PubMed HealthSearch

Biomedical subjects

N A Klitgaard

Publications and source records attributed to N A Klitgaard.

At least 19 recordsLinked to original sources

Methodological aspects of measuring human skeletal muscle electrolyte content and ouabain binding capacity.

The aim of the study was to evaluate the use of freeze-dried and dissected small muscle biopsy specimens ("dry") for the determination of human muscle electrolyte content and ouabain binding capacity, compared with an easier method, without this freeze-drying step ("wet"). Freeze-drying and dissection of muscle biopsy specimens reduced the variation in the determination of muscle potassium and magnesium content. The total coefficient of variation was 8.6% in the dry determination of muscle potassium content and 13.5% in the wet determination (P < 0.05). In the determination of muscle magnesium content, the total coefficient of variation was 7.4% in the dry determination and 13.7% when determined wet (P < 0.005). Muscle sodium content had a very large coefficient of variation, independent of the method used. The content of dry solids was too high in biopsies which were incubated in Tris-vanadate buffer (31.9%), compared to biopsies which were not incubated in Tris-vanadate buffer (24.9%, P < 0.001). Hereby, the measured ouabain binding capacity became too high when measured wet. In conclusion, muscle electrolyte content and ouabain binding capacity should be determined after drying and microdissection of the biopsies, because this method confers the least variation and the highest accuracy.

Aged

Multiple anomalies, hypokalaemic paralysis and partial symptomatic relief by terbutaline.

In this paper a follow-up is presented of a case report initially described by Andersen in 1971. The patient presented with a syndrome including elements of familial periodic paralysis with hypokalaemia, long QT syndrome, ventricular ectopy, myopathy with fibre-type disproportion and dysmorphic features resembling Treacher Collins' syndrome. The main symptom was hypokalaemic paralysis. The episodes were accompanied by a lowered intracellular potassium content and an increase in intracellular sodium. Treatment with terbutaline, a Na/K-ATPase-stimulating drug, resulted in attack-free periods of approximately 9 months, after which the attacks reoccurred. The patient suffered severe attacks whenever treatment with terbutaline was stopped. The patient experienced two attacks of respiratory arrest, the second being fatal.

Abnormalities, Multiple

[Bartter's syndrome. A condition with chronic hypokalemia].

Bartter's syndrome (BS) is a disease with severe hypokalaemia due to renal potassium wasting. The potassium loss is due to lesions at different sites within the renale tubule. Additional features include metabolic alkalosis, excess renal production of prostaglandins, hyperreninaemia, hyperaldosteronism and impaired pressor responses to exogenous angiotensin II. These secondary features are the result of renal potassium wasting. Symptoms are due to potassium deficiency, but many adult patients feel well despite marked hypokalaemia. The hypocalciuric variant of BS is called Gitelman's syndrome. These patients have a more benign course. The diagnosis of BS is one of exclusion, mainly of surreptitious vomiting, diuretic or laxative abuse. The primary treatment is potassium supplementation often in combination with potassium-sparing diuretics, prostaglandin inhibitors or ACE-inhibitors. With coexisting magnesium deficiency, magnesium supplementation might be effective.

Adult

Biological variation of serum and urinary magnesium in apparently healthy males.

The biological variations of serum (S-) magnesium and urinary (U-) magnesium concentrations and excretions have been investigated. Serum samples, 24-h and fasting urinary samples were collected from each of 60 supposedly healthy male volunteers. In addition, 12 volunteers collected additional samples 7 and 112 days after the initial sample. The reference interval for S-magnesium was 0.765-0.997 mmol l-1. The biological variation for S-magnesium was 3.2% within subjects and 7.4% between subjects. This indicated an index of indivduality of 0.5, which means that significant changes in S-magnesium can occur within the limits of the reference interval, and that serial determinations of S-magnesium might prove useful as an indicator of changes in whole body magnesium status. It is, on the other hand, unlikely that a single determination of S-magnesium can be used in assessing whole-body magnesium status in the individual. The reference interval for the 24-h U-magnesium excretion, corrected for surface area, was 1.306-4.762 mumol min-1 1.73 m-2. The 24-h U-magnesium excretion exhibited a biological within-subject variation of 36% and a between-subject variation of 26%. The 24-h U-magnesium excretion did not correlate with S-magnesium, and only slightly (r = 0.58) with the fasting U-magnesium/creatinine concentration. This, and the very large coefficients of variation, make it unlikely that the renal magnesium excretion can be used as a measure of whole body magnesium status, or that changes in the renal magnesium excretion can be used as a measure of changes in whole body magnesium status.

Adult

Insulin increases renal magnesium excretion: a possible cause of magnesium depletion in hyperinsulinaemic states.

The effects of insulin upon renal magnesium excretion were examined. Urinary magnesium excretion rates were measured in seven healthy volunteers (three men, four women) before and during a euglycaemic, hyperinsulinaemic clamp. Insulin was infused at 120 pmol m-2 min-1 and at 240 pmol m-2 min-1. Compared to baseline, the renal magnesium excretion increased 30% during the infusion of insulin at a rate of 120 pmol m-2 min-1. During infusion of insulin, 240 pmol m-2 min-1, renal magnesium excretion increased 50% compared to baseline. There were no changes in either glomerular filtration rates, plasma magnesium, urinary volume or general changes in the renal handling of divalent ions as judged by an unchanged urinary excretion rate of calcium (0% during infusion of insulin, 120 pmol m-2 min-1, and 8% increase during infusion of 240 pmol m-2 min-1 (NS). During the 120 pmol m-2 min-1 insulin infusion rate, plasma insulin rose from 46.1 pmol I-1 to 158.8 pmol I-1 and during the 240 pmol m-2 min-1 insulin infusion rate, mean plasma insulin concentration was 361.4 pmol I-1. Thus, physiological concentrations of insulin induce a specific increase in the renal excretion of magnesium. This might partly explain the magnesium depletion observed in various hyperinsulinaemic states, diabetes mellitus, atherosclerosis, hypertension, and obesity.

Adult

Potassium and magnesium distribution, ECG changes, and ventricular ectopic beats during beta 2-adrenergic stimulation with terbutaline in healthy subjects.

OBJECTIVE: To study the effect of intravenous (i.v.) terbutaline on potassium (K) and magnesium (Mg) distribution, ECG changes, and prevalence of ventricular ectopic beats in healthy subjects. DESIGN: Randomized double-blind, placebo-controlled crossover. Subjects received either placebo or terbutaline (bolus, 0.25 mg; maintenance dose, 5 micrograms/min). SETTING: University Department of Clinical Chemistry. PARTICIPANTS: Ten healthy male volunteers. Mean age was 24.1 (range, 20 to 31) years. MAIN OUTCOME MEASURES: Serum potassium and magnesium muscle potassium and magnesium, and muscle sodium-potassium pump number. Urinary excretion of potassium and magnesium. ECG changes (T-wave and QTC interval) and the number of ventricular ectopic beats. MAIN RESULTS: Terbutaline produced an immediate decrease in serum potassium level from 4.17 (4.04 to 4.30) mmol/L to a nadir of 3.32 (3.06 to 3.58) mmol/L (p < 0.001). The urinary excretion of potassium decreased from 0.077 mmol/min (0.052 to 0.102) to 0.038 mmol/min (0.025 to 0.051) (p < 0.01). There was an increase in the number of sodium potassium pumps from 1,104.1 nmol/kg dry weight (1,030.6 to 1,177.5) to 1,273.3 nmol/kg dry weight (1,193.5 to 1,353.2) (p < 0.01), but no measurable change in muscle potassium. The QTC interval increased from 395 (385 to 405)ms to 449 (432 to 466) ms (p < 0.003). There was no change in the number of ventricular ectopic beats. CONCLUSIONS: Short-term i.v. administration of terbutaline produced hypokalemia partly due to an increase in the number of sodium-potassium pumps. Furthermore, terbutaline induced changes in ECG with a highly significant lengthening of the QTc interval but with an unchanged number of ventricular ectopic beats in healthy subjects.

Adult

Sodium-potassium pump activity in white blood cells from children with an increased risk of developing hypertension--The Odense Schoolchild Study.

We have measured the capacity of the sodium-potassium pump, as assessed by 86rubidium uptake and the number of [3H]-ouabain binding sites on white blood cells, in children aged 9-11 years, partly cross-sectionally and partly longitudinally after a physical training programme. Children from a hypertensive subgroup comprising the upper 5% of the blood pressure distribution and children from a randomly selected normotensive subgroup were eligible for the study. In the cross-sectional study 40 children from the hypertensive subgroup and 40 children from the normotensive subgroup were evaluated. A significant increase in 86rubidium uptake was present in boys as compared to girls. After adjustment for differences in sexual maturation the observed significant difference disappeared. Important correlates of pump activity were height, plasma glucose, and physical fitness. In the training study 10 boys from the hypertensive subgroup and 10 boys from the normotensive subgroup were also evaluated after eight months of physical training. A significant fall in 86rubidium uptake was observed. No control group was examined and probably the changes reflect some effects of sexual maturation on cation handling of cells. These results indicate a significant effect of sexual maturation in capacity of sodium-potassium pump in children.

Child

Effects of detraining on endurance capacity and metabolic changes during prolonged exhaustive exercise.

The effects of 4 wk of detraining on maximal O2 uptake (VO2max) and on endurance capacity defined as the maximal time to exhaustion at 75% of VO2max were studied in nine well-trained endurance athletes. Detraining consisted of one short 35-min high-intensity bout per week as opposed to the normal 6-10 h/wk. Detraining had no effect on VO2max (4.57 +/- 0.10 vs. 4.54 +/- 0.08 l/min), but endurance capacity decreased by 21% from 79 +/- 4 to 62 +/- 4 min (P < 0.001). Endurance exercise respiratory exchange ratio was higher in the detrained than in the trained state (0.91 +/- 0.01 vs. 0.89 +/- 0.01; P < 0.01). Muscle [K+] values were unchanged during exercise and were similar in the trained and detrained states. Muscle [Mg2+] values were similar at rest and at minute 40 (30.3 +/- 0.9 vs. 30.8 +/- 0.6 mmol/kg dry wt) but increased significantly at exhaustion to 33.8 +/- 1.0 mmol/kg dry wt in the trained state and to 33.9 +/- 0.9 mmol/kg dry wt in the detrained state. The elevated muscle [Mg2+] at exhaustion could contribute to fatigue in prolonged exercise through an inhibition of Ca2+ release from sarcoplasmic reticulum. It is concluded that the endurance capacity can vary considerably during detraining without changes in VO2max. Altered substrate utilization or changes in electrolyte regulation may account for the reduced endurance capacity.

Adult

Discrepancy in HbA1c measurements performed at different local laboratories and at a selected central reference laboratory.

As participants in a general practice intervention study, 66 patients had their HbA1c measured both at a local and at a selected central reference laboratory. A discrepancy in the results was observed, as 97% of the results measured locally were lower than the centrally determined results. Bias (as calculated from mean value of measured HbA1c) between local laboratories and the central laboratory was measured to -1.47% HbA1c. A bias of this magnitude gave "problems" both to the general practitioners, patients and laboratories. To reduce the "problems" a bias of 0.5% HbA1c is estimated to be acceptable. But, to avoid these "problems" totally, a bias of 0.25% HbA1c is estimated to be the highest allowed bias. For HbA1c, a control system for both control of method standardisation and for specificity is described.

Evaluation Studies as Topic

[Heart rate disorders in potassium and magnesium deficiency].

Potassium and magnesium deficiencies are common in patients with heart disease. These are often coexistent and pathophysiologically related. Potassium deficiency cannot be treated without correction of concomitant magnesium deficiency. Correlations between serum levels and body stores are very poor for both ions. Therefore diagnosis and treatment of these conditions based on serum levels alone are erroneous. There is some evidence that it is primarily the intracellular depletion of these ions which is arrhythmogenic. Magnesium infusion has been proved effective in treatment of torsade de pointes ventricular tachycardia and arrhythmias induced by digoxin-intoxication, and is recommended in these conditions. Whether it is effective in other forms of arrhythmia is not yet elucidated.

Action Potentials

[Therapy control of perphenazine in paranoid conditions. 1. Organizational aspects].

A prospective investigation was carried out in the Department of Psychiatry, Odense University Hospital, on therapy control by serum monitoring of the neuroleptic, perphenazine for a period of one year. Newly admitted patients requiring treatment for paranoid symptoms, excluding mania, were offered medication with perphenazine (fixed dosage, oral or parenteral (depot)) which would be serum-monitored. A global record was made of the therapeutic effect and the side-effects by the physicians in the department. In the investigation period, 605 admissions were registered in the department, of them 363 were prospectively registered in the investigation. In all 199 were found to satisfy the inclusion criteria. Either one or two blood tests were carried out on each of 141 patients in the treatment period, i.e. six weeks. The gap in registration is consistent with the result from other investigations. Participation in the investigation varied from ward to ward (33%-87%). The reason for the variation is mainly due to different treatment procedures and traditions. The main conclusion drawn from the investigation is that it is possible to set up a stable treatment/serum-monitored system. In the majority of cases, the team of physicians in the department succeeded in finding the dosage most appropriate on the basis of the serum concentration level. Laboratory recommendations were followed in 93% of the cases.

Adult

[Therapy control of perphenazine. 2. Clinical aspects].

Rational use of serum concentration monitoring of the neuroleptic, perphenazine, was evaluated in a prospective investigation. A total of 141 hospitalized patients with paranoid symptoms (excluding mania) requiring treatment were included during the investigation period (one year). Perphenazine was administered (fixed doses) orally (92 patients) and parenterally (depot, decanoate, 45 patients) in a six-week treatment period. Serum concentrations of perphenazine were monitored after 10-14 days oral treatment, on the 14th and 21st days after the commencement of depot treatment. The patients were steered on to the recommended therapeutic range for perphenazine (1.5-6 nmol), according to the serum level measured. Global clinical assessment was carried out by the departmental physicians. Therapy control of perphenazine by serum monitoring was an important supplement to the clinical evaluation of therapeutic effect. Fifteen (65%) out of 23 patients who were treated orally with insufficient therapeutic effect, showed non-compliance or elevated metabolism. On the basis of a single serum concentration measurements (12 hours values), it proved possible to steer the majority of patients onto the recommended therapeutic level. In this way, the individual patient reached optimal therapeutic effect with a minimum of side-effects.

Adult

[Magnesium deficiency and development of late diabetic complications].

Diabetics have a higher prevalence of recurrent angina, myocardial infarction and hypertension compared with healthy individuals. This is partly due to the metabolic control, and partly to the development of nephropathy, but inherited factors also seem to contribute to their development. Another factor, to some extent inherited, could be magnesium-deficiency. Up to 30% of all diabetics suffer from magnesiumdepletion, which in other disease entities has been related to angina pectoris, myocardial infarction, and changes in blood lipids. Furthermore, magnesium-deficiency might be related to the development of hypertension. In diabetes, magnesium-depletion has been linked with the development of retinopathy, and an increase in abortions and malformations in diabetic pregnancies. No intervention trials with magnesium, to elucidate the question of magnesium depletion and diabetic late complications have hitherto been made. No methods for assessing magnesium-status in diabetes are available as yet, to select patients for this type of trial.

Diabetes Mellitus, Type 1

Angiotensin-converting enzyme inhibition as a therapeutic principle in Bartter's syndrome.

The effect of captopril has been investigated in four patients with Bartter's syndrome treated for 12 weeks. Baseline biochemistry showed normal serum aldosterone (mean 347 pmol.l-1) and a mean serum renin of 217 mU-l-1, and a considerable increase in serum renin during captopril treatment. Serum aldosterone decreased gradually during the study period to about half its initial value. The patients presented with a mean serum potassium of 2.5 mmol.l-1, which rose to 3.4 mmol.l-1 on captopril. Lymphocytes showed a substantial captopril-induced increase in intracellular sodium (from 15 to 22.5 mmol.l-1 on average), but no change in the potassium content. Captopril was well-tolerated. It may be an alternative to potassium-sparing diuretics for maintaining normal serum potassium levels in patients with Bartter's syndrome.

Adult

Digitalis enhances exercise-induced hyperkalaemia.

In 9 patients with atrial fibrillation the effect of zero, low and high levels of serum digoxin on exercise-induced hyperkalemia was assessed by bicycle exercise tests. Exercise at each level of serum digoxin was associated with a significant (up to 20%) rise in plasma potassium. At a work load of 75 W the highest level of serum digoxin was associated with a significantly higher maximum plasma potassium concentration as compared to the maximum valueatazero serum digoxin. The enhancement of exercise-induced hyperkalemia may add to the arrhythmogenic effect of digitalis.

Adult

Theophylline and ethylenediamine pharmacokinetics following administration of aminophylline to septic patients with multiorgan failure.

The pharmacokinetics of theophylline and ethylenediamine were examined in 6 patients with septicaemia and multiorgan failure (MOF). The patients received a bolus injection of 4 mg/kg aminophylline. Aminophylline is the ethylenediamine salt of theophylline. The clearance of theophylline was reduced in all our patients ranging from 10-66% of the value obtained in healthy volunteers. The median t 1/2 beta was 18.8 h (range 5.8-25.5) compared to a normal value of 6 h. The median clearance of ethylenediamine was 54% of the normal value, while the peripheral volume of distribution was increased to 650%. Due to this t 1/2 beta was 2.3 (2.0-2.7) h, which is 5 times the normal value of 0.55 h. There was no correlation between clearance of theophylline and ethylenediamine. As theophylline has a narrow therapeutic range, routine monitoring with measurements of serum theophylline is mandatory in patients with MOF.

Adult

Influence of physical exercise on serum digoxin concentration and heart rate in patients with atrial fibrillation.

Heart rate and serum digoxin concentration in eight patients with atrial fibrillation were studied at rest and during exercise when initial serum digoxin concentrations were zero and at low and high therapeutic values. Eight patients with ischemic heart disease and in sinus rhythm were studied for comparison. Though the serum digoxin concentration decreased significantly during exercise, the absolute reduction in heart rate was the same at rest and during exercise in patients with atrial fibrillation. Compared with the control patients in sinus rhythm, the heart rate in patients with atrial fibrillation was not adequately controlled during exercise by any serum digoxin concentration tested despite a reduction in heart rate with increasing digoxin concentration. The effects of digoxin on heart rate regulation in atrial fibrillation are complex and include direct effects on the myocardium as well as indirect effects mediated by modulation of the autonomic nervous system; the present results indicate that the drug is not displaced from the target organs by decreasing serum concentrations during exercise. In atrial fibrillation, because the demands on the filter function of the atrioventricular node are highly unphysiological, the effect of digoxin on heart rate during exercise is not adequate.

Adult