Biomedical subjects

S M Donfield

Publications and source records attributed to S M Donfield.

26 records · Page 2Linked to original sources

PubMed1997

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study.

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.

Adolescent↗

PubMed1996

Ethics of AIDS study.

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Acquired Immunodeficiency Syndrome↗

PubMed1995

Evidence for a shift from a type I lymphocyte pattern with HIV disease progression. Hemophilia Growth and Development Study.

Whether a shift from a type I (cell mediated) immune profile occurs with progressive HIV-related immune dysfunction is a matter of heated debate. We analyzed data for 333 HIV antibody-positive (HIV+) and -negative (HIV-) hemophilic children/adolescents, to examine whether the relationships among immunologic parameters and vaccine-related serology supported a shift with advancing HIV infection. In stepwise logistic regression analysis of HIV+ children's data, anergy to a panel of delayed hypersensitivity skin test antigens was positively associated with serum immunoglobulin A (IgA) levels (p = 0.012) and CD8+ cell counts (p = 0.021) and negatively associated with CD4+ cell counts (p = 0.002). Modeling supported anergy as a positive correlate of log IgA level (p = 0.046) and CD4+ lymphocyte count as a negative correlate, for HIV+ participants only (p < 0.0001). For mumps, the proportion of vaccinated HIV+ participants with protective IgG antibody titers was higher among those with CD4+ lymphocyte counts < 200 cells/mm3 (p = 0.058). For HIV+ participants < 14 years of age, this same trend was seen for measles and rubella, but was not seen in any age group for bacterial vaccine antigens. The intercorrelations among skin test anergy, CD4+ lymphocyte counts, serum IgA levels, and viral vaccine antigen-related serologic titers for HIV+ participants are consistent with an association between progressive HIV-related immune dysfunction and a predominance of type II (humoral immunity) or Type 0 (mixed immunity), relative to type I, lymphocyte profiles.

Adolescent↗

PubMed1994

Immune and serologic profiles of HIV-infected and noninfected hemophilic children and adolescents. Hemophilia Growth and Development Study Group.

OBJECTIVES: To assess relationships among the effects of HIV on hemophilic children and adolescents' immunologic parameters and vaccine-related serology. METHODS: We analyzed data from extensive baseline immunologic evaluations of 207 HIV antibody-positive (HIV+) and 126 HIV antibody-negative (HIV-) hemophilic children and adolescents. RESULTS: HIV+ and HIV- participants differed significantly in T-lymphocyte subpopulation numbers, immunoglobulin levels, and seroprevalence rates for diphtheria toxoid, measles, and mumps antigens, IgG levels, IgM levels, and serologic titers to vaccine antigens showed little correlation with T-cell parameters. Proportionately more HIV+ participants were nonreactive to each and all of a panel of 7 skin test antigens (71% vs 28% anergic, RR 2.6). The odds of anergy increased 1.6 times for every decline of 200 CD4+ cells/microliters. CONCLUSIONS: HIV had significant, largely independent T- and B-lymphocyte effects on this pediatric cohort.

Adolescent↗

PubMed1994

Delayed somatic growth and pubertal development in human immunodeficiency virus-infected hemophiliac boys: Hemophilia Growth and Development Study.

As part of the Hemophilia Growth and Development Study, we investigated the impact of human immunodeficiency virus (HIV) infection on statural growth, weight gain, and skeletal and sexual maturity in more than 300 boys with moderate to severe hemophilia, of whom 62% were infected with HIV. Age-adjusted height and weight were reduced in the HIV-infected subjects (p < 0.001). However, mean weight for height and triceps skin-fold thickness of the infected-boys closely resembled those of the uninfected group. In HIV-infected boys, height for age was positively related to the CD4+ lymphocyte count when the count was < 200 cells/mm3. Age-adjusted serum testosterone levels did not differ by HIV status, but in the infected participants the mean age-adjusted bone age was significantly reduced (p = 0.038) and the distribution of Tanner stages, adjusted for age, differed significantly (p = 0.003). The probability of advancing one or more Tanner stages in the first study year was significantly slowed in HIV-infected boys more than 14 years of age (p = 0.0003). We conclude that linear growth was significantly impaired in boys with hemophilia and HIV infection, but the wasting of malnutrition was not found. The delays in bone age and pubertal maturation strongly suggest that part of the growth failure seen in acquired immunodeficiency syndrome can be attributed to pubertal delay. We speculate that the lack of demonstrable difference in age-adjusted testosterone concentrations might reflect subtle differences in the pattern of secretion of testosterone or in the concentration of sex-hormone binding globulin.

Adolescent↗

PubMed1993

Hemophilia growth and development study. Design, methods, and entry data.

PURPOSE: The study design, research questions, and baseline data are presented from a multicenter longitudinal epidemiologic investigation of the impact of human immunodeficiency virus (HIV) infection on three areas of functioning in children and adolescents with hemophilia: physical growth and sexual maturation, immune function, and neurological and neuropsychological functioning. PATIENTS AND METHODS: Sixty-nine percent (n = 333) of a population of males between the ages of 6 and 19 years with moderate to severe hemophilia participated in a comprehensive baseline examination. Approximately 62% of the study group was HIV seropositive and 38% HIV seronegative. RESULTS: Adjusted for age, HIV-positive participants were three times as likely as HIV-negative participants to exhibit declines in height-for-age attainment (p = 0.05), twice as likely to have delays in sexual maturation (p = 0.414), and more than three times as likely to exhibit antibody levels that were not indicative of prior exposure or vaccination (p < 0.001). In addition, analysis of a comprehensive battery of neuropsychological tests showed that HIV-positive participants were 50% more likely to show scores approximately 1 SD below expected levels in three of nine functional areas (p = NS) compared with HIV-negative participants. CONCLUSIONS: Entry data for this study reveal a greater likelihood for HIV-positive children and adolescents with moderate to severe hemophilia to have abnormal growth, and to exhibit antibody levels not indicative of prior exposure to disease or vaccination, which could be attributed to HIV infection. Lowered neuropsychological test performance in both groups may be attributable to the deleterious effects of chronic illness. Data are being collected from a group of non-HIV infected non-hemophiliac siblings for comparison.

Adolescent↗

PubMed1992

Brain abnormalities in male children and adolescents with hemophilia: detection with MR imaging. The Hemophilia Growth and Development Study Group.

Cranial magnetic resonance (MR) imaging was performed in 124 male patients (aged 7-19 years), from 14 institutions, in whom a diagnosis of moderate to severe hemophilia was made. Blood tests in all subjects were negative for human immunodeficiency virus. Findings in MR studies were abnormal in 25 (20.2%) subjects. Six lesions in five subjects were classified as congenital. The most commonly identified congenital lesion was a posterior fossa collection of cerebrospinal fluid (five cases). Twenty-two subjects had acquired lesions that were probably related to the hemophilia or its treatment. The most commonly acquired lesions were single- or multifocal areas of high signal intensity within the white matter on T2-weighted images noted in 14 (11.3%) subjects. Two subjects had large focal areas of brain atrophy, and six had some degree of diffuse cerebral cortical atrophy. Three subjects (2.4%) had hemorrhagic lesions. To the authors' knowledge, the unexpected finding of small, focal, nonhemorrhagic white matter lesions has not previously been reported.

Adolescent↗

PubMed1991

Physical activity by socioeconomic status in two population based cohorts.

In the current study, we examined physical activity in two population based cohorts of Allegheny County. Pennsylvania, which differed markedly in their socioeconomic status (SES), in order to evaluate the relationship of SES to physical activity patterns. A total of 917 individuals participated in a prevalence survey administered during a home visit in 1981. All of the participants were white. Households were randomly selected. An overall response rate of 84% was achieved. Activity was assessed using the Paffenbarger survey, which included the number of blocks walked, stairs climbed, sports and recreational activities, and hours spent in vigorous, moderate, and light activities. In both high and low SES individuals, activity was inversely associated with age and was higher in males than in females. The relationship of physical activity to SES differed depending on the dimension of activity assessed. Participation in sports was reported more frequently in high status males and females. SES was a significant predictor of walking activity in females, with low status females reporting more walking. The number of hours spent in moderate activities was greater, but the number of hours spent in light activities was lower, in low status males. There was little difference by SES in the composite activity score, average annual kilocalories per week. In summary, our research suggests that SES can impinge differently on separate manifestations of activity, and future research needs to identify how SES affects activity.

Age Factors↗