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Biomedical subjects

R W Steele

Publications and source records attributed to R W Steele.

At least 19 recordsLinked to original sources

Psychological modulation of the delayed type hypersensitivity skin test.

Considerable data have demonstrated that psychological states can influence the immune system in animals. Whether human immune function can be intentionally modulated by the central nervous system is unknown. This article presents data from two studies that sought to demonstrate intentional modulation of the immune system by psychological interventions. It also discusses the methodological complexities involved with this type of research in humans.

Adult

Usefulness of scanning procedures for diagnosis of fever of unknown origin in children.

During a 5-year study period, 109 patients were referred to a large children's hospital for evaluation of prolonged fever of unknown origin, defined as temperature greater than or equal to 38 degrees C (100.4 degrees F) for 3 weeks or longer and negative findings on initial examination. A two-phase protocol of outpatient followed by inpatient diagnostic studies was instituted for most patients. Confirmed diagnoses were achieved in just 36 of these children (33%) in the following disease categories: infectious, 24 (22%); autoimmune, 7 (6%); and neoplastic, 2 (2%). Scanning or special procedures and the number with positive results (in parentheses) were as follows: abdominal ultrasonography, 43 (8); abdominal computed tomography, 14 (3); indium scan 11 (5); gallium scanning, 4 (1), upper gastrointestinal tract series, 13 (2); technetium bone scanning 15 (2); bone marrow examination, 16 (1); and cranial computed tomography, 7 (0). These studies rarely led to an unsuspected diagnosis. It appears most appropriate in evaluating fever of unknown origin in children to obtain only basic laboratory studies such as a complete blood cell count, urinalysis and culture, chest radiograph, tuberculin skin test, and, in the older child, an antinuclear antibody titer. When these test results are negative, almost all children can be observed clinically for progression of illness or a focus that might then direct specific diagnostic procedures.

Adolescent

T-lymphocyte subsets in nephrotic syndrome.

T-lymphocyte subsets when measured in steroid responsive nephrotic syndrome (SRNS) have demonstrated significant variance from normal values. T-cell subsets were studied by using two-color flow cytometric analysis in 32 children (9.2 +/- 5 years of age) with SRNS. The children were divided into four groups: a) SRNS in acute relapse, on prednisone; b) SRNS in acute relapse, off prednisone; c) SRNS in long-term remission, off prednisone (nephrotic controls); d) patients in remission on long-term prednisone therapy; and e) 15 age-matched normal controls. Children suffering an acute relapse of SRNS showed an increase in Leu2a+/DR+ (CD8) activated lymphocytes (P less than 0.05), a decrease in Leu4a+ total T-lymphocytes (P = 0.01) and a decrease in Leu3a+ (CD4) helper T-cells (P less than 0.05) when compared to normal controls and nephrotic controls. Though some subset changes may represent a prednisone effect and the functional role of these lymphocytes in the disease process is unknown, this study provides additional evidence to support a role for abnormal T-cell subsets in the etiology of SRNS.

Adolescent

Enhanced neutrophil function in children on bromide therapy.

The final step in neutrophil bacterial killing is formation of a toxic halide complex. For this reason, we studied neutrophil function in children receiving bromide anticonvulsant therapy. Whole blood and serum were obtained from 7 patients with seizure disorders treated orally with triple bromide elixir to examine neutrophil function as measured by luminol enhanced chemiluminescence (CL). Serum bromide concentrations [Br-] were determined concomitantly. There was a direct correlation between [Br-] and CL activity of neutrophils (r = 0.87) with peak CL responses significantly higher than controls when [Br-] were in the therapeutic range (10-20 mM). With [Br-] above 25 mM, CL activity was reduced. Serum from patients also enhanced CL of control neutrophils with a similar relationship to measured [Br-]. To confirm that enhanced neutrophil activity was attributable to [Br-] use, [Br-] ranging from 0-50 mM were added to control neutrophils in otherwise normal physiologic conditions and the CL assay was performed. Results expressed as percent of control values were as follows: [Br-] 5 mM, 110%; 10 mM, 158%; 15 mM, 194%; 20 mM, 252%; 25 mM, 136%; 30 mM, 364%; and 50 mM, 205%. These data demonstrate that Br- enhances phagocytic and bactericidal activity of neutrophils and suggest that Br- therapy may augment host defense capabilities.

Blood Bactericidal Activity

HLA antigens in tardive dyskinesia.

Fifty-three male, Caucasian, neuroleptic-treated patients with chronic schizophrenia were examined for the presence of tardive dyskinesia (TD) and were tissue typed. The group with TD (n = 25) was compared to the group without TD (n = 28). HLA-DR4 was more prevalent in the group with TD than in the group without TD, with a relative risk of 3.04 for TD with HLA-DR4 present, although this finding is not statistically significant when corrected for the number of nonparametric comparisons. Other investigations reported an association between HLA-B44 and TD, or between HLA-B44 and neuroleptic-induced parkinsonism. Potential explanations relating the findings of these investigations are discussed.

Dyskinesia, Drug-Induced

Effect of prolonged modified fasting in obese persons on in vitro markers of immunity: lymphocyte function and serum effects on normal neutrophils.

The effects of nutritional manipulation on immune function have been extensively studied in animals, but few studies have examined dietary restriction in humans. Obese patients enrolled in a protein-sparing, calorically restricted diet were monitored over a 3-month period with in vitro examination of mitogen- and antigen-induced lymphocyte blastogenesis. The sera from these patients were evaluated for effects on neutrophil chemotaxis, phagocytosis and microbial killing. Significant changes in body weight, triglycerides and glucose occurred during the diet, and most patients exhibited urinary ketosis. The diet was associated with increased blastogenesis in unstimulated cultures and in varicella and candida antigen-stimulated cultures, but blastogenesis was unchanged for phytohemagglutinin, concanavalin A, SK-SD and histoplasma. In assays of serum effects on neutrophil function, patients with urinary ketosis had depression of chemotaxis and microbial killing but not phagocytosis when compared to baseline or nonketotic patients. This study indicates that long-term caloric restriction is associated with significant effects on in vitro lymphocyte stimulation and with significant serum effects on normal neutrophil function.

Blood Glucose

HLA antigens in drug-induced parkinsonism.

The results of two epidemiological studies suggest a hereditary predisposition to develop drug-induced parkinsonism. We investigated human leukocyte antigen (HLA) antigen prevalence rates in patients with neuroleptic-induced parkinsonism. Fifty-two male, white, neuroleptic-treated, chronic in-patients with DSM-III-diagnosed schizophrenia were examined for the presence of parkinsonism. Subjects were tested for 23 type A, 43 type B, 4 type C, and 10 type DR HLA antigens. The group of schizophrenic patients with parkinsonism (n = 29) was compared with the group of schizophrenic patients without parkinsonism (n = 23). There were no significant differences between the two groups with respect to age, duration of neuroleptic exposure, or anticholinergic drug exposure. One HLA antigen, B44, was significantly more prevalent in the group with parkinsonism than in the group without parkinsonism. We derived a relative risk of 7.16 for drug-induced parkinsonism with HLA-B44 present in this group of schizophrenic patients. These data indicate that HLA-B44 may play a role in genetic or immunologic susceptibility to develop drug-induced parkinsonism in white schizophrenic individuals.

Adult

Significance of opacification of the maxillary and ethmoid sinuses in infants.

To evaluate the incidence and significance of radiographic sinus opacification in infants, we performed computed tomography (CT) of the maxillary and ethmoid sinuses in conjunction with routine cranial CT in 100 infants from birth to 12 months of age. CT was performed for indications other than sinusitis. Prospective concurrent clinical history was obtained and physical examination of the upper respiratory tract was performed. Of 100 infants, 16 had hypoplasia of the maxillary sinuses; 81% (13/16) of these were less than 2 months of age. The antra showed progressive increase in size during the first year of life. Of the 100 infants, 70 had CT sinus opacification, including 67% of those without historical or physical evidence of upper respiratory tract infection. There was a positive correlation of CT findings between the maxillary and ethmoid sinuses in 80% of the infants older than 2 months of age but in only 49% of the younger infants. Radiographic sinus opacification in infants is of uncertain significance and is not diagnostic of upper respiratory tract infection, much less of sinusitis.

Age Factors

Antimicrobial therapy for pediatric patients.

New antimicrobial agents are being introduced for clinical use at an increasingly rapid rate. This has required physicians continually to review relevant data and determine unique properties that might guide selection among any new antibiotics as well as older ones. Efficacy, potential toxicity, and comparative cost (in that order) generally guide selection. The present comprehensive review examines currently available antibiotics along with some under investigation, emphasizing these three basic areas of consideration.

Aminoglycosides

Functional capacity of immunoglobulin G preparations and the F(ab')2 split product.

Five immunoglobulin G preparations, including one 5S F(ab')2 split product, were compared for activity against common bacterial, viral, and protozoan pathogens. Standard assays were used to quantitate antibodies to tetanus, diphtheria, cytomegalovirus, herpes simplex virus types 1 and 2, rubella virus, and Toxoplasma gondii. Opsonization and killing of bacteria were examined by chemiluminescence methods using Streptococcus pneumoniae types 5, 12F, and 14 and Staphylococcus aureus. Antibodies to the viral pathogens and T. gondii were not detectable for the 5S immunoglobulin even at high concentrations (50 mg/ml) but were present in all 7S preparations at immunoglobulin concentrations of 10 mg/ml. Relatively lower activities for tetanus and diphtheria antibody were also seen with the F(ab')2 product. Opsonizing capacity against all pneumococcal serotypes and Staphylococcus aureus was lowest for the 5S product and highest for the commercially available intravenous immunoglobulin product that is purified by using a pH 4.25 formulation. These data do not support potential clinical usefulness of immunoglobulin G split products and suggest wide variations of specific antibody among commercial intravenous immunoglobulin preparations.

Animals

Histocompatibility determinants in childhood postinfectious encephalomyelitis.

Postinfectious encephalomyelitis and multiple sclerosis have clinical, immunologic, and neuroradiographic similarities. We studied HLA determinants in six white children consecutively diagnosed with postinfectious encephalomyelitis. Each of the children had HLA determinants which have been associated with multiple sclerosis. Relative risk (RR) calculations demonstrated that these antigens and genotypes occurred significantly more often in patients with postinfectious encephalomyelitis than in the control population (A3, RR 6.14; B7, RR 6.14; DR2, RR 4.51; A3B7, RR 9.36; A3DR2, RR 5.83; B7DR2, RR 6.13; A3B7DR2, RR 10.90). These data suggest that children with postinfectious encephalomyelitis are genetically predisposed to this demyelinating disease. Although the same HLA determinants were found in these patients as in those with multiple sclerosis, studies of a larger number of postinfectious encephalomyelitis patients will be needed before it can be concluded that the two diseases share a common genetic propensity.

Child