm3 at the time of their 5-9 mm tuberculin reactions. CONCLUSION: HIV-infected persons with tuberculin reaction sizes of 5-9 mm are at increased risk for tuberculosis compared to non-anergic persons with smaller (0-4 mm) reaction sizes. However, this increased risk may be limited to those with low CD4+ lymphocyte counts at the time of tuberculin testing.

Adult↗
PubMed2000

Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2.

Monocyte recruitment to the central nervous system (CNS) is a necessary step in the development of pathologic inflammatory lesions in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. Monocyte chemoattractant protein (MCP)-1, a potent agonist for directed monocyte migration, has been implicated in the pathogenesis of EAE. Here we report that deficiency in CC chemokine receptor (CCR)2, the receptor for MCP-1, confers resistance to EAE induced with a peptide derived from myelin oligodendrocyte glycoprotein peptide 35-55 (MOGp35-55). CCR2(-/)- mice immunized with MOGp35-55 failed to develop mononuclear cell inflammatory infiltrates in the CNS and failed to increase CNS levels of the chemokines RANTES (regulated on activation, normal T cell expressed and secreted), MCP-1, and interferon (IFN)-inducible protein 10 (IP-10) as well the chemokine receptors CCR1, CCR2, and CCR5. Additionally, T cells from CCR2(-/)- immunized mice showed decreased antigen-induced proliferation and production of IFN-gamma compared with wild-type immunized controls, suggesting that CCR2 enhances the T helper cell type 1 immune response in EAE. These data indicate that CCR2 plays a necessary and nonredundant role in the pathogenesis of EAE.

Animals↗
PubMed2000

Effect of HIV infection on menstrual cycle length.

HIV serostatus and menstrual function were examined using prospectively collected menstrual data from 802 HIV-seropositive and 273 HIV-seronegative women, ages 20 to 44, enrolled in two cohort studies of HIV infection in North American women. The associations between HIV serostatus and the probabilities of having a cycle lasting >40 days (n = 541 cycles), >90 days (n = 67 cycles), <18 days (n = 316 cycles) and mean length and variability of 18 to 40 day cycles (n = 3,634) were assessed. After adjustment for demographic characteristics, body mass index, and substance use, seropositivity increased the odds of having a very short cycle (< 18 days, odds ratio [OR], 1.45; 95% confidence interval [CI], 1.00-2.11) and a very long cycle (>90 days, OR, 1.32; 95% CI, 0.68-2.58) slightly, although the latter CIs include one. Seropositivity did not increase the odds of having a moderately long cycle (>40 days, OR, 1.14) or affect mean cycle length or variability (beta, 0.30 +/- 0.20; between-woman standard deviation [SD], 2.2 days [HIV-seronegative] and 1.9 days [HIV-seropositive]; within-woman SD, 3.5 days for both). Although seropositivity may slightly increase the probability of very short cycles, HIV serostatus has little overall effect on amenorrhea, menstrual cycle length, or variability. Among HIV-seropositive women, higher viral loads and lower CD4+ counts were associated with increased cycle variability and polymenorrhea.

Adult↗
PubMed2000

Group A streptococcal appendicitis in a patient with AIDS.

A man with AIDS developed appendicitis and bacteremia caused by Group A streptococcus, neither of which is considered an opportunistic infection. Group A streptococcus is rarely implicated in appendicitis in children and has not previously been reported in an adult. Immunodeficiency might have predisposed the patient to this unusual infection.

Acquired Immunodeficiency Syndrome↗
PubMed2000

A prospective study of positive tuberculin reactions in women with or at risk for HIV-1 infection. HER Study Group. HIV Epidemiology Research.

We prospectively studied 1310 women with or at risk for HIV-1 infection to assess subsequent tuberculin reactions in those with > or = 10 mm induration. Forty-seven HIV-positive and 57 negative women had tuberculin reactions > or = 10 mm induration; reversions to reactions < 10 mm occurred in 44% and 46% of those retested, respectively (P = NS). Among seropositives, reversions were associated with lower CD4+ lymphocyte count (P = 0.02). Of a total of 45 subsequent tuberculin tests in seropositive women, only two (4%) resulted in 5-9 mm induration, both at CD4+ counts < 500/mm3. Three (30%) of an additional 10 seropositive women with maximal reactions of 5-9 mm induration reported prior tuberculosis exposure, a significantly lower proportion than the 36/47 (77%) with reactions > or = 10 mm induration (P < 0.01), but not different than women with maximal reaction sizes < 5 mm (219/814, 27%). This study suggests that reversions of > or = 10 mm tuberculin reactions to 5-9 mm are rare. In HIV-positive persons, especially those with CD4+ lymphocyte counts > or = 500/mm3, reaction sizes of 5-9 mm often may not indicate Mycobacterium tuberculosis infection.

AIDS-Related Opportunistic Infections↗
PubMed1999

Effectiveness of isoniazid chemoprophylaxis for HIV-infected drug users at high risk for active tuberculosis.

OBJECTIVE: To define the effectiveness of chemoprophylaxis, outside of a clinical trial setting, in preventing tuberculosis among tuberculin-reactive and anergic HIV-infected drug users at high risk of developing active tuberculosis. DESIGN: An observational cohort study. SETTING: Methadone maintenance treatment program with on-site primary care. PARTICIPANTS: Current or former drug users enrolled in methadone treatment. INTERVENTIONS: Annual skin testing for tuberculosis infection and anergy was performed, and eligible patients were offered daily isoniazid for 12 months and followed prospectively. MAIN OUTCOME MEASURE: The development of active tuberculosis. RESULTS: A total of 155 persons commenced chemoprophylaxis. Among tuberculin reactors, tuberculosis rates were 0.51 and 2.07/100 person-years in those completing 12 months versus those not taking prophylaxis [rate ratio 0.25, 95% confidence interval (CI) 0.06-1.01]. Among anergic individuals, comparable rates were 0 and 1.44/100 person-years. Lower tuberculosis rates among completers were not attributable to differences in immune status between the treated and untreated groups. CONCLUSION: The completion of isoniazid chemoprophylaxis was associated with a marked reduction in tuberculosis risk among tuberculin reactors and anergic persons in this high-risk population. These data support aggressive efforts to provide a complete course of preventative therapy to HIV-infected tuberculin reactors, and lend weight to the findings of others that isoniazid can reduce the rate of tuberculosis in high-risk anergic HIV-infected persons.

AIDS-Related Opportunistic Infections↗
PubMed1999

Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: implications for the neuropathogenesis of AIDS.

Chemokines are believed to play a role in the neuropathogenesis of AIDS through their recruitment of neurotoxin-secreting, virally infected leukocytes into the CNS. Levels of chemokines are elevated in brains of patients and macaques with HIV/SIV-induced encephalitis. The chemokine receptors CCR3, CCR5, and CXCR4 are found on subpopulations of neurons in the cortex of human and macaque brain. We have developed an in vitro system using both macaque and human fetal neurons and astrocytes to further investigate the roles of these receptors in neuronal response to inflammation. Here we report the presence of functional HIV/SIV coreceptors CCR3, CCR5, and CXCR4 on fetal human and macaque neurons and CCR5 and CXCR4 on astrocytes immediately ex vivo and after several weeks in culture. Confocal imaging of immunostained neurons demonstrated different patterns of distribution for these receptors, which may have functional implications. Chemokine receptors were shown to respond to their appropriate chemokine ligands with increases in intracellular calcium that, in the case of neurons, required predepolarization with KCl. These responses were blocked by neutralizing chemokine receptor in mAbs. Pretreatment of neural cells with pertussis toxin abolished responses to stromal-derived factor-1alpha, macrophage inflammatory protein-1beta, and RANTES, indicating coupling of CCR5 and CXCR4 to a Gialpha protein, as in leukocytes. Cultured macaque neurons demonstrated calcium flux response to treatment with recombinant SIVmac239 envelope protein, suggesting a mechanism by which viral envelope could affect neuronal function in SIV infection. The presence of functional chemokine receptors on neurons and astrocytes suggests that chemokines could serve to link inflammatory and neuronal responses.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Stability of cutaneous anergy in women with or at risk for HIV infection. HIV Epidemiology Research Study Group.

OBJECTIVE: To study the stability of cutaneous anergy in women with or at risk for HIV infection. DESIGN: Prospective multicenter cohort study METHODS: Interviews, CD4+ lymphocyte counts, and intradermal skin testing with mumps, Candida, and tetanus toxoid antigens were performed on two occasions at a median interval of 74 weeks in 436 HIV-seropositive and 252 seronegative at-risk women; only 10 (2%) HIV-seropositive women were taking highly active antiretroviral therapy at the time of delayed-type hypersensitivity (DTH) testing. Anergy was defined as induration <2 mm to all three antigens. RESULTS: Skin test reactivity at repeat testing was seen in 202 of 233 (87%) HIV-seronegative women who were not anergic at baseline, compared with 10 (53%) of 19 seronegative women who were anergic at baseline (relative risk [RR], 1.7; 95% confidence interval [CI], 1.07-2.5). Anergy at retesting was seen in 108 of 169 (64%) HIV-seropositive women who were previously anergic, compared with 77 of 267 (29%) who were not previously anergic (RR, 2.2; 95% CI, 1.8-2.8). Among initially anergic seropositive women, CD4+ lymphocyte counts were lower at both initial and follow-up testing in those who remained anergic than in those who reacted at follow-up (p < .001). The relative risks for anergy at retesting of initially anergic seropositive women, compared with initially reactive seropositive women, were related to CD4+ level; 2.5 (95% CI, 1.4-4.3) for CD4+ counts < 200 cells/mm3, 2.0 (95% CI, 1.5-1.7) for CD4+ counts 200-500 cells/mm3, and 1.6 (95% CI, 0.9-2.8) for CD4+ counts >500 cells/mm3. CONCLUSIONS: Although anergic HIV-seropositive women may become reactive, cutaneous anergy predicts a higher likelihood of anergy at retesting as well as lower CD4+ counts. Stability of anergy is greatest in HIV-seropositive women with low CD4+ counts.

CD4 Lymphocyte Count↗
PubMed1999

A prospective study of HIV disease progression in female and male drug users.

OBJECTIVE: To compare HIV disease progression and mortality in a cohort of female and male drug users. DESIGN: A prospective cohort study of 222 HIV-seropositive women and 302 HIV-seropositive men who attended a hospital-affiliated methadone maintenance program with on-site primary care. METHODS: Regression slopes of CD4+ cell decline were compared using the two sample t-test, and the distribution of AIDS-defining illnesses evaluated by Mantel-Haenszel chi2 test. Time to AIDS-defining clinical conditions and death were compared using the Kaplan-Meier log-rank test. Multivariate estimates of progression to clinical AIDS or death, for all participants, stratified by sex, were derived from Cox proportional hazards models. RESULTS: Ninety-five persons (43 women and 52 men) developed AIDS-defining conditions. Analyses of the rates of CD4+ cell decline, the distribution of first AIDS-defining illnesses, and the time to clinical AIDS did not differ by sex. In the multivariate model, sex was not associated with an AIDS outcome, whereas crack-cocaine use [hazards ratio (HR), 1.815; 95% confidence interval (CI), 1.151-2.863], CD4+ cell count (100 x 10(6)/l; HR, 0.589; 95% CI, 0.511-0.679), and two or more HIV-related symptoms (HR, 1.702; 95% CI, 1.125-2.576) were associated. Mortality rates (8.71 per 100 person-years in women and 9.85 per 100 person-years in men) were similar, using univariate or multivariate methods. CONCLUSIONS: There was little difference in clinical outcomes or mortality between HIV-seropositive female and male drug users with access to primary care. However, crack-cocaine use was independently associated with progression to clinical AIDS.

Adult↗
PubMed1999

Gender differences in HIV risk behaviors in an adult emergency department in New York City.

BACKGROUND: The human immunodeficiency virus (HIV) epidemic in the US increasingly involves urban heterosexual adults, particularly women, belonging to ethnic minority groups. An understanding of gender-based differences in HIV risk behaviors within these groups would be of value in the ongoing struggle to limit HIV transmission in metropolitan centers. METHODS: This was a prospective study of demographic and historical characteristics and HIV risk behaviors. The study utilized a structured interview format, which was administered to all patients treated by participating emergency department physicians. RESULTS: On univariate analysis of data obtained from 1,460 patients who had neither a known HIV infection nor a chief complaint or final emergency department diagnosis associated with HIV risk behaviors, men were more likely to be older, homeless, to have ever injected drugs, used crack, engaged in same-gender sex, paid for sex, been incarcerated, or had syphilis or gonorrhea. Women were more likely to report prior chlamydia infection or to report that their sole sex partners had other partners within the past year. On multivariate analysis, variables independently associated with male gender included homelessness, injection drug use, crack use, any prior sexually transmitted disease (in subjects 35 years of age or older), and sex with prostitutes. In a separate analysis of patients admitting to drug use, the male predominance of other risk behaviors was not observed; the only significant differences between genders were a higher rate of prostitution among women and a higher rate of sexual contact with a prostitute among men. CONCLUSIONS: In patients visiting an inner-city emergency department in the Bronx, HIV risk behaviors are generally more common in men, but rates of risk behaviors among male and female drug users are comparable.

Adult↗
PubMed1999

Self-reported legal needs of women with or at risk for HIV infection. The Her Study Group.

Women at risk for human immunodeficiency virus (HIV) infection are often poor and members of racial or ethnic minorities. In addition to legal concerns that might be common among persons with similar sociodemographic characteristics, HIV infection adds the potential of possible stigma and discrimination, as well as the prospect of illness and increased mortality. To determine women's perceptions of need for and access to legal services and whether such perceptions are affected by HIV infection, from November 1993 through September 1995 we interviewed 509 women with or at risk for HIV infection by virtue of injection drug use or high-risk sexual behaviors in New York and Baltimore, Maryland. A majority of women, regardless of HIV serostatus, reported current or future needs for legal assistance with government benefits. More than 25% reported needing current or future legal help with housing, debts, arrangements for care of children, a will, and advance directives. Substantial minorities of women reported other legal needs. HIV-positive women were significantly more likely to report anticipated future need for help with paternal custody or visitation, current need in making a will, and anticipated future assistance with advance directives. For most items, a majority of women thought they knew where to receive help. However, among women reporting a current need, only a minority actually were receiving legal assistance. This study suggests that the extent of legal needs among women with or at risk for HIV infection is substantial, and that few receive legal assistance. With few exceptions, at least for women early in the course of illness, HIV infection does not appear to alter the pattern or extent of legal needs. There are dramatic differences, regardless of HIV status, between expectation and reality in women's access to legal services.

Adult↗
PubMed1999

Arsenic trioxide induces apoptosis of myeloid leukemia cells by activation of caspases.

The primary objective of this study was to determine whether caspases are involved in arsenic trioxide(ATO)-induced apoptosis of human myeloid leukemia cells. A secondary objective was to determine whether apoptosis induced by ATO compared with VP-16 is differentially affected by an activator of protein kinase C (PKC), phorbol 12-myristate 13-acetate (PMA), which has been reported to inhibit apoptosis induced by some chemotherapeutic agents. NB4 and HL60 cells were incubated with ATO in the presence and absence of the caspase protease inhibitors Z-VAD.fmk or Y-VAD.cho. Apoptosis was assessed by morphology, DNA laddering and flow cytometry. Poly (ADP-ribose) polymerase (PARP) cleavage was used as a marker for the activation of caspases. PARP cleavage occurred during ATO-induced apoptosis in both NB4 and HL60 cells. Z-VAD.fmk, a broad-spectrum inhibitor, could block ATO-induced apoptosis and PARP cleavage, whilst Y-VAD.cho, a selective inhibitor of caspase 1, had no such effect. PMA pre-incubation for up to 8 hours under conditions known to activate PKC had no effect on either ATO- or VP-16-induced apoptosis. We conclude that in cultured myeloid leukemia cells ATO-induced apoptosis is executed by caspases from the distal, PARP-cleaving part of the activation cascade and that PKC activation has no effect on apoptosis induced by either ATO or VP-16 in these cells.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Criteria for assessing cutaneous anergy in women with or at risk for HIV infection. HIV Epidemiologic Research Study Group.

BACKGROUND: Controversy exists about both the clinical utility of anergy testing and the optimal criteria for defining anergy. OBJECTIVE: We sought to assess various definitions of cutaneous anergy for ability to distinguish HIV status, level of immunodeficiency, and ability to mount a tuberculin reaction among women with or at risk for HIV infection. METHODS: HIV-seropositive (n = 721) and HIV-seronegative (n = 358) at-risk women at academic medical centers in Baltimore, Detroit, New York, and Providence had cutaneous testing with mumps, Candida, tetanus toxoid, and tuberculin antigens. Associations with HIV status and CD4+ lymphocyte levels were analyzed. RESULTS: Candida, mumps, and tetanus antigens alone or in combination elicited reactions significantly less often in HIV-seropositive than in HIV-seronegative women and less often in seropositive women with lower CD4+ counts, regardless of induration cutpoint chosen to define a positive reaction. The best antigen combinations for distinguishing groups included tetanus and mumps. Some women nonreactive to the 3 antigens ("anergic") had positive tuberculin reactions among both seropositive subjects (range, 1.1% to 2.9% depending on induration cutpoint for defining anergy) and seronegative subjects (range, 8.9% to 14%). CONCLUSION: Absence of reactions to Candida, mumps, and tetanus antigens alone or in combination and at any induration cutpoint is associated with HIV status and with CD4+ level. Combinations, including tetanus and mumps antigens with an induration cutpoint of less than 2 mm, may be the best for defining anergy.

Antigens, Fungal↗
PubMed1999

Prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive and high-risk HIV-seronegative women. HIV Epidemiology Research Study Group.

This study was undertaken to assess whether the prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive women was higher than among high-risk HIV-seronegative women at their baseline visit for the HIV Epidemiology Research Study. Results were available for 851 HIV-seropositive and 434 HIV-seronegative women. Human papilloma virus (HPV) infection was more prevalent among HIV-seropositive women (64% vs. 28%). Bacterial vaginosis was common (35% vs. 33%), followed by trichomoniasis (12% vs. 10%), syphilis (8% vs. 6%), Chlamydia trachomatis infection (4% vs. 5%), candidal vaginitis (3% vs. 2%), and Neisseria gonorrhoeae infection (0.8% vs. 0.3%). Alcohol use (odds ratio [OR], 1.8; 95% confidence interval [CI], 1. 3-2.4) and smoking (OR, 1.8; 95% CI, 1.3-2.5) were associated with bacterial vaginosis. Bacterial vaginosis (OR, 2.3; 95% CI, 1.5-3.4), trichomoniasis (OR, 2.3; 95% CI, 1.1-4.7), and syphilis (OR, 3.1; 95% CI, 1.3-7.4) were found to be more prevalent among black women. Our study showed no statistically significant difference in the prevalence of lower genital tract infections except for HPV between HIV-infected and demographically and behaviorally similar HIV-uninfected high-risk women.

Adult↗