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N Galai

Publications and source records attributed to N Galai.

51 records · Page 3Linked to original sources
PubMed1995

Failure of T-cell homeostasis preceding AIDS in HIV-1 infection. The Multicenter AIDS Cohort Study.

We and others have postulated that a constant number of T lymphocytes is normally maintained without regard to CD4+ or CD8+ phenotype ('blind' T-cell homeostasis). Here we confirm essentially constant T-cell levels (despite marked decline in CD4+ T cells and increase in CD8+ T cells) in homosexual men with incident human immunodeficiency virus, type 1 (HIV-1), infection who remained free of acquired immunodeficiency syndrome (AIDS) for up to eight years after seroconversion. In contrast, seroconverters who developed AIDS exhibited rapidly declining T cells (both CD4+ and CD8+) for approximately two years before AIDS, independent of the time between seroconversion and AIDS, suggesting that homeostasis failure is an important landmark in HIV disease progression. Given the high rate of T-cell turnover in HIV-1 infection, blind T-cell homeostasis may contribute to HIV pathogenesis through a CD8+ T lymphocytosis that interferes with regeneration of lost CD4+ T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Sexual transmission of hepatitis C virus among patients attending sexually transmitted diseases clinics in Baltimore--an analysis of 309 sex partnerships.

The prevalence of antibodies to hepatitis C virus (anti-HCV), the behavioral and laboratory-derived risk factors for anti-HCV, and the quantity and homology of HCV RNA were assessed among 1039 non-injection drug-using sexually transmitted disease (STD) patients representing 309 sex partnerships. Thirty-seven (7%) of 555 males and 19 (4%) of 484 females had anti-HCV. In logistic regression analyses, factors associated with anti-HCV included age (P < .001), greater numbers of lifetime sex partners (P = .023), human immunodeficiency virus infection (P < .001), Trichomonas infection (P < .001), cigarette smoking (P < .001), and male homosexual exposure (P = .012). Among couples, females whose sex partners were anti-HCV positive were 3.7 times more likely to have anti-HCV than females whose sex partners were anti-HCV negative (P = .039). The proportion of RNA homology between anti-HCV positive females and their male partners (94%) was higher than among randomly selected patients (82%). Sexual transmission of HCV may contribute to the high prevalence of anti-HCV reported in urban settings.

Adolescent↗
PubMed1995

Clinical characteristics and prognostic value of acute retroviral syndrome among injecting drug users. Italian Seroconversion Study.

OBJECTIVE: To estimate the frequency of acute retroviral syndrome associated with HIV infection among injecting drug users (IDU), and to determine the extent to which acute retroviral syndrome predicts a faster rate of progression to AIDS and immunosuppression in this population. DESIGN: Prospective study of HIV seroconverters (median follow-up, 50.5 months). SETTING: Sixteen clinical centres throughout Italy established to study the natural history of HIV infection. PATIENTS: Three hundred and ninety-one IDU for whom the date of HIV seroconversion was established with a 9-month precision. MAIN OUTCOME MEASURES AND METHODS: Incidence of acute retroviral syndrome with signs and symptoms that included fever (temperature > 38 degrees C) occurring within 6 months prior to the time of first positive HIV test, progression to AIDS, crude and adjusted relative hazard of AIDS using survival analysis techniques, and trajectories of CD4+ cell counts using a piece-wise linear regression model incorporating the degree of dependency of within-person measurements. RESULTS: Of 391 HIV seroconverters, 39 (10.0%) were diagnosed with acute retroviral syndrome. During follow-up, 13 seroconverters with acute retroviral syndrome and 24 asymptomatic seroconverters developed AIDS. The Kaplan-Meier estimates for the cumulative AIDS incidence during 4.5 years of follow-up were 26.8 and 6.5%, respectively; the relative hazard of developing AIDS for acute retroviral syndrome was 5.59 (95% confidence interval, 2.79-11.20) after adjustment for age, sex and year of seroconversion. Although CD4+ level within the first year from seroconversion was similar, the rate of CD4+ cell decline after 1 year from seroconversion was faster in individuals with acute retroviral syndrome than in those without this syndrome (P < 0.001). CONCLUSIONS: Among HIV-infected IDU, a distinct acute retroviral syndrome is apparent and associated with a faster rate of clinical progression to AIDS and HIV-related immunosuppression.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Cognitive performance after progression to AIDS: a longitudinal study from the Multicenter AIDS Cohort Study.

OBJECTIVE: To describe changes in cognitive functioning before and after development of an acquired immune deficiency syndrome (AIDS)-defining illness or CD4+ lymphocyte count < 200/mm3 in participants in the Multicenter AIDS Cohort Study. METHODS: The study population included participants who either were diagnosed with an AIDS-defining illness (n = 52) or had at least one measurement of CD4+ count < 200/mm3 (n = 57) and who had at least four neuropsychological (NP) evaluations, two or more before and two or more after the AIDS diagnosis. A group of subjects with clinical diagnosis of dementia (n = 29) was also included for comparison. The NP test battery included measures of attention, memory, constructional abilities, and psychomotor speed. Longitudinal data analysis, using the generalized estimating equation, was performed separately for each NP measure. Time was measured in months from the date of clinical AIDS or CD4+ < 200/mm3. RESULTS: Before AIDS< the dementia group showed significant decline (slope different from zero) only on measures of psychomotor speed. For all other measures, there was no evidence of decline in performance before AIDS for the other groups. After development of AIDS, the group with clinical AIDS showed significant decline on psychomotor speed but none on the other cognitive measures. The group with CD4+ < 200/mm3 did not show significant decline on any of the cognitive measures after AIDS. As expected, the dementia group showed significant decline on all measures. Sensory neuropathy was associated with a significant decline in performance on measures of psychomotor speed after AIDS. Antiretroviral therapy was not associated with any measurable changes in NP performance. CONCLUSION: These results are consistent with previous findings showing no significant decline in cognitive functions before AIDS, unless overt dementia is present, and no decline in immunosuppressed subjects who have had no AIDS-defining illness. By contrast, in subjects who have developed clinical AIDS, there is mild decline in fine motor skills but no significant change in other cognitive domains.

AIDS Dementia Complex↗
PubMed1994

Sample size estimation using repeated measurements on biomarkers as outcomes.

The objectives of this paper are to (1) examine methods of using longitudinal data in designing comparative trials and calculating sample sizes or power and (2) show the effect of autocorrelation of repeated measures on the assessment of sample sizes. A statistical model with a simple regression structure for the mean trajectory of the longitudinal data and a two-parameter model for the correlations of within-individual observations given by corr(yt,yt+s) = gamma s theta is used. The methods are illustrated by considering a two-group trial and investigating the effect of different values of the correlation parameters, gamma and theta on the sample size. The results show that taking account of the autocorrelation structure of longitudinal data may lead to more efficient designs. Specifically, the stronger the autocorrelation is, the smaller the sample size that is required.

AIDS Vaccines↗
PubMed1994

Comparison of clinical manifestations of HIV infection between male and female injecting drug users.

OBJECTIVE: To compare occurrence of clinical symptoms, physical examination findings and hematologic variables in male and female HIV-seropositive injecting drug users (IDU) with similar CD4+ lymphocyte counts. METHOD: We interviewed and examined 118 female and 444 male AIDS-free HIV-seropositive IDU for clinical signs and symptoms. HIV serology and T-lymphocyte subset evaluations were performed. Comparisons were analyzed by Mantel-Haenszel procedures. RESULTS: In this population, median age for men was 35 years versus 33 years for women; median CD4 cell count was 490 x 10(6)/l for men versus 480 x 10(6)/l for women. The overall frequency of oral candidiasis increased as CD4 cell count decreased, but did not vary by sex. Recent history of genital herpes was more frequent (P < 0.05) in women than men, but this difference was not significant on physical examination. Symptoms of diarrhea, fatigue, weight loss, shortness of breath, presence of enlarged posterior cervical lymph nodes did not vary by CD4 cell count or sex, and no strong interactions were evident. Although absolute values of hematocrit were higher (P < 0.001) and platelet count lower (P < 0.001) in HIV-seropositive men than women, distributions of hematocrit and platelet count by sex were similar for HIV-seropositive participants and HIV-seronegative controls. CONCLUSION: Our data on IDU prior to a diagnosis of AIDS suggest that constitutional signs and symptoms are generally similar among men and women early in HIV infection. Additional follow-up is needed to determine whether differential rates of signs and symptoms by sex appear with progression of HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1994

Preparations for AIDS vaccine trials. Incident human immunodeficiency virus (HIV) infections in a cohort of injection drug users in Baltimore, Maryland.

In order to prepare for a possible trial of a preventive human immunodeficiency virus (HIV) vaccine in a population of injection drug users (IDUs) we followed a cohort to determine their HIV incidence, compliance with follow-up visits at 3-month intervals (i.e., quarterly) and their attitudes toward HIV vaccine trial participation. A population of 671 HIV-seronegative subjects were recruited from a cohort of IDUs already in follow-up in Baltimore, MD (the ALIVE study). We detected 19 seroconverters in 1677.80 person-quarters of follow-up, an annual incidence of 4.52/100 person-years. Compliance with quarterly follow-up was 93% at 6 months and 89% at 9 months. Although many subjects (n = 104) are not yet due for their 12-month visit, compliance to date has been 76%. The most sensitive risk behaviors associated with HIV seroconversion have been continued injection of illicit drugs and the frequency of drug use. Other reported drug associated risk behaviors, e.g., needle sharing and shooting gallery use, have decreased despite a high HIV incidence; we believe some of the reported reductions in high-risk behavior represent socially desirable responses by the study subjects. Although the difficulties in successfully doing a trial of an HIV vaccine in the population should not be underestimated, our data suggest that such a trial would be feasible.

AIDS Vaccines↗
PubMed1994

Interest in HIV vaccines among injection drug users in Baltimore, Maryland.

To gauge interest about participation in human immunodeficiency virus type 1 (HIV vaccines, we interviewed 375 HIV-seronegative injecting drug users who are participants in an ongoing longitudinal study of HIV infection. Nearly all (93%) responded that they thought it likely that an HIV vaccine would become available, and 85% expressed interest in participating in a study of vaccine effectiveness. However, levels of interest decreased to 47% when respondents were informed that the vaccine might result in a positive HIV test and to 27% when offered to be in a study where the vaccine might contain a piece of the virus. Factors that increased interest in trial participation included assurances of confidentiality, being fully informed about the protocol and remuneration. Most respondents (78%) felt that injecting drug users would maintain other risk reduction activities (e.g., condom use) if they participated in a vaccine study. These data suggest a high level of interest for participation in HIV vaccine trials, but that more education about vaccines and the risks involved is needed. Ongoing communication with the community and responsiveness to community concerns is crucial to achieve a successful vaccine study.

AIDS Vaccines↗
PubMed1993

Tracking of markers and onset of disease among HIV-1 seroconverters.

Repeated measurements on persons infected with HIV-1 indicate that infection has a dynamic impact on several markers of immune suppression and activation. The objectives of this report are: (a) to provide a statistical model for the correlation structure of serial measurements of immunological markers, and (b) to identify features of marker profiles associated with the timing of AIDS diagnoses. We analyse data obtained from 328 seroconverters participating in the Multicenter AIDS Cohort Study on whom the date of HIV-1 seroconversion is known within +/- 4.5 months. Immunological markers considered here are CD4 cell counts, serum beta 2-microglobulin and serum neopterin. The statistical model for HIV-related changes in markers consists of (1) a piecewise linear regression model for the trajectories of markers over time and (2) a two-parameter autocorrelation function that generalizes Markovian and simple random effects autocorrelation structures. Application of this model for marker measurements revealed a high degree of tracking, as the estimated autocorrelation function exhibited sub-exponential decay over time. Though current marker levels are most informative on future values, there is substantial information (memory) in previous measurements. A feature suggested by the analysis of groups formed according to the length of the AIDS-free period, is the sequential divergence of the CD4 trajectories where steeper declines occurred with a two-year lag prior to AIDS onset. For AIDS cases diagnosed 3-5 and 5-7 years after seroconversion, the rates of decline compared with those free of AIDS for at least 4 years were steeper by 95 and 46 per cent respectively at two years prior to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Comparison of clinical symptoms of human immunodeficiency virus disease between intravenous drug users and homosexual men.

BACKGROUND: To compare the prevalence of human immunodeficiency virus (HIV)-related clinical symptoms among male intravenous drug users and homosexual men stratified by HIV serostatus and CD4 cell levels. METHODS: A cross-sectional sample using concurrent longitudinal studies of the natural history of HIV-1 infection among intravenous drug users (N = 539) and homosexual men (N = 932) was recruited in Baltimore, Md. Participants were administered a risk behavior interview and physical examination, and had hematologic tests evaluated in a similar calendar period. RESULTS: Both risk groups demonstrated an inverse relationship between frequency of symptoms and CD4 cell count. Fever, night sweats, and lymphadenopathy were not evaluated because pilot data suggested a confounding association with drug injection. Among those with mild to moderate immune suppression, intravenous drug users were significantly more likely than homosexual men to experience fatigue, weight loss, diarrhea, and shortness of breath; to have oral candidiasis, palpable spleen, and lower mean weight on physical examination; and abnormal hematocrit, platelets, and total lymphocyte counts. However, participants in either risk group with CD4 cell levels below 0.2 x 10(9)/L experienced similar frequency of all clinical symptoms. Self-reported oral candidiasis increased fourfold with HIV infection and was as likely in both groups at all CD4 cell levels. Duration and recency of intravenous drug use was not significantly associated with the higher frequency of most clinical symptoms. CONCLUSION: Social factors are an important consideration in evaluating the association between clinical symptoms and HIV immunosuppression. Except for oral candidiasis, there are limitations for the use of clinical symptoms as intermediate outcome measures for HIV infection among intravenous drug users.

Adult↗
PubMed1993

Cox regression models for intermediate events, with discharge from hospital as an example.

In studies of mortality or morbidity of hospitalized patients, discharge from hospital is an intermediate event between hospital experience and disease outcomes, as disease onset may occur after release from hospital. This study explored the role that discharge might have in risk for surgical infections after hernia repair operations, where follow-up continued for 1 month after operation, and 50% of infections occurred at home. Possible direct and interactive effects were evaluated in the presence of two major methodologic difficulties: waiting-time bias, because patients became candidates for home infections only after leaving the hospital, and selective discharge bias, because discharge carried much prognostic information. It was possible, using Cox models, to correct for the waiting-time bias, but the strong protective effect of termination of hospitalization on the risk for infection remained difficult to interpret. The strengths and limitations of various Cox models in dealing with these issues are discussed.

Adult↗
PubMed1993

Estimation of creatinine clearance without 24-hour urine collection--a useful guide during cisplatin therapy.

The validity of the Cockroft and Gault formula in monitoring renal function during cisplatin therapy was examined in 110 consecutive cancer patients. A good correlation between estimated creatinine clearance (ECC) and the standard measured creatinine clearance (MCC) was found both before and after the onset of cisplatin. The correlation was better in males (r = 0.78 prior to cisplatin and r = 0.79 after the initiation of cisplatin) than in females (r = 0.69 and r = 0.63 respectively). Obesity (> 125% of ideal body weight) had no major effect on the correlation between ECC and MCC. The presence of third-space body fluids, on the other hand, had an influence on the relations between ECC and MCC, particularly in females (r = 0.49). It is concluded that estimation of creatinine clearance, without the cumbersome collection of 24-h urine specimens, is accurate enough for the purpose of adjusting cisplatin dose. It should not be used in females with third-space body fluids.

Adolescent↗
PubMed1992

Discharge from hospital and its effect on surgical wound infections. The Israeli Study of Surgical Infections (ISSI).

A multicenter study of 2846 consecutive hernia operations was conducted to identify risk factors for infections that occurred during the hospitalization and post-discharge from hospital. Operated patients were followed-up for 30 days after surgery, whether at home or still hospitalized, and half the wound infection episodes were found to occur at home. Risk factors for both in-hospital and post-discharge infections seemed to be influenced by; (a) the selective nature of discharge, (b) the differential effect some risk factors had on either early or late infections. On any given day, patients selected by the clinical team to remain in hospital were more "at risk" for infection than those who left. As a result, they had a better chance of being diagnosed as infected during hospitalization. By contrast, those who were discharged home were perceived as low risk for complications. Subsequent infections in these patients occurred either due to factors "causing" late infections, therefore, unappreciated at the time of discharge, or unknown risk factors. More study risk factors were associated with in-hospital than with post-discharge infections, especially those associated with "early" infections. The implications of these findings for future evaluations of medical care in hospitalized patients are discussed.

Female↗
PubMed1992

Differential effect of risk factors on early and late wound infections in patients undergoing herniorrhaphies.

In a prospective follow-up of 2846 patients who underwent hernia repair in 22 general surgery departments in Israel, factors affecting early or late infections were explored. Risk factors included inherent patient characteristics such as old age, ethnic group, and type of hernia prior to the surgery. Patient management factors included duration of the operation, use of urinary catheters, and use of drains. Of the 12 variables studied, only three had a constant effect during the entire 30-day follow-up. The other factors affected the occurrence of either early or late infections, but not both. For example, patients undergoing long operations, or from ethnic minorities, had a high rate of early infection, while those with special wound treatment (such as evacuation of hematomas) had high rates of late infection. It is postulated that factors present at the time of the operative incision tend to "cause" early infections, while factors that accumulate over time, or develop after leaving the operating theater, tend to affect late infections.

Adult↗