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C J Baker

Publications and source records attributed to C J Baker.

At least 73 records · Page 4Linked to original sources
PubMed1997

Direct intraoperative measurement of human brain temperature.

OBJECTIVE: Because hypothermia enhances human tolerance for cerebral ischemia, profound hypothermia is induced in many centers so that the circulation can be arrested while clips are applied to high-risk giant cerebral aneurysms. Brain temperature is measured directly with an intracerebral probe that avoids the uncertainty of surrogate monitoring. However, when there is a large thermal gradient between brain temperature and that of the operating room, even direct measurements can sometimes be misleading. This study was undertaken to determine how deeply a thermal sensor must be embedded in the cerebral parenchyma to ensure that the ambient environment does not distort the measurement of brain temperature. METHODS: Each of 39 normothermic patients had a thermocouple sensor inserted into a temporal lobe seizure focus just before its resection. Brain temperature was measured as the sensor was withdrawn in stages. RESULTS: At both 3 and 2 cm beneath the cortical surface, the temperature of the brain was essentially the same. However, when the sensor was withdrawn to 1 cm, recorded temperature decreased from 35.7 +/- 0.9 to 34.3 +/- 1.4 degrees C (P < 0.001) and irrigation in the vicinity caused major thermal change. At shallower depths, even lower brain temperatures were recorded. No morbidity was attributable to the temperature measurements. CONCLUSION: Direct intraoperative measurement of human brain temperature is feasible and safe, but accuracy requires that the temperature sensor be inserted at least 2 cm into the cerebral cortex.

Body Temperature Regulation↗
PubMed1997

Suppurative thrombophlebitis in children: a ten-year experience.

OBJECTIVE: To determine the clinical and diagnostic features, complications, management and prevention of superficial suppurative thrombophlebitis (ST) in children < 18 years of age. STUDY DESIGN: A retrospective review of medical records was performed for patients in two urban hospitals from January 1, 1985, through June 30, 1995, with a discharge diagnosis of phlebitis. RESULTS: We identified 21 patients, including 12 neonates, with ST. The majority had underlying medical conditions or preceding invasive procedures and administration of broad spectrum antibiotics or total parenteral nutrition as possible predisposing factors. More than two-thirds had localizing signs (swelling, erythema, induration or a palpable cord); one-third had purulent drainage from the vein. Septicemia was present in one-third of patients. Fever and tenderness were present in older children. Nearly one-half had involvement of an upper extremity. Cultures of vein (63%), blood (67%) or abscess (86%) grew pathogens in most. Gram-positive organisms were predominant; Staphylococcus aureus was isolated from 44%, Gram-negative enterics from 16.7% and Candida species from another 16.7% of patients. Eleven children had vein excision, whereas 10 had only incision and drainage. Complications, including death in one patient, occurred in 33% but could not be correlated with age or method of surgical intervention. CONCLUSIONS: ST is a rare but serious nosocomial infection in infants and children that results in substantial morbidity. It should be suspected in any hospitalized child who is or was receiving intravenous fluids and who has fever, localizing signs or persistent bacteremia. Prompt vein excision, with adjunctive antimicrobial therapy, is the recommended treatment.

Abscess↗
PubMed1997

Group B streptococcal infections.

Group B streptococcal disease remains a prominent cause of infectious morbidity in pregnant women and their infants. This article highlights recent developments that are relevant for obstetricians, perinatologists, and neonatologists caring for patients with group B streptococcal disease. The morbidity of group B streptococcal infections in pregnancy and the proposed association of colonization with adverse pregnancy outcome is discussed, as is the emergence of serotype V and the impact of late, late-onset disease for infants. Finally, the recently proposed guidelines for intrapartum chemoprophylaxis are summarized. Implementation of the guidelines should have substantial impact on reduction of early-onset group B streptococcal infections in infancy.

Age Factors↗
PubMed1996

Mutation of arginine 121 in lactoferrin destabilizes iron binding by disruption of anion binding: crystal structures of R121S and R121E mutants.

A conserved arginine residue helps to form the synergistic anion binding site in transferrins. To probe the importance of this residue for anion binding and iron binding, Arg 121 has been mutated to Ser and Glu in N-terminal half-molecule of human lactoferrin. The two mutants, R121S and R121E, have been expressed, purified, and crystallized. Their three-dimensional structures have been determined by X-ray diffraction at 2.3 and 2.5 A resolution, respectively. The structures were determined by molecular replacement and were refined by restrained least squares methods to final R values of 0.185 and 0.204. Both mutants still bind iron but with decreased stability. The crystal structures show that destabilization of iron binding probably results from disruption of the anion binding site; mutation of Arg 121 removes one wall of the anion binding pocket and causes the synergistic carbonate ion to be displaced 0.5 A from its position in the wild-type protein. In the process it becomes partially detached from the helix N-terminus that forms the rest of the anion binding site.

Anions↗
PubMed1996

Immune response to type III group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine.

Group B Streptococcus (GBS) is an important perinatal pathogen. Because transplacentally acquired maternal antibodies to the GBS capsular polysaccharides (CPS) confer protection, prevention of infant disease may be possible after immunization of women. Unfortunately, the purified CPS of GBS are only variably immunogenic in adults; therefore to enhance immunogenicity we have designed and developed a CPS-protein conjugate vaccine. The lability of a conformationally dependent epitope on the III CPS containing a critical sialic acid residue was important to consider in vaccine design. 100 women were randomized to receive GBS type III CPS-tetanus toxoid conjugate (III-TT) vaccine at one of three doses; unconjugated GBS type III CPS; or saline. Serum samples were obtained before immunization and 2, 4, 8, and 26 wk thereafter, and specific antibody to type III CPS was measured. Vaccines were well tolerated. In sera from recipients of the highest dose of III-TT, CPS-specific IgG levels rose from a geometric mean of 0.09 microg/ml before immunization to 4.53 microg/ml 8 wk later, whereas levels in recipients of unconjugated type III CPS rose from 0.21 microg/ml to 1.41 microg/ml. Lower doses resulted in lower antibody levels. A > or = 4-fold rise in antibody concentration was achieved in 90% of recipients of III-TT compared with 50% of those that received III CPS (P = 0.0015). Antibodies evoked by the conjugate vaccine recognized a conformationally dependent epitope of the III-CPS, promoted opsonophagocytosis and killing of GBS, and, after maternal immunization, protected neonatal mice from lethal challenge with type III GBS. We conclude that directed coupling of type III GBS polysaccharide to a carrier protein yielded a conjugate vaccine with preserved expression of a highly labile conformational epitope involving sialic acid and enhanced immunogenicity compared with uncoupled CPS.

Adolescent↗
PubMed1996

Inadequacy of rapid immunoassays for intrapartum detection of group B streptococcal carriers.

OBJECTIVE: To determine the accuracy of two currently used immunoassays and a newly developed optical immunoassay for rapid intrapartum detection of group B streptococcal colonization compared with culture methods. METHODS: Rayon-tipped swabs were used to collect specimens from the distal vagina of 502 women at admission for labor or rupture of membranes. Four tests were performed on specimens from the first 197 patients: culture in selective broth medium, semiquantitative culture on blood agar medium, and ICON Strep B and Quidel Group B Strep Test enzyme immunoassays. For the remaining 305 women, a fifth test, Strep B OIA, a newly developed optical immunoassay, was also performed. RESULTS: The prevalence of group B streptococcal vaginal colonization was 25.1% by selective broth medium and 17.3% when swabs were plated directly onto blood agar medium, giving the latter method a sensitivity of 69%. When compared with selective broth medium results, the sensitivities of the rapid immunoassays were 12% (Quidel), 15% (ICON), and 37% (Strep B OIA). These values rose to 16% (Quidel), 21% (ICON), and 53% (Strep B OIA) when compared with nonselective blood agar medium results. For women with heavy group B streptococcal colonization (more than 10(6) colony forming units/mL), the sensitivities were 36% (Quidel), 46% (ICON), and 100% (Strep B OIA). Specificities for all assays were high (98-100%), but variability was found in positive (79-100%) and negative (77-85%) predictive values. CONCLUSION: Although Strep B OIA reliably detects women with heavy group B streptococcal colonization and is more sensitive than either the ICON or Quidel enzyme immunoassays, none of these rapid assays is sufficiently accurate for routine use in the intrapartum detection of women colonized with group B streptococcus.

Adult↗
PubMed1996

Quantitative determination of antibodies to type III group B streptococcal polysaccharide.

The susceptibility of neonates to invasive infection with type III group B streptococci (GBS) in a radioactive antigen-binding assay (RABA) has been correlated with low maternal serum levels of capsular polysaccharide-specific antibodies. An ELISA was developed using capsular polysaccharide covalently coupled to human serum albumin. In sera from 35 healthy women, the range of IgG antibodies to GBS III polysaccharide was 0.05-33.0 micrograms/mL, and specific IgA antibodies were 0.08-1.1 micrograms/mL; however, no GBS III capsular polysaccharide-specific antibodies of the IgM isotype were detected by the ELISA. The levels of naturally acquired and vaccine-induced antibodies obtained with this ELISA correlated well with the results of the RABA (Spearman's rank correlation coefficient, .92). The ELISA has two major advantages over the RABA: It measures specific isotypes and subclasses of antibodies, and it can detect type III polysaccharide-specific antibodies at lower concentrations.

Animals↗
PubMed1996

Interleukin-6 production by human neonatal monocytes stimulated by type III group B streptococci.

The subcellular components of type III group B streptococci (GBS) that contribute to the host inflammatory response were determined by measuring production of the proinflammatory cytokine interleukin (IL)-6 by cord blood monocytes. Monocytes were stimulated with encapsulated (COH1) or unencapsulated (COH1-13) whole type III GBS or with purified GBS components, including type III capsular polysaccharide (III-PS), group B antigen (GB-Ag), lipoteichoic acid (LTA), or Escherichia coli lipopolysaccharide. Monocytes exposed to COH1 and COH1-13 released similar amounts of IL-6. GBS III-PS, GB-Ag, and LTA each induced IL-6. However, IL-6 release by monocytes was significantly greater after stimulation by GB-Ag than by III-PS or LTA (P < .05). Sera from 16 neonates with systemic GBS disease had IL-6 levels of 8 pg/mL to 4.28 ng/mL. GB-Ag is a potent inducer of IL-6 and may play an important role in tissue inflammation during GBS infection.

Adult↗
PubMed1996

Mild hypothermia reduces penumbral glutamate levels in the rat permanent focal cerebral ischemia model.

Although the cerebroprotective effects of hypothermia in focal models of ischemia are undisputed, the underlying mechanisms of this protection are still subject to much controversy. To analyze whether mild hypothermia attenuates glutamate levels in the penumbra surrounding permanent focal infarcts, extracellular glutamate concentration was analyzed bilaterally by microdialysis 20 minutes before to 120 minutes after a middle cerebral artery occlusion (MCAO) in rats. Normothermic animals (n = 11) had a baseline glutamate concentration of 1.14 +/- 0.40 mumol/ml (standard error of the mean) before the MCAO. Extracellular glutamate levels increased gradually after vessel occlusion to peak at 10.1 +/- 1.45 mumol/ml 80 minutes after the MCAO. This level gradually decreased to 5.72 +/- 1.67 mumol/ml by 120 minutes. Hypothermic animals (n = 11) had a baseline glutamate concentration of 1.73 +/- 0.83 mumol/ml before the MCAO. Extracellular glutamate levels increased after vessel occlusion but stabilized at 3.47 +/- 1.37 mumol/ml 30 minutes after the MCAO and remained stable until completion of the experiment. There were no significant differences in cortical blood flow between the normothermic and hypothermic groups at any time during the experiment. Infarct volumes, expressed as a percentage of the volume of the right (ipsilateral) hemisphere, were 19.8 +/- 2.16% in the normothermic group and 13.0 +/- 1.42% in the hypothermic group (P < 0.02). Although the normothermic penumbral glutamate levels began to increase immediately after the MCAO, they did not peak until 80 minutes after occlusion. In contrast, the normothermic core glutamate levels peaked within 30 minutes after the MCAO. Glutamate diffusion from the core region to the penumbra might account for this delay. Hypothermic cerebroprotection might involve a reduction in the pool of potentially diffusable glutamate in the core region but have little direct effect on glutamate release in the penumbra.

Animals↗
PubMed1996

Clinical and laboratory characteristics of a large cohort of symptomatic, human immunodeficiency virus-infected infants and children. AIDS Clinical Trials Group Protocol 152 Study Team.

BACKGROUND: A large cohort of antiretroviral therapy-naive, symptomatic, HIV-infected children were enrolled into a controlled therapeutic trial (AIDS Clinical Trials Group Protocol 152), providing an opportunity to describe their clinical and laboratory characteristics and determine age-related distinctions. METHODS: Study entry evaluations for 838 of 839 enrolled children were analyzed. Weight, head circumference (if < 30 months of age), neuroradiologic imaging of the head, developmental or cognitive status and neurologic examination were assessed. Laboratory studies included hemoglobin, absolute neutrophil count, CD4 cell count, serum amylase, alanine aminotransaminase, p24 antigen and HIV blood culture. Data were categorized by age (3 to < 12 months, 12 to < 30 months, 30 months to 6 years and > or = 6 years). RESULTS: Younger children had significantly higher rates of abnormalities before antiretroviral therapy, especially factors relating to growth and neurologic or cognitive function. Lower CD4+ cell counts and percentages as well as a positive serum p24 antigen correlated with lower weight-for-age Z scores and developmental indices. CONCLUSIONS: These data provide a description of the clinical characteristics of HIV-infected US children at the time antiretroviral therapy is initiated for HIV-related symptoms. The high rate of abnormalities of growth, development and cognitive ability that were observed in children < 30 months of age demonstrates that treatment strategies should be developed for earlier intervention.

AIDS-Related Opportunistic Infections↗
PubMed1996

Roles of the bacterial cell wall and capsule in induction of tumor necrosis factor alpha by type III group B streptococci.

Group B streptococci (GBS) are the major cause of sepsis and fatal shock in neonates in the United States. The precise role of tumor necrosis factor alpha (TNF-alpha) in the development of human GBS sepsis has not been defined; however, whole GBS have been shown to induce the production of this inflammatory cytokine. We sought to determine which bacterial cell wall components of GBS are responsible for triggering TNF-alpha production. Human cord blood monocytes were stimulated with encapsulated (COH1) or unencapsulated (COH1-13) whole type III GBS or with purified bacterial components, including type III capsular polysaccharide (III-PS), group B polysaccharide (GB-PS), lipoteichoic acid (LTA), or peptidoglycan (PG). Lipopolysaccharide from Escherichia coli served as a control. Supernatants were harvested at specific timed intervals, and TNF-alpha levels were measured by enzyme-linked immunosorbent assay. Monocytes exposed to COH1 and COH1-13 induced similar amounts of TNF-alpha. III-PS, GB-PS, LTA, and PG each induced TNF-alpha in a time- and concentration-dependent manner. However, TNF-alpha release was significantly greater after stimulation by the GB-PS or PG than after stimulation by III-PS or LTA (P < 0.05). Our findings indicate that GB-PS and PG are the bacterial cell wall components primarily evoking TNF-alpha release. These, alone or in concert with other factors, may be responsible for septic shock accompanying GBS sepsis.

Bacterial Capsules↗
PubMed1996

An outbreak of M serotype 1 group A Streptococcus in a neonatal intensive care unit.

OBJECTIVE: To describe the investigation and control of an outbreak of M serotype 1, Streptococcus pyogenes (group A Streptococcus, GAS) infections in a neonatal intensive care unit (NICU). STUDY DESIGN: The study was conducted in an NICU in a large urban university-affiliated hospital. Retrospective review was performed of all infants and health care workers in the NICU, especially those either colonized or infected with GAS during the outbreak and the prospective surveillance period (July through September 1994). Prospective epidemiologic investigation, including cultures of throat, umbilicus, and anorectum (infants), or throat and anus (NICU personnel), identified a possible common source of the disease in case infants. Antimicrobial susceptibility testing and serotyping of all GAS strains were performed; M serotype 1 isolates were examined by DNA analysis with restriction fragment length polymorphism. The M-1 GAS isolates were tested for streptococcal pyrogenic exotoxin (SPE) A and SPE B production. A retrospective chart review and analysis of infants with GAS infection or colonization was conducted. RESULTS: During a 1-week period, two very low birth weight infants more than 3 weeks of age had GAS septicemia and focal infection. Two additional very low birth weight infants with asymptomatic throat colonization were identified during the first week of surveillance. Benzathine penicillin G was administered to all NICU infants, but failed to eradicate throat colonization in the four case subjects. Seven days after completing parenteral antibiotic therapy, the index patient had a recurrence of GAS septicemia that was fatal. Eradication of throat colonization in the remaining three infants was achieved with a 10-day course of intravenous clindamycin therapy. Among 103 NICU personnel, five (4.9%) had asymptomatic GAS colonization with strains that were uniformly susceptible to penicillin. Each colonized adult was successfully treated with oral clindamycin therapy. Serotyping revealed that five isolates of GAS from four infants and one NICU respiratory therapist were M-1 isolates; DNA analysis confirmed that these were the same strain. The five M-1 isolates produced both SPE A and SPE B. CONCLUSIONS: The previously documented increase in prevalence of M-1 strains of GAS in the United States is likely to be associated with their introduction into closed populations including NICUs. Control of such outbreaks may be achieved by isolation, cohorting of case subjects and possible carriers, and successful eradication of colonization in case subjects and carriers. Although GAS organisms are uniformly susceptible to penicillin G, eradication may require agents other than penicillin.

Carrier State↗
PubMed1995

An assay for the determination of reduced methotrexate accumulation in cells displaying limited viability in vitro.

Amongst the mechanisms known to mediate resistance to methotrexate (MTX), a major component in the treatment of childhood leukemia, reduced drug accumulation appears to have direct clinical relevance. However, due to the poor viability of patient-derived acute lymphoblastic leukemia cells in vitro, determination of this parameter in clinical samples is associated with a number of difficulties. We have therefore developed an assay for reduced MTX accumulation, which controls for the metabolic state of the cell population under study by utilizing accumulation of the nucleoside thymidine as an independent indicator of this parameter. To establish this assay, we have utilized pediatric leukemic cell populations maintained as xenografts in nude mice, which, despite displaying sensitivity to MTX, demonstrated reduced accumulation of MTX when assayed using standard methodology. When accumulation of MTX by such cell populations was expressed, however, relative to their accumulation of thymidine, MTX accumulation was shown to be equal to that of drug-sensitive CCRF-CEM cells maintained in long-term culture. In contrast, significantly less MTX was accumulated, in this assay, by xenografted cell populations with demonstrated resistance to MTX. Identical results were obtained using either fresh or cryopreserved cells. The data thus indicate that by controlling for variable metabolic status of leukemic cells, it is possible to accurately assess MTX accumulation in leukemic samples displaying limited viability in culture.

Animals↗
PubMed1995

Invasive group B streptococcal disease in children beyond early infancy.

There is little information available on invasive group B Streptococcus (GBS) infection in pediatric patients older than 3 months of age. Review of infection control records at LeBonheur Children's Medical Center from January 1, 1986, to June 30, 1993, identified 143 patients with a positive GBS culture from normally sterile body fluid. Medical records of 18 (13%) patients > 3 months old with their first GBS infection were reviewed. Age range was 15 weeks to 18 years (median age, 13 months). Ten were black and 11 were girls. Five infants had a history of premature birth and 2 infants were infected with human immunodeficiency virus. The serotype distribution of 12 available GBS isolates was 4 type III, 2 each type V and Ia and 1 each type Ia/c, Ib/c, II and II/c. Bacteremia without a focus (9 patients) was the most common clinical manifestation. All 4 type III isolates were associated with bacteremia. One infant with human immunodeficiency virus infection had sepsis and bullous desquamation; a toxin-producing type V strain was isolated from her blood. Two adolescents with ventriculoperitoneal shunts had meningitis, including one whose cerebrospinal fluid also grew a type V strain. Other clinical manifestations were septic arthritis, endocarditis (Ia, II/c), central venous catheter (Ia/c) and ventriculostomy infections.

Adolescent↗
PubMed1995

Intraischemic hypothermia decreases the release of glutamate in the cores of permanent focal cerebral infarcts.

The cerebroprotective effects of hypothermia in focal models of ischemia are well established, but little is known about the underlying mechanisms of this form of brain protection. Cortical cooling in global transient ischemic models suggests that hypothermia limits glutamate excitotoxicity by decreasing the release of glutamate during ischemia. Few studies have examined glutamate release in the more physiological model of permanent focal ischemia. In this study, we used a rat model of middle cerebral artery occlusion (MCAO) of permanent focal ischemia. Extracellular glutamate concentration was analyzed bilaterally by microdialysis for 30 minutes before MCAO to 120 minutes after MCAO. Normothermic animals (n = 13) had a baseline glutamate concentration of 9.23 +/- 2.5 mumol/ml (mean +/- standard error of the mean) before MCAO. Extracellular glutamate rose quickly after vessel occlusion and peaked at 33.95 +/- 6.3 mumol/ml 30 minutes after MCAO. By 60 minutes after MCAO, this level had decreased to 25.14 +/- 6.3 mumol/ml; glutamate levels decreased slightly to 21.35 +/- 6.8 mumol/ml by 120 minutes. Hypothermic animals (n = 11) had an initial extracellular glutamate concentration of 5.22 +/- 1.3 mumol/ml before MCAO. This value rose gradually to a maximum of 10.69 +/- 3.3 microns/ml at 50 minutes after MCAO and then returned to a baseline value of 2.58 +/- 1.2 mumol/ml by 120 minutes. Contralateral control glutamate dialysates in the normothermic and hypothermic groups remained near baseline throughout the experimental period. The mean percentages of right hemispheric volumes occupied by infarcts were 11.96 +/- 1.68% in the hypothermic group and 19.77 +/- 2.03% in the normothermic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Serum elastase and alpha-1-antitrypsin levels in patients with ruptured and unruptured cerebral aneurysms.

Despite advances in surgical treatment and postoperative care, subarachnoid hemorrhage from ruptured cerebral aneurysms remains a devastating event. Excellent surgical results in treating unruptured aneurysms suggest the utility of screening tests to identify high-risk individuals. Unfortunately, none of the known risk factors for subarachnoid hemorrhage correlates strongly enough with the illness to warrant widespread screening for occult aneurysms. Other disease entities suggest that protease-antiprotease imbalances contribute to somatic vessel wall degradation and aneurysm formation. Detection of similar imbalances in selected patients may identify a predisposition to cerebral aneurysm formation. Serum concentrations of elastase and alpha-1-antitrypsin (AAT), important proteolytic and antiproteolytic enzymes, were measured in a series of 19 patients with unruptured aneurysms, 41 patients with ruptured aneurysms, and 27 age-matched operative and nonoperative controls. The elastase:AAT ratio was nearly twice as high in patients with unruptured aneurysms as in operative controls (0.527 +/- 0.1 versus 0.285 +/- 0.06; P < 0.04). Elastase:AAT ratios in patients with ruptured aneurysms (subarachnoid hemorrhage < 48 h) were roughly twice those of controls (0.582 +/- 0.095; P < 0.01). There was no statistical difference between elastase:AAT ratios for patients with ruptured and unruptured aneurysms. Likewise, elastase-AAT values for operative controls and nonoperative volunteers were not significantly different. Differences in serum elastase:AAT ratios between patients with aneurysms and controls reflected differences in elastase concentration (99 +/- 56 micrograms/ml versus 67 +/- 56 micrograms/ml; P < 0.03), not in AAT levels (147 +/- 56 micrograms/ml versus 141 +/- 56 micrograms/ml; P < 0.72).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗