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Biomedical subjects

S D Kristensen

Publications and source records attributed to S D Kristensen.

At least 55 records · Page 3Linked to original sources

Flow cytometric analysis of the megakaryocyte DNA distribution in whole and partially purified human and rabbit bone marrow.

Megakaryocytes are polyploid cells that constitute less than 0.1% of the nucleated cells in the bone marrow of most mammals including man. The DNA content of megakaryocytes has previously been measured by microdensitometry. Flow cytometry has also been used in the analysis of bone marrow megakaryocytes, but the general prerequisite for prior enrichment has made this technology less attractive. We describe here a modification to the mode of analysis of megakaryocyte DNA content that can be applied to whole, partially purified and elutriated human and rabbit bone marrow. The electronic masking of low-ploidy cells makes it possible to visualize the DNA content of minority, high-ploidy populations of megakaryocytes within a few minutes. In addition, this rapid technique can be combined with monoclonal antibody analysis of bone marrow cells to aid megakaryocyte identification.

Animals↗

Dietary supplementation with n-3 polyunsaturated fatty acids and human platelet function: a review with particular emphasis on implications for cardiovascular disease.

The low incidence of myocardial infarction in Greenland Eskimos may be due to their intake of marine food with a high content of n-3 polyunsaturated fatty acids (PUFAs). In Eskimos the platelet count is lowered, the platelet aggregation is inhibited, the bleeding time is prolonged and the ratio between proaggregatory thromboxanes and anti-aggregatory prostacyclins is decreased, when compared to age- and sex-matched Danes. In this review, studies evaluating the effect of a fish diet or fish-oil supplementation on human platelet function are summarized. Most studies have demonstrated that supplementation with n-3 PUFAs can cause inhibition of platelet behaviour. The optimal dose of n-3 PUFAs and the patient groups most likely to profit from supplementation need to be defined. The safety and the clinical effect of the supplementation should be investigated in long-term studies.

Bleeding Time↗

Megakaryocyte and vascular changes in rabbits on a short-term high cholesterol diet.

The effect of a short-term high cholesterol diet on thrombopoiesis and vascular ultrastructure was evaluated in rabbits. Six pairs of male litter-mate rabbits were randomized pairwise to feeding with either 2 g of cholesterol daily in addition to their normal diet or normal diet alone for 7 days. A significant 12-fold increase in median serum cholesterol (P less than 0.035) and an insignificant decrease in platelet count (P = 0.07) were found in the animals fed a high cholesterol diet. In these animals the total and cytoplasmic megakaryocyte size measured as planimetric areas in bone marrow sections were significantly decreased (P less than 0.035). No statistically significant difference in the megakaryocyte DNA content measured by flow cytometry in marrow suspensions enriched for megakaryocytes by density gradient centrifugation and centrifugal elutriation was observed between the cholesterol-fed animals and controls. Light microscopic, transmission and scanning electron microscopic examination of the aorta in both groups of animals showed a morphologically intact endothelium without any adhesion of blood-borne cells to the luminal surface. Transmission electron microscopic studies showed that cells with ultrastructural features resembling smooth muscle cells were present in the intima of the aortas of the animals on the high cholesterol diet, but not in control animals. A decrease in the size of bone marrow megakaryocytes and the occurrence of intimal smooth muscle cells are found in rabbits fed a high cholesterol diet for 7 days. These cellular events may be important features in early atherogenesis.

Animals↗

Antithrombin III and protein C in stable angina pectoris--influence of dietary supplementation with polyunsaturated fatty acids.

The effect on plasma antithrombin III (AT III) and protein C on a supplement with polyunsaturated fatty acids (PUFA's) was investigated in a double-blind study in 36 patients with stable angina pectoris. All participants were given a supplement to their normal diets of vegetable oil (4.8 g n-6 PUFA's) for 4 weeks and were then randomized to the same oil or to fish oil (4.8 g n-3 PUFA's) for 12 weeks. Both oil supplements resulted in a statistically significant decrease in AT III activity, but there were no differences between the two different types of PUFA's. Antithrombin III antigen, protein C antigen or activity did not change significantly after either oil supplement. The background and significance for the decrease in antithrombin III activity induced by n-3 and n-6 PUFA's in patients with ischaemic heart disease is unknown.

Aged↗

Haemostatic aspects of renal transplantation.

Platelet function and protein C activity and antigen level was studied in 31 renal transplant recipients and 10 healthy controls. The patients were divided into three groups: (I) cyclosporin treated, (II) azathioprine treated, and (III) azathioprine treated patients with chronic rejection. The platelet function in the renal transplant patients was normal and there was no difference between groups I and II. The specific activity of protein C was decreased in patients after renal transplantation and decreasing protein C activity and progressive renal failure was found to be positively correlated in the azathioprine treated groups.

Adult↗

Diagnostic value of ascitic fluid cholesterol levels in the prediction of malignancy.

In a prospective study abdominal paracentesis with ascitic fluid aspiration was performed in 54 consecutive patients with ascites of unknown cause. The ascitic fluid was examined cytologically and bacteriologically. The total cholesterol concentration was measured with an enzymatic colorimetric method. Malignant disease was diagnosed in 34 patients. Two of them had both malignant disease and liver cirrhosis and were excluded. Seventeen patients had liver cirrhosis, one had acute pancreatitis, and two had decompensated heart disease. The diagnostic value of an ascitic cholesterol concentration greater than 1.2 mmol/l in terms of predicting malignant disease was 87.5% (95% confidence limits, 71.0-96.5). The predictive value of an ascitic cholesterol concentration less than or equal to 1.2 mmol/l in terms of benign disease was 80.0% (95% confidence limits, 56.3-94.3). It is concluded that ascitic cholesterol measurement is a valuable supplement to cytologic examination in distinguishing between ascites of malignant and benign origin.

Adult↗

The effect of fish oil on atherogenesis and thrombopoiesis in rabbits on high cholesterol diet.

The effect of fish oil supplementation on atherogenesis and thrombopoiesis was investigated in rabbits fed a high cholesterol diet for 7 weeks. There was no statistically significant difference between the area of lipid accumulation in the aorta of the animals fed fish oil and the control animals. There was no statistically significant difference in platelet count, mean platelet volume, megakarycoyte DNA content or serum cholesterol between the two groups. Serum triglyceride was significantly higher in the fish oil group than in the controls (p less than 0.035). Fish oil supplementation does not change atherogenesis or thrombopoiesis in the cholesterol fed rabbit.

Animals↗

The effect of fish oil on lipids, coagulation and fibrinolysis in patients with angina pectoris.

The effect of fish oil on lipids, coagulation and fibrinolysis was investigated in patients with stable angina pectoris. The patients were given a daily supplement of 4.5 g n-6 polyunsaturated fatty acids (PUFA's) for 4 weeks and were then randomized to the same oil or to fish oil (4.5 g n-3 PUFA's) for 12 weeks. Blood samples were taken before and after 16 weeks of oil supplementation. Lipids, coagulation and fibrinolysis were measured in 14 patients treated with fish oil. There was a significant decrease in triglycerides and very low density lipoproteins but unexpectedly a significant increase in total cholesterol from 5.9 to 6.7 mmol/l after fish oil. The fibrinolytic activity at rest determined by the fibrin plate method showed a decrease after fish oil. Other measurements did not reveal any statistically significant changes. These finding necessitate caution with uncontrolled supplementation with fish oil in patients with stable angina pectoris.

Angina Pectoris↗

Fish oil in angina pectoris.

The effect of 12 weeks supplementation with fish oil on the number of anginal attacks and consumption of glyceryltrinitrate in 36 patients with stable angina pectoris was evaluated in a clinically controlled trial using a vegetable oil as placebo. Fish oil caused a decrease in frequency of angina, but was not significantly superior to placebo. However, due to the small sample size and a high spontaneous variation in number of anginal attacks, a risk of up to 50% of overlooking a 30% reduction in anginal attacks could be estimated. A significant inhibition of the epinephrine-induced platelet aggregation and a significant increase in intraplatelet cyclic AMP were induced by fish oil.

Angina Pectoris↗

Platelet number and volume during myocardial infarction in relation to infarct size.

Platelet number and mean platelet volume (MPV) were measured in 100 patients with acute chest pain, 41 with acute myocardial infarction (AMI), 33 with angina pectoris (AP) and 26 with non-coronary event (NCE), and compared with 21 controls. We found no significant difference in platelet count on admission in the patient groups, but it was lower compared with controls. There were no significant differences in MPV between the patient groups nor between patients and controls. Thirty patients with AMI were followed for 10 days and showed an initial 12% fall in platelet count followed by a 36% increase. Initially there was an increase in MPV (2%) followed by a fall (8%). The fall in platelet count and increase in MPV correlated with infarct size (maximum activity of lactate dehydrogenase (LDH)) and might reflect consumption of platelets. The precise role of platelets in the process of infarction is still unknown.

Aged↗

Exercise decreases the platelet sensitivity to prostacyclin in patients with angina pectoris.

Earlier reports have indicated, that the platelet sensitivity to prostacyclin (PGI2) is decreased in patients with coronary heart disease and that the onset of a spontaneous anginal attack is associated with a further decrease in platelet sensitivity to PGI2. We studied platelet function before and after bicycle exercise testing in 23 patients with angina pectoris and in 11 healthy males. We could not demonstrate any difference in platelet sensitivity to PGI2 between patients with angina pectoris and the controls neither before or after exercise testing. The platelet sensitivity to PGI2 decreased significantly after exercise, both in patients and in controls, but the decrease was not related to the development of myocardial ischemia. Our results could be interpreted in terms of different pathophysiological roles of platelets in spontaneous and in exercise-induced myocardial ischemia.

Angina Pectoris↗

Serum angiotensin-converting enzyme increases during hemodialysis. Evidence for injury of the pulmonary vascular endothelium?

In 19 patients hemodialysis was associated with significant decreases in arterial oxygen tension and leukocyte count. After 240 min of dialysis serum angiotensin-converting enzyme (ACE) corrected for hemoconcentration increased 14.3% (p less than 0.001) indicating injury of the vascular endothelium during hemodialysis. It is suggested that the increase in serum ACE is due to a complement-mediated sequestration of leukocytes in the pulmonary vasculature leading to injury of the vascular endothelium with interstitial edema and pulmonary dysfunction. Furthermore, it is suggested that serum ACE analysis may prove a new method to assess biocompatibility of materials used in devices for extracorporeal circulation.

Adult↗

The effect of dialyser membrane material on intradialytic changes in platelet count, platelet aggregation, circulating platelet aggregates and antithrombin III.

Blood surface interaction during hemodialysis leads to impairment of platelet function and decrease in platelet number, which besides heparinization, may cause or exacerbate bleeding in risk patients. Furthermore, antithrombin III has been shown to increase during dialysis, probably due to vascular endothelial injury caused by infusion of activated platelets into the patient. 23 patients were examined during two successive dialyses, using membranes based on regenerated cellulose (RC) and cellulose acetate (CA). In 12 of the patients, platelet aggregation induced by ADP, circulating platelet aggregates and immunological AT III and AT III activity were determined. Irrespective of the membrane used, hemodialysis was associated with deterioration of platelet function, reflected by a decrease in platelet aggregation with return to predialysis values at the end of dialysis. However, the decline in platelet count and the increase in circulating platelet aggregates were membrane dependent, with RC causing greater changes than CA. No changes in threshold concentration of ADP inducing secondary platelet aggregation or in either immunological AT III or AT III activity were seen during dialysis.

Adolescent↗

Eicosapentaenoic acid potentiates the production of prostacyclin-like material in the arachidonic acid perfused human umbilical vein.

The production of prostacyclin (PGI2)-like material in human umbilical veins perfused continuously at 37 degrees C with Hanks buffer solution with 1% human albumin (HBA) was studied by bioassay. Subsequent perfusion resulted in a time dependent significant decrease in production of PGI2-like material. After addition of 20 mumol/l arachidonic acid (HBA-AA) the production of PGI2-like material increased significantly. The production of PGI2-like material was significant greater when the vein was perfused with HBA-AA than when perfused with HBA with 20 mumol/l eicosapentaenoic acid (HBA-EPA). Examination of the HBA-EPA perfusate by thin layer chromatography showed that it contained a substance that comigrated with genuine 6-keto-PGF1 alpha and a substance that comigrated with delta 17-6-keto-PGF1 alpha. Finally, perfusion with HBA containing 10 mumol/l AA plus 10 mumol/l EPA resulted in a significant greater production of PGI2-like material than perfusion with HBA-AA alone. These results support the hypothesis that EPA has beneficial antithrombotic properties in human.

Arachidonic Acids↗

Decreased platelet sensitivity to prostacyclin (epoprostenol) during hemodialysis.

Evidence is accumulating that activation of platelets occurs during conventional hemodialysis. In ten uremic patients, the ADP-induced platelet aggregation and the platelet sensitivity to prostacyclin (PGI2) were examined before and after 120 and 240 minutes of dialysis. The ADP-induced aggregation was enhanced during dialysis reaching statistical significance after 240 minutes compared to predialysis values. The platelet sensitivity to PGI2 was significantly diminished during dialysis. Our results are in agreement with the concept of platelet activation during hemodialysis and lend support to the clinical use of PGI2 during hemodialysis.

Adolescent↗