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Biomedical subjects

R Baker

Publications and source records attributed to R Baker.

At least 73 records · Page 4Linked to original sources

Search for CP violation in B+/- --> J/psiK+/- and B+/- --> psi(2S)K+/- decays.

We present a search for direct CP violation in B+/--->J/psiK+/- and B+/--->psi(2S)K+/- decays. In a sample of 9.7x10(6) B&Bmacr; meson pairs collected with the CLEO detector, we have fully reconstructed 534 B+/--->J/psiK+/- and 120 B+/--->psi(2S)K+/- decays with very low background. We have measured the CP-violating charge asymmetry to be [+1.8+/-4.3(stat)+/-0.4(syst)]% for B+/--->J/psiK+/- and [+2.0+/-9. 1(stat)+/-1.0(syst)]% for B+/--->psi(2S)K+/-.

Journal Article↗

Influence of human immunodeficiency virus-infected maternal environment on development of infant interleukin-12 production.

Monocyte-derived cytokine production by cord blood mononuclear cells (CBMC) from infants born to human immunodeficiency virus (HIV)-positive and -negative women was measured to determine whether monocyte dysfunction could contribute to the accelerated HIV disease of pediatric patients. Production of interleukin (IL)-12, but not that of tumor necrosis factor-alpha and IL-10, was reduced, compared with adult peripheral blood mononuclear cells (PBMC). This deficiency was more pronounced in infants of HIV-positive women, whose IL-12 production was also deficient. CBMC IL-12 levels were increased by interferon-gamma and CD40 ligand but remained deficient, compared with PBMC. IL-12 production was undetectable in 7 of 8 HIV-positive infants, in contrast to 21 of 26 uninfected infants. Uninfected infants of infected women exhibited an intermediate profile. These findings suggest that the maternal environment and/or exposure in utero to HIV products influence the newborn's immune response and that the differences between infants born to HIV-positive and -negative women may persist.

Adult↗

Jumonji, a nuclear protein that is necessary for normal heart development.

Jumonji (jmj) was cloned in a gene trap screen to identify and mutagenize genes important for heart development. To investigate the role of jmj in heart development, we generated mice homozygous for the jmj mutation. The jmj homozygous mouse embryos showed heart malformations, including ventricular septal defect, noncompaction of the ventricular wall, double-outlet right ventricle, and dilated atria. The jmj mutants died soon after birth, apparently as a result of respiratory insufficiency caused by rib and sternum defects in addition to the heart defects. In situ hybridization analyses suggested that cardiomyocytes were differentiated but developmental regulation of chamber-specific genes was defective in fetal hearts. Expression of jmj was detected in the myocardium, especially in the interventricular septum, ventricular wall, and outflow tract, which correlated well with the locations of defects observed in the hearts of mutant mice. Homozygous embryos failed to express the jmj transcript in all tissues except in the nervous system. Confocal microscopic examination using anti-JMJ antibodies indicated that the JMJ protein was localized in the nuclei of cells transfected with jmj. These data demonstrate that JMJ is a nuclear protein, which is essential for normal heart development and function.

Animals↗

First observation of the decay B --> J/psistraight phiK

We present the first observation of the decay B-->J/psistraight phiK. Using 9.6x10(6) B&Bmacr; meson pairs collected with the CLEO detector, we have observed ten fully reconstructed B-->J/psistraight phiK candidates, whereas the estimated background is 0.5+/-0.2 event. We obtain a branching fraction of B(B-->J/psistraight phiK) = (8. 8(+3.5)(-3.0)[stat]+/-1.3[syst])x10(-5). This is the first observed B meson decay requiring the creation of an additional s&smacr; quark pair.

Journal Article↗

Type 2B von Willebrand's disease in thirteen individuals from five unrelated Australian families: phenotype and genotype correlations.

Type 2B von Willebrand's disease (VWD) is due to a qualitative defect in von Willebrand factor (VWF) in which there is an increased affinity for the platelet glycoprotein Ib-IX-V receptor complex. Spontaneous binding of type 2B VWF to platelets and subsequent clearance from the plasma is thought to account for the characteristic phenotype of type 2B VWD. These gain-of-function mutations are due to single amino substitutions that are clustered within the functionally important A1 domain of VWF. We describe 13 individuals from five unrelated families in Australia with type 2B VWD, report their phenotypic abnormalities, and delineate their causative mutations. We confirm that the mutation Arg543Trp is also particularly common among families with type 2B VWD in Australia.

Amino Acid Substitution↗

The variability of goniometric measurements in ambulatory children with spastic cerebral palsy.

This study assessed the variability of six goniometric measurements commonly used in the assessment of children with cerebral palsy (CP). Three experienced paediatric physiotherapists recorded three consecutive measurements of six joint ranges from 12 children with spastic CP. A fourth measurement was recorded 1 week later. The order of measurement with regards to both joint measurement and tester, was randomised to ensure a balanced experimental design. A blinded procedure was adopted with masked goniometers and a second assessor present to record the measurement. Results, analysed using generalizability theory, showed same day and different day measurement error of +/-10-14 degrees (95% confidence limits) for the foot/thigh angle, abduction and internal rotation of the hip. The source of this was child-assessor and residual error. For ankle dorsiflexion and the popliteal angles, same day measurement error was similar. However, for joint ranges recorded on different days, error ranged from +/-18-28 degrees. The major source of this was systematic differences in measurements recorded on different days. Results show a need for caution when using goniometric measurements in clinical decision making, particularly in the more tone dependent biarticular muscles after an initial assessment.

Ankle Joint↗

Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder.

In a previous study (Comings DE et al. Comparison of the role of dopamine, serotonin, and noradrenergic genes in ADHD, ODD and conduct disorder. Multivariate regression analysis of 20 genes. Clin Genet 2000: 57: 178-196) we examined the role of 20 dopamine, serotonin and norepinephrine genes in attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD), using a multivariate analysis of associations (MAA) technique. We have now brought the total number of genes examined to 42 by adding an additional 22 candidate genes. These results indicate that even with the inclusion of these additional genes the noradrenergic genes still played a greater role in ADHD than any other group. Six other neurotransmitter genes were included in the regression equation - cholinergic, nicotinic, alpha 4 receptor (CHNRA4), adenosine A2A receptor (ADOA2A), nitric oxide synthase (NOS3), NMDAR1, GRIN2B, and GABRB3. In contrast to ADHD and ODD, CD preferentially utilized hormone and neuropeptide genes These included CCK, CYP19 (aromatase cytochrome P-450), ESR1, and INS (p = 0.005). This is consistent with our prior studies indicating a role of the androgen receptor (AR) gene in a range of externalizing behavors. We propose that the MAA technique, by focusing on the additive effect of multiple genes and on the cummulative effect of functionally related groups of genes, provides a powerful approach to the dissection of the genetic basis of polygenic disorders.

Adolescent↗

Effectiveness of screening and monitoring tests for diabetic retinopathy--a systematic review.

AIMS: To determine which screening and monitoring tests for diabetic retinopathy are most effective and under what circumstances. METHODS: A systematic review of the English language literature, published from 1983 to April 1999. RESULTS: Available studies are generally limited in their ability to answer the important questions on the effectiveness of tests for early detection of diabetic retinopathy. No randomized controlled trials were identified although primary studies exist for two screening tests: ophthalmoscopy, either direct or indirect, and retinal photography, using either mydriasis or non-mydriasis. Retinal photography under mydriasis appears to be the most effective test, with the majority reporting levels of sensitivity in excess of 80%. However effectiveness is compromised when photographs are ungradable. Ophthalmoscopy can also reach acceptable standards of sensitivity and specificity. CONCLUSION: Based on an assessment of available cohort studies, the most effective strategy for testing is the use of mydriatic retinal photography with the additional use of ophthalmoscopy for cases where photographs are ungradable. This does not exclude the use of ophthalmoscopy alone for opportunistic case finding but there is evidence of considerable variation in effectiveness of this test.

Diabetic Retinopathy↗

Movement loci of selected points on the femoral head for individual total hip arthroplasty patients using three-dimensional computer simulation.

Wear of ultra-high-molecular-weight polyethylene (UHMWPE) and the subsequent adverse tissue reaction to the wear particles has been cited as the predominant problem affecting total joint arthroplasties. Wear of the UHMWPE acetabular cup in total hip arthroplasties (THAs) is influenced by the sliding distance and direction of individual points on the femoral head, which has as yet been ascertained only for normal subjects. This study seeks to determine the trajectory of specified points on the femoral head for individual THA patients and the distances traversed by these points. A computer program was designed to use gait data from THA patients to simulate the motion of these points. Gait analysis was performed on 19 THA patients at a period of 5 years after operation. The orientation of the acetabular cup was ascertained from radiographs to determine the position of the points on the head most involved in the wear process. The loci of the points differed widely in size, shape, and direction between subjects. The largest average distance traversed was 140% greater than the smallest average distance traversed. Shorter longitudinal paths would tend to cause less wear than larger, wider paths, which cross a greater number of adjacent paths.

Aged↗

Risk factors for acquisition of vancomycin-resistant enterococci among patients on a renal ward during a community hospital outbreak.

BACKGROUND: During an outbreak of vancomycin-resistant enterococcal (VRE) infection and colonization at a community hospital in Indianapolis, Indiana, we performed a case-control study of patients on the hospital's renal unit to determine risk factors for acquisition of VRE among this potentially high-risk patient population. METHODS: Twenty-four renal patients with VRE colonization/infection (ie, case-patients) were compared by univariate and multivariate analyses with 29 renal patients with nosocomially acquired vancomycin-susceptible enterococcal infection and colonization (ie, controls). RESULTS: Age and length of hospitalization were similar between the VRE case-patients and the vancomycin-susceptible enterococcal control-patients, but case-patients had higher Acute Physiology and Chronic Health Evaluation II scores and received significantly greater numbers of antimicrobials and significantly more days of antimicrobials during the 60 days preceding the first positive enterococcal culture. In an assessment of the appropriateness of vancomycin use, one third of vancomycin orders were found to be inappropriate in both patient groups. CONCLUSIONS: Our data show that among renal patients, those who are severely ill and receive multiple and prolonged courses of antimicrobials are at greatest risk for acquiring VRE infection or colonization. The Centers for Disease Control and Prevention recommends that hospitals develop a comprehensive plan to prevent and control infection and colonization of patients with VRE. This plan should include prompt identification of affected patients, initiation of isolation precautions to prevent patient-to-patient transmission of VRE, and prudent use of antimicrobials, including vancomycin.

APACHE↗

Detection of protein S deficiency: a new functional assay compared to an antigenic technique.

Congenital protein S (PS) deficiency is associated with increased risk of venous thrombosis. To investigate the possibility of automating PS testing with decreased turnaround time, a clotting-based functional protein S assay was evaluated and compared to an antigenic method. Samples were collected from 126 patients within 5 days of their first acute cerebral infarction, from 62 controls and from 47 consecutive samples for thrombophilia investigation. The normal range for the clotting-based kit, calculated from the results of 20 healthy controls, was 62-136% (mean +/- 2 SD). Intra- and inter-assay co-efficients of variation were < 3.0 and 10.0% respectively. There was no significant correlation between the two methods (r = 0.30, P > 0.05). Two patients had low PS antigen results with normal functional levels. Both techniques were used to compare a further group of 53 patients with defined abnormalities which included nine antigenic protein S deficiencies, five protein C deficient patients, 10 patients with a lupus anticoagulant (LA), 17 Factor V Leiden (FVL) heterozygotes, two FVL homozygotes and 10 patients on therapeutic levels of heparin. In this group we found that four of nine antigenic PS deficient patients had normal functional PS levels. The test was susceptible to the FVL mutation with four of 17 FVL heterozygotes and both of two FVL homozygotes giving low levels. One of five protein C-deficient patients also had a low functional PS result with a normal antigenic level. Normal results were obtained by both methods for all of the LA and patients on therapeutic heparin. We concluded that the automated protein S clotting assay was rapid and simple to perform but appeared to be influenced by factors other than PS deficiency. Results need to be interpreted with caution but may be useful as part of a full thrombophilia investigation.

Cerebral Infarction↗

Reforming primary care in England--again. Plans for improving the quality of care.

An extensive programme of health service reform has begun in England. Improvement in the quality of care is a key objective of the reforms, and several initiatives are being introduced in response. These include systems to provide national guidance about appropriate treatment and services, a local system to support quality improvement and arrangements to monitor performance, including a new performance framework, an inspection agency and an annual survey of patients. The local quality improvement system has features of particular interest. These include arrangements for setting objectives for quality improvement, the use of various quality improvement methods tailored to local needs and a new system to provide accountability to both the health service and the public. The introduction of clinical governance and all the other reforms presents primary care practitioners with a major challenge. However, if sufficient time is allowed and adequate resources are made available, the reforms do have the potential to improve health care in England.

Decision Making, Organizational↗

Assessment of current diagnostic practice and efficacy in testing for von Willebrand's disorder: results from the second Australasian multi-laboratory survey.

This study reports an evaluation of current laboratory practice for the diagnosis of von Willebrand's disorder (VWD) by means of a multi-laboratory (n = 19) survey (the 'Second Australasian VWD Survey'). Results are compared with a previously conducted but similarly comprehensive survey ('Survey-1'). Samples comprised a new set of seven plasmas: (i) Type 3 VWD; (ii) Type 2B VWD; (iii) Moderate Type 1 VWD/Haemophilia A combined defect; (iv) Normal individual; (v) Mild Type 1 VWD; (vi) Type 2M/2A VWD; (vii) Type 2N VWD. Overall, many current findings confirmed those reported in Survey-1 [including between-method analysis, within-method analysis, inter-laboratory assay variation, sensitivity to low levels of von Willebrand Factor (vWF), detection of functional vWF 'discordance', and appropriateness of diagnostic predictions]. Novel findings include: (i) although vWF:collagen binding activity (vWF:CBA) performed better than vWF:ristocetin cofactor (vWF:RCof) assay in identification of functional discordance in Type 2B VWD, both assays performed equally in identification of discordance in the Type 2M/2A VWD; (ii) most laboratories failed to identify the Type 2N VWD as a potential 2N utilizing vWF antigen (vWF:Ag) and factor VIII coagulant (FVIII:C) testing as a screening process; (iii) this particular survey was followed up by a dry workshop attended by over 45 scientists from Australia and New Zealand, and comprising representatives from most survey participants. Discussion covered many topics including the effect of blood group, the role (if any) of the bleeding time, the role of the PFA-100, confirmatory and additional tests, and the possibility of restricting testing to specialized centres. Consensus was reached on the following points: (i) diagnosis of VWD requires both clinical and laboratory assessment; (ii) testing should comprise FVIII:C, vWF:Ag and either/or both vWF:RCof and vWF:CBA; (iii) laboratory results should be reviewed in the light of clinical findings; and (iv) confirmatory repeat testing should be performed on a sample taken 6 weeks later.

Australia↗

Family satisfaction with end-of-life care in seriously ill hospitalized adults.

OBJECTIVE: To examine factors associated with family satisfaction with end-of-life care in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). DESIGN: A prospective cohort study with patients randomized to either usual care or an intervention that included clinical nurse specialists to assist in symptom control and facilitation of communication and decision-making. SETTING: Five teaching hospitals in the United States. PARTICIPANTS: Family members and other surrogate respondents for 767 seriously ill hospitalized adults who died. MEASUREMENTS: Eight questionnaire items regarding satisfaction with the patient's medical care expressed as two scores, one measuring satisfaction with patient comfort and the other measuring satisfaction with communication and decision-making. RESULTS: Sixteen percent of respondents reported dissatisfaction with patient comfort and 30% reported dissatisfaction with communication and decision-making. Factors found to be significantly associated with satisfaction with communication and decision-making were hospital site, whether death occurred during the index hospitalization (adjusted odds ratio (AOR) 2.2, 95% CI, 1.3-3.9), and for patients who died following discharge, whether the patient received the SUPPORT intervention (AOR 2.0, 1.2-3.2). For satisfaction with comfort, male surrogates reported less satisfaction (0.6, 0.4-1.0), surrogates who reported patients' preferences were followed moderately to not at all had less satisfaction (0.2, 0.1-0.4), and surrogates who reported the patient's illness had greater effect on family finances had less satisfaction (0.4, 0.2-0.8). CONCLUSIONS: Satisfaction scores suggest the need for improvement in end-of-life care, especially in communication and decision making. Further research is needed to understand how factors affect satisfaction with end-of-life care. An intervention like that used in SUPPORT may help family members.

Aged↗

Local regulation of glucocorticoid activity in sites of inflammation. Insights from the study of tuberculosis.

In sites of inflammation there is a change in the equilibrium between the enzymes that inactivate cortisol by conversion to cortisone and those that reactivate cortisone by conversion to cortisol. Current evidence suggests that during an immune response with a Type 1 cytokine profile such as tuberculosis, there is locally enhanced reductase activity with locally increased cortisol concentrations due to recruitment of cortisone. This results in enhanced cortisol mediated feedback on the inflammatory process, and deviation of the response towards Type 2. Preliminary data suggest that eventually, in the presence of Type 2 cytokine polarization, the enzyme equilibrium may reverse again and cortisol is then locally inactivated to cortisone. Together with changes in glucocorticoid receptor expression and function this may result in local cortisol resistance and susceptibility to tissue damage mediated by proinflammatory cytokines. These observations help to explain the sequence of events in several infectious, inflammatory and autoimmune diseases.

Animals↗

Incorporation of zidovudine into cord blood DNA of infants and peripheral blood DNA of their HIV-1-positive mothers.

The nucleoside analogue 3'-azido-3'-deoxythymidine (AZT) is a weak carcinogen in adult female mice and a moderately strong carcinogen in the offspring of female mice given the drug during gestation. In addition, incorporation of AZT into DNA was observed in multiple organs of transplacentally exposed newborn mice. Here we investigate the incorporation of AZT into peripheral leukocyte DNA of HIV-1-positive adult pregnant women given AZT for variable times during gestation and cord blood of infants exposed to AZT in utero. The length of treatment varied between 10 days and 9 months. High molecular weight DNA was extracted from maternal peripheral blood mononuclear cells (PBMC) and infant cord blood. A specific AZT-DNA radioimmunoassay was used to determine the amount of AZT incorporated into leukocyte DNA. Incorporation of AZT into DNA ranged up to 183.3 and 344.5 molecules of AZT/10(6) nucleotides in the mothers and infants, respectively, and was detected in about 70% of samples. Therefore, AZT-induced mutagenic events are possible in the majority of adults and infants. No correlation was found between level of incorporation and length of AZT treatment, suggesting that the differences observed among the individuals arise from variability in AZT metabolism. These data support previous observations that a high degree of inter-individual variability in AZT phosphorylation occurs in primates.

Adult↗