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Biomedical subjects

E Tom

Publications and source records attributed to E Tom.

12 recordsLinked to original sources
PubMed2000

Analysis of p53-regulated gene expression patterns using oligonucleotide arrays.

Oligonucleotide microarrays were employed to quantitate mRNA levels from a large number of genes regulated by the p53 transcription factor. Responses to DNA damage and to zinc-inducible p53 were compared for their transcription patterns in cell culture. A cluster analysis of these data demonstrates that genes induced by gamma radiation, UV radiation, and the zinc-induced p53 form distinct sets and subsets with a few genes in common to all these treatments. Cell type- or cell line-specific p53 responses were detected. When p53 proteins were induced with zinc, the kinetics of induction or repression of mRNAs from p53-responsive genes fell into eight distinct classes, five different kinetics of induction, and three different kinetics of repression. In addition, low levels of p53 in a cell induced or repressed only a subset of genes observed at higher p53 levels. The results of this study demonstrate that the nature of the p53 response in diverse mRNA species depends on the levels of p53 protein in a cell, the type of inducing agent or event, and the cell type employed. Of 6000 genes examined for p53 regulatory responses, 107 induced and 54 repressed genes fell into categories of apoptosis and growth arrest, cytoskeletal functions, growth factors and their inhibitors, extracellular matrix, and adhesion genes.

Chlorides↗
PubMed1999

Increased apoptosis induction by 121F mutant p53.

p53 mutants in tumours have a reduced affinity for DNA and a reduced ability to induce apoptosis. We describe a mutant with the opposite phenotype, an increased affinity for some p53-binding sites and an increased ability to induce apoptosis. The apoptotic function requires transcription activation by p53. The mutant has an altered sequence specificity and selectively fails to activate MDM2 transcription. Loss of MDM2 feedback results in overexpression of the mutant, but the mutant kills better than wild-type p53 even in MDM2-null cells. Thus the apoptotic phenotype is due to a combination of decreased MDM2 feedback control and increased or unbalanced expression of other apoptosis-inducing p53 target genes. To identify these genes, DNA chips were screened using RNA from cells expressing the apoptosis-inducing mutant, 121F, and a sequence-specificity mutant with the reciprocal phenotype, 277R. Two potential new mediators of p53-dependent apoptosis were identified, Rad and PIR121, which are induced better by 121F than wild-type p53 and not induced by 277R. The 121F mutant kills untransformed MDM2-null but not wild-type mouse embryo fibroblasts and kills tumour cells irrespective of p53 status. It may thus expand the range of tumours which can be treated by p53 gene therapy.

Animals↗
PubMed1999

Using a quality scorecard to measure and improve medical groups' performance.

BACKGROUND: Blue Cross of California (BCC) uses an annual Quality Scorecard to measure performance of participating medical groups (PMGs) and independent practice associations (IPAs). The scorecard provides information to the PMGs/IPAs on their performance in several domains relative to the average network score. BCC pays annual bonuses to PMGs/IPAs with superior quality performance. A structured intervention was designed to improve the performance of PMGs/IPAs that performed poorly on the scorecard. METHODS: A cohort study was conducted in a large health maintenance organization in California in 1997. All PMGs/IPAs received a detailed summary of the components of the annual quality scorecard. Scorecard components include an annual audit of quality, utilization management, credentialing, and members' rights and responsibilities, grievance rates, member transfer for quality reasons, a satisfaction survey, and a preventive health review. Twenty-two of 124 PMGs/IPAs with more than 1,000 BCC members during 1996 that had scored lower than 1 standard deviation below the mean were targeted. These 22 outlier PMGs/IPAs received additional information indicating that their performance was below average. A BCC quality team subsequently visited the outlier PMGs/IPAs to provide supplementary information on the deficient areas and provide assistance in making improvements. RESULTS: The outlier groups showed significant improvements in the annual audit of quality score, member satisfaction with access, member satisfaction with last visit, overall member satisfaction with PMGs/IPAs, mammography screening, and the total score. CONCLUSIONS: A structured quality improvement intervention in poorly performing PMGs/IPAs was followed by improvements in specific performance measures.

Benchmarking↗
PubMed1999

Risk and protective factors associated with screening for complications of diabetes in a health maintenance organization setting.

OBJECTIVE: To identify risk and protective factors associated with screening for complications of diabetes, we performed a cross-sectional study of 3,612 diabetic members enrolled in CaliforniaCare, a large network-model health maintenance organization (HMO). RESEARCH DESIGN AND METHODS: We used the Health Plan and Employer Data Information Set (HEDIS) 3.0 technical definition to identify all members (aged > or = 31 years) receiving any diabetes medication(s) during a 12-month period. Using a telephone survey instrument, identified members were interviewed about their diabetes care and screening, patient, and provider history. Survey data were supplemented with HMO claims and demographic information. Multivariate analysis was performed to identify demographic, clinical, and utilization characteristics that affect the odds of diabetic members receiving annual retinal examination, foot examination, and HbA1c testing. RESULTS: While results varied by screening category, the odds of obtaining screening were higher for diabetic members who were older, spoke English, received diabetes nutrition counseling, visited a diabetes specialist physician, belonged to a diabetes association or support group, used insulin, performed glycemic level self-examination at least once a day, and had higher overall prescription drug use (suggesting higher comorbidity). Since this study is a cross-sectional review, these results do not imply a cause-and-effect relationship between dependent and independent variables. CONCLUSIONS: Results of this study suggest barriers, risks, and protective factors associated with screening for complications of diabetes. Diabetic members who do not possess these characteristics may be at increased risk.

Adult↗
PubMed1998

Resource costing for multinational neurologic clinical trials: methods and results.

We present the results of a multinational resource costing study for a prospective economic evaluation of a new medical technology for treatment of subarachnoid hemorrhage within a clinical trial. The study describes a framework for the collection and analysis of international resource cost data that can contribute to a consistent and accurate intercountry estimation of cost. Of the 15 countries that participated in the clinical trial, we collected cost information in the following seven: Australia, France, Germany, the UK, Italy, Spain, and Sweden. The collection of cost data in these countries was structured through the use of worksheets to provide accurate and efficient cost reporting. We converted total average costs to average variable costs and then aggregated the data to develop study unit costs. When unit costs were unavailable, we developed an index table, based on a market-basket approach, to estimate unit costs. To estimate the cost of a given procedure, the market-basket estimation process required that cost information be available for at least one country. When cost information was unavailable in all countries for a given procedure, we estimated costs using a method based on physician-work and practice-expense resource-based relative value units. Finally, we converted study unit costs to a common currency using purchasing power parity measures. Through this costing exercise we developed a set of unit costs for patient services and per diem hospital services. We conclude by discussing the implications of our costing exercise and suggest guidelines to facilitate more effective multinational costing exercises.

Australia↗
PubMed1997

Mathematical models in decision analysis.

Decision analysis offers powerful techniques to understand and evaluate uncertain clinical situations better. Decision analytic models are appearing with increasing frequency in health policy planning, clinical information and decision-support computer systems, evaluations of clinical pathways, development of clinical practice or utilization review guidelines, and epidemiologic research. This article describes the structure, application, and limitations of the more popular decision analytic methods, including decision trees, Markov models, Monte Carlo simulation, survival and hazard functions, fuzzy logic, and sensitivity analysis. Understanding the nature of these methods will help readers to assess better the appropriateness of their use in published reports.

Decision Support Techniques↗
PubMed1996

Human cytomegalovirus clinical isolates carry at least 19 genes not found in laboratory strains.

Nucleotide sequence comparisons were performed on a highly heterogeneous region of three human cytomegalovirus strains, Toledo, Towne, and AD169. The low-passage, virulent Toledo genome contained a DNA segment of approximately 13 kbp that was not found in the Towne genome and a segment of approximately 15 kbp that was not found in the AD169 genome. The Towne strain contained approximately 4.7 kbp of DNA that was absent from the AD169 genome, and only about half of this segment was present, arranged in an inverted orientation, in the Toledo genome. These additional sequences were located at the unique long (UL)/b' (IRL) boundary within the L component of the viral genome. A region representing nucleotides 175082 to 178221 of the AD169 genome was conserved in all three strains; however, substantial reduction in the size of the adjacent b' sequence was found. The additional DNA segment within the Toledo genome contained 19 open reading frames not present in the AD169 genome. The additional DNA segment within the Towne genome contained four new open reading frames, only one of which shared homology with the Toledo genome. This comparison was extended to five additional clinical isolates, and the additional Toledo sequence was conserved in all. These findings reveal a dramatic level of genome sequence complexity that may explain the differences that these strains exhibit in virulence and tissue tropism. Although the additional sequences have not altered the predicted size of the viral genome (230 to 235 kbp), a total of 22 new open reading frames (denoted UL133 to UL154), many of which have sequence characteristics of glycoproteins, are now defined as cytomegalovirus specific. Our work suggests that wild-type virus carries more than 220 genes, some of which are lost by large-scale deletion and rearrangement of the UL/b' region during laboratory passage.

Base Sequence↗
PubMed1980

A study of hospitalized surgical patients on methadone maintenance.

It is possible that admission to hospital of methadone maintenance clients requiring treatment for pain with narcotics may result in an increase in methadone maintenance dose and affect subsequent rehabilitation of the client. The hospital admission itself may modify the subsequent outcome of the client. Fifty clients of a Methadone Maintenance Therapy Program were retrospectively evaluated. Twenty-five had been admitted to the Surgical Service of Bellevue Hospital, New York City, for a variety of conditions and for periods ranging from 2 to 43 days; twenty-five were not admitted to the Hospital. Irrespective of whether or not large amounts of narcotic analgesics had been added to the maintenance methadone, patients were discharged on the same amounts of maintenance methadone as on admission and had eventual courses and outcomes similar to the control group when followed for a mean period of 20 months.

Adult↗
PubMedDate not supplied

Provider group characteristics & quality report card performance: a cross-sectional study in a managed care setting.

We describe 1 health plan's annual, incentive-based, provider group quality report card (Scorecard) and identify trends in Scorecard performance among 142 California provider groups. We explore variation in Scorecard performance by provider group characteristics. Scorecard evaluates provider groups on standardized measures of performance including preventive screening, patient satisfaction, and quality management operations and infrastructure. In a cross-sectional study, we use linear regression to measure associations between provider group characteristics and performance on the 1997 Scorecard. Provider group performance trends (1996-1997) revealed improvement on 6 Scorecard indicators. Regional differences in performance were also shown. Multivariate results indicate that group location in northern California (P = .01), IPA (independent practice association) status (P = .02), older group age (P = .02), and higher mean patient age (P < .01) were independently associated with higher 1997 Scorecard total scores. Member education was marginally associated with performance. Group size, member income, and gender distributions were not independently associated with Scorecard performance. Results of this study suggest that (among Blue Cross of California's contracted provider groups) older, more established groups; groups located in northern California; IPAs; and groups with a patient demographic mix characterized by higher than network average mean age and a lower than network average proportion of members with a college education or greater were more likely to perform well on Scorecard.

Adult↗