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Biomedical subjects

C J Baker

Publications and source records attributed to C J Baker.

At least 145 records · Page 8Linked to original sources

Pharmacokinetics of intravenous immunoglobulin in very low birth weight neonates.

We studied the pharmacokinetics of single doses of intravenous immunoglobulin (IVIG) of 1000, 750 and 500 mg/kg administered to 21 neonates with birth weights from 750 to 1500 g. No adverse effects were detected. Mean pharmacokinetic values for the large, intermediate and small dose groups, respectively, were: elimination half-life, 19.6, 28.7 and 22.1 days; clearance, 5.2, 5.6 and 3.7 ml/kg/day; volume of distribution, 151, 255 and 130 ml/kg. Mean peak IgG concentrations in serum were 1826, 1476 and 1257 mg/dl for the large, intermediate and small dose groups, respectively. Mean IgG on post-infusion Days 1 to 28 were similar for the intermediate and small dose groups but were higher in the larger dose group. Both large and intermediate doses achieved larger increases in IgG over preinfusion values (delta IgG) than the small dose. The differences in delta IgG between the large and intermediate doses were less notable. The wide variability observed indicates that individualization of intravenous immunoglobulin dosage will be required in these patients.

Drug Combinations↗

Role of the Plasmalemma H-ATPase in Pseudomonas syringae-Induced K/H Exchange in Suspension-Cultured Tobacco Cells.

Activation of a host plasma membrane K(+) efflux/net H(+) uptake exchange by pathogenic pseudomonads plays an important role in the development of hypersensitivity in tobacco (Nicotiana tabacum). Involvement of the plasmalemma H(+)-pumping ATPase in this response was investigated. The exchange response of suspension-cultured tobacco cells to Pseudomonas syringae pv syringae was reduced 90% or more by ATPase inhibitors including vanadate, N-ethylmaleimide, and N,N'-dicyclohexylcarbodiimide. The exchange was also strongly inhibited by the protonophore carbonyl cyanide m-chlorophenylhydrazone and by slightly alkaline external pH. Respiratory inhibitors such as oligomycin and sodium azide reduced the exchange by 50% to 75%, while glycolysis inhibitors such as sodium arsenite and sodium iodoacetate decreased exchange by approximately 90%. These results suggest that plasmalemma H(+)-ATPase activity is required for the exchange response and that this may reflect a requirement for a plasmalemma pH and/or electrical potential gradient.

Journal Article↗

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↗

Restriction endonuclease analysis of human and bovine group B streptococci for epidemiologic study.

Group B streptococci, a frequent cause of neonatal sepsis and meningitis, postpartum endometritis, and bovine mastitis, may be acquired by several modes of transmission. Detailed epidemiologic study is hampered by the lack of a sufficiently discriminatory typing system, especially for type III and nontypable strains. We examined 54 epidemiologically well-characterized strains by restriction endonuclease analysis (REA) and compared the results with those obtained by serotyping. REA patterns were inspected without knowledge of the epidemiological or serotyping data. Among 21 type Ia, Ia/c, and Ib/c isolates, we found 10 REA patterns; among 5 type II and IIc isolates, we found 5 REA patterns; among 13 type III isolates, we found 6 REA patterns; and among 15 nontypable human and animal isolates, we found 7 different REA patterns. Double digestion of type III isolates with EcoRI and BglII helped us to distinguish the isolates. In total, 28 REA patterns were found in six serotype groups and one nontypable group. Some geographically and epidemiologically separate isolates had identical REA patterns, suggesting dissemination of a limited number of clones. We conclude that REA is a promising tool for detailed epidemiological study of group B streptococci.

Animals↗

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↗

Group B streptococcal breast abscess in a mother and mastitis in her infant.

Group B streptococcus is a common cause of postpartum infection, but breast abscess in a lactating woman has not been reported. Seven days postpartum, a woman developed mastitis resulting from type Ib/c group B streptococcus. She was treated with oral antibiotics for 1 week, with apparent resolution. Breast-feeding was continued, but at reduced frequency on the affected side. Two days later, local and systemic symptoms recurred, and a large breast abscess was surgically drained. Five days into the mother's initial episode of mastitis, her infant developed type Ib/c group B streptococcal mastitis, requiring hospitalization and parenteral antibiotic therapy. It is likely that the pathogenesis of infection in this mother-infant pair was circular, and that either early abscess formation during the mother's first clinical infection and/or milk stasis due to decreased frequency of breast-feeding resulted in transient group B streptococcal bacteremia, with seeding of breast tissue in the newborn.

Abscess↗

Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus.

Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus is a promising strategy for the prevention of perinatal infections caused by group B streptococci. To explore the feasibility of this strategy, we vaccinated 40 pregnant women at a mean gestation of 31 weeks with a single 50-microgram dose of the Type III capsular polysaccharide of group B streptococcus. The only adverse effect detected was a mild local reaction in nine women (22 percent). Of the 35 women with low or unprotective antibody levels before immunization (less than 2 micrograms per milliliter), 20 (57 percent) responded to the vaccine. The geometric mean antibody level rose from 1.3 to 7.1 micrograms per milliliter four weeks after vaccination (P less than 0.02), and these levels persisted at delivery and three months post partum. Sixty-two percent of the vaccine-induced immunoglobulin in the mothers was IgG, which readily crosses the placenta. Infant antibody levels in cord serum correlated directly with maternal antibody levels at delivery (r = 0.913, P less than 0.001). Of the 25 infants born to women who responded to the vaccine, 80 percent continued to have protective levels of antibody at one month of age and 64 percent had protective levels at three months. Serum samples from infants with greater than or equal to 2 micrograms of antibody to Type III group B streptococcus per milliliter uniformly promoted efficient opsonization, phagocytosis, and bacterial killing in vitro of Type III strains. This effect could be mediated exclusively by the alternative complement pathway. Although this vaccine with an overall response rate of 63 percent is not optimally immunogenic, we conclude that maternal immunization is feasible and can provide passive immunity against systemic infection with Type III group B streptococcus in the majority of newborns. Larger trials with better vaccines will be required to evaluate the safety and clinical effectiveness of this strategy.

Adult↗

Disposition of an immunoglobulin intravenous preparation in very low birth weight neonates.

To assess the disposition, tolerance, and toxicity of an intravenous preparation of immunoglobulin (IGIV) in very low birth weight (VLBW) neonates, we administered single doses of 500 or 750 mg/kg to 20 neonates with birth weights between 750 and 1500 g during the first week of life. The infusion of this product was well tolerated. Modest changes in hemoglobin, hematocrit, and total hemolytic complement occurred as expected. Hepatic toxic effects were not detected. Mean peak IgG concentrations were 1564 and 1316 mg/dL for the high-dose and low-dose groups, respectively. Mean IgG concentrations were very similar for both groups on postinfusion days 1, 4, 7, 14, 21, and 28. IgG concentrations remained above 300 mg/dL in seven of 10 infants in each group by day 21, and in six of the high-dose group and seven of the low-dose group by day 28. Mean elimination half-lives were 22.6 and 22.8 days in the high-dose and low-dose groups, respectively. These data provide a basis for assessment of potential efficacy of IGIV in the prevention of late-onset infection in VLBW neonates.

Humans↗

Candida: an increasingly important pathogen in the nursery.

Advances in neonatal care now permit the survival of very immature infants. Although candidiasis is not a new disease, the spectrum of clinical disease has greatly widened and the rate of invasive disease has increased significantly. This article reviews the history, microbiology, and epidemiology of candidal infections, both superficial and invasive. Particular attention is paid to the pathogenesis of and risk factors associated with the development of invasive disease, as well as its clinical manifestations, diagnosis, and treatment.

Candidiasis↗

A polyclonal human IgG preparation hyperimmune for type III, group B Streptococcus: in vitro opsonophagocytic activity and efficacy in experimental models.

Neonates at risk for disease due to type III, group B Streptococcus (III-GBS) are those born with low serum levels of transplacentally derived, specific III-GBS antibody. Specific antibody is also required in vitro for opsonophagocytosis of III-GBS. Commercially available human immune serum globulins contain only moderate levels of III-GBS antibody. In the present study, IgG that was isolated from the serum of a human volunteer after vaccination with III-GBS polysaccharide contained very high levels of III-GBS antibody. Small amounts of this hyperimmune preparation added in vitro significantly increased the opsonophagocytosis of III-GBS in neonatal sera in the presence of polymorphonuclear leukocytes. Furthermore, small volumes of the preparation were protective in mouse and neonatal rat models of III-GBS disease. The administration of such hyperimmune human IgG preparations should be considered for preventing or treating III-GBS disease in infants.

Animals↗

Molecular cloning of a Pseudomonas syringae pv. syringae gene cluster that enables Pseudomonas fluorescens to elicit the hypersensitive response in tobacco plants.

A cosmid clone isolated from a genomic library of Pseudomonas syringae pv. syringae 61 restored to all Tn5 mutants of this strain studied the ability to elicit the hypersensitive response (HR) in tobacco. Cosmid pHIR11 also enabled Escherichia coli TB1 to elicit an HR-like reaction when high levels of inoculum (10(9) cells per ml) were infiltrated into tobacco leaves. The cosmid, which contains a 31-kilobase DNA insert, was mobilized by triparental matings into Pseudomonas fluorescens 55 (a nonpathogen that normally causes no plant reactions), P. syringae pv. syringae 226 (a tomato pathogen that causes the HR in tobacco), and P. syringae pv. tabaci (a tobacco pathogen that causes the HR in tomato). The plant reaction phenotypes of all of the transconjugants were altered. P. fluorescens(pHIR11) caused the HR in tobacco and tomato leaves and stimulated an apparent proton influx in suspension-cultured tobacco cells that was indistinguishable from the proton influx caused by incompatible pathogenic pseudomonads. P. syringae pv. tabaci(pHIR11) and P. syringae pv. syringae 226(pHIR11) elicited the HR rather than disease symptoms on their respective hosts and were no longer pathogenic. pHIR11 was mutagenized with TnphoA (Tn5 IS50L::phoA). One randomly chosen mutant, pHIR11-18, no longer conferred the HR phenotype to P. fluorescens. The mutation was marker-exchanged into the genomes of P. syringae pv. syringae strains 61 and 226. The TnphoA insertions in the two pseudomonads abolished their ability to elicit any plant reactions in all plants tested. The results indicate that a relatively small portion of the P. syringae genome is sufficient for the elicitation of plant reactions.

Blotting, Southern↗

Functional activity of class-specific antibodies to type III, group B streptococcus.

The functional activity of naturally acquired IgG and IgM with specificity for the capsular polysaccharide of type III, group B Streptococcus (III-GBS) was compared. Sera collected during convalescence from 14 infants who had developed specific antibodies following III-GBS infection were employed for separation of IgG from IgM by ion-exchange chromatography. Bactericidal killing of III-GBS was similar for IgG- and IgM-rich samples (37 and 42%, respectively) in reactions containing a mean of 1.0 or 1.9 micrograms/ml of III-GBS specific IgG or IgM antibody. Purified IgA lacked opsonophagocytic activity for III-GBS. These results indicate that III-GBS-specific IgG and IgM antibodies in infant sera promote opsonophagocytosis at low concentrations, and that their functional capacity is comparable.

Antibodies, Bacterial↗

Group F Streptococcus. An unusual cause of arthritis.

Bacterial arthritis is a serious infection in children occurring either as the result of direct inoculation of organisms into the joint space, of spreading from a contiguous focus of infection, or of hematogenous seeding of the synovium. Although the etiologic agent can be identified in 60% to 70% of cases, joint fluid cultures may remain negative in a substantial number of patients. The most likely etiologic agent depends both on the route of infection and the age of the child. Overall Staphylococcus aureus, Hemophilus influenzae type b and streptococci are the leading causes of bacterial arthritis. Lancefield groups A, B, C, D, and G have all been implicated. However, septic arthritis due to hematogenous seeding with Group F Streptococcus has not been previously reported. A normal 10-month-old boy presented with acute monoarticular arthritis of the knee and had Group F Streptococcus isolated from the blood. Antimicrobial therapy resulted in complete resolution of the arthritis.

Arthritis, Infectious↗