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M Seddon

Publications and source records attributed to M Seddon.

11 recordsLinked to original sources
PubMed2000

Explanation for the decline in coronary heart disease mortality rates in Auckland, New Zealand, between 1982 and 1993.

BACKGROUND: We sought to determine how much of the recent, substantial fall in coronary heart disease (CHD) mortality rates in New Zealand can be attributed to "evidence-based" medical and surgical treatments and how much can be attributed to cardiovascular risk factor reductions. METHODS AND RESULTS: A cell-based mortality model was developed and refined. This model combined (1) the published effectiveness of cardiological treatments and risk factor reductions with (2) data on all medical and surgical treatments administered to all CHD patients and (3) trends in population cardiovascular risk factors (principally smoking, cholesterol, and hypertension) from 1982 to 1993 in Auckland, New Zealand (population 996 000). Between 1982 and 1993, CHD mortality rates fell by 23.6%, with 671 fewer CHD deaths than expected from baseline mortality rates in 1982. Forty-six percent of this fall was attributed to treatments (acute myocardial infarction 12%, secondary prevention 12%, hypertension 7%, heart failure 6%, and angina 9%), and 54% was attributed to risk factor reductions (smoking 30%, cholesterol 12%, population blood pressure 8%, and other, unidentified factors 4%). These proportions remained relatively consistent after a robust sensitivity analysis. CONCLUSIONS: Approximately half the CHD mortality rate fall in Auckland, New Zealand, was attributed to medical therapies, and approximately half was attributed to reductions in major risk factors. These findings emphasize the importance of a comprehensive strategy that maximizes the population coverage of effective treatments and actively promotes a prevention program, particularly for smoking, diet, and blood pressure reduction.

Adult↗
PubMed1997

High frequency of K-ras codon 12 mutations in bronchoalveolar lavage fluid of patients at high risk for second primary lung cancer.

A high frequency of K-ras mutations may indicate preneoplastic changes in the bronchial epithelium as a result of genotoxic injury. With the use of sensitive detection techniques, we report a higher prevalence of K-ras mutations in bronchoalveolar lavage than has been reported previously for lung cancer. A PCR/ligase chain reaction technique was used to determine K-ras codon 12 mutations in a group of 52 bronchoalveolar lavage specimens from patients at risk of a second lung cancer. Of the specimens examined, 84% contained at least one mutation in K-ras codon 12, corroborated by an allele-specific hybridization method. These results suggest that point mutations in K-ras codon 12 are widespread in the bronchial epithelium. Based on these preliminary findings, further evaluation of this efficient sensitive assay to monitor K-ras status should be conducted in larger clinical cohorts where clinical outcomes will ultimately be available. Such a trial will define the utility of K-ras codon 12 mutation status as a marker of lung cancer.

Bronchoalveolar Lavage Fluid↗
PubMed1996

Detection of K-ras oncogene mutations by polymerase chain reaction-based ligase chain reaction.

To evaluate a rapid multiplexed assay to detect three common K-ras codon 12 mutations, primer pairs complementary to the wild-type and mutant loci were developed and tested with lung cancer cell lines with previously identified mutation status. The sensitivity of detection of mutations was determined to be at least 1% using spiked samples containing K-ras codon 12 mutations. This assay was then used to evaluate prospectively K-ras status in airways of individuals at high risk of lung cancer by analysis of bronchoalveolar lavage (BAL) specimens from patients who have been previously treated for lung cancer. DNA was extracted from BAL specimen cell pellets, and PCR-based ligase chain reaction was performed for mutations in the first position of codon 12 of K-ras, with positive and negative controls. Of 10 BAL samples, 4 contained 1 mutation (GGT --> TGT), 1 contained 2 mutations (GGT --> TGT and GGT --> AGT), and the rest were wild-type. The BAL mutations were validated by cloning and screening with mutant-specific probes followed by confirmation sequencing.

Bronchoalveolar Lavage↗
PubMed1990

TGF-beta 1 modulation of urokinase and PAI-1 expression in human bronchial epithelial cells.

Normal human bronchial epithelial (NHBE) cells respond to signals initiated by the binding of transforming growth factor-beta type 1 (TGF-beta 1) to its surface receptors by activating pathways that result in terminal squamous differentiation. By use of both normal and SV40 T-antigen-immortalized cells, it was found that treatment with TGF-beta 1 transiently increases mRNA levels for urokinase (uPA) and plasminogen activator inhibitor type 1 (PAI-1) approximately 5- and 50-fold, respectively, within 4 h. In NHBE cells, PAI-1 protein is increased by TGF-beta 1 in both extracellular matrix and medium. The net effect of TGF-beta 1 on plasminogen activator activity in the medium was a 50% reduction as measured by a caseinolytic assay. A T-antigen-immortalized bronchial epithelial cell line that does not undergo squamous differentiation in response to TGF-beta 1 but binds this growth factor did not respond to TGF-beta 1 by modulation of either uPA or PAI-1 expression. Comparison of human bronchial epithelial, pleural mesothelial, and lung fibroblastic cell strains indicated that the epithelial cells have a constitutively higher ratio of uPA to PAI-1 mRNA expression. These data suggest that modulation of pericellular proteolysis in bronchial epithelial cells in response to TGF-beta 1 represents a significant biological change in their pericellular environment. The induction of uPA and PAI-1 expression in human bronchial epithelial cells may be related to the ability of the cell to undergo squamous differentiation in response to TGF-beta 1. These observations identify specific changes in gene expression that may serve as markers for the differentiation process.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗
PubMed1980

Pharmacokinetics of Ro 13-9904, a broad-spectrum cephalosporin.

The pharmacokinetics of the new cephalosporin Ro-13-9904 were studied in six healthy male volunteers receiving a 500-mg dose as a bolus intravenously. Tissue penetration of the antibiotic was estimated by using a cantharides blister method. The data obtained fitted a two-compartment open model. The mean elimination half-life was about 8 h, which is considerably longer than that of other beta-lactam compounds. The distribution volume was 4.3 liters in the central compartment. Levels of Ro 13-9904 in blister fluid exceeded those in serum after 6.5 h. Approximately 60% of the antibiotic was excreted in the urine.

Adult↗