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Biomedical subjects

P Warmerdam

Publications and source records attributed to P Warmerdam.

6 recordsLinked to original sources
PubMed1999

Stage distribution at first and repeat examinations in breast cancer screening.

OBJECTIVES: To investigate observed stage distributions at first and repeat screenings. To compare the observed outcomes with expected values based on simulation modelling, varying the assumptions about the natural history of the disease. METHODS: An overview is made of observed data on stage distribution at first and repeat screenings and the difference between those distributions is summarised in a Gini coefficient. Four possible explanations for the observations are considered, two of these are worked out as Miscan simulation models, and the outcomes are compared with observations. RESULTS: Often the reported stage distributions at repeat screenings are not or only slightly more favourable than at first screenings and, in the ones that are more favourable, the difference is relatively small. If, in the Miscan model, it is assumed that there is no correlation between the duration of preclinical breast cancer in consecutive tumour size categories and that there is a strong influence of latent cancers, it is not possible to reproduce the observed outcomes. CONCLUSIONS: The two modelled explanations are not sufficient. Decreasing sensitivity seems an unlikely explanation for the discrepancy in many screening programmes. The possibility that the observations may be explained because false reassurance has been given should be seriously considered and investigated.

Adult↗
PubMed1998

Cost effectiveness of shortening screening interval or extending age range of NHS breast screening programme: computer simulation study.

OBJECTIVE: To compare the cost effectiveness of two possible modifications to the current UK screening programme: shortening the screening interval from three to two years and extending the age of invitation to a final screen from 64 to 69. DESIGN: Computer simulation model which first simulates life histories for women in the absence of a screening programme for breast cancer and then assesses how these life histories would be changed by introducing different screening policies. The model was informed by screening and cost data from the NHS breast screening programme. SETTING: North West region of England. MAIN OUTCOME MEASURES: Numbers of deaths prevented, life years gained, and costs. RESULTS: Compared with the current breast screening programme both modifications would increase the number of deaths prevented and the number of life years saved. The current screening policy costs 2522 pounds per life year gained; extending the age range of the programme would cost 2612 pounds and shortening the interval 2709 pounds per life year gained. The marginal cost per life year gained of extending the age range of the screening programme is 2990 pounds and of shortening the screening interval is 3545 pounds. CONCLUSIONS: If the budget for the NHS breast screening programme were to allow for two more invitations per woman, substantial mortality reductions would follow from extending the age range screened or reducing the screening interval. The difference between the two policies is so small that either could be chosen.

Age Factors↗
PubMed1997

Recombinant staphylokinase variants with altered immunoreactivity. III: Species variability of antibody binding patterns.

BACKGROUND: The "charged cluster-to-alanine" substitution variants SakSTAR(K35A,E38A,K74A,E75A,R77A) and SakSTAR(K74A,E75A,R77A,E80A,D82A), previously identified as SakSTAR.M38 and SakSTAR.M89, respectively, induce less antibody formation in patients than wild-type recombinant staphylokinase (SakSTAR), but their specific activities are reduced by 50%. Therefore, the effect of the reversal of one or more of these substituted amino acids on the ratio of activity to antigenicity was studied. METHODS AND RESULTS: Fourteen mutants with one to four "alanine-to-wild-type" reversals were expressed in Escherichia coli and highly purified (> 95%). In rabbits immunized with wild-type SakSTAR, the combined K35,E38,K74,E75,R77 or K74,E75,R77,E80,E82 epitope accounted for only 30% of antibody absorption from plasma, and no clear immunodominant residue could be identified. In baboons immunized with SakSTAR, the K35,E38 and K74,E75,R77 epitopes or the K74,E75,R77 and E80,D82 epitopes contributed equally to account for 50% of total antibody binding, but no immunodominant residues were apparent. In pooled plasma from patients with peripheral arterial occlusion treated with wild-type SakSTAR, about 40% of the antibodies depended on K74 of epitope K74,E75,R77 for binding, whereas epitopes K35,E38 and E80,D82 had a negligible contribution toward antibody recognition. CONCLUSIONS: The recognition pattern by SakSTAR variants of antibodies induced with wild-type SakSTAR differs markedly among species. This implies that a systematic evaluation of reduced antigen recognition and antibody induction in humans will require the development of human or humanized systems. Surprisingly, SakSTAR(K74), with a single substitution of Lys74 with Ala, had an intact specific activity but did not absorb 40% of the antibodies induced in patients by treatment with wild-type SakSTAR.

Animals↗
PubMed1994

Gastric outlet obstruction as a presenting manifestation of systemic lupus erythematosus.

A patient with nausea and vomiting who subsequently proved to have systemic lupus erythematosus is described. Although gastrointestinal involvement is common in systemic lupus erythematosus it is rare as an initial manifestation. Gastric outlet obstruction was shown on the air contrast examination while the mucosa at endoscopy was normal. The gastric symptoms regressed after treatment with high dose corticosteroids and a repeat air contrast examination of the stomach was normal. This stricturing process may have been caused by a local peritonitis.

Adult↗
PubMed1988

Evolution and mutagenesis of the mammalian excision repair gene ERCC-1.

The human DNA excision repair protein ERCC-1 exhibits homology to the yeast RAD10 repair protein and its longer C-terminus displays similarity to parts of the E. coli repair proteins uvrA and uvrC. To study the evolution of this 'mosaic' ERCC-1 gene we have isolated the mouse homologue. Mouse ERCC-1 harbors the same pattern of homology with RAD10 and has a comparable C-terminal extension as its human equivalent. Mutation studies show that the strongly conserved C-terminus is essential in contrast to the less conserved N-terminus which is even dispensible. The mouse ERCC-1 amino acid sequence is compatible with a previously postulated nuclear location signal and DNA-binding domain. The ERCC-1 promoter harbors a region which is highly conserved in mouse and man. Since the ERCC-1 promoter is devoid of all classical promoter elements this region may be responsible for the low constitutive level of expression in all mouse tissues and stages of embryogenesis examined.

Amino Acid Sequence↗