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Biomedical subjects

J Oleske

Publications and source records attributed to J Oleske.

At least 19 recordsLinked to original sources

Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis.

The purpose of this study was to evaluate the immune dysfunction hypothesis of chronic fatigue syndrome (CFS) by comparing immunologic data from patients with CFS with data from patients with other fatiguing illnesses--major depression and multiple sclerosis (MS)--and with data from healthy sedentary controls. The subjects were 65 healthy sedentary controls, 71 CFS patients (41 with no axis-I diagnosis), 23 patients with mild MS, and 21 patients with major depression. Blood was sampled and assayed for the following: (1) immunologic serologic variables--circulating immune complexes (i.e., Raji cell and C1q binding), immunoglobulins A, E, G, and M, and IgG subclasses; (2) cell surface activation markers--the proportion of CD4+ cells expressing CD45RA+ and CD45RO+ and the proportion of CD8+ cells expressing CD38+, CD11b-, HLA-DR+ and CD28+; and (3) natural killer (NK) total cell count as well as the proportion of lymphocytes expressing NK cell surface markers (i.e., CD3-/CD16+ and CD56+. Of the 18 variables studied, differences between CFS patients and controls were found only for IgG1 and IgG3. When CFS patients were stratified by the presence or absence of concurrent axis-I disease, it was the group with axis-I disorder that had the lowest IgG1 values-contrary to expectation. When data from patients with MS and major depression were also evaluated, the subclass deficiency was no longer significant. The one group to show evidence for immune activation (i.e., an elevated proportion of CD4+ cells expressing the CD45RA+ activation marker) was the group with mild MS. These data support neither immune dysfunction nor immune activation in CFS or in major depression, for the variables studied. The reductions in IgG subclasses may be an epiphenomenon of patient or control subject composition. In contrast, MS, even in the mild and early stages, as in the patients studied here, is associated with immune activation.

Adult

The effect of total lymphoid irradiation and low-dose steroids on T lymphocyte populations in multiple sclerosis: correlation with clinical and MRI status.

We have monitored the cell surface phenotypic changes occurring in T, B and NK cells of chronic progressive multiple sclerosis (MS) patients after total lymphoid irradiation (TLI) plus low-dose prednisone (TLI-LDP) therapy in comparison to sham TLI-LDP. TLI-LDP resulted in a marked reduction in the relative and absolute number of total CD3+ T cells, CD4+ helper T cells, CD4+ CD45RA+ naive T cells and CD19+ B cells for at least 1 year after treatment. No change occurred in the percent CD8+ T cells although the number of these cells declined after radiotherapy. The CD4/CD8 T cell ratio was also decreased. The relative percent of CD16+ NK cells increased steadily after TLI-LDP while the number of NK cells transiently declined but returned to baseline values 1 year later. An increase in the percent of CD2+ CD3- cells and a decrease in their number after therapy was also observed. In contrast, no significant changes in the number of T, B or NK cells were seen in the MS patients receiving sham TLI-LDP. These results provide further evidence that radiotherapy causes a reduction of immunocompetent T and B cells and that a population of possibly NK cells and/or immature T cells appears to be repopulating the circulation after TLI. In addition, a correlation was observed between alterations in lymphocyte populations and the presence or absence of contrast enhancing or new T2 lesions on brain magnetic resonance imaging (MRI) in the TLI-LDP treated MS patients. Patients devoid of contrast enhancing or new T2 lesions had a decreased percentage of CD3+ and CD4+ T cells prior to therapy and at six months following TLI-LDP compared to patients with such lesions. An association was also observed between stability in disease activity as determined on the Expanded Disability Status Scale and relative values of CD3 T cells.

Adult

A descriptive survey of pediatric human immunodeficiency virus-infected long-term survivors.

OBJECTIVE: To identify the population of human immunodeficiency virus-infected pediatric long- term survivors (LTS) followed in major medical institutions in California, Florida and New Jersey. METHODS: A cross-sectional survey was performed with data collection forms sent to all investigators. Demographic, clinical, and laboratory data were obtained on all living patients >/=8 years infected in the perinatal period with human immunodeficiency virus. RESULTS: A total of 143 perinatally infected and 54 children infected by neonatal transfusion were identified. Fifty-four children (27%) had absolute CD4 counts >/=500 cells/mm (group 1: mean age 9.8 years), 54 children (27%) had CD4 counts between 200 and 500 cells/mm (group 2: mean age 10.1 years), and 89 children (45%) had CD4 counts <200 cells/mm (group 3: mean age 10.4 years). Ninety-five (48%) patients had developed AIDS defining conditions; 14 (26%) in group 1, 26 (48%) in group 2, and 55 (62%) in group 3. Ninety-two percent of patients had received antiretrovirals. Perinatally human immunodeficiency virus-infected children tended to be younger (mean age 9.8 years) than children infected via a blood transfusion (mean age 11 years). Generalized lymphadenopathy was the most prevalent clinical finding. Lymphoid interstitial pneumonia and recurrent bacterial infections were the most prevalent acquired immune deficiency syndrome-defining conditions. Twenty percent of LTS had CD4 counts >/=500 cells/mm and no immune deficiency syndrome-defining conditions. CONCLUSIONS: Pediatric LTS were in variable stages of disease progression. The proportion of children within each CD4 strata did not differ by mode of acquisition of infection. Increased CD4 counts were inversely proportional to age. Only 20% of pediatric LTS had minimal to no disease progression.

Acquired Immunodeficiency Syndrome

Levodopa therapy improves motor function in HIV-infected children with extrapyramidal syndromes.

Five children with human immunodeficiency virus type-1 (HIV-1) infection, aged 4 to 13 years, manifested extrapyramidal dysfunction characterized by rigidity/stiffness, ambulation difficulties/shuffling gait, dysarthria/drooling/swallowing dysfunction, hypomimetic/inexpressive facies, and bradykinesia. Levodopa therapy caused an initial improvement in all symptoms, and the effect was sustained in most patients. Levodopa is a useful adjunctive therapy in HIV-1-infected children with extrapyramidal syndromes, by enhancing motor function and improving their quality of life.

Child, Preschool

Induction of autologous mixed lymphocyte culture responses by myelin basic protein-reactive T cell clones.

Myelin basic protein is an autoantigen present in the central nervous system suspected to be the target of destruction in multiple sclerosis. In the present study, we have demonstrated that T cell clones specific for myelin basic protein have the ability to induce proliferative responses in resting T lymphocytes in the autologous mixed lymphocyte culture (AMLC). T cell recognition of the AMLC stimulatory determinants on the clones required the presence of autologous monocytes. T lymphocytes primed against an autologous myelin basic protein-specific T cell clone displayed specific memory responses against the original stimulating clone and failed to exhibit secondary reactivity to 'sister' myelin basic protein-reactive clones and to autologous T cell clones specific for another antigen. Monoclonal antibodies specific for class II HLA-DR antigens inhibited secondary AMLC responses. Modulation of the T cell receptor from the surface of the clones decreased their AMLC stimulatory ability. These results indicate that idiotype-like determinants on the T cell receptor of autoantigen-specific T cell clones are capable of triggering anti-idiotypic T cell responses.

Cells, Cultured

Safety, tolerance, and pharmacokinetics of systemic ribavirin in children with human immunodeficiency virus infection.

Eleven pediatric patients, aged 1 to 10 years and with symptomatic human immunodeficiency virus infection, were treated with 6 or 10 mg of oral ribavirin per kg of body weight daily for 60 days. Safety and pharmacokinetic parameters were monitored; five children had comprehensive pharmacokinetic evaluations. The children tolerated the drug well, and treatment was not associated with any clinically significant adverse effects. Peak concentrations in plasma of 2.5 and 3.0 microM were reached at 90 min after single oral doses of 6 and 10 mg/kg, respectively. The mean systemic availability of oral ribavirin was 42.3%. After 60 days of ribavirin administration, mean trough concentrations in plasma of 2.6 and 4.1 microM were obtained. Ribavirin penetrated well into the cerebrospinal fluid, achieving 70% of the concentration in plasma at steady state.

Acquired Immunodeficiency Syndrome

Enzyme immunoassay for detection of human immunodeficiency virus-specific immunoglobulin A antibodies.

Early diagnosis of human immunodeficiency virus (HIV) infection may be difficult in adults with acute or recent HIV infection and in infants with perinatally acquired HIV. Detection of HIV-specific immunoglobulin A (IgA) antibodies in infant serum by Western blot (immunoblot) has been suggested as a reliable method to identify HIV-infected infants, especially those over the age of 6 months, and as an adjunct to diagnosis of acute HIV infection in adults. We developed a simple enzyme immunoassay for detection of HIV-specific IgA, using standard commercially available reagents. Enzyme immunoassay was comparable to Western blot for detection of HIV-specific IgA in sera from adults (n = 216), older children (n = 49), and infants born to HIV-infected mothers (n = 65). Specificity was 100% and sensitivity ranged from 80 to 92%. IgA-enzyme immunoassay is a simple, highly sensitive method for detection of HIV-specific IgA antibodies and is easily adapted to the standard clinical laboratory.

Adolescent

Lymphocyte subsets in healthy children during the first 5 years of life.

OBJECTIVE: To assess whether relative and absolute values of CD4 and CD8 lymphocytes and CD4/CD8 ratio change in relation to age, and to estimate the fifth and 95th percentiles for these values in children of various ages. PATIENTS AND METHODS: Phenotypic analysis of lymphocyte subsets was performed on blood samples from 208 healthy children, aged 1 through 59 months, using standard flow cytometric techniques. RESULTS: Regression analysis demonstrated that CD4 and CD8 lymphocyte counts declined significantly with advancing age (P less than .000001 and P = .03, respectively). Since CD4 and CD8 counts depend on total lymphocyte count, the percentage of total lymphocytes of each phenotype was also analyzed and demonstrated that the CD4 percentage was highly age dependent (P less than .000001). The CD8 percentage increased with age (P = .0001) but not as much as the CD4 percentage decreased. Median CD4 counts (fifth and 95th percentiles) for children 2 through 3, 4 through 8, 12 through 23, and 24 through 59 months of age were 2.83 (1.46 to 5.11), 2.95 (1.69 to 4.61), 2.07 (1.02 to 3.60), and 1.80 (0.90 to 2.86) x 10(9)/L, respectively. CONCLUSION: Healthy children's CD4 lymphocyte counts are considerably higher than previously established adult values. These data demonstrate that age is an important consideration in interpretation of lymphocyte subsets in children. This may be especially relevant in children who are infected with the human immunodeficiency virus, where CD4 lymphocyte values play a central role in monitoring disease progression and determining thresholds for medical interventions.

CD4-CD8 Ratio

Nontuberculous mycobacteria in children with acquired immunodeficiency syndrome.

Among 139 children with acquired immunodeficiency syndrome at Children's Hospital of New Jersey, 20 had positive cultures for non-tuberculous mycobacteria. Eighty-five percent had Mycobacterium avium complex isolated and 70% had definite evidence of disseminated disease. Ninety-three percent had CD4 lymphocyte counts less than 100 cells/mm3 and 95% had met acquired immunodeficiency syndrome criteria before the time of first positive culture. Clinical findings included failure to gain weight, anorexia, fever, abdominal pain/tenderness and anemia. The median age at onset of symptoms was 46 months and the median time between onset of symptoms and positive culture was 9 months. Outcome for patients with positive cultures for nontuberculous mycobacteria was poor, with 75% of the children surviving for less than or equal to 10 months. Nontuberculous mycobacteria are increasingly important causes of morbidity and indirect mortality in human immunodeficiency-infected children. Children with severe immunodeficiency are at particular risk. In addition to M. avium complex, other species of nontuberculous mycobacteria may be involved.

Acquired Immunodeficiency Syndrome

Varicella does not appear to be a cofactor for human immunodeficiency virus infection in children.

We performed a retrospective analysis of longitudinal clinical and immunologic data obtained from 22 children in the early stages of infection with human immunodeficiency virus (HIV) when they developed varicella. We studied the course of HIV infection to determine whether clinical deterioration occurred after chickenpox. We examined the following indices: growth and development; neurologic status; helper T lymphocyte counts; blood values of core (p24) antigen of HIV; changes in the stage of HIV infection; and need for administration of zidovudine. We studied children for a mean of 2.8 years and for as long as 9.8 years after onset of varicella. There was little evidence that chickenpox affected HIV infection. Three (14%) children developed clinical zoster, 2 of whom (9%) had evidence of chronic infection with varicella-zoster virus. One additional child (5%) had 2 episodes of chickenpox. These observations suggest that children with early HIV infection could be considered for immunization with live attenuated varicella vaccine, which would be predicted to decrease their morbidity from varicella-zoster virus.

CD4-Positive T-Lymphocytes

Population-based study of measles and measles immunization in human immunodeficiency virus-infected children.

This study reports the course of measles and results of measles immunization in a cohort of human immunodeficiency virus-infected children. Six cases of measles were identified. All had typical clinical manifestations, 5 of 6 developed pneumonia and 3 of 6 died. A measles intervention program consisting of serologic screening and active immunization (measles-mumps-rubella (MMR)) was instituted in 1990. Among 127 children with data available for analysis (mean age, 6.7 years), only 35% had documentation of prior immunization with MMR. Among 80 children who had preimmunization measles serology reported, 56% were measles antibody-negative and 40% were antibody-positive; following intervention 36% remained measles antibody-negative. Six children lost measles antibody over time. MMR nonresponders had lower CD4 lymphocyte counts (303 +/- 394) compared with responders (865 +/- 677; P = 0.0058). Measles is a potentially fatal illness in human immunodeficiency virus-infected children. Prevention strategies are limited by low rates of age-appropriate MMR immunization, poor antibody responses to MMR in older human immunodeficiency virus-infected children and seroreversion.

Child

Intravenous gamma globulin in progressive MS.

In an attempt to prevent disease exacerbations, intravenous gamma globulin (500 mg to 2 g/kg) plus methylprednisolone was administered monthly to 14 patients with progressive multiple sclerosis, 11 of whom were steroid dependent. Seventeen exacerbations of disease activity were seen in 11 patients over a mean follow-up period of 7.8 months. Four exacerbations occurred in 3 patients within one month of receiving 1.6 to 2.0 g/kg of intravenous gamma globulin (IVGG). Most exacerbations occurred within 2 weeks of steroids being tapered; thus a steroid sparing effect of IVGG could not be demonstrated. We conclude that IVGG plus methylprednisolone can be given safely at monthly intervals for a prolonged period but in the dosage administered did not prevent exacerbations in 80% of patients with progressive multiple sclerosis.

Adult