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2.
AIDS ; 15(16): 2137-47, 2001 Nov 09.
Article in English | MEDLINE | ID: mdl-11684933

ABSTRACT

BACKGROUND: Treatment of latent infection is needed to protect HIV-infected individuals against tuberculosis. A previous report addressed short-term efficacy of three regimens in HIV-infected adults. We now report on long-term efficacy of the study regimens. METHODS: Three daily self-administered regimens were compared in a randomized placebo-controlled trial in 2736 purified protein derivative (PPD)-positive and anergic HIV-infected adults. PPD-positive subjects were treated with isoniazid (INH) for 6 months (6H), INH plus rifampicin for 3 months (3HR), INH plus rifampicin and pyrazinamide for 3 months (3HRZ), or placebo for 6 months. Anergic subjects were randomized to 6H or placebo. RESULTS: 6H initially protected against tuberculosis in PPD-positive individuals; however, benefit was lost within the first year of treatment. Sustained benefit was observed in persons receiving 3HR and 3HRZ. In a Cox regression analysis, the adjusted relative risk for tuberculosis compared with placebo was 0.67 [95% confidence interval (CI), 0.42-1.07] for 6H, 0.49 (95% CI, 0.29-0.82) for 3HR, and 0.41 (95% CI, 0.22-0.76) for 3HRZ. When the rifampicin-containing regimens were combined, the adjusted relative risk for tuberculosis compared with placebo was 0.46 (95% CI, 0.29-0.71). Among anergic subjects, a modest degree of protection with 6H was present (adjusted relative risk, 0.61; 95% CI, 0.32-1.16). Treatment of latent tuberculosis infection had no effect on mortality. CONCLUSION: Six months of INH provided short-term protection against tuberculosis in PPD-positive HIV-infected adults. Three month regimens including INH plus rifampicin or INH, rifampicin and pyrazinamide provided sustained protection for up to 3 years.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Antitubercular Agents/therapeutic use , HIV Infections/complications , Tuberculosis, Pulmonary/drug therapy , AIDS-Related Opportunistic Infections/epidemiology , AIDS-Related Opportunistic Infections/microbiology , Adolescent , Adult , Antitubercular Agents/pharmacology , Drug Therapy, Combination , Female , HIV Infections/drug therapy , Humans , Incidence , Isoniazid/pharmacology , Isoniazid/therapeutic use , Male , Microbial Sensitivity Tests , Middle Aged , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Pyrazinamide/pharmacology , Pyrazinamide/therapeutic use , Rifampin/pharmacology , Rifampin/therapeutic use , Time Factors , Treatment Outcome , Tuberculin Test , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/microbiology
3.
Clin Exp Immunol ; 123(2): 233-8, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11207653

ABSTRACT

Active TB in HIV-1-infected subjects is associated with increased HIV-1-related immunodeficiency and mortality. We assessed plasma viral load in HIV-1-infected patients with pulmonary TB (HIV/TB) and non-TB symptomatic HIV-1-infected patients (HIV). HIV-1 load was higher in HIV/TB compared with HIV at higher CD4 counts (> 500/microl) (P < 0.01), but not at lower CD4 counts (< 500/microl). We also evaluated the status of HIV-1 gene expression in peripheral blood mononuclear cells (PBMC) and serum from HIV/TB and CD4-matched healthy HIV-infected patients (HIV/C) by reverse transcriptase-polymerase chain reaction over a range of CD4 (> 900/microl to < 200/microl). HIV-1 RNA in serum and PBMC correlated to one another, and both were markedly higher in HIV/TB compared with HIV/C with higher CD4 counts. Also, during a longitudinal study of anti-tuberculous chemoprophylaxis in HIV-1-infected patients, 10 subjects who developed TB had serologies before, at the time, and after the diagnosis of TB. These HIV/TB patients had an increase in viral load (average 2.5-fold) at the time of diagnosis of TB (P < 0.05). Overall, these data indicate that the transcriptional activity of HIV-1 is enhanced in HIV-1-infected patients with active TB, especially during early HIV-1 disease. As TB often is an early HIV-1 opportunistic infection, it may particularly favour early viral replication and dissemination, and therefore contribute to progression of HIV-1 disease.


Subject(s)
HIV Infections/virology , HIV-1/physiology , Tuberculosis, Pulmonary/virology , AIDS-Related Opportunistic Infections/microbiology , AIDS-Related Opportunistic Infections/virology , CD4-Positive T-Lymphocytes/immunology , HIV Infections/complications , HIV Infections/immunology , Humans , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/microbiology , Viral Load
4.
J Med Virol ; 62(4): 426-34, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11074470

ABSTRACT

The objective of this study was to determine the use of immune-complex dissociated (ICD) p24 antigen detection for the diagnosis and prognosis of HIV-1 infection in Ugandan children. Plasma collected prospectively from children born to HIV-1 infected Ugandan women was stored and later analyzed for the presence of neutralizable HIV-1 p24 antigen using the Coulter ICD p24 antigen and neutralization kits. HIV-1 infection status, disease progression, and survival of the children were determined. Specimens from 311 children born to HIV-1 infected women, including 138 HIV-1 infected children, and 113 children born to negative women were tested. Sixty-nine (50%) infected children were p24 antigen positive at least once. For early HIV-1 diagnosis, the specificity and positive predictive value of the assay were consistently high (>95% and >83% respectively), but the sensitivity was low (6-53%), especially in the first months of life. The presence of p24 antigenemia in the first two years of life was associated with poor survival (20%) by 80 months of age compared with infected children without antigenemia (43%, P < 0.001). Early detection of p24 antigen (6 months, P < 0.001). The data suggest that ICD p24 antigen detection is not a sensitive method for the determination of infant HIV-1 status in our cohort of HIV-1 infected Ugandan children tested in the first two years of life. There was a strong correlation, however, between the presence and time of onset of p24 antigenemia and mortality among HIV-1 infected children.


Subject(s)
HIV Core Protein p24/blood , HIV Infections/diagnosis , HIV-1/isolation & purification , Biomarkers , Child, Preschool , Disease Progression , Female , HIV Core Protein p24/immunology , HIV Infections/immunology , HIV Infections/physiopathology , HIV Infections/virology , HIV-1/immunology , Humans , Infant , Infant, Newborn , Pregnancy , Pregnancy Complications, Infectious/virology , Prospective Studies , Uganda
5.
AIDS ; 14(9): 1219-28, 2000 Jun 16.
Article in English | MEDLINE | ID: mdl-10894287

ABSTRACT

BACKGROUND: Retrospective cohort studies of tuberculosis suggest that active tuberculosis accelerates the progression of HIV infection. The validity of these findings has been questioned because of their retrospective design, diverse study populations, variable compliance with anti-tuberculous therapy and use of anti-retroviral medication. To assess the impact of tuberculosis on survival in HIV infection we performed a prospective study among HIV-infected Ugandan adults with and without tuberculosis. METHODS: In a prospective cohort study, 230 patients with HIV-associated tuberculosis and 442 HIV-infected subjects without tuberculosis were followed for a mean duration of 19 months for survival. To assess changes in viral load over 1 year, 20 pairs of tuberculosis cases and controls were selected and matched according to baseline CD4 lymphocyte count, age, sex and tuberculin skin test status. RESULTS: During the follow-up period, 63 out of of 230 tuberculosis cases (28%) died compared with 85 out of 442 controls (19%), with a crude risk ratio of 1.4 [95% confidence interval (CI), 1.07-1.87]. Most deaths occurred in patients with CD4 lymphocyte counts < 200 x 10(6) cells/l at baseline (n = 99) and occurred with similar frequency in the tuberculosis cases (46%) and the controls (44%). When the CD4 lymphocyte count was > 200 x 10(6)/l, however, the relative risk of death in HIV-associated tuberculosis was 2.1 (95% CI, 1.27-3.62) compared with subjects without tuberculosis. For subjects with a CD4 lymphocyte count > 200 x 10(6)/l, the 1-year survival proportion was slightly lower in the cases than in the controls (0.91 versus 0.96), but by 2 years the survival proportion was significantly lower in the cases than in the controls (0.84 versus 0.91; P < 0.02; log-rank test). For subjects with a CD4 lymphocyte count of 200 x 10(6) cells/l or fewer, the survival proportion at 1 year for the controls was lower than cases (0.59 versus 0.64), but this difference was not statistically significant (P = 0.53; logrank test). After adjusting for age, sex, tuberculin skin test status, CD4 lymphocyte count, and history of HIV-related infections, the overall relative hazard for death associated with tuberculosis was 1.81 (95% CI, 1.24-2.65). In a nested Cox regression model, the relative hazard for death was 3.0 (95% CI, 1.62-5.63) for subjects with CD4 lymphocyte counts > 200 x 10(6)/l and 1.5 (95% CI, 0.99-2.40) for subjects with a CD4 lymphocyte count of 200 x 10(6)/l or fewer. CONCLUSION: The findings from this prospective study indicate that active tuberculosis exerts its greatest effect on survival in the early stages of HIV infection, when there is a reserve capacity of the host immune response. These observations provide a theoretical basis for the treatment of latent tuberculous infection in HIV-infected persons.


Subject(s)
AIDS-Related Opportunistic Infections/physiopathology , HIV Infections/mortality , HIV Infections/physiopathology , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/mortality , AIDS-Related Opportunistic Infections/mortality , Adult , CD4 Lymphocyte Count , Cohort Studies , Disease Progression , Female , Humans , Male , Prospective Studies , Regression Analysis , Survival Analysis , Time Factors , Treatment Outcome , Tuberculosis, Pulmonary/physiopathology , Uganda/epidemiology , Viral Load
6.
J Infect Dis ; 181(4): 1304-12, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10753731

ABSTRACT

Adjunctive immunotherapy with heat-killed Mycobacterium vaccae was studied in a randomized, placebo-controlled trial of 120 non-human immunodeficiency virus-infected adults with newly diagnosed pulmonary tuberculosis. Patients were randomized to a single dose of M. vaccae or placebo 1 week after beginning chemotherapy and were followed up for 1 year. M. vaccae was safe and well tolerated. The rate of sputum culture conversion after 1 month of tuberculosis treatment was 35% in the M. vaccae group and only 14% in the placebo group (P=.01) but was comparable at 2 months and thereafter. Patients receiving M. vaccae had greater improvement on chest radiography at 6 months (91% vs. 77% for placebo recipients; P=.04) and 12 months (94% vs. 80%; P=.04) after initiation of tuberculosis treatment. These data provide evidence of an early increase in sputum culture conversion and greater radiographic improvement among patients who received M. vaccae. Further studies are warranted.


Subject(s)
Mycobacterium/immunology , Tuberculosis, Pulmonary/therapy , Adult , Female , Health Status Indicators , Humans , Male , Mycobacterium/classification , Radiography, Thoracic , Sputum/microbiology , Uganda , Vaccines, Inactivated
7.
N Engl J Med ; 337(12): 801-8, 1997 Sep 18.
Article in English | MEDLINE | ID: mdl-9295239

ABSTRACT

BACKGROUND: Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common. METHODS: We performed a randomized, placebo-controlled trial in 2736 HIV-infected adults recruited in Kampala, Uganda. Subjects with positive tuberculin skin tests (induration, > or =5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462). Subjects with anergy (0 mm induration in reaction to PPD and candida antigens) were randomly assigned to receive either placebo (323 subjects) or six months of isoniazid (395). The medications were dispensed monthly and were self-administered. RESULTS: Among the PPD-positive subjects, the incidence of tuberculosis in the three groups that received preventive therapy was lower than the rate in the placebo group (P=0.002 by the log-rank test). The relative risk of tuberculosis with isoniazid alone, as compared with placebo, was 0.33 (95 percent confidence interval, 0.14 to 0.77); with isoniazid and rifampin, 0.40 (0.18 to 0.86); and with isoniazid, rifampin, and pyrazinamide, 0.51 (0.24 to 1.08). Among the subjects with anergy, the relative risk of tuberculosis was 0.83 (95 percent confidence interval, 0.34 to 2.04) with isoniazid as compared with placebo. Side effects were more common with the multidrug regimens, and particularly with the regimen containing pyrazinamide. Survival did not differ among the groups, but the subjects with anergy had a higher mortality rate than the PPD-positive subjects. CONCLUSIONS: A six-month course of isoniazid confers short-term protection against tuberculosis among PPD-positive, HIV-infected adults. Multidrug regimens with isoniazid and rifampin taken for three months also reduce the risk of tuberculosis.


Subject(s)
AIDS-Related Opportunistic Infections/prevention & control , Antitubercular Agents/therapeutic use , HIV Infections/drug therapy , Isoniazid/therapeutic use , Tuberculosis, Pulmonary/prevention & control , Adult , Antitubercular Agents/adverse effects , Drug Therapy, Combination , Female , HIV Infections/immunology , Humans , Male , Pyrazinamide/therapeutic use , Rifampin/therapeutic use , Risk , Treatment Outcome , Tuberculin Test
8.
J Acquir Immune Defic Syndr Hum Retrovirol ; 15(5): 375-80, 1997 Aug 15.
Article in English | MEDLINE | ID: mdl-9342258

ABSTRACT

Between July and October 1993, 570 19- to 22-year-old volunteers were screened for HIV-1, with a resulting seroprevalence rate of 18.3% (95% CI: 14.0%, 22.6%). A cohort of 249 HIV-1-noninfected military recruits in the Ugandan Peoples' Defense Forces was followed prospectively for up to 18 months to document rates of HIV-1 seroprevalence, seroconversion, and knowledge and attitudes related to vaccine acceptability. The HIV-1 seroincidence rate was 3.56 per 100 person-years (95% CI: 1.49, 5.62) over 309 person-years of observation. At the 3- and 12-month visits, subjects were interviewed on issues of acceptance and knowledge about vaccines, including anti-HIV vaccines in particular. More than 90% believe that HIV vaccines will not cause HIV infection, and if offered, 88% report that they would take the vaccine if they were not already infected. Nonvaccine prevention methods were considered less reliable; monogamy and condom use were considered effective by only 33.5% and 69.3% of the cohort respectively. After completing the vaccine acceptability questionnaire at the 12-month visit, subjects were offered an approved polyvalent meningococcal vaccine as an indicator of general vaccine acceptance. All subjects reported receiving at least one previous vaccination, and 95% willingly accepted the meningococcal vaccination. The Ugandan military is a stable population at substantial risk for HIV-1 infection and may be a suitable population for vaccine efficacy trials.


Subject(s)
AIDS Vaccines , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV-1/immunology , Military Personnel , Adult , Cohort Studies , Condoms , Follow-Up Studies , HIV Antibodies/blood , HIV Seroprevalence , Health Knowledge, Attitudes, Practice , Humans , Incidence , Male , Patient Acceptance of Health Care , Prospective Studies , Sexual Behavior , Surveys and Questionnaires , Uganda/epidemiology , Vaccination/psychology
10.
Pediatrics ; 98(3 Pt 1): 438-44, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8784370

ABSTRACT

OBJECTIVE: To determine the correlation between the detection of human immunodeficiency virus type 1 (HIV-1) in breast milk, the duration of breastfeeding, and vertical transmission of HIV-1 infection in Ugandan women. METHODS: A prospective study of HIV-1 infection in pregnant Ugandan women and their infants has been ongoing since 1990 with follow-up of mother-infant pairs for at least 2 years. Expressed breast milk specimens were collected from 201 HIV-1-seropositive and 86 HIV-1-seronegative Ugandan women approximately 6 weeks after delivery. The presence of HIV-1 DNA in the cellular fraction of the breast milk was detected by polymerase chain reaction (PCR), and HIV-1 p24 antigen was detected in the cell-free breast milk supernatant using p24 antigen enzyme immunoassay (EIA) after immune complex dissociation (ICD). The duration of breastfeeding and the clinical status of the mothers and their children were recorded. HIV-1 EIA, Western blot, PCR, or p24 antigen detection were used for the determination of the HIV-1 infection status of the children. RESULTS: Of the 201 HIV-1-infected women studied, 47 had HIV-1-infected children, 143 had children who seroreverted, and 11 had children of indeterminate status. Breast milk supernatants were available for ICD p24 antigen testing from 188 of the HIV-1-infected women and none had detectable p24 antigen. Breast milk cell pellets were available and contained amplifiable DNA in 125 of the HIV-1-infected women (20 transmitters, 104 nontransmitters, 1 indeterminate). HIV-1 DNA was detected by PCR in 72% (75/104) of nontransmitters and 80% (16/20) of the transmitters. The duration of breastfeeding by transmitter mothers (15.8 months) was not significantly different from nontransmitter mothers (14.4 months). CONCLUSIONS: No correlation was found between the detection of HIV-1 in breast milk or the duration of breastfeeding and transmission of HIV-1 infection in this study of Ugandan women.


Subject(s)
DNA, Viral/analysis , HIV Core Protein p24/analysis , HIV Infections/virology , HIV-1/genetics , Infectious Disease Transmission, Vertical , Milk, Human/chemistry , Breast Feeding/statistics & numerical data , Cohort Studies , Female , HIV Infections/immunology , HIV Infections/transmission , HIV-1/immunology , Humans , Infant , Infant, Newborn , Milk, Human/immunology , Polymerase Chain Reaction/methods , Prospective Studies , Time Factors , Uganda
11.
Pediatrics. ; 98(3): 438-444, 1996.
Article in English | AIM (Africa) | ID: biblio-1268696

ABSTRACT

OBJECTIVE: To determine the correlation between the detection of human immunodeficiency virus type 1 (HIV-1) in breast milk; the duration of breastfeeding; and vertical transmission of HIV-1 infection in Ugandan women. METHODS: Aprospective study of HIV-1 infection in pregnant Ugandan women and their infants has been ongoing since 1990 with follow-up of mother-infant pairs for at least 2 years. Expressed breast milk specimens were collected from 201 HIV-1 seropositive and 86 HIV-1 seronegative Ugandan women approximately 6 weeks after delivery. The presence of HIV-1 DNA in the cellular fraction of the breast milk was detected by polymerase chain reaction (PCR); and HIV-1 p24 antigen was detected in the cell-free breast milk supernatant using p24 antigen enzyme immunoassay (EIA) after immune complex dissociation (ICD). The duration of breastfeeding and the clinic status of the mothers and their chidlren were recorded. HIV-1 ELIA; Western blot; PCR; or p24 antigen detection were used for the determination of the HIV-1 infection status of the children. RESULTS: Of the 201 HIV-1 infected women studied; 47 had HIV-1 infected children; 143 had children who seroverted; and 11 had children of indeterminate status. Breast milk supernatants were available for ICD p24 antigen testing from 188 of the HIV-1 infected women and none had detectable p24 antigen. Breast milk cell pellets were a vailable and contained amplifiable DNA in 125 of the HIV-i-infected women (20 transmitters; 104 nontransmitters; 1 indeterminante). HIV-1 DNA was detected by PCR in 72(75/104) of nontransmitters and 80(16/20) of the transmitters. The duration of breastfeeding by transmitter mothers (15.8 months) was not significantly different from nontransmitter mothers (14.4 months). CONCLUSIONS: No correlation was found between the detection of HIV-1 in breast milk or the duration of breasfeeding and transmission of HIV-1 infection in this study of Ugandan women


Subject(s)
Breast Feeding , HIV Infections , Women's Health
12.
Pediatr Neurol ; 11(4): 308-12, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7702691

ABSTRACT

When a child is admitted to the hospital with presumed encephalitis, the physician must use clinical criteria to gauge the appropriate level of hospital care and to give a preliminary assessment of outcome to the family because the etiology is unknown. This study attempted to determine which clinical factors gathered on hospital admission would be most helpful to the physician. The records of 106 children (ages 1 month to 20 years), admitted to Rainbow Babies and Childrens Hospital between 1978-1989 who had discharge diagnoses of encephalitis, were reviewed. Seventy-five met the case definition of presumed viral encephalitis, with viral etiology established in 23% of patients. Poor short-term outcome was defined as the presence of an abnormal neurologic examination at hospital discharge, and was present in 32% of patients. Focal signs on neurologic examination (odds risk: 16.30, P < .05) and abnormal neuroimaging studies (odds risk: 5.66, P < .05) were the only 2 factors present at admission that predicted a poor short-term outcome. Glasgow coma scale at admission was predictive of an abnormal neurologic examination at discharge only when profoundly depressed (6 or less); otherwise, this scale was not useful as a prognostic tool. Factors that were not correlated with adverse outcomes included age younger than 1 year, any type of seizure occurrence, status epilepticus, diffuse or focal electroencephalographic abnormalities, or abnormal cerebrospinal fluid findings.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Brain Damage, Chronic/etiology , Encephalitis/etiology , Neurologic Examination , Patient Admission , Adolescent , Adult , Brain Damage, Chronic/diagnosis , Child , Child, Preschool , Critical Care , Encephalitis/complications , Encephalitis/diagnosis , Encephalitis, Viral/complications , Encephalitis, Viral/diagnosis , Encephalitis, Viral/etiology , Female , Glasgow Coma Scale , Humans , Infant , Male , Prognosis , Retrospective Studies , Seizures/etiology
13.
J Infect Dis ; 169(1): 18-27, 1994 Jan.
Article in English | MEDLINE | ID: mdl-8277180

ABSTRACT

The level of human immunodeficiency virus type 1 (HIV-1) in lymphocytes and mononuclear phagocytes (MP) from the blood and pulmonary alveoli from 14 HIV-1-infected subjects during early (asymptomatic) and late (AIDS) stages of disease and the relationship between virus burden in MP and cytokine expression were assessed. Among asymptomatic subjects, HIV-1 was undetectable or low in both blood monocytes and alveolar macrophages (AM). Among subjects with AIDS, there was a significant increase of HIV-1 in AM but not monocytes. The level of HIV-1 in blood lymphocytes was higher than in either monocytes or AM. AM (but not monocytes) expressed increased levels of lipopolysaccharide-stimulated cytokine mRNA (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6) during both early and late stages of HIV-1 infection regardless of virus load. AM thus may serve as a reservoir for virus in late stages of disease yet contribute to the immunopathogenesis of lung disease in both early and late stages through increased cytokine expression.


Subject(s)
Cytokines/biosynthesis , HIV Infections/immunology , HIV-1/immunology , Macrophages, Alveolar/microbiology , Acquired Immunodeficiency Syndrome , Adult , Base Sequence , Blotting, Northern , Cytokines/genetics , DNA Primers/chemistry , DNA, Viral/isolation & purification , Gene Expression Regulation, Viral , Glyceraldehyde-3-Phosphate Dehydrogenases/biosynthesis , HIV Infections/metabolism , HIV Infections/microbiology , Humans , Interleukin-1/biosynthesis , Interleukin-1/genetics , Interleukin-6/biosynthesis , Interleukin-6/genetics , Macrophages, Alveolar/metabolism , Male , Molecular Sequence Data , Monocytes/metabolism , Monocytes/microbiology , Pulmonary Alveoli/pathology , RNA, Messenger/biosynthesis , RNA, Viral/isolation & purification , T-Lymphocytes/metabolism , T-Lymphocytes/microbiology , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/genetics
14.
AIDS ; 7(11): 1475-9, 1993 Nov.
Article in English | MEDLINE | ID: mdl-8280414

ABSTRACT

OBJECTIVES: To evaluate the clinical utility of plasma beta 2-microglobulin (beta 2M) levels, acid-dissociated HIV-1 p24 antigen, and HIV-1 p24-antibody titers in predicting HIV-1 vertical transmission in 227 HIV-1-infected Ugandan pregnant women. DESIGN: Plasma beta 2M levels, acid-dissociated HIV-1 p24-antigen positivity, and HIV-1 p24-antibody titers were determined using commercial enzyme immunoassays (EIA) in a Ugandan cohort of 52 HIV-1-seropositive transmitting mothers, 175 HIV-1-seropositive non-transmitting mothers, and 52 seronegative mothers within 6 weeks prior to delivery. RESULTS: Transmitter mothers had significantly higher plasma concentrations of beta 2M (1.80 +/- 1.13 mg/l) than non-transmitter seropositive mothers (1.32 +/- 0.81 mg/l; P = 0.0013). Similarly, a significantly higher proportion of transmitter mothers had detectable p24 antigen than non-transmitter mothers [six out of 51 (11.8%) versus six out of 173 (3.5%); P = 0.03]. Compared with the vertical transmission rate of 23% in the seropositive group, the positive predictive values of a beta 2M level > 1.5 mg/l or detectable HIV-1 p24 antigen for vertical transmission were 34 and 50%, respectively. Five of six (83.3%) seropositive mothers with both a beta 2M level > 1.5 mg/l and detectable p24 antigenemia transmitted HIV-1 infection to their infants compared with 25 of 124 (20.2%) seropositive mothers with values below the cut-off values for both tests (P = 0.00249). However, beta 2M was not found to be a significant independent predictor of vertical transmission when analyzed in a multivariate model with p24 antigenemia. There was no significant difference in HIV-1 p24-antibody titers in transmitter mothers versus non-transmitter mothers (P = 0.299). CONCLUSION: beta 2M levels and acid-dissociated HIV-1 p24-antigen assays may be used to predict which HIV-1-infected pregnant women are at greatest risk for vertical transmission. However, only the p24-antigen test was independently predictive of vertical transmission and its clinical utility is limited.


Subject(s)
HIV Antibodies/blood , HIV Core Protein p24/analysis , HIV Infections/transmission , HIV-1 , Pregnancy Complications, Infectious , beta 2-Microglobulin/analysis , Adolescent , Adult , Biomarkers , Cohort Studies , Evaluation Studies as Topic , Female , HIV Core Protein p24/immunology , HIV Infections/epidemiology , HIV Infections/immunology , HIV-1/immunology , Humans , Hydrogen-Ion Concentration , Immunoenzyme Techniques , Pregnancy , Uganda/epidemiology
15.
J Rheumatol ; 20(6): 972-6, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8350333

ABSTRACT

The validity of the Health Assessment Questionnaire (HAQ) functional ability instrument was tested in 120 women with definite systemic lupus erythematosus (SLE) from rheumatology clinics at 2 local tertiary care institutions. Reliability and validity results for this population of women (mean age: 41 years +/- 13; age at diagnosis 33 years +/- 13) indicate that (1) the HAQ was internally reliable (standardized alpha = 0.9443) with no interitem correlation exceeding (r = 0.75); (2) confirmatory factor analysis identified 2 predominant factors among the HAQ components suggestive of large limb gross movements (e.g., walking, arising) and small limb fine movements (e.g., the ability to eat and firmly grip objects). Cumulatively, the 2 factors accounted for 64% of the variation in HAQ ability response. The HAQ response was also valid when compared to the overall disability index (r = 0.65 to 0.82) and other common disease variables that were reported by the patient and collected by the physician at the time of clinical examination. In addition, when stratified by active and inactive disease as defined by the Lupus Activity Criteria Count, inactive patients reported lower disability components (dress, arise, eat, walk, hygiene, reach, grip and activity) than active patients. These findings confirm the valid use of the HAQ as a measure of disability, when compared with other clinical measures of disease status and activity, in female patients with SLE.


Subject(s)
Disability Evaluation , Health Status , Lupus Erythematosus, Systemic/physiopathology , Surveys and Questionnaires , Activities of Daily Living , Adult , Cohort Studies , Evaluation Studies as Topic , Female , Humans , Lupus Erythematosus, Systemic/psychology , Middle Aged , Reproducibility of Results , Self-Assessment
16.
Gerontology ; 39(2): 93-108, 1993.
Article in English | MEDLINE | ID: mdl-8514204

ABSTRACT

The waning of cell-mediated immunity during aging has been attributed primarily to defects in T lymphocyte properties and functions. We assessed the potential contribution of accessory dysfunction of monocytes from the elderly on responses of T cells to phytohemagglutinin (PHA) and to tetanus toxoid after in vivo boosting. Accessory function of monocytes from the elderly subjects for T lymphocyte responses to tetanus toxoid was comparable to the young. Expression of the cytokines interleukin-1, interleukin-6 and tumor necrosis factor, the cell adhesion molecules ICAM-1 and LFA-3 and the class II major histocompatibility molecule HLA-DR by monocytes from the elderly and young subjects was similar. T lymphocytes from the elderly responded poorly to PHA. Monocytes from the elderly had a decreased accessory function for PHA-stimulated T cells from young, third donors. Thus, although many accessory properties of monocytes from the elderly are normal, the monocyte and T lymphocyte defects in the elderly for mitogen may represent interactive factors in cell-mediated immunity during aging.


Subject(s)
Aging/physiology , Antigen-Presenting Cells/physiology , Monocytes/physiology , Phytohemagglutinins/pharmacology , T-Lymphocytes/drug effects , Tetanus Toxoid/pharmacology , Biological Assay , Cell Adhesion Molecules/metabolism , Cytokines/metabolism , HLA-DR Antigens/immunology , Humans , Immunoassay , Monocytes/immunology , Monocytes/metabolism , Reference Values
17.
J Gerontol ; 48(1): M19-25, 1993 Jan.
Article in English | MEDLINE | ID: mdl-7678105

ABSTRACT

The diminished in vitro blastogenic response of lymphocytes from the elderly to mitogenic stimuli is cited as evidence of immunosenescence, but the response to specific microbial antigens has not been well characterized. We measured the response to tetanus toxoid before and after boosting in young and elderly subjects. Elderly subjects (age > or = 70) and young controls (age < 35) were subjected to clinical, laboratory, and nutritional evaluation to ensure a cohort of healthy subjects. Responses of lymphocytes from the elderly to the mitogens phytohemagglutinin and concanavalin A were markedly diminished compared to those from the young. For all subjects, the average in vitro blastogenic response to tetanus toxoid of lymphocytes from elderly subjects (n = 23) was significantly diminished compared to young controls (n = 23; 31,985 +/- 4502 vs 14,411 +/- 3714 cpm, p < .01). Following boosting with tetanus in those subjects in whom boosting with tetanus toxoid was indicated, blastogenesis was comparable between elderly (n = 17) and young subjects (n = 7; 38,078 +/- 11,451 vs 42,103 +/- 9247 cpm). The boosted response to tetanus apparently was not sustained, since in the subset of subjects with a history of tetanus immunization in the past 10 years, the response of the elderly was much less than that of the young. Thus, a cohort of healthy elderly with diminished blastogenic responses to mitogens was capable of at least a transiently normal response to tetanus post boosting.


Subject(s)
Aging/immunology , Antibodies, Bacterial/biosynthesis , Immunization, Secondary , Lymphocyte Activation/immunology , Tetanus Toxoid/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Bacterial/analysis , CD3 Complex , Cohort Studies , Concanavalin A , Epitopes/analysis , Female , Humans , Immunologic Memory/immunology , Male , Phytohemagglutinins , T-Lymphocytes/immunology , Tetanus Toxoid/administration & dosage , Time Factors
18.
Arch Clin Neuropsychol ; 7(3): 243-50, 1992.
Article in English | MEDLINE | ID: mdl-14591258

ABSTRACT

The Hooper Visual Organization Test (VOT) is frequently used in measuring the cognitive functioning of brain-damaged patients. It is not clear, however, whether the VOT measures general or specific neurological dysfunction, specifically those resulting from right parietal lesions. The present study addressed this issue by examining archival data from 41 brain-damaged patients who were seen in a medical hospital's acute rehabilitation unit. Patients were selected on the basis of a diagnosis of either right or left hemisphere damage, and VOT scores on these two patient groups were compared. Additionally, lesion site, as measured primarily by CT scan, was compared with VOT scores. No significant hemispheric differences were found on VOT scores. However, VOT scores, when adjusted for age and education, were significantly lower in patients with lesions involving the right parietal lobe. The implications of the findings for the use of the VOT with brain-damaged individuals are discussed.

19.
Arch Ophthalmol ; 108(10): 1427-31, 1990 Oct.
Article in English | MEDLINE | ID: mdl-2222276

ABSTRACT

The clinical records and serial corneal endothelial images of 25 acapsular, pseudophakic eyes with Kelman-style, one-piece, anterior-chamber intraocular lenses and 24 acapsular, pseudophakic eyes with suture-fixated, posterior-chamber intraocular lenses following penetrating keratoplasty were reviewed to determine clinical success and endothelial survival after 1 year. Twenty-two (88%) of 25 grafts in the anterior-chamber intraocular lens group and 23 (96%) of 24 grafts in the sutured posterior-chamber intraocular lens group were clear after 1 year; best corrected visual acuity of 20/40 or better was noted in 25% of the eyes in the anterior-chamber intraocular lens group and 29% of the eyes in the sutured posterior-chamber intraocular lens group. The mean intraocular pressure for the anterior-chamber intraocular lens group was significantly lower than for the sutured posterior-chamber intraocular lens group at 3 months (17 +/- 4 vs 21 +/- 7 mm Hg) and at 6 months (17 +/- 3 vs 20 +/- 5 mm Hg); but did not differ at 1 year. The mean percent of endothelial cell loss after 1 year did not differ between the anterior-chamber intraocular lens group (32% +/- 26%) and the sutured posterior-chamber intraocular lens group (27% +/- 26%). No clinical or endothelial morphometric advantages were noted after 1 year for the suture-fixated, posterior-chamber intraocular lens over the Kelman-style, one-piece anterior chamber, intraocular lens following pseudophakic penetrating keratoplasty; however, a long-term, prospective, randomized study of these two intraocular lens types is recommended.


Subject(s)
Endothelium, Corneal/cytology , Keratoplasty, Penetrating , Lenses, Intraocular , Suture Techniques , Aged , Anterior Chamber/surgery , Aphakia, Postcataract/surgery , Cell Count , Female , Humans , Intraocular Pressure , Male , Prognosis , Retrospective Studies , Tissue Donors , Visual Acuity
20.
Eur J Orthod ; 12(2): 185-9, 1990 May.
Article in English | MEDLINE | ID: mdl-2351203

ABSTRACT

The paired nasomedial processes of the prenatal developing face contribute to the formation of the nasal region as well as the alveolar segment of the maxillary four incisors. The objective of this investigation was to determine whether or not there is a common anatomic relationship between the transverse nasal dimension and the corresponding transverse alveolar dimension that is continued in the post-natal period. The corresponding transverse dimensions were measured on a longitudinal series of 120 A-P cephalograms. In addition, A-P cephalograms of 24 dried skulls and also of 19 individuals having severe craniofacial malformations were analysed. The mean difference between the nasal dimensions and the corresponding alveolar dimensions ranged from 0.14 to 1.72 mm in the various groups. However, the statistically significant correlation coefficients between the measured dimensions were low (range r = 0.36-0.57). The developmental stage did not affect this relationship. Crowding was not found to be a major factor explaining the variability, although sex was seen as a significant factor.


Subject(s)
Alveolar Process/growth & development , Maxilla/growth & development , Nasal Bone/growth & development , Adolescent , Alveolar Process/anatomy & histology , Analysis of Variance , Child, Preschool , Female , Humans , Longitudinal Studies , Male , Malocclusion/pathology , Maxilla/anatomy & histology , Maxillofacial Development , Nasal Bone/anatomy & histology , Sex Factors , Tooth, Deciduous
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