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Biomedical subjects

D W Erkelens

Publications and source records attributed to D W Erkelens.

At least 19 recordsLinked to original sources

[Diabetic patients: no danger on the road].

The evaluation of the risk of traffic accidents among drivers with IDDM and the grounds for excluding them from a driver's license are topical issues, because the E.C. is issuing strict new guidelines. The risk of diabetic patients being involved in traffic accidents as reported in foreign studies and calculated from Dutch data, does not exceed that which is to be expected on account of the prevalence of DM. This justifies a flexible policy for the licensing of drivers with diabetes mellitus.

Accidents, Traffic

[Eve's risk].

Explore the source record for details and available documents.

Adult

Potential use of glutathione for the prevention and treatment of diabetic neuropathy in the streptozotocin-induced diabetic rat.

It has been shown that parameters of oxidative stress are increased in experimental diabetic neuropathy. The glutathione redox system is one of the intracellular scavenger systems for neutralizing free oxygen radicals. In this investigation we studied the effect of glutathione-treatment on the development of diabetic neuropathy in streptozotocin-induced diabetic rats by measuring sensory and motor nerve conduction velocities. The total study period was 10 weeks. Four groups of rats were studied: Group 1 consisted of non-diabetic, age-matched control rats; Group 2, of diabetic rats treated with placebo from week 0 to 10; Group 3, of diabetic rats treated with 200 mg glutathione/kg body weight i.v. two times per week from weeks 0 to 10; and Group 4, of diabetic rats treated with placebo from weeks 0 to 4 and as Group 3 from weeks 4 to 10. The sensory and motor nerve conduction velocity of rats treated prophylactically with glutathione (Group 3) were significantly different from those of rats treated with placebo (Group 2) or with glutathione administered at a later time point (Group 4). Complete restoration of sensory and motor nerve conduction velocity was not reached. There was a significant improvement in motor nerve conduction velocity from weeks 4 to 6 (p less than 0.005), but not in sensory nerve conduction velocity in the delayed treatment group (Group 4). In conclusion, treatment with glutathione, a free radical scavenger, is partially effective in the prevention of diabetic neuropathy in streptozotocin-induced diabetic rats, but is of limited value when the neuropathy is already present.

Animals

Glycated low density lipoprotein catabolism is increased in rabbits with alloxan-induced diabetes mellitus.

Hyperglycaemia in diabetes mellitus is responsible for the process of non-enzymatic glycosylation of different proteins. Since we did not find elevated glycated apolipoprotein B levels in diabetic patients, an altered glycated apolipoprotein B metabolism was suspected in diabetic patients. Experiments in normal rabbits showed that non-reductive (in vitro) glycated low density lipoprotein (gly-LDL) was cleared at a slower rate than control LDL and thus stayed longer in the circulation (vascular mean residence time: 10 vs 8 h, p less than 0.001). The body mean residence time for gly-LDL was 22 h vs 17 h for control LDL. In diabetic animals the catabolic parameters of both LDL preparations changed towards a faster clearance, the effect being greatest for gly-LDL (total mean residence times of gly-LDL pre-diabetic: 19 h, diabetic: 16 h; control LDL pre-diabetic and diabetic: 14 h). The difference in clearance between glycated and control LDL was thus strongly reduced. Virtually no antibody complexed to gly-LDL could be measured. The results suggest an increased activity of the non-receptor mediated pathway in diabetes mellitus, possibly co-responsible for an increased atherosclerotic risk.

Animals

Successful dissolution of cholesterol gallstone during treatment with pravastatin.

This case report describes a 51-year-old hypercholesterolemic male patient who had a large solitary cholesterol gallstone. The patient was treated with the 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin, 40 mg/day. After 3 months of therapy, serum cholesterol level normalized (7.7 mmol/L before and 5.2 mmol/L during treatment), and biliary cholesterol saturation index decreased from 1.3 before to 0.8 during treatment. Repeatedly performed ultrasonography showed complete gallstone dissolution. Pravastatin may be valuable in the nonsurgical treatment of cholesterol gallstone disease particularly when there is an additional indication for HMG-CoA reductase inhibitors because of hypercholesterolemia.

Cholelithiasis

Familial high-density-lipoprotein deficiency causing corneal opacities (fish eye disease) in a family of Dutch descent.

Fish eye disease (FED) is an extremely rare familial disorder characterized by severe HDL deficiency and extensive corneal opacities. This disorder appears to be a variant of familial lecithin: cholesterol acyltransferase (LCAT) deficiency in which the enzyme remains partly active yet the ability of the enzyme to esterify cholesterol in high-density lipoprotein (HDL) has been lost. The rarity of this disorder has limited advances in our understanding of the pathophysiology of the HDL deficiency. However, we here describe the clinical and biochemical presentation of a family with FED who are of Dutch descent. The proposition presented with HDL deficiency and corneal opacity. Subsequently, they were diagnosed as having FED by the absence of LCAT activity against a small proteoliposome substrate despite the presence of half-normal LCAT mass and a near-normal ratio of unesterified to total cholesterol in plasma. Heterozygotes presented with half-normal LCAT activity, but not with decreased HDL. With the identification of this three-generation family, renewed investigation of this intriguing disorder of HDL is now possible.

Adult

Thermal threshold testing for the assessment of small fibre dysfunction: normal values and reproducibility.

Small and large fibre neuropathy are common findings in patients with long-standing diabetes mellitus. The Thermal Threshold Tester was tested to obtain normal values for thermal perception threshold for warmth and cold. This device produces thermal stimuli by means of a Peltier element placed on the skin. Warm and cold thresholds are measured using a forced choice method with an up-and-down-transform rule and expressed in degrees Celsius (degree C). Thresholds were measured at the right wrist and right foot in 80 normal subjects, divided into four age groups; 25-34, 35-44, 45-54, and 55-65 years. The repeatability coefficient was assessed by twice measuring 39 diabetic patients without known neuropathy. Warm thermal threshold in the hand showed a significant increase with age from 0.09 +/- 0.5 (mean +/- SD) in the youngest age group to 0.17 +/- 0.08 degree C (p less than 0.05) in the oldest age group. Cold thermal threshold in the hand (varying between 0.08 +/- 0.04 and 0.14 +/- 0.05 degree C) and warm thermal threshold in the foot (varying between 2.45 +/- 1.93 and 4.06 +/- 2.57 degrees C) did not differ significantly between the four age groups. There was a significant increase in cold thermal threshold in the foot with age, increasing from 0.31 +/- 0.24 to 0.56 +/- 0.44 degree C (p less than 0.05). Reproducibility in the diabetic subjects was good for measurements of warm and cold threshold in the hand, but poor for warm threshold in the foot in the normal range and for cold thermal threshold in the abnormal range.

Adult

Influence of blood glucose levels on peripheral lymphocytes in patients with diabetes mellitus.

Abnormalities in lymphocyte subpopulations in patients with type 1 diabetes have been reported previously. To evaluate the effect of blood glucose levels on peripheral lymphocyte concentrations we studied the proportion and phenotypic composition of the T-cell population in 7 patients with type 1 and in 12 patients with type 2 diabetes at hospitalization because of metabolic dysregulation and in a period of restored control. Both the number of CD-4 and CD-8 positive cells increased significantly (p < 0.05), although no change in the CD-4:CD-8 ratio was observed. After restoring metabolic control there was a significant rise in the mean number of total lymphocytes (1760 +/- 759 x 10(6)/ml vs 2385 +/- 889 x 10(6)/ml, p < 0.05). The number of total lymphocytes increased in all patients but one. It is concluded that metabolic control can influence immunological parameters such as numbers of peripheral lymphocytes of various phenotypes.

Adult

[Revision of consensus cholesterol].

A new text of the Dutch Cholesterol Consensus has been prepared by an expert committee, including general practitioners. Population screening is not advocated since the general cholesterol level in the Netherlands is higher than desired with regard to the atherosclerosis risk. Case-finding is advised in view of mutual enhancement of risk factor effects. Women and the elderly are not excluded from this strategy. Cholesterol levels should be measured repeatedly and if elevated, triglycerides and HDL-cholesterol levels should be measured also. If the cholesterol level is strongly elevated cholesterol synthesis inhibitors are medication of first choice.

Adult

Abnormal platelet functions in a patient with abetalipoproteinemia.

Studies with isolated lipoproteins and washed platelets suggest that lipoproteins may affect platelet functions. We investigated platelet-rich plasma (PRP) from a patient with abetalipoproteinemia (ABL), whose plasma lacks apo-B containing lipoproteins (VLDL, LDL and chylomicrons). ABL-PRP aggregated poorly with different agonists and failed to respond to arachidonate. Thromboxane B2 (TxB2) formation was severely impaired. After gel-filtration most of the aggregation defects persisted in agreement with reduced metabolism of endogenous arachidonate. However, arachidonate-induced aggregation and TxB2 production partially normalized. Normal platelets suspended in ABL-plasma showed similar defects in aggregation and TxB2 production but arachidonate-induced aggregation was much lower than expected on the basis of TxB2. We conclude that the abnormal platelet functions in ABL-PRP are caused by (i) an intrinsic platelet abnormality due to reduced arachidonate mobilization and (ii) a property in ABL plasma that inhibits aggregation partially by trapping the arachidonate and partially by an unidentified mechanism. The latter properties may be the result of the abnormal lipid composition of ABL-plasma.

Abetalipoproteinemia

Hyperlipoproteinemia in one-year-old analbuminemic rats.

Plasma lipoprotein distribution and apolipoprotein concentrations, as well as kidney function and histopathology of heart, aorta, liver and kidney were investigated in 1-year-old Nagase analbuminemic rats (NAR) and control Sprague-Dawley rats (SDR). The NAR, particularly the females, were found to be severely hyperlipidemic. Plasma total cholesterol in non-fasted animals was 6.1 +/- 0.3 mM in the female NAR vs. 2.5 +/- 0.2 mM in the female SDR (P less than 0.01). Most of the cholesterol was located in the LDL (1.019-1.063 g/ml) and HDL2 (1.063-1.125 g/ml) density range. Plasma triglycerides were 6.1 +/- 0.6 mM in the female NAR vs. 1.3 +/- 0.3 mM (P less than 0.01) in the female SDR. Plasma phospholipids were raised up to 5.4 +/- 0.3 mM vs. 2.4 +/- 0.1 mM (P less than 0.01). NAR have increased concentrations of plasma apolipoproteins A-I (about 3-4-fold) and B (about 2-fold), but the levels of apolipoproteins A-IV and E are not increased. There was less proteinuria in the male NAR than in the male SDR (P less than 0.01). Relevant histopathological findings in the NAR included hepatocytic lipofuscinosis and hemosiderosis in Kupffer cells. Tubular lesions were more common in kidneys from NAR than from SDR, and included protein casts, cortical lipofuscinosis, proximal tubular hyperplasia and proliferative interstitial nephritis. Glomerular changes were similar in both strains. Calcinosis of the aortic media and the corticomedullary region of the kidney was characteristically present in the female SDR but absent in the female NAR. Atherosclerotic lesions were not observed. In summary, 1-year-old NAR maintained on standard rat chow, are hyperlipoproteinemic. The increased levels of plasma LDL and HDL cholesterol are not associated with an increase in the incidence or severity of atherosclerotic or glomerular lesions.

Animals

Effect of epidemic influenza on ketoacidosis, pneumonia and death in diabetes mellitus: a hospital register survey of 1976-1979 in The Netherlands.

The influence of epidemic influenza on hospitalizations because of influenza, pneumonia and diabetic acidosis in patients with diabetes mellitus was investigated. Data on the weekly incidence of influenza-like illness were obtained from the Continuous Morbidity Registration and the cumulative data on hospitalizations in short-stay hospitals were obtained from the National Medical Registration. Patients with duodenal ulcer were used as a control population. Epidemic elevations of influenza infections were observed in 1976 and 1978. The estimated relative risk for hospitalization because of influenza infection was 1.1 and 1.0 for the two non-epidemic years 1977 and 1979, respectively. For the epidemic years 1976 and 1978 this risk was calculated to be 5.7 and 6.2, respectively. An increased relative risk was also noted for pneumonia; being 25.6 for both epidemic years. The estimated relative risk of dying during hospitalization rose from 30.9 in 1977 to 91.8 in 1978. The number of hospitalizations for ketoacidosis was 50% higher in 1978 than in the other three years. During the epidemic years, 25.7% of patients hospitalized for pneumonia died, while this percentage was 14.6% in the non-epidemic years (P less than 0.05). Differences in mortality due to diabetic acidosis were similar: 25.4% in epidemic and 14.7% in non-epidemic years (P less than 0.01). During the 1978 epidemic, one out of every 1300 patients with diabetes mellitus was hospitalized because of pneumonia. It is estimated that 1 of every 260 patients with IDDM was hospitalized for diabetic acidosis. It is concluded that patients with diabetes mellitus have indeed a very high influenza-associated morbidity.

Diabetes Complications