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H de Koning

Publications and source records attributed to H de Koning.

15 recordsLinked to original sources
PubMed1999

Reduction in breast cancer mortality due to the introduction of mass screening in The Netherlands: comparison with the United Kingdom.

OBJECTIVE: To assess the impact of the national breast cancer screening programme on breast cancer mortality in the first years after its introduction. SETTING: The Netherlands and United Kingdom. METHODS: MISCAN models, incorporating demographic, epidemiological, and screening characteristics of the region under study, were used to assess the mortality in the presence and absence of screening. RESULTS: Breast cancer mortality decreased in women aged 55-74 as the Dutch nationwide screening programme built up, and was 5% lower in 1996 than before the start of the programme. The mortality reduction due to screening in the age group 55-74 is expected to increase gradually to 18% in 1999, 10 years after the introduction of screening, and to 29% in the long term. In the United Kingdom screening was expected to achieve a mortality reduction of 5% and 18% in the age group 55-69 five and 10 years respectively after screening was started. A maximum mortality reduction of 24% in this age group is predicted. CONCLUSIONS: The effects of screening will be small in the first years after the start of the programme. Accordingly, it was expected that the reduction in breast cancer mortality due to the Dutch nationwide breast screening programme, which started around 1989, would be statistically significant from 1997 onwards, the point at which the target population of women was completely covered; 70% of the reported 12% mortality reduction in England and Wales in 1994 is expected to be attributed to screening.

Age Factors↗
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↗
PubMed1998

Breast cancer screening programmes in 22 countries: current policies, administration and guidelines. International Breast Cancer Screening Network (IBSN) and the European Network of Pilot Projects for Breast Cancer Screening.

BACKGROUND: Currently there are at least 22 countries worldwide where national, regional or pilot population-based breast cancer screening programmes have been established. A collaborative effort has been undertaken by the International Breast Cancer Screening Network (IBSN), an international voluntary collaborative effort administered from the National Cancer Institute in the US for the purposes of producing international data on the policies, funding and administration, and results of population-based breast cancer screening. METHODS: Two surveys conducted by the IBSN in 1990 and 1995 describe the status of population-based breast cancer screening in countries which had or planned to establish breast cancer screening programmes in their countries. The 1990 survey was sent to ten countries in the IBSN and was completed by nine countries. The 1995 survey was sent to and completed by the 13 countries in the organization at that time and an additional nine countries in the European Network. RESULTS: The programmes vary in how they have been organized and have changed from 1990 to 1995. The most notable change is the increase in the number of countries that have established or plan to establish organized breast cancer screening programmes. A second major change is in guidelines for the lower age limit for mammography screening and the use of the clinical breast examination and breast self-examination as additional detection methods. CONCLUSION: As high quality population-based breast cancer screening programmes are implemented in more countries, they will offer an unprecedented opportunity to assess the level of coverage of the population for initial and repeat screening, evaluation of performance, and, in the longer term, outcome of screening in terms of reduction in the incidence of late-stage disease and in mortality.

Adult↗
PubMed1993

Cost-effectiveness of mammographic screening in Australia.

The purpose of this research was to estimate the cost-effectiveness of mammographic screening to supplement the results of the National Evaluation of Breast Cancer Screening which identified the mortality benefit as the most sensitive parameter. This appraisal used a different computer model, MISCAN, which models the effects of introducing a national screening program into a previously unscreened population, rather than basing estimates on the assumption of a fully established program. For the 40 to 49 age group a mortality reduction of 8 per cent was assumed, rather than the 30 per cent estimate utilised in the National Evaluation. The revised estimate is based on the two Swedish trials (Malmo and WE). New estimates for treatment costs were also incorporated into the MISCAN model. The cost-effectiveness of the policy recommended in the National Evaluation Report, $11,000 per life year saved with two-yearly screening of women over 40, is estimated by the MISCAN model to be $20,300. These differences arise partly from the difference in mortality effects for the 40 to 49 age group, but also from differences inherent in the steady-state and dynamic population approaches to modelling premature deaths averted. The MISCAN results confirm that screening for women over 50 is more cost-effective than screening women under 50. Screening all women aged 50 to 69 every two to three years is reasonable value for money. For women aged 40 to 49 the mortality benefit and cost-effectiveness is less clear, and it would be prudent to allow screening in this group until further evidence is available.

Adult↗
PubMed1987

Cytogenetic toxicity of paraquat and streptonigrin in Fanconi's anemia.

We reported earlier that the frequency of chromosomal aberrations observed in Fanconi's anemia lymphocyte cultures depends on the oxygen tension during growth of the cultures, suggesting that "activated oxygen species" (superoxide, O2-; hydrogen peroxide, H2O2; hydoxyl radical, OH; and singlet oxygen, 1O2) or other reactive products generated during oxygen metabolism may be involved in the production of chromosomal damage in this syndrome. Paraquat and streptonigrin, agents that have been proposed as model compounds exerting cellular toxicity through overproduction of superoxide, were tested for their clastogenic potency in lymphocyte cultures from healthy controls and patients with Fanconi's anemia. Paraquat, at concentrations that severely affected mitotic activity (100-200 micrograms/ml), appeared to be a weak clastogen in human lymphocytes, whereas a clastogenic effect of streptonigrin was demonstrable already at a concentration as low as 0.005 microgram/ml. The results indicate that Fanconi's anemia lymphocytes fail to exhibit an increased sensitivity to the antimitotic and clastogenic effects of paraquat and streptonigrin. This suggests that intracellular superoxide is not critically involved in the generation of spontaneous chromosomal aberrations in Fanconi's anemia. We infer from these and previous data that singlet oxygen (1O2) may be a critical contributor to the chromosomal breakage in this disorder.

Adolescent↗
PubMed1983

Unusual response to bifunctional alkylating agents in a case of Fanconi anaemia.

Chromosomal breakage frequencies were determined in Fanconi anaemia (FA) blood cultures treated with various concentrations of the polyfunctional alkylating agents mitomycin C, diepoxybutane, and cis-platinum(II)-diammine-dichloride, for which FA cells have a characteristic hypersensitivity. At concentrations that hardly affected control cultures, three out of four patients tested exhibited a concentration-dependent increase of cells with aberrant chromosomes, with a concomitant increase in the number of chromosomal aberrations per aberrant cell. The fourth patient, a 22-year-old male, was exceptional because with all three clastogens only 40% of his cultured cells exhibited a typical concentration-dependent response, while 60% of his cells responded like those from normal healthy controls. The possible nature and significance of this unusual response is discussed.

Adolescent↗
PubMed1983

DNA ploidy analysis and cytologic examination of sorted cell populations from human breast tumors.

Two different flow cytometric procedures were applied on cell samples from human breast tumors. One procedure involved DNA ploidy analysis on suspensions of isolated nuclei. The mean ploidy ratios of 27 benign breast lesions to chicken erythrocytes and rainbow trout erythrocytes were found to be 2.66 +/- 0.03 and 1.25 +/- 0.02, respectively. From the 45 stemlines found in a series of 43 carcinomas, 12 were diploid, 13 hyperdiploid and 20 near-tetraploid. No association was found between the lymph node status and the DNA ploidy level. The second procedure involved sorting fixed cells from DNA "windows" for the preparation of permanent cytologic specimens. The sorted cells appeared to be shrunken, but the morphologic quality was similar to that of imprint specimens from the same tumors, permitting discrimination between various types of normal cells and tumor cells. The combined use of both flow cytometric procedures may lead to greater insight into the relationship between the cytologic and cytogenetic heterogeneity of breast carcinomas.

Breast Neoplasms↗
PubMed1981

Oxygen-dependence of chromosomal aberrations in Fanconi's anaemia.

Fanconi's anaemia (FA) is an autosomal recessive disorder characterized by a high frequency of 'spontaneous' chromosomal aberrations and an increased risk of cancer. If, as seems plausible, the microscopically visible chromosomal aberrations in this disorder result from DNA or chromatin damage that would normally be repairable, the questions arise as to which step (or steps) in the repair process is deficient and whether the deficiency is intrinsic or the result of secondary factors. We report here that the frequency of chromosomal aberrations in FA lymphocyte cultures is positively related to oxygen tension and suggest that the site primarily affected by the FA mutation is in the complex system of defence (that is, protection and repair) against the genetic toxicity of oxygen.

Adult↗
PubMedDate not supplied

Nucleobase transporters (review).

Purines and pyrimidines play a key role in nucleic acid and nucleotide metabolism of all cells. In addition, they can be used as nitrogen sources in plants and many microorganisms. Transport of nucleobases across biological membranes is mediated by specific transmembrane transport proteins. Nucleobase transporters have been identified genetically and/or physiologically in bacteria, fungi, protozoa, algae, plants and mammals. A limited number of bacterial and fungal transporter genes have been cloned and analysed in great detail at the molecular level. Very recently, nucleobase transporters have been identified in plants. In other systems, with less accessible genetics, such as vertebrates and protozoa, no nucleobase transporter genes have been identified, and the transporters have been characterized and classified by physiological and biochemical approaches instead. In this review, it is shown that nucleobase transporters and similar sequences of unknown function present in databases constitute three basic families, which will be designated NAT, PRT and PUP. The first includes members from archea, eubacteria, fungi, plants and metazoa, the second is restricted to prokaryotes and fungi, and the last one is only found in plants. Interestingly, mammalian ascorbate transporters are homologous to NAT sequences. The function of different nucleobase transporters is also described, as is how their expression is regulated and what is currently known about their structure-function relationships. Common features emerging from these studies are expected to prove critical in understanding what governs nucleobase transporter specificity and in selecting proper model microbial systems for cloning and studying plant, protozoan and mammalian nucleobase transporters of agricultural, pharmacological and medical importance.

Animals↗