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Biomedical subjects

R W Steele

Publications and source records attributed to R W Steele.

At least 109 records · Page 6Linked to original sources
PubMed1983

Treatment of varicella-zoster meningoencephalitis with acyclovir--demonstration of virus in cerebrospinal fluid by electron microscopy.

Disseminated varicella-zoster (V-Z) infection developed in three immunocompromised patients, with direct invasion of the central nervous system by virus. For two of these patients, diagnosis was confirmed by electron microscopic examination of cerebrospinal fluid (CSF) and detection of viral particles. Extensive immunologic evaluation demonstrated impairment of cellular immune function. All were treated with acyclovir at a dose of 1,500 mg/m2/day for 5-7 days. Peak and trough plasma levels of this antiviral agent were monitored during the course of therapy and were shown to be well above V-Z virustatic levels. Clinical response was noted by the third day of therapy. Vesicles and CSF were culture negative at termination of treatment. Administration of this high dose of acyclovir was not associated with hematologic, immunologic, hepatic, renal, or gastrointestinal toxicity as judged by frequent laboratory and clinical evaluation.

Acyclovir↗
PubMed1983

Pharmacokinetics of ceftriaxone in pediatric patients with meningitis.

Pharmacokinetics of ceftriaxone after a single dose of 50 or 75 mg/kg were determined in 30 pediatric patients with bacterial meningitis. Data for doses of 50 and 75 mg/kg, respectively, were as follows (mean +/- standard deviation): maximum plasma concentrations, 230 +/- 64 and 295 +/- 76 mug/ml; elimination rate constant, 0.14 +/- 0.06 and 0.14 +/- 0.04 h(-1); harmonic elimination half-life, 5.8 +/- 2.8 and 5.4 +/- 2.1 h; plasma clearance, 51 +/- 24 and 55 +/- 18 ml/h per kg; volume of distribution, 382 +/- 129 and 387 +/- 56 ml/kg; mean concentration in cerebrospinal fluid 1 to 6 h after infusion, 5.4 and 6.4 mug/ml. A dosage schedule of 50 mg/kg every 12 h for bacterial meningitis caused by susceptible organisms is suggested for pediatric patients over 7 days of age.

Anti-Bacterial Agents↗
PubMed1983

Comparison of flow cytometric analysis and [3H]thymidine incorporation for measurement of the effects of drug toxicity on lymphocyte stimulation.

Human mononuclear cells were exposed to three antiviral agents, stimulated with phytohemagglutinin, and assayed for DNA synthesis with [3H]thymidine uptake and flow cytometric analysis. Cytosine-arabinoside demonstrated inhibition of blastogenic reactivity by both [3H]thymidine uptake and flow cytometric analysis, whereas acyclovir showed no significant suppression. In contrast, (E)-5-(2-bromovinyl)-2'-deoxyuridine, a thymidine analog, demonstrated a lack of correlation between the two methods. The competitive inhibition of some compounds with [3H]thymidine incorporation necessitates the use of other methods to measure DNA synthesis.

Bromodeoxyuridine↗
PubMed1983

Localised immune complexes and slipped upper femoral epiphysis.

Slipped upper femoral epiphysis remains a disease of unknown aetiology. Recent evidence has bolstered speculation that the immune system may play a role in the aetiology or pathogenesis of slipped epiphysis or of one of its complications, chondrolysis. This study reports the finding of immune complexes in the synovial fluid of all but one hip affected with slipped epiphysis in a consecutive series. In seven patients, immune complexes were detected by both the Raji cell assay and C1q-binding assay; in two, by the C1q-assay only; and in one, by the Raji cell assay only. No patients had immune complexes in the serum. Twenty-one patients with synovitis of the knee or hip caused by a variety of disorders served as the control group. Two of these patients had immune complexes in their synovial fluid. It appears that the immune complexes characterise the synovitis found with slipped upper femoral epiphysis as distinct from most other synovitides.

Adolescent↗
PubMed1983

Cellular immunotoxicity of amyl nitrite.

Functional deficits in lymphocyte interaction following occasional or chronic exposure to inhaled nitrites may be a potential contributing but not the etiologic factor in the acquired immunodeficiency syndrome (AIDS). We evaluated the effect of amyl nitrite vapors on mononuclear cell function and demonstrated functional deficits and structural alterations in these cells. In this closed, in vitro system, exposure of cells to amyl nitrite for up to 30 minutes did not effect cell viability. The functional deficits demonstrated were: inhibition of lymphocyte erythrocyte (E) rosette formation, a suppression of lymphocyte mitogen (phytohemagglutinin) and antigen (cytomegalovirus) transformation, a block in the S, G2 and M phases of cell cycling and diminished cell cytotoxicity to CMV infected cells. These effects on cellular function were demonstrated following 5, 10, and 15 minutes of amyl nitrite vapor exposure; some effect on all cellular functions was demonstrated at 5 minutes. The structural alterations seen on scanning and transmission electron micrographs were: reduction of filapodia, smoothing of the cell profile, cytoplasmic protrusions with pseudopod-like extensions, an increase in rough endoplasmic reticulum with swollen cisternae, alterations in size and distribution of golgi components and exocytotic vesicles in the outer membrane of the nuclear envelope. These vesicles and increased membrane proliferation suggests an effect on the membrane synthesis mechanism in these cells. These effects may be a potential factor in the alterations of phenotypic markers on T lymphocyte populations, as well as, a potential contributing factor in the functional deficit of mononuclear cells in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Fatty acids and the inhibition of mitogen-induced lymphocyte transformation by leukemic serum.

The effects of sera from 23 patients with acute lymphocytic leukemia on mitogen-induced transformation of normal human lymphocytes were examined. All sera (100%) at diagnosis and 70% of those obtained during the induction of remission demonstrated inhibition of mitogen-induced lymphocyte transformation as evidenced by decreased uptake of [3H]thymidine. The inhibition could not be overcome by an increase in the mitogen concentration. Eighteen sera demonstrating a mean inhibition of 44.2% had elevated levels of free fatty acids (FFA) compared with five sera showing no inhibition (p value = 0.001). Inhibition, within the range produced by leukemic sera, could be achieved by the purified methyl esters of linoleic and linolenic acid in this system. Flow cytometric analysis of mitogen-induced cycling of normal human lymphocytes suggested that deoxyribonucleic acid (DNA) replication was inhibited by leukemic sera containing elevated levels of FFA after the G1 phase of cell cycling. Similar inhibition could be achieved by the methyl ester of linolenic acid in this system. Gas chromatographic analysis revealed that sera demonstrating inhibition contained linolenic (C18:3) acid (p value = 0.015), and the majority showed one or more of the following: 1) a concentration of oleic (C18:1) acid greater than 2 standard deviations (SD) above the mean of the control leukemic sera (i.e., those not demonstrating inhibition); 2) an arachidonic (C20:4) to C18:1 ratio that is reduced to greater than 2 SD below the mean of the control group; or 3) the presence of an unexpected fatty acid fraction. The data raise the question of an influence of FFA and, specifically, an interplay of unsaturated fatty acids on immune function during the natural history of acute lymphocytic leukemia.

Fatty Acids↗
PubMed1982

Functional bacterial opsonic activity of human amniotic fluid.

There are some data to suggest that amniotic fluid protects the fetus from invasion by pathogenic bacteria. To examine methods by which amniotic fluid may offer such protection, quantitative antibody, complement activity, and functional opsonic capacity were measured. Immunoglobulins were measured by laser nephelometry and total hemolytic complement was determined by radial diffusion; results suggested activity adequate for bactericidal capacity. The chemiluminescence assay was used to quantitate the functional interaction between polymorphonuclear leukocytes and E. coli, group B streptococci (GBS), or zymosan particles preopsonized with amniotic fluid obtained at different stages of gestation. Results were compared to those for normal serum. Data were analyzed by evaluation of the initial slope, area under the curve, and peak chemiluminescence response. Opsonic activity of amniotic fluid for E. coli and GBS was demonstrated, with E. coli showing greater reactivity (maximum = 15,000 to 25,000 cpm) than GBS (10,000 to 20,000 cpm). Specific, as well as nonspecific, opsonic activity was demonstrated by absorption of amniotic fluid with killed bacteria. Concentration of amniotic fluid did not result in an increase in chemiluminescent activity, which demonstrates that optimal opsonic activity already exists. The classical and alternate pathways of complement were assessed for E. coli and GBS. Preterm amniotic fluid did not differ in response from that of amniotic fluid obtained from term pregnancies. This study demonstrates that amniotic fluid can provide the fetus with protection from bacterial pathogens and delineates mechanisms for such protection.

Amniotic Fluid↗
PubMed1982

Brain abscess due to Nocardia caviae. Report of a fatal outcome associated with abnormal phagocyte function.

Nocardia is an uncommon cause of human disease. We report a patient with a fatal brain abscess who had abnormal phagocyte function as measured by neutrophile chemotaxis, adherence, phagocytic function, and chemiluminescence in vitro and by Rebuck skin window in vivo. Antimicrobial agar dilution susceptibility suggested minocycline was more active than sulfamethoxazole.

Brain Abscess↗
PubMed1982

Immune responses to varicella-zoster in the aged.

Skin test reactivity and in vitro lymphocyte stimulation responses to varicella-zoster (VZ) were examined in a large normal population ranging in age from 6 months to 93 years. Warning of cellular immunity, as examined by skin delayed hypersensitivity, began at age 40 years. Skin test responses to phytohemagglutinin, however, remained positive into the eighth decade of life. In vitro lymphocyte stimulation responses to VZ were usually positive (stimulation index greater than or equal to 2.5) until age 60 years, after which time levels, as observed with nonimmune individuals, were often demonstrated. Antibody levels, as measured by fluorescent antibody to membrane antigen, remained positive into the ninth and tenth decades of life. This was especially so with a history of reactivation (zoster) VZ infections, while skin test and in vitro responses were rarely positive in those individuals. This cellular, as contrasted with humoral, immunity decreases with advancing age, which may account for a propensity to reactivation of VZ virus.

Adolescent↗
PubMed1982

Varicella zoster in hospital personnel: skin test reactivity to monitor susceptibility.

An outbreak of chickenpox, involving three patients and one nurse on a pediatric ward, necessitated rapid identification of susceptible employees in conjunction with standard epidemiologic intervention in order to prevent spread to other high-risk patients. Of 46 hospital personnel 15 (33%) gave a negative or unknown history of prior disease. Response to a varicella-zoster skin test was compared with antibody determination as measured by fluorescent antibody to membrane antigen. Correlation of these two screening methods was absolute. Of 46 hospital personnel four (9%) were susceptible to infection (negative skin test and antibody less than 1:4) requiring their removal from the ward. All those with positive histories for prior disease with the virus and 11/15 (73%) with negative or unknown histories were immune as indicated by both tests. A readily available varicella zoster skin test would be an extremely useful epidemiologic tool for screening hospital personnel.

Adolescent↗
PubMed1981

Ketoconazole, amphotericin B, and amphotericin B methyl ester: comparative in vitro and in vivo toxicological effects on neutrophil function.

We investigated a number of parameters for host defense after the in vitro addition of the antifungal agents ketoconazole, amphotericin B (AMB), and amphotericin B methyl ester (AME). Similar assays were repeated before and after patients received the former two drugs. Viability by trypan blue exclusion, adherence by nylon wool columns, chemotaxis by the under-agarose technique, phagocytosis and killing by chemiluminescence, colony counts, and acridine orange direct visualization were assayed. In striking contrast to AMB and AME, ketoconazole demonstrated no significant effect on neutrophils. Adherence in the presence of therapeutic plasma levels of AMB and AME was decreased (P less than or equal to 0.005) at low drug concentrations, whereas at higher concentrations, adherence was increased (P less than 0.001). The chemotactic responses of cells incubated with AMB and AME demonstrated marked suppression. Phagocytic capacity and killing were decreased (P less than or equal to 0.005) with AMB as compared with control assays and assays performed in the presence of ketoconazole and AME. However, no difference were observed between two patients who received AMB and two other treated with ketoconazole.

Amphotericin B↗
PubMed1981

Immune deficiency in fetal alcohol syndrome.

In a review of 13 documented cases of fetal alcohol syndrome (FAS), an increased incidence of life-threatening bacterial infections as well as a propensity to minor infections was observed. Five of 13 patients had had at least one episode of pneumonia, two had meningitis, and one had sepsis. A comprehensive immunologic evaluation of FAS was completed, and results were compared to an age-matched control group of children with intrauterine growth retardation without FAS. Children with FAS were shown to have decreased E rosette-forming lymphocytes (35 +/- 5% versus 55 +/- 5% or 1328 +/- 274 versus 2333 +/- 112 per mm3), low EAC rosette-forming lymphocytes (15 +/- 2% versus 18 +/- 1% or 524 +/- 109 versus 740 +/- 75 per mm3), and diminished mitogen-induced stimulation responses to mitogens: 31616 +/- 5337 versus 58076 +/- 4455 cpm for phytohemagglutinin, 17582 +/- 5436 versus 35018 +/- 5346 for pokeweed mitogen, and 32460 +/- 7044 versus 54996 +/- 5531 for concanavalin A, P less than 0.05. Nine patients had dysgammaglobulinemia, FAS subjects also had a marked eosinophilia (624 +/- 154 versus 72 +/- 27 mm3). Other parameters of immune function including absolute lymphocyte and neutrophil counts, total hemolytic complement, delayed cutaneous hypersensitivity, and nitroblue tetrazolium dye reduction assays, were not different from control children. Impairment of immunity may explain an increased susceptibility to infection in FAS.

Antibody Formation↗
PubMed1981

Depressed neutrophil chemotaxis in infants with cow's milk and/or soy protein intolerance.

Neutrophil chemotaxis and random migration were studied in 11 infants with active cow's milk and/or soy protein intolerance and in an additional four infants following clinical recovery. Results were compared to 15 age-matched control subjects. Infants with active intolerance exhibited depressed chemotaxis and enhanced random migration. The four recovered infants had values similar to those of control subjects.

Animals↗