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Biomedical subjects

R van Strik

Publications and source records attributed to R van Strik.

At least 37 records · Page 2Linked to original sources

General approach to correction for bias in analytical performance in longitudinal studies illustrated by estimating the effect of age on gamma-glutamyltransferase activity.

For studying trends in blood biochemistry analytes of an individual or a group of individuals, the outcome may be influenced by analytical changes that may have occurred during the study. An observed trend may well represent a drift in analytical performance instead of a truly biological finding. We developed a model that allows for retrospective correction of analytical changes with time. This model is based on the concept of adjustment of an individual's longitudinal blood biochemistry data by comparing the long-term results of the laboratory with those of other laboratories in an external quality-control survey program. Factors responsible for the analytical bias of our laboratory were identified by multiple regression analysis. The resulting procedure for assessing analytical bias and variability was applied to study in two mutually exclusive cohorts of employees of the Shell petrochemical complex in Rotterdam (a) the true nature of the changes (analytical or biological) in gamma-glutamyltransferase (GGT) and (b) the effect of age on GGT. The first cohort consisted of employees who attended a periodic health assessment in 1984 and in 1989; the second, employees who attended periodic health assessments in 1985 and in 1988. Thus we studied 3- and 5-year changes of GGT corrected for analytical bias. Whereas standard cross-sectional results apparently showed an increase of GGT up to age 50 years, the longitudinal findings corrected for analytical changes, as indicated above, do not support these cross-sectional results.

Adolescent↗

Uveal melanoma: therapeutic consequences of doubling times and irradiation results; a review.

Thirty-six of 39 published calculated doubling times (Td's) of uveal melanomas appeared to be longer than 60 days. Metastatic death occurs 35-40 Td's after dissemination. The shortest interval between dissemination and metastatic death in individual patients may, therefore, be calculated as 35 x 60 days = 6 years; the interval may extend to 80 years. This suggests, that local therapy cannot influence the survival data within the first 7 post-therapeutic years, because almost all metastatic deaths within these 7 years are due to pretreatment dissemination. For that reason, the published comparative survival analyses after various therapies have within this period failed to show statistically significant death rates differences. Microscopically viable melanoma tissue has been noted in 215 of 231 histopathologically studied irradiated uveal melanomas. Observed mitotic figures 4-6 years after irradiation indicate retained reproductive integrity. This constitutes a--by enucleation avoidable--incremental risk for post-irradiation exponential growth and dissemination. The risk cannot become statistically manifest before a greater than or equal to 10-year follow-up period. Retained, generally poor, visual acuity in a small percentage of patients cannot balance the incremental risk/benefit ratio of irradiation. A few, at present justifiable, indications for radiotherapy on uveal melanomas are enumerated.

Brachytherapy↗

Enrichment of beta cells from the human fetal pancreas by fluorescence activated cell sorting with a new monoclonal antibody.

The aim of this study was to produce an antibody reactive to the surface of endocrine pancreatic cells and use this antibody for the purification of endocrine cells from the human fetal pancreas by fluorescence activated cell sorting. We describe such an antibody, called N1, reacting with the surface and cytoplasm of endocrine cells in the adult and fetal human pancreas (12 to 18 weeks gestational age). While unreactive to exocrine and mesenchymal cells, it was not specific for endocrine cells, as evidenced by its staining pattern in tissues other than pancreas. Almost 40% of the N1-positive pancreatic cells contained either insulin, glucagon or somatostatin. Conversely, more than 90% of each of the hormone-containing cells was N1 positive. An additional 40% of N1-positive cells, not containing other pancreatic hormones, was shown to contain islet amyloid polypeptide, synaptophysin, chromogranin, tyrosine hydroxylase or CA812. A two-step collagenase digestion protocol yielded 1.29 +/- 0.17 x 10(5) cells per mg pancreatic tissue. After Percoll gradient centrifugation, the suspension contained 15.6 +/- 5.7% (n = 25, mean +/- SD) cells reactive with N1. By fluorescence activated cell sorting using the antibody N1, the single-cell suspension was enriched from 3.0 +/- 1.4% to 16.2 +/- 4.8% (n = 10, p less than 0.01) Beta cells. Alpha and Delta cells were also enriched significantly by this procedure. The percentage of N1-positive cells increased from 17 +/- 4% to 83 +/- 6%. This preparation enriched for endocrine cells allows future studies on possible endocrine precursor cells.

Abortion, Spontaneous↗

Acute effects of cigarette smoking on microcirculation of the thumb.

The acute effect of smoking on the microcirculation of the skin of the thumb was investigated in healthy volunteers. Twenty-two were smokers and 10 were non-smokers. The flow was assessed by means of laser Doppler flowmetry. The smokers inhaled 2 cigarettes. During smoking of their first and second cigarette respectively, a mean decrease in laser Doppler flow of 23.8% and 29.0% was seen (p = 0.03; p = 0.01). Ten minutes after smoking this decrease was recovered by half. This experiment confirms that one should prohibit smoking of cigarettes pre- and postoperatively for optimal wound healing conditions.

Adolescent↗

The acute effect of cigarette smoking on the microcirculation of a replanted digit.

Thirty-one patients who had undergone digital replantation or revascularization volunteered to participate in a study of the acute effect of smoking on the microcirculation of the skin of replanted fingers. Fourteen were smokers and 17 were nonsmokers at the time of the study. Blood flow was assessed by means of the laser Doppler flowmeter under standard conditions. Each smoker inhaled 2 cigarettes. During smoking of the first and second cigarettes a mean decrease in laser Doppler flow of 8% and 19%, respectively, was found, whereas the nonsmokers showed a slight increase of 4% and 4%, respectively. Ten minutes after the last cigarette almost no recovery could be detected. The negative effect of smoking on the microcirculation in replanted digits proved to be more pronounced in the patients operated on more recently. This experiment confirms that smoking after replantation surgery should be prohibited to guarantee optimal circulation.

Adult↗

Allogeneic transplantation of the radial side of the hand in the rhesus monkey: I. Technical aspects.

Since allogeneic transplantation of extremities can only be considered if uneventful long-term survival and functional recovery can be achieved, a series of 12 transplantations of the radial side of the hand were performed in rhesus monkeys so that these factors could be assessed. The transplant incorporated the first ray of the hand in conjunction with the radial forearm flap. Graft survival times varied from 21 to 179 days. Ten of 12 transplants showed rejection. In 2 of the 10, rejection could be reversed. Immunosuppressive therapy consisted of cyclosporin A, prednisone, monoclonal antibodies, and preoperative third-party blood transfusions. Monitoring of the microcirculation of the allograft could not provide a predictive value for transplant rejection. The first clinical signs of sensory and motor function recovery were detected after an average of 42 and 44 days, respectively. Indefinite uneventful allograft survival could not be established. Major complications such as sepsis, shock, and lymphoma development leading to death were encountered. The model, however, is technically feasible, and the results for functional recovery under immunosuppression are promising.

Animals↗

Cellular and eicosanoid composition of bronchoalveolar lavage fluid in endotoxin protection against pulmonary oxygen toxicity.

Endotoxin protects against pulmonary oxygen toxicity in rats, and both prostaglandins and polymorphonuclear leukocytes (PMN) are implicated as playing an important role in this protective action. In this study, a bronchoalveolar lavage (BAL) technique was used to analyze cellular and eicosanoid composition of the lavage fluid of endotoxin-protected oxygen-exposed rats. The BAL fluid of the endotoxin-protected oxygen-exposed rats contained the highest number of PMN, while the BAL fluid of the nonprotected oxygen-exposed rats contained the highest number of macrophages. Thus, morbidity due to pulmonary oxygen toxicity was correlated with the number of macrophages but not with the number of PMN present in the BAL fluid. Leukotriene B4, thromboxane B2, and prostaglandin E2 levels were significantly higher in the lavage fluid of nonprotected oxygen-exposed rats compared to the levels in the lavage fluid of air-exposed rats. Eicosanoid levels in the BAL fluid of endotoxin-protected oxygen-exposed rats did not differ significantly from the levels found in air-exposed control rats. These findings suggest that endotoxin protects against hyperoxia-induced changes in eicosanoid metabolism.

6-Ketoprostaglandin F1 alpha↗

Continuous subcutaneous insulin infusion (CSII) versus conventional injection therapy in newly diagnosed diabetic children: two-year follow-up of a randomized, prospective trial.

The effect of continuous subcutaneous insulin infusion (CSII), begun at diagnosis, on blood glucose control and endogenous insulin production was studied in a group of consecutively referred newly diagnosed diabetic children. In a random order, 15 children started CSII (age 9.5 +/- 4.2 (+/- SD) years) and 15 conventional injection therapy (age 7.0 +/- 3.6 years). For 2 years HbA1 and urinary C-peptide were measured monthly, C-peptide responses to glucagon 6-monthly, and insulin antibodies every 3 months. None of the patients requested change of therapy during the study period, but at 28 months 1 adolescent girl changed to injection therapy from CSII. Severe hypoglycaemia was observed once in each group, but ketoacidosis only once, in the injection therapy group. From 2 months after diagnosis onwards the CSII group had significantly lower HbA1 levels. Urinary and plasma C-peptide levels did not differ between the two groups and similar insulin doses were used throughout the study. At the end of the 2 years of therapy, the CSII group had significantly lower insulin antibody levels. The observations suggest that CSII is well accepted in newly diagnosed children and improves metabolic control, but does not prolong endogenous insulin production.

Blood Glucose↗

Measurement of human small airway smooth muscle function in vitro. Comparison of bronchiolar strips and segments.

We have compared isotonic responses to methacholine of human bronchiolar segments and spiral strips. Both types of preparations contracted dose-dependently to methacholine and had a stable intrinsic contractile activity, which was significantly higher in segments (p less than 0.001). ANOVA indicated that the total variation in responses of both strips and segments was similar and was mainly due to a significant between-preparations/within-patients variation. There was a small but significant trend towards a decrease of sensitivity (EC50) in time for both segments and strips. Net contraction, i.e. the difference between resting length and the length at maximal contraction, did not change in time. Limited length-active shortening experiments indicated that 250 mg was a suitable load for both strips and segments. We concluded that, although human bronchiolar strips and segments are functionally comparable, bronchiolar segments are preferable because of their practical and theoretical advantages over bronchiolar strips.

Adult↗

[Irradiation of choroid melanoma: justifiable therapy or medical experiment].

An analysis of published results of irradiation of choroidal melanomas shows that only two reports contain justified statistics. All other statistics are based on insufficiently long follow-up periods, and do not cover all patients irradiated so that artifacts of selection occur which cannot be checked. Arguments are adduced which show that the authors of the two relevant reports mentioned rightly changed their previously positive attitude towards irradiation of these tumors. With the exception of three circumscribed categories of patients, irradiation of choroidal melanomas is still an unjustifiable medical experiment.

Choroid Neoplasms↗

Postoperative monitoring of allogeneic limb transplantation in rats.

Allogeneic limb transplantation with and without immunosuppression has been successfully reported. We used the experimental model described by Fritz and colleagues to investigate the value of different factors in the rejection phase. Twenty rats of inbred strains sustained an allogeneic limb transplantation without immunosuppression. In 6 rats an isologous limb transplantation was performed as a control group. Factors investigated in the transplanted limb were glucose, lactic acid, and blood gases of the peripheral blood, as well as laser Doppler flowmeter (LDF) recordings and histology. All factors were compared with the normal contralateral limb of the rat. All rats were killed between days 2 to 14 following operation. In the allogeneic limb transplantation model in the rat, clinical and histological examination as well as LDF measurements (p less than 0.0001) are good factors for rejection. In contrast, peripheral blood gases, glucose, and lactate were not useful as factors for rejection. In this model, however, LDF values cannot predict an initial onset of the rejection before clinical signs are evident, presumably because of the impossibility of continuous measurements.

Animals↗

The Doppler flow velocity waveform in the fetal internal carotid artery with respect to fetal behavioural states. A longitudinal study.

Doppler flow velocity waveforms in the fetal internal carotid artery were recorded in 21 normal pregnancies during fetal behavioural state IF (quiet sleep) and 2F (active sleep) according to Nijhuis and co-workers, from the 36th week of gestation onwards. The present study confirms the earlier finding of a significant reduction of the pulsatility index (PI) in state 2F as compared to state 1F at 37-38 weeks of gestation and demonstrates that this difference in PI exists throughout the entire period, in which fetal behavioural states have been described. Furthermore, it is demonstrated that there is a significant reduction in PI of this vessel during the last 4 weeks of gestation, suggesting a haemodynamic redistribution, favouring blood supply to the brain during the latter weeks of gestation.

Blood Flow Velocity↗

Urinary C-peptide: a useful tool for evaluating the endogenous insulin reserve in cohort and longitudinal studies of diabetes in childhood.

Increasing research into the remission phase of type I diabetes mellitus stresses the importance of a non-traumatic and reliable method for the evaluation of endogenous insulin production. We compared 24-h urinary C-peptide excretion (UCE) with plasma C-peptide values before and after stimulation with 1 mg glucagon in 24 type I diabetic children. Fasting plasma C-peptide values and stimulated plasma C-peptide values showed a linear correlation with 24 h UCE. Mean plasma C-peptide levels correlated inversely with the exogenous insulin dose. A slightly better correlation was found between the exogenous insulin dose and 24 h UCE. Control data of 24 h UCE were obtained from healthy siblings. A linear correlation with age was found up to 10 years of age above which UCE values seem to reach a plateau. This effect of age, as well as the frequency of sampling was taken into account in the derivation of 95% reference intervals for UCE. The measurement of 24 h UCE appears to be a useful parameter to assess endogenous insulin production in diabetic children, provided that age is taken into account.

C-Peptide↗

Early termination of clinical trials with prolonged observation of individual patients: a case study.

Stopping rules for a placebo controlled clinical trial of anticoagulants after acute myocardial infarction were evaluated by means of computer simulation for the case of five interim analyses. The trial will be terminated and the null hypothesis of no treatment effect rejected when the one-sided P-value (logrank test) is lower than 0.005, 0.005, 0.005, 0.014, and 0.023 at the respective interim analyses, and 0.032 at final evaluation. This implies a total size alpha = 0.05 and a power close to that of fixed sample size testing. The trial will also be terminated, without rejecting the null hypothesis, when the one-sided P-value exceeds 0.95, 0.88, 0.81, 0.74, and 0.67 at the respective interim analyses. This modification hardly affects size and power.

Anticoagulants↗

Comparison of isometric and isotonic responses of human small airway smooth muscle in vitro.

The difference between isometric and isotonic responses of human small airway smooth muscle to a number of pharmacological agonists was studied. The isotonically measured sensitivity to methacholine was 1.4 times less than the isometrically measured value (p less than 0.05), and similar small discrepancies were found for histamine, leukotriene, prostaglandin F2 alpha, isoproterenol, and theophylline. Maximal isometric force and isotonic shortening after methacholine were linearly related (p less than 0.01). The between-methods difference is relatively small. Because the difference was of similar magnitude and in the same direction in all tissues studied, it is of little practical importance for conventional pharmacological experiments.

Bronchi↗

The determination of reference values for hematologic parameters using results obtained from patient populations.

Reference values for hematologic parameters are determined using data from patient populations of a whole year. As a consequence, the authors are not dependent on a limited selected population and can determine reference values for all age and sex groups. It turns out that from the possible compilation technics the gamma distribution gives the best fit. If the results are compared with values stated in the literature, it is remarkable that the total number of leukocytes for men older than 50 years is higher than for women; both the absolute and relative amount of monocytes and eosinophilic granulocytes are higher for men than for women. The platelets are lower for men than for women from the age of 15 years on.

Adolescent↗