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C J Baker

Publications and source records attributed to C J Baker.

At least 37 records · Page 2Linked to original sources

Candidal meningitis in neonates: a 10-year review.

Candidal meningitis may complicate systemic candidiasis in the premature neonate. We conducted a 10-year retrospective review of 106 cases of systemic candidiasis in neonates to define the incidence, clinical features, laboratory findings, treatment, and outcome of candidal meningitis. Twenty-three of the 106 neonates had candidal meningitis (0.4% of admissions to the neonatal intensive care unit). The median gestational age was 26.2 weeks, the median birth weight was 820 g, and the median age at the onset of illness was 8 days. Clinical disease was severe and commonly was manifested by respiratory decompensation. Findings of cerebrospinal fluid (CSF) analyses varied: pleocytosis was inconsistent, hypoglycorrhachia was common, gram staining was uniformly negative, and Candida was isolated from 17 neonates (74%). Each infant was treated with amphotericin B (median cumulative dose, 30 mg/kg); 5 also received flucytosine therapy. In conclusion, initial clinical features of candidal meningitis are indistinguishable from those of other causes of systemic infection in premature neonates, and normal CSF parameters do not exclude meningitis. Timely initiation of amphotericin B monotherapy was associated with an excellent outcome.

Antifungal Agents↗

The CCR5Delta32 allele slows disease progression of human immunodeficiency virus-1-infected children receiving antiretroviral treatment.

The role of the CCR5Delta32 allele in human immunodeficiency virus (HIV)-1-related disease progression was analyzed for 457 antiretroviral-naïve children who had participated in the Pediatric AIDS Clinical Trials Group 152 study, which demonstrated that didanosine (ddI) or zidovudine + ddI treatments were superior to zidovudine alone. The CCR5Delta32 allele was detected at an overall frequency of 6.1% (28/457). At study entry, heterozygote children (wild type [wt]/Delta32) had higher baseline median CD4(+) counts/mm(3) than wt/wt children had (1035 vs. 835 cells/mm(3); P=. 043), higher mean weight-for-age Z scores (-0.15 vs. -0.84; P=.01), and a trend toward less cortical atrophy (P=.059). During antiretroviral treatment and study follow-up, there was a trend toward less disease progression and death among heterozygote children than among wt/wt children (P=.056; relative hazard, 0.28; 95% confidence interval, 0.07-1.13) independent of the antiretroviral treatment to which they were randomized.

Alleles↗

Metal substitution in transferrins: specific binding of cerium(IV) revealed by the crystal structure of cerium-substituted human lactoferrin.

Proteins of the transferrin family play a key role in iron homeostasis through their extremely strong binding of iron, as Fe3+. They are nevertheless able to bind a surprisingly wide variety of other metal ions. To investigate how metal ions of different size, charge and coordination characteristics are accommodated, we have determined the crystal structure of human lactoferrin (Lf) complexed with Ce4+. The structure, refined at 2.2 A resolution (R=20.2%, Rfree=25.7%) shows that the two Ce4+ ions occupy essentially the same positions as do Fe3+, and that the overall protein structure is unchanged; the same closed structure is formed for Ce2Lf as for Fe2Lf. The larger metal ion is accommodated by small shifts in the protein ligands, made possible by the presence of water molecules adjacent to each binding site. The two Ce4+ sites are equally occupied, indicating that the known difference in the pH-dependent release of Ce4+ arises from a specific protonation event, possibly of the His ligand in one of the binding sites. Comparing the effects of binding Ce4+ with those for the binding of other metal ions, we conclude that the ability of transferrins to accommodate metal ions other than Fe3+ depends on an interplay of charge, size, coordination and geometrical preferences of the bound metal ion. However, it is the ability to accept the six-coordinate, approximately octahedral, site provided by the protein that is of greatest importance.

Cerium↗

Platelet activating factor acetylhydrolase decreases lung reperfusion injury.

BACKGROUND: Ischemia-reperfusion injury involves free radical production, polymorphonuclear neutrophil chemotaxis/degranulation, and production of proteolytic enzymes, complement components, coagulation factors, and cytokines. Activated polymorphonuclear neutrophils, endothelial cells, and macrophages produce platelet activating factor, which further promotes these inflammatory reactions. The recently cloned plasma form of platelet activating factor-acetylhydrolase (PAF-AH) demonstrates antiinflammatory effects by degrading platelet activating factor. We evaluated the effects of PAF-AH in an isolated perfused rat lung model by adding it to the flush solutions or to the reperfusion blood. METHODS: Rat lungs were isolated, flushed with EuroCollins (EC) or University of Wisconsin (UW) solution, stored at 4 degrees C for 6 or 12 hours, and reperfused using a cross-circulating syngeneic support rat. During reperfusion, oxygenation, compliance, and capillary filtration coefficient were calculated. There were four groups in the study; group I (control) had no PAF-AH added, group II had PAF-AH added to the flush solution, group III had PAF-AH added to reperfusion blood, and group IV had PAF-AH added to both flush solution and reperfusion blood. RESULTS: After 6 hours of storage, oxygenation, compliance, and capillary filtration coefficient significantly improved for EC in group IV. For UW, oxygenation improved in group IV whereas compliance improved in groups II, III, and IV. After 12 hours of storage, compliance improved for EC in group IV and capillary filtration coefficient improved in groups III and IV. For UW, oxygenation and compliance improved in groups II and IV, whereas capillary filtration coefficient improved in group IV. CONCLUSIONS: Addition of PAF-AH to intracellular organ preservation solutions and to the blood reperfusate significantly improves postreperfusion oxygenation and compliance, and reduces lung capillary permeability.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Group B streptococcal colonization and serotype-specific immunity in pregnant women at delivery.

OBJECTIVE: To describe the relationship between serum concentration of group B streptococcal capsular polysaccharide-specific immunoglobulin (Ig) G, colonization status, race or ethnicity, and age in pregnant women. METHODS: Pregnant women (n = 3307) were enrolled from geographically and ethnically diverse populations. At the time of admission for delivery, swabs of the lower vagina and rectum were obtained for isolation of group B streptococci. In a subset of women whose sera were available, capsular polysaccharide-specific IgG concentrations were quantified by serotype-specific (Ia, Ib, II, III, and V) enzyme-linked immunosorbent assay and compared by group B streptococcal colonization status. RESULTS: Group B streptococcal colonization was detected in 856 women (26%), and the rate was significantly higher among black women (37%) than in other racial or ethnic groups (odds ratio 1.7, 95% confidence interval 1.4, 2.1). Colonization status did not differ by study site or age. Colonization with serotypes Ia, II, III, or V was associated with significantly higher serum concentrations of IgG specific for the capsular polysaccharide of the colonizing serotype compared with noncolonization. However, 48% of colonized women had low capsular polysaccharide-specific IgG levels (less than 0.5 microg/mL) in their delivery sera. Colonized teenagers had the lowest median concentration. CONCLUSION: Colonization with group B streptococcus can elicit a systemic immune response, with a cumulative increase in the prevalence of capsular polysaccharide-specific IgG with increasing age. Conversely, low antibody levels in colonized teenagers might account in part for the reported increased risk of group B streptococcal disease in neonates born to these patients.

Adult↗

Prophylactic photopheresis and chronic rejection: effects on graft intimal hyperplasia in cardiac transplantation.

BACKGROUND: Despite the decreased incidence of acute rejection episodes and improvements in short and intermediate term graft survival with current immunosuppressive agents, there has been little progress in decreasing the morbidity and mortality from chronic rejection. This phenomenon may, in part, be related to the development of a humoral immune response with increases in anti-HLA antibodies, which presents as accelerated graft arteriopathy with intimal hyperplasia. METHODS: Based on prior experimental work, a pilot, prospective, randomized study was performed in 23 primary cardiac transplant recipients to determine whether the addition of prophylactic photopheresis to a cyclosporine, azathioprine and prednisone regimen was safe and resulted in decreased levels of panel reactive antibodies (PRA) and transplant arteriopathy. RESULTS: There was no difference between the two groups in regard to infection or acute rejection incidence. The photopheresis group had a significant reduction in PRA levels at two time points within the first 6 postoperative months. Coronary artery intimal thickness was significantly reduced in the photopheresis group at 1-yr (0.23 vs. 0.49 mm, p < 0.04) and 2-yr (0.28 vs. 0.46 mm, p < 0.02) follow-up compared with the control group. CONCLUSION: In this small pilot study, photopheresis is a safe, well-tolerated immunomodulatory technique that is capable of decreasing the severity of chronic rejection manifesting as post-transplant graft intimal hyperplasia.

Adolescent↗

A 5-year review of recurrent group B streptococcal disease: lessons from twin infants.

Recurrent invasive disease due to group B Streptococcus (GBS) in twin infants has not been reported. We report 2 cases of recurrent GBS afflicting both siblings of a set of dichorionic twin infants. The maternal and infant colonizing and invasive strains were identical by serotyping and pulsed-field gel electrophoresis (PFGE). Despite attempts at eradication with different antibiotic regimens, the infants remained colonized after treatment of the second episode. A 5-year review of recurrent invasive GBS disease in infants in our affiliated hospitals was undertaken, and 6 further cases were identified. Serotyping and PFGE of isolates from initial and second episodes were genotypically identical for each case. Three infants each had GBS serotype Ia or V disease and 2 had GBS serotype III disease. The exact pathogenesis of recurrent GBS disease remains unclear, but our data support the hypothesis that persistent mucosal colonization with the original GBS strain rather than new acquisition is a pivotal factor in disease recurrence.

Bacteremia↗

Invasive disease due to group B Streptococcus in pregnant women and neonates from diverse population groups.

From 1993 through 1996, surveillance for invasive disease due to group B Streptococcus (GBS) in neonates aged <7 days and in peripartum pregnant women was performed in a racially and ethnically diverse cohort in 4 cities in the United States. In a birth population of 157,184, 130 neonatal cases (0.8 per 1000) and 54 maternal cases (0.3 per 1000) were identified. Significant correlates with neonatal disease were black or Hispanic race and a birth weight <2500 g. The attack rate for peripartum maternal infection varied widely by city and may have been influenced by the frequency of administration of intrapartum antibiotics or of evaluating febrile women by performance of blood cultures. Pregnancy loss or GBS disease in the infant occurred in 28% of these maternal cases. Among neonatal and maternal GBS isolates, serotypes Ia (34%-37%) and III (25%-26%) predominated, and type V was frequent (14%-23%). These results provide a description of invasive GBS perinatal infection during the period in which guidelines for prevention were actively disseminated.

Age Distribution↗

Systemic candidiasis in extremely low birth weight infants receiving topical petrolatum ointment for skin care: a case-control study.

BACKGROUND AND OBJECTIVE: An increase in the incidence of systemic candidiasis (SC) followed a change in skin care for extremely low birth weight (ELBW) infants in our neonatal intensive care unit (NICU). We sought to determine whether the use of topical petrolatum ointment (TPO) for skin care of ELBW infants was associated with risk for SC. STUDY DESIGN: Case-control study. SETTING: A 48-bed NICU in a private hospital in Houston, Texas. PATIENTS: Ten ELBW infants with and 30 without SC admitted to the NICU from December 1, 1997 through July 31, 1998. METHODS: ELBW infants with SC were identified using hospital microbiology and infectious disease consultation databases. A case was defined as an infant weighing </=1000 g at birth with Candida spp isolated from a normally sterile body site. Three infants without SC were matched to each case by birth weight, admission date, and survival to the age of SC onset for the case. Data were collected by retrospective medical record review. Molecular analysis of Candida isolates was performed by karyotyping and restriction fragment length polymorphism using pulsed-field gel electrophoresis. RESULTS: Case infants had a mean (+/- standard deviation) age of onset of 21.5 +/- 24 days. Infants with SC and controls did not differ in birth weight, gestational age, or duration of therapy with steroids, antibiotics, insulin, or total parenteral nutrition. Although cases were more likely to be born vaginally and had a longer duration endotracheal intubation than controls, these differences were not significant. The odds ratio for skin care with TPO in case infants versus control infants was 11 (95% confidence interval: 1.9-63). Skin care with TPO was discontinued and the incidence of SC decreased to baseline. Several Candida spp and genetic profiles were identified, suggesting that there was not a common source outbreak. CONCLUSIONS: We conclude that the use of TPO promoted an increase in the incidence of SC in ELBW infants. Additional investigation of potential infectious risks for ELBW infants receiving TPO skin care is warranted.

Administration, Topical↗

Discitis and vertebral osteomyelitis in children: an 18-year review.

BACKGROUND: Discitis and vertebral osteomyelitis are uncommon entities, and diagnosis often is confounded by their similar clinical presentation, because characteristic radiographic findings are not evident until late in the course of illness. OBJECTIVE: To compare the age distribution, clinical manifestations, and radiographic findings, especially magnetic resonance imaging (MRI), in children with discitis or vertebral osteomyelitis. METHODS: A retrospective review of 57 children with a discharge diagnosis of discitis or vertebral osteomyelitis hospitalized from January 1980 through December 1998. RESULTS: Fifty patients met inclusion criteria: 36 with discitis and 14 with vertebral osteomyelitis. The mean age at presentation was younger for children with discitis than for those with vertebral osteomyelitis (2.8 vs 7.5 years of age) and the duration of symptoms longer for children with vertebral osteomyelitis than for those with discitis (33 vs 22 days). The initial symptom for both groups of children was refusal to walk, limp, or back pain, but children with osteomyelitis more often were febrile (79% vs 28%) and ill-appearing than those with discitis. Thirty-three patients with discitis had radiographs of the spine; 25 (76%) had abnormalities that were diagnostic. Ten discitis patients had MRI; 9 (90%) had abnormalities consistent with this diagnosis. Thirteen children with vertebral osteomyelitis had radiographs of the spine, but in only 7 (54%) were these abnormal. However, 11 had MRIs, and in each the diagnosis of vertebral osteomyelitis was established. CONCLUSION: This comparative study suggests that age and clinical presentation distinguish most patients with discitis from those with vertebral osteomyelitis. Although radiographs of the spine usually are sufficient to establish the diagnosis of discitis, MRI is the diagnostic study of choice for pediatric patients with suspected vertebral osteomyelitis.

Adolescent↗

Predicting HIV disease progression in children using measures of neuropsychological and neurological functioning. Pediatric AIDS clinical trials 152 study team.

BACKGROUND: Neuropsychological testing and 2 measures of neurological status, cortical atrophy, and motor dysfunction were assessed for their usefulness in predicting human immunodeficiency virus (HIV) disease progression in infants, children, and adolescents who participated in Pediatric AIDS Clinical Trials Group Protocol 152 (PACTG 152). METHODS: A cohort of 722 antiretroviral therapy-naive children with symptomatic HIV infection were assessed at study entry and at later intervals. Assessments included neurodevelopmental testing, neuroradiologic imaging, and neurological examination of motor function. CD4 cell count and plasma RNA viral load also were measured. RESULTS: Children with the lowest neuropsychological functioning (IQ < 70) at baseline had the highest risk for later HIV disease progression (56%), compared with those with borderline/low (IQ = 70-89) functioning (26%), or with average or above (IQ > 90) functioning (18%). This was also true of week 48 neuropsychological functioning. Motor dysfunction (especially reduced muscle mass) at entry also predicted disease progression. Furthermore, motor dysfunction and week 48 neuropsychological functioning provided predictive information beyond that obtainable from surrogate markers of HIV disease status (eg, CD4 count, HIV RNA level). Children with cortical atrophy also were at higher risk for later disease progression, but when CD4 count and RNA viral load were known, cortical atrophy information provided no additional predictive information. CONCLUSIONS: Measures of neuropsychological and motor function status provide unique information regarding pediatric HIV disease progression. As such, these findings have important implications for predicting long-term outcomes (eg, longevity) in pediatric patients.

AIDS Dementia Complex↗

Addition of a water-soluble alpha-tocopherol analogue to University of Wisconsin solution improves endothelial viability and decreases lung reperfusion injury.

BACKGROUND: Reperfusion injury following lung preservation has been associated with free radical formation and subsequent endothelial cell damage. Trolox is a water-soluble analogue of the free radical scavenger alpha-tocopherol. We hypothesized that addition of this form of vitamin E to University of Wisconsin (UW) solution would decrease reperfusion injury and improve lung function after cold ischemic preservation. MATERIALS AND METHODS: Bovine aortic endothelial cells were cultured and stored at 4 degrees C for 12, 24, and 48 h in UW or UW + Trolox (UWT). Endothelial cell viability after storage was assessed by dimethylthiazole tetrazolium cytotoxicity assay. An isolated rat perfused lung (IPL) model was used and lungs were flushed with the respective solutions with cold storage times of 6 and 12 h. Following storage, the lungs were reperfused with fresh blood and lung function was assessed by blood gas analysis, alveolar-arterial gradient, and compliance. RESULTS: There was no difference in endothelial cell viability between UW and UWT after 12 or 24 h; however, UWT had higher endothelial cell viability than UW with 48 h of cold ischemic storage. Using the IPL model, the pO2 was higher with UWT than UW after 6 and 12 h of cold ischemia. The alveolar-arterial oxygen difference was significantly lower for UWT versus UW at 6 h. UWT provided increased compliance at 6 and 12 h of ischemia. CONCLUSIONS: The addition of a water-soluble vitamin E analogue to UW solution resulted in increased endothelial cell viability after prolonged storage and improved whole lung preservation in the postreperfusion period as evidenced by higher oxygenation and increased compliance. These results are clinically relevant as the lung is extremely sensitive to reperfusion injury and UW solution is being increasingly used in lung transplantation and remains the predominant solution in abdominal organ transplantation.

Adenosine↗

Safety and immunogenicity of capsular polysaccharide-tetanus toxoid conjugate vaccines for group B streptococcal types Ia and Ib.

About 40% of invasive group B streptococcal (GBS) isolates are capsular polysaccharide (CPS) types Ia or Ib. Because infant and maternal GBS infections may be preventable by maternal vaccination, individual GBS CPS have been coupled to tetanus toxoid (TT) to prepare vaccines with enhanced immunogenicity. Immunogenicity in rabbits and protective capacity in mice of a series of type Ia- and Ib-TT conjugates increased with the degree of polysaccharide-to-protein cross-linking. In total, 190 healthy, nonpregnant women aged 18-40 years were randomized in four trials to receive Ia- or Ib-TT conjugate (dose range, 3.75-63 microg of CPS component), uncoupled Ia or Ib CPS, or saline. All vaccines were well-tolerated. CPS-specific IgG serum concentrations peaked 4-8 weeks after vaccination and were significantly higher in recipients of conjugated than of uncoupled CPS. Immune responses to the conjugates were dose-dependent and correlated in vitro with opsonophagocytosis. These results support inclusion of Ia- and Ib-TT conjugates when formulating a multivalent GBS vaccine.

Adolescent↗

Virologic and immunologic response to nucleoside reverse-transcriptase inhibitor therapy among human immunodeficiency virus-infected infants and children.

Plasma human immunodeficiency virus RNA and CD4 lymphocyte response to nucleoside reverse-transcriptase therapy were evaluated in a large, comparative pediatric trial. Both baseline values and changes in the two laboratory markers over time correlated well with clinical outcome and possessed independent predictive value. In comparison of RNA reduction from baseline between the dideoxyinosine (ddI) and zidovudine+ddI therapeutic arms, marginal superiority of the combination arm was not correlated with an observed clinical benefit. Despite the size of this trial and the significantly higher rate of clinical end points in the zidovudine monotherapy group, attempts to establish surrogacy for plasma RNA were difficult. Nevertheless, plasma RNA and CD4 lymphocyte count together possess strong clinical predictive power and are valuable tools for both the clinician and the evaluation of new therapies.

Adolescent↗

Maternal peripartum complications associated with vaginal group B streptococci colonization.

The study was done to determine the risk of clinically diagnosed intra-amniotic infection (IAI) and postpartum endometritis (PPE) associated with vaginal group B streptococci (GBS) colonization. Pregnant women were enrolled in a cross-sectional, observational study from 1992 to 1996 in Houston (n=908), Seattle (n=2676), and Pittsburgh (n=4338). Swab samples were obtained from the lower vagina of participants at admission for delivery and inoculated into selective broth and onto blood agar media. At the combined centers, 2.9% of the women (231/7922) had IAI, and 2.0% (157/7922) had PPE. The risk of IAI was higher for women with heavy GBS colonization (odds ratio [OR], 2.0; 95% confidence interval [95% CI], 1.1-3.7) than for those with light colonization (OR, 1.2; 95% CI, 0.7-1.8). The risk of GBS-associated PPE was not influenced by density of colonization (OR, 1.8; 95% CI, 1.3-2.7). These findings provide further evidence that GBS is associated with maternal intrapartum complications.

Adult↗

Resource utilization associated with initial hospital stays complicated by early onset group B streptococcal disease.

BACKGROUND: The epidemiology of early onset neonatal group B streptococcal (GBS) disease has changed appreciably, but there are no recent assessments of the in-hospital resource utilization it incurs. STUDY DESIGN: We performed a retrospective cohort study of infants delivered from 1987 through 1995 at Massachusetts' largest obstetrics hospital. A matched cohort design was used to assess care occurring after transfer to another acute care hospital. RESULTS: There were 135 cases of early onset neonatal GBS infection complicating 85,062 deliveries (1.6/1,000 births) in 9 years, with a substantial decline beginning in 1994, when maternal intrapartum chemoprophylaxis was widely introduced. Most (73%) infants had birth weights of 2500 g or more; 93% survived. Overall both the median and mean lengths of stay were 8 days longer for infants with GBS disease than for those without this infection (P < 0.001). Total hospital charges for neonates with GBS disease also were higher, with the difference in medians of $5323 and in means of $10,004 (P < 0.001). Differences were greatest among >2500-g birth weight infants; no excess was evident for infants with birth weights of < 1500 g. CONCLUSION: There was a substantial excess length of stay and charges associated with early onset neonatal GBS disease, although this was less than previously reported.

Cost of Illness↗