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The transplantable promyelocytic leukemia in BN rat (BNML) is a relatively slow-growing leukemia which has many characteristics in common with human acute myeloid leukemia (AML). As compared with normal myeloid cells, the leukemic cells have a prolonged transit time in the peripheral blood, a low growth fraction and high cell loss in the spleen and bone marrow, and an increasing doubling time towards the end stage of the disease. The normal hemopoiesis becomes progressively suppressed due to the disappearance of normal hemopoietic stem cells from the bone marrow. At the same time the number of normal stem cells in the peripheral blood and in the spleen increases to very high values, but this extramedullary hemopoiesis cannot adequately compensate for the decrease in the bone marrow. The exact proportion of clonogenic cells among the leukemic cells could not be determined due to a discrepancy between the median lethal tumor dose and the proportion of leukemia cells that produce colonies in the spleen. The survival time of rats receiving one or a few leukimogenic units is considerably longer than would be expected by extrapolation of the exponential growth that occurs between leukemic cell loads of 103 and 107. This initial lag period may be comparable to the prolonged remissions seen in a small proportion of treated patients, but the translation of leukemic cell loads and survival times from rat to man is still subject to a number of uncertainties. The BNML responds better to chemotherapeutic combinations that are effective in human AML than to regimes designed for human acute lymphoid leukemia. For the time being the BNML seems to offer the best opportunities for systematic studies of remission induction and drug selection which are relevant to the situation in human AML.

An inventory of the recently concluded, current and planned gerontological research in the Netherlands has been made. About 160 investigators are committed to this kind of research, on which they spend 71 man years. In terms of manpower, the most effort is spent in social gerontology (76 investigators, 29.23 man years), followed by biomedical gerontology (34 investigators, 23.18 man years) and medical gerontology (50 investigators, 18.60 man years). For the medical and social sciences, it could be calculated that about 0.4 to 1.0%, respectively, of research conducted at the Dutch universities is gerontologically oriented. The emphasis in biomedical gerontology is laid on studies of the immunological system, on general pathology and physiology of laboratory animals, on studies of the liver, heart and vascular system and the central nervous system. The problems are mostly approached from the point of view of biochemistry, physiology and pathology. In medical gerontology the research effort is almost exclusively dedicated to somatic and psychological aspects. Social medical studies in gerontology appeared to be nearly nonexistent. The research interests within medical gerontology are highly diverse. Only vascular diseases and diseases of the skin and sensory organs receive more than 2 man years of scientific research. Most reseach in social gerontology is aimed at psychological and sociological aspects of ageing. In terms of manpower, the following subjects receive more than average attention institutional care and services; home care and services; employment; and housing and housing facilities. A comparable amount of research is devoted to the subjects family conditions and family relations of the aged and social contacts and relations in general. However, the last two subjects are mostly studied in conjunction with other subjects primarily connected with the social roles of the aged in the community. The larger part of the research in gerontology is conducted within a single discipline, such as biomedicine, medicine or the social sciences. Initiative and assignments for investigations originate primarily in the research institutes themselves. These also provide the funding in one-third of the cases. Considerable funding is provided by various department of the government.

If the trend in risk of tuberculosis infection is estimated from the 1967-1976 data alone (which contain only 6 usable annual figures), the estimate is a decrease of 9.3% annually, a figure substantially lower than the estimate from the 1956-1966 data alone, viz. 13.7%. It is as yet impossible to decide whether or not this represents a real change in the rate of decrease of the risk of infection, as more detailed analyses need to be made. At the moment, it is thus preferable to regard the downward trend in log risk as uniform and exponential throughout the whole period, at a rate of 12.0% annually.

In opdracht van het ministerie van Welzijn, Volksgezondheid en Cultuur heeft het Nederlands Instituut voor Praeventieve Gezondheidszorg (NIPG-TNO) de Preventiegids vervaardigd, met een overzicht van de Nederlandse preventieprogramma's.1 Deze gids is in eerste instantie bestemd voor een aantal beroepsgroepen in de eerstelijnsgezondheidszorg en basisgezondheidszorg: huisartsen, verloskundigen en medewerkers van de jeugdgezondheidszorg. Daarmee is nuttig gebruik door anderen in de preventieve gezondheidszorg zeker niet uitgesloten. Bij het opstellen van de gids is een aantal controversen in de preventieve gezondheidszorg aan het licht gekomen, die in 4 artikelen in dit tijdschrift zullen worden besproken. Dit artikel is het eerste van deze reeks, die als doel heeft het losmaken van discussie over zin en onzin van deze preventieve maatregelen.

Chemicals/CAS: Oxygen, 7782-44-7; Radiation-Sensitizing Agents

A statement of general principles and minimal criteria for the screening of chemicals for potential mutagenicity in man that may be used as guidelines for regulatory agencies and industrial organisations. To make clear the potentialities and current limitations of short-term mutagenicity testing for the prediction of genetic and carcinogenic risks in man. Chemicals/CAS: Mutagens

Limited resources for health care and increasing health care costs have led to proposals to expand home care services. Presently, home care technology is rather primitive. Its development and use have been largely unplanned. Nonetheless, home care technology is growing in response to obvious needs, and a number of experiments in the Netherlands have begun to demonstrate some potentials in this area. As technological developments accelerate, opportunities for supporting people in their homes will greatly increase. The major problem with the introduction of technology into home care is the lack of an integrated home care system that can select, provide and assess technology. Without such a system, industrial developments in this area will probably continue to be slow.

Advancing our knowledge on the toxicology of combined exposures to chemicals and implementation of this knowledge in guidelines for health risk assessment of such combined exposures are necessities dictated by the simple fact that humans are continuously exposed to a multitude of chemicals. A prerequisite for successful research and fruitful discussions on the toxicology of combined exposures (mixtures of chemicals) is the use of defined terminology implemented by an authoritative international body such as, for example, the International Union of Pure and Applied Chemistry (IUPAC) Toxicology Committee. The extreme complexity of mixture toxicology calls for new research methodologies to study interactive effects, taking into account limited resources. Of these methodologies, statistical designs and mathematical modelling of toxicokinetics and toxicodynamics seem to be most promising. Emphasis should be placed on low-dose modelling end experimental validation. The scientifically sound so-called bottom-up approach should be supplemented with more pragmatic approaches, focusing on selection of the most hazardous chemicals in a mixture and careful consideration of the mode of action and possible interactive effects of these chemicals. Pragmatic approaches may be of particular importance to study and evaluate complex mixtures; after identification of the 'top ten' (most risky) chemicals in the mixture they can be examined and evaluated as a defined (simple) chemical mixture. In setting exposure limits for individual chemicals, the use of an additional safety factor to compensate for potential increased risk due to simultaneous exposure to other chemicals, has no clear scientific justification. The use of such an additional factor is a political rather than a scientific choice.

Eind 1990 verschenen in dit tijdschrift twee artikelen over het aantal met HIV geïnfecteerden in Nederland. Hieruit bleek dat het aantal HIV-seropositieven lager lag dan eerder werd aangenomen, maar dat desondanks een stijgend aantal AIDS-patiënten verwacht mocht worden. In uitkomsten liepen de twee onderzoeken niet ver uiteen. Jager et al. kwamen uit op 9000-12.000 HIV-seropositieven per 1 januari 1990; wij vonden 5500-6500 seropositieven voor eind 1987 en tussen de 7500 en 9000 voor medio 1990. Verder suggereerde de door ons gevonden epidemische curve dat de HIV-verspreiding in ons land over haar hoogtepunt heen was. Chemicals/CAS: zidovudine, 30516-87-1; Zidovudine, 30516-87-1

During a period of 2 years, every 2 months 126 different food items forming a 'market basket' were purchased, prepared and divided into twelve food commodity groups. The 'market basket' was based on a study of the dietary pattern of 16- to 18-year-old male adolescents. In the (homogenized) food group various additives and components of nutritional importance were determined. From the concentrations of the additives and components in the food groups and the daily consumption of each food groups, a mean daily intake of all components analysed was calculated. The mean daily amounts of benzoic acid (34 mg), sorbic acid (6 mg), glutamic acid (660 mg) and sulphite (3 mg) were all far below the acceptable daily intake (ADI) value. Butylated hydroxytoluene and gallates were not detectable, while butylated hydroxyanisole (BHA) was found in only a few instances; the maximum amount of BHA was also very low (4 mg). The mean daily intakes of fluorine (0.8 mg), iodine (0.21 mg), phosphorus (1860 mg) and ??-tocopherol (9.4 mg) seem safe and adequate. Cholesterol intakes of 25% above the maximum of 300 mg/d, as advised by the Dutch Bureau for Nutrition Education, were found. The mean fat intake appeared to be 40% of total daily energy, protein content 13% of total energy and total energy and total (available) carbohydrate 46% of total energy. The daily dietary fibre content (18 mg) and the daily amount of linoleic+linolenic acid (6% of total energy) were considered too low. The daily level of sodium (4.2 g) was not considered too high. It is recommended that the study should be repeated regularly, e.g. every few years, in order to monitor trends in the concentrations of significant food components in total diets. Chemicals/CAS: Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Food Additives

Chemicals/CAS: calcium chloride, 10043-52-4; calcium, 7440-70-2; citric acid, 126-44-3, 5949-29-1, 77-92-9, 8002-14-0; edetic acid, 150-43-6, 60-00-4

Engineering bacteria for measuring chemicals of environmental or toxicological concern (bioreporter bacteria) has grown slowly into a mature research area. Despite many potential advantages, current bioreporters do not perform well enough to comply with environmental detection standards. Basically, the reasons for this are the lack of engineering principles in the detection chain in the bioreporters. Here, we dissect critical steps in the detection chain and illustrate how bioreporter design could be improved by mutagenizing specificity and selectivity of the sensing and regulatory proteins, by newer expression strategies and application of different signalling networks. Furthermore, we describe how redesigning bioreporter assays with respect to pollutant transport into the cells and application of other detection devices can decrease detection limits and increase the speed of detection.

The Health Council of the Netherlands has published its advisory report on Repetitive Strain Injury (RSI). The report provides clear information on the state of this syndrome, including the definition of the problem, the epidemiology, various hypothetical pathophysiological mechanisms, occupational and personal risk factors, and possible methods of treatment. The council states that with regard to the last aspect, too few data are available to draw any conclusion as to the most promising therapy. Nevertheless, patients should get consistent advice from their GP or company doctor. The council emphasises that encouraging physical exercise and eliminating any possible causative strain should be part of an integrated approach, embracing work-related psychosocial and personal issues. Of particular interest is the council's advice to prevent RSI by improving the physical condition and by selective training of muscle function. The report recommends that more research be carried out in order to provide insight into the effectiveness of the treatment of RSI.

Chemicals/CAS: fibrin, 9001-31-4; plasminogen activator inhibitor, 105844-41-5; plasminogen activator, 9039-53-6; Carrier Proteins; Glycoproteins; Plasminogen Activators, EC 3.4.21.-; Plasminogen Inactivators; Protease Inhibitors; protease-nexin

Regarding risk evaluation of complex mixtures, the Working Group discussed the following topics: evaluation of the mixture as a whole, fractionation of the mixture, identification of the 'top ten' chemicals, and composite standards. It was concluded that no standard methodology for hazard identification and risk assessment of complex mixtures yet exists, but assessment of complex mixtures must proceed, using all available information,methods, technology, expertise and experience. The development of a decision tree for tackling complex mixtures was recommended, and the need to move forward with instituting standards for mixtures, especially in job-oriented situations, was emphasized.

De naam ‘spina bifida’ - letterlijk: gespleten doornuitsteeksel - is eigenlijk een eufemisme. In werkelijkheid duidt de term op een segmentaal defect, meestal lumbosacraal gelegen, in de ontwikkeling van de neurale plaat tot neurale buis. De sluiting van de neurale buis vindt in de eerste 4 weken van de zwangerschap plaats. Het kind dat na een voldragen zwangerschap met spina bifida geboren wordt, is in de meeste gevallen ernstig gehandicapt en heeft zelfs bij inzet van alle therapeutische middelen een sterk verkorte levensduur.1 De verschijnselen bestaan uit verlammingen aan de onderste ledematen, incontinentie van blaas en rectum, meestal hydrocefalus en vaak een kyfotische rugafwijking. Velen zijn rolstoelgebonden. Alhoewel kinderen met spina bifida een normale intelligentie kunnen hebben, is dit bij de meesten niet het geval en bij hen leidt de verstandelijke achterstand tot een verdere beperking van de keuzevrijheid in hun bestaan.