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Biomedical subjects

R Moore

Publications and source records attributed to R Moore.

At least 91 records · Page 5Linked to original sources

Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene.

The constitutively active receptor (CAR) transactivates a distal enhancer called the phenobarbital (PB)-responsive enhancer module (PBREM) found in PB-inducible CYP2B genes. CAR dramatically increases its binding to PBREM in livers of PB-treated mice. We have investigated the cellular mechanism of PB-induced increase of CAR binding. Western blot analyses of mouse livers revealed an extensive nuclear accumulation of CAR following PB treatment. Nuclear contents of CAR perfectly correlate with an increase of CAR binding to PBREM. PB-elicited nuclear accumulation of CAR appears to be a general step regulating the induction of CYP2B genes, since treatments with other PB-type inducers result in the same nuclear accumulation of CAR. Both immunoprecipitation and immunohistochemistry studies show cytoplasmic localization of CAR in the livers of nontreated mice, indicating that CAR translocates into nuclei following PB treatment. Nuclear translocation of CAR also occurs in mouse primary hepatocytes but not in hepatocytes treated with the protein phosphatase inhibitor okadaic acid. Thus, the CAR-mediated transactivation of PBREM in vivo becomes PB responsive through an okadaic acid-sensitive nuclear translocation process.

Animals↗

Cost and price in the NHS: the importance of monetary value in the decision-making framework--the case of purchasing renal replacement therapy.

This paper examines the role of cost, price and health economic evaluation in the National Health Service as demonstrated by reference to renal replacement therapy for patients with end-stage renal failure. In particular, it aims to highlight the problems with monetary value and to illustrate how it may be manipulated by legitimate techniques to produce varying outcome values which may be misleading and thereby distort the healthcare decision-making process. The paper argues for standardization of costing methods and health economic evaluation to enable meaningful intra- and inter-hospital comparisons to be made.

Contract Services↗

Clinical decision making using teleradiology in urology.

OBJECTIVE: Using a personal computer-based teleradiology system, we compared accuracy, confidence, and diagnostic ability in the interpretation of digitized radiographs to determine if teleradiology-imported studies convey sufficient information to make relevant clinical decisions involving urology. Variables of diagnostic accuracy, confidence, image quality, interpretation, and the impact of clinical decisions made after viewing digitized radiographs were compared with those of original radiographs. MATERIALS AND METHODS: We evaluated 956 radiographs that included 94 IV pyelograms, four voiding cystourethrograms, and two nephrostograms. The radiographs were digitized and transferred over an Ethernet network to a remote personal computer-based viewing station. The digitized images were viewed by urologists and graded according to confidence in making a diagnosis, image quality, diagnostic difficulty, clinical management based on the image itself, and brief patient history. The hard-copy radiographs were then interpreted immediately afterward, and diagnostic decisions were reassessed. All analog radiographs were reviewed by an attending radiologist. RESULTS: Ninety-seven percent of the decisions made from the digitized radiographs did not change after reviewing conventional radiographs of the same case. When comparing the variables of clinical confidence, quality of the film on the teleradiology system versus analog films, and diagnostic difficulty, we found no statistical difference (p > .05) between the two techniques. Overall accuracy in interpreting the digitized images on the teleradiology system was 88% by urologists compared with that of the attending radiologist's interpretation of the analog radiographs. However, urologists detected findings on five (5%) analog radiographs that had been previously unreported by the radiologist. CONCLUSION: Viewing radiographs transmitted to a personal computer-based viewing station is an appropriate means of reviewing films with sufficient quality on which to base clinical decisions. Our focus was whether decisions made after viewing the transmitted radiographs would change after viewing the hard-copy images of the same case. In 97% of the cases, the decision did not change. In those cases in which management was altered, recommendation of further imaging studies was the most common factor.

Decision Making↗

Strand displacement amplification and homogeneous real-time detection incorporated in a second-generation DNA probe system, BDProbeTecET.

BACKGROUND: Amplified DNA probes provide powerful tools for the detection of infectious diseases, cancer, and genetic diseases. Commercially available amplification systems suffer from low throughput and require decontamination schemes, significant hands-on time, and specially trained laboratory staff. Our objective was to develop a DNA probe system to overcome these limitations. METHODS: We developed a DNA probe system, the BDProbeTecTMET, based on simultaneous strand displacement amplification and real-time fluorescence detection. The system uses sealed microwells to minimize the release of amplicons to the environment. To avoid the need for specially trained labor, the system uses a simple workflow with predispensed reagent devices; a programmable, expandable-spacing pipettor; and the 96-microwell format. Amplification and detection time was 1 h, with potential throughput up to 564 patient results per shift. We tested 122 total patient specimens obtained from a family practice clinic with the BD ProbeTecET and the Abbott LCx(R) amplified system for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: Based on reportable results, the BDProbeTecET results for both organisms were 100% sensitive and 100% specific relative to the LCx. CONCLUSIONS: The BDProbeTecET is an easy-to-use, high-throughput, closed amplification system for the detection of nucleic acid from C. trachomatis and N. gonorrhoeae and other organisms.

Chlamydia trachomatis↗

The generation and in vivo differentiation of murine embryonal stem cells genetically null for either N-cadherin or N- and P-cadherin.

Many mutations of the murine genome are recessive embryonic lethals precluding phenotype analysis at subsequent stages of development. This is true for embryos genetically lacking either N-cadherin or N- and P-cadherin. To circumvent this, we have generated pluripotent embryonal stem (ES) cells of the same genotype in vitro and differentiated them in vivo in the form of teratomas. All of the ES cells isolated in this study had a normal ES cell morphology in vitro and were able to generate teratomas. Histological analysis revealed that some differentiation and histogenesis had occurred within the teratomas. Epithelial formation was, for example, unaffected in all cadherin null cells. Surprisingly, however, the differentiation of cells lacking both N- and P-cadherin was, in general, even more pronounced both quantitatively and qualitatively. Tumours lacking either N- cadherin or N- and P-cadherin contained more striated muscle (apparently cardiac muscle) than heterozygote controls, and this was most strikingly conspicuous in teratomas from N- and P-cadherin null cells. This more pronounced differentiation was not seen for all tissues, however, as structures with a simple neural tube-like morphology were never found in teratomas lacking both N- and P-cadherin and organoid-like structures were rare in Ncad-/-tissue.

Animals↗

Managing pressure ulcers: a multisite CQI challenge.

Think preventing and tracking pressure ulcers is expensive? Treatment may cost more. The Nurse Executive Council of VHA Alabama partnered with KCI USA, Inc., to implement a CQI project to manage pressure ulcer incidence.

Alabama↗

Measurement of risk for mental disorders and competence in a psychiatric epidemiologic community survey: the National Institute of Mental Health Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study.

This paper describes the implementation of the National Institute of Mental Health Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) study's goals of measuring risk factors and competence. The emphasis is on the development and testing of the measures. Relevant constructs for measurement of risk and competence in relation to psychopathology were selected and pilot tested prior to the field trials. A structured interview was developed and field tested using lay interviewers. Using the full sample from the field trials (n = 1285 caretaker-youth pairs), sample means, standard deviations, internal consistencies, parent-youth agreement, and associations with childhood disorder were computed. Descriptive statistics reveal a range of scores and means consistent with norming samples, when available, Internal consistencies were moderate to high. Parent-youth agreement on factual items was excellent and on scales was consistent with the literature. Several strong associations were found between risk factors and disorder, although most were related to disorder in general and not specific to a diagnostic category. This instrument provides a means of obtaining data that will be useful to researchers conducting epidemiologic and clinical studies designed to contribute to the understanding of mental disorders in children and adolescents, including nosology, risk factors, context, adaptive functioning, and treatment.

Adolescent↗

Conversion of renal transplant recipients from cyclosporin to low-dose tacrolimus for refractory rejection.

Twenty-five patients with refractory rejection following renal transplantation were converted from cyclosporin to tacrolimus in an attempt to salvage the allografts. All patients had received two or three pulses of methylprednisolone, 6 had OKT3, 14 had antithymocyte globulin (ATG) and 2 had both OKT3 and ATG prior to conversion. The median time from transplantation to conversion to tacrolimus was 32 days (range 12-322). Patients underwent a simple switch from cyclosporin- to tacrolimusbased therapy with tacrolimus administered at a median dose of 0.15 mg/kg per day. Doses were adjusted according to clinical response and trough blood levels. Twenty-one of the 25 patients (84%) with refractory rejection showed evidence of reversal of rejection as indicated by a significant reduction in serum creatinine (Student's paired t-test, P < 0.05) following conversion to tacrolimus. None of these patients had further episodes of rejection. Three patients had ongoing rejection and returned to dialysis, and 1 patient showed deteriorating renal function associated with a cytomegalovirus infection. Of 18 patients currently on tacrolimus, 15 have improved renal function and 3 have shown no further deterioration. We conclude that low-dose tacrolimus appears to be effective in salvaging renal allografts with resistant rejection.

Adult↗

Conversion of renal transplant recipients from cyclosporin (neoral) to tacrolimus (prograf) for haemolytic uraemic syndrome.

Five patients with cyclosporin-related haemolytic uraemic syndrome (HUS) following cadaveric renal transplantation were converted from cyclosporin- to tacrolimus-based immunosuppression. All patients had biochemical, haematological and biopsy evidence of HUS at the time of conversion. Four of the patients showed complete resolution of the syndrome within 1 week of conversion with normalisation of haemoglobin, platelets and lactate dehydrogenase levels. In the fifth patient renal function stabilised with slow resolution of the haematological and biochemical parameters. Four of the five patients are still taking tacrolimus, one having converted back to cyclosporin due to marked hair loss. We conclude that conversion to tacrolimus appears to be an effective treatment for cyclosporin-related HUS following renal transplantation.

Adult↗

Prospective randomised study comparing tacrolimus (Prograf) and cyclosporin (Neoral) as primary immunosuppression in cadaveric renal transplants at a single institution: interim report of the first 80 cases.

As part of an ongoing study, 80 patients undergoing cadaveric renal transplantation were randomised to receive either Prograf [PTT (patients receiving Prograf); n = 40]- or Neoral [NTT (patients receiving Neoral); n = 40]-based immunosuppression as part of a triple therapy regimen. Prograf was commenced at a dose of 0.2 mg/kg per day and Neoral at 8 mg/kg per day. Both groups received identical azathioprine and corticosteroid regimens. Trough levels for Prograf were maintained between 5 and 15 ng/ml and for Neoral between 100 and 200 ng/ml. During the 3-month follow up 40% of PTT and 33% of NTT experienced biopsy-proven acute rejection. In each group 81% of rejection episodes were classified as either borderline or grade 1. The median 3-month serum creatinine levels were 128 mumol/l and 135 mumol/l, respectively, for PTT and NTT. Six grafts were lost in the NTT group including three deaths with functioning grafts whilst none were lost in the PTT group (chi 2, P < 0.02). The prevalence of other complications was similar for the two groups. We conclude that Prograf represents an effective and safe therapy as a primary immunosuppressive agent following cadaveric renal transplantation and appears to have a similar side-effect profile to Neoral.

Adult↗

The investigation of placental relaxation and estimation of placental perfusion using echo-planar magnetic resonance imaging.

Echo-planar imaging (EPI) is a form of magnetic resonance imaging (MRI) which acquires images in milliseconds rather than minutes as with conventional MRI. The images produced using EPI are affected by the physiological environment in which the hydrogen atoms producing the signals are found, a process referred to as relaxation. Also by producing images a matter of milliseconds apart, quantification of perfusion within the tissue being imaged is feasible. The objective of this study was to investigate T1 and T2 relaxation times along with perfusion in placentae from normal pregnancies at different gestations and also to compare these to pregnancies complicated by abnormal placental function. A cross-sectional study of normal and compromised pregnancies from 20 weeks to term and a longitudinal study of normal pregnancy were performed. Placental T1, T2 relaxation times, and perfusion were measured using echo-planar magnetic resonance imaging. Placental T1 and T2 relaxation times decreased in normal pregnancy (P<0.001). Relaxation times in pregnancies associated with placental pathology appeared to be reduced for that gestation although the numbers were too small to allow any statistical validation. No differences in placental perfusion with gestation or between normal and compromised pregnancy were demonstrated using this technique. This is the first demonstration of placental magnetic resonance relaxation and perfusion measurements in normal pregnancy using echo-planar magnetic resonance imaging. In the future it may be possible to identify compromised pregnancies by differences in placental T1 and T2 relaxation times, using this novel non-invasive technique.

Adult↗

Limulus amebocyte lysate assay for detection of endotoxin in patients with sepsis syndrome. AMCC Sepsis Project Working Group.

Clinical predictions alone are insufficiently accurate to identify patients with specific types of bloodstream infection; laboratory assays might improve such predictions. Therefore, we performed a prospective cohort study of 356 episodes of sepsis syndrome and did Limulus amebocyte lysate (LAL) assays for endotoxin. The main outcome measures were bacteremia and infection due to gram-negative organisms; other types of infection were secondary outcomes. Assays were defined as positive if the result was > or = 0.4 enzyme-linked immunosorbent assay units per milliliter. There were positive assays in 119 (33%) of 356 episodes. Assay positivity correlated with the presence of fungal bloodstream infection (P < .003) but correlated negatively with the presence of gram-negative organisms in the bloodstream (P = .04). A trend toward higher rates of mortality in the LAL assay-positive episodes was no longer present after adjusting for severity. Thus, results of LAL assay did not correlate with the presence of bacteremia due to gram-negative organisms or with mortality after adjusting for severity but did correlate with the presence of fungal bloodstream infection.

Bacteremia↗