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Biomedical subjects

K Kjeldsen

Publications and source records attributed to K Kjeldsen.

At least 91 records · Page 5Linked to original sources

Revaccination against tetanus 17 to 20 years after primary vaccination: kinetics of antibody response.

In 24 military recruits vaccinated against tetanus 17-20 years earlier antibody responses were studied 4, 11, and 24 days after revaccination. Antitoxin concentration in serum showed a sigmoid increase with titres at day 4 only just above protective level, corresponding to a risk of susceptibility to be expected even 4 days after revaccination (2.0%, 95% confidence limit). Only after 7 days the risk of unprotection was less than 1%. As the incubation period of tetanus can be as short as 24 hours, revaccination only may not be regarded sufficient if more than 17-20 years have elapsed since primary vaccination and conditions favoring rapid development of tetanus are present. The findings may explain some of the cases of tetanus which have occurred in spite of primary vaccination supplemented by emergency booster. The statement that prophylactic tetanus immunoglobulin is never indicated to persons completely vaccinated earlier should be considered for revision.

Adult↗

Susceptibility to diphtheria in populations vaccinated before and after elimination of indigenous diphtheria in Denmark. A comparative study of antitoxic immunity.

The need for routine diphtheria revaccination is still controversial. Only single cases of diphtheria have been observed in Denmark since the mass vaccinations in the 1940s and the introduction of routine vaccination of infants in 1950, despite the fact that general revaccination has not been recommended. An investigation of antitoxin immunity in 1.188 probands 2-69 years of age, randomly or cluster selected, indicated that immunity in the Danish population is still above the limit generally believed to guard against diphtheria epidemics (around 70% being immune in a population). The highest frequency of susceptibility (46%) was found among females 30-39 years of age. Serum antitoxin concentrations in 529 subjects with documentation for complete primary vaccination 1-40 years previously corresponded to a continuous fall-off. Relative to time from vaccination, individuals born when diphtheria occurred frequently in Denmark had significantly higher antitoxin levels than those born later, and among children susceptibility had increased considerably as compared to observations in the 1950s. These phenomena were explained by the effect of natural immune stimulation previously. The present concept of relatively high frequencies of immune subjects also in other western countries may not be valid in the future, when the number of subjects born after the elimination of indigenous diphtheria increases. General revaccinations seem required to maintain herd immunity.

Adolescent↗

Quantification of the maximum capacity for active sodium-potassium transport in rat skeletal muscle.

1. Intact skeletal muscle fibres have been shown to contain a high concentration of [3H]ouabain binding sites (100-800 pmol g wet wt.-1). Under resting conditions, however, it seems that in isolated muscles only 2-6% of the corresponding expected capacity for active Na+-K+ transport is utilized. 2. In order to determine whether all [3H]ouabain binding sites in rat soleus muscle represent functional Na+-K+ pumps, we have measured the maximum rates of the ouabain-suppressible components of isotopic fluxes of Na+ and K+ as well as the net changes in Na+-K+ contents. 3. Experiments with soleus muscles isolated from 4-week-old rats showed that following Na+ loading (I.C. Na+, 126 mmol l-1), the ouabain-suppressible 86Rb+ uptake and 22Na+ efflux as measured during 3 min of exposure to K+-rich buffer were 5800 and 6500 nmol g wet wt.-1 min-1, respectively. 4. These initial high rates of isotopic fluxes were confirmed by flame photometric measurements of Na+-K+ contents. The ouabain-suppressible 86Rb+ uptake had a temperature coefficient of 2.1, was inhibited by 2,4-dinitrophenol, but showed no response to tetracaine, BaCl2, Ca2+-free buffer or tetraethylammonium chloride. 5. In soleus muscles, where the total population of [3H]ouabain binding sites had undergone changes as a result of differentiation, K+ depletion or pre-treatment with thyroid hormone, there was a significant correlation (r = 0.95, P less than 0.005) between the concentration of [3H]ouabain binding sites (260-1170 pmol g wet wt.-1) and the maximum ouabain-suppressible 86Rb+ uptake (2300-10,900 nmol g wet wt.-1 min-1). 6. It is concluded that by the combination of Na+ loading and high extracellular K+, the available Na+-K+ pumps as quantified by the [3H]ouabain binding capacity can be activated to reach a transport rate around 90% of the theoretical maximum at 30 degrees C.

2,4-Dinitrophenol↗

Diabetes decreases Na+-K+ pump concentration in skeletal muscles, heart ventricular muscle, and peripheral nerves of rat.

Na+-K+-ATPase or the Na+-K+ pump is essential for some specific properties of muscle and nerve tissue such as contractility and excitability. Previous studies have shown conflicting variations in Na+-K+-ATPase activity or Na+-K+ pump concentration of muscle cells in experimental diabetes. Our study demonstrates that early untreated diabetes in rats induced by injection of streptozocin is associated with decreases in [3H]ouabain binding-site concentration of 24-48% in various skeletal muscles and 16% in peripheral nerves as well as a decrease in K+-dependent 3-O-methylfluorescein phosphatase activity of 21% in the heart ventricle. These effects could be prevented by insulin treatment. They probably represent a decrease in the concentration of Na+-K+ pumps. There was no evidence for more than one population of Na+-K+ pumps in intact samples of skeletal muscle and nerves from normal, diabetic, and insulin-treated animals. The decrease in Na+-K+ pump concentration in nerve cells may be due to atrophy of the axons. In skeletal muscles, myocardium, and peripheral nerves, the observed decrease in Na+-K+ pump concentration may be important for the pathophysiology of diabetes. We emphasize that quantification of Na+-K+-ATPase or the Na+-K+ pump in muscle and nerve tissue from diabetic animals should preferably be performed with either intact samples or crude homogenates of whole tissue.

Animals↗

Effect of magnesium depletion on 3H-ouabain binding site concentration in rat skeletal muscle.

In young (4-week-old) rats, dietary Mg depletion for 1.5 weeks was followed by a significant decrease in 3H-ouabain binding site or Na,K-pump concentration of up to 21% and in total K content of up to 11% in various hind limb muscles. K depletion was associated with a decrease in 3H-ouabain binding site concentration of up to 64% and in total K content of up to 31%. Mg depletion was associated with a similar correlation between the decrease in 3H-ouabain binding site concentration and total K content, as was K depletion (r = 0.98, p less than 0.001). Taken together, the results indicate that the decrease in the concentration of 3H-ouabain binding sites following Mg depletion is not primarily caused by Mg deficiency per se, but is probably secondary to the associated K deficiency. The decrease in Na,K-pump concentration may be of importance for the retardation of K repletion as well as the increase in digitalis toxicity observed with Mg deficiency.

Age Factors↗

Severe hypertriglyceridemia, large lipoproteins and protection against atherosclerosis.

Alloxan-diabetic cholesterol-fed rabbits exhibiting severe hypertriglyceridemia are protected against atherosclerosis. In such rabbits most of the plasma cholesterol is found in lipoproteins with a diameter of 75 nm or larger. In the present report it is hypothesized, that due to their large sizes, the lipoproteins of the severely hypertriglyceridemic diabetic rabbits are not able to penetrate the endothelial layer of the arteries. Therefore, the macrophages and smooth muscle cells of the intima will only come in contact with relatively small amounts of cholesterol-carrying lipoproteins. Consequently, cellular accumulation of cholesterol, which is a necessary step in the formation of an atherosclerotic lesion, will be retarded. There are certain parallels between hypertriglyceridemic cholesterol-fed alloxan-diabetic rabbits and humans with familial lipoprotein lipase deficiency, familial apolipoprotein C-II deficiency and insulin-dependent diabetes mellitus in the ketoacidotic state. Based on reports about patients with these metabolic disorders, we suggest that cholesterol in very large lipoproteins also in humans is less atherogenic than cholesterol in smaller lipoproteins.

Animals↗

Immunity against tetanus and response to revaccination in surgical patients more than 50 years of age.

Several instances of fatal postoperative tetanus have been reported, and it has recently been stated that failure to secure adequate immunization for surgical patients may have medicolegal repercussions. In order to investigate according to which criteria for the immunization surgical patients can be considered protected, 178 patients who were more than 50 years of age and who were admitted electively during one year to two surgical departments were studied. To investigate immunity relative vaccination history, all patients admitted during the first two months were offered participation in this study. One hundred and twenty-seven (86 per cent) of these patients were studied by detailed registration of vaccination history and determination of antitoxin concentration in serum. Forty-seven per cent had never been vaccinated against tetanus and 67 per cent had antitoxin concentrations in serum below the protective level. To investigate in detail the duration of immunity and the effect of revaccination, patients with documented complete primary vaccination only were studied during the entire period. An additional 51 patients have been entered into the study during the last ten months. Antibody concentration in the serum corresponded to a continuous fall off in immunity after vaccination. Patients who had received a complete three dose primary vaccination within the last five years or a revaccination within the last ten years were well protected. Forty-four patients received revaccination during the study and were controlled by blood sample four weeks later. Every patient obtained satisfactory antibody concentrations, and it was concluded that no special requirements in recommendations for vaccination are needed, even for elderly patients. Thirteen patients who underwent extensive surgical procedures had serial blood samples taken every three days. Antitoxin concentrations in serum increased sigmoidally with time, and the slow initial increase suggested that revaccination should optimally be given some days before the operation to assure protection in the first few postoperative days.

Age Factors↗

Complete quantification of the total concentration of rat skeletal-muscle Na+ + K+-dependent ATPase by measurements of [3H]ouabain binding.

In the standard [3H]ouabain-binding assay for quantification of the Na,K-ATPase (Na+ + K+-dependent ATPase) concentration in rat skeletal muscles, samples are incubated for 2 X 60 min in 1 microM-[3H]ouabain at 37 degrees C followed by a wash-out for 4 X 30 min at 0 degree C. To obtain accurate determinations, values determined by this standard assay should be corrected for non-specific uptake and retention of [3H]ouabain (11% overestimation), loss of specifically bound [3H]ouabain during wash-out (21% underestimation), evaporation from muscle samples during weighing (4% overestimation), impurity of [3H]ouabain (5% underestimation) and incomplete saturation of [3H]ouabain binding sites (6% underestimation). Thus corrected the standard [3H]ouabain-binding assay determines the total Na,K-ATPase concentration. Hence, in the soleus muscle of 12-week-old rats the total [3H]ouabain-binding-site concentration is 278 +/- 20 pmol/g wet wt. This is at variance with the evaluation of the Na,K-ATPase concentration from Na,K-ATPase activity measurements in muscle membrane fractions, where the recovery of Na,K-ATPase is only 2-18%. Quantification of the total Na,K-ATPase concentration is of particular importance since it is a prerequisite for the discussion of quantitative aspects of the Na,K-ATPase.

Animals↗

Training increases the concentration of [3H]ouabain-binding sites in rat skeletal muscle.

Exercise is associated with a net loss of K+ from the working muscles and an increased plasma K+ concentration, indicating that the capacity for intracellular reaccumulation of K+ is exceeded. Training reduces the exercise-induced rise in plasma K+, and an increased plasma [K+] may interfere with physical performance. Since the clearing of K+ from the extracellular space depends on the capacity for active K+ uptake in skeletal muscle, the effects of training and inactivity on the total concentration of (Na+ + K+)-ATPase was determined. Following 6 weeks of swim training, the concentration of [3H]ouabain-binding sites in rat hindlimb muscles was up to 46% (P less than 0.001) higher than in those obtained from age-matched controls. Whereas muscle Na+, K+ contents remained unchanged, the concentration of citrate synthase increased by up to 76% (P less than 0.001). Training induced no change in the [3H]ouabain-binding-site concentration in the diaphragm, but in the heart ventricles, the K+-dependent 3-O-methylfluorescein phosphatase activity increased by 20% (P less than 0.001). Muscle inactivity induced by denervation, plaster immobilisation or tenotomy reduced the [3H]ouabain-binding-site concentration by 20-30% (P less than 0.02-0.001) within 1 week. In conclusion, training leads to a significant and reversible rise in the concentration of (Na+ + K+)-ATPase in muscle cells. This may be of importance for the beneficial effects on physical performance by improving the maximum capacity for K+ clearance.

Animals↗

The effects of thyroid hormones on 3H-ouabain binding site concentration, Na,K-contents and 86Rb-efflux in rat skeletal muscle.

Using a recently developed method based upon vanadate facilitated 3H-ouabain binding, the total concentration of 3H-ouabain binding sites was determined in biopsies of rat skeletal muscles containing varying proportions of slow-twitch fibres. In extensor digitorum longus, diaphragm, gastrocnemius and soleus muscles from mature (12-week-old) hyperthyroid rats the values obtained were respectively 2.6, 3.5, 5.1 and 9.8 times higher than those found in the same muscles from hypothyroid animals. This indicates that the effect of thyroid hormones is more pronounced on slow-twitch than on fast-twitch fibres. The changes in 3H-ouabain binding site concentration with thyroid status could not be accounted for by differences in affinity or the rate of 3H-ouabain binding. In young (4-5 week old) rats, where the K-content and the 3H-ouabain binding site concentration in muscle had been reduced by K-depletion, T3-pretreatment produced an even larger relative increase in the 3H-ouabain binding site concentration than in age-matched controls, but no increase in K-content. Therefore, the downregulation of 3H-ouabain binding sites seen during K-depletion cannot be attributed to a decreased response to thyroid hormones. In normal rats the marked stimulating effect of thyroid hormone on the synthesis of 3H-ouabain binding sites was not associated with any significant change in K-content, but clearly preceded by a significant (P less than 0.001) rise in the efflux of 86Rb.

Animals↗

Effect of verapamil on accumulation of free and esterified cholesterol in the thoracic aorta of cholesterol-fed rabbits.

In order to investigate the effect of the calcium antagonist verapamil on atherogenesis in cholesterol-fed rabbits, 3 groups of 11 animals were fed a 2% cholesterol-enriched diet for 10 weeks. One group received verapamil in a daily dose of 16 mg/kg orally plus 2 mg/kg subcutaneously. This dosage resulted in plasma concentrations of verapamil in the same range as the usual therapeutic levels in humans. Another group received verapamil in a daily dose of 8 mg/kg orally and 0.5 mg/kg subcutaneously. The third group received placebo capsules orally and isotonic saline subcutaneously. Total cholesterol concentrations in plasma over the 10 weeks were 37 +/- 4, 42 +/- 4 and 45 +/- 3 mM (mean +/- SE) in the high verapamil-, in the low verapamil- and in the placebo group, respectively. These values were not significantly different. The distribution of cholesterol between HDL, LDL and VLDL in plasma was similar in the 3 groups. The high verapamil group had a significantly (P less than 0.05) lower concentration of cholesterol in the thoracic aorta than the placebo group (29 +/- 5 vs 43 +/- 9 mumol/g wet weight). The low verapamil group and the placebo group had the same aortic cholesterol concentrations. Neither dosage of verapamil affected the permeability of the aortic endothelium to plasma lipoproteins and albumin, as measured by use of radioactive tracers at the end of the experiment.

Animals↗

Effects of semi-starvation and potassium deficiency on the concentration of [3H]ouabain-binding sites and sodium and potassium contents in rat skeletal muscle.

1. Using vanadate-facilitated [3H]ouabain binding, the effect of semi-starvation on the total concentration of [3H]ouabain-binding sites was determined in samples of rat skeletal muscle. When 12-week-old rats were semi-starved for 1, 2 or 3 weeks on one-third to half the normal daily energy intake, the [3H]ouabain-binding site concentration in soleus muscle was reduced by 19, 24 and 25% respectively. In extensor digitorum longus, diaphragm and gastrocnemius muscles the decrease after 2 weeks of semi-starvation was 15, 18 and 17% respectively. The decrease was fully reversible within 3 d of free access to the diet. Complete deprivation of food for 5 d caused a reduction of 25% in soleus muscle [3H]ouabain-binding-site concentration. It was excluded that the reduction in [3H]ouabain binding was due to a reduced affinity of the binding site for [3H]ouabain. 2. Semi-starvation of 12-week-old rats for 3 weeks caused a reduction of 45 and 53% in 3,5,3'-triiodothyronine (T3) and thyroxine (T4) levels respectively. As reduced thyroid hormone levels have previously been found to decrease [3H]ouabain-binding-site concentration in skeletal muscle, this points to the importance of T3 and T4 in the down-regulation of the [3H]ouabain-binding-site concentration in skeletal muscle with semi-starvation. Whereas potassium depletion caused a decrease in K content as well as in [3H]ouabain-binding-site concentration in skeletal muscles, semi-starvation caused only a tendency to a decrease in K content. Thus, K depletion is not a major cause of the reduction in [3H]ouabain-binding-site concentration with semi-starvation. 3. Due to its high concentration of Na,K pumps, skeletal muscle has a considerable capacity for clearing K from the plasma as well as for the binding of digitalis glycosides. Semi-starvation causes a severe reduction in the total skeletal muscle pool of Na,K pumps and may therefore be associated with impairment of K tolerance and increased digitalis toxicity.

Animals↗

Quantification of the 3H-ouabain binding site concentration in human myocardium: a postmortem study.

The 3H-ouabain binding site concentration in the human myocardium was determined by measuring vanadate facilitated binding of 3H-ouabain to necropsy specimens of the left ventricle. The 3H-ouabain binding to samples weighing 4-6 mg was specific and saturable and appeared to take place to only one population of high affinity binding sites. After death the 3H-ouabain binding capacity degraded relatively slowly. From 6 to 24 h after death a mean decrease of 11% was seen in five patients, being significant in only one. In 15 patients aged 64-86 years the concentration of 3H-ouabain binding sites measured 6 h after death varied from 223 to 577 pmol X g-1 wet weight with no obvious relation to age or sex. The mean (SEM) value (413(26) pmol X g-1 wet weight) was 1.7 times higher than that previously reported for human myocardium. The concentrations of 3H-ouabain and 3H-digoxin binding sites were identical, and an excess of unlabelled ouabain completely prevented the specific binding of 3H-digoxin. In necropsy specimens weighing 1-2 mg from the endomyocardium obtained using a biotome the 3H-ouabain binding site concentration was in the same range as that in the myocardium. These findings indicate that it is possible to determine the concentration of Na, K-pumps in the human myocardium by measuring the 3H-ouabain binding capacity of biopsy specimens obtained during heart catheterisation or of specimens obtained within the first 18 h after death. This finding may be of importance for studying conditions in which the Na, K-pump concentration is suspected of undergoing variation.

Aged↗

The effect of diuretics and lithium on 3H-ouabain binding site concentration and Na,K-content in rat skeletal muscle.

Previous studies have shown an increase in 3H-ouabain binding sites or Na, K-pumps in vitro in cultured cells in response to incubation in low K, diuretics or lithium. However, in the present study the administration in vivo of various diuretics or lithium combined with supplementary K was not associated with any significant changes in Na,K-content or 3H-ouabain binding site concentration in rat skeletal muscle. When the diuretics were administered in combination with only the basal K requirement a decrease in both K-content and 3H-ouabain binding site concentration was seen. This indicates that the decrease in 3H-ouabain binding site concentration is not caused by these drugs per se but is secondary to the associated K-depletion. The discrepancy between the results obtained using isolated cells and rat skeletal muscles could be related to the fact that cultured cells are not subject to the normal growth control of the intact organism. It should be emphasized that results obtained using cultured cells do not necessarily reflect processes taking place in the intact organism.

Amiloride↗

The fall-off in serum concentration of tetanus antitoxin after primary and booster vaccination.

In 196 randomly selected persons with documented complete primary vaccination against tetanus 12-30 years earlier, antitoxin concentration in serum relative to time since last vaccination was studied. In the group of non-revaccinated persons an exponential decrease in antitoxin concentration with time since primary vaccination was found. 25-30 years after primary vaccination, 28% were unprotected (antitoxin concentration in serum below 0.01 IU/ml). In the group that received a single revaccination earlier, a similar exponential fall in antitoxin concentration was found, but all those revaccinated up to 23 years earlier were still protected. 82 persons who had not been revaccinated earlier were revaccinated. All those revaccinated less than 20 years after primary vaccination attained very high antitoxin concentrations (above 6 IU/ml) corresponding to a duration of immunity of at least 20 years. It was suggested that a revaccination program consisting of a single revaccination in childhood and thereafter every 20 years is sufficient to maintain immunity.

Adult↗