[Education. Health is good but we feel poorly].
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Biomedical subjects
Publications and source records attributed to S Stender.
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The aim of this study was to investigate the possibility that the permeability characteristics of the arterial wall are related to the development of atherosclerosis. The in vivo regional variation of aortic permeability to iodinated human low density lipoprotein (LDL) in normal rabbits was compared with the regional variation in aortic cholesterol accumulation in cholesterol-fed rabbits. Aortas were divided into the aortic arch, thoracic aorta, and abdominal aorta, and each of these three parts was further subdivided into four segments of similar size. The permeability to LDL was 40 +/- 7 nl.cm-2.hr-1 (mean +/- SEM, n = 11) in the most proximal segment of the aortic arch and decreased throughout the length of the aorta to 3 +/- 1 nl.cm-2.hr-1 in the most caudal segment of the abdominal aorta. In such normal rabbits the aortic cholesterol content was similar in all 12 arterial segments at 0.08 +/- 0.005 mumol/cm2 (mean +/- SEM, n = 3 x 12). Aortic cholesterol accumulation was determined in other rabbits with an average plasma cholesterol level of 32 +/- 1 mmol/l for 96 days; the cholesterol content in the most proximal segment of the aortic arch was 2.7 +/- 0.5 mumol/cm2 (mean +/- SEM, n = 11) and decreased with increasing distance from the heart to 0.17 +/- 0.03 mumol/cm2 in the most caudal segment of the abdominal aorta. Linear regression analysis showed a close positive association between the permeability to LDL of a given aortic segment and the cholesterol accumulation in that same aortic segment after cholesterol feeding (r2 = 0.96, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Accelerated coronary artery disease has become a major complication to heart transplantation in humans. Therefore, we have developed a surgical model in the rabbit, with transplantation of the thoracic aorta as a bypass graft onto the abdominal aorta of another rabbit. The model permits the study of cholesterol metabolism in transplanted arteries. The graft did not accumulate cholesterol for as long as 298 days, provided that the rabbits were normocholesterolemic, i.e., with plasma cholesterol levels of 0.3-0.7 mmol/l. However, after a few weeks of cholesterol feeding resulting in plasma cholesterol levels of 2-5 mmol/l, the homologous graft accumulated cholesterol compared with intact aortic tissue in the rabbits and also compared with autologous aortic grafts. The intimal clearance of plasma cholesteryl ester, mainly high density lipoprotein cholesteryl ester, in the luminal layer of the aortic graft was 60-150 nl x cm-2 x hr-1 1-2 hours after transplantation. The intimal clearance in the corresponding intact thoracic aorta of the recipient animal was 5-20 nl x cm-2 x hr-1. The values were 1,500-3,000 nl x cm-2 x hr-1 51-298 days after transplantation, while the intimal clearance of the rabbit's own aorta remained unchanged. A pronounced increase in plasma lipoprotein permeability is thus an early event in transplanted arteries. It results in a higher cholesteryl ester influx that leads to cholesterol accumulation in the artery, but only if the rabbits are fed a cholesterol-enriched diet. This rabbit model may be useful in the search for interventional measures to prevent or diminish the accelerated coronary artery disease in transplanted hearts in humans.
Cardiovascular disease is currently the leading cause of death among women in the United States. To investigate the effect of postmenopausal hormone therapy on atherogenesis, we studied 75 cholesterol-fed female rabbits for 19 wk. The rabbits were randomly assigned to five groups. Four groups underwent bilateral ovariectomy followed by treatment with either 17 beta-estradiol, 17 beta-estradiol plus norethisterone acetate, 17 beta-estradiol plus levonorgestrel, or placebo. The fifth group had a sham operation and received placebo. The hormone groups had only one-third of the aortic accumulation of cholesterol found in the placebo groups, a difference that was highly statistically significant (P less than 0.0001). No significant differences in aortic accumulation of cholesterol were found in the hormone groups. This indicates that estrogen attenuates atherogenesis in cholesterol-fed ovariectomized rabbits and that two commonly prescribed progestogens do not counteract the effect. The beneficial effect of estradiol could only partly be explained by its lowering effects on serum total cholesterol or VLDL cholesterol, which implies that estradiol possesses additional beneficial effects, possibly a direct action on the arterial wall.
The section for preventive cardiology within the Danish Society for Cardiology has established a lipid group with representatives from The Danish Society for Clinical Chemistry, The Danish Society for Internal Medicine, The Danish Society for Cardiology, The Danish Society of Hypertension, The Danish College of General Practitioners, and The Danish Paediatric Society. The lipid group has elaborated recommendations for clinical chemical departments regarding lipid and lipoprotein analyses. The group suggests that doctors ordering lipid and lipoprotein analyses are offered the following: S-Cholesterol (total), substance conc., (fPt)S-Triglycerides, substance conc., S-HDL-cholesterol, substance conc., and (fPt)S-LDL-cholesterol, substance conc. (calculated). It is recommended that the biological variation be minimized by sampling in a sitting position after a 15 minutes' rest and by basing the clinical decision on a minimum of 2-3 determinations with an interval of about one month. The analytical variations should be reduced to below 3% (calculated as the variation coefficient), and it is recommended that laboratories participate in external quality control systems at least four times annually by reporting at least two human reference materials with different concentrations. As the use of reference intervals dependent on age and sex, based on random samplings of the background population, are less informative, it is recommended to refer to cutoff values for the clinical decision. The following cutoff values are recommended: S-Cholesterol (total), substance conc.: 6 mmol/l, (fPt)S-Triglycerides, substance conc.; 2.5 mmol/l, S-HDL-cholesterol, substance conc.: 0.9 mmol/l (fPt)-LDL-cholesterol, substance conc. (calculated): 4.5 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
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In a double-blind crossover study, we compared the effects of eight weeks of dietary supplementation with cod-liver oil with the effects of supplementation with olive oil on endothelial permeability, blood pressure, and plasma lipid levels in 18 patients with insulin-dependent diabetes mellitus and albuminuria. When the patients received the cod-liver-oil supplement, the mean (+/- SEM) transcapillary escape rate of albumin (as compared with the base-line rate) decreased from 8.7 +/- 0.5 to 6.9 +/- 0.6 percent per hour (P less than 0.01), and the blood pressure decreased from 146 +/- 4/90 +/- 2 mm Hg to 139 +/- 4/85 +/- 2 mm Hg (P less than 0.05). There was no correlation, however, between cod-liver oil's effect on the transcapillary escape rate of albumin and its effect on blood pressure. There was no change from base line after the patients received the olive-oil supplement. During dietary supplementation with cod-liver oil, the plasma concentration of high-density lipoprotein cholesterol increased and the concentrations of very-low-density lipoprotein cholesterol and triglycerides decreased (P less than 0.05 for all comparisons), but the level of low-density lipoprotein cholesterol did not change. In contrast, during supplementation with olive oil, the concentration of low-density lipoprotein cholesterol decreased and the levels of very-low-density lipoprotein cholesterol and triglyceride increased (P less than 0.05 for all comparisons), but there was no change in the level of high-density lipoprotein. No changes were observed in the glomerular filtration rate, degree of albuminuria, insulin requirement, glycosylated hemoglobin level, or blood glucose level during supplementation with either oil. We conclude that dietary supplementation with cod-liver oil lowers the elevated transcapillary escape rate of albumin characteristic of patients with insulin-dependent diabetes and albuminuria, independently of its effect on blood pressure--perhaps by decreasing vascular permeability. We did not find any effect of cod-liver oil on urinary albumin excretion.
During the past decade, determinations of enzyme concentrations in the blood in patients admitted with suspected acute myocardial infarction has been of increasing significance not only for early elucidation but also for establishing the correct diagnosis. This is partly the result of methods which can demonstrate the presence of myocardium-related isoenzymes and also because of the physiological basis for the release of enzymes and their metabolism bas been elucidated. In the present report, guidelines for clinical employment of enzyme investigations in acute myocardial infarction are presented. By means of blood sampling twice or thrice within a time interval af approximately 8-24 hours after the presumed time of infarction and determination of a limited number of enzymes in these samples, it is possible to exclude or confirm the presence of an infarct with high probability.
We describe a surgical procedure in pigs which makes it possible to follow the influx into, the penetration through and the efflux from the arterial wall of labeled lipoproteins. After 4 h exposure of the luminal side of the arterial wall to labeled lipoproteins, labeled esterified cholesterol was found in all layers of the aortic wall, whereas labeled free cholesterol gained access only to the most luminal layer. The data suggest that at least 40%, if not 80-90%, of the cholesteryl ester that enters the aortic wall from the luminal side, passes through the entire wall and leaves the aortic wall through vasa vasorum and lymphatics. They also suggest that free cholesterol in the lipoproteins exchanges extensively with cellular free cholesterol while the lipoproteins penetrate through the most luminal layer. More than 90% of the labeled cholesteryl ester disappeared from the arterial wall during a cold chase period of 4 days. By the simultaneous use of [3H]cholesterol and [14C]cholesterol it was shown that only 10-20% of this disappearance can be explained by cholesteryl ester hydrolysis in the arterial wall.
We compared sodium phosphotungstic acid and magnesium chloride precipitation method for high-density lipoprotein (HDL) cholesterol quantitation with the ultracentrifugation method in 64 insulin-dependent diabetic patients with plasma triglyceride less than 3 mmol/l. The cholesterol content of HDL after precipitation of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was 86% +/- 3% of the cholesterol content of HDL (q greater than 1.063) determined after ultracentrifugation at q = 1.063 (1.33 +/- 0.05 mmol/l vs 1.55 +/- 0.06 mmol/l; p less than 0.001). HDL cholesterol determined after precipitation closely correlated to HDL cholesterol determined after ultracentrifugation (r = 0.97; p less than 0.001). The absolute difference between the HDL cholesterol values obtained by the two methods was correlated to HDL cholesterol (ultracentrifugation) (r = 0.75; p less than 0.001), but it was not correlated to VLDL cholesterol, LDL cholesterol, triglyceride, HbA1c, blood glucose or serum albumin. LDL cholesterol calculated by use of Friedewald's formula was 108% +/- 4% of the cholesterol content of LDL (q = 1.019 to 1.063), determined after ultracentrifugation, but the calculated and the ultracentrifugally determined LDL cholesterol values were closely correlated (r = 0.98; p less than 0.001). These results suggest that during sodium phosphotungstic acid and magnesium chloride precipitation of plasma from diabetic patients, a constant fraction of HDL cholesterol is co-precipitated, resulting in a systematic difference in HDL cholesterol quantitation when compared with the ultracentrifugation method.
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This paper reports on the application in practice of a program for diagnosis and basic cognitive achievement training. The program concentrates on performance and its growth in children with encephalopathy-typical behavior. It is demonstrated how deficient cognitive performance may be influenced by level-raising training and transfer effects.
Through the work of the committee for reference methods in NORDKEM and the Scandinavian Society for Clinical Chemistry, a hierarchy of methods was established in Denmark in 1982 for accuracy assurance of determination of total cholesterol in serum. The hierarchy makes it possible for any laboratory to relate their results of measurements on fresh samples from humans, to the results obtained on the same samples by reference methods, which have been adjusted to definitive methodology. Proficiency studies in 1985 and 1988 gave consensus values (mean of all participants data) for total cholesterol in frozen human serum almost identical to values obtained by reference methods. Interlaboratory coefficients of variations were 4-5%. It is essential for the clinical chemist as well as for the clinician to be aware of the relative quantitative importance of preanalytical, analytical and biological variation and to realize to what extent replicate measurements on the same sample and on several samples from the same person reduce the total intraperson variation of serum cholesterol concentrations.
Type 1 (insulin-dependent) diabetic patients with clinical nephropathy have a more than ten-fold increase in mortality of cardiovascular diseases compared with diabetic patients without nephropathy. The risk factors for cardiovascular disease, plasma concentrations of lipoproteins and fibrinogen, were investigated in 74 long-term diabetic patients: 37 with normal urinary albumin excretion, 20 with incipient nephropathy and 17 with overt clinical nephropathy based on urinary albumin excretion. The groups were matched according to sex, age and diabetes duration. The concentration of plasma cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride and fibrinogen rose with increasing urinary albumin excretion. The plasma concentrations of these lipoproteins and fibrinogen were 11-14% higher in the patients with incipient nephropathy and 26-87% higher in the patients with overt clinical nephropathy compared with the patients without nephropathy. The plasma concentration of high density lipoprotein cholesterol was unaffected by albuminuria. Patients with normal urinary albumin excretion and HbA1c greater than 8.0% had significantly higher very low density lipoprotein- and lower high density lipoprotein cholesterol concentrations compared with patients with HbA1c less than 8.0%. Simple addition of the described risk factors can only account for a minor part of the greatly increased cardiovascular mortality in patients with diabetic nephropathy. An additional and possibly more decisive factor might be a change in the arterial wall, a change which promotes lipid accumulation and/or facilitates thrombus formation.
Factor VIII concentrates are usually prediluted in Owrens buffer, before use of the one-stage assay for VIII:C determinations. We found that predilution of high purity Factor VIII concentrates in fresh VIII:C deficient plasma gave VIII:C estimates about 3 times higher than predilution in Owrens buffer. Predilution in reconstituted lyophilized VIII:C deficient plasma gave VIII:C estimates about 1.6 times higher. Likewise the VIII:C in a plasma sample can be estimated to e.g. 0.03, 0.06 or 0.10 IU/ml depending on whether the reference curve is established by predilution of the reference plasma in fresh VIII:C deficient plasma, in reconstituted lyophilized VIII:C deficient plasma or in Owrens buffer, respectively. It is shown that the major part of the differences between the effects of the various prediluents on the VIII:C determinations, can be accounted for by differences in the content of Factor V, Fibrinogen, and vitamin K dependent coagulation factors in the assay mixtures.
The paper deals with some early results of the employment of Roethers method for determining reactions and retentivity in adults in the diagnosis and treatment of alcoholic patients. The tests practicability is set forth, and an attempt made to establish a Value of Instability for visual memory as an additional parameter. The first comparative results indicate significantly greater instability in the case of gamma alcoholics in the chronic stage than in the oase of gamma alcoholics in the critical stage and alpha alcoholics and epsilon alcoholics.
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The arterial walls of 3 cholesterol-fed rabbits were exposed for 3--4 hours in vivo to homologous cholesterol-labelled plasma with a 20-fold higher [3H/14C] ratio in esterified cholesterol (EC) than in free cholesterol (FC). The [3H/14C] ratio in total cholesterol (TC) in the thoracic aorta was 0.6--0.9 times the ratio prevailing in TC in plasma. This corresponds to a transfer from plasma into the arterial wall of relatively more FC, with the low ratio, than EC with the higher ratio. The [3H/14C] ratio in FC in the arterial wall was 1.4--2.0 times the ratio in FC in plasma. This corresponds to hydrolysis of some of the entered EC, adding cholesterol with the high ratio to FC with the lower ratio. The [3H/14C] ratio in EC in the arterial wall was 0.1--1.1 times the ratio in EC in plasma. This corresponds to no esterification in the arterial wall of entered FC. The same method applied to normolipidemic cockerels gave similar results. In a kinetic model the arterial influx from plasma of FC and EC combined (lipoprotein influx) corresponded in both groups to 20--90 nl plasma per cm2 arterial surface per hour with subsequent hydrolysis of 10--50% of the entered EC. The arterial influx of FC without EC (influx by exchange) accounted for 10--25% of the total influx of cholesterol in the rabbits and 40--70% in the cockerels.