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Biomedical subjects

R S Klein

Publications and source records attributed to R S Klein.

At least 55 records · Page 3Linked to original sources

Self-assessment of tuberculin skin test reactions by drug users with or at risk for human immunodeficiency virus infection.

SETTING: Self-assessment of tuberculin test results, if accurate, could enhance tuberculosis screening efforts by reducing the need for follow-up visits for skin test reading. We investigated tuberculin test self-assessment in a longitudinal study of tuberculosis infection among drug users. OBJECTIVE: To determine the accuracy of tuberculin reaction self-assessment by drug users at high risk for tuberculosis infection. DESIGN: Two readings were compared of the same skin test, performed 48-72 hours after placement: 1) self-assessment using a simple yes-no approach to induration, versus 2) trained examiner reading. Self-assessments were performed immediately prior to trained examiner readings. RESULTS: Participants were 137 human immunodeficiency virus (HIV) seropositive and 344 HIV-seronegative current and former drug users. Ten per cent (35/344) of reactions read by participants as 'flat' were read by trained examiners as > or =5 mm (54% of which were > or =10 mm). Twenty-three per cent (19/82) of reactions read by trained examiners as > or =10 mm and 32% (35/110) of reactions read by trained examiners as being > or =5 mm were self-read by participants as 'flat'. Sensitivity (0.68) and specificity (0.83) of self-read tuberculin reactions were sub-optimal. Inter-reader reliability was poorer between participants and trained examiners than between trained examiners. CONCLUSION: Self-assessments of tuberculin skin test responses by drug users with or at risk for HIV infection are not reliable.

Adult↗

The effect of immunodeficiency on cutaneous delayed-type hypersensitivity testing in HIV-infected women without anergy: implications for tuberculin testing. HER Study Group. HIV Epidemiology Research.

SETTING: A collaborative study in four urban medical centers in the United States. OBJECTIVE: To determine the effect of human immunodeficiency virus (HIV) infection and immunodeficiency on delayed type hypersensitivity (DTH) responses and the implications for interpretation of tuberculin reactions in non-anergic women with or at risk for HIV infection. DESIGN: Demographic and behavioral information, HIV antibody testing, CD4+ lymphocyte counts, and cutaneous responses to DTH testing with mumps, Candida, tetanus toxoid, and tuberculin (purified protein derivative-PPD) antigens were obtained in 1184 women. RESULTS: Reactions to one or more of the four antigens occurred in 436 HIV-seropositive and 356 high-risk seronegative women. Among non-anergic women, HIV-seropositives were less likely (P < or = 0.05) to react to mumps (62% vs 81%), tetanus (72% vs 84%), and PPD (13% vs 19%). Induration in HIV-seropositive reactors was associated with CD4+ cell level for mumps (P = 0.004) and tetanus (P < 0.001), but not for Candida or PPD. HIV-seropositive reactors with CD4+ cell counts >500/mm3 did not have significantly smaller reactions than HIV-seronegatives for any antigen tested. PPD sizes were similar among HIV-seropositive reactors with CD4+ cell counts >500/mm3 (12.4 +/- 7.4 mm) and HIV-seronegative reactors (12.0 +/- 8.3 mm); induration > or =10 mm was seen in 16/173 (9.2%) seropositive women with CD4+ cell counts >500/mm3 and 41/356 (11.5%) seronegative women, respectively (P = 0.5). CONCLUSION: Among HIV-infected women able to react to a DTH antigen, induration in response to that antigen was relatively intact at CD4+ counts >500/mm3. This suggests that degree of immunodeficiency should be considered when interpreting PPD reactions in HIV-infected persons.

Adolescent↗

Constitutive expression of cellular retinoic acid binding protein II and lack of correlation with sensitivity to all-trans retinoic acid in acute promyelocytic leukemia cells.

The up-regulation of cellular retinoic acid binding protein-II (CRABP-II) has been invoked as an important mechanism of clinically acquired resistance to all-trans retinoic acid (RA) therapy in acute promyelocytic leukemia (APL). To test this hypothesis, we used quantitative reverse transcription-PCR and fast performance liquid chromatography procedures to examine the levels of CRABP-II mRNA and RA binding activity in APL patient samples. We found that CRABP-II mRNA in APL cells from pretreatment patients (n = 36) was constitutively expressed at relatively high levels (median, 0.92; range, 0.16-4.13) relative to the level in CRABP-H protein-expressing NB4 cells (arbitrarily set at 1.0 unit). Consistent with this finding, the RA binding activity of CRABP in APL cells from three pretreatment cases (range, 27.2-53.2 fmol/mg protein) was similar to that of NB4 cells (22.6 +/- 5.4 fmol/mg protein). Furthermore, in the pretreatment samples, there was no association between CRABP-H mRNA expression level and APL cellular sensitivity to RA-induced differentiation in vitro. After 45 days of remission induction therapy on Eastern Cooperative Oncology Group protocol E2491, CRABP-II mRNA was modestly increased from day 0 values in patients treated with either RA (median increase, 0.41) or chemotherapy (median increase, 0.56), and there was no significant difference between the two treatment groups (P = 0.91). In patients studied after relapse from RA therapy (n = 7), there was a significant decline in APL cell sensitivity to RA-induced differentiation in vitro compared with patients after relapse from chemotherapy (n = 5; P = 0.015-0.055 at three RA concentrations tested), but in the RA relapse cases, there was no change from pretreatment levels of CRABP-II mRNA (median, 0.98) or, in three relapse cases studied, of RA protein binding activity (range, 22.1-70.7 fmol/mg protein). Taken together, our data strongly imply that variations in CRABP-II expression and RA binding activity are not causally related to the development of clinically acquired APL cellular RA resistance, but rather, they suggest that constitutive expression of CRABP-II could have a facilitative role in the response of APL cells to RA.

Cell Differentiation↗

A prospective study of tuberculosis and HIV disease progression.

OBJECTIVE: To determine whether active tuberculosis alters the rate of progression of HIV infection in dually infected patients. METHODS: HIV-seropositive patients at two Bronx, New York hospitals with tuberculosis confirmed by culture from July 1992 to February 1995, who survived the initial hospitalization for tuberculosis, were matched on gender, age, CD4+ percentage, and calendar time with HIV-seropositive patients without tuberculosis participating in a study of the natural history of HIV infection. Patients received follow-up observation prospectively until May 23, 1995 to determine survival rates and development of AIDS-defining opportunistic infections (OIs). RESULTS: 70 patients had tuberculosis; 120 did not. Mean CD4+ percentages were 12.4% and 12.5%, respectively. At study entry, 27% of those with tuberculosis had prior AIDS-defining OIs other than tuberculosis, compared with 10% of those without tuberculosis (p = .004). In multivariate survival analysis, controlling for CD4+ level, tuberculosis was not an independent predictor of increased other causes of AIDS-related mortality. However, in a logistic regression model, independent predictors of subsequent OIs included tuberculosis (hazard ratio, 4.1; 95% confidence intervals [CI], 1.9, 8.7), CD4+ count <100/mm3 (hazard ratio, 2.4; 95% CI, 1.1, 5.0) and prior OIs (hazard ration, 3.3; 95% CI, 1.3, 8.3). CONCLUSIONS: Tuberculosis was not an independent predictor of increased non-tuberculosis-related mortality in HIV-seropositive patients but was associated with increased risk of development of OIs.

AIDS-Related Opportunistic Infections↗

Oral lesions among women living with or at risk for HIV infection. HIV Epidemiology Research Study (HERS) Group.

PURPOSE: Our objectives were to compare the prevalence of oropharyngeal mucosal lesions among human immunodeficiency virus (HIV) seropositive and demographically similar seronegative women, and to determine the association of oral lesions with immunosuppression, substance abuse, use of medications, and utilization of dental services. POPULATION AND METHODS: Participants in a multicenter, longitudinal cohort study of HIV infection in women were evaluated at baseline by interview, physical examination, and laboratory studies. RESULTS: Oropharyngeal pathology was found in 40% of seropositive and 23% of seronegative women. Oral candidiasis was identified in 15% of seropositive and 3% of seronegative women. Among seropositive women, history of previous oral candidiasis, lower CD4 lymphocyte counts, and current antibiotic use were associated with oral candidiasis. Hairy leukoplakia was identified in 5% of seropositive women and was significantly associated with lower CD4 lymphocyte counts. Gingival erythema and ulcerative gingivitis were found in 23% of participants overall, but were unrelated to HIV serostatus or CD4 lymphocyte count. Substance abuse, lack of dental care, and African-American race were associated with gingival pathology. CONCLUSION: The high prevalence of oral lesions among HIV seropositive and at-risk seronegative women underscores the need for routine oral examination and targeted treatment of this population.

AIDS-Related Opportunistic Infections↗

Serum IgE levels in patients with human immunodeficiency virus infection.

BACKGROUND: Increased serum IgE levels are associated with advanced HIV infection. The magnitude of the increase has varied greatly between studies which generally did not assess potential confounding factors. OBJECTIVE: To determine whether the increased serum IgE levels reported with HIV infection is affected by demographic or behavioral factors, we studied injection drug users, women, and minority ethnic and racial groups with HIV infection, for whom little data now exist. METHODS: A prospective cross-sectional study of ambulatory patients with or at risk for HIV infection was performed. We enrolled 83 injection drug users and 56 non-drug users seropositive for HIV and 43 seronegative at-risk individuals from an Infectious Diseases clinic and a longitudinal study of HIV infection in injection drug users in the Bronx, New York City. Fifteen HIV-seronegative non-atopic controls were also studied. Total serum IgE levels were measured by a solid phase fluorescent assay and lymphocyte phenotypes were measured by monoclonal antibodies. RESULTS: On multiple linear regression analysis, HIV infection (P=.01) and advanced HIV disease (P < or =.01) were independently associated with increased serum IgE levels, controlling for gender, race, age, and use of injection drugs. In both HIV-seronegative and seropositive individuals, female gender was independently associated with lower IgE levels (P < or = .001). We did not find an independent effect of race or injection drug use on IgE levels. CONCLUSIONS: Increased serum IgE levels were associated with HIV infection, the highest levels existing in those with advanced HIV disease. Women had lower IgE levels than men, independent of HIV status. Active or past drug use, race, and age were not found to be independently associated with serum IgE levels. Further studies are necessary to elucidate the mechanisms underlying the increased serum IgE levels seen with HIV infection and its associated immunodeficiency, and to substantiate and explore the decreased levels found in women.

Adult↗

Mucosal candidal colonization and candidiasis in women with or at risk for human immunodeficiency virus infection. HIV Epidemiology Research Study (HERS) Group.

The epidemiology of mucosal candidal colonization and candidiasis was studied in a multicenter cohort of 871 human immunodeficiency virus (HIV)-seropositive and 439 demographically and behaviorally similar HIV-seronegative women. Cross-sectional analyses at baseline revealed that oropharyngeal colonization with Candida species was more prevalent among seropositive women and among women reporting recent cigarette smoking and injection drug use. Oropharyngeal candidiasis was also more prevalent among seropositive women. Both oropharyngeal colonization and candidiasis were significantly associated with a lower median CD4 lymphocyte count among seropositive women. Vaginal candidal colonization was more prevalent among seropositive women and among those reporting recent injection drug use and current insulin or oral antihyperglycemic therapy. Vaginal candidiasis was equally likely to be diagnosed in seropositive and seronegative women and was not significantly related to recent sexual contact. Neither vaginal colonization nor candidiasis was significantly related to a lower median CD4 lymphocyte count among seropositive women. Baseline evaluation indicated differences in the epidemiology of oropharyngeal and vaginal candidal colonization and candidiasis in HIV-seropositive women and suggested possible variation in pathogenesis of candidal infection at these two mucosal sites.

AIDS-Related Opportunistic Infections↗

Overview of HIV and AIDS: biology and epidemiology of the virus.

HIV-1 infects mononuclear cells using the CD4+ molecule and the chemical receptors of those cells. After a prolonged clinical latency period, the ability to replace destroyed cells is outpaced by ongoing cellular destruction, leading to the characteristic immunodeficiency of AIDS and its opportunistic infections and neoplasms. In the United States, the number of new cases of AIDS has diminished in recent years, although in some groups, such as women, the number of new cases continues to rise. In the developing world, AIDS remains a pandemic of huge proportions. In the absence of an effective vaccine, culturally appropriate efforts at education and behavior modification offer the best hope of controlling AIDS.

Acquired Immunodeficiency Syndrome↗

Temporal trends in the progression of human immunodeficiency virus disease in a cohort of drug users.

We evaluated changes over time in rates of progression to AIDS, mortality, and distribution of AIDS-defining illnesses in 524 human immunodeficiency virus (HIV)-seropositive injection drug users enrolled between 1986 and 1995 in a prospective study of HIV infection in the Bronx, NY. At enrollment, participants attended a hospital-affiliated methadone maintenance program with on-site primary care. Using the 1993 clinical definition of AIDS, we found that the hazard ratio (HR) of progression to AIDS declined for enrollees over time in comparison with the referent group of persons enrolled in 1986-1987. For program enrollees in 1988-1989, the HR was 1.0 [95% confidence interval (CI) = 0.6-1.6]; for enrollees in 1990-1991, the HR was 0.3 (95% CI = 0.1-0.9); for enrollees in 1992-1993, the HR was 0.5 (95% CI = 0.3-0.9); and for enrollees in 1994-1995, the HR was 0.2 (95% CI = 0.1-0.7), after controlling on initial CD4+ cell counts and age. Nevertheless, the greater AIDS-free time of later study entrants was not associated with reduced mortality. The study provides evidence that drug users with access to primary care likely benefited from improved management of HIV disease in prolonging AIDS-free time but, through 1996, did not experience greater survival.

Acquired Immunodeficiency Syndrome↗

Staphylococcus aureus nasal colonization in HIV-seropositive and HIV-seronegative drug users.

Nasal colonization plays an important role in the pathogenesis of Staphylococcus aureus infections. To identify characteristics associated with colonization, we studied a cross-section of a well-described cohort of HIV-seropositive and -seronegative active and former drug users considered at risk for staphylococcal infections. Sixty percent of the 217 subjects were Hispanic, 36% were women, 25% actively used injection drugs, 23% actively used inhalational drugs, 23% received antibiotics, and 35% were HIV-seropositive. Forty-one percent of subjects had positive nasal cultures for S. aureus. The antibiotic susceptibility patterns were similar to the local hospital's outpatient isolates and no dominant strain was identified by arbitrarily primed polymerase chain reaction (AB-PCR). Variables significantly and independently associated with colonization included antibiotic use (odds ratio [OR] = 0.37; confidence interval [CI] = 0.18-0.77), active inhalational drug use within the HIV-seropositive population (OR = 2.36; CI = 1.10-5.10) and female gender (OR = 1.97; CI = 1.09-3.57). Characteristics not independently associated included injection drug use, HIV status, and CD4 count. The association with active inhalational drug use, a novel finding, may reflect alterations in the integrity of the nasal mucosa. The lack of association between HIV infection and S. aureus colonization, which is contrary to most previous studies, could be explained by our rigorous control for confounding variables or by a limited statistical power due to the sample sizes.

AIDS-Related Opportunistic Infections↗

Rates of and factors associated with self-reported prior HIV testing among adult medical patients in an inner city emergency department in the Bronx, New York City.

We studied the rates of and factors associated with self-reported prior human immunodeficiency virus (HIV) testing in adult patients visiting an emergency department (ED) in the Bronx, New York City. A total of 1,744 consecutive noncritical adult medical emergency patients responded to a standardized interview administered by ED physicians. The interview included questions pertaining to demographic characteristics, prior HIV testing, and HIV risk behaviors. On multivariate analysis, female gender, younger age, history of weight loss, injecting drug use (IDU), syphilis, and genital herpes were all associated with increased reported prior testing rates. Race (i.e., black race) was an independent predictor of increased rates among male subjects; comparatively low rates were reported by patients with a first language other than English, patients lacking medical insurance, and highly sexually active, nonblack men. Increased HIV testing rates were reported by subjects with recognized HIV risk behaviors in a New York City ED population; however, substantial proportions of subjects at risk had not been tested. Programs of HIV testing and counseling need to include older, uninsured, and non-English-speaking segments of the population who engage in high-risk behaviors.

Adolescent↗

A prospective study of tuberculosis and human immunodeficiency virus infection: clinical manifestations and factors associated with survival.

We prospectively studied the effect of human immunodeficiency virus (HIV) infection on the presentation and outcome of tuberculosis. A total of 216 patients with tuberculosis were identified; 162 (75%) of these patients were tested for antibodies to HIV; 92 (57%) were seropositive. The patients who were seropositive for HIV were more likely to be male and Hispanic and to have been homeless or incarcerated. Eighty-one percent of these patients had CD4 lymphocyte counts of < or =200/mm3. The seropositive patients had extrapulmonary tuberculosis more often than did the seronegative patients (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2-4.8). Smears for acid-fast bacilli were positive more often for non-HIV-infected patients with pulmonary tuberculosis (74.5%) than for HIV-infected patients (54.3%) [OR, 2.46; 95% CI, 1.01-6.02]-even those with focal or cavitary disease. A delay in initiating therapy was associated with in-hospital mortality: the median time from admission to the start of treatment was 4 days for patients who survived and 15 days for those who died (P = .02). The median survival was 22.7 months for HIV-infected patients who did not die during the initial hospitalization. Factors independently associated with reduced rates of survival included the severity of immunodeficiency, nonuse of directly observed therapy, infection due to drug-resistant Mycobacterium tuberculosis, and a history of injection drug use.

AIDS-Related Opportunistic Infections↗

Comparison of the InPouch TV culture system and Diamond's modified medium for detection of Trichomonas vaginalis.

This study compared the use of Diamond's modified medium to InPouch for the culture of Trichomonas vaginalis from pooled vaginal secretions. The sensitivity for InPouch was 82.4% (61/74) versus 87.8% (65/74) for Diamond's modified medium. There were no significant differences in the sensitivity and negative predictive value of InPouch compared to Diamond's modified medium.

Adult↗

PCR detection of human papillomavirus: comparison between MY09/MY11 and GP5+/GP6+ primer systems.

Human papillomavirus (HPV) is an etiologic agent of cervical cancer and is the most common sexually transmitted disease in women. PCR amplification of HPV genomes is the most sensitive method for the detection of cervicovaginal HPV. We have compared the two most commonly used PCR primer sets, MY09/MY11 (MY-PCR) and GP5+/GP6+ (GP+-PCR), for the detection of HPV DNA in cervicovaginal lavage samples from 208 women. Oligonucleotide probes for 39 different HPV types were used. Both primer sets amplified a wide spectrum of HPV genotypes and detected similar overall prevalences of 45% (94 of 208) and 43% (89 of 208), respectively. The MY-PCR system detected 27 of 30 (90%) samples with multiple HPV types, whereas the GP+-PCR system detected 14 of 30 (47%) samples with multiple HPV types. Differences in the detection of HPV types 35, 53, and 61 were noted between the two primer systems. Serial dilution of plasmid templates indicated a 3-log decrease in the amplification of HPV type 35 by MY-PCR and HPV types 53 and 61 by GP+-PCR. These results indicate that although the MY-PCR and GP+-PCR identified nearly equivalent prevalences of HPV in a set of clinical samples, differences in the detection of specific types and infections with multiple types were found. Differences in the sensitivities and characteristics of the PCR systems for the detection of HPV within clinical samples should be considered when comparing data between studies and/or in designing new studies or clinical trials.

DNA Primers↗

Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation.

The prevalence of Mycobacterium tuberculosis (MTB) has increased worldwide, in part due to the HIV epidemic. Epidemiology data have demonstrated that HIV-infected individuals are more susceptible to MTB disease, which may lead to an acceleration in the progression of HIV disease. The purpose of this study was to determine whether MTB modulates HIV infection in vivo and to delineate the mechanisms involved by using in vitro model systems. Plasma viral load was measured in HIV-infected individuals before, during, and after the development of MTB disease; a 5- to 160-fold increase in viral replication was observed during the acute phase of MTB disease. In order to evaluate the mechanisms involved in this MTB-induced HIV replication, we used an in vitro system of primary PBMC and lymph node mononuclear cells isolated from HIV-infected individuals. The data demonstrated that MTB induced HIV replication in CD8+ T cell-depleted lymphocytes from HIV-infected individuals with a history of purified protein derivative (PPD) positivity but not in those who were PPD negative; this induction of HIV replication correlated with the level of cellular activation. In an in vitro acute HIV infection model, MTB increased HIV replication in PBMC from healthy donors with a history of PPD positivity, but not in PBMC from PPD-negative donors and this induction of viral replication also correlated with cellular activation. In conclusion, MTB increased HIV replication in vivo and in an in vitro model. This MTB-mediated viral production likely occurs through Ag-specific activation and infection of responding T cells.

Acquired Immunodeficiency Syndrome↗