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Biomedical subjects

A van der Linde

Publications and source records attributed to A van der Linde.

8 recordsLinked to original sources

Estimation of non-parametric multivariate risk functions in matched case-control studies with application to the assessment of interactions of risk factors in the study of cancer.

In epidemiological studies one is interested in investigating the probability of disease depending on risk factors and in particular in detecting interactions of risk factors. Within the setting of parametric logistic regression, interactions can be modelled only in a clumsy and limited way. Modelling the risk function non-parametrically, estimating it, for example, by a smoothing (thin plate) spline is attractive as a more explorative approach. For prospective studies this amounts to smoothing within the framework and distributional assumptions of generalized regression models (for binary observations). Case-control studies as retrospective studies with exposure to risk factors being observed do not immediately fit into this setting. In the special case of one-to-one matched studies, however, there is an appropriate likelihood again within the range of generalized models. Inferences will be illustrated using simulated and real data.

Adult↗

Estimating biotransformation rate constants of organic chemicals from modeled and measured elimination rates.

In this study, biotransformation rate constants are estimated for a large set of organic compounds. Biotransformation (km) is considered part of the total elimination, further consisting of physico-chemical elimination to water (kw), depuration by feces (kf) and growth dilution (gamma). Existing models are used to estimate kw and kf, and gamma. The difference between measured elimination rate constants and the sum of predicted elimination rate constants for water, feces and growth indicates the ration of biotransformation in the total elimination. In all examined animal classes, polycyclic aromatic hydrocarbons seem to be metabolized at an intermediate rate. Because of the relative low hydrophobicity of some of the studied compounds, their physico-chemical elimination rate constant is relatively high, and the relative contribution of metabolism to total elimination of these compounds is therefore relatively low. Fish seem to be capable of metabolizing chlorodibenzo-p-dioxins and -furans, DDT, chloroanilines and phenol.

Animals↗

The power of size. 1. Rate constants and equilibrium ratios for accumulation of organic substances related to octanol-water partition ratio and species weight.

Most of the thousands of substances and species that risk assessment has to deal with are not investigated empirically because of financial, practical, and ethical constraints. To facilitate extrapolation, we have developed a model for accumulation kinetics of organic substances as a function of the octanol-water partition ratio (Kow) of the chemical and the weight, lipid content, and trophic level of the species. The ecological parameters were obtained from a previous review on allometric regressions. The chemical parameters, that is, resistances that substances encounter in water and lipid layers of organisms, were calibrated on 1,939 rate constants for absorption from water for assimilation from food and for elimination. Their ratio was validated on 37 laboratory bioconcentration and biomagnification regressions and on 2,700 field bioaccumulation data. The rate constant for absorption increased with the hydrophobicity of the substances with a Kow up to about 1,000 and then leveled off, decreasing with the weight of the species. About 39% of the variation was explained by the model, while deviations of more than a factor of 5 were noted for labile, large, and less hydrophobic molecules as well as for algae, mollusks, and arthropods. The efficiency for assimilation of contaminants from food was determined mainly by the food digestibility and thus by the trophic level of the species. A distinction was made between substances that are stable, that is, with a minimum elimination only, and those that are labile, that is, with an excess elimination probably largely due to biotransformation. The rate constant for minimum elimination decreased with the hydrophobicity of the substance and the weight of the species. About 70% of the variation was explained by the model, while deviations of more than a factor of 5 were noted for algae, terrestrial plants, and benthic animals. Labile substances were eliminated faster than isolipophilic stable compounds, but differences in laboratory elimination and accumulation were small compared with those in field accumulation. Excess elimination by vertebrates was faster than by invertebrates. Differences between terrestrial and aquatic species were attributed to water turnover rates, whereas differences between trophic levels were due to the food digestibility. Food web accumulation, expressed as organism-organic solids and organism-food concentrations ratios could be largely explained by ecological variables only. The model is believed to facilitate various types of scientific interpretation as well as environmental risk assessment.

Absorption↗

Spatial-temporal analysis of mortality using splines.

A method for constructing contour maps in disease mapping using smoothing splines is presented. Smoothing errors are discussed and error maps suggested. The approach is illustrated for mortality data on cardiovascular diseases in northwestern Germany (Lower Saxony and Bremen) 1970-1979.

Biometry↗

Diagnostic and prognostic criteria for heat stroke with special reference to plasma enzyme and isoenzyme release patterns.

1. The aim of this study was to investigate the potential value of isoenzyme release patterns as parameters of hyperthermic injury in improving the diagnostic protocol for heat stroke. 2. Rats were exposed to combinations of exercise and hyperthermic stress. Following exposure, respective release patterns of isoenzymes were determined. 3. Isoenzyme release patterns following hyperthermic injury portray both the type and extent of tissue damage more clearly than do plasma total enzyme release patterns. 4. The sensitivity of isoenzymes as a diagnostic criterion is extended to include both a temporal component (i.e. an accurate diagnosis will be possible at an earlier stage subsequent to hyperthermic exposure) and at the same time to be indicative of the exposure.

Alanine Transaminase↗

Physiologic and biochemical changes during a triathlon competition.

The triathlon has come to be recognized as a distinct endurance event and although a substantial body of research information exists with regard to the individual components (canoeing, cycling, running, etc.), the physiologic demands imposed by combining the respective activities into one continuous event have not yet been assessed. Twenty-three male athletes (age = 33 +/- 5.2 yr; mass = 71.79 +/- 7.42 kg; height = 176.0 +/- 7.21 cm; means +/- SD) participated in the study on the basis of informed consent. Venous blood samples, taken immediately prior to and on completion of the Iron Man Triathlon held in Johannesburg during 1983, were assayed for parameters of energy metabolism, fluid and electrolyte balance, and stress (tissue enzymes in serum). On the basis of post-race blood glucose (6.17 mmol. l-1), free fatty acids (1943 mumol. l-1), and blood lactate (3.45 mmol. l-1) changes, it was concluded that the triathlon is primarily, in an overall sense, an aerobic event. With the exception of magnesium and iron, serum electrolyte changes agreed with literature findings. However, body mass reductions (average 3.23 kg, i.e., 4.5%) indicated that the extent of dehydration is more severe in the triathlon than in comparable endurance events. Post-race enzyme levels (LD, CK, and AST) were significantly elevated, and LD negatively correlated with total performance time (P less than 0.01). The general conclusion is that the physiologic demand of the triathlon exceeds that of other comparable endurance events.

Adult↗

A comparative study on the effect of training at altitude and at sea level on endurance and certain biochemical variables.

The aim of this study was to ascertain the effects of training at altitude (1750 m. PB = 630mmHg) and at sea level (10m, PB = 760mmHg) as well as that of a period of adaptation of originally sea level-trained rats at altitude on endurance capacity. The average run time to exhaustion was 185.3 +/- 3.7 min for rats trained at altitude in comparison with 150.0 +/- 10.3 min for sea level-trained rats. After 14 days of adaptation at altitude, no significant difference in running time to exhaustion between rats trained at altitude (189.0 +/- 16.4 min) and those trained at sea level (177.2 +/- 11.6 min) was apparent. The improved endurance capacity of rats trained at altitude (when tested at altitude) is probably attributable to an increased respiratory capacity as is evident from the significantly increased levels of the citric acid cycle marker enzyme, citrate synthase (citrate oxaloacetate-lyase, EC 4.1.3.7) in the liver and gastrocnemius muscle of rats trained at altitude as compared to those trained at sea level.

Altitude↗

Vitamin E deprivation in rats: some behavioral and histochemical observations.

Rats deprived of vitamin E from age of 4 weeks were tested in four independent behavioral experiments and compared with a group fed a control diet. During a 14-minute session in a hole-board, no differences in the level and the course of habituation of parameters of activity and exploration were found. A second group of animals was trained in an automatically controlled six-arm radial tunnel maze. Although no differences were found in various activity measurements, the deprived animals showed a slightly impaired spatial concept formation during 8 acquisition sessions. Testing their relearning ability of the same maze 18 days later, the vitamin E deprived animals showed a significant impairment. In a third experiment, animals were trained 16 days in the same maze configuration and at day 17 they were exposed to the mirror image of the radial maze. Both groups mastered this reversal with an increased level of activity but without differences in patrolling efficiency. In a fourth behavioral experiment, the effects of scopolamine on deprived animals were examined. Compared to the controls, the vitamin E deprived animals were relatively insensitive to the effects of scopolamine. Autofluorescent neuronal lipofuscin accumulation was found especially in the hippocampus (CA3) of vitamin E deprived animals. Based on these results, the usefulness of vitamin E deprivation as an animal model for accelerated normal aging is discussed.

Aging↗