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Biomedical subjects

E O Mason

Publications and source records attributed to E O Mason.

At least 73 records · Page 4Linked to original sources
PubMed1989

Invasion of the inner ear by Haemophilus influenzae type b in experimental meningitis.

Bacterial interstrain variation for cochlear invasion was studied by intraperitoneal inoculation of infant rats with Haemophilus influenzae type b. Eight pairs of CSF isolates from children with or without deafness due to meningitis were injected into half of each litter in separate experiments. At 48 h, quantitative CSF culture results and CSF white blood cell counts were equivalent for the two groups. Organisms within the cochlea were detected in four of eight animals in each group. There was no difference between the deaf and nondeaf isolates in the degree or frequency of inner ear inflammation in formalin-fixed sections. In separate experiments, animals were inoculated with H. influenzae type b and 24 h later treated with ampicillin, or ampicillin plus dexamethasone. At 48 h, although CSF white blood cell counts were significantly reduced in the steroid group, no difference was noted in the degree of cochlear inflammation between the two groups. The ability of H. influenzae type b to invade the inner ear of infant rats does not correlate with the development of sensorineural deafness in children following H. influenzae type b meningitis. Steroid administration does not appear to diminish the inflammatory reaction within the cochlea more than antibiotics alone in this model, but may delay CSF sterilization by ampicillin.

Ampicillin↗
PubMed1989

Penetration of cefuroxime into ventricular fluid in cerebrospinal fluid shunt infections.

The penetration of intravenously administered cefuroxime into ventricular fluid was assessed in five pediatric patients with ventriculoperitoneal shunt infections and in one with a ventriculostomy infection. Patients received a total dose of 200 to 230 mg of cefuroxime per kg of body weight per day administered at 8-h intervals. Levels of cefuroxime in ventricular fluid ranged from 1.6 to 22.5 micrograms/ml and were associated with cerebrospinal fluid bactericidal titers ranging from less than 1:2 to 1:16 against infecting staphylococcal isolates. Five infections were cured with cefuroxime monotherapy. On the basis of MIC data, one patient had vancomycin substituted for cefuroxime and the infection was cured.

Adolescent↗
PubMed1989

Epidemiologic marker system for Citrobacter diversus using outer membrane protein profiles.

Investigations of nursery outbreaks of Citrobacter diversus sepsis and meningitis have been hampered by lack of adequate epidemiologic markers for the organism. We studied outer membrane protein profiles from clinical isolates of C. diversus by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine whether this method might be useful in the epidemiologic differentiation of strains. Paired cerebrospinal fluid isolates from each of three separate nursery outbreaks of C. diversus meningitis, paired isolates from the vagina of a postpartum woman and the cerebrospinal fluid of her newborn infant, one isolate from an infant with pneumonia and two from colonized nursery cohorts, and 30 epidemiologically unrelated clinical isolates were included. Eleven distinct profiles were differentiated by the presence or absence of five outer membrane proteins. Complete concordance of profiles was observed for epidemiologically related isolates. Unrelated epidemic strains had outer membrane protein profiles distinct from one another. Biotyping complemented determination of outer membrane protein profiles; the two markers differentiated each of the five epidemic strains from all but one of 30 unrelated nonepidemic isolates. Determination of outer membrane protein profiles is potentially useful in epidemiologic investigations of disease caused by C. diversus.

Bacterial Outer Membrane Proteins↗
PubMed1989

Adherence kinetics of Haemophilus influenzae type b to eucaryotic cells.

Haemophilus influenzae type b (Hib) adhere in vitro to buccal epithelial cells (BEC) via pili (fimbriae). In vivo studies have conflicting lines of evidence concerning the role of pili in adherence. This study characterizes the kinetics of Hib binding to BEC and compares pilus versus nonpilus adherence. Adherence was assessed using radioactive, immunofluorescence, and electron microscopic techniques. Paired Hib strains were obtained from three children with Hib meningitis; piliated Hib were isolated from the nasopharynx and nonpiliated isolates from the cerebrospinal fluid. Piliated strains adhered avidly to BEC after a 1-h incubation, whereas nonpiliated strains adhered poorly (p = 0.002). Kinetic analysis revealed increased adherence to BEC by piliated and nonpiliated strains with time, with maximum adherence occurring between 24-36 h. Immunofluorescence and electron microscopic assays visually confirmed the radioactive adherence findings. These results characterize the kinetics of Hib adherence to BEC. BEC incubated with nonpiliated Hib for 30 h were found to be coated with piliated strains, suggesting the induction of pilus production or the selection of a piliated subpopulation.

Bacterial Adhesion↗
PubMed1989

Persistent bacteremia due to coagulase-negative staphylococci in low birth weight neonates.

During a 6-month period in 1987, 13 low birth weight neonates without indwelling central intravascular catheters had persistent (positive blood cultures for greater than or equal to 6 days) coagulase-negative staphylococcal bacteremia despite adequate antibiotic therapy. Daily blood cultures remained persistently positive for a mean of 13 days (range 6 to 25 days). This group of infants was compared with other low birth weight infants with similar birth weights and nonpersistent coagulase-negative staphylococcal bacteremia, defined as two or more positive blood cultures accompanied by supporting clinical manifestations of sepsis. During this period, coagulase-negative staphylococcal represented 29% of all bacteremias, and 33% of coagulase-negative staphylococcal bacteremias were persistent. Other than soft tissue abscesses, none of the infants with persistent coagulase-negative staphylococcal bacteremia had a defined focus of infection. Abdominal distention (P = .001) and thrombocytopenia (P less than .03) occurred significantly more frequently in the patients with persistent coagulase-negative staphylococcal bacteremia than in those with nonpersistent bacteremia. Of the 13 patients with persistent coagulase-negative staphylococcal bacteremia, 2 received methicillin and 11 received vancomycin. No antibiotic tolerance to either antibiotic could be demonstrated. Serum concentrations of vancomycin far exceeded the minimum bactericidal concentration in all cases in which vancomycin was prescribed. No in vitro differences could be demonstrated between persistent and nonpersistent coagulase-negative staphylococcal strains for slime production, biotype, proteins from modified whole cell lysates developed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and opsonophagocytosis by adult neutrophils in the presence of pooled human sera. Additionally, plasmid profile analysis and phage typing revealed no common strain causing the persistent bacteremia.(ABSTRACT TRUNCATED AT 250 WORDS)

Amikacin↗
PubMed1988

Contribution of Haemophilus influenzae type b lipopolysaccharide to pathogenesis of infection.

The mechanism(s) by which the lipopolysaccharide (LPS) of Haemophilus influenzae type b may contribute to the virulence of this organism is unclear. Purified LPS of Haemophilus influenzae type b or phosphate buffered saline was administered intranasally to infant rats prior to the intranasal instillation of approximately 2-20 x 10(6) cfu of Hib two or three times per day for three consecutive days. The preadministration of 2.0 micrograms Hib LPS resulted in a significantly greater incidence of bacteremia (P = 0.0006) than PBS 30 min after the completion of the intranasal inoculation. Four days following completion of intranasal Hib inoculation the incidence of bacteremia was greater (P = 0.017) in the animals pretreated with LPS at 2.0 micrograms compared to the PBS pretreated animals. Preadministration of 0.2 micrograms LPS had no effect on the incidence of bacteremia or meningitis. There were no differences in the histology of the nasal cavities or turbinates of infant rats inoculated intranasally only with LPS or PBS. There were no differences in the frequency or density of bacteremia following intranasal administration of LPS from either Hib or E. coli. Although the mechanism is unknown, our findings suggest that the LPS of Hib may contribute to the ability of H. influenzae type b to invade the nasal mucosa in this infant rat model.

Administration, Intranasal↗
PubMed1988

Immunogenicity of the Haemophilus influenzae type b capsular polysaccharide conjugate vaccine in children after systemic Haemophilus influenzae type b infections.

We immunized 24 patients (mean age 15.2 +/- 9.3 months) with polyribosylribitol phosphate-diphtheria toxoid conjugate vaccine (PRP-D) 2 months after a systemic Haemophilus influenzae type b infection. Children less than 24 months of age were immunized twice. Serum was obtained for antibody to PRP before and 1 or 2 months after immunization. Three of five children greater than 24 months of age and three of six children 18 to 24 months of age developed greater than 1 microgram/ml of antibody after immunization, and geometric mean postimmunization levels were significantly greater than preimmunization levels for both groups. However, two children who failed to respond to conventional PRP vaccine did not respond as expected to one dose of PRP-D. For children 7 to 17 months of age, the geometric mean PRP antibody levels increased as follows: preimmunization, 0.05 micrograms/ml; after the first dose, 0.28 micrograms/ml (p = 0.003); and after the second dose, 3.39 micrograms/ml (p = 0.001). Of 13 children, 10 developed antibody values greater than 1.0 micrograms/ml. PRP conjugate vaccines are immunogenic in young children who have not developed protective PRP antibody levels after a systemic H. Influenzae type b infection.

Antibodies, Bacterial↗
PubMed1988

Follow-up of prospective randomized trial of ampicillin or chloramphenicol versus moxalactam treatment of Haemophilus influenzae type b meningitis.

In a prospective randomized trial, moxalactam administered to 66 children was compared with ampicillin or chloramphenicol given to 68 children for the treatment of Haemophilus influenzae type b meningitis. Acute morbidity and mortality rates were equivalent between the two treatment groups. At 2 years after discharge, the results of psychologic tests (Bayley Scales of Infant Development or McCarthy Scales of Children's Abilities) were also equivalent between the two treatment groups for patients remaining in the study.

Ampicillin↗
PubMed1988

Methicillin-resistant Staphylococcus aureus: pediatric perspective.

Methicillin-resistant S. aureus has emerged as a nosocomial pathogen of major importance in pediatric patients. Infection occurs most often in hospitalized individuals with underlying predisposing medical conditions. Any body site may be involved, and bacteremia frequently occurs concomitantly. Vancomycin is the antibiotic of choice for serious MRSA infections; PRPs and cephalosporins generally are not effective. The likelihood of an adverse outcome of infection increases with the severity of an underlying condition and delay in institution of appropriate therapy. Infection control measures have met with only limited success in eradicating MRSA from the hospital environment. Methicillin-resistant S. aureus is likely to remain of considerable clinical significance to physicians caring for seriously ill children.

Child↗
PubMed1988

Characterization of Citrobacter diversus strains causing neonatal meningitis.

We studied 17 strains of Citrobacter diversus isolated from the cerebrospinal fluid of infants with meningitis and compared these strains with 21 strains isolated from other body sites. The two groups of strains were similar with respect to biotype, piliation, hemolysin production, and resistance to the killing effects of serum. By using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we found that 14 (82%) of 17 strains from cerebrospinal fluid, but only two (10%) of 21 strains isolated from other body sites, possessed a minor outer membrane protein with a molecular weight of 32,000 (P less than .0001). This protein may serve as a marker for strains of C. diversus that are likely to cause meningitis or brain abscess in human neonates.

Bacterial Outer Membrane Proteins↗
PubMed1988

Pathogenesis of brain abscess formation in an infant rat model of Citrobacter diversus bacteremia and meningitis.

The pathogenesis of Citrobacter diversus meningitis and brain abscess was studied in infant rats. Two-day-old rats were inoculated intraperitoneally and intranasally with C. diversus. C. diversus strain 4277, lacking the 32,000-molecular-weight outer membrane protein that appears to be a marker for strains causing meningitis in human neonates, was more likely to produce bacteremia, meningitis, and death in rats than was strain 4036, which possesses this outer membrane protein. Strain 4036 was, however, more likely than strain 4277 to produce ventriculitis and brain abscess. In the infant rat, central nervous system involvement by C. diversus begins with bacteremia and leptomeningitis, followed by ventriculitis and direct extension of infection into periventricular brain parenchyma. Large numbers of bacteria persist inside inflammatory cells, an observation suggesting resistance to intraphagocytic killing. Bacterial strain differences, possibly related to the presence of a 32,000-molecular-weight outer membrane protein, may account for histopathologic differences in the brains of infant rats with C. diversus meningitis.

Animals↗
PubMed1987

Pharmacokinetics of amphotericin B in infants and children.

The pharmacokinetics of amphotericin B (AmB) have not previously been evaluated in children. Five very small, premature infants and five older children received 0.25-1.0 mg of AmB/kg per 24 hr for Candida infections. Serum concentrations of AmB, measured by bioassay, were used to determine various pharmacokinetic parameters of AmB. A one-compartment model of drug distribution was most consistent with the data. The volume of AmB distributed per kilogram of body weight was smaller and the elimination clearance more rapid than those previously reported for adults. Serum levels were approximately one-half those seen in adults given comparable doses. The mean concentrations of AmB after various doses were as follows: at 0.25 mg/kg, 0.08 microgram/ml; at 0.50 mg/kg, 0.20 microgram/ml; at 0.75 mg/kg, 0.42 microgram/ml; and at 1.0 mg/kg, 0.54 microgram/ml. Interpatient variability was, however, marked, especially among the premature infants. AmB pharmacokinetics are different in infants and children than in adults; these differences may have implications for determining optimal pediatric dosing regimens.

Adolescent↗
PubMed1987

Comparative in-vitro activity of LY146032 and eight other antibiotics against gram-positive bacteria isolated from children.

LY146032, a cyclic peptide antibiotic active against many Gram-positive bacteria, was compared to methicillin, vancomycin, clindamycin, cefuroxime and gentamicin against methicillin-resistant and methicillin-susceptible strains of Staphylococcus aureus and Staph. epidermidis. LY146032 was uniformly active against clinical isolates of staphylococci, inhibiting 90% of strains of Staph. aureus and Staph. epidermidis at a concentration of 0.5 mg/l. Vancomycin was slightly less active than LY146032 against Staph. aureus and Staph. epidermidis, inhibiting 90% of strains at concentrations of 1.0 and 2.0 mg/l, respectively. All other antibiotics tested were less active than LY146032 or vancomycin against staphylococci. LY146032 was compared to penicillin, ampicillin, vancomycin and chloramphenicol against strains of Streptococcus pneumoniae, group B streptococcus, group D streptococcus (enterococcus) and Listeria monocytogenes and was found to inhibit 90% of the strains at concentrations of 0.25, 1.0, 32.0 and 16.0 mg/l respectively. The combination of LY146032 and chloramphenicol was antagonistic in vitro for one strain each of Staph. aureus and group D streptococcus and showed indifference against other strains of Staph. aureus(2), Staph. epidermidis(2), group D streptococcus(1) and L. monocytogenes(2). LY146032 in combination with gentamicin showed indifference against the same bacteria. On the basis of its in-vitro activity, LY146032 appears to be a promising agent for the treatment of serious community- and hospital-acquired staphylococcal infections.

Anti-Bacterial Agents↗
PubMed1987

Effect of Haemophilus influenzae type b lipopolysaccharide on complement activation and polymorphonuclear leukocyte function.

Purified lipopolysaccharide (LPS) from Haemophilus influenzae type b (Hib) was examined for its capacity to interact with human hemolytic complement, generate conversion products of C3, C4, and factor B, stimulate C5a activity, and affect human neutrophil chemiluminescence and phagocytosis. Salmonella typhimurium LPS and Salmonella minnesota Rb LPS (R345 mutant) were examined for comparison. Incubation of Hib LPS with human serum deficient in gamma-globulin or with normal human serum containing 10 mM EGTA and 7 mM MgCl2 resulted in some depletion of hemolytic complement and conversion of C3 to degradation products (determined by inhibition of passive hemolysis and electrophoresis/immunofixation, respectively), indicating that complement activation occurred by the alternative pathway. Complement activation by Hib LPS and S. minnesota Rb LPS was similar, but significantly less effective than by S. typhimurium LPS (p less than 0.01). Solubilized Hib lipid A, but not LPS, induced conversion products of C4 in hypogammaglobulinemic serum, indicating activation of the classical pathway. Similar levels of C5a activity were generated by incubation of Hib LPS and S. typhimurium LPS in hypogammaglobulinemic serum, as determined by neutrophil shape change and neutrophil aggregation. Hib LPS directly stimulated neutrophil chemiluminescence, whereas S. typhimurium LPS had little effect. Phagocytosis of radiolabeled, opsonized Hib by neutrophils was diminished by S. minnesota Rb LPS, Hib LPS, or solubilized Hib lipid A (p less than 0.001), but was slightly increased by S. typhimurium LPS. Neither the oligosaccharide of Hib LPS or Hib capsular polysaccharide was capable of interacting with complement or altering neutrophil chemiluminescence or phagocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement Activation↗
PubMed1986

Pathogenesis of labyrinthitis associated with Haemophilus influenzae type b meningitis in infant rats.

The pathogenesis of labyrinthitis associated with bacterial meningitis was studied by histopathologic examination of inner ears of 114 rats with Haemophilus influenzae type b meningitis produced by ip inoculation of one of 13 clinical isolates. Findings consisted of inflammation of the perilymphatic spaces of the cochlea and semicircular canals with sparing of the endolymphatic space, cochlear nerve fibers, and middle ear. The degree of inflammation peaked at 48 hr after inoculation, then declined by 96 to 144 hr. No interstrain differences in type or degree of pathology were observed. Immunofluorescent staining of cochleae from 15 animals demonstrated that bacteria were present in areas of inflammation and also in the endolymphatic space and organ of Corti. One isolate displayed a tendency to accumulate in the perilymphatic spaces in larger numbers than those seen with three other isolates. These findings suggest that, in this model, inflammation reaches the inner ear by spreading from the subarachnoid space. Bacterial invasion of the organ of Corti may be one mechanism by which deafness occurs in bacterial meningitis.

Animals↗
PubMed1986

Protective effect of subinhibitory polymyxin B alone and in combination with ampicillin for overwhelming Haemophilus influenzae type B infection in the infant rat: evidence for in vivo and in vitro release of free endotoxin after ampicillin treatment.

The potential endotoxin modifying effects of subinhibitory doses of polymyxin B were evaluated in an animal model of overwhelming septicemia. Five to six day old Sprague-Dawley rats were infected intraperitoneally with 10(6)-10(7) cfu of Haemophilus influenzae type b. At 12 h after infection, at which time mortality was 18%, subinhibitory doses of polymyxin b (0.0125 mg/kg X 3 q 3 h) either alone or in combination with 500 mg/kg ampicillin significantly increased survival at 17 and 20 h (p = 0.009, 0.01 and p = 0.003, 0.01) compared to animals treated with 0.5 mg/kg of ampicillin alone. Prolonged survival at 36 h (p = 0.009) was seen in animals receiving both ampicillin and low dose polymyxin compared to either ampicillin dose alone. Ampicillin significantly reduced the number of bacteria in blood of survivors (p less than 0.023 at 30 min) compared to untreated animals but increased the activity of free endotoxin at 30 min compared to controls (p = 0.006). In vitro endotoxin release from H. influenzae type b increased 5-fold after addition of 100 micrograms/ml of ampicillin, whereas a six-fold reduction in endotoxin activity was measured after the addition of 7 micrograms/ml of polymyxin B. Subinhibitory doses of polymyxin B modulate the ethal effects of overwhelming H. influenzae type b infection in infant rats and might be beneficial as adjunct treatment in gram-negative septicemia.

Ampicillin↗
PubMed1985

Effect of piliation on interactions of Haemophilus influenzae type b with human polymorphonuclear leukocytes.

Piliated, adherent (P+) and nonpiliated, nonadherent (P-) strains of Haemophilus influenzae type b (Hib) were compared with respect to their ability to induce polymorphonuclear leukocyte (PMN) chemiluminescence (CL) and superoxide (O2-) generation and their susceptibility to phagocytosis by PMNs. P+ strains opsonized in normal human serum (NHS) induced significantly greater CL than did P- strains (500 X 10(5) +/- 112 X 10(5) versus 242 X 10(5) +/- 65 X 10(5) total counts per 60 min; P less than 0.001) when reacted with normal PMNs. Contributions of immunoglobulin and complement to CL activity in these mixtures were shown by findings of lower overall levels of CL when hypogammaglobulinemic serum or heat-inactivated NHS was used to opsonize either P+ or P- organisms. Results obtained with mixtures of hypogammaglobulinemic plus adsorbed heat-inactivated NHS (with P+ or P- organisms) suggested a role for an antipilus antibody in the enhancement of CL by these strains. NHS-opsonized P+ strains also induced significantly greater (P less than 0.002) O2- generation than did P- strains (2.83 +/- 0.08 versus 1.94 +/- 0.14 nmol of ferricytochrome c reduced per 10 min/10(6) PMN). Comparable ingestion of P+ or P- strains opsonized in NHS by PMNs was demonstrated by a radiolabeled uptake technique and transmission electron microscopy, and primary granule release (beta-glucuronidase) was comparable during ingestion of P+ or P- strains. The basis for the observed enhanced capacity of P+ Hib to stimulate PMN oxidative metabolism as compared with P- organisms is uncertain. Possible clinical implications of these findings deserve further study.

Antibodies, Bacterial↗