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D Brambilla

Publications and source records attributed to D Brambilla.

At least 37 records · Page 2Linked to original sources

Absolute copy number and relative change in determinations of human immunodeficiency virus type 1 RNA in plasma: effect of an external standard on kit comparisons.

Use of a common set of human immunodeficiency virus type 1 (HIV-1) RNA standards eliminated differences among absolute HIV-1 RNA copy number estimates made with three commercially available assays. The relative changes in the viral RNA levels determined by the commercial assays were similar and were unaffected by the use of a common set of standards.

Female↗

Ultrasensitive reverse transcription-PCR assay for quantitation of human immunodeficiency virus type 1 RNA in plasma.

With the recent introduction of combination therapy, human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma have been dramatically reduced, frequently to below the limit of quantitation (400 copies/ml of plasma) of the AMPLICOR HIV-1 MONITOR Test (Roche Diagnostic Systems). To achieve enhanced sensitivity of the AMPLICOR HIV-1 MONITOR Test, a modified specimen preparation procedure that allows input of RNA from 10-fold more plasma per amplification reaction was developed. This "ultrasensitive" method allows the accurate quantitation of plasma HIV-1 RNA levels as low as 50 copies/ml. A precision study yielded average within-run and between-run coefficients of variation (CV) of 24.8 and 9.6%, respectively. A multicenter reproducibility study demonstrated that the laboratory-to-laboratory reproducibility of this assay is good, with an average CV of 32%. The linear range of this test is between 50 and 50,000 copies/ml of plasma. RNA concentrations measured by the ultrasensitive and standard HIV-1 MONITOR tests exhibited good agreement within the shared linear range of the two methods. The two measurements were within a factor of 2 for 91% of the specimens tested, with the concentration measured by the ultrasensitive method being only slightly lower (median, 22% lower). Preliminary studies suggest that this assay will prove to be useful for predicting the stability of viral suppression in patients whose RNA levels drop below 400 copies/ml in response to highly active antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗

Long-term stroke risk in children with sickle cell disease screened with transcranial Doppler.

Stroke is an important complication of sickle cell disease. Stroke prediction is clinically important because it offers the possibility of primary prevention. In 1992, transcranial Doppler (TCD) evidence of elevated intracranial internal carotid or middle cerebral artery velocity was demonstrated to be associated strongly with an increased risk of ischemic stroke. This study extends the original study and includes 125 more children, longer follow-up, and intracranial hemorrhage in the stroke-risk model. Elevated time averaged mean maximum blood flow velocity, especially when velocity is 200 cm/sec or greater by TCD, was associated strongly with stroke risk. The cases not predicted by TCD point to the need for more information on the optimal timing of TCD surveillance for stroke risk.

Adolescent↗

Lymphocyte phenotyping in infants: maturation of lymphocyte subpopulations and the effects of HIV infection.

Changes in the distribution of lymphocyte subpopulations in infants with perinatally acquired HIV infection are confounded by the rapid changes that are the result of normal maturation of the immune system. We describe the changes in seven lymphocyte phenotypes (CD3+ CD4+, CD3+ CD8+, CD8+ HLA- DR+, CD8+ CD38+, CD8+ CD57+, CD3-/ CD16+ 56+, and CD19+) over the first 2 years of life in 390 HIV-1 exposed but uninfected and 98 HIV-1-infected infants enrolled in the Women and Infants Transmission Study. The greatest changes in uninfected infants were declines in the CD3+ CD4+ lymphocytes and increases in CD8+ HLA- DR+ and CD19+ lymphocytes. All phenotypes were affected by HIV infection but the greatest changes were declines in the CD3+ CD4+ subset and increases in the CD3+ CD8+ and CD8+ HLA- DR+ subsets. Thus, this study provides reference data for the maturational changes in lymphocyte phenotypes in HIV-exposed but uninfected infants and describes the overall changes that occur with perinatally acquired HIV infection.

Adult↗

Maternal immunologic and virologic risk factors for infant human immunodeficiency virus type 1 infection: findings from the Women and Infants Transmission Study.

Maternal virus load of human immunodeficiency virus 1 (HIV-1) and maternal immunity are both associated with risk of an infected infant. The interrelationship of these two variables in describing that risk was assessed in a multisite study of 475 mother-infant pairs. Infant infection was associated with low CD4 cell percentage, high CD8, CD8/CD38, and CD8/DR cell percentages, persistently positive HIV-1 cultures, and high HIV-1 titer (P < .001, .001, .005, .006, .001, and .013, respectively). The association of CD4 cell percentage and increased CD8, CD8/CD38, and CD8/DR cell percentages with transmission was restricted to the 42% of women whose HIV-1 cultures were not persistently positive (all P < .001). Women with at least 1 negative culture and high CD4 cell percentage or low CD8 cell percentage were at very low risk (0-4%) of transmitting HIV-1, while those with always positive cultures transmitted at a high rate (18%-27%), regardless of immune status.

Adolescent↗

Stabilities of free and complexed human immunodeficiency virus p24 antigens during short- and long-term storage.

By the standard p24 assay there was a 25 to 27% decrease in free p24 antigen in serum after storage at 4 degrees C over 14 days but no loss at -70 degrees C. There was no loss at either temperature by the immune complex dissociation (ICD) procedure. Furthermore, there was no significant loss of detectable p24 in serum by either the ICD or the standard p24 assay after 700 days of storage at -70 degrees C.

Antigen-Antibody Complex↗

Diagnosis of infection with human immunodeficiency virus type 1 by a DNA polymerase chain reaction assay among infants enrolled in the Women and Infants' Transmission Study.

Early diagnosis of infection with human immunodeficiency virus type 1 (HIV- 1) in young infants is essential to decisions on their medical and social care. Whereas studies have suggested that polymerase chain reaction (PCR) is a sensitive and timely method of diagnosing HIV infection in children, these evaluations have been limited by the number of specimens studied. Recently, Roche Molecular Systems developed a complete HIV-1 DNA PCR testing kit (from specimen preparation to detection). In this study, use of this PCR test kit was evaluated for the detection of HIV infection in infants of seropositive mothers who were enrolled in the longitudinal, multicenter Women and Infants' Transmission Study. A total of 1209 blood specimens from 483 infants were tested and analyzed. The overall sensitivity and specificity of a single PCR test in determining HIV infection status in infants more than 1 but less than 36 months of age were 95% and 97%, respectively. For infected infants 1 to 6 months of age the sensitivity of the DNA-PCR test was 90% to 100%. In a direct comparison with coculture, the Roche DNA-PCR test was significantly more sensitive than coculture in the detection of HIV-1 in infected infants and was equivalent to coculture for the diagnosis of HIV in infants when a standardized algorithm was used to define infection status.

Algorithms↗

Evaluation of a quality assurance program for quantitation of human immunodeficiency virus type 1 RNA in plasma by the AIDS Clinical Trials Group virology laboratories.

A number of quantitative assays have been developed by using amplification techniques to measure human immunodeficiency virus type 1 RNA in the plasma of infected individuals. The Virology Committee of the AIDS Clinical Trials Group in the Division of AIDS, National Institute of Allergy and Infectious Diseases, has established a quality assurance program (QAP) for quantitative assays of HIV-1 RNA levels in plasma. The primary objective of the QAP was to ascertain that a laboratory could maintain the precision required to have a 90% power to detect a fivefold difference in RNA copy number between two samples in the same batch. To achieve this goal, the QAP required an intra-assay standard deviation of no greater than 0.15 log10 RNA copies per ml. Panels for proficiency testing consisted of coded replicate samples and a common set of standards. To date, 41 laboratories have participated in the program and have used both commercial and in-house assays. We demonstrated that 65% of the laboratories were capable of attaining the necessary level of intra-assay precision. The fitted regressions indicated that the differences among laboratories that used the same kit were generally greater than the differences among population-average regressions for the kits themselves. The use of an external QAP and a common set of standards reduced differences both among laboratories that used the same kit and among laboratories that used different kits. Thus, use of a common set of standards across clinical trial protocols would allow for cross-protocol comparisons.

Clinical Protocols↗

Evaluation of an infectivity standard for real-time quality control of human immunodeficiency virus type 1 quantitative micrococulture assays. Participating Laboratories of The AIDS Clinical Trials Group.

Quantitative microculture assays of cryopreserved human immunodeficiency virus type 1-infected cell suspensions and culture supernatants were compared among seven assays sites. There was no significant change in titer during 1 year of storage. The overall standard deviation for infected cell suspensions was approximately 0.8 log10 virus titer. A method for detecting deviant assay results was developed and was used to identify two donor cell preparations (n = 54) that gave consistently low titers.

Cell Culture Techniques↗

Mycobacterium tuberculosis infection in pregnant and nonpregnant women infected with HIV in the Women and Infants Transmission Study.

BACKGROUND: Prevalence of Mycobacterium tuberculosis (TB) infection and anergy were evaluated in a cohort of pregnant and nonpregnant women infected with the human immunodeficiency virus who were enrolled in a prospective natural history study (the Women and Infants Transmission Study) conducted in New York, NY; Boston and Worcester, Mass; Chicago, Ill; and San Juan, Puerto Rico. METHODS: One hundred eighty-three women (65 pregnant, 118 nonpregnant) were evaluated for TB. The TB history and risk factors were assessed by interview and medical record review. Intradermal skin testing with tuberculin, mumps, and tetanus antigens and CD4+ lymphocyte count were performed. RESULTS: Overall prevalence of TB infection or disease by documented medical history and/or a tuberculin skin test induration of 5 mm or more was 14% (26 of 183). History of TB infection or disease was documented in 11% of the women who were interviewed. Tuberculin and anergy skin test results were evaluable for 124 women; 6% (seven of 124) had tuberculin skin test induration of 5 mm or more, including 11% (five of 46) of the pregnant women who were tested. Induration between 2 and 5 mm was observed in four more women, three of whom were pregnant. Anergy was observed in 42% (52 of 124); prevalence of anergy was higher in nonpregnant women (38 [49%] of 78) than in pregnant women (14 [30%] of 46). While anergy was more common in women with a CD4+ cell count of 0.5 x 10(9)/L or less, 27% of those with a CD4+ cell count of more than 0.5 x 10(9)/L were also anergic. CONCLUSION: These data support current Public Health Service recommendations for tuberculin skin testing in persons infected with the human immunodeficiency virus, and emphasize that evaluation should include pregnant as well as nonpregnant women. The prevalence of anergy does not appear increased in pregnancy in women infected with the human immunodeficiency virus. Health care providers should include tuberculin and anergy skin testing as part of the standard prenatal care for women infected with the human immunodeficiency virus.

Adult↗

Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions.

OBJECTIVE: To determine the effect of a transfusion program on risk of stroke recurrence in children with sickle cell disease. DESIGN: The clinical course and experience with transfusion therapy at eight centers were reviewed for subjects whose initial stroke occurred after January 1988. RESULTS: Sixty subjects were observed for 191.7 patient-years. Eight had a single recurrent stroke (two intracranial hemorrhages and six infarctions) for a prevalence of 13.3%, or one recurrence for each 24 patient-years of observation. Thirteen subjects had 15 transient neurologic events; two of these had subsequent strokes, but the overall risk was similar for those who did and those did not have transient events. Hemoglobin S levels were greater than the desired maximum of 30% at the time of 7 of 16 transient events and five of six recurrent infarctions. The stroke recurrence rate was similar to those in previous reports of children receiving long-term transfusion therapy but significantly less than that reported for children who did not receive transfusions (p < 0.001). CONCLUSIONS: We conclude that maintenance of hemoglobin S at a level less than 30% appears to be effective in reducing the rate of recurrent infarction but does not prevent transient neurologic events. Transient neurologic events are common but do not appear to be related to recurrent stroke.

Adolescent↗

Interlaboratory variability of CD8 subset measurements by flow cytometry and its applications to multicenter clinical trials. NAID/NICHD Women and Infants Transmission Study Group.

Recent studies have demonstrated the utility of measuring subsets of CD8+ T cells as prognostic markers in epidemiology cohort studies of human immunodeficiency virus (HIV)-infected patients. Most of these studies evaluating the value of CD8+ T-cell subsets have been performed at single centers, and few data are available on variability in the measurement of the CD8+ cell populations in multicenter trials. In the current study, we addressed this question by evaluating interlaboratory variability from the five laboratories enrolled in the Women and Infants Transmission Study sponsored by the National Institutes of Health. This study evaluated 35 HIV-positive and 28 HIV-negative proficiency testing samples sent to the laboratories for evaluation. The study focused on the robust coefficient of variation (RCV) for CD38 (11%), HLA-DR (21%), and CD57 (15%) expression on the CD8+ population. Data from the current study indicated that the variability in these measurements is greater than that for CD3+ CD4+ (RCV, 5%) and CD3+ CD8+ (RCV, 5%) cells. Knowledge of the variability of the CD8+ subset measurements should guide investigators in the design and analysis of clinical trials and epidemiology studies. Ability to obtain improved interlaboratory agreement on CD8+ subset measurements will facilitate further evaluation of these markers in HIV studies.

CD3 Complex↗

A longitudinal analysis of the association between menopause and depression. Results from the Massachusetts Women's Health Study.

The present article prospectively examines the effect of change in menopause status on depression, while controlling for prior depression. This is a longitudinal follow-up of previous cross-sectional analyses reported by McKinlay, McKinlay, and Brambilla who examined the relative contribution of menopause to depression. The data derive from the Massachusetts Women's Health Study, a 5-year longitudinal study of a cohort of 2565 women aged 45 to 55 years at baseline (1981 to 1982). Results show that prior depression is the variable most predictive of subsequent depression, as measured by the Center for Epidemiologic Studies-Depression (CES-D) scale. Onset of natural menopause was not associated with increased risk of depression. Experiencing a long perimenopausal period (at least 27 months), however, was associated with increased risk of depression. The association between a long perimenopause and depression appeared to be explained by increased menopausal symptoms rather than by the menopause status itself. The observed increase in depression during a lengthy perimenopause appears to be transitory.

Climacteric↗

Blood culture in the first 6 months of life for the diagnosis of vertically transmitted human immunodeficiency virus infection. The Women and Infants Transmission Study Group.

Serial blood cultures over the first 6 months of life in 310 infants with vertical exposure to human immunodeficiency virus (HIV) in the Women and Infants Transmission Study were analyzed to determine their value for early diagnosis of HIV infection. Cultures were done at 0-7 days and 1, 2, 4, and 6 months of age: 55 infants were infected. Blood culture sensitivity in infected children was 24% (7/29) during the first week of life and 85%, 91%, 82%, and 88%, respectively, at 1, 2, 4, and 6 months. The sensitivity, specificity, and positive and negative predictive values of a single culture between 1 and 6 months of age were, respectively, 86.9%, 99.6%, 97.9%, and 97.5%. Two negative cultures between 1 and 6 months of age defined an uninfected infant with a specificity of 99.2%-100.0%. Blood culture done between 1 and 6 months of age in children of HIV-positive mothers is a sensitive and specific test for HIV infection, with high positive and negative predictive values.

Blood↗

Hyperinsulinemia and macrosomia in the fetus of the diabetic mother.

OBJECTIVE: To determine 1) whether macrosomia in the fetus of the diabetic mother is related to fetal hyperinsulinemia and 2) whether hyperinsulinemia and macrosomia are related to maternal metabolic control. RESEARCH DESIGN AND METHODS: Normal pregnant women (n = 95) were compared with insulin-treated pregnant women (n = 155), who were subdivided according to White's class, hypertension, and mode of delivery. All women were treated to achieve optimal metabolic control. HbA1c was determined at each visit. At delivery, umbilical plasma was analyzed for glucose, insulin antibodies, total insulin, free insulin, C-peptide, proinsulin components, and total and individual amino acids. RESULTS: Macrosomia, defined as > 2 standard deviation units (97.75%), was found in 10-27% of the diabetic groups. It was not related to maternal mass or size, but was significantly correlated with umbilical total insulin, free insulin, and C-peptide. Proinsulin components were not different among groups. Amino acids also were not different. Glycosylated hemoglobin was a weak predictor of birth weight and fetal hyperinsulinism. CONCLUSIONS: Macrosomia in the fetus of the diabetic mother remains inadequately explained. In a large population of pregnant women with strict metabolic control, macrosomia was mainly independent of glycosylated hemoglobin. Nevertheless, fetal hyperinsulinism remains the driving force for excessive fetal growth. The stimulus for fetal insulin excess in humans remains to be defined.

Birth Weight↗