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Biomedical subjects

R W Steele

Publications and source records attributed to R W Steele.

At least 73 records · Page 4Linked to original sources

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↗

Immunotoxicology.

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Environmental Exposure↗

Changing presentation of herpes simplex virus infection in neonates.

We compared the clinical presentation of 95 newborns with herpes simplex virus (HSV) infection from 1973 through 1981 (first period) with data from 196 newborns evaluated from 1982 through 1987 (second period). There was a significant change in the presentation of infection in these infants. From the first to the second period, the frequency of disseminated disease decreased from 50.5% to 22.9%, whereas the frequency of skin, eye, and mouth (SEM) diseases increased from 17.9% to 43.4% (P less than .001). The frequency of infants with central nervous system (CNS) disease remained relatively unchanged--31.6% versus 33.7%. We also compared the demographic and clinical characteristics of the infants and their mothers. For neonates with CNS or disseminated infection, disease duration and frequency of prematurity were significantly decreased in the second period, as was the frequency of skin vesicles for newborns with SEM or disseminated infection. These changes are most likely the consequence of recognizing and treating SEM infection before its progression to more-severe disease.

Central Nervous System↗

Effects of ribavirin on neutrophil function.

Ribavirin, a broad spectrum antiviral agent, has been shown to exhibit immunosuppressive activity. This property has raised concerns during clinical trials because candidates for antiviral therapy are those who may develop secondary bacterial infection. We therefore investigated a number of parameters of neutrophil function after the in vitro addition of various concentrations of ribavirin. At pharmacologic concentrations (1.25-7.5 micrograms/mL), percent killing of phagocytized bacteria was increased as measured by an acridine orange fluorochrome microassay, significantly higher at a concentration of 5 micrograms/mL (p less than .02). There was no concomitant adverse effect on adherence, random migration, chemotaxis, opsonization or phagocytosis. The present data indicate that ribavirin has no acute suppressive effect on granulocyte function and may even enhance bacterial killing capabilities for treated patients.

Blood Bactericidal Activity↗

Intravenous immunoglobulin: new clinical applications.

At the present time there are three commercially available intravenous immunoglobulin (IVIG) preparations. There is no distinct therapeutic advantage for any one product over any other. Intravenous immunoglobulin is currently approved for the treatment of antibody deficiency syndromes and for acute and chronic idiopathic thrombocytopenic purpura. In addition, controlled clinical trials have demonstrated efficacy for the treatment of Kawasaki disease and for the prevention of the following infections: sepsis in preterm neonates, sepsis in infants with AIDS, and cytomegalovirus infection in the immune-compromised host. Open (uncontrolled) studies have suggested benefit in the treatment of neonatal sepsis, chronic Epstein-Barr virus infection, and a number of autoimmune diseases. Additional carefully designed studies must be completed before IVIG therapy can be recommended for these latter categories. In published reports, dosage of IVIG and intervals between infusions have varied considerably. For all current indications, the physician must therefore individualize treatment and thoroughly review any recent literature that may clarify guidelines to IVIG therapy. Significant adverse reactions are rare but high cost remains the main obstacle to more routine implementation.

Clinical Trials as Topic↗

Complement: function and clinical relevance.

There is a remarkable array of proteins participating in the complement cascade, regulating the activation of the system, or recognizing a fragment of a component as a biologic signal. The classical pathway of complement activation depends on antigen-antibody interaction and is important as an effector arm of acquired humoral immunity to microorganisms. The alternative pathway functions as a form of innate humoral immunity by attacking membranes not having the characteristics of self-membrane. In addition, the alternative path provides amplification after triggering by either path. Absence or dysfunction of many of the components is associated with autoimmune or immunodeficiency disease. Absence of the inhibitor C1INH is associated with the unique syndrome of hereditary angioedema.

Complement Activation↗

A comparison of native and modified intravenous immunoglobulin for the management of hypogammaglobulinemia.

Ten patients with severe hypogammaglobulinemia received 6 monthly infusions of either native or modified intravenous immunoglobulin (IVIG) followed by 6 monthly infusions of the other product in a double-blind, crossover protocol. Clinical parameters were monitored on a daily basis and serum was obtained at 24 hours, 3 weeks, and 4 weeks after each infusion for measurement of total IgG, specific antibodies, and opsonizing antibodies against Streptococcus pneumoniae types 5, 12F, and 14. No differences between the products were seen for total IgG or antibodies against herpes simplex virus types 1 and 2, rubella, toxoplasma cytomegalovirus, diphtheria, or tetanus. Greater opsonizing antibody to the three strains of pneumococci were apparent for native IVIG until the third infusion, after which time products were equal. Clinical parameters (febrile or symptomatic days, missed work/school, time on antibiotics, culture positive infection, and hospitalizations) were equivalent during the treatment period with each preparation. This study showed equivalent efficacy of native IVIG as compared with reduced and alkylated IVIG during maintenance therapy for hypogammaglobulinemia.

Agammaglobulinemia↗

Functional capacity of marginated and bone marrow reserve granulocytes.

Marginated and bone marrow reserve granulocytes were obtained from young healthy volunteers after subcutaneous administration of aqueous epinephrine (0.4 ml/m2) or intravenous administration of hydrocortisone sodium succinate (250 mg), respectively. These leukocytes were compared with circulating granulocytes for the ability to adhere to surfaces, migrate in a random fashion, respond to chemoattractants, interact with autologous serum opsonins, and phagocytize and kill five common bacterial pathogens. As contrasted with circulating neutrophils, marginated cells had enhanced phagocytic and killing capacity for some pathogens, whereas adherence, random migration, chemotaxis, and chemiluminescence for the two cell populations were equivalent. Bone marrow reserve cells demonstrated increased activity for three functional mechanisms; chemotaxis for these cells averaged 21% higher than that for circulating cells, and phagocytosis was 32% higher, with 6 to 17% greater killing of the five bacterial species studied. All of these differences were statistically significant (P less than 0.05). Random migration and interaction with serum opsonins were unchanged in bone marrow granulocytes. These enhanced functional properties of neutrophils which are outside of the circulating pool may represent important host defense mechanisms during episodes of bacterial infection.

Bacteria↗

Immune modulators as antiviral agents.

Immune modulators have exhibited some limited efficacy in the prevention or treatment of viral infection. Such agents have included transfer factor, thymosin, thymic humoral factors, levamisole, isoprinosine, immune RNA, young lymphocytes, vitamin C, and BCG. This article focuses on data that have examined clinical application of immune adjuvant therapy.

Adjuvants, Immunologic↗

Bacterial meningitis presenting with normal cerebrospinal fluid.

At a large children's hospital cases of bacterial meningitis with normal initial cerebrospinal fluid determinations other than culture or antigen detection assays were reviewed in an attempt to determine clinical or other laboratory findings accompanying this presentation. During a 5-year period from January, 1980, through December, 1985, 7 of 261 pediatric meningitis patients (2.7%) fulfilled these criteria. Ages ranged from 3 weeks to 18 months. All 7 patients were hospitalized for observation with all but 1 begun on empiric antibiotic therapy. Laboratory parameters such as a complete blood count, sedimentation rate or C-reactive protein did not influence decisions for management. Cerebrospinal fluid antigen detection assays were negative in all but one patient with pneumococcal meningitis. Review of these cases did not reveal unique indicators for bacterial meningitis. The results emphasize that the physician must rely on clinical judgment in initiating empiric antimicrobial therapy once apparently normal cerebrospinal fluid parameters are observed.

Antigens, Bacterial↗

Influence of operations with cardiopulmonary bypass on polymorphonuclear leukocyte function in infants.

To determine the effect of operations with cardiopulmonary bypass on the immunologic function of polymorphonuclear leukocytes in infants, we studied polymorphonuclear leukocyte function and immunologic profile in 16 infants undergoing repair of congenital heart lesions. An oxygen/air/high-dose fentanyl anesthetic was used for all patients. Absolute neutrophil count increased significantly (p less than 0.05) after bypass and remained increased 48 hours afterward. Chemotaxis, random migration of polymorphonuclear leukocytes, and phagocytic index were unaffected, but bactericidal capacity decreased significantly immediately after cardiopulmonary bypass and remained decreased 48 hours later. Serum opsonizing capacity to bacterial and fungal antigens was variably altered, and complement factors 3 and 4 decreased significantly after cardiopulmonary bypass. Total hemolytic complement decreased significantly immediately after cardiopulmonary bypass and returned to normal by 48 hours. These data suggest that operations with cardiopulmonary bypass in infants significantly affect the immunologic function of polymorphonuclear leukocytes and result in consumption of complement.

Blood Bactericidal Activity↗

Immunologic responses following serial skin testing.

Twenty volunteers underwent intradermal skin testing with tetanus toxoid (TT) and varicella-zoster (VZ) antigens weekly for 7 weeks. In addition to measurements of delayed hypersensitivity skin test responses, in vitro antigen specific lymphocyte stimulation and antibody levels were monitored. Data for TT exhibited more variability than VZ, demonstrating a marked boost in antibody titers after the first skin test and a shift in the kinetics of the skin test reaction to later maximum responses after the first 3 weeks. In contrast, serial skin testing with VZ was not associated with changes in cellular immune assays. Following the initial VZ skin test there was a slight rise in antibody levels for one-third of studied individuals. These observations suggest that VZ skin test antigen is ideal for monitoring immune function and that repeated testing should not significantly influence in vitro assays.

Adolescent↗

Immunotoxicology of brown recluse spider (Loxosceles reclusa) venom.

A purified toxic protein from Loxosceles reclusa venom was assayed for its in vitro effects on the human immunological and blood clotting systems. The toxin caused inhibition of neutrophil chemotaxis, depletion of serum hemolytic complement, prolongation of the activated partial thromboplastin time and depletion of clotting factors XII, XI, IX and VIII by an average of 44% in human plasma. The prothrombin time of human plasma was also prolonged by 1.5-2.0 sec. No effect of the purified toxin was observed on microbicidal ability of neutrophils, the release of enzymes from neutrophils or the adherence of neutrophils to glass beads.

Arthropod Venoms↗